Biology subjects

Roe, A. W.

Publications and source records attributed to Roe, A. W..

17 recordsLinked to original sources

bioRxiv2026

From sensation to action: distributed mesoscale dynamics in the primate brain

Perceptual decisions engage distributed brain networks, yet how decision-related signals are organized across and within brain areas remains unclear. Mesoscale functional domains are established in visual cortex, but whether spatially distinct domains organize perceptual decisions across the brain is unknown. Here we used 7-T functional MRI at 1-mm isotropic resolution in two awake macaques performing a contrast-discrimination task to map brain-wide activity during sensation, decision formation and saccadic report. Voxel timecourses separated into three groups with distinct temporal profiles, associated with sensory, decision-related and action-related activity. Their spatial distributions formed a broad progression from visual cortex to parietal, prefrontal and motor regions, while revealing distinct response domains within these regions. Choice-related signals were distributed across sensory, associative, and motor systems before movement, including in visual cortex responses to physically identical stimuli that differed according to the animal's eventual choice. Moreover, within the intraparietal sulcus and other regions, mesoscale domains preferentially responsive to near-threshold conditions carried choice information under uncertainty, whereas domains responsive to high-contrast conditions carried choice information when evidence was strong. These findings reveal that perceptual decisions are organized across the brain through spatially differentiated mesoscale networks whose activity varies with task phase and sensory certainty. This spatial organization provides a framework for investigating how distributed neural signals support flexible choice.

neuroscience↗

bioRxiv2026

Brain state shapes the polarity of pulsed infrared neural stimulation responses in individual cortical neurons

Pulsed infrared neural stimulation (INS, 1875nm the peak of energy absorption by water) is a non-viral method developed to activate single submillimeter sites in the brain. When used in ultrahigh-field fMRI, it reveals functionally specific brain-wide columnar networks comprising synaptically activated nodes. INS is non-damaging and effective for use in the human cortex and is useful for neural and behavioral neuromodulation in primates. To investigate how physiological state influences its cellular effects, we performed in vivo two-photon calcium imaging with GCaMP6s in mice and tracked identified cortical neurons in awake vs anesthetized states. Across the tested radiant exposures, INS-evoked responses differed markedly between states: under anesthesia, stimulation produced predominantly positive-going calcium responses, whereas during wakefulness the same identified neurons exhibited negative-going responses. Pharmacological manipulation of this baseline level by GABAergic signaling shifted response polarity in opposite directions: picrotoxin under anesthesia produced awake-like negative responses, whereas muscimol during wakefulness produced anesthetized-like positive responses. Trial-by-trial analyses further showed that the relationship between pre-stimulus baseline level and INS-evoked response depended on physiological state. Because INS relies on transient tissue heating, we also developed an in situ EGFP-based calibration approach to estimate temperature-related fluorescence changes. These fluoro-thermal contributions were modest at lower radiant exposures and became increasingly important at higher exposures, particularly near the fiber pathway. The low-intensity results are consistent with, but do not establish, a state-dependent feed-forward inhibitory framework. Together, these findings show that the neuronal response to focal INS is shaped by ongoing brain state and provide a practical framework for separating state-dependent calcium responses from temperature-related fluorescence effects, making INS a potentially versatile tool for neuroscience and clinical applications.

neuroscience↗

bioRxiv2026

INS-fMRI: a novel method for mapping mesoscale connectome networks in vivo in nonhuman primates

Mapping brain connections is paramount in neuroscience. Lacking has been a method that can systematically map mesoscale (<1mm) connections in the brain in vivo at brainwide scale. Mesoscale mapping is particularly important for NHPs in which information is represented in submillimeter clusters (e.g. cortical columns, striosomes, thalamic rods). Here, we present a method called INS-fMRI, which comprises optical stimulation of single sites in the brain using pulsed Infrared Neural Stimulation (INS), coupled with mapping of functionally connected sites in the brain using ultrahigh field fMRI. It is the only method available for mapping mesoscale connections rapidly (multiple networks mapped within single MRI sessions), systematically (allowing comparison of networks within single individuals), in vivo (no animal sacrifice needed), at whole brain scale, and without viral transfection. This method has broad applicability to a wide range of neuroscience questions. It can be used at any brain site, on different animal models, and on different MRI platforms. The ability to probe circuits repeatedly within single individuals also opens doors for studying changes in mesoscale circuits over time (e.g. for development, aging, disease studies). In addition, as this method circumvents the need for viral transfection, there is exciting potential for human clinical application.

