Magnetoencephalography for Epilepsy Presurgical Evaluation.

PURPOSE OF THE REVIEW: Magnetoencephalography (MEG) is a functional neuroimaging technique that records neurophysiology data with millisecond temporal resolution and localizes it with subcentimeter accuracy. Its capability to provide high resolution in both of these domains makes it a powerful tool both in basic neuroscience as well as clinical applications. In neurology, it has proven useful in its ability to record and localize epileptiform activity. Epilepsy workup typically begins with scalp electroencephalography (EEG), but in many situations, EEG-based localization of the epileptogenic zone is inadequate. The complementary sensitivity of MEG can be crucial in such cases, and MEG has been adopted at many centers as an important resource in building a surgical hypothesis. In this paper, we review recent work evaluating the extent of MEG influence of presurgical evaluations, novel analyses of MEG data employed in surgical workup, and new MEG instrumentation that will likely affect the field of clinical MEG. RECENT FINDINGS: MEG consistently contributes to presurgical evaluation and these contributions often change the plan for epilepsy surgery. Extensive work has been done to develop new analytic methods for localizing the source of epileptiform activity with MEG. Systems using optically pumped magnetometry (OPM) have been successfully deployed to record and localize epileptiform activity. MEG remains an important noninvasive tool for epilepsy presurgical evaluation. Continued improvements in analytic methodology will likely increase the diagnostic yield of the test. Novel instrumentation with OPM may contribute to this as well, and may increase accessibility of MEG by decreasing cost.

Spatiotemporal dynamics of selective attention and visual conflict monitoring using a Stroop task.

Selective attention and conflict monitoring are daily human phenomena, yet the spatial and temporal neurological underpinnings of these processes are not fully understood. Current literature suggests these executive functions occur via diverse and highly interconnected neural networks, including top-down, bottom-up, and conflict-control loops. To investigate the spatiotemporal activity of these processes, we collected neuromagnetic data using magnetoencephalography (MEG) in 28 healthy adults (age 19-36), while they performed a computerized Stroop task based on color naming. We focused on low-frequency oscillations in the context of top-down control and hypothesized that conflict monitoring-related activity would first be observed in the left anterior cingulate cortex, followed by the left dorsolateral prefrontal cortex, and subsequently in the parietal and temporal lobes. Significant activity between 600-1000 ms post-stimulus onset was found for incongruent vs. congruent/neutral contrasts. Interestingly, spatiotemporal analysis did not provide evidence for a top-down pattern of activation, instead revealing a simultaneous pattern of activation in the frontal and temporal lobes. Most notable is the involvement of the left posterior inferior temporal cortex (pITC) and the left temporoparietal junction (TPJ), which have not conventionally been considered active players in attentional control. These results may be largely driven by alpha and beta oscillations from our sample population. Our findings challenge early theoretical models of top-down processing in the context of cognitive control from an attention perspective and also suggest a need to investigate attentional centers in the temporal lobe. Furthermore, the study highlights the valuable temporal data provided by MEG, which has been missing from previous studies.

An integrated full-head OPM-MEG system based on 128 zero-field sensors.

Compact optically-pumped magnetometers (OPMs) are now commercially available with noise floors reaching 10 fT/Hz1/2. However, to be used effectively for magnetoencephalography (MEG), dense arrays of these sensors are required to operate as an integrated turn-key system. In this study, we present the HEDscan, a 128-sensor OPM MEG system by FieldLine Medical, and evaluate its sensor performance with regard to bandwidth, linearity, and crosstalk. We report results from cross-validation studies with conventional cryogenic MEG, the Magnes 3,600 WH Biomagnetometer by 4-D Neuroimaging. Our results show high signal amplitudes captured by the OPM-MEG system during a standard auditory paradigm, where short tones at 1000 Hz were presented to the left ear of six healthy adult volunteers. We validate these findings through an event-related beamformer analysis, which is in line with existing literature results.

The aging slow wave: a shifting amalgam of distinct slow wave and spindle coupling subtypes define slow wave sleep across the human lifespan.

