Low-Beta Oscillations Turn Up the Gain During Category Judgments.

Synchrony between local field potential (LFP) rhythms is thought to boost the signal of attended sensory inputs. Other cognitive functions could benefit from such gain control. One is categorization where decisions can be difficult if categories differ in subtle ways. Monkeys were trained to flexibly categorize smoothly varying morphed stimuli, using orthogonal boundaries to carve up the same stimulus space in 2 different ways. We found evidence for category-specific patterns of low-beta (16-20 Hz) synchrony in the lateral prefrontal cortex (PFC). This synchrony was stronger when a given category scheme was relevant. We also observed an overall increase in low-beta LFP synchrony for stimuli that were near the category boundary and thus more difficult to categorize. Beta category selectivity was evident in partial field-field coherence measurements, which measure local synchrony, but the boundary enhancement was not. Thus, it seemed that category selectivity relied on local interactions while boundary enhancement was a more global effect. The results suggest that beta synchrony helps form category ensembles and may reflect recruitment of additional cortical resources for categorizing challenging stimuli, thus serving as a form of gain control.

Compressed Timeline of Recent Experience in Monkey Lateral Prefrontal Cortex.

Cognitive theories suggest that working memory maintains not only the identity of recently presented stimuli but also a sense of the elapsed time since the stimuli were presented. Previous studies of the neural underpinnings of working memory have focused on sustained firing, which can account for maintenance of the stimulus identity, but not for representation of the elapsed time. We analyzed single-unit recordings from the lateral prefrontal cortex of macaque monkeys during performance of a delayed match-to-category task. Each sample stimulus triggered a consistent sequence of neurons, with each neuron in the sequence firing during a circumscribed period. These sequences of neurons encoded both stimulus identity and elapsed time. The encoding of elapsed time became less precise as the sample stimulus receded into the past. These findings suggest that working memory includes a compressed timeline of what happened when, consistent with long-standing cognitive theories of human memory.

PFC neurons reflect categorical decisions about ambiguous stimuli.

We examined whether PFC neuron activity reflects categorical decisions in monkeys categorizing ambiguous stimuli. A morphing system was used to systematically vary stimulus shape and precisely define category boundaries. Ambiguous stimuli were centered on a category boundary, that is, they were a mix of 50% of two prototypes and therefore had no category information, so monkeys guessed at their category membership. We found that the monkeys' trial-by-trial decision about the category membership of an ambiguous image was reflected in PFC activity. Activity to the same ambiguous image differed significantly, depending on which category the monkey had assigned it to. This effect only occurred when that scheme was behaviorally relevant. These indicate that PFC activity reflects categorical decisions.

Neural substrates of cognitive capacity limitations.

Cognition has a severely limited capacity: Adult humans can retain only about four items "in mind". This limitation is fundamental to human brain function: Individual capacity is highly correlated with intelligence measures and capacity is reduced in neuropsychiatric diseases. Although human capacity limitations are well studied, their mechanisms have not been investigated at the single-neuron level. Simultaneous recordings from monkey parietal and frontal cortex revealed that visual capacity limitations occurred immediately upon stimulus encoding and in a bottom-up manner. Capacity limitations were found to reflect a dual model of working memory. The left and right halves of visual space had independent capacities and thus are discrete resources. However, within each hemifield, neural information about successfully remembered objects was reduced by adding further objects, indicating that resources are shared. Together, these results suggest visual capacity limitation is due to discrete, slot-like, resources, each containing limited pools of neural information that can be divided among objects.

Convergent effects of different anesthetics are due to changes in phase alignment of cortical oscillations.

Many different anesthetics cause loss of responsiveness despite having diverse underlying molecular and circuit actions. To explore the convergent effects of these drugs, we examined how ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, and dexmedetomidine, an α2 adrenergic receptor agonist, affected neural oscillations in the prefrontal cortex of nonhuman primates. Previous work has shown that anesthesia increases phase locking of low-frequency local field potential activity across cortex. We observed similar increases with anesthetic doses of ketamine and dexmedetomidine in the ventrolateral and dorsolateral prefrontal cortex, within and across hemispheres. However, the nature of the phase locking varied between regions. We found that oscillatory activity in different prefrontal subregions within each hemisphere became more anti-phase with both drugs. Local analyses within a region suggested that this finding could be explained by broad cortical distance-based effects, such as a large traveling wave. By contrast, homologous areas across hemispheres increased their phase alignment. Our results suggest that the drugs induce strong patterns of cortical phase alignment that are markedly different from those in the awake state, and that these patterns may be a common feature driving loss of responsiveness from different anesthetic drugs.

Prefrontal cortex activity during flexible categorization.

