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Mitchell, J. F.

Publications and source records attributed to Mitchell, J. F..

10 recordsLinked to original sources

Active sensing explains cortical variability and improves visual information

Active vision is often considered at the scale of saccades, with each fixation treated as a static visual sample. Yet the eyes continue to move during fixation, continually transforming the retinal input. Here we measured these movements at high precision while recording neuronal populations in the foveal primary visual cortex of awake marmosets viewing repeated flashed natural images. Fixational eye movements accounted for most conditional firing-rate variability and nearly all shared variability not explained by the trial-averaged response. An image-computable model captured this modulation largely from gaze-dependent retinal input; explicit eye-position and eye-velocity signals added little predictive power. Under natural viewing, retinal motion redistributed image power across temporal frequencies, and motion effects grew when this power engaged spatiotemporal tuning. In model-derived populations, fixational motion increased the spatial information carried per spike relative to stabilized input, with sharpening growing across successive nonlinear stages. Thus, activity commonly assigned to cortical noise is not just structured visual reafference generated by the movement of the observer, but is beneficial signal which sharpens spatial representations.

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Neural subpopulations in marmoset area MT/MTC detect and discount saccade-related retinal motion

Primates rely on eye movements made 2-3 times every second to scan their visual environment. Each eye movement induces substantial retinal motion, yet observers readily suppress it to stitch together the percept of a stable world. Neurons in the middle temporal (MT) and medial superior temporal (MST) areas respond to motion, but also suppress that response during eye movements (Bremmer et al., 2009; Leopold & Logothetis, 1998; Thiele et al., 2002). This saccadic suppression could reflect the influence of corollary feedback from eye movement related brain structures (Berman et al., 2017). However, visual signals that detect wide-field motion characteristic of a saccade could also contribute to suppression, akin to visual masking (Idrees et al., 2020). We sought to disentangle the relative contributions of visual signals and corollary discharge in driving saccadic suppression in areas MT and MTC in marmoset monkeys. Marmosets freely viewed natural images, blank backgrounds, or externally moving images that simulated saccades, and also made saccades in complete darkness. We found a diversity of saccadic modulation across the population. Some neurons showed short latency excitatory responses to saccades while others showed suppression. Still others showed a bi-phasic response that began with suppression followed by an excitatory rebound. Neurons with early responses were frequently tuned for the direction of saccades on natural images and retained that same tuning for saccades on blank screens or in complete darkness, thus supporting a role for corollary feedback. However, these neurons also responded with similar directional tuning for retinal motion created by simulating saccades while the eyes were fixed, and thus also appear to integrate visual cues for saccadic motion. More so, these units were biased towards having narrow spike waveforms consistent with putative inhibitory cells, which drive suppression observed in the rest of the population. We also found a subset of neurons that responded robustly to simulated saccadic motion but had negligible response to motion from real saccades, such that they discounted saccade induced motion. Those neurons were biased to have broader spike waveforms, consistent with being putative excitatory projection neurons and could support our percept of stability during eye movements.

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Active gaze behavior organizes V1 activity in freely-moving marmosets

Human and nonhuman primates rely heavily on vision to actively explore and navigate their environment. Although primate visual cortex has been studied extensively in head-fixed animals, little is known about how the primate visual system supports natural, active vision in freely moving animals. Here, we address this gap in the primary visual cortex (V1) by leveraging a head-mounted eye-tracking system while simultaneously recording the activity of ensembles of single V1 neurons in freely moving marmosets. Our results reveal that primate neural activity is tightly driven by visual input and organized by the temporal structure of natural gaze behavior, and these gaze-related responses are largely abolished in the absence of visual input. We further show that distinct phases of gaze movement, i.e. rapid redirection (gaze shift) and subsequent stabilization (fixation), engage separable suppression and enhancement of the V1 responses. The enhancement during fixation was clearly linked to visual input. Moreover, the amplitudes of naturally-occurring gaze shifts organize RF input across successive fixations, and adaptively shapes fixation-associated enhancement. These findings define the dynamics in V1 that link natural gaze behavior and stimulus-driven responses in freely moving primates. The work opens a previously inaccessible but fundamental regime of primate vision and establishes freely moving paradigms as a foundation for understanding real-world visual processing during ethologically relevant behaviors.