STUDY OBJECTIVES: Slow wave and spindle coupling supports memory consolidation, and loss of coupling is linked with cognitive decline and neurodegeneration. Coupling is proposed to be a possible biomarker of neurological disease, yet little is known about the different subtypes of coupling that normally occur throughout human development and aging. Here we identify distinct subtypes of spindles within slow wave upstates and describe their relationships with sleep stage across the human lifespan. METHODS: Coupling within a cross-sectional cohort of 582 subjects was quantified from stages N2 and N3 sleep across ages 6-88 years old. Results were analyzed across the study population via mixed model regression. Within a subset of subjects, we further utilized coupling to identify discrete subtypes of slow waves by their coupled spindles. RESULTS: Two different subtypes of spindles were identified during the upstates of (distinct) slow waves: an "early-fast" spindle, more common in stage N2 sleep, and a "late-fast" spindle, more common in stage N3. We further found stages N2 and N3 sleep contain a mixture of discrete subtypes of slow waves, each identified by their unique coupled-spindle timing and frequency. The relative contribution of coupling subtypes shifts across the human lifespan, and a deeper sleep phenotype prevails with increasing age. CONCLUSIONS: Distinct subtypes of slow waves and coupled spindles form the composite of slow wave sleep. Our findings support a model of sleep-dependent synaptic regulation via discrete slow wave/spindle coupling subtypes and advance a conceptual framework for the development of coupling-based biomarkers in age-associated neurological disease.

An extended motor network generates beta and gamma oscillatory perturbations during development.

This study examines the time course and neural generators of oscillatory beta and gamma motor responses in typically-developing children. Participants completed a unilateral flexion-extension task using each index finger as whole-head magnetoencephalography (MEG) data were acquired. These MEG data were imaged in the frequency-domain using spatial filtering and the resulting event-related synchronizations and desynchronizations (ERS/ERD) were subjected to voxel-wise statistical analyses to illuminate time-frequency specific activation patterns. Consistent with adult data, these children exhibited a pre-movement ERD that was strongest over the contralateral post-central gyrus, and a post-movement ERS response with the most prominent peak being in the contralateral precentral gyrus near premotor cortices. We also observed a high-frequency (approximately 80 Hz) ERS response that coincided with movement onset and was centered on the contralateral precentral gyrus, slightly superior and posterior to the beta ERS. In addition to pre- and post-central gyri activations, these children exhibited beta and gamma activity in supplementary motor areas (SMA) before and during movement, and beta activation in cerebellar cortices before and after movement. We believe the gamma synchronization may be an excellent candidate signal of basic cortical motor control, as the spatiotemporal dynamics indicate the primary motor cortex generates this response (and not the beta oscillations) which is closely yoked to the initial muscle activation. Lastly, these data suggest several additional neural regions including the SMA and cerebellum are involved in basic movements during development.

Schizoaffective disorder - a possible MEG auditory evoked field biomarker.

We recorded magnetoencephalographic auditory steady state responses (SSR) from eight schizoaffective (SAD) subjects and compared the resulting data with previously published findings in persons with schizophrenia (SZ) and controls. SAD subjects exhibited SSR responses similar to controls in the left hemisphere and greater than controls in the right hemisphere, whereas SZ subjects exhibited deficits in both amplitude and phase control in both hemispheres. Our findings suggest preservation of GABAergic inhibitory interneuronal control of layer 3 pyramidal cell activity in primary auditory cortex in SAD.

Brain size and brain/intracranial volume ratio in major mental illness.

