Neuromagnetic Beta-Band Oscillations during Motor Imitation in Youth with Autism.

Children with ASD often exhibit early difficulties with action imitation, possibly due to low-level sensory or motor impairments. Impaired cortical rhythms have been demonstrated in adults with ASD during motor imitation. While those oscillations reflect an age-dependent process, they have not been fully investigated in youth with ASD. We collected magnetoencephalography data to examine patterns of oscillatory activity in the mu (8-13 Hz) and beta frequency (15-30 Hz) range in 14 adolescents with and 14 adolescents without ASD during a fine motor imitation task. Typically developing adolescents exhibited adult-like patterns of motor signals, e.g., event-related beta and mu desynchronization (ERD) before and during the movement and a postmovement beta rebound (PMBR) after the movement. In contrast, those with ASD exhibited stronger beta and mu-ERD and reduced PMBR. Behavioral performance was similar between groups despite differences in motor cortical oscillations. Finally, we observed age-related increases in PBMR and beta-ERD in the typically developing children, but this correlation was not present in the autism group. These results suggest reduced inhibitory drive in cortical rhythms in youth with autism during intact motor imitation. Furthermore, impairments in motor brain signals in autism may not be due to delayed brain development. In the context of the excitation-inhibition imbalance perspectives of autism, we offer new insights into altered organization of neurophysiological networks.

Insula and orbitofrontal cortical morphology in substance dependence is modulated by sex.

BACKGROUND AND PURPOSE: Frontolimbic circuits are involved in learning and decision-making processes thought to be affected in substance-dependent individuals. We investigated frontolimbic cortical morphometry in substance-dependent men and women and determined whether morphometric measurements correlated with decision-making performance. MATERIALS AND METHODS: Twenty-eight abstinent SDI (17 men/11 women) were compared with 28 controls (13 men/15 women). Cortical thicknesses and volumes were computed by using FreeSurfer. After controlling for age and intracranial volume, group and sex effects were analyzed in 3 a priori regions of interest: the insula, orbitofrontal cortex, and anterior cingulate cortex by using analysis of covariance. A secondary whole-brain analysis was conducted to verify region-of-interest results and to explore potential differences in other brain regions. RESULTS: Region-of-interest analyses revealed a main effect of group on the left insula cortex, which was thinner in SDI compared with controls (P = .02). There was a group by sex interaction on bilateral insula volume (left, P = .02; right, P = .001) and right insula cortical thickness (P = .007). Compared with same-sex controls, female SDI had smaller insulae, whereas male SDI had larger insulae. Neither ACC nor OFC significantly differed across group. Performance on a decision-making task was better in controls than SDI and correlated with OFC measurements in the controls. CONCLUSIONS: SDI and controls differed in insula morphology, and those differences were modulated by sex. No group differences in OFC were observed, but OFC measurements correlated with negative-reinforcement learning in controls. These preliminary results are consistent with a hypothesis that frontolimbic pathways may be involved in behaviors related to substance dependence.

Auditory evoked magnetic fields in adults with fragile X syndrome.

Hyper-reactivity and anxiety to sensory stimuli have been described in patients with fragile X syndrome (FXS), and may be related to abnormal processing in afferent sensory pathways. We used magnetoencephalography (MEG) to measure auditory responses to pure tones in 11 adults with FXS and 11 non-FXS subjects. The amplitude for the N100m auditory evoked field component was significantly higher for patients with FXS than for subjects. FXS subjects also had less lateralized N100m anterior-posterior dipole locations. These data may suggest that more neurons are activated by acoustic stimuli in FXS, consistent with subjective experience of increased stimulus intensity. Anomalous cerebral lateralization may suggest an early critical window for effects on neocortical development of the fragile X mental retardation protein (FMRP) produced by the FMR1 gene in individuals with FXS.

Reduced hippocampal volume in association with p50 nonsuppression following traumatic brain injury.

