The Early Psychosis Screener for Internet (EPSI)-SR: Predicting 12 month psychotic conversion using machine learning.

INTRODUCTION: A faster and more accurate self-report screener for early psychosis is needed to promote early identification and intervention. METHODS: Self-report Likert-scale survey items were administered to individuals being screened with the Structured Interview for Psychosis-risk Syndromes (SIPS) and followed at eight early psychosis clinics. An a priori analytic plan included Spectral Clustering Analysis to reduce the item pool, followed by development of Support Vector Machine (SVM) classifiers. RESULTS: The cross-validated positive predictive value (PPV) of the EPSI at the default cut-off (76.5%) exceeded that of the clinician-administered SIPS (68.5%) at separating individuals who would not convert to psychosis within 12 months from those who either would convert within 12 months or who had already experienced a first episode psychosis (FEP). When used in tandem with the SIPS on clinical high risk participants, the EPSI increased the combined PPV to 86.6%. The SVM classified as FEP/converters only 1% of individuals in non-clinical and 4% of clinical low risk populations. Sensitivity of the EPSI, however, was 51% at the default cut-off. DISCUSSION: The EPSI identifies, comparably to the SIPS but in less time and with fewer resources, individuals who are either at very high risk to develop a psychotic disorder within 12 months or who are already psychotic. At its default cut-off, EPSI misses 49% of current or future psychotic cases. The cut-off can, however, be adjusted based on purpose. The EPSI is the first validated assessment to predict 12-month psychotic conversion. An online screening system, www.eps.telesage.org, is under development.

The Early Psychosis Screener (EPS): Quantitative validation against the SIPS using machine learning.

Machine learning techniques were used to identify highly informative early psychosis self-report items and to validate an early psychosis screener (EPS) against the Structured Interview for Psychosis-risk Syndromes (SIPS). The Prodromal Questionnaire-Brief Version (PQ-B) and 148 additional items were administered to 229 individuals being screened with the SIPS at 7 North American Prodrome Longitudinal Study sites and at Columbia University. Fifty individuals were found to have SIPS scores of 0, 1, or 2, making them clinically low risk (CLR) controls; 144 were classified as clinically high risk (CHR) (SIPS 3-5) and 35 were found to have first episode psychosis (FEP) (SIPS 6). Spectral clustering analysis, performed on 124 of the items, yielded two cohesive item groups, the first mostly related to psychosis and mania, the second mostly related to depression, anxiety, and social and general work/school functioning. Items within each group were sorted according to their usefulness in distinguishing between CLR and CHR individuals using the Minimum Redundancy Maximum Relevance procedure. A receiver operating characteristic area under the curve (AUC) analysis indicated that maximal differentiation of CLR and CHR participants was achieved with a 26-item solution (AUC=0.899±0.001). The EPS-26 outperformed the PQ-B (AUC=0.834±0.001). For screening purposes, the self-report EPS-26 appeared to differentiate individuals who are either CLR or CHR approximately as well as the clinician-administered SIPS. The EPS-26 may prove useful as a self-report screener and may lead to a decrease in the duration of untreated psychosis. A validation of the EPS-26 against actual conversion is underway.

Nociceptive afferent activity alters the SI RA neuron response to mechanical skin stimulation.

Procedures that reliably evoke cutaneous pain in humans (i.e., 5-7 s skin contact with a 47-51 °C probe, intradermal algogen injection) are shown to decrease the mean spike firing rate (MFR) and degree to which the rapidly adapting (RA) neurons in areas 3b/1 of squirrel monkey primary somatosensory cortex (SI) entrain to a 25-Hz stimulus to the receptive field center (RF(center)) when stimulus amplitude is "near-threshold" (i.e., 10-50 µm). In contrast, RA neuron MFR and entrainment are either unaffected or enhanced by 47-51 °C contact or intradermal algogen injection when the amplitude of 25-Hz stimulation is 100-200 µm (suprathreshold). The results are attributed to an "activity dependence" of γ-aminobutyric acid (GABA) action on the GABA(A) receptors of RA neurons. The nociceptive afferent drive triggered by skin contact with a 47-51 °C probe or intradermal algogen is proposed to activate nociresponsive neurons in area 3a which, via corticocortical connections, leads to the release of GABA in areas 3b/1. It is hypothesized that GABA is hyperpolarizing/inhibitory and suppresses stimulus-evoked RA neuron MFR and entrainment whenever RA neuron activity is low (as when the RF(center) stimulus is weak/near-threshold) but is depolarizing/excitatory and augments MFR and entrainment when RA neuron activity is high (when the stimulus is strong/suprathreshold).

