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In vivo electrophysiology requires direct access to brain tissue, necessitating the development and refinement of surgical procedures and techniques that promote the health and well-being of animal subjects. Here, we report a series of findings noted on structural magnetic resonance imaging (MRI) scans in monkeys with MRI-compatible implants following small craniotomies that provide access for intracranial electrophysiology. We found distinct brain regions exhibiting hyperintensities in T2-weighted scans that were prominent underneath the sites at which craniotomies had been performed. We interpreted these hyperintensities as edema of the neural tissue and found that they were predominantly present following electric and piezoelectric drilling, but not when manual, hand-operated drills were used. Furthermore, the anomalies subsided within 2-3 wk following surgery. Our report highlights the utility of MRI-compatible implants that promote clinical examination of the animal's brain, sometimes revealing findings that may go unnoticed when incompatible implants are used. We show replicable differences in outcome when using electric versus mechanical devices, both ubiquitous in the field. If electric drills are used, our report cautions against electrophysiological recordings from tissue directly underneath the craniotomy for the first 2-3 wk following the procedure due to putative edema.bNEWamp; NOTEWORTHY/bClose examination of structural MRI in eight nonhuman primates following craniotomy surgeries for intracranial electrophysiology highlights a prevalence of hyperintensities on T2-weighted scans following surgeries conducted using electric and piezoelectric drills, but not when using mechanical, hand-operated drills. We interpret these anomalies as edema of neural tissue that resolved 2-3 wk postsurgery. This finding is especially of interest as electrophysiological recordings from compromised tissue may directly influence the integrity of collected data immediately following surgery.

In-vivo electrophysiology requires direct access to brain tissue, necessitating the development and refinement of surgical procedures and techniques that promote the health and well-being of the animal subjects. Here, we report a series of findings noted on structural magnetic resonance imaging (MRI) scans in monkeys with MRI-compatible implants following small craniotomies that provide access for intracranial electrophysiology. We found distinct brain regions exhibiting hyperintensities in T2-weighted scans that were prominent underneath the sites at which craniotomies had been performed. We interpreted these hyperintensities as edema of the neural tissue and found that they were predominantly present following electric drilling, but not when manual, hand-operated drills were used. Further, the anomalies subsided within 2-3 weeks following surgery. Our report highlights the utility of MRI-compatible implants that promote clinical examination of the animal’s brain, sometimes revealing findings that may go unnoticed when incompatible implants are used. We show replicable differences in outcome when using electric vs. mechanical devices, both ubiquitous in the field. If electric drills are used, our report cautions electrophysiological recordings from tissue directly underneath the craniotomy for the first 2-3 weeks following the procedure due to putative edema.

Contains fulltext : 239574.pdf (Publisher’s version ) (Closed access) Open science initiatives are creating opportunities to increase research coordination and impact in nonhuman primate (NHP) imaging. The PRIMatE Data and Resource Exchange community recently developed a collaboration-based strategic plan to advance NHP imaging as an integrative approach for multiscale neuroscience. 5 p.

Summary Theta (3–9 Hz) and gamma (30–100 Hz) oscillations have been observed at different levels along the hierarchy of cortical areas and across a wide set of cognitive tasks. In the visual system, the emergence of both rhythms in primary visual cortex (V1) and mid-level cortical areas V4 has been linked with variations in perceptual reaction times. 1 , 2 , 3 , 4 , 5 Based on analytical methods to infer causality in neural activation patterns, it was concluded that gamma and theta oscillations might both reflect feedforward sensory processing from V1 to V4. 6 , 7 , 8 , 9 , 10 Here, we report on experiments in macaque monkeys in which we experimentally assessed the presence of both oscillations in the neural activity recorded from multi-electrode arrays in V1 and V4 before and after a permanent V1 lesion. With intact cortex, theta and gamma oscillations could be reliably elicited in V1 and V4 when monkeys viewed a visual contour illusion and showed phase-to-amplitude coupling. Laminar analysis in V1 revealed that both theta and gamma oscillations occurred primarily in the supragranular layers, the cortical output compartment of V1. However, there was a clear dissociation between the two rhythms in V4 that became apparent when the major feedforward input to V4 was removed by lesioning V1: although V1 lesioning eliminated V4 theta, it had little effect on V4 gamma power except for delaying its emergence by >100 ms. These findings suggest that theta is more tightly associated with feedforward processing than gamma and pose limits on the proposed role of gamma as a feedforward mechanism.

