Unisensory processing and multisensory integration in schizophrenia: a high-density electrical mapping study

In real-world settings, information from multiple sensory modalities is combined to form a complete, behaviorally salient percept - a process known as multisensory integration. While deficits in auditory and visual processing are often observed in schizophrenia, little is known about how multisensory integration is affected by the disorder. The present study examined auditory, visual, and combined audio-visual processing in schizophrenia patients using high-density electrical mapping. An ecologically relevant task was used to compare unisensory and multisensory evoked potentials from schizophrenia patients to potentials from healthy normal volunteers. Analysis of unisensory responses revealed a large decrease in the N100 component of the auditory-evoked potential, as well as early differences in the visual-evoked components in the schizophrenia group. Differences in early evoked responses to multisensory stimuli were also detected. Multisensory facilitation was assessed by comparing the sum of auditory and visual evoked responses to the audio-visual evoked response. Schizophrenia patients showed a significantly greater absolute magnitude response to audio-visual stimuli than to summed unisensory stimuli when compared to healthy volunteers, indicating significantly greater multisensory facilitation in the patient group. Behavioral responses also indicated increased facilitation from multisensory stimuli. The results represent the first report of increased multisensory facilitation in schizophrenia and suggest that, although unisensory deficits are present, compensatory mechanisms may exist under certain conditions that permit improved multisensory integration in individuals afflicted with the disorder.     

A multisensory zone in rat parietotemporal cortex: intra- and extracellular physiology and thalamocortical connections

Multisensory integration is essential for the expression of complex behaviors in humans and animals. However, few studies have investigated the neural sites where multisensory integration may occur. Therefore, we used electrophysiology and retrograde labeling to study a region of the rat parietotemporal cortex that responds uniquely to auditory and somatosensory multisensory stimulation. This multisensory responsiveness suggests a functional organization resembling multisensory association cortex in cats and primates. Extracellular multielectrode surface mapping defined a region between auditory and somatosensory cortex where responses to combined auditory/somatosensory stimulation were larger in amplitude and earlier in latency than responses to either stimulus alone. Moreover, multisensory responses were nonlinear and differed from the summed unimodal responses. Intracellular recording found almost exclusively multisensory cells that responded to both unisensory and multisensory stimulation with excitatory postsynaptic potentials (EPSPs) and/or action potentials, conclusively defining a multisensory zone (MZ). In addition, intracellular responses were similar to extracellular recordings, with larger and earlier EPSPs evoked by multisensory stimulation, and interactions suggesting nonlinear postsynaptic summation to combined stimuli. Thalamic input to MZ from unimodal auditory and somatosensory thalamic relay nuclei and from multisensory thalamic regions support the idea that parallel thalamocortical projections may drive multisensory functions as strongly as corticocortical projections. Whereas the MZ integrates uni- and multisensory thalamocortical afferent streams, it may ultimately influence brainstem multisensory structures such as the superior colliculus.     

Response properties of neurons in the caudate–putamen and globus pallidus to noxious and non-noxious thermal stimulation in anesthetized rats

To investigate the possible mechanisms by which neurons in the caudate–putamen (CPu) and globus pallidus (GP) participate in pain and nociception, the present study characterized the response properties of CPu and GP neurons to non-noxious and noxious thermal stimuli in anesthetized rats. Nociceptive CPu and GP neurons were capable of encoding noxious thermal stimuli and 79% of these thermally responsive neurons also responded to noxious mechanical stimuli. Thermally responsive neurons were activated during the phasic rise and fall of the thermal shift in addition to the plateau temperature. The ability of CPu and GP neurons to encode noxious thermal stimulation intensity and respond during the dynamic phase of the stimulus suggests that these neurons may contribute to the behavioral response to minimize bodily harm.     

