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.
- MeSH
- dospělí MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mapování mozku MeSH
- mozek patofyziologie MeSH
- nervová síť patofyziologie MeSH
- pohybová aktivita fyziologie MeSH
- schizofrenie patofyziologie MeSH
- vermis cerebelli patofyziologie MeSH
- vnímání času fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
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.
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- dospělí MeSH
- funkční lateralita MeSH
- lidé MeSH
- lineární modely MeSH
- magnetická rezonanční tomografie MeSH
- mapování mozku * MeSH
- mladý dospělý MeSH
- mozek MeSH
- nervové dráhy MeSH
- počítačové zpracování obrazu MeSH
- pohybové poruchy etiologie patologie MeSH
- progrese nemoci MeSH
- psychomotorický výkon fyziologie MeSH
- psychosomatické poruchy etiologie MeSH
- schizofrenie komplikace MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
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.
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- dospělí MeSH
- funkční lateralita MeSH
- hipokampus patologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mladý dospělý MeSH
- počítačové zpracování obrazu MeSH
- psychiatrické posuzovací škály MeSH
- psychotické poruchy etiologie patologie MeSH
- schizofrenie komplikace MeSH
- studie případů a kontrol MeSH
- věkové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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 SQ(abn) group (n = 7), and those with normal performance, the SQ(norm) group (n = 17). Schizophrenia patients of the SQ(norm) subgroup had significantly reduced FA and increased RD values in the right CST in comparison to the control group; the SQ(abn) subgroup did not differ from the controls. However, the SQ(abn) subgroup showed impaired integrity of the left SCP, whereas the SQ(norm) subgroup did not. Abnormalities in the right CST in the SQ(norm) and in the left SCP in SQ(abn) groups suggest that the patients with SQ(abn) represent subgroups with distinct deficits. Moreover, these results demonstrate the involvement of the SCP in the pathogenesis of movement sequencing in schizophrenia.
- MeSH
- analýza rozptylu MeSH
- anizotropie MeSH
- bílá hmota patologie MeSH
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mozeček patologie MeSH
- nervové dráhy patologie MeSH
- neurologické vyšetření MeSH
- počítačové zpracování obrazu MeSH
- pohyb fyziologie MeSH
- pohybové poruchy etiologie patologie MeSH
- pons patologie MeSH
- schizofrenie komplikace patologie MeSH
- studie případů a kontrol MeSH
- zobrazování difuzních tenzorů MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
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.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mapování mozku MeSH
- mladiství MeSH
- motorické dovednosti fyziologie MeSH
- motorické korové centrum patofyziologie MeSH
- mozeček patofyziologie MeSH
- nervová síť patofyziologie MeSH
- nervové dráhy patofyziologie MeSH
- počítačové zpracování obrazu MeSH
- pohyb fyziologie MeSH
- prsty ruky fyziologie MeSH
- schizofrenie patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- neurozobrazování * metody MeSH
- schizofrenie * diagnostické zobrazování MeSH
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- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- elektroencefalografie metody MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- schizofrenie * patofyziologie MeSH
- zraková percepce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
