EyeLink Non-Human Primate Publications
All EyeLink non-human primate research publications up until 2021 (with some early 2022s) are listed below by year. You can search the publications using keywords such as Temporal Cortex, Macaque, Antisaccade, etc. You can also search for individual author names. If we missed any EyeLink non-human primate articles, please email us!
Weikang Shi; Sébastien Ballesta; Camillo Padoa-Schioppa
In: Journal of Neuroscience, vol. 42, no. 1, pp. 33–43, 2022.
A series of studies in which monkeys chose between two juices offered in variable amounts identified in the orbitofrontal cortex (OFC) different groups of neurons encoding the value of individual options ( offer value ), the binary choice outcome ( chosen juice ) and the chosen value . These variables capture both the input and the output of the choice process, suggesting that the cell groups identified in OFC constitute the building blocks of a decision circuit. Several lines of evidence support this hypothesis. However, in previous experiments offers were presented simultaneously, raising the question of whether current notions generalize to when goods are presented or are examined in sequence. Recently, [Ballesta and Padoa-Schioppa (2019)] examined OFC activity under sequential offers. An analysis of neuronal responses across time windows revealed that a small number of cell groups encoded specific sequences of variables. These sequences appeared analogous to the variables identified under simultaneous offers, but the correspondence remained tentative. Thus in the present study we examined the relation between cell groups found under sequential versus simultaneous offers. We recorded from the OFC while monkeys chose between different juices. Trials with simultaneous and sequential offers were randomly interleaved in each session. We classified cells in each choice modality and we examined the relation between the two classifications. We found a strong correspondence – in other words, the cell groups measured under simultaneous offers and under sequential offers were one and the same. This result indicates that economic choices under simultaneous or sequential offers rely on the same neural circuit. Significance Statement Research in the past 20 years has shed light on the neuronal underpinnings of economic choices. A large number of results indicates that decisions between goods are formed in a neural circuit within the orbitofrontal cortex (OFC). In most previous studies, subjects chose between two goods offered simultaneously. Yet, in daily situations, goods available for choice are often presented or examined in sequence. Here we recorded neuronal activity in the primate OFC alternating trials under simultaneous and under sequential offers. Our analyses demonstrate that the same neural circuit supports choices in the two modalities. Hence current notions on the neuronal mechanisms underlying economic decisions generalize to choices under sequential offers. ### Competing Interest Statement The authors have declared no competing interest. : #ref-2
Koji Kuraoka; Kae Nakamura
In: Neuroscience Research, 2022.
Studies in human subjects have revealed that autonomic responses provide objective and biologically relevant information about cognitive and affective states. Measures of autonomic responses can also be applied to studies of non-human primates, which are neuro-anatomically and physically similar to humans. Facial temperature and pupil size are measured remotely and can be applied to physiological experiments in primates, preferably in a head-fixed condition. However, detailed guidelines for the use of these measures in non-human primates is lacking. Here, we review the neuronal circuits and methodological considerations necessary for measuring and analyzing facial temperature and pupil size in non-human primates. Previous studies have shown that the modulation of these measures primarily reflects sympathetic reactions to cognitive and emotional processes, including alertness, attention, and mental effort, over different time scales. Integrated analyses of autonomic, behavioral, and neurophysiological data in primates are promising methods that reflect multiple dimensions of emotion and could potentially provide tools for understanding the mechanisms underlying neuropsychiatric disorders and vulnerabilities characterized by cognitive and affective disturbances.
Aravind Krishna; Seiji Tanabe; Adam Kohn
In: Cerebral Cortex, vol. 31, no. 1, pp. 169–183, 2021.
The neural basis of perceptual decision making has typically been studied using measurements of single neuron activity, though decisions are likely based on the activity of large neuronal ensembles. Local field potentials (LFPs) may, in some cases, serve as a useful proxy for population activity and thus be useful for understanding the neural basis of perceptual decision making. However, little is known about whether LFPs in sensory areas include decision-related signals. We therefore analyzed LFPs recorded using two 48-electrode arrays implanted in primary visual cortex (V1) and area V4 of macaque monkeys trained to perform a fine orientation discrimination task. We found significant choice information in low (0-30 Hz) and higher (70-500 Hz) frequency components of the LFP, but little information in gamma frequencies (30-70 Hz). Choice information was more robust in V4 than V1 and stronger in LFPs than in simultaneously measured spiking activity. LFP-based choice information included a global component, common across electrodes within an area. Our findings reveal the presence of robust choice-related signals in the LFPs recorded in V1 and V4 and suggest that LFPs may be a useful complement to spike-based analyses of decision making.
Heng Ma; Pengcheng Li; Jiaming Hu; Xingya Cai; Qianling Song; Haidong D. Lu
Processing of motion-boundary orientation in macaque V2 Journal Article
In: eLife, vol. 10, pp. e61317, 2021.
Human and non-human primates are good at identifying an object based on its motion, a task that is believed to be carried out by the ventral visual pathway. However, the neural mechanisms underlying such ability remains unclear. We trained macaque monkeys to do orientation discrimination for motion-boundaries (MB) and recorded neuronal response in area V2 with microelectrode arrays. We found 10.9% of V2 neurons exhibited robust orientation-selectivity to MBs, and their responses correlated with monkeys' orientation-discrimination performances. Furthermore, the responses of V2 direction-selective neurons recorded at the same time showed correlated activity with MB neurons for particular MB stimuli, suggesting that these motion-sensitive neurons made specific functional contributions to MB discrimination tasks. Our findings support the view that V2 plays a critical role in MB analysis and may achieve this through a neural circuit within area V2.
David J. N. Maisson; Tyler V. Cash-Padgett; Maya Z. Wang; Benjamin Y. Hayden; Sarah R. Heilbronner; Jan Zimmermann
In: Nature Communications, vol. 12, pp. 4830, 2021.
Choice-relevant brain regions in prefrontal cortex may progressively transform information about options into choices. Here, we examine responses of neurons in four regions of the medial prefrontal cortex as macaques performed two-option risky choices. All four regions encode economic variables in similar proportions and show similar putative signatures of key choice-related computations. We provide evidence to support a gradient of function that proceeds from areas 14 to 25 to 32 to 24. Specifically, we show that decodability of twelve distinct task variables increases along that path, consistent with the idea that regions that are higher in the anatomical hierarchy make choice-relevant variables more separable. We also show progressively longer intrinsic timescales in the same series. Together these results highlight the importance of the medial wall in choice, endorse a specific gradient-based organization, and argue against a modular functional neuroanatomy of choice.
Tatiana Malevich; Antimo Buonocore; Ziad M. Hafed
In: Journal of Neurophysiology, vol. 125, no. 1, pp. 282–295, 2021.
Microsaccades have a steady rate of occurrence during maintained gaze fixation, which gets transiently modulated by abrupt sensory stimuli. Such modulation, characterized by a rapid reduction in microsaccade frequency followed by a stronger rebound phase of high microsaccade rate, is often described as the microsaccadic rate signature, owing to its stereotyped nature. Here, we investigated the impacts of stimulus polarity (luminance increments or luminance decrements relative to background luminance) and size on the microsaccadic rate signature. We presented brief, behaviorally irrelevant visual flashes consisting of large or small, white or black stimuli over an otherwise gray image background. Both large and small stimuli caused robust early microsaccadic inhibition, but postinhibition microsaccade rate rebound was significantly delayed and weakened for large stimuli when compared with small ones. Critically, small black stimuli were associated with stronger modulations in the microsaccade rate signature than small white stimuli, particularly in the postinhibition rebound phase, and black stimuli also amplified the incidence of early stimulus-directed microsaccades. Our results demonstrate that the microsaccadic rate signature is sensitive to stimulus size and polarity, and they point to dissociable neural mechanisms underlying early microsaccadic inhibition after stimulus onset and later microsaccadic rate rebound at longer times thereafter. These results also demonstrate early access of oculomotor control circuitry to diverse sensory representations, particularly for momentarily inhibiting saccade generation with short latencies. NEW & NOTEWORTHY Microsaccade rate is transiently reduced after sudden stimulus onsets, and then strongly rebounds before returning to baseline. We explored the influence of stimulus polarity (black vs. white) and size on this “rate signature.” Large stimuli caused more muted microsaccadic rebound than small ones, and microsaccadic rebound was also differentially affected by black versus white stimuli, particularly with small stimuli. These results suggest dissociated neural mechanisms for microsaccadic inhibition and rebound in the microsaccadic rate signature.
Nicolas Meirhaeghe; Hansem Sohn; Mehrdad Jazayeri
In: Neuron, vol. 109, no. 18, pp. 2995–3011.e5, 2021.
The theory of predictive processing posits that the brain computes expectations to process information predictively. Empirical evidence in support of this theory, however, is scarce and largely limited to sensory areas. Here, we report a precise and adaptive mechanism in the frontal cortex of non-human primates consistent with predictive processing of temporal events. We found that the speed of neural dynamics is precisely adjusted according to the average time of an expected stimulus. This speed adjustment, in turn, enables neurons to encode stimuli in terms of deviations from expectation. This lawful relationship was evident across multiple experiments and held true during learning: when temporal statistics underwent covert changes, neural responses underwent predictable changes that reflected the new mean. Together, these results highlight a precise mathematical relationship between temporal statistics in the environment and neural activity in the frontal cortex that may serve as a mechanism for predictive temporal processing.
Lara Merken; Marco Davare; Peter Janssen; Maria C. Romero
In: Scientific Reports, vol. 11, pp. 4511, 2021.
The neural mechanisms underlying the effects of continuous Theta-Burst Stimulation (cTBS) in humans are poorly understood. Animal studies can clarify the effects of cTBS on individual neurons, but behavioral evidence is necessary to demonstrate the validity of the animal model. We investigated the behavioral effect of cTBS applied over parietal cortex in rhesus monkeys performing a visually-guided grasping task with two differently sized objects, which required either a power grip or a pad-to-side grip. We used Fitts' law, predicting shorter grasping times (GT) for large compared to small objects, to investigate cTBS effects on two different grip types. cTBS induced long-lasting object-specific and dose-dependent changes in GT that remained present for up to two hours. High-intensity cTBS increased GTs for a power grip, but shortened GTs for a pad-to-side grip. Thus, high-intensity stimulation strongly reduced the natural GT difference between objects (i.e. the Fitts' law effect). In contrast, low-intensity cTBS induced the opposite effects on GT. Modifying the coil orientation from the standard 45-degree to a 30-degree angle induced opposite cTBS effects on GT. These findings represent behavioral evidence for the validity of the nonhuman primate model to study the neural underpinnings of non-invasive brain stimulation.
Yaser Merrikhi; Mohammad Shams-Ahmar; Hamid Karimi-Rouzbahani; Kelsey Clark; Reza Ebrahimpour; Behrad Noudoost
In: Journal of Cognitive Neuroscience, vol. 33, no. 10, pp. 2167–2180, 2021.
Before saccadic eyemovements, our perception of the saccade targets is enhanced. Changes in the visual representation of saccade targets, which presumably underlie this perceptual benefit, emerge even before the eye begins to move. This perisaccadic enhancement has been shown to involve changes in the response magnitude, selectivity, and reliability of visual neurons. In this study, we quantified multiple aspects of perisaccadic changes in the neural response, including gain, feature tuning, contrast response function, reliability, and correlated activity between neurons. Wethen assessed the contributions of these various perisaccadic modulations to the population's enhanced perisaccadic representation of saccade targets. We found a partial dissociation between the motor information, carried entirely by gain changes, and visual information,which depended on all three types ofmodulation. These findings expand our understanding of the perisaccadic enhancement of visual representations and further support the existence of multiple sources of motor modulation and visual enhancement within extrastriate visual cortex.
Nardin Nakhla; Yavar Korkian; Matthew R. Krause; Christopher C. Pack
Neural selectivity for visual motion in macaque area v3a Journal Article
In: eNeuro, vol. 8, no. 1, pp. 1–14, 2021.
The processing of visual motion is conducted by dedicated pathways in the primate brain. These pathways originate with populations of direction-selective neurons in the primary visual cortex, which projects to dorsal structures like the middle temporal (MT) and medial superior temporal (MST) areas. Anatomical and imaging studies have suggested that area V3A might also be specialized for motion processing, but there have been very few studies of single-neuron direction selectivity in this area. We have therefore performed electrophysiological recordings from V3A neurons in two macaque monkeys (one male and one female) and measured responses to a large battery of motion stimuli that includes translation motion, as well as more complex optic flow patterns. For comparison, we simultaneously recorded the responses of MT neurons to the same stimuli. Surprisingly, we find that overall levels of direction selectivity are similar in V3A and MT and moreover that the population of V3A neurons exhibits somewhat greater selectivity for optic flow patterns. These results suggest that V3A should be considered as part of the motion processing machinery of the visual cortex, in both human and non-human primates.
Tomoyuki Namima; Anitha Pasupathy
In: Journal of Neuroscience, vol. 41, no. 26, pp. 5662–5666, 2021.
Object segmentation-the process of parsing visual scenes-is essential for object recognition and scene understanding. We investigated how responses of neurons in macaque inferior temporal (IT) cortex contribute to object segmentation under partial occlusion. Specifically, we asked whether IT responses to occluding and occluded objects are bound together as in the visual image or linearly separable reflecting their segmentation. We recorded the activity of 121 IT neurons while two male animals performed a shape discrimination task under partial occlusion. We found that for a majority (60%) of neurons, responses were enhanced by partial occlusion, but they were only weakly shape selective for the discriminanda at all levels of occlusion. Enhancement of IT responses in these neurons depended largely on the area of occlusion but only minimally on the color and shape of the occluding dots. In contrast to the above group of neurons, a sizable minority responded best to the unoccluded stimulus and showed strong selectivity for the shape of the discriminanda. In these neurons, response magnitude and shape selectivity declined with increasing levels of occlusion. Simulations revealed that the response characteristics of both classes of neurons were consistent with a model in which the responses to the occluded shape and the occluders are weighted separately and linearly combined. Overall, our results support the hypothesis that information about occluded and occluding stimuli are linearly separable and easily decodable from IT responses and that IT neurons encode a segmented representation of the visual scene.
Sunny Nigam; Sorin Pojoga; Valentin Dragoi
In: Science Advances, vol. 7, no. 8, pp. eabc5837, 2021.
Color is a key feature of natural environments that higher mammals routinely use to detect food, avoid predators, and interpret social signals. The distribution of color signals in natural scenes is widely variable, ranging from uniform patches to highly nonuniform regions in which different colors lie in close proximity. Whether individual neurons are tuned to this high degree of variability of color signals is unknown. Here, we identified a distinct population of cells in macaque visual cortex (area V4) that have a heterogeneous receptive field (RF) structure in which individual subfields are tuned to different colors even though the full RF is only weakly tuned. This spatial heterogeneity in color tuning indicates a higher degree of complexity of color-encoding mechanisms in visual cortex than previously believed to efficiently extract chromatic information from the environment.
Taihei Ninomiya; Atsushi Noritake; Masaki Isoda
In: Proceedings of the National Academy of Sciences, vol. 118, no. 44, pp. e2109653118, 2021.
