Cerebellar circuits, timing, and cognition

摘要

ABSTRACT 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. !