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Projection-Specific Intersectional Optogenetics for Precise Excitation and Inhibition in the Marmoset Brain

The primate cerebral cortex relies on long-range connections to integrate information across spatially distributed and functionally specialized areas, yet tools for selectively modulating these pathways remain limited. Here, we present an optimized intersectional viral and optogenetic strategy for precisely exciting and inhibiting projection-specific neurons in the common marmoset. Building on a mouse-to-marmoset pipeline, we first validated that optogenetic activation of inhibitory neurons (via AAV9-Dlx-ChR2) enables robust local cortical inhibition. We then combined retrograde delivery of Cre-recombinase (AAVretro-Cre) with locally injected Cre-dependent vectors encoding excitatory or inhibitory opsins (AAV8-FLEx-ChR2 or Jaws) to achieve directionally selective expression in callosal and frontoparietal pathways. Dual-opsin co-expression enabled precise stimulation or suppression of projection neurons in vivo with minimal off-target labeling. These results establish a scalable framework for projection-specific optogenetic interrogation of distributed circuits in primates, expanding the experimental toolkit for causal studies of higher-order brain function with enhanced anatomical precision and functional specificity. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=71 SRC="FIGDIR/small/660378v2_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@1b88c22org.highwire.dtl.DTLVardef@f831fdorg.highwire.dtl.DTLVardef@9a1403org.highwire.dtl.DTLVardef@197d351_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Pre-saccadic neural enhancements in marmoset area MT mimic covert attention

Each time we make an eye movement, attention moves before the eyes, resulting in a perceptual enhancement at the target. Recent psychophysical studies suggest that this pre-saccadic attention enhances the visual features at the saccade target, whereas covert attention causes only spatially-selective enhancements. While previous non-human primate studies have found that pre-saccadic attention does enhance neural responses spatially, no studies have tested if changes in neural tuning reflects an automatic feature enhancement. Here we examined pre-saccadic attention using a saccade foraging task developed for marmoset monkeys. We recorded from neurons in the middle temporal (MT) area with peripheral receptive fields that contained a motion stimulus which would either be the target of a saccade or a distracter as a saccade was made to another location. We established that marmosets, like macaques, show enhanced pre-saccadic neural responses for saccades towards the receptive field, including increases in firing rate and motion information. We then examined if the specific changes in neural tuning might support feature enhancements for the target. Neurons exhibited diverse changes in tuning, but predominantly showed additive and multiplicative increases that were uniformly applied across motion directions. These findings confirm that marmoset monkeys, like macaques, exhibit pre-saccadic neural enhancements during saccade foraging tasks with minimal training requirements. However, at the level of individual neurons, the lack of feature-tuned enhancements is similar to neural effects reported during covert spatial attention. Significance StatementAttention leads eye movements producing perceptual enhancements at saccade targets. Recent psychophysical studies indicate that increases in pre-saccadic sensitivity are concentrated around features of the target. We tested at the neural level how pre-saccadic attention modulates the tuning curves of visual neurons in area MT of marmoset monkeys. While neurons exhibited clear pre-saccadic enhancements that were consistent with previous studies in macaques, the changes in tuning were uniform across tuning. These results show pre-saccadic enhancements are a general feature of visual processing, shared by New World monkeys, but at the level of individual neurons enhancements are uniform across features much like what has been reported previously for covert attention.

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Post-saccadic following in the marmoset monkey as a read-out of pre-saccadic attention

Primates move their eyes 2-3 times per second to bring objects of interest to central, high-resolution vision. For moving objects, they use a combination of rapid saccadic eye movements along with smooth following movements to track targets continuously. Each saccadic eye movement produces perceptual enhancements for the target. And for saccades that are made to moving targets, or stationary apertures that contain motion, there is a smooth post-saccadic following response (PFR) of the target motion (Kwon et al, 2019). This PFR occurs involuntarily even when the motion is task irrelevant and could provide an automatic behavioral read-out of the targets motion. However, PFR movements are small, so it is unclear how reliable they would be as a trial-by-trial read-out. Here we examined PFR in marmoset monkeys performing a foraging task that requires almost no training and which has been shown to involve pre-saccadic neural enhancements of motion selective responses in visual area MT (Coop et al., 2024). We found that PFR in marmosets is highly consistent with humans and could be used to read-out the target motion. More so, we found that the motion in non-target apertures also influenced PFR but to a lesser extent than the target. The gain of PFR was distributed equally between target and non-target apertures before the saccade, and then was rapidly enhanced only for the target motion in driving the post-saccadic following. Thus, PFR provides a behavioral measure of target enhancement relative to distracters in addition to providing a read-out of the targets motion. Significance StatementUsing a saccade foraging paradigm in marmoset monkeys we measured visual motion integration and pre-saccadic enhancement based on the smooth following eye movements made after a saccade to a motion aperture. We find that marmosets exhibit post-saccadic following behaviors akin to humans, underscoring the evolutionary continuity in visual processing across primates. This following response provided an estimate of target motion that was half as accurate as explicitly trained reports but required minimal training to achieve. It also provided an estimate of the pre-saccadic enhancement for the target relative to distracters in the visual field.

