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.

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.