Multisensory auditory-somatosensory interactions in early cortical processing revealed by high-density electrical mapping

We investigated the time-course and scalp topography of multisensory interactions between simultaneous auditory and somatosensory stimulation in humans. Event-related potentials (ERPs) were recorded from 64 scalp electrodes while subjects were presented with auditory-alone stimulation (1000-Hz tones), somatosensory-alone stimulation (median nerve electrical pulses), and simultaneous auditory-somatosensory (AS) combined stimulation. Interaction effects were assessed by comparing the responses to combined stimulation with the algebraic sum of responses to the constituent auditory and somatosensory stimuli when they were presented alone. Spatiotemporal analysis of ERPs and scalp current density (SCD) topographies revealed AS interaction over the central/postcentral scalp which onset at approximately 50 ms post-stimulus presentation. Both the topography and timing of these interactions are consistent with multisensory integration early in the cortical processing hierarchy, in brain regions traditionally held to be unisensory.     

The timing and laminar profile of converging inputs to multisensory areas of the macaque neocortex

Two fundamental requirements for multisensory integration are convergence of unisensory (e.g. visual and auditory) inputs and temporal alignment of the neural responses to convergent inputs. We investigated the anatomic mechanisms of multisensory convergence by examining three areas in which convergence occurs, posterior auditory association cortex, superior temporal polysensory area (STP) and ventral intraparietal sulcus area (VIP). The first of these was recently shown to be a site of multisensory convergence and the latter two are more well known as 'classic' multisensory regions. In each case, we focused on defining the laminar profile of response to the unisensory inputs. This information is useful because two major types of connection, feedforward and feedback, have characteristic differences in laminar termination patterns, which manifest physiologically. In the same multisensory convergence areas we also examined the timing of the unisensory inputs using the same standardized stimuli across all recordings. Our findings indicate that: (1) like somatosensory input [J. Neurophysiol., 85 (2001) 1322], visual input is available at very early stages of auditory processing, (2) convergence occurs through feedback, as well as feedforward anatomical projections and (3) input timing may be an asset, as well as a constraint in multisensory processing.     

Auditory-somatosensory multisensory interactions in front and rear space

The information conveyed by our senses can be combined to facilitate perception and behaviour. One focus of recent research has been on the factors governing such facilitatory multisensory interactions. The spatial register of neuronal receptive fields (RFs) appears to be a prerequisite for multisensory enhancement. In terms of auditory-somatosensory (AS) interactions, facilitatory effects on simple reaction times and on brain responses have been demonstrated in caudo-medial auditory cortices, both when auditory and somatosensory stimuli are presented to the same spatial location and also when they are separated by 100 degrees in frontal space. One implication is that these brain regions contain large spatial RFs. The present study further investigated this possibility and, in particular, the question of whether AS interactions are restricted to frontal space, since recent research has revealed some fundamental differences between the sensory processing of stimuli in front and rear space. Twelve participants performed a simple reaction time task to auditory, somatosensory, or simultaneous auditory-somatosensory stimuli. The participants placed one of their arms in front of them and the other behind their backs. Loudspeakers were placed close to each hand. Thus, there were a total of eight stimulus conditions - four unisensory and four multisensory - including all possible combinations of posture and loudspeaker location. A significant facilitation of reaction times (RTs), exceeding that predicted by probability summation, was obtained following multisensory stimulation, irrespective of whether the stimuli were in spatial register or not. These results are interpreted in terms of the likely RF organization of previously identified auditory-somatosensory brain regions.     

Auditory-somatosensory multisensory interactions in humans: Dissociating detection and spatial discrimination

Simple reaction times (RTs) to auditory-somatosensory (AS) multisensory stimuli are facilitated over their unisensory counterparts both when stimuli are delivered to the same location and when separated. In two experiments we addressed the possibility that top-down and/or task-related influences can dynamically impact the spatial representations mediating these effects and the extent to which multisensory facilitation will be observed. Participants performed a simple detection task in response to auditory, somatosensory, or simultaneous AS stimuli that in turn were either spatially aligned or misaligned by lateralizing the stimuli. Additionally, we also informed the participants that they would be retrogradely queried (one-third of trials) regarding the side where a given stimulus in a given sensory modality was presented. In this way, we sought to have participants attending to all possible spatial locations and sensory modalities, while nonetheless having them perform a simple detection task. Experiment 1 provided no cues prior to stimulus delivery. Experiment 2 included spatially uninformative cues (50% of trials). In both experiments, multisensory conditions significantly facilitated detection RTs with no evidence for differences according to spatial alignment (though general benefits of cuing were observed in Experiment 2). Facilitated detection occurs even when attending to spatial information. Performance with probes, quantified using sensitivity (d′), was impaired following multisensory trials in general and significantly more so following misaligned multisensory trials. This indicates that spatial information is not available, despite being task-relevant. The collective results support a model wherein early AS interactions may result in a loss of spatial acuity for unisensory information.     