Traumatic brain injury (TBI) may produce persistently impaired auditory gating. This cholinergic-dependent, hippocampally mediated preattentive cognitive function that facilitates filtering of auditory stimuli may be indexed by the P50 evoked waveform to paired auditory stimuli. Abnormal P50 suppression post TBI is believed to result from injury to the hippocampus and/or its afferent cholinergic projections. This hypothesis was tested by comparing hippocampal and total brain volumes on MRI between ten P50-nonsuppressing TBI patients and ten normal control subjects matched for age, gender, and education. TBI subjects had highly significant bilateral hippocampal volume reductions, even when covaried for reductions in total brain volume. Degree of volume loss was not correlated with initial TBI severity. Findings support the hypothesis that hippocampal injury underlies P50 nonsuppression post TBI and suggest that such structural abnormalities may be observed even in "mildly" injured persons.

Effects of image orientation on the comparability of pediatric brain volumes using three-dimensional MR data.

PURPOSE: The purpose of this study was to examine the comparability of morphometric measurements made on pediatric data sets collected at five scanner locations, each using variations on a 3D spoiled gradient-recalled echo (SPGR) pulse sequence. METHOD: Archived MR data from 60 typically developing children were collected and separated into seven groups based on the pulse sequence used. A highly automated image-processing procedure was used to segment the brain data into white tissue, gray tissue, and CSF compartments and into various neuroanatomic regions of interest. RESULTS: Volumetric comparisons between groups revealed differences in areas of the temporal and occipital lobes. These differences were observed when comparing data sets with different image orientations and appeared to be due to partial volume averaging (PVA) and susceptibility-induced geometric distortions. CONCLUSION: Our results indicate that slice selection and image resolution should be controlled in volumetric studies using aggregated data from multiple centers to minimize the effects of PVA and susceptibility-induced geometric distortions.

Fine structure of the auditory M100 in schizophrenia and schizoaffective disorder.

BACKGROUND: Several studies have demonstrated anomalous asymmetry of the 100-msec latency auditory-evoked field (M100) in schizophrenia. Recent evidence suggests this may be a compound component, however. Our study examines the localization of two M100 subcomponents in patients with schizophrenia and schizoaffective disorder. METHODS: Magnetoencephalographic recordings of auditory-evoked fields were obtained for 14 subjects with schizophrenia, 12 with schizoaffective disorder, and 23 control subjects. Two M100 subcomponents were identified and localized in each hemisphere. RESULTS: Both patient groups exhibited different lateralization compared with control subjects, with the second subcomponent tending to be less lateralized. CONCLUSIONS: The second subcomponent may be the major contributor to previously reported laterality differences. Future studies might benefit by separating M100 subcomponents so that specific functions could be addressed.

Neuromagnetic alpha suppression during an auditory sternberg task. Evidence for a serial, self-terminating search of short-term memory.

Reaction times (RT) during the Sternberg memory paradigm generally increase with memory set size, but do not differ for positive and negative probe stimuli. Sternberg proposed that this indicated that short-term memory (STM) scanning is both exhaustive and serial. However, this notion has received much criticism, primarily because RT must also reflect response selection factors. Magnetoencephalographic (MEG) recordings of auditory alpha-suppression have previously demonstrated that suppression duration is correlated with set size, potentially providing a physiological index of memory scanning time related specifically to sensory cortices. The current study expands earlier research into this metric by separately analyzing positive and negative probes. Thirteen normal adults participated in an auditory Sternberg paradigm. Pure tones were presented in memory set/probe combinations where the probe had a 50 percent chance of being within the memory set, and RT and accuracy were measured. Magnetic alpha-band activity (8-12 Hz) was quantified for pre- and post-stimulus regions. Although RT did not differ for positive and negative probes, alpha-suppression duration was greater for negative probes than positive ones, potentially indicating that scanning time was slightly faster in the positive condition. This may indicate that STM scanning is serial, but self-terminates when matching occurs.