Mentalizing, the ability to infer the mental states of others, is a cornerstone of adaptive social intelligence. While functional brain mapping of human mentalizing has progressed considerably, its evolutionary signature in nonhuman primates remains debated. The discovery that the middle part of the macaque superior temporal sulcus (mid-STS) region has a connectional fingerprint most similar to the human temporoparietal junction (TPJ)-a crucial node in the mentalizing network-raises the possibility that these cortical areas may also share basic functional properties associated with mentalizing. Here, we show that this is the case in aspects of a preference for live social interactions and in a theoretical framework of predictive coding. Macaque monkeys were trained to perform a turn-taking choice task with another real monkey partner sitting directly face-to-face or a filmed partner appearing in prerecorded videos. We found that about three-fourths of task-related mid-STS neurons exhibited agent-dependent activity, most responding selectively or preferentially to the partner's action. At the population level, activities of these partner-type neurons were significantly greater under live-partner compared to videorecorded- partner task conditions. Furthermore, a subset of the partner-type neurons responded proactively when predictions about the partner's action were violated. This prediction error coding was specific to the action domain; almost none of the neurons signaled error in the prediction of reward. The present findings highlight unique roles of the macaque mid-STS at the singleneuron level and further delineate its functional parallels with the human TPJ in social cognitive processes associated with mentalizing.
Mineki Oguchi; Shingo Tanaka; Xiaochuan Pan; Takefumi Kikusui; Keiko Moriya-Ito; Shigeki Kato; Kazuto Kobayashi; Masamichi Sakagami
In: Communications Biology, vol. 4, no. 1, pp. 1088, 2021.
The lateral prefrontal cortex (LPFC) has a strong monosynaptic connection with the caudate nucleus (CdN) of the striatum. Previous human MRI studies have suggested that this LPFC-CdN pathway plays an important role in inhibitory control and working memory. We aimed to validate the function of this pathway at a causal level by pathway-selective manipulation of neural activity in non-human primates. To this end, we trained macaque monkeys on a delayed oculomotor response task with reward asymmetry and expressed an inhibitory type of chemogenetic receptors selectively to LPFC neurons that project to the CdN. Ligand administration reduced the inhibitory control of impulsive behavior, as well as the task-related neuronal responses observed in the local field potentials from the LPFC and CdN. These results show that we successfully suppressed pathway-selective neural activity in the macaque brain, and the resulting behavioral changes suggest that the LPFC-CdN pathway is involved in inhibitory control.
Gouki Okazawa; Christina E. Hatch; Allan Mancoo; Christian K. Machens; Roozbeh Kiani
In: Cell, vol. 184, no. 14, pp. 3748–3761, 2021.
Lateral intraparietal (LIP) neurons represent formation of perceptual decisions involving eye movements. In circuit models for these decisions, neural ensembles that encode actions compete to form decisions. Consequently, representation and readout of the decision variables (DVs) are implemented similarly for decisions with identical competing actions, irrespective of input and task context differences. Further, DVs are encoded as partially potentiated action plans through balance of activity of action-selective ensembles. Here, we test those core principles. We show that in a novel face-discrimination task, LIP firing rates decrease with supporting evidence, contrary to conventional motion-discrimination tasks. These opposite response patterns arise from similar mechanisms in which decisions form along curved population-response manifolds misaligned with action representations. These manifolds rotate in state space based on context, indicating distinct optimal readouts for different tasks. We show similar manifolds in lateral and medial prefrontal cortices, suggesting similar representational geometry across decision-making circuits.
John Orczyk; Charles E. Schroeder; Ilana Y. Abeles; Manuel Gomez-Ramirez; Pamela D. Butler; Yoshinao Kajikawa
Comparison of scalp ERP to faces in macaques and humans Journal Article
In: Frontiers in Systems Neuroscience, vol. 15, pp. 667611, 2021.
Face recognition is an essential activity of social living, common to many primate species. Underlying processes in the brain have been investigated using various techniques and compared between species. Functional imaging studies have shown face-selective cortical regions and their degree of correspondence across species. However, the temporal dynamics of face processing, particularly processing speed, are likely different between them. Across sensory modalities activation of primary sensory cortices in macaque monkeys occurs at about 3/5 the latency of corresponding activation in humans, though this human simian difference may diminish or disappear in higher cortical regions. We recorded scalp event-related potentials (ERPs) to presentation of faces in macaques and estimated the peak latency of ERP components. Comparisons of latencies between macaques (112 ms) and humans (192 ms) suggested that the 3:5 ratio could be preserved in higher cognitive regions of face processing between those species.
Matthew F. Panichello; Timothy J. Buschman
In: Nature, vol. 592, no. 7855, pp. 601–605, 2021.
Cognitive control guides behaviour by controlling what, when, and how information is represented in the brain1. For example, attention controls sensory processing; top-down signals from prefrontal and parietal cortex strengthen the representation of task-relevant stimuli2–4. A similar ‘selection' mechanism is thought to control the representations held ‘in mind'—in working memory5–10. Here we show that shared neural mechanisms underlie the selection of items from working memory and attention to sensory stimuli. We trained rhesus monkeys to switch between two tasks, either selecting one item from a set of items held in working memory or attending to one stimulus from a set of visual stimuli. Neural recordings showed that similar representations in prefrontal cortex encoded the control of both selection and attention, suggesting that prefrontal cortex acts as a domain-general controller. By contrast, both attention and selection were represented independently in parietal and visual cortex. Both selection and attention facilitated behaviour by enhancing and transforming the representation of the selected memory or attended stimulus. Specifically, during the selection task, memory items were initially represented in independent subspaces of neural activity in prefrontal cortex. Selecting an item caused its representation to transform from its own subspace to a new subspace used to guide behaviour. A similar transformation occurred for attention. Our results suggest that prefrontal cortex controls cognition by dynamically transforming representations to control what and when cognitive computations are engaged.
Mohsen Parto Dezfouli; Philipp Schwedhelm; Michael Wibral; Stefan Treue; Mohammad Reza Daliri; Moein Esghaei
In: NeuroImage, vol. 229, pp. 117757, 2021.
We effortlessly perceive visual objects as unified entities, despite the preferential encoding of their various visual features in separate cortical areas. A ‘binding' process is assumed to be required for creating this unified percept, but the underlying neural mechanism and specific brain areas are poorly understood. We investigated ‘feature-binding' across two feature dimensions, using a novel stimulus configuration, designed to disambiguate whether a given combination of color and motion direction is perceived as bound or unbound. In the “bound” condition, two behaviorally relevant features (color and motion) belong to the same object, while in the “unbound” condition they belong to different objects. We recorded local field potentials from the lateral prefrontal cortex (lPFC) in macaque monkeys that actively monitored the different stimulus configurations. Our data show a neural representation of visual feature binding especially in the 4–12 Hz frequency band and a transmission of binding information between different lPFC neural subpopulations. This information is linked to the animal's reaction time, suggesting a behavioral relevance of the binding information. Together, our results document the involvement of the prefrontal cortex, targeted by the dorsal and ventral visual streams, in binding visual features from different dimensions, in a process that includes a dynamic modulation of low frequency inter-regional communication.
Tyler R. Peel; Suryadeep Dash; Stephen G. Lomber; Brian D. Corneil
In: Journal of Computational Neuroscience, vol. 49, no. 3, pp. 229–249, 2021.
Saccades require a spatiotemporal transformation of activity between the intermediate layers of the superior colliculus (iSC) and downstream brainstem burst generator. The dynamic linear ensemble-coding model (Goossens and Van Opstal 2006) proposes that each iSC spike contributes a fixed mini-vector to saccade displacement. Although biologically-plausible, this model assumes cortical areas like the frontal eye fields (FEF) simply provide the saccadic goal to be executed by the iSC and brainstem burst generator. However, the FEF and iSC operate in unison during saccades, and a pathway from the FEF to the brainstem burst generator that bypasses the iSC exists. Here, we investigate the impact of large yet reversible inactivation of the FEF on iSC activity in the context of the model across four saccade tasks. We exploit the overlap of saccade vectors generated when the FEF is inactivated or not, comparing the number of iSC spikes for metrically-matched saccades. We found that the iSC emits fewer spikes for metrically-matched saccades during FEF inactivation. The decrease in spike count is task-dependent, with a greater decrease accompanying more cognitively-demanding saccades. Our results show that FEF integrity influences the readout of iSC activity in a task-dependent manner. We propose that the dynamic linear ensemble-coding model be modified so that FEF inactivation increases the gain of a readout parameter, effectively increasing the influence of a single iSC spike. We speculate that this modification could be instantiated by FEF and iSC pathways to the cerebellum that could modulate the excitability of the brainstem burst generator.
Alina Peter; Benjamin Johannes Stauch; Katharine Shapcott; Kleopatra Kouroupaki; Joscha Tapani Schmiedt; Liane Klein; Johanna Klon-Lipok; Jarrod Robert Dowdall; Marieke Louise Schölvinck; Martin Vinck; Michael Christoph Schmid; Pascal Fries
Stimulus-specific plasticity of macaque V1 spike rates and gamma Journal Article
In: Cell Reports, vol. 37, no. 10, pp. 110086, 2021.
When a visual stimulus is repeated, average neuronal responses typically decrease, yet they might maintain or even increase their impact through increased synchronization. Previous work has found that many repetitions of a grating lead to increasing gamma-band synchronization. Here, we show in awake macaque area V1 that both repetition-related reductions in firing rate and increases in gamma are specific to the repeated stimulus. These effects show some persistence on the timescale of minutes. Gamma increases are specific to the presented stimulus location. Further, repetition effects on gamma and on firing rates generalize to images of natural objects. These findings support the notion that gamma-band synchronization subserves the adaptive processing of repeated stimulus encounters.
Katrina R. Quinn; Lenka Seillier; Daniel A. Butts; Hendrikje Nienborg
In: Nature Communications, vol. 12, pp. 4473, 2021.
Feedback in the brain is thought to convey contextual information that underlies our flexibility to perform different tasks. Empirical and computational work on the visual system suggests this is achieved by targeting task-relevant neuronal subpopulations. We combine two tasks, each resulting in selective modulation by feedback, to test whether the feedback reflected the combination of both selectivities. We used visual feature-discrimination specified at one of two possible locations and uncoupled the decision formation from motor plans to report it, while recording in macaque mid-level visual areas. Here we show that although the behavior is spatially selective, using only task-relevant information, modulation by decision-related feedback is spatially unselective. Population responses reveal similar stimulus-choice alignments irrespective of stimulus relevance. The results suggest a common mechanism across tasks, independent of the spatial selectivity these tasks demand. This may reflect biological constraints and facilitate generalization across tasks. Our findings also support a previously hypothesized link between feature-based attention and decision-related activity.
Milena Raffi; Andrea Meoni; Alessandro Piras
In: Neuroscience Letters, vol. 743, pp. 135581, 2021.
The spatial location indicated by a visual cue can bias microsaccades directions towards or away from the cue. Aim of this work was to evaluate the microsaccades characteristics during the monkey's training, investigating the relationship between a shift of attention and practice. The monkey was trained to press a lever at a target onset, then an expanding optic flow stimulus appeared to the right of the target. After a variable time delay, a visual cue appeared within the optic flow stimulus and the monkey had to release the lever in a maximum reaction time (RT) of 700 ms. In the control task no visual cue appeared and the monkey had to attend a change in the target color. Data were recorded in 9 months. Results revealed that the RTs at the control task changed significantly across time. The microsaccades directions were significantly clustered toward the visual cue, suggesting that the animal developed an attentional bias toward the visual space where the cue appeared. The microsaccades amplitude differed significantly across time. The microsaccades peak velocity differed significantly both across time and within the time delays, indicating that the monkey made faster microsaccades when it expected the cue to appear. The microsaccades number was significantly higher in the control task with respect to discrimination. The lack of change in microsaccades rate, duration, number and direction across time indicates that the experience acquired during practicing the task did not influence microsaccades generation.
Ehsan Rezayat; Mohammad Reza A. Dehaqani; Kelsey Clark; Zahra Bahmani; Tirin Moore; Behrad Noudoost
In: Nature Communications, vol. 12, pp. 1103, 2021.
Neurons in some sensory areas reflect the content of working memory (WM) in their spiking activity. However, this spiking activity is seldom related to behavioral performance. We studied the responses of inferotemporal (IT) neurons, which exhibit object-selective activity, along with Frontal Eye Field (FEF) neurons, which exhibit spatially selective activity, during the delay period of an object WM task. Unlike the spiking activity and local field potentials (LFPs) within these areas, which were poor predictors of behavioral performance, the phase-locking of IT spikes and LFPs with the beta band of FEF LFPs robustly predicted successful WM maintenance. In addition, IT neurons exhibited greater object-selective persistent activity when their spikes were locked to the phase of FEF LFPs. These results reveal that the coordination between prefrontal and temporal cortex predicts the successful maintenance of visual information during WM.
Kathryn M. Rothenhoefer; Tao Hong; Aydin Alikaya; William R. Stauffer
Rare rewards amplify dopamine responses Journal Article
In: Nature Neuroscience, vol. 24, no. 4, pp. 465–469, 2021.
Dopamine prediction error responses are essential components of universal learning mechanisms. However, it is unknown whether individual dopamine neurons reflect the shape of reward distributions. Here, we used symmetrical distributions with differently weighted tails to investigate how the frequency of rewards and reward prediction errors influence dopamine signals. Rare rewards amplified dopamine responses, even when conventional prediction errors were identical, indicating a mechanism for learning the complexities of real-world incentives.
Megan Roussy; Rogelio Luna; Lyndon Duong; Benjamin Corrigan; Roberto A. Gulli; Ramon Nogueira; Rubén Moreno-Bote; Adam J. Sachs; Lena Palaniyappan; Julio C. Martinez-Trujillo
In: Molecular Psychiatry, vol. 26, pp. 6688–6703, 2021.
Ketamine is a dissociative anesthetic drug, which has more recently emerged as a rapid-acting antidepressant. When acutely administered at subanesthetic doses, ketamine causes cognitive deficits like those observed in patients with schizophrenia, including impaired working memory. Although these effects have been linked to ketamine's action as an N-methyl-D-aspartate receptor antagonist, it is unclear how synaptic alterations translate into changes in brain microcircuit function that ultimately influence cognition. Here, we administered ketamine to rhesus monkeys during a spatial working memory task set in a naturalistic virtual environment. Ketamine induced transient working memory deficits while sparing perceptual and motor skills. Working memory deficits were accompanied by decreased responses of fast spiking inhibitory interneurons and increased responses of broad spiking excitatory neurons in the lateral prefrontal cortex. This translated into a decrease in neuronal tuning and information encoded by neuronal populations about remembered locations. Our results demonstrate that ketamine differentially affects neuronal types in the neocortex; thus, it perturbs the excitation inhibition balance within prefrontal microcircuits and ultimately leads to selective working memory deficits.
Alexander Schielke; Bart Krekelberg
In: Journal of Vision, vol. 21, no. 6, pp. 1–11, 2021.
Visual cognition is finely tuned to the elements in a scene but also relies on contextual integration to improve visual detection and discrimination. This integration is impaired in patients with schizophrenia. Studying impairments in contextual integration may lead to biomarkers of schizophrenia, tools to monitor disease progression, and, in animal models, insight into the underlying neural deficits. We developed a nonhuman primate model to test the hypothesis that hypofunction of the N-methyl D-aspartate receptor (NMDAR) impairs contextual integration. Two male rhesus macaques (Macaca mulatta)were trained to indicate which of two patterns on the screen had the highest contrast. One of these patterns appeared in isolation, and the other was surrounded by a high-contrast pattern. In humans, this high-contrast context is known to lead to an underestimation of contrast. This so-called Chubb illusion is thought to result from surround suppression, a key contextual integration mechanism. To test the involvement of NMDAR in this process, we compared animals' perceptual bias with and without intramuscular injections of a subanesthetic dose of the NMDAR antagonist ketamine. In the absence of ketamine, the animals reported a Chubb illusion - matching reports in healthy humans. Hence, monkeys - just like humans - perform visual contextual integration. This reaffirms the importance of nonhuman primates to help understand visual cognition. Injection of ketamine significantly reduced the strength of the illusion and thus impaired contextual integration. This supports the hypothesis that NMDAR hypofunction plays a causal role in specific behavioral impairments observed in schizophrenia.