Duration-dependent response of SI to vibrotactile stimulation in squirrel monkey.

In previous studies, we showed that the spatial and intensive aspects of the SI response to skin flutter stimulation are modified systematically as stimulus amplitude is increased. In this study, we examined the effects of duration of skin flutter stimulation on the spatiotemporal characteristics of the response of SI cortex. Optical intrinsic signal (OIS) imaging was used to study the evoked response in SI of anesthetized squirrel monkeys to 25-Hz sinusoidal vertical skin displacement stimulation. Four stimulus durations were tested (0.5, 1.0, 2.0, and 5.0 s); all stimuli were delivered to a discrete site on the glabrous skin of the contralateral forelimb. Skin stimulation evoked a prominent increase in absorbance within the forelimb regions in SI of the contralateral hemisphere. Responses to brief (0.5 s) stimuli were weaker and spatially more extensive than responses to longer duration stimuli (1.0, 2.0, and 5.0 s). Stimuli >or=1 s in duration suppressed responses to below background levels (decreased absorbance) in regions that surrounded the maximally activated region. The magnitude of the suppression in the surrounding regions was nonuniform and usually was strongest medial and posterior to the maximally activated region. The results show that sustained (>or=1.0 s) stimulation decreases the spatial extent of the responding SI cortical population. Registration of the optical responses with the previously documented SI topographical organization strongly suggests that the cortical regions that undergo the strongest suppression represent skin sites that are normally co-stimulated during tactile exploration.

Effects of high-frequency skin stimulation on SI cortex: mechanisms and functional implications.

Optical intrinsic signal (OIS) imaging methods were used to record the responses of contralateral SI cortex to 25 Hz ("flutter") and also to 200 Hz ("vibration") stimulation of the skin. Anesthetized cats and squirrel monkeys were subjects. Separate series of experiments were carried out to evaluate the contralateral SI response to continuous, multisecond 25 Hz vs. 200 Hz stimulation (a) at multiple skin sites arranged along the proximal-distal axis of the fore- or hindlimb (Series I); (b) in the presence and absence of a ring placed in firm contact with the skin surrounding the stimulus site (Series II); (c) before and after topical application of local anesthetic to the stimulus site (Series III); and, finally, (c) to continuous 25 Hz or 200 Hz stimulation applied independently, and also concomitantly ("complex waveform stimulation") to the same skin site (Series IV). The principal findings are: (a) the relationship between the SI optical responses to 25 Hz vs. 200 Hz stimulation of a skin site varies systematically with position of the stimulus site on the limb-at a distal site both 25 Hz and 200 Hz stimulation evoke a well-maintained increase in absorbance, and as the stimulus site is shifted proximally on the limb the response to 200 Hz, but not the response to 25 Hz stimulation, converts to a frank decrease in absorbance; (b) placement of a ring about a skin site at which in the absence of a ring 200 Hz stimulation evoked a decrease in SI absorbance converts the response to 200 Hz to one consistent with increased SI RA neuronal activation (i.e., with the ring in place 200 Hz stimulation evokes a change in SI absorbance approximating the response to 25 Hz stimulation); (c) topical local anesthetic preferentially and reversibly decreases the magnitude of the absorbance increase associated with 25 Hz flutter stimulation; and (d) complex waveform stimulation consistently is associated with a smaller increase in absorbance than obtained with same-site 25 Hz stimulation. Collectively, the findings are consistent with the idea that the Pacinian (PC) afferent activity which unavoidably accompanies cutaneous flutter stimulation triggers CNS mechanisms that "funnel" (sharpen) the spatially distributed contralateral SI response to the flutter stimulus. Viewed in this context, the fact that a flutter stimulus unavoidably co-activates RA and PC afferents appears functionally beneficial because the CNS mechanisms activated by PC afferent drive modify the SI response to skin flutter in a manner predicted to enable more accurate perceptual localization than would be possible if the flutter stimulus only activated RA afferents.

