Ilya E. Monosov

Optogenetic Inactivation Modifies Monkey Visuomotor Behavior

A critical technique for understanding how neuronal activity contributes to behavior is determining whether perturbing it changes behavior. The advent of optogenetic techniques allows the immediately reversible alteration of neuronal activity in contrast to chemical approaches lasting minutes to hours. Modification of behavior using optogenetics has had substantial success in rodents but has not been as successful in monkeys. Here, we show how optogenetic inactivation of superior colliculus neurons in awake monkeys leads to clear and repeatable behavioral deficits in the metrics of saccadic eye movements. We used our observations to evaluate principles governing the use of optogenetic techniques in the study of the neuronal bases of behavior in monkeys, particularly how experimental design must address relevant parameters, such as the application of light to subcortical structures, the spread of viral injections, and the extent of neuronal inactivation with light.

Measurements of Simultaneously Recorded Spiking Activity and Local Field Potentials Suggest that Spatial Selection Emerges in the Frontal Eye Field

The frontal eye field (FEF) participates in selecting the location of behaviorally relevant stimuli for guiding attention and eye movements. We simultaneously recorded local field potentials (LFPs) and spiking activity in the FEF of monkeys performing memory-guided saccade and covert visual search tasks. We compared visual latencies and the time course of spatially selective responses in LFPs and spiking activity. Consistent with the view that LFPs represent synaptic input, visual responses appeared first in the LFPs followed by visual responses in the spiking activity. However, spatially selective activity identifying the location of the target in the visual search array appeared in the spikes about 30 ms before it appeared in the LFPs. Because LFPs reflect dendritic input and spikes measure neuronal output in a local brain region, this temporal relationship suggests that spatial selection necessary for attention and eye movements is computed locally in FEF from spatially nonselective inputs.

Regionally Distinct Processing of Rewards and Punishments by the Primate Ventromedial Prefrontal Cortex

The ventromedial prefrontal cortex (vmPFC) is thought to be related to emotional experience and to the processing of stimulus and action values. However, little is known about how single vmPFC neurons process the prediction and reception of rewards and punishments. We recorded from monkey vmPFC neurons in an experimental situation with alternating blocks, one in which rewards were delivered and one in which punishments were delivered. Many vmPFC neurons changed their activity between blocks. Importantly, neurons in ventral vmPFC were persistently more active in the appetitive “reward” block, whereas neurons in dorsal vmPFC were persistently more active in the aversive “punishment” block. Furthermore, within ventral vmPFC, posterior neurons phasically encoded probability of reward, whereas anterior neurons tonically encoded possibility of reward. We found multiple distinct nonlinear valuation mechanisms within the primate prefrontal cortex. Our findings suggest that different subregions of vmPFC contribute differentially to the processing of valence. By conveying such multidimensional and nonlinear signals, the vmPFC may enable flexible control of decisions and emotions to adapt to complex environments.

What and Where Information in the Caudate Tail Guides Saccades to Visual Objects

We understand the world by making saccadic eye movements to various objects. However, it is unclear how a saccade can be aimed at a particular object, because two kinds of visual information, what the object is and where it is, are processed separately in the dorsal and ventral visual cortical pathways. Here, we provide evidence suggesting that a basal ganglia circuit through the tail of the monkey caudate nucleus (CDt) guides such object-directed saccades. First, many CDt neurons responded to visual objects depending on where and what the objects were. Second, electrical stimulation in the CDt induced saccades whose directions matched the preferred directions of neurons at the stimulation site. Third, many CDt neurons increased their activity before saccades directed to the preferred objects and directions of the neurons in a free-viewing condition. Our results suggest that CDt neurons receive both “what” and “where” information and guide saccades to visual objects.

Frontal Eye Field Activity Enhances Object Identification During Covert Visual Search

We investigated the link between neuronal activity in the frontal eye field (FEF) and the enhancement of visual processing associated with covert spatial attention in the absence of eye movements. We correlated activity recorded in the FEF of monkeys manually reporting the identity of a visual search target to performance accuracy and reaction time. Monkeys were cued to the most probable target location with a cue array containing a popout color singleton. Neurons exhibited spatially selective responses for the popout cue stimulus and for the target of the search array. The magnitude of activity related to the location of the cue prior to the presentation of the search array was correlated with trends in behavioral performance across valid, invalid, and neutral cue trial conditions. However, the speed and accuracy of the behavioral report on individual trials were predicted by the magnitude of spatial selectivity related to the target to be identified, not for the spatial cue. A minimum level of selectivity was necessary for target detection and a higher level for target identification. Muscimol inactivation of FEF produced spatially selective perceptual deficits in the covert search task that were correlated with the effectiveness of the inactivation and were strongest on invalid cue trials that require an endogenous attention shift. These results demonstrate a strong functional link between FEF activity and covert spatial attention and suggest that spatial signals from FEF directly influence visual processing during the time that a stimulus to be identified is being processed by the visual system.

