Cortex controls multisensory depression in superior colliculus

Multisensory depression is a fundamental index of multisensory integration in superior colliculus (SC) neurons. It is initiated when one sensory stimulus (auditory) located outside its modality-specific receptive field degrades or eliminates the neuron's responses to another sensory stimulus (visual) presented within its modality-specific receptive field. The present experiments demonstrate that the capacity of SC neurons to engage in multisensory depression is strongly dependent on influences from two cortical areas (the anterior ectosylvian and rostral lateral suprasylvian sulci). When these cortices are deactivated, the ability of SC neurons to synthesize visual-auditory inputs in this way is compromised; multisensory responses are disinhibited, becoming more vigorous and in some cases indistinguishable from responses to the visual stimulus alone. Although obtaining a more robust multisensory SC response when cortex is nonfunctional than when it is functional may seem paradoxical, these data may help explain previous observations that the loss of these cortical influences permits visual orientation behavior in the presence of a normally disruptive auditory stimulus.     

The influence of stimulus properties on multisensory processing in the awake primate superior colliculus.

Evaluated the influence of physical properties of sensory stimuli (visual intensity, direction, and velocity; auditory intensity and location) on sensory activity and multisensory integration of superior colliculus (SC) neurons in awake, behaving primates. Two male monkeys were trained to fixate a central visual fixation point while visual and/or auditory stimuli were presented in the periphery. Visual stimuli were always presented within the contralateral receptive field of the neuron whereas auditory stimuli were presented at either ipsi- or contralateral locations. 66 of the 84 SC neurons responsive to these sensory stimuli had stronger responses when the visual and auditory stimuli were combined at contralateral locations than when the auditory stimulus was located on the ipsilateral side. This trend was significant across the population of auditory-responsive neurons. In addition, 31 SC neurons were presented a battery of tests in which the quality of one stimulus of a pair was systematically manipulated. Eight of these neurons showed preferential responses to stimuli with specific physical properties, and these preferences were not significantly altered when multisensory stimulus combinations were presented. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Development of multisensory neurons and multisensory integration in cat superior colliculus

The development of multisensory neurons and multisensory integration was examined in the deep layers of the superior colliculus of kittens ranging in age from 3 to 135 d postnatal (dpn). Despite the high proportion of multisensory neurons in adult animals, no such neurons were found during the first 10 d of postnatal life. Rather, all sensory-responsive neurons were unimodal. The first multisensory neurons (somatosensory-auditory) were found at 12 dpn, and visually responsive multisensory neurons were not found until 20 dpn. Early multisensory neurons responded weakly to sensory stimuli, had long latencies, large receptive fields, and poorly developed response selectivities. Most surprising, however, was their inability to integrate combinations of sensory cues to produce significant response enhancement (or depression), a characteristic feature of the adult. Responses to combinations of sensory cues differed little from responses to their modality-specific components. At 28 dpn an abrupt physiological change was noted. Some multisensory neurons now integrated combinations of cross-modality cues and exhibited significant response enhancements when these cues were spatially coincident and response depressions when the cues were spatially disparate. During the next 2 months the incidence of multisensory neurons, and the proportion of these neurons capable of adult-like multisensory integration, gradually increased. Once multisensory integration appeared in a given neuron, its properties changed little with development. Even the youngest integrating neurons showed superadditive enhancements and spatial characteristics of multisensory integration that were indistinguishable from the adult. Nevertheless, neonatal and adult multisensory neurons differed in the manner in which they integrated temporally asynchronous stimuli, a distribution that may reflect the very different behavioral requirements at different ages. The possible maturational role of corticotectal projections in the abrupt gating of multisensory integration is discussed.     