Human vibrotactile frequency discriminative capacity after adaptation to 25 Hz or 200 Hz stimulation.

A two-interval forced-choice (2-IFC) tracking procedure was used to evaluate the effects of a 15-s pre-exposure to either 25 Hz or 200 Hz stimulation ("25 Hz or 200 Hz adaptation") on human vibrotactile frequency discrimination threshold (frequency DL/Weber fraction). Three subjects were studied. All stimuli (standard and comparison) were delivered to a central location on the thenar eminence of the hand. The frequency DL/Weber fraction was determined for each subject under the following conditions: (1) no recent prior exposure to vibrotactile stimulation ("unadapted"); (2) after 15 s adaptation to 25 Hz stimulation; and (3) after 15 s adaptation to 200 Hz stimulation. The results demonstrate that the effects of frequency of adaptation on frequency discriminative capacity when the standard stimulus is 25 Hz are not the same as when the standard stimulus is 200 Hz. The differential changes in the capacity of subjects to discriminate frequency of cutaneous flutter (10-50 Hz) or vibratory (>200 Hz) stimulation that occur subsequent to a 15-s exposure of the thenar to 25 Hz or 200 Hz stimulation are proposed to reflect frequency-specific, adaptation-induced modification of the response of contralateral primary somatosensory cortex (SI and SII) to skin mechanoreceptor afferent drive.

Optically recorded response of the superficial dorsal horn: dissociation from neuronal activity, sensitivity to formalin-evoked skin nociceptor activation.

In rat spinal cord, slice repetitive electrical stimulation of the dorsal root at an intensity that activates C-fibers evokes a slow-to-develop and prolonged (30-50 s) change in light transmittance (OIS(DR)) in the superficial part of the ipsilateral dorsal horn (DH(s)). Inhibition of astrocyte metabolism [by bath-applied 400 microM fluoroacetate and 200 microM glutamine (FAc + Gln)] or interference with glial and neuronal K+ transport [by 100 microM 4-aminopyridine (4-AP)] leads to dissociation of the OIS(DR) and the postsynaptic DH(s) response to a single-pulse, constant-current dorsal root stimulus (P-PSP(DR)). The OIS(DR) decreases under FAc+Gln, whereas the P-PSP(DR) remains unaltered; under 4-AP, the P-PSP(DR) increases, but the OIS(DR) decreases. In contrast, both the OIS(DR) and P-PSP(DR) increase when K(+)o is elevated to 8 mM. These observations from slices from normal subjects are interpreted to indicate that the OIS(DR) mainly reflects cell volume and light scattering changes associated with DH(s) astrocyte uptake of K+ and glutamate (GLU). In slices from subjects that received an intracutaneous injection of formalin 3-5 days earlier, both the OIS(DR) and the response of the DH(s) ipsilateral to the injection site to 100-ms local application (via puffer pipette) of 15 mM K+ or 100 microM GLU were profoundly reduced, and the normally exquisite sensitivity of the DH(s) to elevated K(+)o is decreased. Considered collectively, the observations raise the possibility that impaired regulation of DH(s) K(+)o and GLU(o) may contribute to initiation and maintenance of the CNS pain circuit and sensorimotor abnormalities that develop following intracutaneous formalin injection.

Time-dependence of SI RA neuron response to cutaneous flutter stimulation.

Spike discharge activity of RA-type SI cortical neurons was recorded extracellularly in anesthetized monkeys and cats. Multiple applications (trials) of 10-50 Hz sinusoidal vertical skin displacement stimulation ("flutter") were delivered to the receptive field (RF). Analysis revealed large and systematic temporal trends not only in SI RA neuron responsivity (measured as spikes/s and as spikes/stimulus cycle), but also in entrainment, and in phase angle of the entrained responses. In contrast to SI RA neurons, the response of RA skin afferents to comparable conditions of skin flutter stimulation exhibited little or no dynamics. The occurrence and form of the SI RA neuron response dynamics that accompany skin flutter stimulation are shown to depend on factors such as stimulus frequency and the locus of the recording site in the global cortical response pattern. Comparison of recordings obtained in near-radial vs tangential microelectrode penetrations further reveals that the SI RA neuron response dynamics that occur during skin flutter stimulation are relatively consistent within, but heterogeneous across column-sized regions. The observed SI RA neuron response dynamics are suggested to account, in part, for the improved capacity to discriminate stimulus frequency after an exposure ("adaptation") to skin flutter stimulation (Goble and Hollins, J Acoust Soc Am 96: 771-780, 1994). Parallels with recent proposals about the contributions to visual perception of short-term primary sensory cortical neuron dynamics and synchrony in multineuron spike activity patterns are identified and discussed.