Multisensory integration in the basal ganglia

Sensorimotor co-ordination in mammals is achieved predominantly via the activity of the basal ganglia. To investigate the underlying multisensory information processing, we recorded the neuronal responses in the caudate nucleus (CN) and substantia nigra (SN) of anaesthetized cats to visual, auditory or somatosensory stimulation alone and also to their combinations, i.e. multisensory stimuli. The main goal of the study was to ascertain whether multisensory information provides more information to the neurons than do the individual sensory components. A majority of the investigated SN and CN multisensory units exhibited significant cross-modal interactions. The multisensory response enhancements were either additive or superadditive; multisensory response depressions were also detected. CN and SN cells with facilitatory and inhibitory interactions were found in each multisensory combination. The strengths of the multisensory interactions did not differ in the two structures. A significant inverse correlation was found between the strengths of the best unimodal responses and the magnitudes of the multisensory response enhancements, i.e. the neurons with the weakest net unimodal responses exhibited the strongest enhancement effects. The onset latencies of the responses of the integrative CN and SN neurons to the multisensory stimuli were significantly shorter than those to the unimodal stimuli. These results provide evidence that the multisensory CN and SN neurons, similarly to those in the superior colliculus and related structures, have the ability to integrate multisensory information. Multisensory integration may help in the effective processing of sensory events and the changes in the environment during motor actions controlled by the basal ganglia.     

Good times for multisensory integration: Effects of the precision of temporal synchrony as revealed by gamma-band oscillations

The synchronous occurrence of the unisensory components of a multisensory stimulus contributes to their successful merging into a coherent perceptual representation. Oscillatory gamma-band responses (GBRs, 30-80 Hz) have been linked to feature integration mechanisms and to multisensory processing, suggesting they may also be sensitive to the temporal alignment of multisensory stimulus components. Here we examined the effects on early oscillatory GBR brain activity of varying the precision of the temporal synchrony of the unisensory components of an audio-visual stimulus. Audio-visual stimuli were presented with stimulus onset asynchronies ranging from -125 to +125 ms. Randomized streams of auditory (A), visual (V), and audio-visual (AV) stimuli were presented centrally while subjects attended to either the auditory or visual modality to detect occasional targets. GBRs to auditory and visual components of multisensory AV stimuli were extracted for five subranges of asynchrony (e.g., A preceded by V by 100+/-25 ms, by 50+/-25 ms, etc.) and compared with GBRs to unisensory control stimuli. Robust multisensory interactions were observed in the early GBRs when the auditory and visual stimuli were presented with the closest synchrony. These effects were found over medial-frontal brain areas after 30-80 ms and over occipital brain areas after 60-120 ms. A second integration effect, possibly reflecting the perceptual separation of the two sensory inputs, was found over occipital areas when auditory inputs preceded visual by 100+/-25 ms. No significant interactions were observed for the other subranges of asynchrony. These results show that the precision of temporal synchrony can have an impact on early cross-modal interactions in human cortex.     