Sex differences in the refractory period of the 100 ms auditory evoked magnetic field.

The 100 ms latency auditory evoked magnetic response (M100) has been implicated in the earliest stage of acoustic memory encoding in the brain. Sex differences in this response have been found in its location within the brain and its functional properties. We recorded the M100 in 25 adults in response to changes in interstimulus interval of an auditory stimulus. Response amplitudes of the M100 were used to compute a measure of the M100 refractory period, which has been proposed to index the decay time constant of echoic memory. This time constant was significantly longer in both hemispheres of the female participants when compared to the male participants. Possible implications of this for behavioral sex differences in human memory performance are discussed.

Bipolar disorder: anomalous brain asymmetry associated with psychosis.

OBJECTIVE: Anomalous cerebral asymmetry in schizophreniform disorders has been described, but its presence in psychotic mood disorders has not been established. Measures of cerebral asymmetry may distinguish patients with psychotic mood disorders from those with nonpsychotic mood disorders and from comparison subjects. To test this hypothesis, the authors examined functional cerebral asymmetry by using a metric based on magnetic source imaging. METHOD: A total of 33 subjects participated. Nine were patients with bipolar I disorder and a negative history of psychotic symptoms during mood disorder episodes, 12 were patients with bipolar I disorder and a positive history of psychotic symptoms during mood disorder episodes, and 12 were nonpsychiatric comparison subjects. Equivalent current dipole generators in both hemispheres were estimated for the 20-msec-latency somatosensory evoked field (M20) component produced by stimulation of the contralateral median nerve. RESULTS: The comparison subjects demonstrated asymmetry in anterior-posterior equivalent current dipole locations of the M20 (right anterior to left), and the bipolar subjects with no history of psychosis were similarly asymmetric. The bipolar subjects with a history of psychosis during mood episodes, however, demonstrated a reversal of cerebral asymmetry of the M20 (left anterior to right). CONCLUSIONS: Cerebral lateralization of the M20 distinguished bipolar subjects with psychosis from those without psychosis and comparison subjects. The M20 is generated in area 3b of the postcentral gyrus. These findings suggest anatomical displacement of the postcentral gyrus in psychotic disorders and support the hypothesis that anomalous cerebral asymmetry is a feature of psychotic disorders generally, including psychotic mood disorders.

Schizoaffective disorder: evidence for reversed cerebral asymmetry.

BACKGROUND: Schizoaffective disorder is one of the most severe of the affective psychoses, but its pathophysiology is poorly understood. Because cerebral lateralization may be disturbed in psychotic disorders generally, studies examining cerebral asymmetry may improve understanding of the neurobiology specific to schizoaffective disorder. This study examines cerebral lateralization in this patient population using magnetic source localization. METHODS: We studied 16 subjects with schizoaffective disorder and 16 controls. Magnetic source localization was used to identify the location of the 20 msec latency somatosensory evoked field component (M20). RESULTS: In control subjects, the source location was further anterior in the right hemisphere. The subjects with schizoaffective disorder were reverse lateralized. CONCLUSIONS: The findings of a reversed asymmetry of the M20 in patients with schizoaffective disorder suggest an anatomical shift in the placement of the post central gyrus in this disorder, compatible with a disorder of cerebral lateralization. Whether this finding converges or diverges with measurement of the M20 in other psychotic disorders will require further investigation.

The thalamus and the schizophrenia phenotype: failure to replicate reduced volume.

BACKGROUND: Thalamic abnormalities resulting in impaired attention and information processing may form a foundation for cognitive and perceptual disturbances in schizophrenia. Measurements of the thalamus in patients with schizophrenia have shown reductions relative to normal comparison subjects. METHODS: In the current project, magnetic resonance images of the brain were obtained in 10 male and 11 female subjects with paranoid-type schizophrenia, and 15 male and 12 female normal comparison subjects. Total brain and bilateral thalamic volumes were calculated. RESULTS: There were no significant diagnosis, hemisphere, or gender differences in thalamic volumes. CONCLUSIONS: Structural thalamic abnormalities are not likely to universally and parsimoniously explain the schizophrenia phenotype. Abnormal thalamic size in patients with schizophrenia should be understood as reflecting one of several possible structural abnormalities contributing to production of the schizophrenia phenotype, but must be regarded with caution unless paired with functional studies.