Spurious dynamics in somatosensory cortex.

Cortical networks are dynamical systems whose task is to process information. However, in addition to 'intended' dynamical behaviors, the sheer complexity of a cortical network's structure-regardless of its precise details-should generate additional 'unintended' dynamical behaviors. Dynamics observed in cortical network models and in the somatosensory cortex suggest that such spurious dynamical behaviors are likely to be pervasive but relatively simple, contributing to-rather than dominating-a network's response to stimuli. Spurious dynamics may be responsible for a variety of experimentally observed intriguing features of cortical dynamics. Because of their distributed origins and emergent nature, such dynamical features, while clearly identifiable, will resist attempts at identifying specific mechanisms to explain them. We describe some of the spurious dynamical phenomena associated with somatosensory cortical response to brushing stimulation, to illustrate how spurious dynamics can affect neurons' functional properties, cortical stimulus representation and, ultimately, perception.

Responses of contralateral SI and SII in cat to same-site cutaneous flutter versus vibration.

The methods of (14)C-2-deoxyglucose ((14)C-2DG) metabolic mapping and optical intrinsic signal (OIS) imaging were used to evaluate the response evoked in the contralateral primary somatosensory receiving areas (SI and SII) of anesthetized cats by either 25 Hz ("flutter") or 200 Hz ("vibration") sinusoidal vertical skin displacement stimulation of the central pad on the distal forepaw. Unilateral 25-Hz stimulation consistently evoked a localized region of elevated (14)C-2DG uptake in both SI and SII in the contralateral hemisphere. In contrast, 200-Hz stimulation did not evoke elevated (14)C-2DG uptake in the contralateral SI but evoked a prominent, localized region of increased (14)C-2DG uptake in the contralateral SII. Experiments in which the OIS was recorded yielded results that complemented and extended the findings obtained with the 2DG method. First, 25-Hz central-pad stimulation evoked an increase in absorbance in a region in the contralateral SI and SII that corresponded closely to the region in which a similar stimulus evoked increased (14)C-2DG uptake. Second, 200-Hz stimulation of the central pad consistently evoked a substantial increase in absorbance in the contralateral SII but very little or no increase in absorbance in the contralateral SI. And third, 200-Hz central-pad stimulation usually evoked a decrease in absorbance in the same contralateral SI region that underwent an increase in absorbance during same-site 25-Hz stimulation. Experiments in which the OIS responses of both SI and SII were recorded simultaneously demonstrated that continuous (>1 s) 25-Hz central-pad stimulation evokes a prominent increase in absorbance in both SI and SII in the contralateral hemisphere, whereas only SII undergoes a sustained prominent increase in absorbance in response to 200-Hz stimulation to the same central-pad site. SI exhibits an initial, transient increase in absorbance in response to 200-Hz stimulation and at durations of stimulation >1 s, undergoes a decrease in absorbance. It was found that the stimulus-evoked absorbance changes in the contralateral SI and SII are correlated significantly during vibrotactile stimulation of the central pad-positively with 25-Hz stimulation and negatively with 200-Hz stimulation. The findings are interpreted to indicate that 25-Hz central-pad stimulation of the central pad evokes spatially localized and vigorous neuronal activation within both SI and SII in the contralateral hemisphere and that although 200-Hz stimulation evokes vigorous and well maintained neuronal activation within the contralateral SII, the principal effect on the contralateral SI of a 200-Hz stimulus lasting >1 s is inhibitory.

Response of anterior parietal cortex to cutaneous flutter versus vibration.