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A dynamic sequence of visual processing initiated by gaze shifts

Animals move their head and eyes as they explore and sample the visual scene. Previous studies have demonstrated neural correlates of head and eye movements in rodent primary visual cortex (V1), but the sources and computational roles of these signals are unclear. We addressed this by combining measurement of head and eye movements with high density neural recordings in freely moving mice. V1 neurons responded primarily to gaze shifts, where head movements are accompanied by saccadic eye movements, but not to head movements where compensatory eye movements stabilize gaze. A variety of activity patterns immediately followed gaze shifts, including units with positive, biphasic, or negative responses, and together these responses formed a temporal sequence following the gaze shift. These responses were greatly diminished in the dark for the vast majority of units, replaced by a uniform suppression of activity, and were similar to those evoked by sequentially flashed stimuli in head-fixed conditions, suggesting that gaze shift transients represent the temporal response to the rapid onset of new visual input. Notably, neurons responded in a sequence that matches their spatial frequency preference, from low to high spatial frequency tuning, consistent with coarse-to-fine processing of the visual scene following each gaze shift. Recordings in foveal V1 of freely gazing head-fixed marmosets revealed a similar sequence of temporal response following a saccade, as well as the progression of spatial frequency tuning. Together, our results demonstrate that active vision in both mice and marmosets consists of a dynamic temporal sequence of neural activity associated with visual sampling. HighlightsO_LIDuring free movement, neurons in mouse V1 respond to head movements that are accompanied by a gaze-shifting saccadic eye movement, but not a compensatory eye movement. C_LIO_LINeurons respond to gaze shifts with diverse temporal dynamics that form a sequence across the population, from early positive responses to biphasic and negative responses. C_LIO_LIIn darkness, most neurons show a uniform suppression following a gaze shift. C_LIO_LITemporal dynamics of responses correspond to a neurons temporal and spatial frequency preferences, consistent with a coarse-to-fine processing sequence. C_LIO_LIA similar temporal sequence following saccades is observed in foveal V1 of freely gazing head-fixed marmosets, demonstrating shared aspects of active visual processing across species. C_LI

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Beyond Fixation: detailed characterization of neural selectivity in free-viewing primates

Virtually all vision studies use a fixation point to stabilize gaze, rendering stimuli on video screens fixed to retinal coordinates. This approach requires trained subjects, is limited by the accuracy of fixational eye movements, and ignores the role of eye movements in shaping visual input. To overcome these limitations, we developed a suite of hardware and software tools to study vision during natural behavior in untrained subjects. We show this approach recovers receptive fields and tuning properties of visual neurons from multiple cortical areas of marmoset monkeys. Combined with high-precision eye-tracking, it achieves sufficient resolution to recover the receptive fields of foveal V1 neurons. These findings demonstrate the power of free viewing to characterize neural response while simultaneously studying the dynamics of natural behavior. HighlightsO_LIWe introduce a free-viewing paradigm for studying neural mechanisms of visual processing during active vision C_LIO_LIReceptive fields (RFs) and neural selectivity in primary visual cortex (V1) and area MT can be extracted during free-viewing in minimally-trained subjects C_LIO_LINovel high-resolution eye tracking in this context supports detailed measurements of receptive fields in foveal V1 C_LI

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Perceptual restoration fails to recover unconscious processing for smooth eye movements after occipital stroke

The visual pathways that guide actions do not necessarily mediate conscious perception. Patients with primary visual cortex (V1) damage lose conscious perception but often retain unconscious abilities (e.g. blindsight). Here, we asked if saccade accuracy and post-saccadic following responses (PFRs) that automatically track target motion upon saccade landing are retained when conscious perception is lost. We contrasted these behaviors in the blind and intact-fields of 11 chronic V1-stroke patients, and in 8 visually-intact controls. Saccade accuracy was relatively normal in all cases. Stroke patients also had normal PFR in their intact-fields, but no PFR in their blind-fields. Thus, V1 damage did not spare the unconscious visual processing necessary for automatic, post-saccadic smooth eye movements. Importantly, visual training that recovered motion perception in the blind-field did not restore the PFR, suggesting a clear dissociation between pathways mediating perceptual restoration and automatic actions in the V1-damaged visual system.

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Motion perception in the common marmoset

Visual motion processing is a well-established model system for studying neural population codes in primates. The common marmoset, a small new world primate, offers unparalleled opportunities to probe these population codes in key motion processing areas, such as cortical areas MT and MST, because these areas are accessible for imaging and recording at the cortical surface. However, little is currently known about the perceptual abilities of the marmoset. Here, we introduce a paradigm for studying motion perception in the marmoset and compare their psychophysical performance to human observers. We trained two marmosets to perform a motion estimation task in which they provided an analog report of their perceived direction of motion with an eye movement to a ring that surrounded the motion stimulus. Marmosets and humans exhibited similar trade-offs in speed vs. accuracy: errors were larger and reaction times were longer as the strength of the motion signal was reduced. Reverse correlation on the temporal fluctuations in motion direction revealed that both species exhibited short integration windows, however, marmosets had substantially less non-decision time than humans. Our results provide the first quantification of motion perception in the marmoset and demonstrate several advantages to using analog estimation tasks.

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