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.     

Visuo-spatial neural response interactions in early cortical processing during a simple reaction time task: a high-density electrical mapping study

The timecourse and scalp topography of interactions between neural responses to stimuli in different visual quadrants, straddling either the vertical or horizontal meridian, were studied in 15 subjects. Visual evoked potentials (VEPs) were recorded from 64 electrodes during a simple reaction time (RT) task. VEPs to single stimuli displayed in different quadrants were summed ('sum') and compared to the VEP response from simultaneous stimulation of the same two quadrants ('pair'). These responses would be equivalent if the neural responses to the single stimuli were independent. Divergence between the 'pair' and 'sum' VEPs indicates a neural response interaction. In each visual field, interactions occurred within 72-86 ms post-stimulus over parieto-occipital brain regions. Independent of visual quadrant, RTs were faster for stimulus pairs than single stimuli. This replicates the redundant target effect (RTE) observed for bilateral stimulus pairs and generalizes the RTE to unilateral stimulus pairs. Using Miller's 'race' model inequality (Miller J. Divided attention: evidence for coactivation with redundant signals, Cognitive Psychology 1982;14:247-79), we found that probability summation could fully account for the RTE in each visual field. Although measurements from voltage waveforms replicated the observation of earlier peak P1 latencies for the 'pair' versus 'sum' comparison (Miniussi C, Girelli M, Marzi CA. Neural site of the redundant target effect: electrophysiological evidence. Journal of Cognitive Neuroscience 1998;10:216-30), this did not hold with measurements taken from second derivative (scalp current density) waveforms. Since interaction effects for bilateral stimulus pairs occurred within 86 ms and require interhemispheric transfer, transcallosal volleys must arrive within 86 ms, which is earlier than previously calculated. Interaction effects for bilateral conditions were delayed by approximately 10 ms versus unilateral conditions, consistent with current estimates of interhemispheric transmission time. Interaction effects place an upper limit on the time required for neuronal ensembles to combine inputs from different quadrants of visual space ( approximately 72 ms for unilateral and approximately 82 ms for bilateral conditions).     

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.     

Visual sensory processing deficits in patients with bipolar disorder revealed through high-density electrical mapping

Background

Etiological commonalities are apparent between bipolar disorder and schizophrenia. For example, it is becoming clear that both populations show similar electrophysiological deficits in the auditory domain. Recent studies have also shown robust visual sensory processing deficits in patients with schizophrenia using the event-related potential technique, but this has not been formally tested in those with bipolar disorder. Our goal here was to assess whether early visual sensory processing in patients with bipolar disorder, as indexed by decreased amplitude of the P1 component of the visual evoked potential (VEP), would show a similar deficit to that seen in those with schizophrenia. Since the P1 deficit has already been established as an endophenotype in schizophrenia, a finding of commonality between disorders would raise the possibility that it represents a measure of common genetic liability.

Methods

We visually presented isolated-check stimuli to euthymic patients with a diagnosis of bipolar disorder and age-matched healthy controls within a simple go/no-go task and recorded VEPs using high-density (72-channel) electroencephalography.

Results

The P1 VEP amplitude was substantially reduced in patients with bipolar disorder, with an effect size of f = 0.56 (large according to Cohen’s criteria).

Limitations

Our sample size was relatively small and as such, did not allow for an examination of potential relations between the physiologic measures and clinical measures.

Conclusion

This reduction in P1 amplitude among patients with bipolar disorder represents a dysfunction in early visual processing that is highly similar to that found repeatedly in patients with schizophrenia and their healthy first-degree relatives. Since the P1 deficit has been related to susceptibility genes for schizophrenia, our results raise the possibility that the deficit may in fact be more broadly related to the development of psychosis and that it merits further investigation as a candidate endophenotype for bipolar disorder.     

