Abstract
Objective Neuroimaging studies have demonstrated aberrant structure and function of the “cognitive-affective cerebellum” in Major Depressive Disorder (MDD), although the specific role of the cerebello-cerebral circuitry in this population remains largely uninvestigated. The objective of this study was to delineate the role of cerebellar functional networks in depression.
Methods A total of 308 unmedicated participants completed resting-state functional magnetic resonance imaging scans, of which 247 (148 MDD; 99 Healthy Controls, HC) were suitable for this study. Seed-based resting-state functional connectivity (RsFc) analysis was performed using three cerebellar regions of interest (ROIs): ROI1 corresponded to default mode network (DMN) / inattentive processing; ROI2 corresponded to attentional networks including frontoparietal, dorsal attention, and ventral attention; ROI3 corresponded to motor processing. These ROIs were delineated based on prior functional gradient analyses of the cerebellum. A general linear model was used to perform within-group and between-group comparisons.
Results In comparison to HC, participants with MDD displayed increased RsFc within the cerebello-cerebral DMN (ROI1) and significantly elevated RsFc between the cerebellar ROI1 and bilateral angular gyrus at a voxel threshold (p < 0.001, two-tailed) and at a cluster level (p < 0.05, FDR-corrected). Group differences were non-significant for ROI2 and ROI3.
Conclusions These results contribute to the development of a systems neuroscience approach to the diagnosis and treatment of MDD. Specifically, our findings confirm previously reported associations between MDD, DMN, and cerebellum, and highlight the promising role of these functional and anatomical locations for the development of novel imaging-based biomarkers and targets for neuromodulation therapies.
Competing Interest Statement
SAA, XG, YJL, JR, ID, NWC, BNF, SH, GMM, TAS, and SWG have no conflicts of interest to declare. RWL has received honoraria or research funds from Allergan, Asia-Pacific Economic Cooperation, BC Leading Edge Foundation, CIHR, CANMAT, Canadian Psychiatric Association, Hansoh, Healthy Minds Canada, Janssen, Lundbeck, Lundbeck Institute, MITACS, Myriad Neuroscience, Ontario Brain Institute, Otsuka, Pfizer, St. Jude Medical, University Health Network Foundation, and VGH-UBCH Foundation. RM has received consulting and speaking honoraria from AbbVie, Allergan, Eisai, Janssen, KYE, Lallemand, Lundbeck, Otsuka, and Sunovion, and research grants from CAN-BIND, CIHR, Janssen, Lallemand, Lundbeck, Nubiyota, OBI and OMHF. SCS reports partial support from Canadian Biomarker Integration Network in Depression and CIHR (MOP 137097) grants during the conduct of the study, and grants from Ontario Brain Institute, Canadian Foundation for Innovation and Brain Canada, outside the submitted work. He is also the chief scientific officer of the neuroimaging data analysis company ADMdx, Inc (www.admdx.com), which specializes in brain image analysis to enable diagnosis, prognosis and drug effect detection for Alzheimer disease and various other forms of dementia. SHK has received honoraria or research funds from Abbott, Alkermes, Allergan, Boehringer Ingelheim, Brain Canada, CIHR, Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute, Ontario Research Fund, Otsuka, Pfizer, Servier, Sunovion, Sun Pharmaceuticals, and holds stock in Field Trip Health. VB is supported by an Academic Scholar Award from the UofT Dept of Psychiatry, and has received research support from CIHR, Brain & Behavior Foundation, MOH Innovation Funds, RCPSC, Department of Defense, Canada, NFRF, and an investigator-initiated trial from Roche Canada.
