Widespread spatial integration in primary somatosensory cortex.

Tactile discrimination depends on integration of information from the discrete receptive fields (RFs) of peripheral sensory afferents. Because this information is processed over a hierarchy of subcortical nuclei and cortical areas, the integration likely occurs at multiple levels. The current study presents results indicating that neurons across most of the extent of the hand representation in monkey primary somatosensory cortex (area 3b) interact, even when these neurons have separate RFs. We obtained simultaneous recordings by using a 100-electrode array implanted in the hand representation of primary somatosensory cortex of two anesthetized owl monkeys. During a series of 0.5-s skin indentations with single or dual probes, the distance between electrodes from which neurons with synchronized spike times were recorded exceeded 2 mm. The results provide evidence that stimuli on different parts of the hand influence the degree of synchronous firing among a large population of neurons. Because spike synchrony potentiates the activation of commonly targeted neurons, synchronous neural activity in primary somatosensory cortex can contribute to discrimination of complex tactile stimuli.

Modular processing in the hand representation of primate primary somatosensory cortex coexists with widespread activation.

Neurons in the hand representation of primary somatosensory cortex (area 3b) are known to have discretely localized receptive fields; and these neurons form modules that can be visualized histologically as distinct digit and palm representations. Despite these indicators of the importance of local processing in area 3b, widespread interactions between stimuli presented to locations across the hand have been reported. We investigated the relationship of neuron firing rate with distance from the site of maximum activation in cortex by recording from a 100-electrode array with electrodes spaced 400 µm apart, implanted into the area 3b hand representation in anesthetized owl monkeys. For each stimulated location on the hand, the electrode site where neurons had the highest peak firing rate was defined as the peak activation site. The lesser firing rates of neurons at all other electrode sites in the grid were compared with the firing rates of neurons at the peak activation site. On average, peak firing rates of neurons decreased rapidly with distance away from the peak activation site. The effect of distance on the variance of firing rates was highly significant (P < 0.0001). However, individual neurons retained high firing rates for distances over 3 mm. The clear decline in firing rate with distance from the most activated location indicates that local processing is emphasized in area 3b, while the distance of neurons with reduced but maintained firing rates ≤3-4 mm from the site of best activation demonstrated widespread activation in primary somatosensory cortex.

Response properties of neurons in primary somatosensory cortex of owl monkeys reflect widespread spatiotemporal integration.

Receptive fields of neurons in somatosensory area 3b of monkeys are typically described as restricted to part of a single digit or palm pad. However, such neurons are likely involved in integrating stimulus information from across the hand. To evaluate this possibility, we recorded from area 3b neurons in anesthetized owl monkeys with 100-electrode arrays, stimulating two hand locations with electromechanical probes simultaneously or asynchronously. Response magnitudes and latencies of single- and multiunits varied with stimulus conditions, and multiunit responses were similar to single-unit responses. The mean peak firing rate for single neurons stimulated within the preferred location was estimated to be ∼26 spike/s. Simultaneous stimulation with a second probe outside the preferred location slightly decreased peak firing rates to ∼22 spike/s. When the nonpreferred stimulus preceded the preferred stimulus by 10-500 ms, peak firing rates were suppressed with greatest suppression when the nonpreferred stimulus preceded by 30 ms (∼7 spike/s). The mean latency for single neurons stimulated within the preferred location was ∼23 ms, and latency was little affected by simultaneous paired stimulation. However, when the nonpreferred stimulus preceded the preferred stimulus by 10 ms, latencies shortened to ∼16 ms. Response suppression occurred even when stimuli were separated by long distances (nonadjacent digits) or long times (500 ms onset asynchrony). Facilitation, though rare, occurred most often when the stimulus onsets were within 0-30 ms of each other. These findings quantify spatiotemporal interactions and support the hypothesis that area 3b is involved in widespread stimulus integration.

Deconstruction of spatial integrity in visual stimulus detected by modulation of synchronized activity in cat visual cortex.