Brightening prospects for early cortical coding of perceived luminance: a high-density electrical mapping study

Establishing the computational rules and neural substrates of brightness coding is a topic of both historical and contemporary interest. Two major classes of explanations for brightness illusions, such as brightness contrast, can be traced to Hering and Helmholtz. Hering's legacy is a low-level account in which brightness contrast results from obligatory lateral inhibitory interactions occurring at some level(s) in the visual system. Helmholtz offered a high-level account, positing a causal role for factors such as perceptual grouping, inferred illumination, and the extraction of surface properties such as orientation and reflectance. The tension between these theoretical viewpoints persists unabated to date. Intracranial electrophysiological recordings have revealed that brightness is represented in the firing rates of striate neurons, a fact consistent with low-level explanations. However, since the time-course of brightness-related responses relative to the onset of striate activity is undisclosed, it remains possible that striate activation might be temporally and causally secondary to higher-level computational processes. Knowledge of the timing of brightness-related neural activity is thus crucial to both constrain and adjudicate between these competing theories. We utilize high-density electrophysiological recording and a tachistoscopic brightness discrimination task to measure the time-course and scalp topography of brightness-related electrical potentials in human observers. Brightness perception is correlated with electrical activity at the earliest stages of visual cortical processing. These findings are interpreted to support Hering's low-level account of brightness for White's effect, and the results are discussed in the context of current theories of brightness perception.     

Early visual processing deficits in schizophrenia: impaired P1 generation revealed by high-density electrical mapping.

Integrity of early visual sensory processing in schizophrenia was assessed using the well characterized P1 and N1 components of the visual evoked potential (VEP) as our dependent measures. VEPs were recorded in response to successively less fragmented line drawings of common objects. P1 amplitudes were significantly reduced across all stimulus conditions for patients versus controls. Further, this decrement was relatively greater at parieto-occipital than occipito-temporal electrode sites. No differences in N1 amplitude were found. The finding of P1 deficits in patients, particularly over dorsal scalp, supports the view that schizophrenia is associated with impairment of early dorsal visual stream processing. On the other hand, the finding of normal N1 amplitudes in patients suggests that early stages of ventral stream processing may be relatively more intact. These results imply that the cognitive impairment seen in schizophrenia is not just due to deficits in higher order aspects of cognition but also encompasses significant deficits in early sensory processing.     

Cross-modal processing of auditory-visual stimuli in a no-task paradigm: a topographic event-related potential study

OBJECTIVE: The aim of this study was to investigate in healthy adults the electrophysiological correlates of auditory-visual interactions involved in perception of bimodal events in a no-task paradigm. METHODS: Event-related potentials were recorded in response to unimodal auditory (A), unimodal visual (V) and bimodal (AV) stimuli. Cross-modal interactions were estimated using the additive [AV-(A+V)] model. RESULTS: The spatio-temporal analysis of ERPs and scalp current densities revealed several interaction patterns occurring at both early and late stages of sensory cortical processing: (1) amplitude decrease of the unimodal auditory N1 wave as early as 55ms, (2) amplitude increase of the unimodal auditory P2 wave from 150 to 195ms concomitant with new neural activity over the right fronto-temporal region, and (3) amplitude increase of the late unimodal visual response within 245-350ms post-stimulus. CONCLUSIONS: Our study provides evidence that several patterns of cross-modal interactions can be generated even if no task is required from subjects. SIGNIFICANCE: The paradigm used here can thus be utilized for studying the maturation of the cross-modal processes in young children and in children with pathological development.     

Auditory processing in schizophrenia during the middle latency period (10-50 ms): high-density electrical mapping and source analysis reveal subcortical antecedents to early cortical deficits

INTRODUCTION: Auditory sensory processing dysfunction is a core component of schizophrenia, with deficits occurring at 50 ms post-stimulus firmly established in the literature. Given that the initial afference of primary auditory cortex occurs at least 35 ms earlier, however, an essential question remains: how early in sensory processing do such deficits arise, and do they occur during initial cortical afference or earlier, which would implicate subcortical auditory dysfunction. OBJECTIVE: To establish the onset of the earliest deficits in auditory processing, we examined the time window demarcating the transition from subcortical to cortical processing: 10 ms to 50 ms during the so-called middle latency responses (MLRs). These remain to be adequately characterized in patients with schizophrenia. METHODS: We recorded auditory evoked potentials (AEPs) to simple tone-pips from 15 control subjects and 21 medicated patients with longer-term schizophrenia or schizoaffective disorder (illness duration 16 yr, standard deviation [SD] 9.4 yr), using high-density electrical scalp recordings. Between-group analyses assessed the integrity of the MLRs across groups. In addition, 2 source-localization models were conducted to address whether a distinction between subcortical and cortical generators of the MLRs can be made and whether evidence for differential dorsal and ventral pathway contributions to auditory processing deficits can be established. RESULTS: Robust auditory processing deficits were found for patients as early as 15 ms. Evidence for subcortical generators of the earliest MLR component (P20) was provided by source analysis. Topographical mapping and source localization also pointed to greater decrements in processing in the dorsal auditory pathway of patients, providing support for a theory of pervasive deficits that are organized along the lines of a dorsal-ventral distinction. CONCLUSIONS: Auditory sensory dysfunction in schizophrenia begins extremely early in processing, is evident during initial cortical afference and is also seen at earlier subcortical processing stages in the thalamus. The implication is that well-established sensory processing deficits in schizophrenia may be secondary to earlier subcortical dysfunction. Our findings do not preclude the possibility of even earlier deficits in auditory sensory processing during the auditory brainstem responses.     

