Kacie Dougherty

Microcircuitry of agranular frontal cortex: contrasting laminar connectivity between occipital and frontal areas.

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.

Ongoing Alpha Activity in V1 Regulates Visually Driven Spiking Responses

Abstract 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.

Anisotropy of ongoing neural activity in the primate visual cortex

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.

Adaptation of Intracortical Signaling Concurs with Enhanced Encoding Efficiency

Stimulus repetitions improve performance despite decreased brain responses, suggesting that the brain is more efficient when processing familiar stimuli. Previous work demonstrated that stimulus repetition enhances encoding efficiency in primary visual cortex (V1) by increasing synchrony and sharpening the orientation tuning of neurons. Here we show that these adaptive changes are supported by an altered flow of sensory activation across the V1 laminar microcircuit. Using a repeating stimulus sequence, we recorded laminar responses in V1 of two fixating monkeys. We found repetition-related response reductions that were most pronounced outside V1 layers that receive the main retinogeniculate input. This repetition-induced suppression was robust to alternating stimuli between the eyes, in line with the notion that repetition suppression is predominantly of cortical origin. Congruent with earlier reports, we found that V1 adaptation to repeating stimuli is accompanied by sharpened neural tuning as well as increased neural synchrony. Current source density (CSD) analysis, which provides an estimate of net synaptic activation, revealed that the responses to repeated stimuli were most profoundly affected within layers that harbor the bulk of cortico-cortical connections. Together, these results suggest that stimulus repetition induces an altered state of intracortical processing resulting in enhanced encoding efficiency of sensory stimuli.

Binocular Integration Manifests as a Transient Spiking Increase Followed by Selective Suppression in Primary Visual Cortex

Research throughout the past decades revealed that neurons in primate primary visual cortex (V1) rapidly integrate the two eyes’ separate signals into a combined binocular response. The exact mechanisms giving underlying this binocular integration remain elusive. One open question is whether binocular integration occurs at a single stage of sensory processing or in a sequence of computational steps. To address this question, we examined the temporal dynamics of binocular integration across V1’s laminar microcircuit of awake behaving monkeys. We find that V1 processes binocular stimuli in a dynamic sequence that comprises at least two distinct phases: A transient phase, lasting 50-150ms from stimulus onset, in which neuronal population responses are significantly enhanced for binocular stimulation compared to monocular stimulation, followed by a sustained phase characterized by widespread suppression in which feature-specific computations emerge. In the sustained phase, incongruent binocular stimulation resulted in response reduction relative to monocular stimulation across the V1 population. By contrast, sustained responses for binocular congruent stimulation were either reduced or enhanced relative to monocular responses depending on the neurons’ selectivity for one or both eyes (i.e., ocularity). These results suggest that binocular integration in V1 occurs in at least two sequential steps, with an initial additive combination of the two eyes’ signals followed by the establishment of interocular concordance and discordance. Significance Statement Our two eyes provide two separate streams of visual information that are merged in the primary visual cortex (V1). Previous work showed that stimulating both eyes rather than one eye may either increase or decrease activity in V1, depending on the nature of the stimuli. Here we show that V1 binocular responses change over time, with an early phase of general excitation and followed by stimulus-dependent response suppression. These results provide important new insights into the neural machinery that supports the combination of the two eye’s perspectives into a single coherent view.

Binocular modulation of monocular V1 neurons

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.

Binocular response modulation in the lateral geniculate nucleus

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.

Spiking Suppression Precedes Cued Attentional Enhancement of Neural Responses in Primary Visual Cortex

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.

Visual spiking responses in V1 couple to alpha fluctuations in deep layers.

Alpha-range (8-12 Hz) neural rhythms, prominent over occipital cortex, can serve as a predictor of performance on visual tasks. Specifically, visual performance and attentional selection have been shown to co-vary with the ongoing alpha cycle recorded on the scalp. Despite their impact on visual performance, little is known about the intracortical origins of alpha rhythms and how alpha cycles impact visual processing. Here, we study laminar neural activity in primate visual cortex in order to determine a mechanistic link between alpha cycles and visually evoked spiking responses. Two macaque monkeys (Macaca radiata) fixated while static grating stimuli were presented inside of the receptive field under study. During this time, we recorded alpha-range local field potentials and multiunit spiking activity from all layers of V1 simultaneously. We found that throughout several hundred milliseconds of visual stimulation, spiking activity in all layers was strongly decreased at the time of alpha troughs recorded in the deep, feedback-recipient cortical layers compared to the level of columnar spiking at alpha peaks. Specifically, the magnitude of population spiking activity at the time of alpha troughs was nearly half that at alpha peaks, suggesting that alpha induces pulsed inhibition of visual responses at the earliest stages of cortical processing. Lastly in order to probe the potential role of feedback afferences, we will present a comparison of intracolumnar coupling between alpha and visual spiking responses between the two attentional states. Meeting abstract presented at VSS 2015.