Aberrant cerebellothalamic projections to thalamic subregions in first-episode psychosis

Abstract

The involvement of thalamo-cortical circuits in the pathophysiology of schizophrenia has been widely recognized. However, cerebellar influence on the thalamus has not been investigated in schizophrenia research. We examined the distribution of cerebellothalamic tracts to thalamic subregions using probabilistic tractography of diffusion tensor imaging in patients with first-episode psychosis (FEP).

Forty patients who experienced FEP and 40 healthy controls were investigated. Probabilistic tractography was performed by seeding the deep cerebellar nuclei targeting the contralateral thalamus. The proportion (percent) of cerebellothalamic tracts to each thalamic subregion (i.e., the thalamic entrance point) and the integrity of cerebellothalamic tracts (fractional anisotropy, FA) were compared between groups. Clinical rating scores were correlated with tractography findings.

We found that the proportion of tracts that projected to the left ventrolateral anterior thalamic nucleus (VLa) was significantly reduced in FEP patients compared with healthy controls. This was associated with increased severity of psychomotor poverty syndrome scores. By contrast, FEP patients had a higher proportion of tracts that projected to the right parafascicular nucleus (Pf, a nonspecific thalamic nucleus in the medial thalamus). This was associated with lower general assessment of functioning (GAF) scores and higher disorganization syndrome scores. In addition, we found significantly increased FA values of cerebellothalamic tracts from the left deep cerebellar nuclei to the right thalamus in FEP patients.

We provide the first evidence for altered topography of cerebellar tracts to the thalamus in first-episode psychosis. The VLa projects mainly to Brodmann area 6, which is involved in planning, organizing, monitoring, and generating movements. Diminished cerebellar influence on the VLa may then be the neural basis of the poverty of thought and action in patients. The Pf has diffuse projections to the cortex to subserve arousal and alertness. An increased proportion of cerebellothalamic tracts entering the Pf could indicate too much cerebellar influence, associated with poor functioning and the disorganization of thought and action in patients. Further studies are warranted to determine whether these alterations are predictors of risk for psychosis.