The cerebellum is densely connected to the cerebral cortex allowing it to powerfully modulate diverse cognitive networks. The specific mechanisms by which the cerebellum modulates the frontal cortex are unknown. In neuropsychiatric diseases such as schizophrenia and autism, deficits in working memory, attention, reasoning, and timing are accompanied by cerebellar abnormalities ? both structural and functional. There are currently no effective treatments for cognitive dysfunction in neuropsychiatric disease. Understanding cerebellar modulation of frontal circuits may lead to novel treatments targeting the cerebellum for cognitive dysfunction in human disease. For instance, cerebellar transcranial magnetic stimulation has been effective in improving cognitive dysfunction in schizophrenia. Our goal is to understand how the cerebellum encodes timing for key cognitive events in order to understand how cerebellar stimulation influences cognition and frontal cortical activity. We will determine the lateral cerebellar nuclear and cerebellar cortical contribution to timing of key cognitive events by investigating how these regions encode time-dependent neuronal activity. We will determine if cerebellar stimulation can correct dysfunctional frontal cortical activity, rescuing timing and cognitive performance. Additionally, we will characterize long-term changes to performance, frontal cortical plasticity, and cerebellar-frontal circuitry. Results from the proposed experiments will provide fundamental mechanistic insight into the role of the cerebellum in cognition and may advance cerebellar stimulation as a therapy for schizophrenia and other brain diseases. !

Public Health Relevance

The cerebellum is essential for motor timing, but very little is known about cerebellar timing of key cognitive events. We investigate how the cerebellum computes and communicates temporal information and how the cerebellum can be targeted therapeutically to modulate frontal cortical activity and restore cognitive function. This may have relevance for psychiatric diseases that involve impaired cognition.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH118240-03
Application #
10071095
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Rossi, Andrew
Project Start
2018-12-01
Project End
2023-11-30
Budget Start
2020-12-01
Budget End
2021-11-30
Support Year
3
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Iowa
Department
Psychiatry
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242