Spatiotemporal relationships among contour segments can influence synchronization of neural responses in the primary visual cortex. We performed a systematic study to dissociate the impact of spatial and temporal factors in the signaling of contour integration via synchrony. In addition, we characterized the temporal evolution of this process to clarify potential underlying mechanisms. With a 10 x 10 microelectrode array, we recorded the simultaneous activity of multiple cells in the cat primary visual cortex while stimulating with drifting sine-wave gratings. We preserved temporal integrity and systematically degraded spatial integrity of the sine-wave gratings by adding spatial noise. Neural synchronization was analyzed in the time and frequency domains by conducting cross-correlation and coherence analyses. The general association between neural spike trains depends strongly on spatial integrity, with coherence in the gamma band (35-70 Hz) showing greater sensitivity to the change of spatial structure than other frequency bands. Analysis of the temporal dynamics of synchronization in both time and frequency domains suggests that spike timing synchronization is triggered nearly instantaneously by coherent structure in the stimuli, whereas frequency-specific oscillatory components develop more slowly, presumably through network interactions. Our results suggest that, whereas temporal integrity is required for the generation of synchrony, spatial integrity is critical in triggering subsequent gamma band synchronization.

Cortical plasticity in monocularly deprived immobilized kittens depends on eye movement.

A marked reduction of binocular cells in striate cortex is found if 4-week-old kittens are visually stimulated monocularly while anesthetized and held in a stereotaxic apparatus. If the kittens are paralyzed and artificially respirated, changes are not found unless an eye is moved mechanically. It appears that eye movement and visual stimulation are necessary conditions for deactivation of binocular connections, but neither is sufficient to induce such changes alone.

Cooperation between area 17 neuron pairs enhances fine discrimination of orientation.

We examined 66 complex cells in area 17 of cats that were paralyzed and anesthetized with propofol and N2O. We studied changes in ensemble responses for small (<10 degrees ) and large (>10 degrees ) differences in orientation. Examination of temporal resolution and discharge history revealed advantages in discrimination from both dependent (e.g., synchronization) and independent (e.g., bursting) interspike interval properties. For 27 pairs of neurons, we found that the average cooperation (the advantage gained from the joint activity) was 57.6% for fine discrimination of orientation but <5% for gross discrimination. Dependency (probabilistic quantification of the interaction between the cells) was measured between 29 pairs of neurons while varying orientation. On average, the dependency tuning for orientation was 35.5% narrower than the average firing rate tuning. The changes in dependency around the peak orientation (at which the firing rate remains relatively constant) lead to substantial cooperation that can improve discrimination in this region. The narrow tuning of dependency and the cooperation provide evidence to support a population-encoding scheme that is based on biologically plausible mechanisms and that could account for hyperacuities.

Spatial adaptation of the cortical visual evoked potential of the cat.

Adaptation that is spatially specific for the adapting pattern has been seen psychophysically in humans. This is indirect evidence for independent analyzers (putatively single units) that are specific for orientation and spatial frequency in the human visual system, but it is unclear how global adaptation characteristics may be related to single unit performance. Spatially specific adaptation was sought in the cat visual evoked potential (VEP), with a view towards relating this phenomenon with what we know of cat single units. Adaptation to sine-wave gratings results in a temporary loss of cat VEP amplitude, with induction and recovery similar to that seen in human psychophysical experiments. The amplitude loss was specific for both the spatial frequency and orientation of the adapting pattern. The bandwidth of adaptation was not unlike the average selectivity of a population of cat single units.

Induced movement of receptor alignment toward a new pupillary aperture.

Bonds and MacLeod (1978) reported on an individual whose receptors, as measured by the peak of the Stiles-Crawford function, were oriented in the direction of a traumatically displaced pupil. In an attempt to demonstrate that this orientational response is caused by an active alignment process and not simply a result of passive forces due to the traumatic ocular injury, we attempted to influence receptor alignment in the same eye by artificially creating a centered pupil. This was accomplished by placing on the subject's dilated eye a soft contact lens containing a centered 2mm artificial pupil. Receptor alignment (inferred from the entrance pupil location of the peak of the Stiles-Crawford function) significantly changed (0.8 mm) in the direction of the "new pupil" over a time course of 5 days. This alignment persisted for as long as the pupil was worn (1 month). With removal of the artificial pupil, the receptor alignment returned to its original eccentric orientation in 5 days. The results indicate that an active phototropic mechanism significantly influences receptor alignment toward the pupillary aperture.