Attending to a visual stimulus increases its detectability, even if gaze is directed elsewhere. This covert attentional selection is known to enhance spiking across many brain areas, including the primary visual cortex (V1). Here we investigate the temporal dynamics of attention-related spiking changes in V1 of macaques performing a task that separates attentional selection from the onset of visual stimulation. We found that preceding attentional enhancement there was a sharp, transient decline in spiking following presentation of an attention-guiding cue. This disruption of V1 spiking was not observed in a task-naïve subject that passively observed the same stimulus sequence, suggesting that sensory activation is insufficient to cause suppression. Following this suppression, attended stimuli evoked more spiking than unattended stimuli, matching previous reports of attention-related activity in V1. Laminar analyses revealed a distinct pattern of activation in feedback-associated layers during both the cue-induced suppression and subsequent attentional enhancement. These findings suggest that top-down modulation of V1 spiking can be bidirectional and result in either suppression or enhancement of spiking responses.

Whenever we open our eyes, our brain quickly integrates the two eyes' perspectives into a combined view. This process of binocular integration happens so rapidly that even incompatible stimuli are briefly fused before one eye's view is suppressed in favor of the other (binocular rivalry). The neuronal basis for this brief period of fusion during incompatible binocular stimulation is unclear. Neuroanatomically, the eyes provide two largely separate streams of information that are integrated into a binocular response by the primary visual cortex (V1). However, the temporal dynamics underlying the formation of this binocular response are largely unknown. To address this question, we examined the temporal profile of binocular responses in V1 of fixating monkeys. We found that V1 processes binocular stimuli in a dynamic sequence that comprises at least two distinct temporal phases. An initial transient phase is characterized by enhanced spiking responses for both compatible and incompatible binocular stimuli compared to monocular stimulation. This transient is followed by a sustained response that differed markedly between congruent and incongruent binocular stimulation. Specifically, incompatible binocular stimulation resulted in overall response reduction relative to monocular stimulation (binocular suppression). In contrast, responses to compatible stimuli were either suppressed or enhanced (binocular facilitation) depending on the neurons' ocularity (selectivity for one eye over the other) and laminar location. These results suggest that binocular integration in V1 occurs in at least two sequential steps that comprise initial additive combination of the two eyes' signals followed by widespread differentiation between binocular concordance and discordance.

The vast majority of mammalian neocortex consists of a stereotypical microcircuit, the canonical cortical microcircuit (CCM), consisting of a granular input layer, positioned between superficial and deep layers. Due to this uniform layout, neuronal activation tends to follow a similar laminar sequence, with unique information extracted at each step. For example, the primate primary visual cortex (V1) combines the two eyes’ signals, extracts stimulus orientation and modulates its activity depending on stimulus history. Several theories have been proposed on when and where these processes happen within the CCM’s laminar activation sequence, but it has been methodologically challenging to test these hypotheses. Here, we use time-resolved multivariate pattern analysis (MVPA) to decode information regarding the eye-of-origin, stimulus orientation and stimulus repetition from simultaneously measured spiking responses across V1’s laminar microcircuit. We find that eye-of-origin information was decodable for the entire duration of stimulus presentation, but diminished in the deepest layers of V1, consistent with the notion that two eyes’ signals are combined within the upper layers. Conversely, orientation information was transient and equally pronounced across the microcircuit, in line with the idea that this information is relayed to other areas for further processing. Moreover, when stimuli were repeated, information regarding orientation was enhanced at the expense of eye-of origin information, suggesting that V1 modulates information flow to optimize specific stimulus dimensions. Taken together, these findings provide empirical evidence that adjudicates between long-standing hypotheses and reveals how information transfer within the CCM supports unique cortical functions.Significance StatementDespite the brain’s daunting complexity, there are common organizing principles across brain areas. For example, neocortical activation follows a stereotypical pattern that spreads from input layers towards layers above and below. While this activation pattern is well known, it has been challenging to ascertain how unique types of information are extracted within this common sequence in different brain areas. Here we use machine learning to track the flow of stimulus-specific information across the layers of visual cortex. We found that information regarding several separate stimulus dimensions was routed uniquely within the common activation sequence in a manner that confirmed prior model predictions. This finding demonstrates how differences in information flow within the stereotypical neocortical activation sequence shape area-specific functions.