neuroscience↗

bioRxiv2026

Precise Functional Localization of the Foveolar Representation in Anesthetized Macaque Visual Cortex

The foveola-the central ~1{degrees} of the visual field-supports the highest-acuity spatial vision, yet localizing its cortical representation is technically demanding, particularly under anesthesia where gaze cannot be behaviorally controlled. Here we describe a hierarchical, meridian-based 7T BOLD fMRI strategy for sub-degree localization of the foveolar representation in anesthetized macaques. Drifting grating bars presented at three successively finer scales (4.5{degrees}, 1.5{degrees}, 0.5{degrees}) independently refined the vertical and horizontal meridian representations, each identified by a characteristic activation signature: bilateral convergence at the V1/V2 border for the vertical meridian, and simultaneous dorsal and ventral V2/V3 activation at the fundus of the calcarine sulcus for the horizontal. Their functional intersection defined candidate foveolar coordinates, which were refined using 0.2{degrees} spot stimuli. Surface-based rendering resolved discrete foveolar loci at the lateral end of the V1/V2, V2/V3, V3/V4 and V4/TEO borders, together delimiting the previously described 'foveolar core'. Pooling these with awake data, we place the loci in a common stereotaxic frame, yielding a first anatomical atlas of the core. Intrinsic-signal optical imaging further shows that this territory lacks the ocular-dominance and orientation columns of surrounding cortex. The approach provides a reproducible framework for locating and targeting foveolar cortex in anesthetized primates.

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bioRxiv2026

Toward Optimizing Thalamic Deep Brain Stimulation for Cortical Modulation: A Surrogate Brain Approach

The thalamus is a central hub that interfaces with widespread cortical and subcortical nodes. Thalamic deep brain stimulation (DBS) offers a principled strategy for distributed cortical modulation: since distinct thalamic nuclei project to spatially segregated cortical territories, stimulation at a single thalamic site can influence multiple cortical nodes. Realizing this potential requires accurate subject-specific estimates of directed thalamocortical effective connectivity (EC) and a computational framework for optimizing stimulation parameters that achieve desired cortical responses. Here, we address both challenges using Neural Perturbational Inference (NPI), a surrogate-brain approach that estimates EC by applying virtual perturbations to a nonlinear dynamical model fitted to resting-state fMRI data. We extend NPI to a high-resolution thalamocortical network comprising 360 cortical regions and 442 thalamic voxels spanning 12 nuclei. We introduce two innovations in training: (i) a temporal signal-to-noise ratio (tSNR)-weighted loss accounting for signal heterogeneity, and (ii) a multi-resolution, cross-scale consistency loss that regularizes model complexity. These strategies yield improved performance in synthetic benchmarks across varying tSNR regimes. Leveraging the inferred subject-specific EC, we further formulate a constrained linear control problem to identify sparse thalamic stimulation targets that achieve desired cortical activation patterns. We validate the inferred EC structure on two independent datasets: the MacStim dataset comprising two macaque monkeys with infrared neural stimulation on medial pulvinar, and the HumanTC resting-state fMRI dataset comprising twelve human subjects. Our results reveal site-specific thalamocortical EC profiles, producing interpretable predictions that align with known ground-truth structures. Together, this work establishes a computationally grounded pathway toward personalized optimization of thalamic DBS in both human and nonhuman primates.

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bioRxiv2026

INS-fMRI reveals a mesoscale limbic organization associated with medial pulvinar in primates

The experience of emotion comprises not only the feelings (happiness, sadness), but also behavioral expression, internal awareness, and the bodys physiological response. However, it remains unclear how the brain integrates these disparate aspects of emotion. Here, to examine functional connectivity in the limbic system of macaque monkeys, we combined focal Infrared Neural Stimulation of a sensory gateway (medial pulvinar PM), with ultra-high-field 7T functional magnetic resonance imaging (INS-fMRI). We find connected sites are mesoscale (millimeter-scale) in size and arranged in patchy patterns across cingulate, insula, and amygdala. Non-overlapping connections evoked from three sequential stimulation sites in PM form clusters of multi-site integration, and appear related to known functional organization within these limbic regions. We suggest these mesoscale functional connections link the limbic axes of motor expression (cingulate), interoception (insula), and emotion-related processing (amygdala), and that, much like visual system, the limbic system is fundamentally quite orderly at mesoscale. Our results underscore the importance of millimeter-scale precision and organization in diagnosis and treatment of affective disorders.