The response of anesthetized squirrel monkey anterior parietal (SI) cortex to 25 or 200 Hz sinusoidal vertical skin displacement stimulation was studied using the method of optical intrinsic signal (OIS) imaging. Twenty-five-Hertz ("flutter") stimulation of a discrete skin site on either the hindlimb or forelimb for 3-30 s evoked a prominent increase in absorbance within cytoarchitectonic areas 3b and 1 in the contralateral hemisphere. This response was confined to those area 3b/1 regions occupied by neurons with a receptive field (RF) that includes the stimulated skin site. In contrast, same-site 200-Hz stimulation ("vibration") for 3-30 s evoked a decrease in absorbance in a much larger territory (most frequently involving areas 3b, 1, and area 3a, but in some subjects area 2 as well) than the region that undergoes an increase in absorbance during 25-Hz flutter stimulation. The increase in absorbance evoked by 25-Hz flutter developed quickly and remained relatively constant for as long as stimulation continued (stimulus duration never exceeded 30 s). At 1-3 s after stimulus onset, the response to 200-Hz stimulation, like the response to 25-Hz flutter, consisted of a localized increase in absorbance limited to the topographically appropriate region of area 3b and/or area 1. With continuing 200-Hz stimulation, however, the early response declined, and by 4-6 s after stimulus onset, it was replaced by a prominent and spatially extensive decrease in absorbance. The spike train responses of single quickly adapting (QA) neurons were recorded extracellularly during microelectrode penetrations that traverse the optically responding regions of areas 3b and 1. Onset of either 25- or 200-Hz stimulation at a site within the cutaneous RF of a QA neuron was accompanied by a substantial increase in mean spike firing rate. With continued 200-Hz stimulation, however, QA neuron mean firing rate declined rapidly (typically within 0.5-1.0 s) to a level below that recorded at the same time after onset of same-site 25-Hz stimulation. For some neurons, the mean firing rate after the initial 0.5-1 s of an exposure to 200-Hz stimulation of the RF decreased to a level below the level of background ("spontaneous") activity. The decline in both the stimulus-evoked increases in absorbance in areas 3b/1 and spike discharge activity of area 3b/1 neurons within only a few seconds of the onset of 200-Hz skin stimulation raised the possibility that the predominant effect of continuous 200-Hz stimulation for >3 s is inhibition of area 3b/1 QA neurons. This possibility was evaluated at the neuronal population level by comparing the intrinsic signal evoked in areas 3b/1 by 25-Hz skin stimulation to the intrinsic signal evoked by a same-site skin stimulus containing both 25- and 200-Hz sinusoidal components (a "complex waveform stimulus"). Such experiments revealed that the increase in absorbance evoked in areas 3b/1 by a stimulus having both 25- and 200-Hz components was substantially smaller (especially at times >3 s after stimulus onset) than the increase in absorbance evoked by "pure" 25-Hz stimulation of the same skin site. It is concluded that within a brief time (within 1-3 s) after stimulus onset, 200-Hz skin stimulation elicits a powerful inhibitory action on area 3b/1 QA neurons. The findings appear generally consistent with the suggestion that the activity of neurons in cortical regions other than areas 3b and 1 play the leading role in the processing of high-frequency (>/=200 Hz) vibrotactile stimuli.

Response of anterior parietal cortex to different modes of same-site skin stimulation.

Response of anterior parietal cortex to different modes of same-site skin stimulation. J. Neurophysiol. 80: 3272-3283, 1998. Intrinsic optical signal (IOS) imaging was used to study responses of the anterior parietal cortical hindlimb region (1 subject) and forelimb region (3 subjects) to repetitive skin stimulation. Subjects were four squirrel monkeys anesthetized with a halothane/nitrous oxide/oxygen gas mixtures. Cutaneous flutter of 25 Hz evoked a reflectance decrease in the sectors of cytoarchitectonic areas 3b and/or 1 that receive input from the stimulated skin site. The intrinsic signal evoked by 25-Hz flutter attained maximal intensity

Stimulus-response diversity in local neuronal populations of the cerebral cortex.

In cortex, neighboring 0.05 mm minicolumns have distinctly different receptive fields (RFs). Within minicolumns, neighboring cells have very similar RFs, but differ prominently in their stimulus-evoked temporal behaviors. This is reproduced in a cortical model that has strong inhibition and semi-random lateral connections among cells with similar RFs. Within modeled minicolumns, non-linear dynamics amplify small differences in cells' lateral inputs into large differences in temporal behaviors. Cells' stimulus-evoked behaviors, though complex, are surprisingly orderly, in that (1) time courses of cells' responses are very stimulus-specific and (2) in the presence of a stimulus, activities of some cells fluctuate coherently, and the patterns of coherence are also stimulus-specific. Thus the model, like real cortex, represents stimulus information in the overall strengths and temporal patterns of cells' responses and in patterns of temporal coherence among cells.