Mechanisms of within- and cross-modality suppression in the superior colliculus

The present studies were initiated to explore the basis for the response suppression that occurs in cat superior colliculus (SC) neurons when two spatially disparate stimuli are presented simultaneously or in close temporal proximity to one another. Of specific interest was examining the possibility that suppressive regions border the receptive fields (RFs) of unimodal and multisensory SC neurons and, when activated, degrade the neuron's responses to excitatory stimuli. Both within- and cross-modality effects were examined. An example of the former is when a response to a visual stimulus within its RF is suppressed by a second visual stimulus outside the RF. An example of the latter is when the response to a visual stimulus within the visual RF is suppressed when a stimulus from a different modality (e. g., auditory) is presented outside its (i.e., auditory) RF. Suppressive regions were found bordering visual, auditory, and somatosensory RFs. Despite significant modality-specific differences in the incidence and effectiveness of these regions, they were generally quite potent regardless of the modality. In the vast majority (85%) of cases, responses to the excitatory stimulus were degraded by >/=50% by simultaneously stimulating the suppressive region. Contrary to expectations and previous speculations, the effects of activating these suppressive regions often were quite specific. Thus powerful within-modality suppression could be demonstrated in many multisensory neurons in which cross-modality suppression could not be generated. However, the converse was not true. If an extra-RF stimulus inhibited center responses to stimuli of a different modality, it also would suppress center responses to stimuli of its own modality. Thus when cross-modality suppression was demonstrated, it was always accompanied by within-modality suppression. These observations suggest that separate mechanisms underlie within- and cross-modality suppression in the SC. Because some modality-specific tectopetal structures contain neurons with suppressive regions bordering their RFs, the within-modality suppression observed in the SC simply may reflect interactions taking place at the level of one input channel. However, the presence of modality-specific suppression at the level of one input channel would have no effect on the excitation initiated via another input channel. Given the modality-specificity of tectopetal inputs, it appears that cross-modality interactions require the convergence of two or more modality-specific inputs onto the same SC neuron and that the expression of these interactions depends on the internal circuitry of the SC. This allows a cross-modality suppressive signal to be nonspecific and to degrade any and all of the neuron's excitatory inputs.     

Sensory modality distribution in the anterior ectosylvian cortex (AEC) of cats

Modality specificity of neuronal responses to visual, somesthetic and auditory stimuli was investigated in the anterior ectosylvian cortex (AEC) of cats, using single-unit recording techniques. Seven classes of neurons were found, and according to their responsiveness to sensory stimuli regrouped into three categories: unimodal, bimodal and trimodal. Unimodal cells that responded to only one of the three stimulus modalities formed 59% of the units; 30.2% were bimodal, in that they showed a clear increase of neuronal discharges to two of the three stimulus types; 10.8% were defined as trimodal because they responded to all three stimulus modalities. Although the different categories of cells were intermingled within the AEC, indicating a certain degree of overlap between sensory modalities, some clustering of cell types was nonetheless evident. Thus, the somatosensory responsive cells were mainly located in the anterior two-thirds of the dorsal bank of the anterior ectosylvian sulcus. Visually responsive cells were concentrated on the ventral bank of the sulcus, whereas neurons with an auditory response occupied the banks and fundus of the posterior three-quarters of the sulcus. The histological distribution and physiological properties of AEC neurons suggest that this cortical region is a higher-order associative area whose function may be to integrate information from different sensory modalities.     

A theory of cerebral learning regulated by the reward system. I. Hypotheses and mathematical description

Hypothetical mechanisms of the neocorticohippocampal system are presented. Neurophysiological and neuroanatomical findings concerning the system are integrated to demonstrate how animals associate sensory stimuli with rewarding actions: (1) cortical plasticity regulated by cholinergic/noradrenergic inputs from the hypothalamic reward system reinforces association connections between the most activated columns in the cortex; (2) the repetitive reinforcement forms association pathways connecting sensory cortical columns activated by the stimuli with motor cortical columns producing the rewarding actions; (3) after the pathways are formed, the cortex is capable of temporarily memorizing the stimuli by producing long-term potentiation through the cortico-hippocampal circuits; and (4) the memory allows the cortex to extend correct association pathways even in an environment where sensory stimuli rapidly change. A mathematical model of parts of the nervous system is presented to quantitatively examine the mechanisms. Membrane characteristics of single neurons are given by the Hodgkin-Huxley electric circuit. According to anatomical data, neural circuits of the neocortico-hippocampal system are composed by connecting populations of the model neurons. Computer simulation using physiological data concerning ion channels demonstrates how the mechanisms work and how to test the hypotheses presented.     

Deconstructing the McGurk–MacDonald illusion.

