Jitka Hüttlová

Abnormalities in Myelination of the Superior Cerebellar Peduncle in Patients with Schizophrenia and Deficits in Movement Sequencing

Deficits in the execution of a sequence of movements are common in schizophrenia. Previous studies reported reduced functional activity in the motor cortex and cerebellum in schizophrenic patients with deficits in movement sequencing. The corticospinal tract (CST) and superior cerebellar peduncle (SCP) are fiber tracts that are involved in movement sequencing. However, the integrity of these tracts has not been evaluated in schizophrenic patients with respect to the performance of movement sequencing yet. Diffusion tensor magnetic resonance images (DT-MRI) were acquired from 24 patients with schizophrenia and 23 matched control subjects. Tractography was applied to reconstruct the CST and SCP and DT-MRI-specific parameters such as fractional anisotropy (FA) and radial diffusivity (RD) were reported. The patient group was further subdivided based on the score of sequencing of complex motor acts subscale of the Neurological Evaluation Scale into those with deficits in sequencing motor acts, the SQabn group (n = 7), and those with normal performance, the SQnorm group (n = 17). Schizophrenia patients of the SQnorm subgroup had significantly reduced FA and increased RD values in the right CST in comparison to the control group; the SQabn subgroup did not differ from the controls. However, the SQabn subgroup showed impaired integrity of the left SCP, whereas the SQnorm subgroup did not. Abnormalities in the right CST in the SQnorm and in the left SCP in SQabn groups suggest that the patients with SQabn represent subgroups with distinct deficits. Moreover, these results demonstrate the involvement of the SCP in the pathogenesis of movement sequencing in schizophrenia.

Neuronal substrate and effective connectivity of abnormal movement sequencing in schizophrenia

Movement sequencing difficulties are part of the neurological soft signs (NSS), they have high clinical value because they are not always present in schizophrenia. We investigated the neuronal correlates of movement sequencing in 24 healthy controls and 24 schizophrenia patients, with (SZP SQ+) or without (SZP SQ-) sequencing difficulties. We characterized simultaneous and lagged functional connectivity between brain regions involved in movement sequencing using psychophysiological interaction (PPI) and the Granger causality modeling (GCM), respectively. Left premotor cortex (PMC) and superior parietal lobule (SPL) were specifically activated during sequential movements in all participants. Right PMC and precuneus, ipsilateral to the hand executing the task, activated during sequential movements only in healthy controls and SZP SQ-. SZP SQ+ showed hyperactivation in contralateral PMC, as compared to the other groups. PPI analysis revealed a deficit in inhibitory connections within this fronto-parietal network in SZP SQ+ during sequential task. GCM showed a significant lagged effective connectivity from right PMC to left SPL during task and rest periods in all groups and from right PMC to right precuneus in SZP SQ+ group only. Both SZP groups had a significant lagged connectivity from right to left PMC, during sequential task. Our results indicate that aberrant fronto-parietal network connectivity with cortical inhibition deficit and abnormal reliance on previous network activity are related to movement sequencing in SZP. The overactivation of motor cortex seems to be a good compensating strategy, the hyperactivation of parietal cortex is linked to motor deficit symptoms.

Predictive Motor Timing and the Cerebellar Vermis in Schizophrenia: An fMRI Study

Abnormalities in both time processing and dopamine (DA) neurotransmission have been observed in schizophrenia. Time processing seems to be linked to DA neurotransmission. The cognitive dysmetria hypothesis postulates that psychosis might be a manifestation of the loss of coordination of mental processes due to impaired timing. The objective of the present study was to analyze timing abilities and their corresponding functional neuroanatomy in schizophrenia. We performed a functional magnetic resonance imaging (fMRI) study using a predictive motor timing paradigm in 28 schizophrenia patients and 27 matched healthy controls (HC). The schizophrenia patients showed accelerated time processing compared to HC; the amount of the acceleration positively correlated with the degree of positive psychotic symptoms and negatively correlated with antipsychotic dose. This dysfunctional predictive timing was associated with BOLD signal activity alterations in several brain networks, especially those previously described as timing networks (basal ganglia, cerebellum, SMA, and insula) and reward networks (hippocampus, amygdala, and NAcc). BOLD signal activity in the cerebellar vermis was negatively associated with accelerated time processing. Several lines of evidence suggest a direct link between DA transmission and the cerebellar vermis that could explain their relevance for the neurobiology of schizophrenia.

Psychosis effect on hippocampal reduction in schizophrenia

INTRODUCTION In schizophrenia, disruption of the neurodevelopmental processes may lead to brain changes and subsequent clinical manifestations of the illness. Reports of the progressive nature of these morphological brain changes raise questions about their causes. The possible toxic effects of repeated stressful psychotic episodes may contribute to the disease progression. OBJECTIVES To analyze the influence of illness duration and previous psychotic episodes on hippocampal gray matter volume (GMV) in schizophrenia. METHODS We performed an analysis of hippocampal GMV correlations with illness duration, number of previous psychotic episodes, and age in 24 schizophrenia patients and 24 matched healthy controls. RESULTS We found a cluster of GMV voxels in the left hippocampal tail that negatively correlated with the number of previous psychotic episodes, independent from the effect of age. On the other hand we found no effect of illness duration independent of age on the hippocampal GMV. Finally, we found a cluster of significant group-by-age interaction in the left hippocampal head. CONCLUSIONS We found an additive adverse effect of psychotic episodes on hippocampal morphology in schizophrenia. Our findings support toxicity of psychosis concept, together with etiological heterogeneity of brain changes in schizophrenia.