BACKGROUND: This paper summarizes the findings of a long term study addressing the question of how several brain volume measure are related to three major mental illnesses in a Colorado subject group. It reports results obtained from a large N, collected and analyzed by the same laboratory over a multiyear period, with visually guided MRI segmentation being the primary initial analytic tool. METHODS: Intracerebral volume (ICV), total brain volume (TBV), ventricular volume (VV), ventricular/brain ratio (VBR), and TBV/ICV ratios were calculated from a total of 224 subject MRIs collected over a period of 13 years. Subject groups included controls (C, N = 89), and patients with schizophrenia (SZ, N = 58), bipolar disorder (BD, N = 51), and schizoaffective disorder (SAD, N = 26). RESULTS: ICV, TBV, and VV measures compared favorably with values obtained by other research groups, but in this study did not differ significantly between groups. TBV/ICV ratios were significantly decreased, and VBR increased, in the SZ and BD groups compared to the C group. The SAD group did not differ from C on any measure. CONCLUSIONS: In this study TBV/ICV and VBR ratios separated SZ and BD patients from controls. Of interest however, SAD patients did not differ from controls on these measures. The findings suggest that the gross measure of TBV may not reliably differ in the major mental illnesses to a degree useful in diagnosis, likely due to the intrinsic variability of the measures in question; the differences in VBR appear more robust across studies. Differences in some of these findings compared to earlier reports from several laboratories finding significant differences between groups in VV and TBV may relate to phenomenological drift, differences in analytic techniques, and possibly the "file drawer problem".

MEG auditory evoked fields suggest altered structural/functional asymmetry in primary but not secondary auditory cortex in bipolar disorder.

OBJECTIVES: Objective physiological indices independently characterizing affective and schizophreniform psychoses would contribute to our understanding of the nature of their relationships. Magnetoencephalography (MEG)-based metrics of altered structural/functional asymmetry in the superior temporal gyrus have previously been found to characterize schizophrenia at the level of both the primary auditory (AI) and the secondary auditory (AII) cortex. This study examines these markers in patients with bipolar disorder, with the goal of improved understanding of the patterns of brain asymmetry that may independently characterize affective and schizophreniform psychosis. METHODS: We studied 17 euthymic bipolar subjects and 17 matched controls. Auditory evoked fields were generated by both 40 Hz auditory stimuli eliciting steady state gamma band (SSR), activating the AI cortex, and discrete 1 kHz tone pips, activating the AII cortex. MEG was recorded from the hemisphere contralateral to the ear stimulated using a 37-channel MEG system. Source location estimates were calculated in both left and right hemispheres. Neuroanatomical location estimates for medial Heschl's gyri were determined from magnetic resonance images for correlation with MEG source locations. RESULTS: Bipolar subjects failed to demonstrate normal laterality of SSR AI responses, indicating altered patterns of asymmetry at the level of AI cortex, but demonstrated normal asymmetry of AII responses (right anterior to left). Medial Heschl's gyri centroids were similarly lateralized in both groups, however (right anterior to left), dissociating function from structure in the AI cortex in the bipolar group. CONCLUSIONS: The findings are compatible with altered functional/structural relationships, including diminished left-right hemisphere asymmetry of the AI, but not the AII cortex in bipolar disorder. In schizophrenia, both the AI and AII cortices exhibit such derangements; thus, the findings support both shared and nonshared features of auditory cortical disruption between the two disorders. This functional disorganization may help explain previously reported decreases in amplitude and phase synchrony of SSR gamma band responses in bipolar subjects, suggesting impaired neocortical synchrony in AI, possibly at a cortico-thalamic level, but perhaps not extending to heteromodal association cortex, and may relate to the cognitive impairments found in bipolar disorder.

Aberrant high-frequency desynchronization of cerebellar cortices in early-onset psychosis.