Cross-modal illusions such as the McGurk–MacDonald effect have been used to illustrate the automatic, encapsulated nature of multisensory integration. This characterization is based in the widespread assumption that the illusory percept arising from intersensory conflict reflects only the end-product of the multisensory integration process, with the mismatch between the original unisensory events remaining largely hidden from awareness. Here the authors show that when presented with desynchronized audiovisual speech syllables, observers are often able to detect the temporal mismatch while experiencing the McGurk–MacDonald illusion. Thus, contrary to previous assumptions, it seems possible to gain access to information about the individual sensory components of a multisensory (integrated) percept. On the basis of this and similar findings, the authors argue that multisensory integration is a multifaceted process during which different attributes of the (multisensory) object might be bound by different mechanisms and possibly at different times. This proposal contrasts with classic conceptions of multisensory integration as a homogeneous process whereby all the attributes of a multisensory event are treated in a unified manner. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reproducibility and variability in neural spike trains

To provide information about dynamic sensory stimuli, the pattern of action potentials in spiking neurons must be variable. To ensure reliability these variations must be related, reproducibly, to the stimulus. For H1, a motion-sensitive neuron in the fly's visual system, constant-velocity motion produces irregular spike firing patterns, and spike counts typically have a variance comparable to the mean, for cells in the mammalian cortex. But more natural, time-dependent input signals yield patterns of spikes that are much more reproducible, both in terms of timing and of counting precision. Variability and reproducibility are quantified with ideas from information theory, and measured spike sequences in H1 carry more than twice the amount of information they would if they followed the variance-mean relation seen with constant inputs. Thus, models that may accurately account for the neural response to static stimuli can significantly underestimate the reliability of signal transfer under more natural conditions.     

Modulation of calcium-dependent postsynaptic depression contributes to an adaptive sensory filter

Modulation of calcium-dependent postsynaptic depression contributes to an adaptive sensory filter. J. Neurophysiol. 80: 3352-3355, 1998. The ability of organisms to ignore unimportant patterns of sensory input may be as critical as the ability to attend to those that are behaviorally relevant. Mechanisms used to reject irrelevant inputs range from peripheral filters, which allow only restricted portions of the spectrum of possible inputs to pass, to higher-level processes, which actively select stimuli to be "attended to." Recent studies of several lower vertebrates demonstrate the presence of adaptive sensory filters, which "learn," with a time course of a few minutes, to cancel predictable patterns of sensory input without compromising responses to novel stimuli. Predictable stimuli include "reafferent" stimuli, which occur as a result of an animal's own activity, as well as stimuli that are simply repetitive. The adaptive characteristic of these filters depends on an anti-Hebbian form of synaptic plasticity that modulates the strength of multisensory dendritic inputs resulting in the genesis of "negative image" signals, which cancel the predicted pattern of sensory afference. This report provides evidence that the mechanism underlying the anti-Hebbian plasticity involves the modulation of a calcium-dependent form of postsynaptic depression.     

Converging levels of analysis in the cognitive neuroscience of visual attention

Experiments using behavioural, lesion, functional imaging and single neuron methods are considered in the context of a neuropsychological model of visual attention. According to this model, inputs compete for representation in multiple visually responsive brain systems, sensory and motor, cortical and subcortical. Competition is biased by advance priming of neurons responsive to current behavioural targets. Across systems competition is integrated such that the same, selected object tends to become dominant throughout. The behavioural studies reviewed concern divided attention within and between modalities. They implicate within-modality competition as one main restriction on concurrent stimulus identification. In contrast to the conventional association of lateral attentional focus with parietal lobe function, the lesion studies show attentional bias to be a widespread consequence of unilateral cortical damage. Although the clinical syndrome of unilateral neglect may indeed be associated with parietal lesions, this probably reflects an assortment of further deficits accompanying a simple attentional imbalance. The functional imaging studies show joint involvement of lateral prefrontal and occipital cortex in lateral attentional focus and competition. The single unit studies suggest how competition in several regions of extrastriate cortex is biased by advance priming of neurons responsive to current behavioural targets. Together, the concepts of competition, priming and integration allow a unified theoretical approach to findings from behavioural to single neuron levels.     