Anterior parietal cortical response to tactile and skin-heating stimuli applied to the same skin site.

1. The response of anterior parietal cortex to skin stimuli was evaluated with optical intrinsic signal imaging and extracellular microelectrode recording methods in anesthetized squirrel monkeys. 2. Nonnoxious mechanical stimulation (vibrotactile or skin tapping) of the contralateral radial interdigital pad was accompanied by a decrease in reflectance (at 833 nm) in sectors of cytoarchitectonic areas 3b and 1. This intrinsic signal was in register with regions shown by previous receptive field mapping studies to receive low-threshold mechanoreceptor input from the radial interdigital pad. 3. A skin-heating stimulus applied to the contralateral radial interdigital pad with a stationary probe/thermode evoked no discernable intrinsic signal in areas 3b and 1, but evoked a signal within a circumscribed part of area 3a. The region of area 3a responsive to skin heating with the stationary probe/thermode was adjacent to the areas 3b and 1 regions that developed an intrinsic signal in response to vibrotactile stimulation of the same skin site. Skin heating with a stationary probe/thermode also evoked intrinsic signal in regions of areas 4 and 2 neighboring the area 3b/1 regions activated by vibrotactile stimulation of the contralateral radial interdigital pad. 4. The intrinsic signal evoked in area 3a by a series of heating stimuli to the contralateral radial interdigital pad (applied with a stationary probe/thermode) increased progressively in magnitude with repeated stimulation (exhibited slow temporal summation) and remained above prestimulus levels for a prolonged period after termination of repetitive stimulation. 5. Brief mechanical stimuli ("taps") applied to the contralateral radial interdigital pad with a probe/thermode maintained either at 37 degrees C or at 52 degrees C were accompanied by the development of an intrinsic signal in both area 3a and areas 3b/1. For the 52 degrees C stimulus, the area 3a intrinsic signal was larger and the intrinsic signal in areas 3b/1 smaller than the corresponding signals evoked by the 37 degrees C stimulus. 6. Spike discharge activity was recorded from area 3a neurons during a repetitive heating stimulus applied with a stationary probe/ thermode to the contralateral radial interdigital pad. Like the area 3a intrinsic signal elicited by repetitive heating of the same skin site, the area 3a neuron spike discharge activity also exhibited slow temporal summation and poststimulus response persistence. 7. The experimental findings suggest 1) a leading role for area 3a in the anterior parietal cortical processing of skin-heating stimuli, and 2) the presence of inhibitory interactions between the anterior parietal responses to painful and vibrotactile stimuli consistent with those demonstrated in recent cortical imaging and psychophysical studies of human subjects.

Minicolumnar organization within somatosensory cortical segregates: I. Development of afferent connections.

This series of two articles develops a hypothesis on the modular organization of somatosensory cortex. The hypothesis is built around two functional entities: the segregate, a discrete somatosensory cortical macrocolumn approximately 0.5 mm in diameter, and the minicolumn, a smaller column approximately 0.05 mm in diameter, 40-80 of which make up a segregate. The hypothesis proposes that during perinatal development, minicolumns, acting via their short-range inhibitory and longer-range excitatory lateral connections, play an important role in the selection of thalamic connections to neighboring minicolumns. More specifically, the thalamic connections to each minicolumn are shaped by the interaction of that minicolumn primarily with those neighbors that belong to the same segregate. The outcome of this within-segregate self-organizational process is that (1) the minicolumns in a segregate acquire a complex but orderly pattern of afferent connections; (2) this connectional pattern, along with lateral inhibition, gives the minicolumns diverse receptive fields, arranged in a shuffled but orderly manner; and, most importantly, (3) the minicolumns and the segregate as a whole acquire a variety of stimulus feature-extracting properties. A computer-based model of a segregate is developed to show that under conditions found in the developing cerebral cortex, the thalamocortical connections within a segregate readily form complex patterns as proposed by the hypothesis. Furthermore, the connectional patterns developed by the model segregate, its receptive field organization, and its feature-extracting properties (the latter are described in the following article) reproduce many experimentally observed features of real cortical networks.