Sensorimotor integration deficits are routinely observed in both schizophreniform and mood-disordered psychoses. Neurobiological theories of schizophrenia and related psychoses have proposed that aberrations in large-scale cortico-thalamic-cerebellar-thalamic-cortical loops may underlie integration abnormalities, and that such dysfunctional connectivity may be central to the pathophysiology. In this study, we utilized a basic mechanoreception task to probe cortical-cerebellar circuitry in early-onset psychosis. Ten adolescents with psychosis and 10 controls completed unilateral tactile stimulation of the right and left index finger, as whole-head magnetoencephalography (MEG) data were acquired. MEG data were imaged in the frequency domain, using spatial filtering, and the resulting event-related synchronizations and desynchronizations (ERS/ERD) were subjected to voxel-wise analyses of group and task effects using statistical parametric mapping. Our results indicated bilateral ERD activation of cerebellar regions and postcentral gyri in both groups during stimulation of either hand. Interestingly, during left finger stimulations, adolescents with psychosis exhibited greater alpha and gamma ERD activity in right cerebellar cortices relative to controls. Subjects with psychosis also showed greater ERD in bilateral cerebellum and the right postcentral gyrus during right finger stimulation, and these differences were statistically stronger for higher frequency bins. Lastly, controls exhibited greater alpha ERS of the right postcentral gyrus during right finger stimulation. These findings provide new data on the neurodevelopmental trajectory of basic mechanoreception in adolescents, and also indicate aberrant cerebellar functioning in early-onset psychoses, especially in the right cerebellum, which may be the crucial dysfunctional node in cortico-thalamic-cerebellar-thalamic-cortical circuits.

Cortical gamma generators suggest abnormal auditory circuitry in early-onset psychosis.

Neurobiological theories of schizophrenia and related psychoses have increasingly emphasized impaired neuronal coordination (i.e., dysfunctional connectivity) as central to the pathophysiology. Although neuroimaging evidence has mostly corroborated these accounts, the basic mechanism(s) of reduced functional connectivity remains elusive. In this study, we examine the developmental trajectory and underlying mechanism(s) of dysfunctional connectivity by using gamma oscillatory power as an index of local and long-range circuit integrity. An early-onset psychosis group and a matched cohort of typically developing adolescents listened to monaurally presented click-trains, as whole-head magnetoencephalography data were acquired. Consistent with previous work, gamma-band power was significantly higher in right auditory cortices across groups and conditions. However, patients exhibited significantly reduced overall gamma power relative to controls, and showed a reduced ear-of-stimulation effect indicating that ipsi- versus contralateral presentation had less impact on hemispheric power. Gamma-frequency oscillations are thought to be dependent on gamma-aminobutyric acidergic interneuronal networks, thus these patients' impairment in generating and/or maintaining such activity may indicate that local circuit integrity is at least partially compromised early in the disease process. In addition, patients also showed abnormality in long-range networks (i.e., ear-of-stimulation effects) potentially suggesting that multiple stages along auditory pathways contribute to connectivity aberrations found in patients with psychosis.

Auditory entrainment of motor responses in older adults with and without Parkinson's disease: An MEG study.

Medical therapies applied to Parkinson's disease (PD) have advanced tremendously since the 1960's based on advances in our understanding of the underlying neurophysiology. Behavioral therapies, such as rhythmic auditory stimulation (RAS), have been developed more recently and demonstrated efficacy. However, the neural mechanisms of RAS are only vaguely understood. In this study, we examined the neurophysiology of RAS using magnetoencephalography (MEG) in a sample of older adults with (21 people) and without PD (23 participants). All participants underwent high-density MEG during a beat-based cued tapping task with rhythmic and non-rhythmic patterns, and the resulting data were analyzed using a Bayesian image reconstruction method. Complex wavelet based time-frequency decomposition was used to compute inter-trial phase locking factor (PLF) to auditory stimuli for left and right signal space projection vectors. Tapping with a rhythm compared to a non-rhythmic sequence resulted in differential brain activity in each group: (i) a greater activation of temporal, motor and parietal areas was found in healthy adults; (ii) a greater reliance on parietal and frontal gyri was found in PD participants. During rhythmic tapping, older adults without PD had significantly stronger neural activity in bilateral frontal, supplementary and primary motor areas compared to those with PD. Conversely, older adults with PD exhibited significantly stronger activity in the bilateral parietal regions, as well as the rolandic operculum and bilateral supramarginal gyri, relative to their healthy peers. These data suggest that RAS mobilizes diverse oscillatory networks; Healthy controls may shift to frontal areas mobilization whereas PD patients rely on parietal areas to a greater extent, which may reflect frontal network dysfunction with compensation in PD, and could serve as specific regions of interest for further RAS studies.

Cortical source estimates of gamma band amplitude and phase are different in schizophrenia.