The deployment of intersensory selective attention: a high-density electrical mapping study of the effects of theanine

OBJECTIVE:: Ingestion of the nonproteinic amino acid theanine (5-N-ethylglutamine) has been shown to increase oscillatory brain activity in the so-called alpha band (8-14 Hz) during resting electroencephalographic recordings in humans. Independently, alpha band activity has been shown to be a key component in selective attentional processes. Here, we set out to assess whether theanine would cause modulation of anticipatory alpha activity during selective attentional deployments to stimuli in different sensory modalities, a paradigm in which robust alpha attention effects have previously been established. METHODS:: Electrophysiological data from 168 scalp electrode channels were recorded while participants performed a standard intersensory attentional cuing task. RESULTS:: As in previous studies, significantly greater alpha band activity was measured over parieto-occipital scalp for attentional deployments to the auditory modality than to the visual modality. Theanine ingestion resulted in a substantial overall decrease in background alpha levels relative to placebo while subjects were actively performing this demanding attention task. Despite this decrease in background alpha activity, attention-related alpha effects were significantly greater for the theanine condition. CONCLUSION:: This increase of attention-related anticipatory alpha over the right parieto-occipital scalp suggests that theanine may have a specific effect on the brain's attention circuitry. We conclude that theanine has clear psychoactive properties, and that it represents a potentially interesting, naturally occurring compound for further study, as it relates to the brain's attentional system.     

Spatiotemporal differences between cognitive processes of spatially possible and impossible objects: a high-density electrical mapping study

Differences in cognitive processing between spatially possible and impossible figures were investigated using event-related potentials (ERPs). Two types of figures with identical luminance and equivalent spatial frequency were used as visual stimuli: possible three-dimensional figures (drawn with perspective and existing in the three-dimensional world) and impossible figures (drawn with perspective but not existing in the three-dimensional world). High-density electroencephalographic recording (72 channels) was performed for analysis of ERPs accompanying perception of each figure type; amplitude differences between the conditions were considered neurophysiologic correlates to perceptual differences between possible and impossible objects. Low-resolution brain electromagnetic tomography (LORETA) was used to identify the current source related to the differences. Compared with impossible three-dimensional figures, perception of possible figures showed a significant negative potential increase in the right inferior occipitotemporal region between 350 and 389 ms of latency. The current source was localized to the right fusiform gyrus. The results suggest that right fusiform gyrus is involved in discrimination between spatially possible and impossible objects.     

Time course of early audiovisual interactions during speech and nonspeech central auditory processing: a magnetoencephalography study

Cross-modal fusion phenomena suggest specific interactions of auditory and visual sensory information both within the speech and nonspeech domains. Using whole-head magnetoencephalography, this study recorded M50 and M100 fields evoked by ambiguous acoustic stimuli that were visually disambiguated to perceived /ta/ or /pa/ syllables. As in natural speech, visual motion onset preceded the acoustic signal by 150 msec. Control conditions included visual and acoustic nonspeech signals as well as visual-only and acoustic-only stimuli. (a) Both speech and nonspeech motion yielded a consistent attenuation of the auditory M50 field, suggesting a visually induced "preparatory baseline shift" at the level of the auditory cortex. (b) Within the temporal domain of the auditory M100 field, visual speech and nonspeech motion gave rise to different response patterns (nonspeech: M100 attenuation; visual /pa/: left-hemisphere M100 enhancement; /ta/: no effect). (c) These interactions could be further decomposed using a six-dipole model. One of these three pairs of dipoles (V270) was fitted to motion-induced activity at a latency of 270 msec after motion onset, that is, the time domain of the auditory M100 field, and could be attributed to the posterior insula. This dipole source responded to nonspeech motion and visual /pa/, but was found suppressed in the case of visual /ta/. Such a nonlinear interaction might reflect the operation of a binary distinction between the marked phonological feature "labial" versus its underspecified competitor "coronal." Thus, visual processing seems to be shaped by linguistic data structures even prior to its fusion with auditory information channel.     