Items are categorized differently depending on the behavioral context. For instance, a lion can be categorized as an African animal or a type of cat. We recorded lateral prefrontal cortex (PFC) neural activity while monkeys switched between categorizing the same image set along two different category schemes with orthogonal boundaries. We found that each category scheme was largely represented by independent PFC neuronal populations and that activity reflecting a category distinction was weaker, but not absent, when that category was irrelevant. We suggest that the PFC represents competing category representations independently to reduce interference between them.

Comparison of primate prefrontal and premotor cortex neuronal activity during visual categorization.

Previous work has shown that neurons in the PFC show selectivity for learned categorical groupings. In contrast, brain regions lower in the visual hierarchy, such as inferior temporal cortex, do not seem to favor category information over information about physical appearance. However, the role of premotor cortex (PMC) in categorization has not been studied, despite evidence that PMC is strongly engaged by well-learned tasks and reflects learned rules. Here, we directly compare PFC neurons with PMC neurons during visual categorization. Unlike PFC neurons, relatively few PMC neurons distinguished between categories of visual images during a delayed match-to-category task. However, despite the lack of category information in the PMC, more than half of the neurons in both PFC and PMC reflected whether the category of a test image did or did not match the category of a sample image (i.e., had match information). Thus, PFC neurons represented all variables required to solve the cognitive problem, whereas PMC neurons instead represented only the final decision variable that drove the appropriate motor action required to obtain a reward. This dichotomy fits well with PFC's hypothesized role in learning arbitrary information and directing behavior as well as the PMC's role in motor planning.

Different Levels of Category Abstraction by Different Dynamics in Different Prefrontal Areas.

Categories can be grouped by shared sensory attributes (i.e., cats) or a more abstract rule (i.e., animals). We explored the neural basis of abstraction by recording from multi-electrode arrays in prefrontal cortex (PFC) while monkeys performed a dot-pattern categorization task. Category abstraction was varied by the degree of exemplar distortion from the prototype pattern. Different dynamics in different PFC regions processed different levels of category abstraction. Bottom-up dynamics (stimulus-locked gamma power and spiking) in the ventral PFC processed more low-level abstractions, whereas top-down dynamics (beta power and beta spike-LFP coherence) in the dorsal PFC processed more high-level abstractions. Our results suggest a two-stage, rhythm-based model for abstracting categories.

Dissociating self-generated from passively applied head motion: neural mechanisms in the vestibular nuclei.

The ability to distinguish sensory inputs that are a consequence of our own actions from those that result from changes in the external world is essential for perceptual stability and accurate motor control. To accomplish this, it has been proposed that an internal prediction of the consequences of our actions is compared with the actual sensory input to cancel the resultant self-generated activation. Here, we provide evidence for this hypothesis at an early stage of processing in the vestibular system. Previous studies have shown that neurons in the vestibular nucleus, which receive direct inputs from vestibular afferent fibers, are responsive to passively applied head movements. However, these same neurons do not reliably encode head velocity resulting from self-generated movements of the head on the body. In this study, we examined the mechanism that underlies the selective elimination of vestibular sensitivity to active head-on-body rotations. Individual neurons were recorded in monkeys making active head movements. The correspondence between intended and actual head movement was experimentally controlled. We found that a cancellation signal was gated into the vestibular nuclei only in conditions in which the activation of neck proprioceptors matched that expected on the basis of the neck motor command. This finding suggests that vestibular signals that arise from self-generated head movements are inhibited by a mechanism that compares the internal prediction of the sensory consequences by the brain to the actual resultant sensory feedback. Because self-generated vestibular inputs are selectively cancelled early in processing, we propose that this gating is important for the computation of spatial orientation and control of posture by higher-order structures.

Representation of multiple, independent categories in the primate prefrontal cortex.

Neural correlates of visual categories have been previously identified in the prefrontal cortex (PFC). However, whether individual neurons can represent multiple categories is unknown. Varying degrees of generalization versus specialization of neurons in the PFC have been theorized. We recorded from lateral PFC neural activity while monkeys switched between two different and independent categorical distinctions (Cats versus Dogs, Sports Cars versus Sedans). We found that many PFC neurons reflected both categorical distinctions. In fact, these multitasking neurons had the strongest category effects. This stands in contrast to our lab's recent report that monkeys switching between competing categorical distinctions (applied to the same stimulus set) showed independent representations. We suggest that cognitive demands determine whether PFC neurons function as category "multitaskers."

Vestibuloocular reflex signal modulation during voluntary and passive head movements.