Reductions in gamma band phase synchrony and evoked power have been reported in schizophrenic subjects in response to auditory stimuli. These results have been observed in the EEG at one or two electrode sites. We wished to extend these results using magnetic field data to estimate the responses at the neural generators themselves in each hemisphere. Whole head magnetoencephalographic (MEG) recordings were used to estimate the phase and amplitude behavior of sources in primary auditory cortex in both hemispheres of schizophrenic and comparison subjects. Both ipsi- and contralateral cases were evaluated using a driving (40 Hz modulated 1 kHz carrier) and a non-driving (1 kHz tone) stimulus. We used source space projection (SSP) to collapse the magnetic field data into estimates of the time course of source strengths in individual trials. Complex wavelet based time-frequency decomposition was used to compute inter-trial phase locking factor (PLF), and mean evoked and induced amplitude for each cortical generator. Schizophrenic subjects showed reduced SSP PLF and evoked source strength for contralateral generators responding to the driving stimulus in both hemispheres. For the pure tone stimulus, only the left hemisphere PLF's in the transient window were reduced. In contrast, subjects with schizophrenia exhibited higher induced 40 Hz power to both stimulus types, consistent with the reduced PLF findings. The method of SSP combined with wavelet based complex demodulation produces a significant improvement in signal-to-noise ratio, and directly estimates the activity of the cortical generators responsible for gamma band auditory MEG evoked fields. Schizophrenic subjects exhibit significant impairment of generation and phase locking of this activity in auditory cortex, suggesting an impairment of GABA-ergic inhibitory interneuronal modulation of pyramidal cell activity.

Reduced neural synchronization of gamma-band MEG oscillations in first-degree relatives of children with autism.

BACKGROUND: Gamma-band oscillations recorded from human electrophysiological recordings, which may be associated with perceptual binding and neuronal connectivity, have been shown to be altered in people with autism. Transient auditory gamma-band responses, however, have not yet been investigated in autism or in the first-degree relatives of persons with the autism. METHODS: We measured transient evoked and induced magnetic gamma-band power and inter-trial phase-locking consistency in the magnetoencephalographic recordings of 16 parents of children with autism, 11 adults with autism and 16 control participants. Source space projection was used to separate left and right hemisphere transient gamma-band measures of power and phase-locking. RESULTS: Induced gamma-power at 40 Hz was significantly higher in the parent and autism groups than in controls, while evoked gamma-band power was reduced compared to controls. The phase-locking factor, a measure of phase consistency of neuronal responses with external stimuli, was significantly lower in the subjects with autism and the autism parent group, potentially explaining the difference between the evoked and induced power results. CONCLUSION: These findings, especially in first degree relatives, suggest that gamma-band phase consistency and changes in induced versus induced power may be potentially useful endophenotypes for autism, particularly given emerging molecular mechanisms concerning the generation of gamma-band signals.

Children and adolescents with autism exhibit reduced MEG steady-state gamma responses.

BACKGROUND: Recent neuroimaging studies of autism have indicated reduced functional connectivity during both cognitive tasks and rest. These data suggest long-range connectivity may be compromised in this disorder, and current neurological theories of autism contend disrupted inter-regional interactions may be an underlying mechanism explaining behavioral symptomatology. However, it is unclear whether deficient neuronal communication is attributable to fewer long-range tracts or more of a local deficit in neural circuitry. This study examines the integrity of local circuitry by focusing on gamma band activity in auditory cortices of children and adolescents with autism. METHODS: Ten children and adolescents with autism and 10 matched controls participated. Both groups listened to 500 ms duration monaural click trains with a 25 ms inter-click interval, as magnetoencephalography was acquired from the contralateral hemisphere. To estimate 40 Hz spectral power density, we performed time-frequency decomposition of the single-trial magnetic steady-state response data using complex demodulation. RESULTS: Children and adolescents with autism exhibited significantly reduced left hemispheric 40 Hz power from 200-500 ms post-stimulus onset. In contrast, no significant between group differences were observed for right hemispheric cortices. CONCLUSIONS: The production and/or maintenance of left hemispheric gamma oscillations appeared abnormal in participants with autism. We interpret these data as indicating that in autism, particular brain regions may be unable to generate the high-frequency activity likely necessary for binding and other forms of inter-regional interactions. These findings augment connectivity theories of autism with novel evidence that aberrations in local circuitry could underlie putative deficiencies in long-range neural communication.