Constanze Schmitt; Jakob C. B. Schwenk; Adrian Schütz; Jan Churan; André Kaminiarz; Frank Bremmer
In: Progress in Neurobiology, vol. 205, pp. 102117, 2021.
The visually-based control of self-motion is a challenging task, requiring – if needed – immediate adjustments to keep on track. Accordingly, it would appear advantageous if the processing of self-motion direction (heading) was predictive, thereby accelerating the encoding of unexpected changes, and un-impaired by attentional load. We tested this hypothesis by recording EEG in humans and macaque monkeys with similar experimental protocols. Subjects viewed a random dot pattern simulating self-motion across a ground plane in an oddball EEG paradigm. Standard and deviant trials differed only in their simulated heading direction (forward-left vs. forward-right). Event-related potentials (ERPs) were compared in order to test for the occurrence of a visual mismatch negativity (vMMN), a component that reflects preattentive and likely also predictive processing of sensory stimuli. Analysis of the ERPs revealed signatures of a prediction mismatch for deviant stimuli in both humans and monkeys. In humans, a MMN was observed starting 110 ms after self-motion onset. In monkeys, peak response amplitudes following deviant stimuli were enhanced compared to the standard already 100 ms after self-motion onset. We consider our results strong evidence for a preattentive processing of visual self-motion information in humans and monkeys, allowing for ultrafast adjustments of their heading direction.
Elena Selezneva; Michael Brosch; Sanchit Rathi; T. Vighneshvel; Nicole Wetzel
In: Frontiers in Psychology, vol. 12, pp. 754604, 2021.
Pupil dilation in response to unexpected stimuli has been well documented in human as well as in non-human primates; however, this phenomenon has not been systematically compared between the species. This analogy is also crucial for the role of non-human primates as an animal model to investigate neural mechanisms underlying the processing of unexpected stimuli and their evoked pupil dilation response. To assess this qualitatively, we used an auditory oddball paradigm in which we presented subjects a sequence of the same sounds followed by occasional deviants while we measured their evoked pupil dilation response (PDR). We used deviants (a frequency deviant, a pink noise burst, a monkey vocalization and a whistle sound) which differed in the spectral composition and in their ability to induce arousal from the standard. Most deviants elicited a significant pupil dilation in both species with decreased peak latency and increased peak amplitude in monkeys compared to humans. A temporal Principal Component Analysis (PCA) revealed two components underlying the PDRs in both species. The early component is likely associated to the parasympathetic nervous system and the late component to the sympathetic nervous system, respectively. Taken together, the present study demonstrates a qualitative similarity between PDRs to unexpected auditory stimuli in macaque and human subjects suggesting that macaques can be a suitable model for investigating the neuronal bases of pupil dilation. However, the quantitative differences in PDRs between species need to be investigated in further comparative studies.
Janahan Selvanayagam; Kevin D. Johnston; Raymond K. Wong; David Schaeffer; Stefan Everling
In: Journal of Neurophysiology, vol. 126, no. 1, pp. 330–339, 2021.
Faces are stimuli of critical importance for primates. The common marmoset (Callithrix jacchus) is a promising model for investigations of face processing, as this species possesses oculomotor and face-processing networks resembling those of macaques and humans. Face processing is often disrupted in neuropsychiatric conditions such as schizophrenia (SZ), and thus, it is important to recapitulate underlying circuitry dysfunction preclinically. The N-methyl-D-aspartate (NMDA) noncompetitive antagonist ketamine has been used extensively to model the cognitive symptoms of SZ. Here, we investigated the effects of a subanesthetic dose of ketamine on oculomotor behavior in marmosets during face viewing. Four marmosets received systemic ketamine or saline injections while viewing phase-scrambled or intact videos of conspecifics' faces. To evaluate effects of ketamine on scan paths during face viewing, we identified regions of interest in each face video and classified locations of saccade onsets and landing positions within these areas. A preference for the snout over eye regions was observed following ketamine administration. In addition, regions in which saccades landed could be significantly predicted by saccade onset region in the saline but not the ketamine condition. Effects on saccade control were limited to an increase in saccade peak velocity in all conditions and a reduction in saccade amplitudes during viewing of scrambled videos. Thus, ketamine induced a significant disruption of scan paths during viewing of conspecific faces but limited effects on saccade motor control. These findings support the use of ketamine in marmosets for investigating changes in neural circuits underlying social cognition in neuropsychiatric disorders. NEW & NOTEWORTHY Face processing, an important social cognitive ability, is impaired in neuropsychiatric conditions such as schizophrenia. The highly social common marmoset model presents an opportunity to investigate these impairments. We administered subanesthetic doses of ketamine to marmosets to model the cognitive symptoms of schizophrenia. We observed a disruption of scan paths during viewing of conspecifics' faces. These findings support the use of ketamine in marmosets as a model for investigating social cognition in neuropsychiatric disorders.
Adam C. Snyder; Byron M. Yu; Matthew A. Smith
In: Journal of Neuroscience, vol. 41, no. 44, pp. 9163–9176, 2021.
Attention often requires maintaining a stable mental state over time while simultaneously improving perceptual sensitivity. These requirements place conflicting demands on neural populations, as sensitivity implies a robust response to perturbation by incoming stimuli, which is antithetical to stability. Functional specialization of cortical areas provides one potential mechanism to resolve this conflict. We reasoned that attention signals in executive control areas might be highly stable over time, reflecting maintenance of the cognitive state, thereby freeing up sensory areas to be more sensitive to sensory input (i.e., unstable), which would be reflected by more dynamic attention signals in those areas. To test these predictions, we simultaneously recorded neural populations in prefrontal cortex (PFC) and visual cortical area V4 in rhesus macaque monkeys performing an endogenous spatial selective attention task. Using a decoding approach, we found that the neural code for attention states in PFC was substantially more stable over time compared with the attention code in V4 on a moment-bymoment basis, in line with our guiding thesis. Moreover, attention signals in PFC predicted the future attention state of V4 better than vice versa, consistent with a top-down role for PFC in attention. These results suggest a functional specialization of attention mechanisms across cortical areas with a division of labor. PFC signals the cognitive state and maintains this state stably over time, whereas V4 responds to sensory input in a manner dynamically modulated by that cognitive state.
Norihiro Takakuwa; Kaoru Isa; Hirotaka Onoe; Jun Takahashi; Tadashi Isa
In: Journal of Neuroscience, vol. 41, no. 8, pp. 1755–1768, 2021.
After damage to the primary visual cortex (V1), conscious vision is impaired. However, some patients can respond to visual stimuli presented in their lesion-affected visual field using residual visual pathways bypassing V1. This phenomenon is called “blindsight.” Many studies have tried to identify the brain regions responsible for blindsight, and the pulvinar and/or lateral geniculate nucleus (LGN) are suggested to play key roles as the thalamic relay of visual signals. However, there are critical problems regarding these preceding studies in that subjects with different sized lesions and periods of time after lesioning were investigated; furthermore, the ability of blindsight was assessed with different measures. In this study, we used double dissociation to clarify the roles of the pulvinar and LGN by pharmacological inactivation of each region and investigated the effects in a simple task with visually guided saccades (VGSs) using monkeys with a unilateral V1 lesion, by which nearly all of the contralesional visual field was affected. Inactivating either the ipsilesional pulvinar or LGN impaired VGS toward a visual stimulus in the affected field. In contrast, inactivation of the contralesional pulvinar had no clear effect, but inactivation of the contralesional LGN impaired VGS to the intact visual field. These results suggest that the pulvinar and LGN play key roles in performing the simple VGS task after V1 lesioning, and that the visuomotor functions of blindsight monkeys were supported by plastic changes in the visual pathway involving the pulvinar, which emerged after V1 lesioning.
Ryuji Takeya; Shuntaro Nakamura; Masaki Tanaka
In: PLoS ONE, vol. 16, no. 3, pp. e0248530, 2021.
Sequential movements are often grouped into several chunks, as evidenced by the modulation of the timing of each elemental movement. Even during synchronized tapping with a metronome, we sometimes feel subjective accent for every few taps. To examine whether motor segmentation emerges during synchronized movements, we trained monkeys to generate a series of predictive saccades synchronized with visual stimuli which sequentially appeared for a fixed interval (400 or 600 ms) at six circularly arranged landmark locations. We found two types of motor segmentations that featured periodic modulation of saccade timing. First, the intersaccadic interval (ISI) depended on the target location and saccade direction, indicating that particular combinations of saccades were integrated into motor chunks. Second, when a task-irrelevant rectangular contour surrounding three landmarks ("inducer") was presented, the ISI significantly modulated depending on the relative target location to the inducer. All patterns of individual differences seen in monkeys were also observed in humans. Importantly, the effects of the inducer greatly decreased or disappeared when the animals were trained to generate only reactive saccades (latency >100 ms), indicating that the motor segmentation may depend on the internal rhythms. Thus, our results demonstrate two types of motor segmentation during synchronized movements: one is related to the hierarchical organization of sequential movements and the other is related to the spontaneous grouping of rhythmic events. This experimental paradigm can be used to investigate the underlying neural mechanism of temporal grouping during rhythm production.
Michael R. Traner; Ethan S. Bromberg-Martin; Ilya E. Monosov
Classic foraging theory predicts that humans and animals aim to gain maximum reward per unit time. However, in standard instrumental conditioning tasks individuals adopt an apparently suboptimal strategy: they respond slowly when the expected value is low. This reward-related bias is often explained as reduced motivation in response to low rewards. Here we present evidence this behavior is associated with a complementary increased motivation to search the environment for alternatives. We trained monkeys to search for reward-related visual targets in environments with different values. We found that the reward-related bias scaled with environment value, was consistent with persistent searching after the target was already found, and was associated with increased exploratory gaze to objects in the environment. A novel computational model of foraging suggests that this search strategy could be adaptive in naturalistic settings where both environments and the objects within them provide partial information about hidden, uncertain rewards.
Akash Umakantha; Rudina Morina; Benjamin R. Cowley; Adam C. Snyder; Matthew A. Smith; Byron M. Yu
Bridging neuronal correlations and dimensionality reduction Journal Article
In: Neuron, vol. 109, no. 17, pp. 2740–2754.e12, 2021.
Two commonly used approaches to study interactions among neurons are spike count correlation, which describes pairs of neurons, and dimensionality reduction, applied to a population of neurons. Although both approaches have been used to study trial-to-trial neuronal variability correlated among neurons, they are often used in isolation and have not been directly related. We first established concrete mathematical and empirical relationships between pairwise correlation and metrics of population-wide covariability based on dimensionality reduction. Applying these insights to macaque V4 population recordings, we found that the previously reported decrease in mean pairwise correlation associated with attention stemmed from three distinct changes in population-wide covariability. Overall, our work builds the intuition and formalism to bridge between pairwise correlation and population-wide covariability and presents a cautionary tale about the inferences one can make about population activity by using a single statistic, whether it be mean pairwise correlation or dimensionality.
Geoffrey K. Adams; Wei Song Ong; John M. Pearson; Karli K. Watson; Michael L. Platt
In: Philosophical Transactions of the Royal Society B: Biological Sciences, vol. 376, pp. 20190666, 2021.
Information about social partners is innately valuable to primates. Decisions about which sources of information to consume are highly naturalistic but also complex and place unusually strong demands on the brain's decision network. In particular, both the orbitofrontal cortex (OFC) and lateral prefrontal cortex (LPFC) play key roles in decision making and social behaviour, suggesting a likely role in social information-seeking as well. To test this idea, we developed a 'channel surfing' task in which monkeys were shown a series of 5 s video clips of conspecifics engaged in natural behaviours at a field site. Videos were annotated frame-by-frame using an ethogram of species-typical behaviours, an important source of social information. Between each clip, monkeys were presented with a choice between targets that determined which clip would be seen next. Monkeys' gaze during playback indicated differential engagement depending on what behaviours were presented. Neurons in both OFC and LPFC responded to choice targets and to video, and discriminated a subset of the behaviours in the ethogram during video viewing. These findings suggest that both OFC and LPFC are engaged in processing social information that is used to guide dynamic information-seeking decisions. This article is part of the theme issue 'Existence and prevalence of economic behaviours among non-human primates'.
Amir Akbarian; Kelsey Clark; Behrad Noudoost; Neda Nategh
In: Nature Communications, vol. 12, pp. 6449, 2021.
Saccadic eye movements (saccades) disrupt the continuous flow of visual information, yet our perception of the visual world remains uninterrupted. Here we assess the representation of the visual scene across saccades from single-trial spike trains of extrastriate visual areas, using a combined electrophysiology and statistical modeling approach. Using a model-based decoder we generate a high temporal resolution readout of visual information, and identify the specific changes in neurons' spatiotemporal sensitivity that underly an integrated perisaccadic representation of visual space. Our results show that by maintaining a memory of the visual scene, extrastriate neurons produce an uninterrupted representation of the visual world. Extrastriate neurons exhibit a late response enhancement close to the time of saccade onset, which preserves the latest pre-saccadic information until the post-saccadic flow of retinal information resumes. These results show how our brain exploits available information to maintain a representation of the scene while visual inputs are disrupted.
Ariana R. Andrei; Samantha Debes; Mircea Chelaru; Xiaoqin Liu; Elsa Rodarte; John L. Spudich; Roger Janz; Valentin Dragoi
In: eLife, vol. 10, pp. e66400, 2021.
Cortical inactivation represents a key causal manipulation allowing the study of cortical circuits and their impact on behavior. A key assumption in inactivation studies is that the neurons in the target area become silent while the surrounding cortical tissue is only negligibly impacted. However, individual neurons are embedded in complex local circuits composed of excitatory and inhibitory cells with connections extending hundreds of microns. This raises the possibility that silencing one part of the network could induce complex, unpredictable activity changes in neurons outside the targeted inactivation zone. These off-target side effects can potentially complicate inter-pretations of inactivation manipulations, especially when they are related to changes in behavior. Here, we demonstrate that optogenetic inactivation of glutamatergic neurons in the superficial layers of monkey primary visual cortex (V1) induces robust suppression at the light-targeted site, but destabilizes stimulus responses in the neighboring, untargeted network. We identified four types of stimulus-evoked neuronal responses within a cortical column, ranging from full suppression to facil-itation, and a mixture of both. Mixed responses were most prominent in middle and deep cortical layers. These results demonstrate that response modulation driven by lateral network connectivity is diversely implemented throughout a cortical column. Importantly, consistent behavioral changes induced by optogenetic inactivation were only achieved when cumulative network activity was homogeneously suppressed. Therefore, careful consideration of the full range of network changes outside the inactivated cortical region is required, as heterogeneous side effects can confound inter-pretation of inactivation experiments.
