Focused ultrasound is a promising noninvasive technology for neural stimulation. Here we use the isolated salamander retina to characterize the effect of ultrasound on an intact neural circuit and compared these effects with those of visual stimulation of the same retinal ganglion cells. Ultrasound stimuli at an acoustic frequency of 43 MHz and a focal spot diameter of 90 m delivered from a piezoelectric transducer evoked stable responses with a temporal precision equal to strong visual responses but with shorter latency. By presenting ultrasound and visual stimulation together, we found that ultrasonic stimulation rapidly modulated visual sensitivity but did not change visual temporal filtering. By combining pharmacology with ultrasound stimulation, we found that ultrasound did not directly activate retinal ganglion cells but did in part activate interneurons beyond photoreceptors. These results suggest that, under conditions of strong localized stimulation, timing variability is largely influenced by cells beyond photoreceptors. We conclude that ultrasonic stimulation is an effective and spatiotemporally precise method to activate the retina. Because the retina is the most accessible part of the CNS in vivo, ultrasonic stimulation may have diagnostic potential to probe remaining retinal function in cases of photoreceptor degeneration, and therapeutic potential for use in a retinal prosthesis. In addition, because of its noninvasive properties and spatiotemporal resolution, ultrasound neurostimulation promises to be a useful tool to understand dynamic activity in pharmacologically defined neural pathways in the retina.

For binocular animals viewing a three-dimensional scene, the left and right eyes receive slightly different information, and the brain uses this 'binocular disparity' to interpret stereoscopic depth. An important theoretical conjecture in this mechanism is that coarse processing precedes and constrains finely detailed processing. We present three types of neurophysiological data from the cat's visual cortex that are consistent with a temporal coarse-to-fine tuning of disparity information. First, the disparity tuning of cortical cells generally sharpened during the time course of response. Second, cells responsive to large and small spatial scale had relatively shorter and longer temporal latencies, respectively. Third, cross-correlation analysis between simultaneously recorded pairs of cortical cells showed that connections between disparity-tuned neurons were generally stronger for coarse-to-fine processing than for fine-to-coarse processing. These results are consistent with theoretical and behavioral studies and suggest that rapid, coarse percepts are refined over time in stereoscopic depth perception.

. To solve the stereo correspondence problem (i.e., find the matching features of a visual scene in both eyes), it is advantageous to combine information across spatial scales. The details of how this is accomplished are not clear. Psychophysical studies and mathematical models have suggested various types of interactions across spatial scale, including coarse to fine, fine to coarse, averaging, and population coding. In this study, we investigate dynamic changes in disparity tuning of simple and complex cells in the cat's striate cortex over a short time span. We find that disparity frequency increases and disparity ranges decrease while optimal disparity remains constant, and this conforms to a coarse-to-fine mechanism. We explore the origin of this mechanism by examining the frequency and size dynamics exhibited by binocular simple cells and neurons in the lateral geniculate nucleus (LGN). The results suggest a strong role for a feed-forward mechanism, which could originate in the retina. However, we find that the dynamic changes seen in the disparity range of simple cells cannot be predicted from their left and right eye monocular receptive field (RF) size changes. This discrepancy suggests the possibility of a dynamic nonlinearity or disparity specific feedback that alters tuning or a combination of both mechanisms. I N T R O D U C T I O NStereoscopic depth perception has been studied from theoretical, behavioral, and neurophysiological perspectives. Most behavior work has been aimed at establishing empirical parameters of stereoscopic function and performance levels. Early neurophysiological studies neglected mechanisms and assumed that cells with responses that changed with retinal disparity of the stimulus were depth detectors. More recent physiological work has included theoretical proposals that were tested experimentally. The result is a modified energy model that accounts for basic features of the neural mechanism of stereopsis (e.g., Freeman and Ohzawa 1990;Ohzawa et al. 1990;).An early theoretical proposal was concerned with the correspondence problem in stereopsis (Marr and Poggio 1979). This refers to the ambiguity of correspondence between left and right images that occurs from binocular viewing. The brain must choose the correct depth plane from several possible ones to process appropriate stereoscopic information. To solve this problem, coarse scale disparity matches were proposed to occur first. This would be followed by fine scale matches (Marr and Poggio 1979). In other words, a coarse-to-fine scaling process could be used to provide correct stereoscopic matching. Other theoretical ideas envisioned similar coarse scale disparity matches that were followed by fine scale adjustments (Anderson and Van Essen 1987;Nishihara and Kimura 1987;Quam 1987).These theoretical notions have been explored in behavioral studies. Sensitivity has been found to improve for line length, orientation, curvature and stereoscopic depth over a period of Ն1 s (Watt 1987). The interpretation of these findings may be ...

Different mechanisms have been proposed concerning how disparity-tuned neurons might be connected to produce the signals for depth perception. Here we present neurophysiological evidence providing insight on this issue. We have recorded simultaneously from pairs of disparity-tuned neurons in the cat's striate cortex. The purpose was to determine the relationships between disparity tuning and functional connectivity revealed through neural cross-correlograms. Monosynaptic connections tend to be stronger between pairs of cells with similar disparity tuning. Pairs of complex cells tend to have either similar tuning or nearly opposite tuning with an absence of quadrature relations. Pairs with at least one simple cell do have some nearly quadrature relationships when they are recorded from the same electrode. Coarse-to-fine connections (i.e., the presynaptic cell has lower disparity frequency and larger disparity range) tend to be stronger but less frequent than those of a fine-to-coarse nature. Our results are consistent with a system that produces weighted averaging across cells that are tuned to similar disparities but different disparity scales to reduce false matches.

In multifocal visually evoked potentials (mfVEP), we find reversals in waveform near the horizontal meridian due to convolutions in the cortex. This renders the mfVEP very sensitive to small changes in gaze position. In this study we tested the effects of very small amounts of fixation instability on the mfVEP topography under controlled conditions using four normal subjects. In order to simulate unstable fixation, subjects were instructed to move their fixation point systematically in a clockwise direction between the endpoints of a fixation cross every few seconds (two degree diameter cross = one degree fixation error). Results were compared against a control condition with stable, central fixation. The effects of 0.5 degrees fixation error are small, but 1.0 degrees fixation error can produce a large decrease in root mean square signal amplitude (e.g., 60%) in the central foveal region (i.e., within 1.4 degrees eccentricity). The size of the effect drops off rapidly with eccentricity and varies greatly between areas within a subject, and between the four subjects. Beyond 3.0 degrees eccentricity the effects are minimal. Unstable fixation with relatively small fixation errors caused a dramatic decrease in mfVEP amplitude within three degrees of eccentricity, which can be misinterpreted as loss of macular function. Fixation monitoring is essential to obtain accurate results in the macular area when recording mfVEPs.