Neuromagnetic evidence of broader auditory cortical tuning in schizophrenia.

Deficits in basic auditory perception have been described in schizophrenia. Previous electrophysiological imaging research has documented a structure-function disassociation in the auditory system and altered tonotopic mapping in schizophrenia. The present study examined auditory cortical tuning in patients with schizophrenia. Eighteen patients with schizophrenia and 15 comparison subjects were recorded in a magnetoencephalographic (MEG) experiment of auditory tuning. Auditory cortical tuning at 1 kHz was examined by delivering 1 kHz pure tones in conjunction with pure tones at 5 frequencies surrounding and including 1 kHz. Source reconstruction data were examined for evidence of frequency specificity for the M100 component. There was a significant broadening of tuning in the schizophrenia group evident for the source amplitude of the M100. The frequently reported reduction in anterior-posterior source asymmetry for individuals with schizophrenia was replicated in this experiment. No relationships between symptom severity ratings and MEG measures were observed. This finding suggests that the frequency specificity of the M100 auditory evoked field is disturbed in schizophrenia, and may help explain the relatively poor behavioral performance of schizophrenia patients on simple frequency discrimination tasks.

Aberrant functional organization and maturation in early-onset psychosis: evidence from magnetoencephalography.

Studies of the location of somatosensory and auditory cortical responses have shown anomalous hemispheric asymmetries in a variety of neurodevelopmental disorders. To date, abnormal asymmetries in the somatosensory region have shown greater specificity, being reported only in psychotic adults. This study examines the functional organization of the somatosensory cortices using magnetoencephalography in adolescents with childhood-onset psychotic disorders. Eighteen young outpatients with history of psychotic illness and 15 healthy adolescents participated. Both groups underwent stimulation of the index finger as magnetoencephalography was acquired from the contralateral hemisphere. Neural generators of the M50 somatosensory response were modeled using an equivalent current dipole for each hemisphere, and later investigated for systematic variation with diagnosis. Consistent with adult psychosis data, adolescent patients showed hemispheric symmetry in the anterior-posterior dimension. In controls, a reversed pattern of hemispheric asymmetry was observed relative to previous findings in normal adults [Reite, M., Teale, P., Rojas, D.C., Benkers, T.L., Carlson, J., 2003. Anomalous somatosensory cortical localization in schizophrenia. American Journal of Psychiatry 160, 2148-2153], but trend-level correlations suggested source location became more adult-like during the transition from adolescence to adulthood. Source parameters also exhibited robust inter-hemispheric correlations only in adolescent controls. In sum, source locations, patterns of cerebral lateralization, and inter-hemispheric correlations all distinguish patients from their normally developing cohort. These findings suggest aberrant maturation underlies the reduction in cerebral laterality associated with psychosis.

Development of the 40Hz steady state auditory evoked magnetic field from ages 5 to 52.

OBJECTIVE: Adults exhibit strong auditory 40 Hz magnetic steady state responses (SSR). Although EEG measured SSR has been studied in children, the developmental course of the magnetic SSR is unknown. METHODS: Sixty-nine healthy subjects ranging in age from 5 to 52 years participated in a magnetoencephalographic (MEG) study. Stimuli were monaural 500 ms duration click trains with a 25 ms inter-click interval. Contralateral magnetic responses for both hemispheres were recorded with a 37-channel MEG system. Responses were averaged and examined using wavelet-based time-frequency analysis. Source analyses were also conducted on a subset of the data. RESULTS: Gamma power from 200 to 500 ms post-stimulus onset was computed and was significantly related to subject age in both hemispheres. Hemispheric asymmetry was observed for the anterior-posterior SSR source locations, suggestive of asymmetry similar to that previously described for the SSR and other auditory evoked magnetic field components. CONCLUSIONS: The 40 Hz power findings are generally consistent with previous EEG studies of steady state responses in children showing age-related changes in the 40 Hz SSR. SIGNIFICANCE: Age-related changes in the strength of the magnetic 40 Hz SSR may continue to develop well beyond early childhood, which should be taken into consideration in planning future studies using adolescents and young adults.