Early auditory-visual interactions in human cortex during nonredundant target identification

A common finding of behavioral studies is that objects characterized by redundant multisensory cues are identified more rapidly than the same objects presented in either unimodal condition. In a previous electrophysiological study in humans, we have described a network of crossmodal interactions that could be associated with this facilitation effect [M.H. Giard, F. Peronnet, J. Cogn. Neurosci. 11(5) (1999) 473-490]. Here, we sought to determine whether the recognition of objects characterized by nonredundant bimodal components may still induce crossmodal neural interactions. Subjects had to identify three objects defined either by auditory or visual features alone, or by the combination of nonredundant auditory and visual features. As expected, behavioral measures showed no sign of facilitation in bimodal processing. Yet, event-related potential analysis revealed the existence of early (<200 ms latency) crossmodal activities in sensory-specific and nonspecific cortical areas, that were partly dependent on the sensory dominance of the subjects to perform the task. Comparative analysis of the interaction patterns involved in redundant and nonredundant cue processing provides evidence for the robustness of the principle of crossmodal neural synergy that applies whatever the stimulus content (redundant or nonredundant information), and for the high flexibility of the neural networks of integration that are sensitive both to the nature of the perceptual task and to the sensory skill of the individual in that particular task.     

The role of cingulate cortex in the detection of errors with and without awareness: a high-density electrical mapping study

Error-processing research has demonstrated that the brain uses a specialized neural network to detect errors during task performance but the brain regions necessary for conscious awareness of an error are poorly understood. In the present study we show that two well-known error-related event-related potential (ERP) components, the error-related negativity (ERN) and error positivity (Pe) have a differential relationship with awareness during performance of a manual response inhibition task optimized to examine error awareness. While the ERN was unaffected by the participants' conscious experience of errors, the Pe was only seen when participants were aware of committing an error. Source localization of these components indicated that the ERN was generated by a caudal region of the anterior cingulate cortex (ACC) while the Pe was associated with contributions from a more anterior ACC region and the posterior cingulate-precuneus. Tonic EEG measures of cortical arousal were correlated with individual rates of error awareness and showed a specific relationship with the amplitude of the Pe. The latter finding is consistent with evidence that the Pe represents a P3-like facilitation of information processing modulated by subcortical arousal systems. Our data suggest that the ACC might participate in both preconscious and conscious error detection and that cortical arousal provides a necessary setting condition for error awareness. These findings may be particularly important in the context of clinical studies in which a proper understanding of self-monitoring deficits requires an explicit measurement of error awareness.     

Abnormalities of sensory processing and sensorimotor interactions in secondary dystonia: a neurophysiological study in two patients.

Experimental data suggest that abnormalities of sensory processing and sensorimotor integration may play a role in the genesis of symptoms in primary dystonia. We studied 2 patients with dystonia secondary to lesions in the somatosensory pathways. We documented sensorimotor alterations in these patients that strongly resemble those found in primary dystonia. Our data are consistent with the hypothesis that abnormalities in sensorimotor processing may contribute to the pathogenesis of dystonic conditions.     

Auditory sensory processing in autism: a magnetoencephalographic study.