Benjamin M. Basile; Jessica A. Joiner; Olga Dal Monte; Nicholas A. Fagan; Chloe L. Karaskiewicz; Daniel R. Lucas; Steve W. C. Chang; Elisabeth A. Murray
In: Behavioral Neuroscience, vol. 135, no. 3, pp. 443–452, 2021.
The evolutionary and neural underpinnings of human prosociality are still being identified. A growing body of evidence suggests that some species find the sight of another individual receiving a reward reinforcing, called vicarious reinforcement, and that this capacity is supported by a network of brain areas including the anterior cingulate cortex (ACC) and the amygdala. At the same time, analyses of autonomic arousal have been increasingly used to contextualize and guide neural research, especially for studies of reward processing. Here, we characterized the autonomic pupil response of eight monkeys across two laboratories in two different versions of a vicarious reinforcement paradigm. Monkeys were cued as to whether an upcoming reward would be delivered to them, another monkey, or nobody and could accept or decline the offer. As expected, all monkeys in both laboratories showed a marked preference for juice to the self, together with a reliable prosocial preference for juice to a social partner compared to juice to nobody. However, contrary to our expectations, we found that pupils were widest in anticipation of juice to the self, moderately sized in anticipation of juice to nobody, and narrowest in anticipation of juice to a social partner. This effect was seen across both laboratories and regardless of specific task parameters. The seemingly paradoxical pupil effect can be explained by a model in which pupil size tracks outcome salience, prosocial tendencies track outcome valence, and the relation between salience and valence is U-shaped. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
André M. Bastos; Jacob A. Donoghue; Scott L. Brincat; Meredith Mahnke; Jorge Yanar; Josefina Correa; Ayan S. Waite; Mikael Lundqvist; Jefferson Roy; Emery N. Brown; Earl K. Miller
In: eLife, vol. 10, pp. e60824, 2021.
The specific circuit mechanisms through which anesthetics induce unconsciousness have not been completely characterized. We recorded neural activity from the frontal, parietal, and temporal cortices and thalamus while maintaining unconsciousness in non-human primates (NHPs) with the anesthetic propofol. Unconsciousness was marked by slow frequency ($sim$1 Hz) oscillations in local field potentials, entrainment of local spiking to Up states alternating with Down states of little or no spiking activity, and decreased coherence in frequencies above 4 Hz. Thalamic stimulation ‘awakened' anesthetized NHPs and reversed the electrophysiologic features of unconsciousness. Unconsciousness is linked to cortical and thalamic slow frequency synchrony coupled with decreased spiking, and loss of higher-frequency dynamics. This may disrupt cortical communication/integration.
Amarender R. Bogadhi; Leor N. Katz; Anil Bollimunta; David A. Leopold; Richard J. Krauzlis
In: Neuron, vol. 109, no. 4, pp. 690–699.e5, 2021.
Recent fMRI experiments identified an attention-related region in the macaque temporal cortex, here called the floor of the superior temporal sulcus (fSTS), as the primary cortical target of superior colliculus (SC) activity. However, it remains unclear which aspects of attention are processed by fSTS neurons and how or why these might depend on SC activity. Here, we show that SC inactivation decreases attentional modulations in fSTS neurons by increasing their activity for ignored stimuli in addition to decreasing their activity for attended stimuli. Neurons in the fSTS also exhibit event-related activity during attention tasks linked to detection performance, and this link is eliminated during SC inactivation. Finally, fSTS neurons respond selectively to particular visual objects, and this selectivity is reduced markedly during SC inactivation. These diverse, high-level properties of fSTS neurons all involve visual signals that carry behavioral relevance. Their dependence on SC activity could reflect a circuit that prioritizes cortical processing of events detected subcortically. Bogadhi and Katz et al. determine how activity from the midbrain superior colliculus (SC) is necessary for expression of high-level visual properties—attention-related modulation, event detection activity, and object-selective responses—in a newly identified region of the temporal cortex (fSTS) in primates.
Anna Bognár; Rufin Vogels
In: Journal of Neuroscience, vol. 41, no. 30, pp. 6484–6501, 2021.
Current models of object recognition are based on spatial representations build from object features that are simultaneously present in the retinal image. However, one can recognize an object when it moves behind a static occlude, and only a small fragment of its shape is visible through a slit at a given moment in time. Such anorthoscopic perception requires spatiotemporal integration of the successively presented shape parts during slit-viewing. Human fMRI studies suggested that ventral visual stream areas represent whole shapes formed through temporal integration during anorthoscopic perception. To examine the time course of shape-selective responses during slit-viewing, we recorded the responses of single inferior temporal (IT) neurons of rhesus monkeys to moving shapes that were only partially visible through a static narrow slit. The IT neurons signaled shape identity by their response when that was cumulated across the duration of the shape presentation. Their shape preference during slit-viewing equaled that for static, whole-shape presentations. However, when analyzing their responses at a finer time scale, we showed that the IT neurons responded to particular shape fragments that were revealed by the slit. We found no evidence for temporal integration of slit-views that result in a whole-shape representation, even when the monkey was matching slit-views of a shape to static whole-shape presentations. These data suggest that, although the temporally integrated response of macaque IT neurons can signal shape identity in slit-viewing conditions, the spatiotemporal integration needed for the formation of a whole-shape percept occurs in other areas, perhaps downstream to IT.
Scott L. Brincat; Jacob A. Donoghue; Meredith K. Mahnke; Simon Kornblith; Mikael Lundqvist; Earl K. Miller
Interhemispheric transfer of working memories Journal Article
In: Neuron, vol. 109, no. 6, pp. 1055–1066, 2021.
Visual working memory (WM) storage is largely independent between the left and right visual hemifields/cerebral hemispheres, yet somehow WM feels seamless. We studied how WM is integrated across hemifields by recording neural activity bilaterally from lateral prefrontal cortex. An instructed saccade during the WM delay shifted the remembered location from one hemifield to the other. Before the shift, spike rates and oscillatory power showed clear signatures of memory laterality. After the shift, the lateralization inverted, consistent with transfer of the memory trace from one hemisphere to the other. Transferred traces initially used different neural ensembles from feedforward-induced ones, but they converged at the end of the delay. Around the time of transfer, synchrony between the two prefrontal hemispheres peaked in theta and beta frequencies, with a directionality consistent with memory trace transfer. This illustrates how dynamics between the two cortical hemispheres can stitch together WM traces across visual hemifields.
Sophie Brulé; Bastien Herlin; Pierre Pouget; Marcus Missal
Ketamine reduces temporal expectation in the rhesus monkey Journal Article
In: Psychopharmacology, vol. 238, no. 2, pp. 559–567, 2021.
Rationale: Ketamine, a well-known general dissociative anesthetic agent that is a non-competitive antagonist of the N-methyl-D-aspartate receptor, perturbs the perception of elapsed time and the expectation of upcoming events. Objective: The objective of this study was to determine the influence of ketamine on temporal expectation in the rhesus monkey. Methods: Two rhesus monkeys were trained to make a saccade between a central warning stimulus and an eccentric visual target that served as imperative stimulus. The delay between the warning and the imperative stimulus could take one of four different values randomly with the same probability (variable foreperiod paradigm). During experimental sessions, a subanesthetic low dose of ketamine (0.25–0.35 mg/kg) was injected i.m. and the influence of the drug on movement latency was measured. Results: We found that in the control conditions, saccadic latencies strongly decreased with elapsed time before the appearance of the visual target showing that temporal expectation built up during the delay period between the warning and the imperative stimulus. However, after ketamine injection, temporal expectation was significantly reduced in both subjects. In addition, ketamine also increased average movement latency but this effect could be dissociated from the reduction of temporal expectation. Conclusion: In conclusion, a subanesthetic dose of ketamine could have two independent effects: increasing reaction time and decreasing temporal expectation. This alteration of temporal expectation could explain cognitive deficits observed during ketamine use.
Matan Cain; Yehudit Botschko; Mati Joshua
In: eNeuro, vol. 8, no. 2, pp. 1–12, 2021.
Motor adaptation is commonly thought to be a trial-and-error process in which the accuracy of movement improves with repetition of behavior. We challenged this view by testing whether erroneous movements are necessary for motor adaptation. In the eye movement system, the association between movements and errors can be disentangled, since errors in the predicted stimulus trajectory can be perceived even without movements. We modified a smooth pursuit eye movement adaptation paradigm in which monkeys learn to make an eye movement that predicts an upcoming change in target direction. We trained the monkeys to fixate on a target while covertly, an additional target initially moved in one direction and then changed direction after 250 ms. The monkeys showed a learned response to infre-quent probe trials in which they were instructed to follow the moving target. Additional experiments confirmed that probing learning or residual eye movements during fixation did not drive learning. These results show that motor adaptation can be elicited in the absence of movement and provide an animal model for studying the implementation of passive motor learning. Current models assume that the interaction between movement and error signals underlies adaptive motor learning. Our results point to other mechanisms that may drive learning in the absence of movement.
I. Caprara; P. Janssen
The causal role of three frontal cortical areas in grasping Journal Article
In: Cerebral Cortex, vol. 31, no. 9, pp. 4274–4288, 2021.
Efficient object grasping requires the continuous control of arm and hand movements based on visual information. Previous studies have identified a network of parietal and frontal areas that is crucial for the visual control of prehension movements. Electrical microstimulation of 3D shape-selective clusters in AIP during functional magnetic resonance imaging activates areas F5a and 45B, suggesting that these frontal areas may represent important downstream areas for object processing during grasping, but the role of area F5a and 45B in grasping is unknown. To assess their causal role in the frontal grasping network, we reversibly inactivated 45B, F5a, and F5p during visually guided grasping in macaque monkeys. First, we recorded single neuron activity in 45B, F5a, and F5p to identify sites with object responses during grasping. Then, we injected muscimol or saline to measure the grasping deficit induced by the temporary disruption of each of these three nodes in the grasping network. The inactivation of all three areas resulted in a significant increase in the grasping time in both animals, with the strongest effect observed in area F5p. These results not only confirm a clear involvement of F5p, but also indicate causal contributions of area F5a and 45B in visually guided object grasping.
Valeria C. Caruso; Daniel S. Pages; Marc A. Sommer; Jennifer M. Groh
In: Journal of Neurophysiology, vol. 126, pp. 82–94, 2021.
Stimulus locations are detected differently by different sensory systems, but ultimately they yield similar percepts and behavioral responses. How the brain transcends initial differences to compute similar codes is unclear. We quantitatively compared the reference frames of two sensory modalities, vision and audition, across three interconnected brain areas involved in generating saccades, namely the frontal eye fields (FEF), lateral and medial parietal cortex (LIP/MIP), and superior colliculus (SC). We recorded from single neurons in head-restrained monkeys performing auditory- and visually-guided saccades from variable initial fixation locations, and evaluated whether their receptive fields were better described as eye-centered, head-centered, or hybrid (i.e. not anchored uniquely to head- or eye-orientation). We found a progression of reference frames across areas and across time, with considerable hybrid-ness and persistent differences between modalities during most epochs/brain regions. For both modalities, the SC was more eye-centered than the FEF, which in turn was more eye-centered than the predominantly hybrid LIP/MIP. In all three areas and temporal epochs from stimulus onset to movement, visual signals were more eye-centered than auditory signals. In the SC and FEF, auditory signals became more eye-centered at the time of the saccade than they were initially after stimulus onset, but only in the SC at the time of the saccade did the auditory signals become predominantly eye-centered. The results indicate that visual and auditory signals both undergo transformations, ultimately reaching the same final reference frame but via different dynamics across brain regions and time. SIGNIFICANCE STATEMENT Models for visual-auditory integration posit that visual signals are eye-centered throughout the brain, while auditory signals are converted from head-centered to eye-centered coordinates. We show instead that both modalities largely employ hybrid reference frames: neither fully head-nor eye-centered. In three multimodal regions involved in orienting behaviors (Intraparietal Cortex, Frontal Eye Field and Superior Colliculus) these mixed codes persist in various proportions, shifting towards eye-centeredness both across time and across brain areas. Throughout, visual signals are more eye-centered than auditory signals, until a common predominantly eye-centered code for sound finally emerges during the saccade burst in the Superior Colliculus. In summary, visual and auditory signals reach the same final reference frame but via different dynamics across brain regions and time.
Mircea I. Chelaru; Sarah Eagleman; Ariana R. Andrei; Russell Milton; Natasha Kharas; Valentin Dragoi
In: Neuron, vol. 109, no. 24, pp. 3954–3961, 2021.
One influential view in neuroscience is that pairwise cell interactions explain the firing patterns of large populations. Despite its prevalence, this view originates from studies in the retina and visual cortex of anesthetized animals. Whether pairwise interactions predict the firing patterns of neurons across multiple brain areas in behaving animals remains unknown. Here, we performed multi-area electrical recordings to find that 2nd-order interactions explain a high fraction of entropy of the population response in macaque cortical areas V1 and V4. Surprisingly, despite the brain-state modulation of neuronal responses, the model based on pairwise interactions captured ∼90% of the spiking activity structure during wakefulness and sleep. However, regardless of brain state, pairwise interactions fail to explain experimentally observed entropy in neural populations from the prefrontal cortex. Thus, while simple pairwise interactions explain the collective behavior of visual cortical networks across brain states, explaining the population dynamics in downstream areas involves higher-order interactions.
Jan Churan; Andre Kaminiarz; Jakob C. B. Schwenk; Frank Bremmer
In: Journal of Neurophysiology, vol. 125, no. 6, pp. 2432–2443, 2021.
Successful interaction with the environment requires the dissociation of self-induced from externally induced sensory stimulation. Temporal proximity of action and effect is hereby often used as an indicator of whether an observed event should be interpreted as a result of own actions or not. We tested how the delay between an action (press of a touch bar) and an effect (onset of simulated self-motion) influences the processing of visually simulated self-motion in the ventral intraparietal area (VIP) of macaque monkeys. We found that a delay between the action and the start of the self-motion stimulus led to a rise of activity above the baseline activity before motion onset in a subpopulation of 21% of the investigated neurons. In the responses to the stimulus, we found a significantly lower sustained activity when the press of a touch bar and the motion onset were contiguous compared to the condition when the motion onset was delayed. We speculate that this weak inhibitory effect might be part of a mechanism that sharpens the tuning of VIP neurons during self-induced motion and thus has the potential to increase the precision of heading information that is required to adjust the orientation of self-motion in everyday navigational tasks. NEW & NOTEWORTHY Neurons in macaque ventral intraparietal area (VIP) are responding to sensory stimulation related to self-motion, e.g. visual optic flow. Here, we found that self-motion induced activation depends on the sense of agency, i.e., it differed when optic flow was perceived as self- or externally induced. This demonstrates that area VIP is well suited for study of the interplay between active behavior and sensory processing during self-motion.
Jan Churan; Andre Kaminiarz; Jakob C. B. Schwenk; Frank Bremmer
In: Brain Structure and Function, vol. 226, no. 8, pp. 2707–2723, 2021.
