Abnormal gamma and beta MEG activity during finger movements in early-onset psychosis.

Patients with psychosis often exhibit abnormalities in basic motor control, but little is known about the neural basis of these deficits. This study examines the neuro-dynamics of movement using magnetoencephalography (MEG) in adolescents with early-onset psychosis and typically developing controls. MEG data were imaged using beamforming then evaluated for task and group effects before, during, and after movement onsets. Primary findings included weaker activation in patients during movement execution in cerebellar cortices. Such aberrations likely contribute to the decreased motor control exhibited by patients with psychosis, and may reflect GABAergic-based inhibitory deficits comparable to those seen in cellular and system-level studies.

Estimates of milk constituents from lactating bonnet macaque (Macaca radiata) mothers between two and seven months post-partum.

BACKGROUND: The literature regarding milk composition in non-human primates collected across offspring development is limited. We assayed milk samples from bonnet macaque (Macaca radiata) mothers as part of studies characterizing development of this species. METHODS: Milk was obtained when possible longitudinally from seven lactating bonnet macaque mothers. Samples were frozen until analysis. Individual samples were analyzed to determine the concentrations of electrolytes including sodium, potassium, calcium, chloride, and magnesium, as well as urea, protein, lipids, glucose, and lactose. RESULTS: A trend for increased lipids as well as protein percentage was noted with increasing infant age. Chloride and calcium showed an increase with age, whereas other electrolytes remained relatively stable across development. CONCLUSIONS: The composition of the milk of this particular macaque species was similar to other Old World primates as well as humans. These data add to the limited information available on milk constituents among mammals.

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.

Fluctuation of gamma-band phase synchronization within the auditory cortex in schizophrenia.

OBJECTIVE: To study the phase stability of the 40Hz auditory steady-state response (ASSR) in Sz, and in addition, to investigate inter-hemispheric phase synchronization using ipsilateral and contralateral hemisphere gamma band ASSRs. METHODS: Whole head magnetoencephalography (MEG) was used to detect ASSR from both hemispheres in Sz patients and their control counterparts. Source localization, spatial and temporal filtering were performed to infer gamma band activity from the neural generators of the ASSR. The response gamma band phase stability relative to a reference signal was quantified using the phase synchronization index (PSI). RESULTS: Results indicated reduced phase synchronization of the ASSR and the stimulus reference signal in Sz patients compared to control subjects, in addition to reduced inter-hemispheric phase synchronization between contralateral and ipsilateral hemispheric responses in Sz patients. CONCLUSIONS: Greater intra and inter hemispheric fluctuations of ASSR gamma band phase synchronization in Sz add to previous studies suggesting timing deficiencies within neural populations, possibly caused by impairments of neural network parameters. SIGNIFICANCE: This study provides experimental support that may aid in understanding the dynamics of neural phase synchrony caused by modifications of underlying neurotransmitter systems, as reflected in disease states such as schizophrenia.

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.

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.

Neurological signs and cognitive performance distinguish between adolescents with and without psychosis.

Neurological and cognitive aspects of adolescent psychotic disorders are understudied. The authors assessed 19 adolescents with psychosis and 16 healthy comparison subjects using the Neurological Evaluation Scale (NES) and age-appropriate Wechsler intelligence quotient (IQ) scales. NES scores were highest and IQ scores were lowest among subjects with psychosis. Subjects with psychosis did not demonstrate age-related decreases in NES score. The combination of NES and IQ scores predicted both the presence of psychosis and psychiatric diagnosis. There were no relationships between medication status and either NES or IQ scores. These results support a broadly conceived neurodevelopmental formulation of adolescent psychotic disorders.

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.

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.

Regional gray matter volumetric changes in autism associated with social and repetitive behavior symptoms.

BACKGROUND: Although differences in brain anatomy in autism have been difficult to replicate using manual tracing methods, automated whole brain analyses have begun to find consistent differences in regions of the brain associated with the social cognitive processes that are often impaired in autism. We attempted to replicate these whole brain studies and to correlate regional volume changes with several autism symptom measures. METHODS: We performed MRI scans on 24 individuals diagnosed with DSM-IV autistic disorder and compared those to scans from 23 healthy comparison subjects matched on age. All participants were male. Whole brain, voxel-wise analyses of regional gray matter volume were conducted using voxel-based morphometry (VBM). RESULTS: Controlling for age and total gray matter volume, the volumes of the medial frontal gyri, left pre-central gyrus, right post-central gyrus, right fusiform gyrus, caudate nuclei and the left hippocampus were larger in the autism group relative to controls. Regions exhibiting smaller volumes in the autism group were observed exclusively in the cerebellum. Significant partial correlations were found between the volumes of the caudate nuclei, multiple frontal and temporal regions, the cerebellum and a measure of repetitive behaviors, controlling for total gray matter volume. Social and communication deficits in autism were also associated with caudate, cerebellar, and precuneus volumes, as well as with frontal and temporal lobe regional volumes. CONCLUSION: Gray matter enlargement was observed in areas that have been functionally identified as important in social-cognitive processes, such as the medial frontal gyri, sensorimotor cortex and middle temporal gyrus. Additionally, we have shown that VBM is sensitive to associations between social and repetitive behaviors and regional brain volumes in autism.

