The cerebellum is the second largest structure in the human brain. Until recently, the cerebellum was considered solely a motor structure. Discoveries from neuroanatomy, study of patients with cerebellar lesions, and human neuroimaging have all converged to suggest that major zones of the cerebellum participate in advanced forms of cognition. Relevant to mental health, cerebellar dysfunction has been implicated in psychiatric illness and preliminary reports suggest noninvasive stimulation of the cerebellum may benefit symptoms in schizophrenia. However our detailed understanding of cerebellar organization is far behind that of the cerebral cortex, leading to debates about the spatial organization of cerebellar zones linked to human thought and emotion, and even debate about the degree to which the functional organization of the cerebellum is consistent from one person to the next. The goal of the present work is to provide a detailed understanding of cerebellar organization with particular focus on zones implicated in higher-order cognition that include regions accessible to neuromodulation. (1) First, advanced human high-field MRI methods will be used to map networks across the cerebellum fully within individuals preserving the anatomical details that would otherwise be lost with lower resolution approaches or by averaging findings across individuals. To achieve this level of precision each individual will be imaged repeatedly. (2) Second, to establish that the spatially separate regions of the cerebellum are functionally distinct, the same individuals will be administered challenging tasks that probe language, social, and memorial functions to rigorously establish separation between cerebellar zones that may be as little as a few millimeters apart. (3) Enabled by the precision maps of cerebellar organization, open debates will be resolved that include questions about how many times high-order cognitive zones repeat across the cerebellum and whether small, difficult to map, isolated zones of function contribute to the uniqueness of each person?s brain. (4) Critical to the long-term objective of this work to benefit patient care, the precision maps of each individual?s cerebellum will be used to model the possible effects of non-invasive stimulation. In doing so, a path from precision mapping of the cerebellum to neuromodulation will be provided openly as well as high-resolution maps and raw data that can be utilized by the community to further improve available methods for neuromodulation. Most broadly, the present work seeks to better understand the detailed organization of the human cerebellum to serve as a foundation for understanding and further developing novel interventions in the battle against mental illness.

Public Health Relevance

Using repeat scanning at high field, the proposed research seeks to map the organization of the human cerebellum within individual participants to a level of precision not possible previously. Using these network estimates, the functional selectivity of closely adjacent regions of the cerebellum will be tested for involvement in specific domains of higher-order cognition and used as the basis for modeling the potential of non-invasive neuromodulation to selectively target zones of the cerebellum important to mental illness.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH124004-01
Application #
10028768
Study Section
Clinical Neuroscience and Neurodegeneration Study Section (CNN)
Program Officer
Mcmullen, David
Project Start
2020-06-01
Project End
2023-04-30
Budget Start
2020-06-01
Budget End
2021-04-30
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Harvard University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138