Faculty Bibliography

Intracortical arterioles are key locations for blood flow regulation and oxygen supply in the brain and are critical to brain health and disease. However, imaging such small (<100-μm-sized) vessels in humans is challenging. Here, using non-human primates as a model, we developed a capability for imaging microvasculature in vivo with a clinical 7 T MRI scanner. Using simulations, we identified parameters for imaging intracortical vessels with slow flow and combined this with high-resolution imaging (64 × 64 μm² in-plane). Across large swaths of occipital, parietal, and temporal cortex, arrays of intracortical arterioles and venules were observed in gyral crowns and deep within sulcal folds. Systematic arteriole-venule patterns revealed potential architecture of input-output flow relationships. Even single vessels could be followed across cortical laminae. As a first step toward imaging microvasculature in humans, this method introduces a new technology and animal model for understanding relationships between functional and vascular architectures.

The primate amygdala serves to evaluate the emotional content of sensory inputs and modulate emotional and social behaviors; it modulates cognitive, multisensory and autonomic circuits predominantly via the basal, lateral and central nuclei, respectively. Recent evidence has suggested the mesoscale (millimeter-scale) nature of intra-amygdala functional organization. However, the connectivity patterns by which these mesoscale regions interact with brainwide networks remain unclear. Using infrared neural stimulation of single mesoscale sites coupled with mapping in ultrahigh field 7-T functional magnetic resonance imaging, we have discovered that these mesoscale sites exert influence over a surprisingly extensive scope of the brain. Our findings strongly indicate that mesoscale sites within the amygdala modulate brainwide networks through a 'one-to-many' (integral) way. Meanwhile, these connections exhibit a point-to-point (focal) topography. Our work provides new insights into the functional architecture underlying emotional and social behavioral networks, thereby opening up possibilities for individualized modulation of psychological disorders.

To restore vision in the blind, advances in visual cortical prosthetics (VCPs) have offered high-channel-count electrical interfaces. Here, we design a 100-fiber optical bundle interface apposed to known feature-specific (color, shape, motion, and depth) functional columns that populate the visual cortex in humans, primates, and cats. Based on a non-viral optical stimulation method (INS, infrared neural stimulation; 1,875 nm), it can deliver dynamic patterns of stimulation, is non-penetrating and non-damaging to tissue, and is movable and removable. In addition, its magnetic resonance (MR) compatibility (INS-fMRI) permits systematic mapping of brain-wide circuits. In the MRI, we illustrate (1) the single-point activation of functionally specific networks, (2) shifting cortical networks activated via shifting points of stimulation, and (3) "moving dot" stimulation-evoked activation of higher-order motion-selective areas. We suggest that, by mimicking patterns of columnar activation normally activated by visual stimuli, a columnar VCP opens doors for the planned activation of feature-specific circuits and their associated visual percepts.

In humans and nonhuman primates, the central 1° of vision is processed by the foveola, a retinal structure that comprises a high density of photoreceptors and is crucial for primate-specific high-acuity vision, color vision and gaze-directed visual attention. Here, we developed high-spatial-resolution ultrahigh-field 7T functional magnetic resonance imaging methods for functional mapping of the foveolar visual cortex in awake monkeys. In the ventral pathway (visual areas V1-V4 and the posterior inferior temporal cortex), viewing of a small foveolar spot elicits a ring of multiple (eight) foveolar representations per hemisphere. This ring surrounds an area called the 'foveolar core', which is populated by millimeter-scale functional domains sensitive to fine stimuli and high spatial frequencies, consistent with foveolar visual acuity, color and achromatic information and motion. Thus, this elaborate rerepresentation of central vision coupled with a previously unknown foveolar core area signifies a cortical specialization for primate foveation behaviors.

Major depressive disorder (MDD) is characterized by psychomotor retardation whose underlying neural source remains unclear. Psychomotor retardation may either be related to a motor source like the motor cortex or, alternatively, to a psychomotor source with neural changes outside motor regions, like input regions such as visual cortex. These two alternative hypotheses in main (n = 41) and replication (n = 18) MDD samples using 7 Tesla MRI are investigated. Analyzing both global and local connectivity in primary motor cortex (BA4), motor network and middle temporal visual cortex complex (MT+), the main findings in MDD are: 1) Reduced local and global synchronization and increased local-to-global output in motor regions, which do not correlate with psychomotor retardation, though. 2) Reduced local-to-local BA4 - MT+ functional connectivity (FC) which correlates with psychomotor retardation. 3) Reduced global synchronization and increased local-to-global output in MT+ which relate to psychomotor retardation. 4) Reduced variability in the psychophysical measures of MT+ based motion perception which relates to psychomotor retardation. Together, it is shown that visual cortex MT+ and its relation to motor cortex play a key role in mediating psychomotor retardation. This supports psychomotor over motor hypothesis about the neural source of psychomotor retardation in MDD.

The orientation map is one of the most well-studied functional maps of the visual cortex. However, results from the literature are of different qualities. Clear boundaries among different orientation domains and blurred uncertain distinctions were shown in different studies. These unclear imaging results will lead to an inaccuracy in depicting cortical structures, and the lack of consideration in experimental design will also lead to biased depictions of the cortical features. How we accurately define orientation domains will impact the entire field of research. In this study, we test how spatial frequency (SF), stimulus size, location, chromatic, and data processing methods affect the orientation functional maps (including a large area of dorsal V4, and parts of dorsal V1) acquired by intrinsic signal optical imaging. Our results indicate that, for large imaging fields, large grating stimuli with mixed SF components should be considered to acquire the orientation map. A diffusion model image enhancement based on the difference map could further improve the map quality. In addition, the similar outcomes of achromatic and chromatic gratings indicate two alternative types of afferents from LGN, pooling in V1 to generate cue-invariant orientation selectivity.

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 deliver infrared stimulation through these arrays in anesthetized cat visual cortex and monitor effects by optical imaging in contralateral visual cortex. Infrared neural stimulation modulation of response to ongoing visual oriented gratings produce 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 include 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.

SIGNIFICANCE/UNASSIGNED:Pulsed 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. AIM/UNASSIGNED:Estimates of summed population neuronal response time courses provide a potential basis for neural and hemodynamic signals described in other studies. APPROACH/UNASSIGNED:Using 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. RESULTS/UNASSIGNED:We 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 focal. Also, a contralateral activation is observed when INS applied. CONCLUSIONS/UNASSIGNED:In 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.

In human and nonhuman primate brains, columnar (mesoscale) organization has been demonstrated to underlie both lower and higher order aspects of visual information processing. Previous studies have focused on identifying functional preferences of mesoscale domains in specific areas; but there has been little understanding of how mesoscale domains may cooperatively respond to single visual stimuli across dorsal and ventral pathways. Here, we have developed ultrahigh-field 7 T fMRI methods to enable simultaneous mapping, in individual macaque monkeys, of response in both dorsal and ventral pathways to single simple color and motion stimuli. We provide the first evidence that anatomical V2 cytochrome oxidase-stained stripes are well aligned with fMRI maps of V2 stripes, settling a long-standing controversy. In the ventral pathway, a systematic array of paired color and luminance processing domains across V4 was revealed, suggesting a novel organization for surface information processing. In the dorsal pathway, in addition to high quality motion direction maps of MT, MST and V3A, alternating color and motion direction domains in V3 are revealed. As well, submillimeter motion domains were observed in peripheral LIPd and LIPv. In sum, our study provides a novel global snapshot of how mesoscale networks in the ventral and dorsal visual pathways form the organizational basis of visual objection recognition and vision for action.