Somatosensory inputs modify auditory spike timing in dorsal cochlear nucleus principal cells

In addition to auditory inputs, dorsal cochlear nucleus (DCN) pyramidal cells in the guinea pig receive and respond to somatosensory inputs and perform multisensory integration. DCN pyramidal cells respond to sounds with characteristic spike-timing patterns that are partially controlled by rapidly inactivating potassium conductances. Deactivating these conductances can modify both spike rate and spike timing of responses to sound. Somatosensory pathways are known to modify response rates to subsequent acoustic stimuli, but their effect on spike timing is unknown. Here, we demonstrate that preceding tonal stimulation with spinal trigeminal nucleus (Sp5) stimulation significantly alters the first spike latency, the first interspike interval and the average discharge regularity of firing evoked by the tone. These effects occur whether the neuron is excited or inhibited by Sp5 stimulation alone. Our results demonstrate that multisensory integration in DCN alters spike-timing representations of acoustic stimuli in pyramidal cells. These changes likely occur through synaptic modulation of intrinsic excitability or synaptic inhibition.     

Auditory response properties of neurons in the anterior ectosylvian sulcus of the cat

The auditory response properties of single neurons in the fundus and banks of the anterior ectosylvian sulcus (AES) were studied with simple dichotic stimuli (viz. noise- and tone-bursts) in cats anaesthetized with -chloralose. Neurons within AES showed simple onset responses, were most commonly excited by stimulation of both ears, and showed either broad tuning or multiple high best frequencies. Some neurons were also tested for visual responsiveness and it was found that auditory cells and visual cells were intermingled within the sulcus. A small percentage of cells responded to both auditory and visual stimulation. Overall, the response properties of AES neurons differed from those of nearby auditory cortical fields. The region of AES studied appears to be outside the recently defined fourth somatosensory area (SIV), but overlaps para-SIV found deeper in the sulcus. It appears that deep within the sulcus and along most of its length there is a population of auditory, somatosensory and visual cells; to delineate this auditory population from the surrounding auditory cortical fields this region has been designated Field AES.     

Multisensory and unisensory neurons in ferret parietal cortex exhibit distinct functional properties

Despite the fact that unisensory and multisensory neurons are comingled in every neural structure in which they have been identified, no systematic comparison of their response features has been conducted. Towards that goal, the present study was designed to examine and compare measures of response magnitude, latency, duration and spontaneous activity in unisensory and bimodal neurons from the ferret parietal cortex. Using multichannel single‐unit recording, bimodal neurons were observed to demonstrate significantly higher response levels and spontaneous discharge rates than did their unisensory counterparts. These results suggest that, rather than merely reflect different connectional arrangements, unisensory and multisensory neurons are likely to differ at the cellular level. Thus, it can no longer be assumed that the different populations of bimodal and unisensory neurons within a neural region respond similarly to a given external stimulus.     

体感刺激激活人脑听觉皮层

目的 初步探讨体感刺激是否可以激活听觉皮层,为听觉皮层作为多重感觉皮层提供证据.方法 5例颞叶占位的患者术中暴露颞上回后,分别接受声音(100 dB)和体感刺激,通过光学成像在红光下(610±10)nm观察初级、次级听觉皮层(BA41、42)反射内源光信号变化特征.结果 红光(610±lO)nm下我们观察到听觉刺激后听觉皮层(BA41、42)明显激活(n=5),体感刺激后可观察到和听觉刺激时相似区域的激活,且响应的方式与听觉刺激无明显差异(n=4).结论 体感刺激可激活听觉皮层,这可能是听觉皮层作为多重感觉皮层的一个证据.

Abstract：

Objective This paper is to explore whether somatosensory stimulation could activate human anditory cortex(AI)and provide a new evidence for the multisensory center.Methods Intrinsic optical signals from the superior temporal gyrus were measured intraoperatively in five anesthetized patients with temporal lobe tumors.We detected the activation of the auditory cortex(BA41、42)during auditory and somatosensory stimuli respectively under red illuminating light(610±10)nm.Results Under the illumination of red light wavelength we clearly detected hemodynamic responses in the primary and secondary auditory cortex(BA 41,42)by the stimulus of the 100 dB clicks(n=5)and similar response area during the somatosensory paradigm(n=4).Conclusion Somatosensory stimulation can activate the auditory cortex which may be a new evidence of the multisensory center.     