Selective and graded coding of reward uncertainty by neurons in the primate anterodorsal septal region

Natural environments are uncertain. Uncertainty of emotional outcomes can induce anxiety and raise vigilance, promote and signal the opportunity for learning, modulate economic choice and regulate risk-seeking. Here we demonstrate that a subset of neurons in the anterodorsal region of the primate septum (ADS) are primarily devoted to processing uncertainty in a highly specific manner. Those neurons were selectively activated by visual cues indicating probabilistic delivery of reward (for example, 25%, 50% and 75% reward) and did not respond to cues indicating certain outcomes (0% and 100% reward). The average ADS uncertainty response was graded with the magnitude of reward uncertainty and selectively signaled uncertainty about rewards rather than punishments. The selective and graded information about reward uncertainty encoded by many neurons in the ADS may underlie modulation of uncertainty of value- and sensorimotor-related areas to regulate goal-directed behavior.

Paired neuron recordings in the prefrontal and inferotemporal cortices reveal that spatial selection precedes object identification during visual search

We addressed the question of how we locate and identify objects in complex natural environments by simultaneously recording single neurons from two brain regions that play different roles in this familiar activity—the frontal eye field (FEF), an area in the prefrontal cortex that is involved in visual spatial selection, and the inferotemporal cortex (IT), which is involved in object recognition—in monkeys performing a covert visual search task. Although the monkeys reported object identity, not location, neural activity specifying target location was evident in FEF before neural activity specifying target identity in IT. These two distinct processes were temporally correlated implying a functional linkage between the end stages of ”where” and “what” visual processing and indicating that spatial selection is necessary for the formation of complex object representations associated with visual perception.

The effects of prefrontal cortex inactivation on object responses of single neurons in the inferotemporal cortex during visual search

Inferotemporal cortex (IT) is believed to be directly involved in object processing and necessary for accurate and efficient object recognition. The frontal eye field (FEF) is an area in the primate prefrontal cortex that is involved in visual spatial selection and is thought to guide spatial attention and eye movements. We show that object-selective responses of IT neurons and behavioral performance are affected by changes in frontal eye field activity. This was found in monkeys performing a search classification task by temporarily inactivating subregions of FEF while simultaneously recording the activity from single neurons in IT. The effect on object selectivity and performance was specific, occurring in a predictable spatially dependent manner and was strongest when the IT neurons preferred target was presented in the presence of distractors. FEF inactivation did not affect IT responses on trials in which the nonpreferred target was presented in the search array.

A perceptual representation in the frontal eye field during covert visual search that is more reliable than the behavioral report

Neuronal activity in the frontal eye field (FEF) identifies locations of behaviorally important objects for guiding attention and eye movements. We recorded neural activity in the FEF of monkeys trained to manually turn a lever towards the location of a pop‐out target of a visual search array without shifting gaze. We examined whether the reliability of the neural representation of the salient target location predicted the monkeys’ accuracy of reporting target location. We found that FEF neurons reliably encoded the location of the target stimulus not only on correct trials but also on error trials. The representation of target location in FEF persisted until the manual behavioral report but did not increase in magnitude. This result suggests that, in the absence of an eye movement report, FEF encodes the perceptual information necessary to perform the task but does not accumulate this sensory evidence towards a perceptual decision threshold. These results provide physiological evidence that, under certain circumstances, accurate perceptual representations do not always lead to accurate behavioral reports and that variability in processes outside of perception must be considered to account for the variability in perceptual choice behavior.

Neurons in the primate medial basal forebrain signal combined information about reward uncertainty, value, and punishment anticipation

It has been suggested that the basal forebrain (BF) exerts strong influences on the formation of memory and behavior. However, what information is used for the memory-behavior formation is unclear. We found that a population of neurons in the medial BF (medial septum and diagonal band of Broca) of macaque monkeys encodes a unique combination of information: reward uncertainty, expected reward value, anticipation of punishment, and unexpected reward and punishment. The results were obtained while the monkeys were expecting (often with uncertainty) a rewarding or punishing outcome during a Pavlovian procedure, or unexpectedly received an outcome outside the procedure. In vivo anterograde tracing using manganese-enhanced MRI suggested that the major recipient of these signals is the intermediate hippocampal formation. Based on these findings, we hypothesize that the medial BF identifies various contexts and outcomes that are critical for memory processing in the hippocampal formation.