The oculomotor system can initiate remarkably accurate saccades towards moving targets (interceptive saccades) the processing of which is still under debate. The generation of these saccades requires the oculomotor centers to have information about the motion parameters of the target that then must be extrapolated to bridge the inherent processing delays. We investigated to what degree the information about motion of a saccade target is available in the lateral intra-parietal area (area LIP) of macaque monkeys for generation of accurate interceptive saccades. When a multi-layer neural network was trained based on neural discharges from area LIP around the time of saccades towards stationary targets, it was also able to predict the end points of saccades directed towards moving targets. This prediction, however, lagged behind the actual post-saccadic position of the moving target by $sim$ 80 ms when the whole neuronal sample of 105 neurons was used. We further found that single neurons differentially code for the motion of the target. Selecting neurons with the strongest representation of target motion reduced this lag to $sim$ 30 ms which represents the position of the moving target approximately at the onset of the interceptive saccade. We conclude that—similarly to recent findings from the Superior Colliculus (Goffart et al. J Neurophysiol 118(5):2890–2901)—there is a continuum of contributions of individual LIP neurons to the accuracy of interceptive saccades. A contribution of other gaze control centers (like the cerebellum or the frontal eye field) that further increase the saccadic accuracy is, however, likely.
Thomas Decramer; Elsie Premereur; Irene Caprara; Tom Theys; Peter Janssen
In: NeuroImage, vol. 236, pp. 118088, 2021.
The cortical network controlling the arm and hand when grasping objects consists of several areas in parietal and frontal cortex. Recently, more anterior prefrontal areas have also been implicated in object grasping, but their exact role is currently unclear. To investigate the neuronal encoding of objects during grasping in these prefrontal regions and their relation with other cortical areas of the grasping network, we performed large-scale recordings (more than 2000 responsive sites) in frontal cortex of monkeys during a saccade-reach-grasp task. When an object appeared in peripheral vision, the first burst of activity emerged in prearcuate areas (the FEF and area 45B), followed by dorsal and ventral premotor cortex, and a buildup of activity in primary motor cortex. After the saccade, prearcuate activity remained elevated while primary motor and premotor activity rose in anticipation of the upcoming arm and hand movement. Remarkably, a large number of premotor and prearcuate sites responded when the object appeared in peripheral vision and remained active when the object came into foveal vision. Thus, prearcuate and premotor areas continuously encode object information when directing gaze and grasping objects.
Kacie Dougherty; Brock M. Carlson; Michele A. Cox; Jacob A. Westerberg; Wolf Zinke; Michael C. Schmid; Paul R. Martin; Alexander Maier
In: eNeuro, vol. 8, no. 2, pp. 1–12, 2021.
The lateral geniculate nucleus (LGN) of the dorsal thalamus is the primary recipient of the two eyes' outputs. Most LGN neurons are monocular in that they are activated by visual stimulation through only one (dominant) eye. However, there are both intrinsic connections and inputs from binocular structures to the LGN that could provide these neurons with signals originating from the other (non-dominant) eye. Indeed, previous work introducing luminance differences across the eyes or using a single-contrast stimulus showed binocular modulation for single unit activity in anesthetized macaques and multiunit activity in awake macaques. Here, we sought to determine the influence of contrast viewed by both the non-dominant and dominant eyes on LGN single-unit responses in awake macaques. To do this, we adjusted each eye's signal strength by independently varying the contrast of stimuli presented to the two eyes. Specifically, we recorded LGN single unit spiking activity in two awake macaques while they viewed drifting gratings of varying contrast. We found that LGN neurons of all types [parvocellular (P), magno-cellular (M), and koniocellular (K)] were significantly suppressed when stimuli were presented at low contrast to the dominant eye and at high contrast to the non-dominant eye. Further, the inputs of the two eyes showed antagonistic interaction, whereby the magnitude of binocular suppression diminished with high contrast in the dominant eye, or low contrast in the non-dominant eye. These results suggest that the LGN represents a site of precortical binocular processing involved in resolving discrepant contrast differences between the eyes.
Yang Zhou; Matthew C. Rosen; Sruthi K. Swaminathan; Nicolas Y. Masse; Ou Zhu; David J. Freedman
In: eLife, vol. 10, pp. 1–30, 2021.
Comparing sequential stimuli is crucial for guiding complex behaviors. To understand mechanisms underlying sequential decisions, we compared neuronal responses in the prefrontal cortex (PFC), the lateral intraparietal (LIP), and medial intraparietal (MIP) areas in monkeys trained to decide whether sequentially presented stimuli were from matching (M) or nonmatching (NM) categories. We found that PFC leads M/NM decisions, whereas LIP and MIP appear more involved in stimulus evaluation and motor planning, respectively. Compared to LIP, PFC showed greater nonlinear integration of currently visible and remembered stimuli, which correlated with the monkeys' M/NM decisions. Furthermore, multi-module recurrent networks trained on the same task exhibited key features of PFC and LIP encoding, including nonlinear integration in the PFC-like module, which was causally involved in the networks' decisions. Network analysis found that nonlinear units have stronger and more widespread connections with input, output, and within-area units, indicating putative circuit-level mechanisms for sequential decisions.
Mengxi Yun; Masafumi Nejime; Masayuki Matsumoto
Single-unit recording in awake behaving non-human primates Journal Article
In: Bio-protocol, vol. 11, no. 8, pp. 1–16, 2021.
Non-human primates (NHPs) have been widely used as a species model in studies to understand higher brain functions in health and disease. These studies employ specifically designed behavioral tasks in which animal behavior is well-controlled, and record neuronal activity at high spatial and temporal resolutions while animals are performing the tasks. Here, we present a detailed procedure to conduct single-unit recording, which fulfils high spatial and temporal resolutions while macaque monkeys (i.e., widely used NHPs) perform behavioral tasks in a well-controlled manner. This procedure was used in our previous study to investigate the dynamics of neuronal activity during economic decision-making by the monkeys. Monkeys' behavior was quantitated by eye position tracking and button press/release detection. By inserting a microelectrode into the brain, with a grid system in reference to magnetic resonance imaging, we precisely recorded the brain regions. Our experimental system permits rigorous investigation of the link between neuronal activity and behavior.
Beizhen Zhang; Janis Ying Ying Kan; Mingpo Yang; Xiaochun Wang; Jiahao Tu; Michael Christopher Dorris
In: Nature Communications, vol. 12, no. 1, pp. 3410, 2021.
Value-based decision making involves choosing from multiple options with different values. Despite extensive studies on value representation in various brain regions, the neural mechanism for how multiple value options are converted to motor actions remains unclear. To study this, we developed a multi-value foraging task with varying menu of items in non-human primates using eye movements that dissociates value and choice, and conducted electrophysiological recording in the midbrain superior colliculus (SC). SC neurons encoded “absolute” value, independent of available options, during late fixation. In addition, SC neurons also represent value threshold, modulated by available options, different from conventional motor threshold. Electrical stimulation of SC neurons biased choices in a manner predicted by the difference between the value representation and the value threshold. These results reveal a neural mechanism directly transforming absolute values to categorical choices within SC, supporting highly efficient value-based decision making critical for real-world economic behaviors.
Manoj K Eradath; Mark A Pinsk; Sabine Kastner
In: Journal of Comparative Neurology, vol. 529, no. 17, pp. 3772–3784, 2021.
The pulvinar is the largest nucleus in the primate thalamus and has topographically organized connections with multiple cortical areas, thereby forming extensive cortico-pulvino-cortical input–output loops. Neurophysiological studies have suggested a role for these transthalamic pathways in regulating information transmission between cortical areas. However, evidence for a causal role of the pulvinar in regulating cortico–cortical interactions is sparse and it is not known whether pulvinar's influences on cortical networks are task-dependent or, alternatively, reflect more basic large-scale network properties that maintain functional connectivity across networks regardless of active task demands. In the current study, under passive viewing conditions, we conducted simultaneous electrophysiological recordings from ventral (area V4) and dorsal (lateral intraparietal area [LIP]) nodes of macaque visual system, while reversibly inactivating the dorsal part of the lateral pulvinar (dPL), which shares common anatomical connectivity with V4 and LIP, to probe a causal role of the pulvinar. Our results show a significant reduction in local field potential phase coherence between LIP and V4 in low frequencies (4–15 Hz) following muscimol injection into dPL. At the local level, no significant changes in firing rates or LFP power were observed in LIP or in V4 following dPL inactivation. Synchronization between pulvinar spikes and cortical LFP phase decreased in low frequencies (4–15 Hz) both in LIP and V4, while the low frequency synchronization between LIP spikes and pulvinar phase increased. These results indicate a causal role for pulvinar in synchronizing neural activity between interconnected cortical nodes of a large-scale network, even in the absence of an active task state.
Francesco Fabbrini; Rufin Vogels
In: Journal of Neurophysiology, vol. 125, no. 1, pp. 1–20, 2021.
The decrease in response with stimulus repetition is a common property observed in many sensory brain areas. This repetition suppression (RS) is ubiquitous in neurons of macaque inferior temporal (IT) cortex, the end-stage of the ventral visual pathway. The neural mechanisms of RS in IT are still unclear, and one possibility is that it is inherited from areas upstream to IT that show also RS. Since neurons in IT have larger receptive fields compared to earlier visual areas, we examined the inheritance hypothesis by presenting adapter and test stimuli at widely different spatial locations along both vertical and horizontal meridians, and across hemifields. RS was present for distances between adapter and test stimuli up to 22°, and when the two stimuli were presented in different hemifields. Also, we examined the position tolerance of the stimulus selectivity of adaptation by comparing the responses to a test stimulus following the same (repetition trial) or a different adapter (alternation trial) at a different position than the test stimulus. Stimulus-selective adaptation was still present and consistently stronger in the later phase of the response for distances up to 18°. Finally, we observed stimulus-selective adaptation in repetition trials even without a measurable excitatory response to the adapter stimulus. To accommodate these and previous data, we propose that at least part of the stimulus-selective adaptation in IT is based on short-term plasticity mechanisms within IT and/or reflects top-down activity from areas downstream to IT.
Francesco Fabbrini; Rufin Vogels
In: Journal of Neurophysiology, vol. 125, no. 1, pp. 120–139, 2021.
The decrease in response with stimulus repetition is a common property observed in many sensory brain areas. This repetition suppression (RS) is ubiquitous in neurons of macaque inferior temporal (IT) cortex, the end-stage of the ventral visual pathway. The neural mechanisms of RS in IT are still unclear, and one possibility is that it is inherited from areas upstream to IT that show also RS. Since neurons in IT have larger receptive fields compared with earlier visual areas, we examined the inheritance hypothesis by presenting adapter and test stimuli at widely different spatial locations along both vertical and horizontal meridians and across hemifields. RS was present for distances between adapter and test stimuli up to 22° and when the two stimuli were presented in different hemifields. Also, we examined the position tolerance of the stimulus selectivity of adaptation by comparing the responses to a test stimulus following the same (repetition trial) or a different (alternation trial) adapter at a position different from the test stimulus. Stimulus-selective adaptation was still present and consistently stronger in the later phase of the response for distances up to 18°. Finally, we observed stimulus-selective adaptation in repetition trials even without a measurable excitatory response to the adapter stimulus. To accommodate these and previous data, we propose that at least part of the stimulusselective adaptation in IT is based on short-term plasticity mechanisms within IT and/or reflects top-down activity from areas downstream to IT.
Dylan Festa; Amir Aschner; Aida Davila; Adam Kohn; Ruben Coen-Cagli
In: Nature Communications, vol. 12, pp. 3635, 2021.
Neuronal activity in sensory cortex fluctuates over time and across repetitions of the same input. This variability is often considered detrimental to neural coding. The theory of neural sampling proposes instead that variability encodes the uncertainty of perceptual inferences. In primary visual cortex (V1), modulation of variability by sensory and non-sensory factors supports this view. However, it is unknown whether V1 variability reflects the statistical structure of visual inputs, as would be required for inferences correctly tuned to the statistics of the natural environment. Here we combine analysis of image statistics and recordings in macaque V1 to show that probabilistic inference tuned to natural image statistics explains the widely observed dependence between spike count variance and mean, and the modulation of V1 activity and variability by spatial context in images. Our results show that the properties of a basic aspect of cortical responses—their variability—can be explained by a probabilistic representation tuned to naturalistic inputs.
Ian C. Fiebelkorn; Sabine Kastner
In: Neuron, vol. 109, no. 1, pp. 177–188, 2021.
There has been little evidence linking changes in spiking activity that occur prior to a spatially predictable target (i.e., prior to target selection) to behavioral outcomes, despite such preparatory changes being widely assumed to enhance the sensitivity of sensory processing. We simultaneously recorded from frontal and parietal nodes of the attention network while macaques performed a spatial cueing task. When anticipating a spatially predictable target, different patterns of coupling between spike timing and the oscillatory phase in local field potentials—but not changes in spike rate—were predictive of different behavioral outcomes. These behaviorally relevant differences in local and between-region synchronization occurred among specific cell types that were defined based on their sensory and motor properties, providing insight into the mechanisms underlying enhanced sensory processing prior to target selection. We propose that these changes in neural synchronization reflect differential anticipatory engagement of the network nodes and functional units that shape attention-related sampling.
Supriya Ghosh; John H. R. Maunsell
In: Nature Communications, vol. 12, pp. 2003, 2021.
Understanding how activity of visual neurons represents distinct components of attention and their dynamics that account for improved visual performance remains elusive because single-unit experiments have not isolated the intensive aspect of attention from attentional selectivity. We isolated attentional intensity and its single trial dynamics as determined by spatially non-selective attentional performance in an orientation discrimination task while recording from neurons in monkey visual area V4. We found that attentional intensity is a distinct cognitive signal that can be distinguished from spatial selectivity, reward expectations and motor actions. V4 spiking on single trials encodes a combination of sensory and cognitive signals on different time scales. Attentional intensity and the detection of behaviorally relevant sensory signals are well represented, but immediate reward expectation and behavioral choices are poorly represented in V4 spiking. These results provide a detailed representation of perceptual and cognitive signals in V4 that are crucial for attentional performance.
Jay A. Hennig; Emily R. Oby; Matthew D. Golub; Lindsay A. Bahureksa; Patrick T. Sadtler; Kristin M. Quick; Stephen I. Ryu; Elizabeth C. Tyler-Kabara; Aaron P. Batista; Steven M. Chase; Byron M. Yu
Learning is shaped by abrupt changes in neural engagement Journal Article
In: Nature Neuroscience, vol. 24, no. 5, pp. 727–736, 2021.
Internal states such as arousal, attention and motivation modulate brain-wide neural activity, but how these processes interact with learning is not well understood. During learning, the brain modifies its neural activity to improve behavior. How do internal states affect this process? Using a brain–computer interface learning paradigm in monkeys, we identified large, abrupt fluctuations in neural population activity in motor cortex indicative of arousal-like internal state changes, which we term ‘neural engagement.' In a brain–computer interface, the causal relationship between neural activity and behavior is known, allowing us to understand how neural engagement impacted behavioral performance for different task goals. We observed stereotyped changes in neural engagement that occurred regardless of how they impacted performance. This allowed us to predict how quickly different task goals were learned. These results suggest that changes in internal states, even those seemingly unrelated to goal-seeking behavior, can systematically influence how behavior improves with learning.
Jerome Herpers; John T. Arsenault; Wim Vanduffel; Rufin Vogels
In: Cell Reports, vol. 37, no. 6, pp. 109998, 2021.
fMRI studies have shown that pairing a task-irrelevant visual feature with electrical micro-stimulation of the ventral tegmental area (VTA-EM) is sufficient to increase the sensory cortical representation of the paired feature and to improve perceptual performance. However, since fMRI provides an indirect measure of neural activity, the neural response changes underlying the fMRI activations are unknown. Here, we pair a task-irrelevant grating orientation with VTA-EM while attention is directed to a difficult orthogonal task. We examine the changes in neural response properties in macaques by recording spiking activity in the posterior inferior temporal cortex, the locus of fMRI-defined plasticity in previous studies. We observe a relative increase in mean spike rate and preference for the VTA-EM paired orientation compared to an unpaired orientation, which is unrelated to attention. These results demonstrate that VTA-EM-stimulus pairing is sufficient to induce sensory cortical plasticity at the spiking level in nonhuman primates.
