Romesh D. Kumbhani

Cellular Mechanisms of Temporal Sensitivity in Visual Cortex Neurons

The ability of cortical neurons to accurately encode the temporal pattern of their inputs has important consequences for cortical function and perceptual acuity. Here we identify cellular mechanisms underlying the sensitivity of cortical neurons to the timing of sensory-evoked synaptic inputs. We find that temporally coincident inputs to layer 4 neurons in primary visual cortex evoke an increase in spike precision and supralinear spike summation. Underlying this nonlinear summation are changes in the evoked excitatory conductance and the associated membrane potential response, and a lengthening of the window between excitation and inhibition. Furthermore, fast-spiking inhibitory interneurons in layer 4 exhibit a shorter window of temporal sensitivity compared with excitatory neurons. In contrast to the enhanced response to synchronous inputs by layer 4 neurons, sensory input integration in downstream cortical layers is more linear and less sensitive to timing. Neurons in the input layer of cortex are thus uniquely optimized to detect and encode synchronous sensory-evoked inputs.

Population representation of visual information in areas V1 and V2 of amblyopic macaques

Amblyopia is a developmental disorder resulting in poor vision in one eye. The mechanism by which input to the affected eye is prevented from reaching the level of awareness remains poorly understood. We recorded simultaneously from large populations of neurons in the supragranular layers of areas V1 and V2 in 6 macaques that were made amblyopic by rearing with artificial strabismus or anisometropia, and 1 normally reared control. In agreement with previous reports, we found that cortical neuronal signals driven through the amblyopic eyes were reduced, and that cortical neurons were on average more strongly driven by the non-amblyopic than by the amblyopic eyes. We analyzed multiunit recordings using standard population decoding methods, and found that visual signals from the amblyopic eye, while weakened, were not degraded enough to explain the behavioral deficits. Thus additional losses must arise in downstream processing. We tested the idea that under monocular viewing conditions, only signals from neurons dominated by - rather than driven by - the open eye might be used. This reduces the proportion of neuronal signals available from the amblyopic eye, and amplifies the interocular difference observed at the level of single neurons. We conclude that amblyopia might arise in part from degradation in the neuronal signals from the amblyopic eye, and in part from a reduction in the number of signals processed by downstream areas.

Visual response properties of V1 neurons projecting to V2 in macaque.

Visual area V2 of the primate cortex receives the largest projection from area V1. V2 is thought to use its striate inputs as the basis for computations that are important for visual form processing, such as signaling angles, object borders, illusory contours, and relative binocular disparity. However, it remains unclear how selectivity for these stimulus properties emerges in V2, in part because the functional properties of the inputs are unknown. We used antidromic electrical stimulation to identify V1 neurons that project directly to V2 (10% of all V1 neurons recorded) and characterized their electrical and visual responses. V2-projecting neurons were concentrated in the superficial and middle layers of striate cortex, consistent with the known anatomy of this cortico-cortical circuit. Most were fast conducting and temporally precise in their electrical responses, and had broad spike waveforms consistent with pyramidal regular-spiking excitatory neurons. Overall, projection neurons were functionally diverse. Most, however, were tuned for orientation and binocular disparity and were strongly suppressed by large stimuli. Projection neurons included those selective and invariant to spatial phase, with roughly equal proportions. Projection neurons found in superficial layers had longer conduction times, broader spike waveforms, and were more responsive to chromatic stimuli; those found in middle layers were more strongly selective for motion direction and binocular disparity. Collectively, these response properties may be well suited for generating complex feature selectivity in and beyond V2.