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.

Planum temporale volume in children and adolescents with autism.

Previous research has revealed a lack of planum temporale (PT) asymmetry in adults with autism. This finding is now extended to children and adolescents with the disorder. MRI scans were obtained from 12 children with autism and 12 gender, handedness and age-matched comparison participants. The volume of gray matter in the PT and Heschl's gyrus (HG) in both hemispheres was measured. PT volume was larger in the left hemisphere than in the right in the comparison, but not the autism group. This specifically reflected reduced volume of the left PT in the autism group. There were noted differences in the overall morphological appearance of the right Sylvian fissure in the autism group, but no volumetric difference in the right PT. No differences in HG volumes were observed between the two groups. Lack of PT asymmetry may suggest an early neurodevelopmental disturbance in autism.

EEG correlates of methylphenidate response in ADHD: association with cognitive and behavioral measures.

The authors examined the association between EEG correlates of medication response and concomitant cognitive and behavioral changes among children with attention-deficit hyperactivity disorder (ADHD). Subjects were 36 children with ADHD, aged 8 to 12 years. EEG activity was recorded from nine active electrodes during placebo and medication conditions. Medication administration resulted in increased alpha activity in central and parietal regions during both the baseline and cognitive activation conditions. Children who were medication responders exhibited increased frontal beta activity whereas nonresponders showed decreased beta activity in the same region. Increased frontal beta activity was significantly correlated with medication-related improvement in performance on Conners'Continuous Performance Test and parent behavior ratings in attention and hyperactivity. Decreased right frontal theta activity was associated with improvements in parent-rated attention, but not in CPT performance. Stimulant medication increases beta activity in children with ADHD, particularly in frontal regions. Increased cortical arousal and activation in the frontal cortex is strongly associated with sustained attention and response inhibition and with parent-rated attention and hyperactivity/impulsivity.

Hippocampus and amygdala volumes in parents of children with autistic disorder.

OBJECTIVE: Structural and functional abnormalities in the medial temporal lobe, particularly the hippocampus and amygdala, have been described in people with autism. The authors hypothesized that parents of children with a diagnosis of autistic disorder would show similar changes in these structures. METHOD: Magnetic resonance imaging scans were performed in 17 biological parents of children with a diagnosis of DSM-IV autistic disorder. The scans were compared with scans from 15 adults with autistic disorder and 17 age-matched comparison subjects with no personal or familial history of autism. The volumes of the hippocampus, amygdala, and total brain were measured in all participants. RESULTS: The volume of the left hippocampus was larger in both the parents of children with autistic disorder and the adults with autistic disorder, relative to the comparison subjects. The hippocampus was significantly larger in the adults with autistic disorder than in the parents of children with autistic disorder. The left amygdala was smaller in the adults with autistic disorder, relative to the other two groups. No differences in total brain volume were observed between the three groups. CONCLUSIONS: The finding of larger hippocampal volume in autism is suggestive of abnormal early neurodevelopmental processes but is partly consistent with only one prior study and contradicts the findings of several others. The finding of larger hippocampal volume for the parental group suggests a potential genetic basis for hippocampal abnormalities in autism.

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.

Smaller left hemisphere planum temporale in adults with autistic disorder.

The structure of the planum temporale is often disturbed in disorders with associated communication problems, particularly in auditory and language processing areas in the brain. We hypothesized that people with autism would have reduced left hemisphere volumes in the planum temporale, a language related brain structure. We performed magnetic resonance imaging scans of 15 adults with autistic disorder and 15 comparison subjects, and measured the volume of gray matter in the planum temporale and Heschl's gyrus (HG) in both hemispheres. Planum temporale volume reduced in the left hemisphere of the autism group (P<0.003). No differences in HG volumes were observed between the two groups. The volume reduction seen in the left hemisphere of the autism group may suggest an early neurodevelopmental disturbance in autism that impacts language development.

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.