Our brains combine the separate streams of sensory signals from the two eyes into a singular view. Where the separate streams from the two eyes first converge in the primary visual pathway is unclear. At the initial stage of visual processing following transduction in the retina, neurons in the lateral geniculate nucleus of the thalamus (LGN) are deemed monocular because they are excited by stimulation of one eye and not the other. At the next stage of visual processing, in the primary visual cortex (V1), there are many neurons that are deemed binocular because they are excited by stimulation of either eye, signifying that binocular convergence has happened by that stage. Visual stimulation evokes a specific sequence of activation across the laminar microcircuit of V1. During which part of this sequence binocular convergence occurs is unresolved. Here we investigate where binocular convergence occurs in the V1 laminar microcircuit by examining the extent to which macaque V1 neurons in all layers are sensitive to both eyes. We found that more than 94% of V1 neurons across all layers were binocular in the sense that they were driven by stimulation of either eye. As expected, monocular neurons were largely located in the primary geniculate input layer of V1. Interestingly, these monocular neurons showed systematic firing rate differences between stimulation of their driving eye alone compared to stimulation of both eyes, revealing that these so-called monocular neurons actually encode what is shown to both eyes. This finding suggests that, while geniculate inputs to V1 are largely segregated by eye, the outputs of their V1 target neurons are sensitive to what both eyes view, marking this processing stage as the primary point of binocular convergence in the primate visual system.

Neocortex is striking in its laminar architecture. Tracer studies have uncovered anatomical connectivity among laminae, but the functional connectivity between laminar compartments is still largely unknown. Such functional connectivity can be discerned through spontaneous neural correlations during rest. Previous work demonstrated a robust pattern of mesoscopic resting-state connectivity in macaque primary visual cortex (V1) through interlaminar cross-frequency coupling. Here we investigated whether this pattern generalizes to other cortical areas by comparing resting-state laminar connectivity between V1 and the supplementary eye field (SEF), a frontal area lacking a granular layer 4 (L4). Local field potentials (LFPs) were recorded with linear microelectrode arrays from all laminae of granular V1 and agranular SEF while monkeys rested in darkness. We found substantial differences in the relationship between the amplitude of gamma-band (>30 Hz) LFP and the phase of alpha-band (7–14 Hz) LFP between these areas. In V1, gamma amplitudes in L2/3 and L5 were coupled with alpha-band LFP phase in L5, as previously described. In contrast, in SEF phase-amplitude coupling was prominent within L3 and much weaker across layers. These results suggest that laminar interactions in agranular SEF are unlike those in granular V1. Thus the intrinsic functional connectivity of the cortical microcircuit does not seem to generalize across cortical areas.

Repeated stimulus presentations reduce neuronal responses across many brain areas (repetition suppression) while improving performance in associated tasks (repetition priming). The neuronal mechanisms that enhance performance in the face of reduced brain activity are unknown. Here we demonstrate that stimulus repetition increases encoding efficiency among cortical neurons, which enhances stimulus representations despite reduced spiking activity. Using a repetition priming-evoking stimulus sequence, we recorded laminar responses in monkey primary visual cortex (V1). We found that repetition suppression is most pronounced outside the V1 layers that receive retinogeniculate input and is robust to alternating stimuli between the two eyes, suggesting that repetition suppression is of cortical origin. This V1 spiking suppression is accompanied by sharpened neural tuning as well as increased neuronal synchrony, however not by decreased response latency. These results suggest that repetition priming and repetition suppression arise from modulated cortical neuronal processing that enhances encoding efficiency as stimuli repeat.