neuroscience↗

bioRxiv2024

A Unified Theory of Response Sparsity and Variability for Energy-Efficient Neural Coding

Understanding how cortical neurons use dynamic firing patterns to represent sensory signals is a central challenge in neuroscience. Decades of research have shown that cortical neuronal activities exhibit high variance, typically quantified by the coefficient of variation (CV), suggesting intrinsic randomness. Conversely, substantial evidence indicates that cortical neurons display high response sparseness, indicative of efficient encoding. The apparent contradiction between these neural coding properties--stochastic yet efficient--has lacked a unified theoretical framework. This study aims to resolve this discrepancy. We conducted a series of analyses to establish a direct relational function between CV and sparseness, proving they are intrinsically correlated or equivalent across different statistical distributions in neural activities. We further derive a function showing that both irregularity and sparsity in neuronal activities are positive functions of energy-efficient coding capacity, quantified by Information-Cost Efficiency (ICE). This suggests that the observed high irregularity and sparsity in cortical activities result from a shared mechanism optimized for maximizing information encoding capacity while minimizing cost. Furthermore, we introduce a CV-maximization algorithm to generate kernel functions replicating the receptive fields of the primary visual cortex. This finding indicates that the neuronal functions in the visual cortex are optimal energy-efficient coding operators for natural images. Hence, this framework unifies the concepts of irregularity and sparsity in neuronal activities by linking them to a common mechanism of coding efficiency, offering deeper insights into neural coding strategies.

neuroscience↗

bioRxiv2024

Emergence of Orientation Pinwheels in a Self-Evolving Spiking Neural Network: Enhancing Visual Coding Efficiency and Reliability

Orientation preference maps (OPMs) in the primary visual cortex of primates organize orientation-tuned neurons into columnar structures, forming pinwheel-like patterns. However, lower-level animals like rodents typically exhibit a lack of OPMs, with neurons either randomly distributed or aggregated in small clusters. This distinction prompts an inquiry into whether more structured cortical columns correlate with improved visual computational or coding efficiency. To explore this, we propose a novel self-evolving spiking neural network (SESNN). To the best of our knowledge, the SESNN is the first spiking network, incorporating mechanisms of neural plasticity in forming neural connections without explicit objective functions. We reveal that the emergence of pinwheel structures is primarily driven by sparse coding constraints and local synaptic plasticity as fundamental mechanisms. Second, for higher mammals with expansive iso-orientation domains (IODs), the firing responses in pinwheel structures primarily emanate from pinwheel centers (PCs) and progressively extend toward the periphery, encompassing adjacent IODs. Third, the size and organization of these IODs across species are significantly influenced by the receptive fields ability to process overlapping visual information. Lastly, PCs within large IODs demonstrate enhanced robustness and population sparseness in detecting a variety of orientation features. These results indicate that the spatial pinwheel structure facilitates highly efficient and reliable coding performance.

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bioRxiv2024

Two-photon imaging of excitatory and inhibitory neural response to infrared neural stimulation

SignificancePulsed infrared neural stimulation (INS, 1875 nm) is an emerging neurostimulation technology that delivers focal pulsed heat to activate functionally specific mesoscale networks and holds promise for clinical application. However, little is known about its effect on excitatory and inhibitory cell types in cerebral cortex. AimEstimates of summed population neuronal response timecourses provide a potential basis for neural and hemodynamic signals described in other studies. ApproachUsing two-photon calcium imaging in mouse somatosensory cortex, we have examined the effect of INS pulse train application on hSyn neurons and mDlx neurons tagged with GCaMP6s. ResultsWe find that, in anesthetized mice, each INS pulse train reliably induces robust response in hSyn neurons exhibiting positive going responses. Surprisingly, mDlx neurons exhibit negative going responses. Quantification using the index of correlation illustrates responses are reproducible, intensity-dependent, and distance-dependent. Also, a contralateral activation is observed when INS application. ConclusionsIn sum, the population of neurons stimulated by INS includes both hSyn and mDlx neurons; within a range of stimulation intensities, this leads to overall excitation in the stimulated population, leading to the previously observed activations at distant post-synaptic sites.