Behavioural benefits of multisensory processing in ferrets

Enhanced detection and discrimination, along with faster reaction times, are the most typical behavioural manifestations of the brain's capacity to integrate multisensory signals arising from the same object. In this study, we examined whether multisensory behavioural gains are observable across different components of the localization response that are potentially under the command of distinct brain regions. We measured the ability of ferrets to localize unisensory (auditory or visual) and spatiotemporally coincident auditory–visual stimuli of different durations that were presented from one of seven locations spanning the frontal hemifield. During the localization task, we recorded the head movements made following stimulus presentation, as a metric for assessing the initial orienting response of the ferrets, as well as the subsequent choice of which target location to approach to receive a reward. Head‐orienting responses to auditory–visual stimuli were more accurate and faster than those made to visual but not auditory targets, suggesting that these movements were guided principally by sound alone. In contrast, approach‐to‐target localization responses were more accurate and faster to spatially congruent auditory–visual stimuli throughout the frontal hemifield than to either visual or auditory stimuli alone. Race model inequality analysis of head‐orienting reaction times and approach‐to‐target response times indicates that different processes, probability summation and neural integration, respectively, are likely to be responsible for the effects of multisensory stimulation on these two measures of localization behaviour.     

Modification of median nerve somatic evoked potentials by prior median nerve, peroneal nerve, and auditory stimulation

In a recovery function design, changes were measured in the somatic evoked potential (SEP) to right median nerve (RMN) shocks preceded by stimulation of: the same nerve (RMN-RMN); the left median nerve having primary input to the homologous sensory area in the contralateral hemisphere (LMN-RMN); the right peroneal nerve having primary input to a different region of the same hemisphere (RPN-RMN); and the auditory nerve with primary input to a different sensory modality (AUD-RMN). Eight inter-stimulus intervals ranged from zero (simultaneous) to 2.5 sec. It was assumed that the degree of interaction between evoked potentials would be related to the degree to which common neural structures are activated or modulated in response to the stimuli. Results were: (a) the primary somatosensory response N20-P30 was little influenced by other somatic or auditory stimulation, interaction occurring predominantly in the RMN-RMN condition; (b) with increasing latency, components showed increasing interaction across modalities; (c) preceding homolateral stimulation (RPN-RMN) showed no greater interaction than preceding contralateral stimulation (LMN-RMN); (d) N55-P100 differed from the primary somatosensory response N20-P30 by showing greater interaction with other somatic stimuli; and (e) N140-P190 showed similarly shaped recovery functions across stimulus pairs but significant differences in magnitude of interaction. These results show that components with similar wave form and topographical characteristics can have different neurophysiological properties.     

Multisensory integration in the dorsal cochlear nucleus: unit responses to acoustic and trigeminal ganglion stimulation

A necessary requirement for multisensory integration is the convergence of pathways from different senses. The dorsal cochlear nucleus (DCN) receives auditory input directly via the VIIIth nerve and somatosensory input indirectly from the Vth nerve via granule cells. Multisensory integration may occur in DCN cells that receive both trigeminal and auditory nerve input, such as the fusiform cell. We investigated trigeminal system influences on guinea pig DCN cells by stimulating the trigeminal ganglion while recording spontaneous and sound-driven activity from DCN neurons. A bipolar stimulating electrode was placed into the trigeminal ganglion of anesthetized guinea pigs using stereotaxic co-ordinates. Electrical stimuli were applied as bipolar pulses (100 micros per phase) with amplitudes ranging from 10 to 100 microA. Responses from DCN units were obtained using a 16-channel, four-shank electrode. Current pulses were presented alone or preceding 100- or 200-ms broadband noise (BBN) bursts. Thirty percent of DCN units showed either excitatory, inhibitory or excitatory-inhibitory responses to trigeminal ganglion stimulation. When paired with BBN stimulation, trigeminal stimulation suppressed or facilitated the firing rate in response to BBN in 78% of units, reflecting multisensory integration. Pulses preceding the acoustic stimuli by as much as 95 ms were able to alter responses to BBN. Bimodal suppression may play a role in attenuating body-generated sounds, such as vocalization or respiration, whereas bimodal enhancement may serve to direct attention in low signal-to-noise environments.     