Georgin Jacob; Harish Katti; Thomas Cherian; Jhilik Das; K. A. Zhivago; S. P. Arun
In: eLife, vol. 10, pp. 1–30, 2021.
Macaque monkeys are widely used to study vision. In the traditional approach, monkeys are brought into a lab to perform visual tasks while they are restrained to obtain stable eye tracking and neural recordings. Here, we describe a novel environment to study visual cognition in a more natural setting as well as other natural and social behaviors. We designed a naturalistic environment with an integrated touchscreen workstation that enables high-quality eye tracking in unrestrained monkeys. We used this environment to train monkeys on a challenging same-different task. We also show that this environment can reveal interesting novel social behaviors. As proof of concept, we show that two naïve monkeys were able to learn this complex task through a combination of socially observing trained monkeys and through solo trialand-error. We propose that such naturalistic environments can be used to rigorously study visual cognition as well as other natural and social behaviors in freely moving monkeys.
Patrick Jendritza; Frederike J. Klein; Gustavo Rohenkohl; Pascal Fries
In: eNeuro, vol. 8, no. 3, pp. 1–16, 2021.
The marmoset has emerged as a promising primate model system, in particular for visual neuroscience. Many common experimental paradigms rely on head fixation and an extended period of eye fixation during the pre-sentation of salient visual stimuli. Both of these behavioral requirements can be challenging for marmosets. Here, we present two methodological developments, each addressing one of these difficulties. First, we show that it is possible to use a standard eye-tracking system without head fixation to assess visual behavior in the marmoset. Eye-tracking quality from head-free animals is sufficient to obtain precise psychometric functions from a visual acuity task. Second, we introduce a novel method for efficient receptive field (RF) mapping that does not rely on moving stimuli but uses fast flashing annuli and wedges. We present data recorded during head-fixation in areas V1 and V6 and show that RF locations are readily obtained within a short period of recording time. Thus, the methodological advancements presented in this work will contribute to establish the marmoset as a valuable model in neuroscience.
Ahmad Jezzini; Ethan S. Bromberg-Martin; Lucas R. Trambaiolli; Suzanne N. Haber; Ilya E. Monosov
In: Neuron, vol. 109, no. 14, pp. 2339–2352, 2021.
Humans and animals can be strongly motivated to seek information to resolve uncertainty about rewards and punishments. In particular, despite its clinical and societal relevance, very little is known about information seeking about punishments. We show that attitudes toward information about punishments and rewards are distinct and separable at both behavioral and neuronal levels. We demonstrate the existence of prefrontal neuronal populations that anticipate opportunities to gain information in a relatively valence-specific manner, separately anticipating information about either punishments or rewards. These neurons are located in anatomically interconnected subregions of anterior cingulate cortex (ACC) and ventrolateral prefrontal cortex (vlPFC) in area 12o/47. Unlike ACC, vlPFC also contains a population of neurons that integrate attitudes toward both reward and punishment information, to encode the overall preference for information in a bivalent manner. This cortical network is well suited to mediate information seeking by integrating the desire to resolve uncertainty about multiple, distinct motivational outcomes.
Elizabeth J. Jun; Alex R. Bautista; Michael D. Nunez; Daicia C. Allen; Jung H. Tak; Eduardo Alvarez; Michele A. Basso
In: Nature Neuroscience, vol. 24, no. 8, pp. 1121–1131, 2021.
Trained monkeys performed a two-choice perceptual decision-making task in which they reported the perceived orientation of a dynamic Glass pattern, before and after unilateral, reversible, inactivation of a brainstem area—the superior colliculus (SC)—involved in preparing eye movements. We found that unilateral SC inactivation produced significant decision biases and changes in reaction times consistent with a causal role for the primate SC in perceptual decision-making. Fitting signal detection theory and sequential sampling models to the data showed that SC inactivation produced a decrease in the relative evidence for contralateral decisions, as if adding a constant offset to a time-varying evidence signal for the ipsilateral choice. The results provide causal evidence for an embodied cognition model of perceptual decision-making and provide compelling evidence that the SC of primates (a brainstem structure) plays a causal role in how evidence is computed for decisions—a process usually attributed to the forebrain.
Joonyoung Kang; Hyeji Kim; Seong Hwan Hwang; Minjun Han; Sue Hyun Lee; Hyoung F. Kim
In: Nature Communications, vol. 12, pp. 2100, 2021.
The ventral striatum (VS) is considered a key region that flexibly updates recent changes in reward values for habit learning. However, this update process may not serve to maintain learned habitual behaviors, which are insensitive to value changes. Here, using fMRI in humans and single-unit electrophysiology in macaque monkeys we report another role of the primate VS: that the value memory subserving habitual seeking is stably maintained in the VS. Days after object-value associative learning, human and monkey VS continue to show increased responses to previously rewarded objects, even when no immediate reward outcomes are expected. The similarity of neural response patterns to each rewarded object increases after learning among participants who display habitual seeking. Our data show that long-term memory of high-valued objects is retained as a single representation in the VS and may be utilized to evaluate visual stimuli automatically to guide habitual behavior.
Kohitij Kar; James J. DiCarlo
In: Neuron, vol. 109, no. 1, pp. 164–176, 2021.
Distributed neural population spiking patterns in macaque inferior temporal (IT) cortex that support core object recognition require additional time to develop for specific, “late-solved” images. This suggests the necessity of recurrent processing in these computations. Which brain circuits are responsible for computing and transmitting these putative recurrent signals to IT? To test whether the ventrolateral prefrontal cortex (vlPFC) is a critical recurrent node in this system, here, we pharmacologically inactivated parts of vlPFC and simultaneously measured IT activity while monkeys performed object discrimination tasks. vlPFC inactivation deteriorated the quality of late-phase (>150 ms from image onset) IT population code and produced commensurate behavioral deficits for late-solved images. Finally, silencing vlPFC caused the monkeys' IT activity and behavior to become more like those produced by feedforward-only ventral stream models. Together with prior work, these results implicate fast recurrent processing through vlPFC as critical to producing behaviorally sufficient object representations in IT.
Amit P. Khandhadia; Aidan P. Murphy; Lizabeth M. Romanski; Jennifer K. Bizley; David A. Leopold
Audiovisual integration in macaque face patch neurons Journal Article
In: Current Biology, vol. 31, no. 9, pp. 1826–1835, 2021.
Primate social communication depends on the perceptual integration of visual and auditory cues, reflected in the multimodal mixing of sensory signals in certain cortical areas. The macaque cortical face patch network, identified through visual, face-selective responses measured with fMRI, is assumed to contribute to visual social interactions. However, whether face patch neurons are also influenced by acoustic information, such as the auditory component of a natural vocalization, remains unknown. Here, we recorded single-unit activity in the anterior fundus (AF) face patch, in the superior temporal sulcus, and anterior medial (AM) face patch, on the undersurface of the temporal lobe, in macaques presented with audiovisual, visual-only, and auditory-only renditions of natural movies of macaques vocalizing. The results revealed that 76% of neurons in face patch AF were significantly influenced by the auditory component of the movie, most often through enhancement of visual responses but sometimes in response to the auditory stimulus alone. By contrast, few neurons in face patch AM exhibited significant auditory responses or modulation. Control experiments in AF used an animated macaque avatar to demonstrate, first, that the structural elements of the face were often essential for audiovisual modulation and, second, that the temporal modulation of the acoustic stimulus was more important than its frequency spectrum. Together, these results identify a striking contrast between two face patches and specifically identify AF as playing a potential role in the integration of audiovisual cues during natural modes of social communication.
Taekjun Kim; Wyeth Bair; Anitha Pasupathy
In: Journal of Neuroscience, pp. 1–51, 2021.
Texture is an important visual attribute for surface pattern discrimination and therefore object segmentation, but the neural bases of texture perception are largely unknown. Previously, we demonstrated that the responses of V4 neurons to naturalistic texture patches are sensitive to four key features of human texture perception: coarseness, directionality, regularity, and contrast. To begin to understand how distinct texture perception emerges from the dynamics of neuronal responses, in 2 macaque monkeys (1 male, 1 female), we investigated the relative contribution of the four texture attributes to V4 responses in terms of the strength and timing of response modulation. We found that the different feature dimensions are associated with different temporal dynamics. Specifically, the response modulation associated with directionality and regularity was significantly delayed relative to that associated with coarseness and contrast, suggesting that the latter are fundamentally simpler feature dimensions. The population of texture-selective neurons could be grouped into multiple clusters based on the combination of feature dimensions encoded, and those subpopulations displayed distinct temporal dynamics characterized by the weighted combinations of multiple features. Finally, we applied a population decoding approach to demonstrate that texture category information can be obtained from short temporal windows across time. These results demonstrate that the representation of different perceptually relevant texture features emerge over time in the responses of V4 neurons. The observed temporal organization provides a framework to interpret how the processing of surface features unfolds in early and midlevel cortical stages, and could ultimately inform the interpretation of perceptual texture dynamics.Significance Statement:To delineate how neuronal responses underlie our ability to perceive visual textures, we related four key perceptual dimensions (coarseness, directionality, regularity, and contrast) of naturalistic textures to the strength and timing of modulation of neuronal responses in area V4, an intermediate stage in the form-processing, ventral visual pathway. Our results provide the first characterization of V4 temporal dynamics for texture encoding along perceptually defined axes.
Eric B. Knudsen; Joni D. Wallis
Hippocampal neurons construct a map of an abstract value space Journal Article
In: Cell, vol. 184, no. 18, pp. 4640–4650, 2021.
The hippocampus is thought to encode a “cognitive map,” a structural organization of knowledge about relationships in the world. Place cells, spatially selective hippocampal neurons that have been extensively studied in rodents, are one component of this map, describing the relative position of environmental features. However, whether this map extends to abstract, cognitive information remains unknown. Using the relative reward value of cues to define continuous “paths” through an abstract value space, we show that single neurons in primate hippocampus encode this space through value place fields, much like a rodent's place neurons encode paths through physical space. Value place fields remapped when cues changed but also became increasingly correlated across contexts, allowing maps to become generalized. Our findings help explain the critical contribution of the hippocampus to value-based decision-making, providing a mechanism by which knowledge of relationships in the world can be incorporated into reward predictions for guiding decisions.
Kenji W. Koyano; Adam P. Jones; David B. T. McMahon; Elena N. Waidmann; Brian E. Russ; David A. Leopold
In: Current Biology, vol. 31, no. 1, pp. 1–12, 2021.
The visual perception of identity in humans and other primates is thought to draw upon cortical areas specialized for the analysis of facial structure. A prominent theory of face recognition holds that the brain computes and stores average facial structure, which it then uses to efficiently determine individual identity, though the neural mechanisms underlying this process are controversial. Here, we demonstrate that the dynamic suppression of average facial structure plays a prominent role in the responses of neurons in three fMRI-defined face patches of the macaque. Using photorealistic face stimuli that systematically varied in identity level according to a psychophysically based face space, we found that single units in the AF, AM, and ML face patches exhibited robust tuning around average facial structure. This tuning emerged after the initial excitatory response to the face and was expressed as the selective suppression of sustained responses to low-identity faces. The coincidence of this suppression with increased spike timing synchrony across the population suggests a mechanism of active inhibition underlying this effect. Control experiments confirmed that the diminished responses to low-identity faces were not due to short-term adaptation processes. We propose that the brain's neural suppression of average facial structure facilitates recognition by promoting the extraction of distinctive facial characteristics and suppressing redundant or irrelevant responses across the population.
Rishi Rajalingham; Kohitij Kar; Sachi Sanghavi; Stanislas Dehaene; James J. DiCarlo
In: Nature Communications, vol. 11, pp. 3886, 2020.
The ability to recognize written letter strings is foundational to human reading, but the underlying neuronal mechanisms remain largely unknown. Recent behavioral research in baboons suggests that non-human primates may provide an opportunity to investigate this question. We recorded the activity of hundreds of neurons in V4 and the inferior temporal cortex (IT) while naïve macaque monkeys passively viewed images of letters, English words and non-word strings, and tested the capacity of those neuronal representations to support a battery of orthographic processing tasks. We found that simple linear read-outs of IT (but not V4) population responses achieved high performance on all tested tasks, even matching the performance and error patterns of baboons on word classification. These results show that the IT cortex of untrained primates can serve as a precursor of orthographic processing, suggesting that the acquisition of reading in humans relies on the recycling of a brain network evolved for other visual functions.
Jacob A. Westerberg; Alexander Maier; Geoffrey F. Woodman; Jeffrey D. Schall
Performance monitoring during visual priming Journal Article
In: Journal of Cognitive Neuroscience, vol. 32, no. 3, pp. 515–526, 2020.
Repetitive performance of single-feature (efficient or popout) visual search improves RTs and accuracy. This phenomenon, known as priming of pop-out, has been demonstrated in both humans and macaque monkeys. We investigated the relationship between performance monitoring and priming of pop-out. Neuronal activity in the supplementary eye field (SEF) contributes to performance monitoring and to the generation of performance monitoring signals in the EEG. To determine whether priming depends on performance monitoring, we investigated spiking activity in SEF as well as the concurrent EEG of two monkeys performing a priming of pop-out task. We found that SEF spiking did not modulate with priming. Surprisingly, concurrent EEG did covary with priming. Together, these results suggest that performance monitoring contributes to priming of pop-out. However, this performance monitoring seems not mediated by SEF. This dissociation suggests that EEG indices of performance monitoring arise from multiple, functionally distinct neural generators.
Guillaume Doucet; Roberto A. Gulli; Benjamin W. Corrigan; Lyndon R. Duong; Julio C. Martinez-Trujillo
In: Hippocampus, vol. 30, no. 3, pp. 192–209, 2020.
Primates use saccades to gather information about objects and their relative spatial arrangement, a process essential for visual perception and memory. It has been proposed that signals linked to saccades reset the phase of local field potential (LFP) oscillations in the hippocampus, providing a temporal window for visual signals to activate neurons in this region and influence memory formation. We investigated this issue by measuring hippocampal LFPs and spikes in two macaques performing different tasks with unconstrained eye movements. We found that LFP phase clustering (PC) in the alpha/beta (8–16 Hz) frequencies followed foveation onsets, while PC in frequencies lower than 8 Hz followed spontaneous saccades, even on a homogeneous background. Saccades to a solid grey background were not followed by increases in local neuronal firing, whereas saccades toward appearing visual stimuli were. Finally, saccade parameters correlated with LFPs phase and amplitude: saccade direction correlated with delta (≤4 Hz) phase, and saccade amplitude with theta (4–8 Hz) power. Our results suggest that signals linked to saccades reach the hippocampus, producing synchronization of delta/theta LFPs without a general activation of local neurons. Moreover, some visual inputs co-occurring with saccades produce LFP synchronization in the alpha/beta bands and elevated neuronal firing. Our findings support the hypothesis that saccade-related signals enact sensory input-dependent plasticity and therefore memory formation in the primate hippocampus.
Ramina Adam; Kevin D. Johnston; Ravi S. Menon; Stefan Everling
In: NeuroImage, vol. 207, pp. 116339, 2020.