The interlaminar connections in the primate primary visual cortex (V1) are well described, as is the presence of ongoing alpha-range (7-14 Hz) fluctuations in this area. Less well understood is how these interlaminar connections and ongoing fluctuations contribute to the regulation of visual spiking responses. Here, we investigate the relationship between alpha fluctuations and spiking responses to visual stimuli across cortical layers. Using laminar probes in macaque V1, we show that neural firing couples with the phase of alpha fluctuations, and that magnitude of this coupling is particularly pronounced during visual stimulation. The strongest modulation of spiking activity was observed in layers 2/3. Alpha-spike coupling and current source density analysis pointed to an infragranular origin of the alpha fluctuations. Taken together, these results indicate that ongoing infragranular alpha-range fluctuations in V1 play a role in regulating columnar visual activity.

The mammalian neocortex features distinct anatomical variation in its tangential and radial extents. This review consolidates previously published findings from our group in order to compare and contrast the spatial profile of neural activity coherence across these distinct cortical dimensions. We focus on studies of ongoing local field potential (LFP) data obtained simultaneously from multiple sites in the primary visual cortex in two types of experiments in which electrode contacts were spaced either along the cortical surface or at different laminar positions. These studies demonstrate that across both dimensions the coherence of ongoing LFP fluctuations diminishes as a function of interelectrode distance, although the nature and spatial scale of this falloff is very different. Along the cortical surface, the overall LFP coherence declines gradually and continuously away from a given position. In contrast, across the cortical layers, LFP coherence is discontinuous and compartmentalized as a function of depth. Specifically, regions of high LFP coherence fall into discrete superficial and deep laminar zones, with an abrupt discontinuity between the granular and infragranular layers. This spatial pattern of ongoing LFP coherence is similar when animals are at rest and when they are engaged in a behavioral task. These results point to the existence of partially segregated laminar zones of cortical processing that extend tangentially within the laminar compartments and are thus oriented orthogonal to the cortical columns. We interpret these electrophysiological observations in light of the known anatomical organization of the cortical microcircuit.

The dorsal lateral geniculate nucleus of the thalamus (LGN) receives the main outputs of both eyes and relays those signals to the visual cortex. Each retina projects to separate layers of the LGN so that each LGN neuron is innervated by a single eye. In line with this anatomical separation, visual responses of almost all of LGN neurons are driven by one eye only. Nonetheless, many LGN neurons are sensitive to what is shown to the other eye as their visual responses differ when both eyes are stimulated compared to when the driving eye is stimulated in isolation. This, predominantly suppressive, binocular modulation of LGN responses might suggest that the LGN is the first location in the primary visual pathway where the outputs from the two eyes interact. Indeed, the LGN features several anatomical structures that would allow for LGN neurons responding to one eye to modulate neurons that respond to the other eye. However, it is also possible that binocular response modulation in the LGN arises indirectly as the LGN also receives input from binocular visual structures. Here we review the extant literature on the effects of binocular stimulation on LGN spiking responses, highlighting findings from cats and primates, and evaluate the neural circuits that might mediate binocular response modulation in the LGN.

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 (parvo-, magno-, and koniocellular) 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 pre-cortical binocular processing involved in resolving discrepant contrast differences between the eyes. Significance A fundamental feature of the primate visual system is its binocular arrangement, which affords stereovision and hyperacuity. A consequence of this arrangement is that the two eyes’ views need to be resolved to yield singular vision, which is normally accomplished by fusion or suppression of one of the eye’s inputs. This binocular processing has been shown to occur in cortex, subsequent to thalamic processing. Here, we show that neurons in the lateral geniculate nucleus receiving excitatory retinal input from one eye can be suppressed by high-contrast visual stimulation of the other eye, indicating that the geniculate serves as a pre-cortical site of binocular processing.