Visual, somatosensory, auditory and nociceptive modality properties in the feline suprageniculate nucleus

Response properties of 252 single-units to visual, auditory, somatosensory and noxious stimulation were recorded by means of extracellular microelectrodes in the suprageniculate nucleus of anaesthetized, immobilized cats. Of the 141 units tested for modality properties the majority (n=113, 80.1%) was found unimodal in the sense that stimuli of exclusively one sensory modality were able to elicit an activation of the unit. Twenty-four (17.0%) cells were bimodal and four (2.8%) were trimodal (visual, somatosensory and auditory). The visual modality dominated the unimodal cells (n=74, 65.5%), while cells responsive to somatic stimulation (n=20, 17.6%), auditory stimulation (n=16, 14.1%) or noxious stimulation of the tooth pulp (n=3, 2.6%) were less frequently encountered. Visual sensitivity dominated the multisensory cells, too. The visually responsive units were characterized by having a sensitivity to stimuli moving in a rather large, uniform receptive field that covered the contralateral lower quadrant, and encompassed a flanking area of about 20 degree width in both the upper contralateral and lower ipsilateral visual fields. Many cells (n=52, 47%) were sensitive to the direction of the stimulation and reacted to stimuli moving at a high velocity (20-200 deg/s). Most cells responded differently to stimuli of a variety of sizes. Somatosensory units reacted to stimuli presented over a wide area on the contralateral side of the body, thus showing no sign of somatotopic organization. The auditory sensitivity fell within a wide range of acoustic stimuli in extremely large auditory receptive fields. The physiological properties of suprageniculate nucleus cells strongly resemble the sensory properties of cells found along the ventral bank of the anterior ectosylvian sulcus and the deeper layers of the superior colliculus. Our results provide further support for the notion of a separate tecto-suprageniculate-anterior ectosylvian sulcus/insular pathway that takes part in the processing of multimodal signals important for various types of sensory related behaviours.     

Optimal integration of auditory and vibrotactile information for judgments of temporal order.

Recent research that assessed spatial judgments about multisensory stimuli suggests that humans integrate multisensory inputs in a statistically optimal manner by weighting each input by its normalized reciprocal variance. Is integration similarly optimal when humans judge the temporal properties of bimodal stimuli? Twenty-four participants performed temporal order judgments (TOJs) about 2 spatially separated stimuli. Stimuli were auditory, vibrotactile, or both. The temporal profiles of vibrotactile stimuli were manipulated to produce 3 levels of precision for TOJs. In bimodal conditions, the asynchrony between the 2 unimodal stimuli that comprised a bimodal stimulus was manipulated to determine the weight given to touch. Bimodal performance on 2 measures—judgment uncertainty and tactile weight—was predicted with unimodal data. A model relying exclusively on audition was rejected on the basis of both measures. A second model that selected the best input on each trial did not predict the reduced judgment uncertainty observed in bimodal trials. Only the optimal maximum-likelihood-estimation model predicted both judgment uncertainties and weights; the model’s validity is extended to TOJs. Alternatives for modeling the process of event sequencing based on integrated multisensory inputs are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A local circuit approach to understanding integration of long-range inputs in primary visual cortex

Integration of inputs by cortical neurons provides the basis for the complex information processing performed in the cerebral cortex. Here, we have examined how primary visual cortical neurons integrate classical and nonclassical receptive field inputs. The effect of nonclassical receptive field stimuli and, correspondingly, of long-range intracortical inputs is known to be context-dependent: the same long-range stimulus can either facilitate or suppress responses, depending on the level of local activation. By constructing a large-scale model of primary visual cortex, we demonstrate that this effect can be understood in terms of the local cortical circuitry. Each receptive field position contributes both excitatory and inhibitory inputs; however, the inhibitory inputs have greater influence when overall receptive field drive is greater. This mechanism also explains contrast-dependent modulations within the classical receptive field, which similarly switch between excitatory and inhibitory. In order to simplify analysis and to explain the fundamental mechanisms of the model, self-contained modules that capture nonlinear local circuit interactions are constructed. This work supports the notion that receptive field integration is the result of local processing within small groups of neurons rather than in single neurons.     