Asymmetric dichoptic masking in visual cortex of amblyopic macaque monkeys

In amblyopia, abnormal visual experience leads to an extreme form of eye dominance, in which vision through the nondominant eye is degraded. A key aspect of this disorder is perceptual suppression: the image seen by the stronger eye often dominates during binocular viewing, blocking the image of the weaker eye from reaching awareness. Interocular suppression is the focus of ongoing work aimed at understanding and treating amblyopia, yet its physiological basis remains unknown. We measured binocular interactions in visual cortex of anesthetized amblyopic monkeys (female Macaca nemestrina), using 96-channel “Utah” arrays to record from populations of neurons in V1 and V2. In an experiment reported recently (Hallum et al., 2017), we found that reduced excitatory input from the amblyopic eye (AE) revealed a form of balanced binocular suppression that is unaltered in amblyopia. Here, we report on the modulation of the gain of excitatory signals from the AE by signals from its dominant fellow eye (FE). Using a dichoptic masking technique, we found that AE responses to grating stimuli were attenuated by the presentation of a noise mask to the FE, as in a normal control animal. Responses to FE stimuli, by contrast, could not be masked from the AE. We conclude that a weakened ability of the amblyopic eye to modulate cortical response gain creates an imbalance of suppression that favors the dominant eye. SIGNIFICANCE STATEMENT In amblyopia, vision in one eye is impaired as a result of abnormal early visual experience. Behavioral observations in humans with amblyopia suggest that much of their visual loss is due to active suppression of their amblyopic eye. Here we describe experiments in which we studied binocular interactions in macaques with experimentally induced amblyopia. In normal monkeys, the gain of neuronal response to stimulation of one eye is modulated by contrast in the other eye, but in monkeys with amblyopia the balance of gain modulation is altered so that the weaker, amblyopic eye has little effect while the stronger fellow eye has a strong effect. This asymmetric suppression may be a key component of the perceptual losses in amblyopia.

Altered Balance of Receptive Field Excitation and Suppression in Visual Cortex of Amblyopic Macaque Monkeys

In amblyopia, a visual disorder caused by abnormal visual experience during development, the amblyopic eye (AE) loses visual sensitivity whereas the fellow eye (FE) is largely unaffected. Binocular vision in amblyopes is often disrupted by interocular suppression. We used 96-electrode arrays to record neurons and neuronal groups in areas V1 and V2 of six female macaque monkeys (Macaca nemestrina) made amblyopic by artificial strabismus or anisometropia in early life, as well as two visually normal female controls. To measure suppressive binocular interactions directly, we recorded neuronal responses to dichoptic stimulation. We stimulated both eyes simultaneously with large sinusoidal gratings, controlling their contrast independently with raised-cosine modulators of different orientations and spatial frequencies. We modeled each eyes receptive field at each cortical site using a difference of Gaussian envelopes and derived estimates of the strength of central excitation and surround suppression. We used these estimates to calculate ocular dominance separately for excitation and suppression. Excitatory drive from the FE dominated amblyopic visual cortex, especially in more severe amblyopes, but suppression from both the FE and AEs was prevalent in all animals. This imbalance created strong interocular suppression in deep amblyopes: increasing contrast in the AE decreased responses at binocular cortical sites. These response patterns reveal mechanisms that likely contribute to the interocular suppression that disrupts vision in amblyopes. SIGNIFICANCE STATEMENT Amblyopia is a developmental visual disorder that alters both monocular vision and binocular interaction. Using microelectrode arrays, we examined binocular interaction in primary visual cortex and V2 of six amblyopic macaque monkeys (Macaca nemestrina) and two visually normal controls. By stimulating the eyes dichoptically, we showed that, in amblyopic cortex, the binocular combination of signals is altered. The excitatory influence of the two eyes is imbalanced to a degree that can be predicted from the severity of amblyopia, whereas suppression from both eyes is prevalent in all animals. This altered balance of excitation and suppression reflects mechanisms that may contribute to the interocular perceptual suppression that disrupts vision in amblyopes.

Can Major Depression Improve the Perception of Visual Motion

It has always been the promise of basic research to eventually bring its dearly earned knowledge to bear on practical matters. At the same time, it is understood that one should first get a good grasp of the complex workings of the healthy nervous system before being able to meaningfully treat its

Receptive field properties of V1 and V2 neurons in amblyopic macaque monkeys revealed with local spectral reverse correlation

Amblyopia is a visual disorder associated with a disruption of conjugate binocular vision early in life, resulting in decreased visual performance in one eye. Previous studies have explored the neurophysiological basis of this disorder using single-unit recordings, but the results incompletely explain the perceptual deficits. New advances in recording techniques now allow us to simultaneously sample multiple sites over large areas of visual cortex. Introduction