Minicolumnar organization within somatosensory cortical segregates: II. Emergent functional properties.

In this article we describe some functional properties of the model of a somatosensory cortical macrocolumn--the segregate--described in the preceding companion article. These functional properties emerged in the model network in the course of stimulus-driven self-organization of its afferent connections under control of short-range inhibitory and longer-range excitatory lateral interactions among its minicolumns. In general, self-organization leads the model network to develop complex, nonlinear functional properties, and makes its neurons sensitive to the shape and temporal features of peripheral stimuli. The properties acquired reproduce some of the known properties of somatosensory and visual cortical networks. In particular, it is shown that, even though the network is exposed only to stationary point stimuli during self-organization, neurons in the model still acquire the ability to discriminate the direction of a moving stimulus, as well as the orientation of a stationary bar stimulus. Different stimulus directions and orientations are represented by different neurons in the model network, and the maps of neurons having these preferences have many properties in common with real cortical maps. In addition, we demonstrate the model network's ability to discriminate among spatially complex stimuli, such as letters of the alphabet. The parallels between the emergent structural and functional properties of the model network and the properties of sensory neocortex suggest that the model captures some of the basic mechanisms by which sensory cortical modules develop and maintain their elegantly detailed and appreciable information-processing capabilities.

Demonstration of discrete place-defined columns--segregates--in the cat SI.

The SI forelimb area of cats was examined with receptive field (RF) mapping techniques. Arrays of closely spaced, near-radial microelectrode penetrations were inserted into the crown of postsigmoid gyrus of ketamine anesthetized subjects and minimal RFs were obtained at several depths. The minimal RF was defined as the skin site providing the strongest input to each recorded cluster of neurons. Data analysis showed that all studied cortical territories contained groups of discrete cortical columns, 300-400 microns in diameter. The columns were regarded as topographic entities because no change in minimal RF location could be observed within their boundaries. The boundaries of columns were sharp and could be unequivocally distinguished because the minimal RFs sampled on opposite sides of a boundary occupied displaced, nonoverlapping positions. Pair-wise comparison of single neuron maximal RFs (defined as the entire skin area providing input to the recorded neuron) further clarified the nature of the SI place-defined columns: (1) no systematic differences in maximal RF position could be demonstrated for different parts of the same column (even though the maximal RFs in most columns varied extensively in size and skin areas covered), and (2) at the boundary between neighboring columns maximal RFs shifted en masse to center on a new skin locus. These minimal and maximal RF observations strongly support our recent proposal that body surface is represented in SI by a honeycomblike mosaic of discrete place-defined cortical columns, segregates.

Evidence for a mosaic representation of the body surface in area 3b of the somatic cortex of cat.

A discontinuous representation of the forelimb body surface in area 3b is proposed. Two different methods were used: single-neuron receptive-field (RF) mapping in unanesthetized cats (maximal RF) and multiunit RF mapping in deeply anesthetized cats (minimal RF). Ten or more maximal RFs were sampled in each of 14 near-radial microelectrode penetrations. In 6 penetrations, the maximal RFs of all sampled neurons (despite prominent variations in RF size and shape) shared in common a small skin area--termed the "RF center." Each of the remaining penetrations had to be divided into at least two segments (6 penetrations) or three segments (2 penetrations), for all maximal RFs mapped in a segment to include a common skin site. In six penetrations, after maximal RFs were mapped, deep general anesthesia was induced and minimal RFs were mapped in the same penetration at cortical sites separated by 150 microns. Minimal RFs closely matched the RF centers defined by maximal RFs in the same penetration. In penetrations that mapped two or three RF centers, a rapid transition in minimal RF position was detected at the same cortical site where the shift in RF center was detected. Closely spaced penetrations revealed discrete cortical columns, having the size and shape of 350- to 400-microns-diameter irregular hexagons, such that the identical minimal RF was mapped at any site within a column. The forelimb body surface in cat 3b thus appears to be represented by a mosaic of discrete columns--an organization similar to the whisker representation in rodent primary somatosensory cortex.