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bioRxiv2024

A novel interface for cortical columnar neuromodulation with multi-point infrared neural stimulation

Cutting edge advances in electrical visual cortical prosthetics have evoked perception of shapes, motion, and letters in the blind. Here, we present an alternative optical approach using pulsed infrared neural stimulation. To interface with dense arrays of cortical columns with submillimeter spatial precision, both linear array and 100-fiber bundle array optical fiber interfaces were devised. We delivered infrared stimulation through these arrays in anesthetized cat visual cortex and monitored effects by optical imaging in contralateral visual cortex. INS modulation of response to ongoing visual oriented gratings produced enhanced responses in orientation-matched domains and suppressed responses in non-matched domains, consistent with a known higher order integration mediated by callosal inputs. Controls included dynamically applied speeds, directions and patterns of multipoint stimulation. This provides groundwork for a distinct type of prosthetic targeted to maps of visual cortical columns.

neuroscience↗

bioRxiv2024

Brainwide mesoscale functional networks revealed by focal infrared neural stimulation of the amygdala

The primate amygdala serves to evaluate emotional content of sensory inputs and modulate emotional and social behaviors; it modulates cognitive, multisensory and autonomic circuits predominantly via the basal (BA), lateral (LA), and central (CeA) nuclei, respectively. Based on recent electrophysiological evidence suggesting mesoscale (millimeters-scale) nature of intra-amygdala functional organization, we have investigated the connectivity of these nuclei using Infrared Neural Stimulation of single mesoscale sites coupled with mapping in ultrahigh field 7T functional Magnetic Resonance Imaging (INS-fMRI). Stimulation of multiple sites within amygdala of single individuals evoked mesoscale functional connectivity maps, allowing comparison of BA, LA and CeA connected brainwide networks. This revealed a mesoscale nature of connected sites, complementary spatial patterns of functional connectivity, and topographic relationships of nucleus-specific connections. Our data reveal a functional architecture of systematically organized brainwide networks mediating sensory, cognitive, and autonomic influences from the amygdala.

neuroscience↗

bioRxiv2024

Multiple Loci for Foveolar Vision in Macaque Monkey

A common tenet of neural sensory representation is that species-specific behaviors are reflected in specialized brain organizations1. In humans and nonhuman primates, the central one degree of vision is processed by the foveola2, a retinal structure which comprises a high density of photoreceptors and is crucial for primate-specific high acuity vision, color vision, and gaze-directed visual attention3,4,5. In this study, we have developed high spatial resolution ultrahigh field 7T fMRI methods for functional mapping of foveolar visual cortex in awake monkeys. We provide evidence that, in the ventral pathway (V1-V4 and TEO), viewing of a central small spot elicits a ring of multiple (at least 8) foveolar representations per hemisphere. This ring surrounds a large area called the foveolar core. This is an area populated by millimeter-scale functional domains sensitive to fine stimuli and high spatial frequencies, consistent with foveolar visual acuity, as well as color and achromatic information, and motion. The unique position of the foveolar core suggests it may be a hub subserving higher order needs of foveolar function, such as integrating different spatial scales of representation, integrating local and global features in object perception, and bringing together the four quadrants of visual space. Thus, this elaborate re-representation of central vision signifies a cortical specialization for various foveation behaviors.

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bioRxiv2022

Spatial frequency representation in V2 and V4 of macaque monkey

Spatial frequency (SF) is an important attribute in the visual scene and is a defining feature of visual processing channels. However there remains many unsolved questions about how primate visual cortex, in particular extrastriate areas V2 and V4, codes this fundamental information. Here, using intrinsic signal optical imaging in visual cortex of Macaque monkeys, we quantify the relationship between spatial frequency maps and (1) visual topography, (2) color and orientation maps, and (3) across visual areas V1, V2, and V4. We find that in orientation regions, low to high spatial frequency is mapped orthogonally to orientation; however, in color regions, which is reported to contain orthogonal axes of color and lightness, only low spatial frequencies are represented without a gradient of SF representation. This produces the first observation of a population spatial frequency fluctuation related to the repeating color/orientation organizations. These findings support a generalized hypercolumn model across cortical areas, comprised of two orthogonal parameters with additional parameters.