A displaced Stiles-Crawford effect associated with an eccentric pupil.

Receptors tend to be oriented toward a point near the center of the pupil in the normal eye. We report psychophysical studies of receptor orientation and directional sensitivity in a subject whose right pupil is displaced nearly 3 mm nasally as a result of injury sustained 25 years ago. The Stiles-Crawford effect was measured for foveal cones and for parafoveal cones and rods. Greatest sensitivity was found in all cases at a point close to the center of the natural pupil, indicating that the receptors in this eye are trained toward the abnormally situated pupil. At large angles of incidence, foveal cones exhibited a clear asymptote of sensitivity 0.83 log units below the sensitivity for axially incident light. Parafoveal cones were more directionally sensitive, with a suggestion of an asymptote for oblique incidence about 1.2 log units below the sensitivity for axial incidence. Rods showed a sensitivity pattern decentered like that of the cones, with a greatest observed sensitivity loss of 0.28 log units. Best acuity for cones was observed for entrance pupils close to the optical axis of the eye, remote from the pupillary region for best sensitivity.

Real-time visualization of neural synchrony for identifying coordinated cell assemblies.

We introduce a synchrony map that translates the fine temporal organization of multi-unit responses in the visual cortex into an easily interpreted spatial display. We test the synchrony map on microelectrode array recordings in Area 17 of anesthetized and paralyzed cats. We first examine the synchrony map using averaged data and probability calculations to demonstrate orientation-dependent changes in synchrony. We then demonstrate how the synchrony map can be implemented for real-time visualization of synchrony among neural assemblies.

Classification of non-stationary neural signals.

Although a number of methods have been proposed for classification of individual action potentials embedded in multi-unit activity, they have been challenged by non-stationarity. The waveform shapes of action potentials can change rapidly over time as a result of shifts in membrane conductances during extended burst firing sequences and more slowly over time due to electrode drift. These changes are typically non-Gaussian. We present an algorithm for waveform identification that makes no assumptions on the distribution of these shapes other than the change in waveform shape for a particular neuron should not be discontinuous. We apply this algorithm to the resolution of multi-unit neural signals recorded in the cat visual cortex and we compare this approach to a spike sorting method that is based on the Bayesian likelihood of a spike fitting a particular model (Lewicki, M. Bayesian modeling and classification of neural signals. Neural Comput 1994;6(5):1005-1030.

Contrast adaptation in cat visual cortex is not mediated by GABA.

The possible involvement of gamma-aminobutyric acid (GABA) in contrast adaptation in single cells in area 17 of the cat was investigated. Iontophoretic application of N-methyl bicuculline increased cell responses, but had no effect on the magnitude of adaptation. These results suggest that contrast adaptation is the result of inhibition through a parallel pathway, but that GABA does not mediate this process.

Anticholinesterase agents affect contrast gain of the cat cortical visual evoked potential.

The effects of the anticholinesterase agents physostigmine, pyridostigmine, diisopropylfluorophosphate and soman on the cortical visual evoked potential (VEP) were examined using phase reversed sine wave gratings of varying contrasts. All 4 agents decreased the slope (gain) of the response vs log contrast function while the intercept with the noise level (threshold, an indicator of contrast sensitivity) was unaffected. These results suggest that anticholinesterases modify the VEP by changing a contrast gain control mechanism.

Visual evoked potential responses of the anesthetized cat to contrast modulation of grating patterns.

Contrast modulation affords independent control of static contrast (C) and changes in contrast (delta C). We found that in anesthetized, paralyzed cats, the visual evoked potential (VEP) was dependent only on magnitude of delta C at each pattern transition, and was independent of the starting or ending contrast level. Increasing modulation frequency to above 2 Hz reduced the VEP monotonically, implying that the time constant for differentiation by the VEP is of the order of 250 msec. The essentially perfect a.c. coupling suppresses standing contrast completely, permitting the full dynamic range of the VEP response system to be used for detection of contrast increments (which results in a decreasing Weber fraction). The difference between our results and those of behavioral studies using contrast modulation can be explained by eye movements present in the behavioral studies which refresh the retinal image of the static contrast in a way uncorrelated to temporal modulation of the stimulus, thus introducing a masking effect.