Otx/otd homeobox genes specify distinct sensory neuron identities in C. elegans

The mechanisms by which the diverse functional identities of neurons are generated are poorly understood. C. elegans responds to thermal and chemical stimuli using 12 types of sensory neurons. The Otx/otd homolog ttx-1 specifies the identities of the AFD thermosensory neurons. We show here that ceh-36 and ceh-37, the remaining two Otx-like genes in the C. elegans genome, specify the identities of AWC, ASE, and AWB chemosensory neurons, defining a role for this gene family in sensory neuron specification. All C. elegans Otx genes and rat Otx1 can substitute for ceh-37 and ceh-36, but only ceh-37 functionally substitutes for ttx-1. Functional substitution in the AWB neurons is mediated by activation of the same downstream target lim-4 by different Otx genes. Misexpression experiments indicate that although the specific identity adopted upon expression of an Otx gene may be constrained by the cellular context, individual Otx genes preferentially promote distinct neuronal identities.     

How the owl resolves auditory coding ambiguity

The barn owl (Tyto alba) uses interaural time difference (ITD) cues to localize sounds in the horizontal plane. Low-order binaural auditory neurons with sharp frequency tuning act as narrow-band coincidence detectors; such neurons respond equally well to sounds with a particular ITD and its phase equivalents and are said to be phase ambiguous. Higher-order neurons with broad frequency tuning are unambiguously selective for single ITDs in response to broad-band sounds and show little or no response to phase equivalents. Selectivity for single ITDs is thought to arise from the convergence of parallel, narrow-band frequency channels that originate in the cochlea. ITD tuning to variable bandwidth stimuli was measured in higher-order neurons of the owl's inferior colliculus to examine the rules that govern the relationship between frequency channel convergence and the resolution of phase ambiguity. Ambiguity decreased as stimulus bandwidth increased, reaching a minimum at 2-3 kHz. Two independent mechanisms appear to contribute to the elimination of ambiguity: one suppressive and one facilitative. The integration of information carried by parallel, distributed processing channels is a common theme of sensory processing that spans both modality and species boundaries. The principles underlying the resolution of phase ambiguity and frequency channel convergence in the owl may have implications for other sensory systems, such as electrolocation in electric fish and the computation of binocular disparity in the avian and mammalian visual systems.     

Response properties of corticotectal and corticostriatal neurons in the posterior lateral suprasylvian cortex of the cat

Lateral suprasylvian cortex (LS) is an important source of visual projections to both the striatum and superior colliculus. Although these two LS efferent systems are likely to be involved in different aspects of visual processing, little is known about their functional properties. In the present experiments, 86 neurons in halothane-anesthetized, paralyzed cats were recorded along the posterior aspects of the medial and lateral banks of LS (PMLS and PLLS). Neurons were selected for analysis on the basis of antidromic activation from electrodes chronically implanted in the superior colliculus and caudate nucleus. The segregated nature of corticostriatal and corticotectal neurons was apparent; in no instance could a neuron be antidromically activated from both the superior colliculus and the caudate nucleus. Many common features were revealed between corticotectal and corticostriatal neurons; the majority of neurons in both populations were binocular and contralaterally dominant, showed similar responses to stationary flashed light, and expressed within-field spatial summation and surround inhibition. However, a number of information-processing features distinguished between corticotectal and corticostriatal neurons; the former were generally tuned to lower velocities than were the latter, and, for a given eccentricity in visual space, corticotectal neurons had smaller receptive fields than did corticostriatal neurons. Moreover, most corticotectal neurons displayed a marked preference for movements toward temporal visual space, whereas corticostriatal neurons revealed no specialization for a particular direction of movement. In addition, whereas corticotectal neurons were selective for receding stimuli, corticostriatal neurons were selective for approaching stimuli. The presence of these two corticofugal pathways is discussed in relation to their presumptive functional roles in the facilitation of attentive and orientation behaviors.     

