Brain functional connectivity of male patients in remission after the first episode of schizophrenia.

OBJECTIVES: Abnormal task-related activation and connectivity is present in schizophrenia. The aim of this study was the analysis of functional networks in schizophrenia patients in remission after the first episode. EXPERIMENTAL DESIGN: Twenty-nine male patients in remission after the first episode of schizophrenia and 22 healthy controls underwent examination by functional magnetic resonance during verbal fluency tasks (VFT). The functional connectivity of brain networks was analyzed using independent component analysis. RESULTS: The patients showed lower activation of the salience network during VFT. They also showed lower deactivation of the default mode network (DMN) during VFT processing. Spectral analysis of the component time courses showed decreased power in slow frequencies of signal fluctuations in the salience and DMNs and increased power in higher frequencies in the left frontoparietal cortex reflecting higher fluctuations of the network activity. Moreover, there was decreased similarity of component time courses in schizophrenia­the patients had smaller negative correlation between VFT activated and deactivated networks, and smaller positive correlations between DMN subcomponents. CONCLUSIONS: There is still an abnormal functional connectivity of several brain networks in remission after the first episode of schizophrenia. The effect of different treatment modalities on brain connectivity, together with temporal dynamics of this functional abnormality should be the objective of further studies to assess its potential as a marker of disease stabilization.

Cortico-cerebellar functional connectivity and sequencing of movements in schizophrenia.

BACKGROUND: Abnormal execution of several movements in a sequence is a frequent finding in schizophrenia. Successful performance of such motor acts requires correct integration of cortico-subcortical processes, particularly those related to cerebellar functions. Abnormal connectivity between cortical and cerebellar regions with resulting cognitive dysmetria has been proposed as the core dysfunction behind many signs and symptoms of schizophrenia. The aim of the present study was to assess if these proposed abnormalities in connectivity are a unifying feature of schizophrenia, or, rather, reflect a specific symptom domain of a heterogeneous disease. We predicted that abnormal functional connectivity between the motor cortex and cerebellum would be linked with abnormal performance of movement sequencing. METHODS: We examined 24 schizophrenia patients (SCH) and 24 age-, sex-, and handedness-matched healthy controls (HC) using fMRI during a modified finger-tapping task. The ability to perform movement sequencing was tested using the Neurological Evaluation Scale (NES). The subjects were categorized into two groups, with (SQ+) and without (SQ-) movement sequencing abnormalities, according to the NES-SQ score. The effects of diagnosis and movement sequencing abnormalities on the functional connectivity parameters between the motor cortex and cerebellum (MC-CRBL) and the supplementary motor cortex and cerebellum (SMA-CRBL) activated during the motor task were analyzed. RESULTS: We found no effect of diagnosis on the functional connectivity measures. There was, however, a significant effect on the SQ group: SQ + patients showed a lower level of MC-CRBL connectivity than SQ- patients and healthy controls. Moreover, the level of MC-CRBL and SMA-CRBL negatively correlated with the magnitude of NES-SQ abnormalities, but with no other NES domain. CONCLUSIONS: Abnormal cortico-cerebellar functional connectivity during the execution of a motor task is linked with movement sequencing abnormalities in schizophrenia, but not with the diagnosis of schizophrenia per se. It seems that specific patterns of inter-regional connectivity are linked with corresponding signs and symptoms of clinically heterogeneous conditions such as schizophrenia.

Aberrant EEG responses to gamma-frequency visual stimulation in schizophrenia.

Disturbance in the integration of visual information is one of the hallmarks of schizophrenia. In the spatial domain, visual integration is compromised, resulting in impaired perceptual grouping and contour integration. In the time domain, in contrast, visual integration is enhanced, as manifested by increased backward masking and lower ability of patients to detect successively presented visual stimuli as asynchronous. There is much evidence that integrative processes in the brain are supported by dynamic synchronization, or phase-locking, of neural firing. In particular, synchrony in the gamma band (>30 Hz) has been related to local visual information binding whereas synchrony in lower frequencies has been linked to global-scale integration. We recorded EEG signals evoked by steady-state gamma-frequency (40 Hz) photic stimulation in order to directly test the phase-locking of neural responses in schizophrenia. Compared with healthy control subjects, patients showed higher phase-locking of early evoked activity in the gamma band (36-44 Hz) over the posterior cortex, but lower phase-locking in theta (4-8 Hz), alpha (8-13 Hz) and beta (13-24 Hz) frequencies over the anterior cortex. Phase-locking of evoked responses separated schizophrenia and control subjects with accuracy of 86%. This result suggests that schizophrenia is associated with an enhanced early low-level integration in the visual cortex but a deficient high-level integration of visual information within the brain global workspace.