Inhibitory refinement of spatial frequency selectivity in single cells of the cat striate cortex.

Single cells in the cat striate cortex are more selective for the spatial frequency of sinewave grating stimuli than are cells of the retina or lateral geniculate nucleus. We have explored the possibility that this enhancement of selectivity results from spatial-frequency-selective inhibition. Stimulation with two superimposed gratings, one to excite the cell and one to prove for inhibition, revealed spatial frequency-dependent response suppression in 74% of the total population studied. Suppression was slightly more prevalent in simple cells (80%) than in complex cells (68%). In 93% of the cases where suppression was found, its tuning was complementary to excitatory spatial frequency tuning, and the strongest suppression was usually found where the excitatory tuning function approached zero imp./sec. Characteristics of the phenomenon were independent of cortical layers. We conclude that organized inhibitory mechanisms serve to refine the spatial frequency bandpass of striate cortical cells. This provides evidence for another degree of nonlinearity in the organization of cortical receptive fields and supports the hypothesis that a fundamental function of the visual cortex is image dissection in the domain of spatial frequency.

Visual resolution and sensitivity in a nocturnal primate (galago) measured with visual evoked potentials.

Visual resolution and contrast sensitivity were examined in anesthetized, paralyzed galagos using visual evoked potentials (VEPs) resulting from stimulation with phase-reversed sinewave gratings. Spatial frequency vs contrast response functions were band-pass with peak sensitivity at 0.2-0.4 c/deg and a high frequency cut-off between 1.6 and 3 c/deg. Peak contrast sensitivities (estimated from extrapolation of contrast response functions) varied across animals from 10 to 170. Variation of the stimulus modulation rate showed that best responses occurred at 1 Hz with an upper limit of 6-16 Hz. As in other primates, an oblique effect was seen in 6 of 8 animals. The contrast sensitivity function (CSF) determined from cortical VEPs agrees well with the CSFs of cells in the lateral geniculate nucleus, but peak sensitivity and spatial frequency are slightly lower than found for the behavioral CSF. Overall visual performance resembled closely that of another nocturnal species, the cat.

Classifying simple and complex cells on the basis of response modulation.

Hubel and Wiesel (1962; Journal of Physiology, London, 160, 106-154) introduced the classification of cortical neurons as simple and complex on the basis of four tests of their receptive field structure. These tests are partly subjective and no one of them unequivocally places neurons into distinct classes. A simple, objective classification criterion based on the form of the response to drifting sinusoidal gratings has been used by several laboratories, although it has been criticized by others. We review published and unpublished evidence which indicates that this simple and objective criterion reliability divides neurons of the striate cortex in both cats and monkeys into two groups that correspond closely to the classically-described simple and complex classes.

Depression of the cat cortical visual evoked potential by soman.

The effects of intravenous administration of the anticholinesterase agent soman (pinacolyl methylphosphonofluoridate, 3-15 micrograms/kg) on the visual evoked potential (VEP) were examined in cats using phase-reversed sine wave grating stimuli of different spatial frequencies and contrasts. Doses of 5-7 micrograms/kg caused a depression of the VEP across all spatial frequencies in an abrupt, non-graded fashion. Studies in which contrast was varied showed that VEP depression resulted primarily from a decrease in the system gain rather than a change in the contrast sensitivity, and that response depression increased with increasing contrast. The dominant changes in gain revealed by these studies are consistent with a modulation of potassium conductance in the cell membrane which previous studies have shown to be dependent on a cholinergic mechanism.

Pretreatment with physostigmine, mecamylamine and atropine reduces the impact of soman on the cortical visual evoked potential of the cat.

A pretreatment regimen of physostigmine, mecamylamine and atropine was evaluated for its ability to alleviate the impact of soman on visual system function as measured by changes in the cortical visual evoked potential (VEP) of the cat. Data from unprotected animals showed a threshold (30% depression in the VEP) of 6.4 micrograms/kg, while in pretreated animals, the threshold dose was 32.7 micrograms/kg, yielding a protection ratio of 5:1. Extending the time between pretreatment and exposure reduced the degree of protection. Pretreatment also reduced the degree of VEP depression at suprathreshold doses, indicating a therapeutic effect even in cases of severe exposure.