Magnetoencephalography: applications in psychiatry.

Magnetoencephalography (MEG) measures the extracranial magnetic fields produced by intraneuronal ionic current flow within appropriately oriented cortical pyramidal cells. Based upon superconducting quantum interference device technology operating at liquid helium temperatures (4 K), MEG offers excellent temporal and spatial resolution for selected sources, and complements information obtained from electroencephalograms and other functional imaging strategies. Current instrumentation permits recording up to several hundred channels simultaneously with head-shaped dewars, although the cost of such systems is high. The fact that magnetic fields fall off with the square of the distance from the source is both a benefit (when separating activity in the two hemispheres) and a limitation (when attempting to record deep sources). The lack of skin contact facilitates using MEG to record direct current and very high frequency (> 600 Hz) brain activity. The clinical utility of MEG includes presurgical mapping of sensory cortical areas and localization of epileptiform abnormalities, and localization of areas of brain hypoperfusion in stroke patients. MEG studies in psychiatric disorders have contributed materially to improved understanding of anomalous brain lateralization in the psychoses, have suggested that P50 abnormalities may reflect altered gamma band activity, and have provided evidence of hemisphere-specific abnormalities of short-term auditory memory function.

Magnetoencephalography and magnetic source imaging: technology overview and applications in psychiatric neuroimaging.

Magnetoencephalography (MEG) is an electrophysiologic brain imaging technology that has been applied to the study of mental illness, particularly schizophrenia. Like electroencephalography, it provides excellent temporal resolution, and in combination with magnetic resonance imaging, can also provide good spatial resolution. Studies of the auditory system in schizophrenia using MEG have demonstrated an abnormality in functional cerebral asymmetry, in which persons with schizophrenia typically show reduced, or reversed, cerebral asymmetry compared with normal subjects. This abnormality is sex-specific; it is more pronounced in males with schizophrenia. These findings have not been demonstrated using other neuroimaging strategies. Thus, MEG appears to offer a unique and valuable contribution to psychiatric neuroimaging. Current research and clinical applications of MEG are limited, however, by the high cost of instrumentation. The cost of MEG systems should improve as more applications are developed, in schizophrenia as well as other neuropsychiatric conditions, and hospitals begin to invest in the technology.

Sequential source of the M100 exhibits inter-hemispheric asymmetry.

The most prominent auditory evoked field component occurs at about 100 ms latency and is termed the M100. We recorded M100 data from 20 subjects, in both hemispheres. We modeled the generators with a single equivalent current dipole in a 10 ms sliding window from 0 to 245 ms post-stimulus. A residual error curve was plotted, and a search for local minima identified two latencies at about 75 and 100 ms. In the left hemisphere, the early generator was about 6 mm above the later source; in the right hemisphere the early source was about 3 mm above the later, and 11 mm posterior. The M100 is a compound source, and the model may provide additional information in cases with reported laterality differences.

Developmental changes in refractoriness of the neuromagnetic M100 in children.

Considerable evidence exists for developmental changes in latency and amplitude of the auditory evoked potential termed N100. However, it is widely recognized that the N100 wave comprises multiple, temporally overlapping neural generators, and few data are available addressing either individual generator development or mechanisms behind such change. Using magnetoencelphalographic (MEG) measurements of the magnetic analog of the N100 termed the M100, which derives primarily from supra-temporal auditory generators, it is demonstrated here that changes in the response of that waveform to manipulation of interstimulus interval (ISI) occur between the ages of 6 and 18 years of age.

Sex-specific expression of Heschl's gyrus functional and structural abnormalities in paranoid schizophrenia.

