Reza Rajimehr

A high-light sensitivity optical neural silencer: development and application to optogenetic control of non-human primate cortex.

Technologies for silencing the electrical activity of genetically targeted neurons in the brain are important for assessing the contribution of specific cell types and pathways toward behaviors and pathologies. Recently we found that archaerhodopsin-3 from Halorubrum sodomense (Arch), a light-driven outward proton pump, when genetically expressed in neurons, enables them to be powerfully, transiently, and repeatedly silenced in response to pulses of light. Because of the impressive characteristics of Arch, we explored the optogenetic utility of opsins with high sequence homology to Arch, from archaea of the Halorubrum genus. We found that the archaerhodopsin from Halorubrum strain TP009, which we named ArchT, could mediate photocurrents of similar maximum amplitude to those of Arch (∼900 pA in vitro), but with a >3-fold improvement in light sensitivity over Arch, most notably in the optogenetic range of 1–10 mW/mm2, equating to >2× increase in brain tissue volume addressed by a typical single optical fiber. Upon expression in mouse or rhesus macaque cortical neurons, ArchT expressed well on neuronal membranes, including excellent trafficking for long distances down neuronal axons. The high light sensitivity prompted us to explore ArchT use in the cortex of the rhesus macaque. Optical perturbation of ArchT-expressing neurons in the brain of an awake rhesus macaque resulted in a rapid and complete (∼100%) silencing of most recorded cells, with suppressed cells achieving a median firing rate of 0 spikes/s upon illumination. A small population of neurons showed increased firing rates at long latencies following the onset of light stimulation, suggesting the existence of a mechanism of network-level neural activity balancing. The powerful net suppression of activity suggests that ArchT silencing technology might be of great use not only in the causal analysis of neural circuits, but may have therapeutic applications.

An anterior temporal face patch in human cortex, predicted by macaque maps

Increasing evidence suggests that primate visual cortex has a specialized architecture for processing discrete object categories such as faces. Human fMRI studies have described a localized region in the fusiform gyrus [the fusiform face area (FFA)] that responds selectively to faces. In contrast, in nonhuman primates, electrophysiological and fMRI studies have instead revealed 2 apparently analogous regions of face representation: the posterior temporal face patch (PTFP) and the anterior temporal face patch (ATFP). An earlier study suggested that human FFA is homologous to the PTFP in macaque. However, in humans, no obvious homologue of the macaque ATFP has been demonstrated. Here, we used fMRI to map face-selective sites in both humans and macaques, based on equivalent stimuli in a quantitative topographic comparison. This fMRI evidence suggests that such a face-selective area exists in human anterior inferotemporal cortex, comprising the apparent homologue of the fMRI-defined ATFP in macaques.

The radial bias: a different slant on visual orientation sensitivity in human and nonhuman primates.

It is generally assumed that sensitivity to different stimulus orientations is mapped in a globally equivalent fashion across primate visual cortex, at a spatial scale larger than that of orientation columns. However, some evidence predicts instead that radial orientations should produce higher activity than other orientations, throughout visual cortex. Here, this radial orientation bias was robustly confirmed using (1) human psychophysics, plus fMRI in (2) humans and (3) behaving monkeys. In visual cortex, fMRI activity was at least 20% higher in the retinotopic representations of polar angle which corresponded to the radial stimulus orientations (relative to tangential). In a global demonstration of this, we activated complementary retinotopic quadrants of visual cortex by simply changing stimulus orientation, without changing stimulus location in the visual field. This evidence reveals a neural link between orientation sensitivity and the cortical retinotopy, which have previously been considered independent.

Scene-Selective Cortical Regions in Human and Nonhuman Primates

fMRI studies have revealed three scene-selective regions in human visual cortex [the parahippocampal place area (PPA), transverse occipital sulcus (TOS), and retrosplenial cortex (RSC)], which have been linked to higher-order functions such as navigation, scene perception/recognition, and contextual association. Here, we document corresponding (presumptively homologous) scene-selective regions in the awake macaque monkey, based on direct comparison to human maps, using identical stimuli and largely overlapping fMRI procedures. In humans, our results showed that the three scene-selective regions are centered near—but distinct from—the gyri/sulci for which they were originally named. In addition, all these regions are located within or adjacent to known retinotopic areas. Human RSC and PPA are located adjacent to the peripheral representation of primary and secondary visual cortex, respectively. Human TOS is located immediately anterior/ventral to retinotopic area V3A, within retinotopic regions LO-1, V3B, and/or V7. Mirroring the arrangement of human regions fusiform face area (FFA) and PPA (which are adjacent to each other in cortex), the presumptive monkey homolog of human PPA is located adjacent to the monkey homolog of human FFA, near the posterior superior temporal sulcus. Monkey TOS includes the region predicted from the human maps (macaque V4d), extending into retinotopically defined V3A. A possible monkey homolog of human RSC lies in the medial bank, near peripheral V1. Overall, our findings suggest a homologous neural architecture for scene-selective regions in visual cortex of humans and nonhuman primates, analogous to the face-selective regions demonstrated earlier in these two species.