Sensory responsiveness of "broad-spike" neurons in the laterodorsal tegmental nucleus, locus coeruleus and dorsal raphe of awake rats: implications for cholinergic and monoaminergic neuron-specific responses

Although cholinergic neurons in the laterodorsal and pedunculopontine tegmental nuclei have been shown to have a pivotal role in neural mechanisms of paradoxical sleep, their function during wakefulness is less understood. To examine the latter, we have recorded from "broad-spike neurons", which were distinguished by their long spike duration, in the laterodorsal tegmental nucleus of undrugged, head-restrained rats, and examined their response properties to sensory stimuli such as light touch to the tail, air puff to the face, 2 kHz pure tone and flashes of light. Broad-spike neurons from the locus coeruleus and dorsal raphe nucleus were studied for comparison; these neurons have been demonstrated to be noradrenergic and serotonergic, respectively. The broad-spike neurons in the laterodorsal tegmental nucleus have also been suggested to be cholinergic. There were two kinds of responses: (1) a simple increase or decrease in firing, reflecting an elevated level of vigilance; and (2) a phasic response composed of a single spike or brief, high frequency burst, usually diminishing or disappearing upon repetition of the stimulus. When two or more types of stimuli were effective in a neuron, they evoked responses of the same quality. Most of the dorsal raphe neurons displayed only the simple increase of firing, whereas the locus coeruleus neurons gave a phasic response with rather weak attenuation upon repetition. Compared with these, the laterodorsal tegmental neurons were heterogeneous: about one-quarter showing only a simple change of firing (half increasing, half decreasing); and two-thirds displaying phasic responses. The latter response of many neurons attenuated strongly upon repetition. The laterodorsal tegmental neurons were classified into several groups according to their spontaneous firing behavior during sleep and wakefulness, but every neuron in a group did not show the same type of response. For example, some of the neurons which were most active during paradoxical sleep and essentially silent during wakefulness decreased or stopped firing upon sensory stimulation, while others in this group had strong phasic responses. These results suggest that putative cholinergic neurons in the laterodorsal tegmental nucleus have heterogenous properties not only with respect to their spontaneous activity during sleep and wakefulness but also with respect to their response to sensory stimulation. Some of these neurons may function to induce a global attentive state in response to a novel stimulus.     

The variable discharge of cortical neurons: implications for connectivity, computation, and information coding

Cortical neurons exhibit tremendous variability in the number and temporal distribution of spikes in their discharge patterns. Furthermore, this variability appears to be conserved over large regions of the cerebral cortex, suggesting that it is neither reduced nor expanded from stage to stage within a processing pathway. To investigate the principles underlying such statistical homogeneity, we have analyzed a model of synaptic integration incorporating a highly simplified integrate and fire mechanism with decay. We analyzed a "high-input regime" in which neurons receive hundreds of excitatory synaptic inputs during each interspike interval. To produce a graded response in this regime, the neuron must balance excitation with inhibition. We find that a simple integrate and fire mechanism with balanced excitation and inhibition produces a highly variable interspike interval, consistent with experimental data. Detailed information about the temporal pattern of synaptic inputs cannot be recovered from the pattern of output spikes, and we infer that cortical neurons are unlikely to transmit information in the temporal pattern of spike discharge. Rather, we suggest that quantities are represented as rate codes in ensembles of 50-100 neurons. These column-like ensembles tolerate large fractions of common synaptic input and yet covary only weakly in their spike discharge. We find that an ensemble of 100 neurons provides a reliable estimate of rate in just one interspike interval (10-50 msec). Finally, we derived an expression for the variance of the neural spike count that leads to a stable propagation of signal and noise in networks of neurons-that is, conditions that do not impose an accumulation or diminution of noise. The solution implies that single neurons perform simple algebra resembling averaging, and that more sophisticated computations arise by virtue of the anatomical convergence of novel combinations of inputs to the cortical column from external sources.     

Electrophysiologic analysis of the functional organization of cortico-cerebellar connections

The influence of associative (orbital-anterior, parietal) and projective (auditory, sensomotor) cerebral cortex areas stimulation on activity of the Purkinje neurons of cerebellar cortex was studied in adult cats under chloralose-nembutal or nembutal anesthesia. These reactions were compared with the responses to peripheral stimuli. Definite similarity in responses of the Purkinje cells to different cortical (associative, projective) stimuli was found both for types of neurons and their responsiveness. In responses of the Purkinje cells to peripheral stimulation there was no sharp similarity as it was in responses to cortical stimuli. So, in cortical stimulation almost similar number of neurons (above 50%) was excited and in peripheral stimulation the responsiveness of neurons had marked difference: to electrical stimulation of skin there were 44.6%, to auditory 34.2%, to visual 18.8% of neuron responses.