Big contributions of the little brain for precision psychiatry

Abstract

Our previous work using 3T functional Magnetic Resonance Imaging (fMRI) parcellated the human dentate nuclei (DN), the primary output of the cerebellum, to three distinct functional zones each contributing uniquely to default-mode, salience-motor, and visual brain networks. In this perspective piece, we highlight the possibility to target specific functional territories within the cerebellum using non-invasive brain stimulation, potentially leading to the refinement of cerebellar-based therapeutics for precision psychiatry. Significant knowledge gap exists in our functional understanding of cerebellar systems. Intervening early, gauging severity of illness, developing intervention strategies and assessing treatment response, are all dependent on our understanding of the cerebello-cerebral networks underlying the pathology of psychotic disorders. A promising yet under-examined avenue for biomarker discovery is disruptions in cerebellar output circuitry. This is primarily because most 3T MRI studies in the past had to exclude cerebellum from the field of view due to limitations in spatiotemporal resolutions. Using recent technological advances in 7T MRI (e.g., parallel transmit head coils) to identify functional territories of the DN, with a focus on dentato-cerebello-thalamo-cortical (CTC) circuitry can lead to better characterization of brain-behavioral correlations and assessments of co-morbidities. Such an improved mechanistic understanding of psychiatric illnesses can reveal aspects of CTC circuitry that can aid in neuroprognosis, identification of subtypes, and generate testable hypothesis for future studies.

Keywords: cerebello-thalamo-cortical circuitry; cerebellum; dentate nuclei; functional connectivity; psychotic disorder.

Figure 1

DN plays a central node in the cerebellar connections to other extracerebellar areas, and is part of a highly complex system of reverberating connections linking the nuclei of the cerebellum to the rest of the brain. Based on (, , –40).

Figure 2

Top panel: RsFc results for CHR+ vs. CHR– contrast at a voxel-level height threshold of p < 0.005 (2-sided) and cluster size FDR corrected threshold of p < 0.05. (A–C) correspond to DMN, salience-motor, and visual functional territories of DN. Bottom panel: Bar plots for each of the significant clusters in the healthy control, CHR+, and CHR– groups. Notably, for each of these group contrasts, CHR– participants were not significantly different compared to healthy controls (43).