Unconscious Orientation Processing

Recent findings have shown that certain attributes of visual stimuli, like orientation, are registered in cortical areas when the stimulus is unresolvable or perceptually invisible; however, there is no evidence to show that complex forms of orientation processing (e.g., modulatory effects of orientation on the processing of other features) could occur in the absence of awareness. To address these questions, different psychophysical paradigms were designed in six experiments to probe unconscious orientation processing. First we demonstrated orientation-selective adaptation and color-contingent orientation adaptation for peripheral unresolvable Gabor patches. The next experiments showed the modulatory effects of perceptually indiscriminable orientations on apparent motion processing and attentional mechanisms. Finally we investigated disappearance patterns of unresolvable Gabor stimuli during motion-induced blindness (MIB). Abrupt changes in local unresolvable orientations truncated MIB; however, orientation-based grouping failed to affect the MIB pattern when the orientations were unresolvable. Overall results revealed that unresolvable orientations substantially influence perception at multiple levels.

Does retinotopy influence cortical folding in primate visual cortex

In humans and other Old World primates, much of visual cortex comprises a set of retinotopic maps, embedded in a cortical sheet with well known, identifiable folding patterns. However, the relationship between these two prominent cortical variables has not been comprehensively studied. Here, we quantitatively tested this relationship using functional and structural magnetic resonance imaging in monkeys and humans. We found that the vertical meridian of the visual field tends to be represented on gyri (convex folds), whereas the horizontal meridian is preferentially represented in sulci (concave folds), throughout visual cortex in both primate species. This relationship suggests that the retinotopic maps may constrain the pattern of cortical folding during development.

Attentional modulation of adaptation to illusory lines

Selective visual attention modulates neuronal activation in various cortical areas. This type of neuronal modulation could happen even in the early stages of visual processing where specific attributes of visual stimuli are processed. It has been shown that different forms of visual aftereffects, such as tilt aftereffect, motion aftereffect, and figural aftereffect, are modulated by attention. In this study, we investigated the effect of visual attention on adaptation to illusory lines. In the first experiment, orientation selective adaptation to a peripheral illusory line was measured in three conditions: (1) poor attention condition in which subjects performed a dual task (even-odd judgment) at the fixation point during the adaptation period, (2) partial attention condition in which subjects only observed successively presented digits at the fixation point and did not perform the task during the adaptation period, and (3) full attention condition in which no visual stimuli were presented at the fixation point. Results showed that the magnitude of adaptation systematically decreased as the attentional load at the fixation point increased. In the second experiment, two transparent illusory contours were presented during the adaptation period, and tilt aftereffects to attended and non-attended illusory lines were compared. The magnitude of tilt aftereffect to the attended illusory line was significantly greater than that to the non-attended illusory line even when non-attended illusory contour was more visually salient. Because visual areas V2 and V1 are the first stage in the processing of illusory contours, we could conclude that visual attention has modulatory effects on the activation of neurons in these areas.

Subliminal attentional modulation in crowding condition.

In the crowding phenomenon, recognition of a visual target is impaired by other similar visual stimuli (distracters) presented near the target. This effect may be due largely to insufficient resolution of spatial attention. We showed that attention could subliminally enhance orientation selective adaptation to illusory lines in the crowding condition where target-distractor separation is beyond the limit of spatial resolution of attention. Despite the traditionally held close link between attention and awareness, here we provided evidence for subliminal attentional modulation for orientation stimuli that could not have been consciously perceived.

Adaptation to apparent motion in crowding condition

Visual adaptation has been successfully used for studying the neural activity of different cortical areas in response to visual stimuli when observers do not have explicit conscious access to those stimuli. We compared the orientation selective adaptation to apparent motion and its effect on the perception of stimuli with bistable apparent motion in crowded and non-crowded conditions. In the crowding paradigm conscious access to a visual stimulus is severely impaired when it is flanked by other similar stimuli in the peripheral visual field. As expected, adaptation to the target stimulus occurred in the non-crowded condition in all of the individual subjects (n=4; P<0.001). Although in the crowded condition subjects were not able to discriminate the target stimulus, adaptation to that stimulus was still preserved (P<0.001). There was no significant difference between the adaptations in the two conditions of the apparent motion (P>0.05). Imaging studies have shown that V5 cortex is the earliest visual area that specifically responds to apparent motion. Our results suggest that in certain conditions V5 may be activated while there is no explicit conscious access to the apparent motion.

fMRI mapping of a morphed continuum of 3D shapes within inferior temporal cortex.

Here, we mapped fMRI responses to incrementally changing shapes along a continuous 3D morph, ranging from a head (“face”) to a house (“place”). The response to each shape was mapped independently by using single-stimulus imaging, and stimulus shapes were equated for lower-level visual cues. We measured activity in 2-mm samples across human inferior temporal cortex from the fusiform face area (FFA) (apparently selective for faces) to the parahippocampal place area (PPA) (apparently selective for places), testing for (i) incremental changes in the topography of FFA and PPA (predicted by the continuous-mapping model) or (ii) little or no response to the intermediate morphed shapes (predicted by the category model). Neither result occurred; instead, we found approximately linearly graded changes in the response amplitudes to graded-shape changes, without changes in topography—similar to visual responses in different lower-tier cortical areas.