The vestibuloocular reflex (VOR) effectively stabilizes the visual world on the retina over the wide range of head movements generated during daily activities by producing an eye movement of equal and opposite amplitude to the motion of the head. Although an intact VOR is essential for stabilizing gaze during walking and running, it can be counterproductive during certain voluntary behaviors. For example, primates use rapid coordinated movements of the eyes and head (gaze shifts) to redirect the visual axis from one target of interest to another. During these self-generated head movements, a fully functional VOR would generate an eye-movement command in the direction opposite to that of the intended shift in gaze. Here, we have investigated how the VOR pathways process vestibular information across a wide range of behaviors in which head movements were either externally applied and/or self-generated and in which the gaze goal was systematically varied (i.e., stabilize vs. redirect). VOR interneurons [i.e., type I position-vestibular-pause (PVP) neurons] were characterized during head-restrained passive whole-body rotation, passive head-on-body rotation, active eye-head gaze shifts, active eye-head gaze pursuit, self-generated whole-body motion, and active head-on-body motion made while the monkey was passively rotated. We found that regardless of the stimulation condition, type I PVP neuron responses to head motion were comparable whenever the monkey stabilized its gaze. In contrast, whenever the monkey redirected its gaze, type I PVP neurons were significantly less responsive to head velocity. We also performed a comparable analysis of type II PVP neurons, which are likely to contribute indirectly to the VOR, and found that they generally behaved in a quantitatively similar manner. Thus our findings support the hypothesis that the activity of the VOR pathways is reduced "on-line" whenever the current behavioral goal is to redirect gaze. By characterizing neuronal responses during a variety of experimental conditions, we were also able to determine which inputs contribute to the differential processing of head-velocity information by PVP neurons. We show that neither neck proprioceptive inputs, an efference copy of neck motor commands nor the monkey's knowledge of its self-motion influence the activity of PVP neurons per se. Rather we propose that efference copies of oculomotor/gaze commands are responsible for the behaviorally dependent modulation of PVP neurons (and by extension for modulation of the status of the VOR) during gaze redirection.

Signal processing in the vestibular system during active versus passive head movements.

In everyday life, vestibular receptors are activated by both self-generated and externally applied head movements. Traditionally, it has been assumed that the vestibular system reliably encodes head-in-space motion throughout our daily activities and that subsequent processing by upstream cerebellar and cortical pathways is required to transform this information into the reference frames required for voluntary behaviors. However, recent studies have radically changed the way we view the vestibular system. In particular, the results of recent single-unit studies in head-unrestrained monkeys have shown that the vestibular system provides the CNS with more than an estimate of head motion. This review first considers how head-in-space velocity is processed at the level of the vestibular afferents and vestibular nuclei during active versus passive head movements. While vestibular information appears to be similarly processed by vestibular afferents during passive and active motion, it is differentially processed at the level of the vestibular nuclei. For example, one class of neurons in vestibular nuclei, which receives direct inputs from semicircular canal afferents, is substantially less responsive to active head movements than to passively applied head rotations. The projection patterns of these neurons strongly suggest that they are involved in generating head-stabilization responses as well as shaping vestibular information for the computation of spatial orientation. In contrast, a second class of neurons in the vestibular nuclei that mediate the vestibuloocular reflex process vestibular information in a manner that depends principally on the subject's current gaze strategy rather than whether the head movement was self-generated or externally applied. The implications of these results are then discussed in relation to the status of vestibular reflexes (i.e., the vestibuloocular, vestibulocollic, and cervicoocular reflexes) and implications for higher-level processing of vestibular information during active head movements.

Brain stem pursuit pathways: dissociating visual, vestibular, and proprioceptive inputs during combined eye-head gaze tracking.

Eye-head (EH) neurons within the medial vestibular nuclei are thought to be the primary input to the extraocular motoneurons during smooth pursuit: they receive direct projections from the cerebellar flocculus/ventral paraflocculus, and in turn, project to the abducens motor nucleus. Here, we recorded from EH neurons during head-restrained smooth pursuit and head-unrestrained combined eye-head pursuit (gaze pursuit). During head-restrained smooth pursuit of sinusoidal and step-ramp target motion, each neuron's response was well described by a simple model that included resting discharge (bias), eye position, and velocity terms. Moreover, eye acceleration, as well as eye position, velocity, and acceleration error (error = target movement - eye movement) signals played no role in shaping neuronal discharges. During head-unrestrained gaze pursuit, EH neuron responses reflected the summation of their head-movement sensitivity during passive whole-body rotation in the dark and gaze-movement sensitivity during smooth pursuit. Indeed, EH neuron responses were well predicted by their head- and gaze-movement sensitivity during these two paradigms across conditions (e.g., combined eye-head gaze pursuit, smooth pursuit, whole-body rotation in the dark, whole-body rotation while viewing a target moving with the head (i.e., cancellation), and passive rotation of the head-on-body). Thus our results imply that vestibular inputs, but not the activation of neck proprioceptors, influence EH neuron responses during head-on-body movements. This latter proposal was confirmed by demonstrating a complete absence of modulation in the same neurons during passive rotation of the monkey's body beneath its neck. Taken together our results show that during gaze pursuit EH neurons carry vestibular- as well as gaze-related information to extraocular motoneurons. We propose that this vestibular-related modulation is offset by inputs from other premotor inputs, and that the responses of vestibuloocular reflex interneurons (i.e., position-vestibular-pause neurons) are consistent with such a proposal.