Visual extinction has been characterized by the failure to respond to a visual stimulus in the contralesional hemifield when presented simultaneously with an ipsilesional stimulus (Corbetta and Shulman, 2011). Unilateral damage to the macaque frontoparietal cortex commonly leads to deficits in contralesional target selection that resemble visual extinction. Recently, we showed that macaque monkeys with unilateral lesions in the caudal prefrontal cortex (PFC) exhibited contralesional target selection deficits that recovered over 2–4 months (Adam et al., 2019). Here, we investigated the longitudinal changes in functional connectivity (FC) of the frontoparietal network after a small or large right caudal PFC lesion in four macaque monkeys. We collected ultra-high field resting-state fMRI at 7-T before the lesion and at weeks 1–16 post-lesion and compared the functional data with behavioural performance on a free-choice saccade task. We found that the pattern of frontoparietal network FC changes depended on lesion size, such that the recovery of contralesional extinction was associated with an initial increase in network FC that returned to baseline in the two small lesion monkeys, whereas FC continued to increase throughout recovery in the two monkeys with a larger lesion. We also found that the FC between contralesional dorsolateral PFC and ipsilesional parietal cortex correlated with behavioural recovery and that the contralesional dorsolateral PFC showed increasing degree centrality with the frontoparietal network. These findings suggest that both the contralesional and ipsilesional hemispheres play an important role in the recovery of function. Importantly, optimal compensation after large PFC lesions may require greater recruitment of distant and intact areas of the frontoparietal network, whereas recovery from smaller lesions was supported by a normalization of the functional network.
Habiba Azab; Benjamin Y. Hayden
In: Behavioral Neuroscience, vol. 134, no. 4, pp. 296–308, 2020.
Evaluation often involves integrating multiple determinants of value, such as the different possible outcomes in risky choice. A brain region can be placed either before or after a presumed evaluation stage by measuring how responses of its neurons depend on multiple determinants of value. A brain region could also, in principle, show partial integration, which would indicate that it occupies a middle position between (preevaluative) nonintegration and (postevaluative) full integration. Existing mathematical techniques cannot distinguish full from partial integration and therefore risk misidentifying regional function. Here we use a new Bayesian regression-based approach to analyze responses of neurons in dorsal anterior cingulate cortex (dACC) to risky offers. We find that dACC neurons only partially integrate across outcome dimensions, indicating that dACC cannot be assigned to either a pre- or postevaluative position. Neurons in dACC also show putative signatures of value comparison, thereby demonstrating that comparison does not require complete evaluation before proceeding.
Marzyeh Azimi; Mariann Oemisch; Thilo Womelsdorf
In: Psychopharmacology, vol. 237, no. 4, pp. 997–1010, 2020.
Rationale: Nicotinic acetylcholine receptors (nAChRs) modulate attention, memory, and higher executive functioning, but it is unclear how nACh sub-receptors mediate different mechanisms supporting these functions. Objectives: We investigated whether selective agonists for the alpha-7 nAChR versus the alpha-4/beta-2 nAChR have unique functional contributions for value learning and attentional filtering of distractors in the nonhuman primate. Methods: Two adult rhesus macaque monkeys performed reversal learning following systemic administration of either the alpha-7 nAChR agonist PHA-543613 or the alpha-4/beta-2 nAChR agonist ABT-089 or a vehicle control. Behavioral analysis quantified performance accuracy, speed of processing, reversal learning speed, the control of distractor interference, perseveration tendencies, and motivation. Results: We found that the alpha-7 nAChR agonist PHA-543613 enhanced the learning speed of feature values but did not modulate how salient distracting information was filtered from ongoing choice processes. In contrast, the selective alpha-4/beta-2 nAChR agonist ABT-089 did not affect learning speed but reduced distractibility. This dissociation was dose-dependent and evident in the absence of systematic changes in overall performance, reward intake, motivation to perform the task, perseveration tendencies, or reaction times. Conclusions: These results suggest nicotinic sub-receptor specific mechanisms consistent with (1) alpha-4/beta-2 nAChR specific amplification of cholinergic transients in prefrontal cortex linked to enhanced cue detection in light of interferences, and (2) alpha-7 nAChR specific activation prolonging cholinergic transients, which could facilitate subjects to follow-through with newly established attentional strategies when outcome contingencies change. These insights will be critical for developing function-specific drugs alleviating attention and learning deficits in neuro-psychiatric diseases.
Pragathi Priyadharsini Balasubramani; Meghan C. Pesce; Benjamin Y. Hayden
In: European Journal of Neuroscience, vol. 51, no. 10, pp. 2033–2051, 2020.
Stopping, or inhibition, is a form of self-control that is a core element of flexible and adaptive behavior. Its neural origins remain unclear. Some views hold that inhibition decisions reflect the aggregation of widespread and diverse pieces of information, including information arising in ostensible core reward regions (i.e., outside the canonical executive system). We recorded activity of single neurons in the orbitofrontal cortex (OFC) of macaques, a region associated with economic decisions, and whose role in inhibition is debated. Subjects performed a classic inhibition task known as the stop signal task. Ensemble decoding analyses reveal a clear firing rate pattern that distinguishes successful from failed inhibition and that begins after the stop signal and before the stop signal reaction time (SSRT). We also found a different and orthogonal ensemble pattern that distinguishes successful from failed stopping before the beginning of the trial. These signals were distinct from, and orthogonal to, value encoding, which was also observed in these neurons. The timing of the early and late signals was, respectively, consistent with the idea that neuronal activity in OFC encodes inhibition both proactively and reactively.
Kévin Blaize; Fabrice Arcizet; Marc Gesnik; Harry Ahnine; Ulisse Ferrari; Thomas Deffieux; Pierre Pouget; Frédéric Chavane; Mathias Fink; José Alain Sahel; José Alain Sahel; José Alain Sahel; Mickael Tanter; Serge Picaud
In: Proceedings of the National Academy of Sciences, vol. 117, no. 25, pp. 14453–14463, 2020.
Deep regions of the brain are not easily accessible to investigation at the mesoscale level in awake animals or humans. We have recently developed a functional ultrasound (fUS) technique that enables imaging hemodynamic responses to visual tasks. Using fUS imaging on two awake nonhuman primates performing a passive fixation task, we constructed retinotopic maps at depth in the visual cortex (V1, V2, and V3) in the calcarine and lunate sulci. The maps could be acquired in a single-hour session with relatively few presentations of the stimuli. The spatial resolution of the technology is illustrated by mapping patterns similar to ocular dominance (OD) columns within superficial and deep layers of the primary visual cortex. These acquisitions using fUS suggested that OD selectivity is mostly present in layer IV but with extensions into layers II/III and V. This imaging technology provides a new mesoscale approach to the mapping of brain activity at high spatiotemporal resolution in awake subjects within the whole depth of the cortex.
Amarender R. Bogadhi; Antimo Buonocore; Ziad M. Hafed
In: Journal of Neuroscience, vol. 40, no. 49, pp. 9496–9506, 2020.
Covert and overt spatial selection behaviors are guided by both visual saliency maps derived from early visual features as well as priority maps reflecting high-level cognitive factors. However, whether mid-level perceptual processes associated with visual form recognition contribute to covert and overt spatial selection behaviors remains unclear. We hypothesized that if peripheral visual forms contribute to spatial selection behaviors, then they should do so even when the visual forms are task-irrelevant. We tested this hypothesis in male and female human subjects as well as in male macaque monkeys performing a visual detection task. In this task, subjects reported the detection of a suprathreshold target spot presented on top of one of two peripheral images, and they did so with either a speeded manual button press (humans) or a speeded saccadic eye movement response (humans and monkeys). Crucially, the two images, one with a visual form and the other with a partially phase-scrambled visual form, were completely irrelevant to the task. In both manual (covert) and oculomotor (overt) response modalities, and in both humans and monkeys, response times were faster when the target was congruent with a visual form than when it was incongruent. Importantly, incongruent targets were associated with almost all errors, suggesting that forms automatically captured selection behaviors. These findings demonstrate that mid-level perceptual processes associated with visual form recognition contribute to covert and overt spatial selection. This indicates that neural circuits associated with target selection, such as the superior colliculus, may have privileged access to visual form information. SIGNIFICANCE STATEMENT Spatial selection of visual information either with (overt) or without (covert) foveating eye movements is critical to primate behavior. However, it is still not clear whether spatial maps in sensorimotor regions known to guide overt and covert spatial selection are influenced by peripheral visual forms. We probed the ability of humans and monkeys to perform overt and covert target selection in the presence of spatially congruent or incongruent visual forms. Even when completely task-irrelevant, images of visual objects had a dramatic effect on target selection, acting much like spatial cues used in spatial attention tasks. Our results demonstrate that traditional brain circuits for orienting behaviors, such as the superior colliculus, likely have privileged access to visual object representations.
Ting Yu Chang; Raymond Doudlah; Byounghoon Kim; Adhira Sunkara; Lowell W. Thompson; Meghan E. Lowe; Ari Rosenberg
In: eLife, vol. 9, pp. 1–27, 2020.
Three-dimensional (3D) representations of the environment are often critical for selecting actions that achieve desired goals. The success of these goal-directed actions relies on 3D sensorimotor transformations that are experience-dependent. Here we investigated the relationships between the robustness of 3D visual representations, choice-related activity, and motor-related activity in parietal cortex. Macaque monkeys performed an eight-alternative 3D orientation discrimination task and a visually guided saccade task while we recorded from the caudal intraparietal area using laminar probes. We found that neurons with more robust 3D visual representations preferentially carried choice-related activity. Following the onset of choice-related activity, the robustness of the 3D representations further increased for those neurons. We additionally found that 3D orientation and saccade direction preferences aligned, particularly for neurons with choice-related activity, reflecting an experience-dependent sensorimotor association. These findings reveal previously unrecognized links between the fidelity of ecologically relevant object representations, choice-related activity, and motor-related activity.
Ting Yu Chang; Lowell Thompson; Raymond Doudlah; Byounghoon Kim; Adhira Sunkara; Ari Rosenberg
In: eNeuro, vol. 7, no. 1, pp. 1–18, 2020.
Reconstructing three-dimensional (3D) scenes from two-dimensional (2D) retinal images is an ill-posed problem. Despite this, 3D perception of the world based on 2D retinal images is seemingly accurate and precise. The integration of distinct visual cues is essential for robust 3D perception in humans, but it is unclear whether this is true for non-human primates (NHPs). Here, we assessed 3D perception in macaque monkeys using a planar surface orientation discrimination task. Perception was accurate across a wide range of spatial poses (orientations and distances), but precision was highly dependent on the plane's pose. The monkeys achieved robust 3D perception by dynamically reweighting the integration of stereoscopic and perspective cues according to their pose-dependent reliabilities. Errors in performance could be explained by a prior resembling the 3D orientation statistics of natural scenes. We used neural network simulations based on 3D orientation-selective neurons recorded from the same monkeys to assess how neural computation might constrain perception. The perceptual data were consistent with a model in which the responses of two independent neuronal populations representing stereoscopic cues and perspective cues (with perspective signals from the two eyes combined using nonlinear canonical computations) were optimally integrated through linear summation. Perception of combined-cue stimuli was optimal given this architecture. However, an alternative architecture in which stereoscopic cues, left eye perspective cues, and right eye perspective cues were represented by three independent populations yielded two times greater precision than the monkeys. This result suggests that, due to canonical computations, cue integration for 3D perception is optimized but not maximized.
Chih-Yang Chen; Denis Matrov; Richard Veale; Hirotaka Onoe; Masatoshi Yoshida; Kenichiro Miura; Tadashi Isa
In: Journal of Neurophysiology, 2020.
The saccade is a stereotypic behavior whose investigation improves our understanding of how primate brains implement precise motor control. Furthermore, saccades offer an important window into the cognitive and attentional state of the brain. Historically, saccade studies have largely relied on macaque. However, the cortical network giving rise to the saccadic command is difficult to study in macaque because relevant cortical areas lie in sulci and are difficult to access. Recently, a New World monkey – the marmoset – has garnered attention as an attractive alternative to macaque because of its smooth cortical surface, its smaller body, and its amenability to transgenic technology. However, adoption of marmoset for oculomotor research has been limited due to a lack of in-depth descriptions of marmoset saccade kinematics and their ability to perform psychophysical and cognitive tasks. Here, we directly compare free-viewing and visually-guided behavior of marmoset, macaque, and human engaged in identical tasks under similar conditions. In video free-viewing task, all species exhibited qualitatively similar saccade kinematics including saccade main sequence up to 25° in amplitude. Furthermore, the conventional bottom-up saliency model predicted gaze targets at similar rates for all species. We further verified their visually-guided behavior by training them with step and gap saccade tasks. All species showed similar gap effect and express saccades in the gap paradigm. Our results suggest that the three species have similar natural and task-guided visuomotor behavior. The marmoset can be trained on saccadic tasks and thus can serve as a model for oculomotor, attention, and cognitive research.
Xiaomo Chen; Marc Zirnsak; Gabriel M. Vega; Eshan Govil; Stephen G. Lomber; Tirin Moore
In: Neuron, vol. 106, no. 1, pp. 177–187.e4, 2020.
Chen et al. show that inactivation of parietal cortex selectively reduces salience signals within prefrontal cortex and diminishes the influence of salience on visually guided behavior. The results demonstrate a causal role of parietal cortex in regulating salience signals within the brain and in controlling salience-driven behavior.
Xiaomo Chen; Marc Zirnsak; Gabriel M. Vega; Tirin Moore
In: Progress in Neurobiology, vol. 195, pp. 101881, 2020.
The consequences of individual actions are typically unknown until well after they are executed. This fact necessitates a mechanism that bridges delays between specific actions and reward outcomes. We looked for the presence of such a mechanism in the post-movement activity of neurons in the frontal eye field (FEF), a visuomotor area in prefrontal cortex. Monkeys performed an oculomotor gamble task in which they made eye movements to different locations associated with dynamically varying reward outcomes. Behavioral data showed that monkeys tracked reward history and made choices according to their own risk preferences. Consistent with previous studies, we observed that the activity of FEF neurons is correlated with the expected reward value of different eye movements before a target appears. Moreover, we observed that the activity of FEF neurons continued to signal the direction of eye movements, the expected reward value, and their interaction well after the movements were completed and when targets were no longer within the neuronal response field. In addition, this post-movement information was also observed in local field potentials, particularly in low-frequency bands. These results show that neural signals of prior actions and expected reward value persist across delays between those actions and their experienced outcomes. These memory traces may serve a role in reward-based learning in which subjects need to learn actions predicting delayed reward.
E. Cleeren; I. D. Popivanov; W. Van Paesschen; Peter Janssen
In: Scientific Reports, vol. 10, pp. 14956, 2020.
Visual information reaches the amygdala through the various stages of the ventral visual stream. There is, however, evidence that a fast subcortical pathway for the processing of emotional visual input exists. To explore the presence of this pathway in primates, we recorded local field potentials in the amygdala of four rhesus monkeys during a passive fixation task showing images of ten object categories. Additionally, in one of the monkeys we also obtained multi-unit spiking activity during the same task. We observed remarkably fast medium and high gamma responses in the amygdala of the four monkeys. These responses were selective for the different stimulus categories, showed within-category selectivity, and peaked as early as 60 ms after stimulus onset. Multi-unit responses in the amygdala were lagging the gamma responses by about 40 ms. Thus, these observations add further evidence that selective visual information reaches the amygdala of nonhuman primates through a very fast route.