OBJECTIVE: Evidence supports abnormal temporal lobe structure and function in schizophrenia. Some abnormalities, particularly involving the auditory cortex, appear to be sex specific. These findings were extended to anatomical and physiological descriptors. METHOD: The authors quantified the volume, surface area, and three-dimensional location of Heschl's gyri on magnetic resonance imaging (MRI) images of 21 patients with paranoid schizophrenia and 24 healthy comparison subjects. Neuromagnetic localizations of the 100-msec latency auditory evoked field (M100) were compared with MRI-determined locations of Heschl's gyri, computed as the geometric center of mass of the volume. RESULTS: Volumetric measures revealed small Heschl's gyri only in male patients. Asymmetry was found in the location of the Heschl's gyrus centroid (more anterior on the right) across all groups. Male comparison subjects had M100 locations posterior to the Heschl's gyrus centroid in the left hemisphere and close to the Heschl's gyrus centroid on the right, while male patients had M100 sources anterior to the Heschl's gyrus centroid on the left. All women had M100 locations posterior to the Heschl's gyrus centroid on the left and anterior to it on the right. CONCLUSIONS: These results demonstrate that some temporal lobe abnormalities in schizophrenia are sex specific. They also suggest that the anomalous lateralization of the auditory evoked field cannot be explained by a shift in the underlying anatomy, since the anatomical substrate is lateralized in both comparison subjects and patients of both sexes. These findings may indicate a sex-specific functional reorganization in the auditory cortex in schizophrenia.

Magnetic source imaging evidence of sex differences in cerebral lateralization in schizophrenia.

BACKGROUND: It has been postulated that schizophrenia represents a disorder of anomalous cerebral lateralization. This study is a replication of earlier preliminary findings using a multichannel neuromagnetometer, suggesting altered lateralization in schizophrenia in male subjects, with an extension of the findings to female subjects. METHODS: We used magnetoencephalography-based magnetic source imaging to estimate the intracranial location of the 100-millisecond latency auditory-evoked field component (M100) in both left and right hemispheres of 20 patients with paranoid schizophrenia and 20 controls without schizophrenia. Neuroanatomical data were obtained by means of magnetic resonance imaging, from which we segmented and computed volumes of both total brain and left and right superior temporal gyri. RESULTS: Locations of M100 source were compatible with neuronal generators located in the transverse gyri of Heschl on the superior temporal gyri in both study groups; M100 sources were asymmetric in all the control subjects. The male patient subgroup exhibited significantly less asymmetry than the control group, while the female patient subgroup actually showed significantly more asymmetry. The male patient subgroup generally had smaller superior temporal gyri than the control group. No evidence of total brain volume differences was observed. CONCLUSIONS: Our findings support previous magnetoencephalography-based studies suggesting anomalous cerebral lateralization in schizophrenia. Further, in extending our studies to female patients, our data suggest that the nature of this anomaly is sex specific, a finding that, to our knowledge, has not previously been reported.

Single versus composite score discriminative validity with the Halstead-Reitan Battery and the Stroop Test in mild brain injury.

The predictive validity of single measures from the Halstead-Reitan Neuropsychological Test Battery and Stroop Neuropsychological Screening Test were evaluated in a sample of 25 mild traumatic brain-injured and 25 neurologically normal subjects and compared to the accuracy of composite score measures, specifically the General Neuropsychological Deficit Scale and the Halstead Impairment Index. Whereas several measures from the Halstead Impairment Index achieved significantly better than chance prediction, the two summary measures from the Halstead-Reitan Neuropsychological Test Battery predicted the neurological status of the subjects with the most accuracy. The Stroop Neuropsychological Screening Test did not perform well as a single predictor. Together, these results suggest that single-measure screening tests do not predict mild brain-injury as well as composite neuropsychological measures. The results also give credence to the argument of comprehensive testing for brain-injured patients whose injuries are deemed medically mild.