BACKGROUND: Patients with autism show clinical features suggestive of abnormal processing of auditory and other sensory information. We hypothesized that low-functioning autistic subjects present abnormalities in discriminating simple auditory stimuli at sensory system preconscious stages of cortical processing. METHODS: To verify our hypothesis, we used magnetoencephalographic measurements of mismatch field (MMF), which reflects the detection of a change in the physical characteristics of a repetitive sound. Fourteen patients (aged 8-32 years) who met DSM-IV diagnostic criteria for autistic disorder participated in an auditory oddball experiment. Ten healthy participants matched for age and gender acted as control subjects. RESULTS: Significant differences in cerebral responses between patients and control subjects were recorded. Whereas control subjects showed a clearly identifiable MMF, with distinct generators in the M100 brain wave with regard to latency, position, and strength, no identifiable MMF was present in the autistic group. CONCLUSIONS: Our findings suggest that low-functioning autistic subjects present a dysfunction at preconscious stages of cortical auditory discrimination, playing a role in the abnormal processing of auditory sensory afferences. The attention independence of the MMF allows for exclusion of an effect related to impaired attention or task-related responses.     

Opossum somatic sensory cortex: a microelectrode mapping study.

Organization of opossum somatic sensory cortex has been investigated utilizing closely spaced microelectrode penetrations (0.25-0.5 mm apart) and delicate mechanical stimulation of body surfaces including the facial vibrissae. Results may be summarized as follows: (1) the general organization of somatic sensory cortex, as originally defined by Lende ('63a) has been confirmed; (2) a double representation of the contralateral mystacial vibrissae and rhinarium, implicit in Lende's original data, was revealed in detail, the two representations being orderly, adjacent, mirror-images of each other; (3) units at a given cortical locus responded to deflection of between one and five mystacial vibrissae, about half responding to movement of a single vibrissa only; (4) about 40% of mystacial vibrissa units showed a directional specificity to the extent that they responded to deflections in only one or two cardinal directions; (5) units located in the medial vibrissa area showed a greater directional specificity than did units located in the lateral vibrissa area; (6) the surface area of rhinarial receptive fields was about ten times the area of first-order rhinarial unit receptive fields (B. Pubols et al., '73); (7) representation of the contralateral forelimb, especially the ventral surface of the forepaw, is extensive, orderly, and precise; (8) representation of the contralateral hindlimb, foot, and tail is minimal, and is confined to the midline convexity; (9) the presence of a small region of bilateral representation, lateral to the regions of contralateral representation, was confirmed. It is suggested that the region of contralateral postcranial representation plus the medial rhinarium and mystacial vibrissa areas are the homologue of SmI in placental mammals, and the region of bilateral representation is homologous to SmII of placental mammals, but that the lateral vibrissa and rhinarium areas are a specialization of somatic sensory cortex unique to the Virginia opossum.     

The second sensory area in humans: evoked potential and electrical stimulation studies

A patient with intractable seizures originating from a right frontal focus was evaluated for surgical treatment. This evaluation was carried out using a chronically implanted array of 96 stainless steel electrodes 1 cm apart and covering the perirolandic and frontal areas. Somatosensory evoked potentials and electrical stimulation of the subdural electrodes localized the primary sensory hand area. Evoked potentials of identical waveform but of lower amplitude and 2.4 ms longer latency were recorded in the inferior frontal gyrus immediately anterior to the face area of the motor strip. Electrical stimulation of that area elicited: (1) a "paralyzing" feeling in the left arm and face; (2) inhibition of rapid alternating movements of left fingers, left hand, and tongue; (3) inability to maintain a strong voluntary muscle contraction of the left hand or tongue; and (4) speech arrest. This appears to be the first report of a secondary sensory area in humans demonstrated by both electrical stimulation and evoked potential studies. Electrical stimulation showed that the secondary sensory area overlapped an area of complex motor control, suggesting that the secondary sensory area provides direct sensory feedback information for appropriate motor integration.     

Top-down effects on early visual processing in humans: a predictive coding framework

An increasing number of human electroencephalography (EEG) studies examining the earliest component of the visual evoked potential, the so-called C1, have cast doubts on the previously prevalent notion that this component is impermeable to top-down effects. This article reviews the original studies that (i) described the C1, (ii) linked it to primary visual cortex (V1) activity, and (iii) suggested that its electrophysiological characteristics are exclusively determined by low-level stimulus attributes, particularly the spatial position of the stimulus within the visual field. We then describe conflicting evidence from animal studies and human neuroimaging experiments and provide an overview of recent EEG and magnetoencephalography (MEG) work showing that initial V1 activity in humans may be strongly modulated by higher-level cognitive factors. Finally, we formulate a theoretical framework for understanding top-down effects on early visual processing in terms of predictive coding.