Peter Teale

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.

Functional effects of the DAT1 polymorphism on EEG measures in ADHD.

OBJECTIVE This paper examines whether dopamine transporter gene (DAT1) allele status mediates medication-related change in cognitive and neurophysiological measures among children with attention-deficiency/hyperactivity disorder (ADHD). METHOD A single 10-mg dose of methylphenidate was given in a double-blind, placebo-controlled fashion to children with ADHD who were seen for cognitive testing and EEG recording. Buccal samples were obtained and genotyped for the DAT1 polymorphism. RESULTS DAT1 allele status was associated with performance on a sustained attention task and medication-related EEG changes. Compared with those with one or more copies of the DAT1 9-repeat allele (9R), children with two copies of the 10-repeat allele (10R) exhibited poorer performance on the vigilance task. In addition, children with 10R exhibited medication-related EEG changes of increased central and parietal beta power, decreased right frontal theta power, and lower theta/beta ratios; 9R carriers showed the opposite pattern. CONCLUSIONS The data suggest that the DAT1 polymorphism mediates medication-related changes in cortical activity among children with ADHD.

Source location of a 50 msec latency auditory evoked field component

We recorded auditory evoked magnetic fields in response to 128 15 msec duration 1 kHz tone pips from both hemispheres of 6 normal adult males. Auditory evoked potentials were recorded conventionally from a vertex lead. An approximately 50 msec latency component was identified in both the magnetic (called the M50) and EEG (called the P50) recordings. Isofield topographical contour maps were used to estimate M50 source location and depth. With respect to extracranial bony landmarks, M50 source locations were significantly higher and tended to be more posterior, over the left hemisphere. M50 and P50 latencies were not significantly different in 5 of 6 subjects; in one, M50 latencies were significantly longer than P50 latencies over the left hemisphere. Magnetic resonance images in 5 subjects were used to identify the neuroanatomical structure(s) present at the estimated source location. M50 sources appeared to reside in the cortex of the planum temporale in both left and right hemispheres in all 5 subjects.

Auditory M100 component 1: relationship to Heschl's gyri

This study was designed to localize the neuroanatomic generator of the 100 ms latency magnetic auditory evoked field (EF) component (M100) activated by an unattended tone pip. Magnetic EFs in response to 25 ms duration, 90 dB, 1 kHz tone pips were recorded from both hemispheres of nine normal adults, five males and four females, using a seven-channel second-order gradiometer. The source of the M100 was estimated, with confidence intervals, by a least squares based inverse solution algorithm. Magnetic resonance (MR) images of the brain were acquired with a 1.5 T system using a standard head coil. The superior temporal gyri (STG) were manually segmented from 1.7 mm thick coronal images, and the superior surfaces were then rendered from the 3-D volume data. Translation and rotation matrices were identified to locate the magnetoencephalography (MEG) determined sources within the reconstructed STGs. This population of 18 STGs in 9 individuals demonstrated two transverse gyri in 4 of 9 left hemispheres, and 5 of 9 right hemispheres. All 9 left hemisphere M100 sources were in or included Heschls gyrus(i) in the confidence intervals. Seven of the 9 included Heschls gyrus(i) on the right: the remaining two, both males, had sources slightly anterior to Heschls gyrus(i). We conclude that all M100 source location estimates were compatible with an auditory koniocortex source in or adjacent to Heschls gyri.

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

BackgroundGamma-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.MethodsWe 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.ResultsInduced 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.ConclusionThese 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.

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 PLFs 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.

EEG correlates of methylphenidate response among children with ADHD: a preliminary report

BACKGROUND Recent electrophysiologic studies have found fairly consistent differences between children with attention-deficit/hyperactivity disorder (ADHD) and age-matched control subjects. The present study examined electroencephalogram (EEG) changes associated with a double blind, placebo-controlled administration of methylphenidate among children with ADHD. METHODS Subjects were 10 children, ages 8 to 13, with a primary diagnosis of ADHD. Brain electrical activity was recorded with 7 electrodes in the frontal, central, and midline areas during baseline and cognitive activation conditions. RESULTS Repeated-measures ANOVAs indicate that children exhibiting a positive medication response had reductions of theta and alpha as well as increased beta in the frontal regions, while nonresponders showed the opposite pattern (p < .05). Significant correlations between improvement on a vigilance task and changes in beta activity in the frontal electrodes emerged as well. CONCLUSIONS These preliminary findings indicate that there are different electrophysiologic correlates to methylphenidate among ADHD children who are medication responders and nonresponders.

Transient and steady-state auditory gamma-band responses in first-degree relatives of people with autism spectrum disorder

BackgroundStimulus-related γ-band oscillations, which may be related to perceptual binding, are reduced in people with autism spectrum disorders (ASD). The purpose of this study was to examine auditory transient and steady-state γ-band findings in first-degree relatives of people with ASD to assess the potential familiality of these findings in ASD.MethodsMagnetoencephalography (MEG) recordings in 21 parents who had a child with an autism spectrum disorder (pASD) and 20 healthy adult control subjects (HC) were obtained. Gamma-band phase locking factor (PLF), and evoked and induced power to 32, 40 and 48 Hz amplitude-modulated sounds were measured for transient and steady-state responses. Participants were also tested on a number of behavioral and cognitive assessments related to the broad autism phenotype (BAP).ResultsReliable group differences were seen primarily for steady-state responses. In the left hemisphere, pASD subjects exhibited lower phase-locked steady-state power in all three conditions. Total γ-band power, including the non-phase-locked component, was also reduced in the pASD group. In addition, pASD subjects had significantly lower PLF than the HC group. Correlations were seen between MEG measures and BAP measures.ConclusionsThe reduction in steady-state γ-band responses in the pASD group is consistent with previous results for children with ASD. Steady-state responses may be more sensitive than transient responses to phase-locking errors in ASD. Together with the lower PLF and phase-locked power in first-degree relatives, correlations between γ-band measures and behavioral measures relevant to the BAP highlight the potential of γ-band deficits as a potential new autism endophenotype.

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.

Neuropsychological test performance and MEG-based brain lateralization: Sex differences

Magnetoencephalographic (MEG) auditory evoked fields (EF) were recorded from left and right hemispheres of 9 normal males and 12 normal females. Source location of the 100 ms latency component (M100) was localized to superior temporal lobes bilaterally using an inverse solution algorithm. All subjects also were administered the Wechsler block design and visual reproduction subtests, and the California Verbal Learning Test (CVLT). M100 source locations demonstrated significant sex differences in interhemispheric asymmetry. Males had source locations further anterior than females, with the differences most pronounced in the right hemisphere. Expected sex differences were found in neuropsychological test performance, with males performing better on block design ad visual reproduction, and females performing better on the CVLT. Across both sexes, block design scores correlated significantly with right hemisphere M100 location, with more anterior source locations associated with better performance. CVLT scores were negatively correlated with right hemisphere M100 source locations. These findings suggest MEG-based measures of interhemispheric asymmetry may be related to specific neuropsychological test performance measures.