Evidence for training-induced crossmodal reorganization of cortical functions in trumpet players

The aim of this study was to compare multimodal information processing in the somatosensory and auditory cortices and related multimodal areas in musicians (trumpet players) and non-musicians. Magnetoencephalographic activity (MEG) was recorded in response to five stimulus conditions from 10 professional trumpet players and nine musically untrained control subjects. Somatosensory and auditory stimuli were presented alone or in combination. Our data suggest that musicians, in general, process multisensory stimuli differently to the control group. When stimulating the lip in professional trumpet players, a multimodal interaction (expressed as difference between the multimodal response and the sum of unimodal responses) in the corresponding somatosensory cortex showed a positive peak at 33 ms, which was not found in the control group. Conversely, the control group shows a significant interaction of opposite polarity around 60-80 ms. We suggest that training-induced reorganization in musicians leads to a qualitatively different way to process multisensory information. It favors an early stage of cortical processing, which is modified by the connections between multimodal and auditory neurons from thalamus to primary somatosensory area.     

Auditory cortical projection from the anterior ectosylvian sulcus (Field AES) to the superior colliculus in the cat: an anatomical and electrophysiological study

Sensory activity in the deep layers of the superior colliculus (SC) is strongly influenced by descending cortical inputs. Elimination (permanent or reversible) of specific regions of visual or somatosensory cortex, known to have direct access to the SC, abolishes or dramatically reduces SC responses to stimuli from those modalities. While many SC neurons are also responsive to auditory cues, the origin of auditory corticotectal connections is not clear at present and their affect on activity in the SC is unknown. Therefore, the present study was undertaken to determine the origin, organization, and functional characteristics of auditory corticotectal projections. Of the auditory cortices (AI; AII; Fields A, P, and VP), only the auditory subregion of the banks of the anterior ectosylvian sulcus (Field AES) showed a robust anatomical projection to the SC. These data were confirmed physiologically: auditory neurons in Field AES projected to the SC and auditory SC neurons responded to stimulation of the Field AES. However, neither anatomical nor physiological techniques revealed a clear topographic relationship between the Field AES and the SC but suggested instead a diffuse and extremely divergent/convergent projection. Stimulation and cryoblockade of Field AES demonstrated the excitatory nature of this corticotectal pathway, whose influence was most evident on SC responses to stimuli of reduced intensity. Given the short latency of this ear-cortex-SC circuit and its excitatory influence on unimodal as well as on multisensory auditory neurons, it seems likely that Field AES plays a significant role in facilitating SC responses to auditory stimuli.     

Sensory and multisensory representations within the cat rostral suprasylvian cortex

Because the posterior limb of the rostral suprasylvian sulcus (RSp) of the cat resides in close proximity to representations of the somatosensory, auditory, and visual modalities, the surrounding cortices would be expected to be a region where a high degree of multisensory convergence and integration is found. The present experiments tested this notion by using anatomical and electrophysiological methods. Tracer injections into somatosensory, auditory, and visual cortical areas almost all produced terminal labeling within the RSp, albeit at different locations and in different proportions. Inputs from somatosensory cortices primarily targeted the inner portion of the anterior RSp; inputs from auditory cortices generally filled the outer portion of the middle and posterior RSp; inputs from visual cortices terminated in the inner portion of the posterior RSp. These projections did not have sharp borders but often overlapped one another, thereby providing a substrate for multisensory convergence. Electrophysiological recordings confirmed this anatomical organization as well as identifying the presence of multisensory (bimodal) neurons in the areas of overlap between representations. Curiously, however, the proportion of bimodal neurons was only 24% of the neurons sampled in this region, and the majority of these did not show multisensory interactions when combined-modality stimuli were presented. In summary, these experiments indicate that the RSp is primarily auditory in nature, but this representation could be further subdivided into an outer sulcal anterior auditory field (sAAF) and an inner field of the rostral suprasylvian sulcus (FRS).