Reduction of cerebellar grey matter in Crus I and II in schizophrenia

Abstract

Structural deficiencies within the cerebellum have been associated with schizophrenia. Whereas several region-of-interest-based studies have shown deviations in cerebellar volume, meta-analyses on conventional whole-brain voxel-based morphometry (VBM) studies do not implicate abnormalities in the cerebellum. Since this discrepancy could be due to methodological problems of VBM, we used a cerebellum-optimized VBM procedure. We acquired high-resolution MRI scans from 29 schizophrenia patients and 45 healthy controls and used a VBM approach utilizing the Spatially Unbiased Infratentorial toolbox (Diedrichsen in Neuroimage 33:127-138, 2006). Relative to healthy controls, schizophrenia patients showed reductions of grey matter volume in the left cerebellum Crus I/II that were correlated with thought disorder (p < 0.05; one-sided) and performance in the Trail-making test B (p < 0.01). No cerebellar group differences were detected employing conventional whole-brain VBM. The results derived from the cerebellum analysis provide evidence for distinct grey matter deficits in schizophrenia located in Crus I/II. The association of this area with thought disorder and Trail-making performance supports the previously suggested role of the cerebellum in coordination of mental processes including disordered thought in schizophrenia. The failure of conventional VBM to detect such effects suggests that previous studies might have underestimated the importance of cerebellar structural deficits in schizophrenia.

Cerebellar contributions to neurological soft signs in healthy young adults

“…There may be a clear methodological argument to explain previous negative findings, i.e., that techniques that are not optimized for cerebellar morphometry, such as regions-of-interest approaches and VBM analyses using standard templates, may not be sensitive enough for detecting significant relationships between NSS and cerebellar structure and function [46,47]. Being aware of the heterogeneous cerebellar landmarks and the high interindividual spatial variance, we used cerebellum-optimized data analysis techniques which have been previously shown to outperform conventional VBM methods [27,28]. Yet despite an increased morphometric precision, we were not able to identify any significant relationship between cerebellar structure and NSS levels in our sample.…”

“…The template preserves anatomical detail of cerebellar subregions using automated nonlinear normalization methods, thus achieving a more accurate intersubject alignment compared to whole-brain methods. SUIT has been successfully used to identify changes in cerebellar subdivisions in patients with neuropsychiatric diseases, and in some cases, SUIT has been shown to be more sensitive to cerebellar change compared to conventional whole-brain voxel-based morphometry (VBM) approaches [27,28]. After controlling the data for scanner artifacts and gross anatomical abnormalities, and setting the image origin at the anterior commissure in each subject, infratentorial structures (i.e., cerebellum and brainstem) were isolated from the surrounding tissue.…”

Abnormal cerebellar volume in acute and remitted major depression

“…Given considerable cerebellar variability between individuals and relatively small sizes of cerebellar subdivisions, cerebellar segmentation is particularly susceptible to neuroanatomical imprecision (Diedrichsen 2006, Kuhn et al 2011.…”

“…The cerebellar template preserves anatomical detail of cerebellar subregions using automated nonlinear normalization methods, thus achieving a more accurate intersubject-alignment compared to whole-brain methods. SUIT has been successfully used to identify differences in cerebellar subdivisions in both psychiatric and neurological patient samples (Diedrichsen 2006, Kuhn et al 2011, and SUIT has been shown to be more sensitive to cerebellar structural differences compared to conventional whole-brain VBM (Diedrichsen 2006, Kuhn et al 2011.…”

Disrupted Modular Architecture of Cerebellum in Schizophrenia: A Graph Theoretic Analysis

“…Specifically, the schizophrenia group showed a different modular architecture where the hemispheric and vermal regions of crus II were classified together as a distinct module (ie, module 5 in figure 3), whereas in healthy controls these 2 regions were classified with a larger set of regions (ie, module 1 in figure 3). Given that crus II receives inputs from the prefrontal regions of the cerebrum associated with higher cognitive functions 17 and given recent anatomical evidence of volumetric reduction in crus II in schizophrenia, 87 this finding may indicate that within-cerebellar integration of such prefrontal cerebral inputs may not occur normally in schizophrenia, thus contributing to cerebellar-mediated impairment in functions such as memory, [14][15][16] learning, 6-9 eyeblink conditioning, 38 and decision making. 88 Additional findings from this study might also indicate that abnormal modular organization in this region contribute to the symptom severity of individuals with schizophrenia ( figure 5).…”