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bioRxiv2022

Precision 1070 nm Ultrafast Laser-induced Photothrombosis (PLP) of Depth-targeted Vessels in vivo

The cerebrovasculature plays an essential role in neurovascular and homeostatic functions in health and disease conditions. Many efforts have been made for developing vascular thrombosis methods to study vascular dysfunction in vivo, while technical challenges remain, such as accuracy and depth-selectivity to target single vessel in the cerebral cortex. Herein, we first demonstrates the evaluation and quantification of the feasibility and effects of Rose Bengal (RB)-induced photothrombosis with 720-1070 nm ultrafast lasers in raster scan. A flexible and reproducible approach is then proposed to employ a 1070 nm ultrafast laser with spiral scan for producing RB-induced occlusion, which is described as precision ultrafast laser-induced photothrombosis (PLP). Combine with two-photon microscopy imaging, this PLP displays highly precise and fast occlusion induction of various vessel types, sizes, and depths, which enhances the precision and power of the photothrombosis protocol. Overall, the PLP method provides a real-time, practical, precise, and depth-selected single-vessel photothrombosis technology in cerebral cortex with commercially available optical equipment, which is crucial for exploring brain vascular function with high spatial temporal resolution in brain.

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bioRxiv2021

Imaging microvasculature network evolution and neurodegeneration with precise photothrombosis approach

In the cerebral cortex, the vasculature plays important homeostatic functions, especially at the highly connected complex capillary networks. The association of focal capillary ischemia with the neurodegenerative disease as well as the laminar vascular dynamics have prompted studies of vascular micro-occlusion via photothrombosis. However, technical challenges of this approach remain, including increased temporal precision of occlusion, increasing the depth of vascular occlusion, understanding how such micro-occlusion impacts local blood flow, and ultimately the neuronal effects of such changes. Here, we have developed a novel approach that employs ultra-fast multiphoton light to induce focal Rose Bengal-induced photothrombosis. We demonstrated induction of highly precise and fast occlusion of microvessels at various types and depths. The change of the microvascular architecture and hemodynamics after occlusion revealed the autoregulation and significant difference between upstream vs downstream in layer 2/3. Further, we found that micro-occlusion at two different layers within the same vascular arbor results in distinct effects on the acute flow redistribution mechanism. To examine neuronal effects of such micro-occlusion, we produced infarct of capillaries surrounding a labeled target neuron and found this induces dramatic and rapid lamina-specific degeneration in neuronal dendritic architecture. In sum, our technique enhanced the precision and power of the photothrombotic study of microvascular function. The current results pointed to the importance of laminar scale regulation within the microvascular network, a finding which may be relevant for models of neurovascular disease.

neuroscience↗

bioRxiv2020

Curvature domains in V4 of Macaque Monkey

An important aspect of visual object recognition is the ability to perceive object shape. How the brain encodes fundamental aspects of shape information remains poorly understood. Models of object shape representation describe a multi-stage process that includes encoding of contour orientation and curvature. While modules encoding contour orientation are well established (orientation domains in V1 and V2 visual cortical areas), whether there are modules for curvature is unknown. In this study, we identify a module for curvature representation in area V4 of monkey visual cortex and illustrate a systematic representation of low to high curvature and of curvature orientation, indicative of curvature hypercolumns in V4. We suggest that identifying systematic modular organizations at each stage of the visual cortical hierarchy signifies the key computations performed. SignificanceWe use intrinsic signal optical imaging in area V4 of anesthetized macaque monkey to study the functional organization of curvature representation. We find a modular basis for cue-invariant curvature representation in area V4 of monkey visual cortex and illustrate a systematic representation from low to high curvature and of curvature orientation, replete with curvature pinwheels. This is the first report of systematic functional organization for curvature representation in the visual system. The use of optical imaging has revealed at a population level spatial details of cortical responses, something which has not been evident from previous studies of single neurons. These data support a representational architecture underlying a curvature hypercolumn in V4.

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bioRxiv2019

NIR-II fluorescence microscopic imaging of cortical vasculature in non-human primates

Vasculature architecture in the brain can provide revealing information about mental and neurological function and disease. Fluorescence imaging in the second near-infrared (NIR-II) regime with less light scattering is a more promising method for detecting cortical vessels than traditional visible and NIR-I modes. Here, for the first time, we developed, NIR-II fluorescence microscopy capabilities for imaging brain vasculature in macaque monkey. The first is a wide-field microscope with high temporal resolution (25 frames/second) for measuring blood flow velocity and cardiac impulse period, and the second is a high spatial resolution (<10 m) confocal microscope producing three-dimensional maps of the cortical microvascular network ([~]500 m deep). Both were designed with flexibility to image various cortical locations on the head. Use of a clinically approved dye provided high brightness in NIR-II region. This comprises an important advance towards studies of neurovascular coupling, stroke, and other diseases relevant to neurovascular health in humans.

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