Reduced laterality of the source locations for generators of the auditory steady-state field in schizophrenia.

BACKGROUND: Reduced hemispheric asymmetry of evoked field generators in schizophrenia in secondary auditory cortex has been replicated with mixed success. This disparity is possibly due to the complex nature of the 100-msec generators typically investigated. In this study, we evaluated a source located in primary auditory cortex, responsible for the steady-state response, to determine whether similar asymmetries were present. METHODS: Contralateral evoked fields were recorded with a 37-channel neuromagnetometer in response to 40-Hz pulse trains. Dipole models were used to localize the sources in both hemispheres of schizophrenic subjects (n = 17) and normal control subjects (n = 18). RESULTS: Control subjects were asymmetrically lateralized, with sources in the right hemisphere approximately 6 mm further anterior than those on the left. In contrast, schizophrenic subjects showed no significant difference between hemispheres. CONCLUSIONS: The findings support theories linking schizophrenia to disturbed asymmetry of temporal lobe function. The steady-state response, having a more discrete Heschl's gyrus generator location, may be better suited for evaluating auditory asymmetry.

Alterations in tonotopy and auditory cerebral asymmetry in schizophrenia.

BACKGROUND: Deficits in basic auditory perception have been described in schizophrenia. Previous electrophysiologic imaging research has documented a structure-function disassociation in the auditory system in schizophrenia. This study examines whether the most fundamental level of auditory cortical organization, tonotopy, is altered in schizophrenia. METHODS: The tonotopic organization for five tone frequencies in 19 patients with schizophrenia and 22 comparison subjects was evaluated using magnetoencephalography. Auditory evoked magnetic field dipole locations were examined for the N100m component for each frequency. RESULTS: The expected linear relationship between depth and frequency was found in the comparison subjects but not in the schizophrenia group (p <.004). In addition, normal anterior-posterior asymmetry of the N100m was found to be reduced at all five stimulation frequencies employed in the study (p <.04). No relationships between clinical symptom ratings and either tonotopy or asymmetry were observed. CONCLUSIONS: This finding suggests that the tonotopic organization of the auditory cortex in schizophrenia is disturbed and may help explain the relatively poor behavioral performance of schizophrenia patients on simple frequency discrimination tasks. Alterations in fundamental sensory organization may underlie or interact with higher order cognitive mechanisms to produce changes in cognitive task performance.

Anomalous somatosensory cortical localization in schizophrenia.

OBJECTIVE: Schizophrenia has been reported to be associated with altered localization of regions responding to sound in the auditory cortex, suggesting possible cortical reorganization accompanying the disorder, but it is not clear whether such disturbances are present in any primary sensory cortex other than the auditory. This study examines magnetoencephalographic localization of field sources evoked by tactile stimulation generated in area 3b of the primary somatosensory cortex in patients with schizophrenia compared with normal subjects. METHOD: A total of 29 subjects participated; 14 were patients with schizophrenia, and 15 were normal comparison subjects. Equivalent current dipole generators in both hemispheres were used to model the sources of the 50-msec latency somatosensory evoked field (M50) components produced by contralateral tactile mechanoreceptor stimulation of the tip of the index finger. RESULTS: Compared with normal subjects, patients with schizophrenia demonstrated reversed asymmetry (left anterior to right) and relatively anterior and inferior displacement of the M50 equivalent current dipole location in the left hemisphere. CONCLUSIONS: Cerebral lateralization and localization of the M50 distinguished patients with schizophrenia from normal subjects. These findings suggest the possibility of anatomical displacement and/or disturbed organization of the primary sensory cortex in schizophrenia.