Benjamin R. Cowley; Adam C. Snyder; Katerina Acar; Ryan C. Williamson; Byron M. Yu; Matthew A. Smith
In: Neuron, vol. 108, no. 3, pp. 551–567, 2020.
The ability to make a perceptual decision depends both on sensory inputs and on internal cognitive state. Cowley et al. find a slow drift embedded in populations of neurons in visual and prefrontal cortex. Rather than biasing sensory evidence, the slow drift reflects the likelihood of an impulsive decision.
Olga Dal Monte; Cheng C. J. Chu; Nicholas A. Fagan; Steve W. C. Chang
In: Nature Neuroscience, vol. 23, no. 4, pp. 565–574, 2020.
Social behaviors recruit multiple cognitive operations that require interactions between cortical and subcortical brain regions. Interareal synchrony may facilitate such interactions between cortical and subcortical neural populations. However, it remains unknown how neurons from different nodes in the social brain network interact during social decision-making. Here we investigated oscillatory neuronal interactions between the basolateral amygdala and the rostral anterior cingulate gyrus of the medial prefrontal cortex while monkeys expressed context-dependent positive or negative other-regarding preference (ORP), whereby decisions affected the reward received by another monkey. Synchronization between the two nodes was enhanced for a positive ORP but suppressed for a negative ORP. These interactions occurred in beta and gamma frequency bands depending on the area contributing the spikes, exhibited a specific directionality of information flow associated with a positive ORP and could be used to decode social decisions. These findings suggest that specialized coordination in the medial prefrontal–amygdala network underlies social-decision preferences.
Seng Bum Michael Yoo; Benjamin Y. Hayden
In: Neuron, vol. 105, no. 4, pp. 712–724.e4, 2020.
Economic choice proceeds from evaluation, in which we contemplate options, to selection, in which we weigh options and choose one. These stages must be differentiated so that decision makers do not proceed to selection before evaluation is complete. We examined responses of neurons in two core reward regions, orbitofrontal (OFC) and ventromedial prefrontal cortex (vmPFC), during two-option choice with asynchronous offer presentation. Our data suggest that neurons selective during the first (presumed evaluation) and second (presumed comparison and selection) offer epochs come from a single pool. Stage transition is accompanied by a shift toward orthogonality in the low-dimensional population response manifold. Nonetheless, the relative position of each option in driving responses in the population subspace is preserved. The orthogonalization we observe supports the hypothesis that the transition from evaluation to selection leads to reorganization of response subspace and suggests a mechanism by which value-related signals are prevented from prematurely driving choice.
Vanessa A. D. Wilson; Carolin Kade; Sebastian Moeller; Stefan Treue; Igor Kagan; Julia Fischer
In: Frontiers in Psychology, vol. 11, pp. 1645, 2020.
Following the expanding use and applications of virtual reality in everyday life, realistic virtual stimuli are of increasing interest in cognitive studies. They allow for control of features such as gaze, expression, appearance, and movement, which may help to overcome limitations of using photographs or video recordings to study social responses. In using virtual stimuli however, one must be careful to avoid the uncanny valley effect, where realistic stimuli can be perceived as eerie, and induce an aversion response. At the same time, it is important to establish whether responses to virtual stimuli mirror responses to depictions of a real conspecific. In the current study, we describe the development of a new virtual monkey head with realistic facial features for experiments with nonhuman primates, the “Primatar.” As a first step toward validation, we assessed how monkeys respond to facial images of a prototype of this Primatar compared to images of real monkeys (RMs), and an unrealistic model. We also compared gaze responses between original images and scrambled as well as obfuscated versions of these images. We measured looking time to images in six freely moving long-tailed macaques (Macaca fascicularis) and gaze exploration behavior in three rhesus macaques (Macaca mulatta). Both groups showed more signs of overt attention to original images than scrambled or obfuscated images. In addition, we found no evidence for an uncanny valley effect; since for both groups, looking times did not differ between real, realistic, or unrealistic images. These results provide important data for further development of our Primatar for use in social cognition studies and more generally for cognitive research with virtual stimuli in nonhuman primates. Future research on the absence of an uncanny valley effect in macaques is needed, to elucidate the roots of this mechanism in humans.
Mengxi Yun; Takashi Kawai; Masafumi Nejime; Hiroshi Yamada; Masayuki Matsumoto
In: Science Advances, vol. 6, no. 27, pp. eaba4962, 2020.
When we make economic choices, the brain first evaluates available options and then decides whether to choose them. Midbrain dopamine neurons are known to reinforce economic choices through their signal evoked by outcomes after decisions are made. However, although critical internal processing is executed while decisions are being made, little is known about the role of dopamine neurons during this period. We found that dopamine neurons exhibited dynamically changing signals related to the internal processing while rhesus monkeys were making decisions. These neurons encoded the value of an option immediately after it was offered and then gradually changed their activity to represent the animal's upcoming choice. Similar dynamics were observed in the orbitofrontal cortex, a center for economic decision-making, but the value-to-choice signal transition was completed earlier in dopamine neurons. Our findings suggest that dopamine neurons are a key component of the neural network that makes choices from values during ongoing decision-making processes.
Steven Wiesner; Ian W. Baumgart; Xin Huang
In: Journal of Neuroscience, vol. 40, no. 9, pp. 1834–1848, 2020.
Natural scenes often contain multiple objects and surfaces. However, how neurons in the visual cortex represent multiple visual stimuli is not well understood. Previous studies have shown that, when multiple stimuli compete in one feature domain, the evoked neuronal response is biased toward the stimulus that has a stronger signal strength. We recorded from two male macaques to investigate how neurons in the middle temporal cortex (MT) represent multiple stimuli that compete in more than one feature domain. Visual stimuli were two random-dot patches moving in different directions. One stimulus had low luminance contrast and moved with high coherence, whereas the other had high contrast and moved with low coherence. We found that how MT neurons represent multiple stimuli depended on the spatial arrangement. When two stimuli were overlapping, MT responses were dominated by the stimulus component that had high contrast. When two stimuli were spatially separated within the receptive fields, the contrast dominance was abolished. We found the same results when using contrast to compete with motion speed. Our neural data and computer simulations using a V1-MT model suggest that the contrast dominance found with overlapping stimuli is due to normalization occurring at an input stage fed to MT, and MT neurons cannot overturn this bias based on their own feature selectivity. The interaction between spatially separated stimuli can largely be explained by normalization within MT. Our results revealed new rules on stimulus competition and highlighted the impact of hierarchical processing on representing multiple stimuli in the visual cortex.
Polina Zamarashkina; Dina V. Popovkina; Anitha Pasupathy
In: Journal of Neurophysiology, vol. 123, no. 6, pp. 2311–2325, 2020.
In the primate visual cortex, both the magnitude of the neuronal response and its timing can carry important information about the visual world, but studies typically focus only on response magnitude. Here, we examine the onset and offset latency of the responses of neurons in area V4 of awake, behaving macaques across several experiments in the context of a variety of stimuli and task paradigms. Our results highlight distinct contributions of stimuli and tasks to V4 response latency. We found that response onset latencies are shorter than typically cited (median = 75.5 ms), supporting a role for V4 neurons in rapid object and scene recognition functions. Moreover, onset latencies are longer for smaller stimuli and stimulus outlines, consistent with the hypothesis that longer latencies are associated with higher spatial frequency content. Strikingly, we found that onset latencies showed no significant dependence on stimulus occlusion, unlike in inferotemporal cortex, nor on task demands. Across the V4 population, onset latencies had a broad distribution, reflecting the diversity of feedforward, recurrent, and feedback connections that inform the responses of individual neurons. Response offset latencies, on the other hand, displayed the opposite tendency in their relationship to stimulus and task attributes: they are less influenced by stimulus appearance but are shorter in guided saccade tasks compared with fixation tasks. The observation that response latency is influenced by stimulus- and task-associated factors emphasizes a need to examine response timing alongside firing rate in determining the functional role of area V4.NEW & NOTEWORTHY Onset and offset timing of neuronal responses can provide information about visual environment and neuron's role in visual processing and its anatomical connectivity. In the first comprehensive examination of onset and offset latencies in the intermediate visual cortical area V4, we find neurons respond faster than previously reported, making them ideally suited to contribute to rapid object and scene recognition. While response onset reflects stimulus characteristics, timing of response offset is influenced more by behavioral task.
Jan Kubanek; Julian Brown; Patrick Ye; Kim Butts Pauly; Tirin Moore; William Newsome
In: Science Advances, vol. 6, no. 21, pp. eaaz4193, 2020.
The ability to modulate neural activity in specific brain circuits remotely and systematically could revolutionize studies of brain function and treatments of brain disorders. Sound waves of high frequencies (ultrasound) have shown promise in this respect, combining the ability to modulate neuronal activity with sharp spatial focus. Here, we show that the approach can have potent effects on choice behavior. Brief, low-intensity ultrasound pulses delivered noninvasively into specific brain regions of macaque monkeys influenced their decisions regarding which target to choose. The effects were substantial, leading to around a 2:1 bias in choices compared to the default balanced proportion. The effect presence and polarity was controlled by the specific target region. These results represent a critical step towards the ability to influence choice behavior noninvasively, enabling systematic investigations and treatments of brain circuits underlying disorders of choice.;.
Marcin Leszczyński; Annamaria Barczak; Yoshinao Kajikawa; Istvan Ulbert; Arnaud Y. Falchier; Idan Tal; Saskia Haegens; Lucia Melloni; Robert T. Knight; Charles E. Schroeder
In: Science Advances, vol. 6, no. 33, pp. eabb0977, 2020.
Broadband High-frequency Activity (BHA; 70-150 Hz), also known as “high gamma,” a key analytic signal in human intracranial recordings is often assumed to reflect local neural firing (multiunit activity; MUA). Accordingly, BHA has been used to study neuronal population responses in auditory (1,2), visual (3,4), language (5), mnemonic processes (6-9) and cognitive control (10,11). BHA is arguably the electrophysiological measure best correlated with the Blood Oxygenation Level Dependent (BOLD) signal in fMRI (12-13). However, beyond the fact that BHA correlates with neuronal spiking (12, 14-16), the neuronal populations and physiological processes generating BHA are not precisely defined. Although critical for interpreting intracranial signals in human and non-human primates, the precise physiology of BHA remains unknown. Here, we show that BHA dissociates from MUA in primary visual and auditory cortex. Using laminar multielectrode data in monkeys, we found a bimodal distribution of stimulus-evoked BHA across depth of a cortical column: an early-deep, followed by a later-superficial layer response. Only, the early-deep layer BHA had a clear local MUA correlate, while the more prominent superficial layer BHA had a weak or undetectable MUA correlate. In many cases, particularly in V1 (70%), supragranular sites showed strong BHA in lieu of any detectable increase in MUA. Due to volume conduction, BHA from both the early-deep and the later-supragranular generators contribute to the field potential at the pial surface, though the contribution may be weighted towards the late-supragranular BHA. Our results demonstrate that the strongest generators of BHA are in the superficial cortical layers and show that the origins of BHA include a mixture of the neuronal action potential firing and dendritic processes separable from this firing. It is likely that the typically-recorded BHA signal emphasizes the latter processes to a greater extent than previously recognized.
Baowang Li; Brandy N. Routh; Daniel Johnston; Eyal Seidemann; Nicholas J. Priebe
In: Neuron, vol. 107, no. 1, pp. 185–196.e4, 2020.
Li et al. used whole-cell recording to reveal a large and unexpected voltage-gated intrinsic conductance that dramatically alters the integrative properties of primate V1 neurons. Therefore, a standard computational model of sensory neurons that incorporates linear integration of synaptic inputs followed by a threshold nonlinearity requires revision.
Zhongqiao Lin; Chechang Nie; Yuanfeng Zhang; Yang Chen; Tianming Yang
In: Proceedings of the National Academy of Sciences, vol. 117, no. 48, pp. 30728–30737, 2020.
A key step of decision making is to determine the value associated with each option. The evaluation process often depends on the accumulation of evidence from multiple sources, which may arrive at different times. How evidence is accumulated for value computation in the brain during decision making has not been well studied. To address this problem, we trained rhesus monkeys to perform a decision-making task in which they had to make eye movement choices between two targets, whose reward probabilities had to be determined with the combined evidence from four sequentially presented visual stimuli. We studied the encoding of the reward probabilities associated with the stimuli and the eye movements in the orbitofrontal (OFC) and the dorsolateral prefrontal (DLPFC) cortices during the decision process. We found that the OFC neurons encoded the reward probability associated with individual pieces of evidence in the stimulus domain. Importantly, the representation of the reward probability in the OFC was transient, and the OFC did not encode the reward probability associated with the combined evidence from multiple stimuli. The computation of the combined reward probabilities was observed only in the DLPFC and only in the action domain. Furthermore, the reward probability encoding in the DLPFC exhibited an asymmetric pattern of mixed selectivity that supported the computation of the stimulus-to-action transition of reward information. Our results reveal that the OFC and the DLPFC play distinct roles in the value computation during evidence accumulation.
Ye Liu; Ming Li; Xian Zhang; Yiliang Lu; Hongliang Gong; Jiapeng Yin; Zheyuan Chen; Liling Qian; Yupeng Yang; Ian Max Andolina; Stewart Shipp; Niall Mcloughlin; Shiming Tang; Wei Wang
In: Neuron, vol. 108, no. 3, pp. 538–550.e5, 2020.
How does our visual brain generate perceptual color space? Liu et al. find that within a uniform blob-like architecture of hue responses, chromotopic maps develop progressively in scale and precision along the visual hierarchy of macaque V1, V2, and V4. Such hierarchical refinement improves spectral uniformity, better reflecting color perception.
Adi Lixenberg; Merav Yarkoni; Yehudit Botschko; Mati Joshua
In: Journal of Neurophysiology, vol. 123, no. 2, pp. 786–799, 2020.
The cerebellum exhibits both motor and reward-related signals. However, it remains unclear whether reward is processed independently from the motor command or might reflect the motor consequences of the reward drive. To test how reward-related signals interact with sensorimotor processing in the cerebellum, we recorded Purkinje cell simple spike activity in the cerebellar floccular complex while monkeys were engaged in smooth pursuit eye movement tasks. The color of the target signaled the size of the reward the monkeys would receive at the end of the target motion. When the tracking task presented a single target, both pursuit and neural activity were only slightly modulated by the reward size. The reward modulations in single cells were rarely large enough to be detected. These modulations were only significant in the population analysis when we averaged across many neurons. In two-target tasks where the monkey learned to select based on the size of the reward outcome, both behavior and neural activity adapted rapidly. In both the single- and two-target tasks, the size of the reward-related modulation matched the size of the effect of reward on behavior. Thus, unlike cortical activity in eye movement structures, the reward-related signals could not be dissociated from the motor command. These results suggest that reward information is integrated with the eye movement command upstream of the Purkinje cells in the floccular complex. Thus reward-related modulations of the simple spikes are akin to modulations found in motor behavior and not to the central processing of the reward value. NEW & NOTEWORTHY Disentangling sensorimotor and reward signals is only possible if these signals do not completely overlap. We recorded activity in the floccular complex of the cerebellum while monkeys performed tasks designed to separate representations of reward from those of movement. Activity modulation by reward could be accounted for by the coding of eye movement parameters, suggesting that reward information is already integrated into motor commands upstream of the floccular complex.