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Delta-frequency stimulation of cerebellar projections can compensate for schizophrenia-related medial frontal dysfunction
Journal article   Peer reviewed

Delta-frequency stimulation of cerebellar projections can compensate for schizophrenia-related medial frontal dysfunction

K L Parker, Y C Kim, R M Kelley, A J Nessler, K-H Chen, V A Muller-Ewald, N C Andreasen and N S Narayanan
Molecular psychiatry, Vol.22(5), pp.647-655
03/28/2017
DOI: 10.1038/mp.2017.50
PMCID: PMC5873945
PMID: 28348382
url
https://www.ncbi.nlm.nih.gov/pmc/articles/5873945View
Open Access

Abstract

Schizophrenia involves abnormalities in the medial frontal cortex that lead to cognitive deficits. Here we investigate a novel strategy to normalize medial frontal brain activity by stimulating cerebellar projections. We used an interval timing task to study elementary cognitive processing that requires both frontal and cerebellar networks that are disrupted in patients with schizophrenia. We report three novel findings. First, patients with schizophrenia had dysfunctional delta rhythms between 1–4 Hz in the medial frontal cortex. We explored cerebellar-frontal interactions in animal models and found that both frontal and cerebellar neurons were modulated during interval timing and had delta-frequency interactions. Finally, delta-frequency optogenetic stimulation of thalamic synaptic terminals of lateral cerebellar projection neurons rescued timing performance as well as medial frontal activity in a rodent model of schizophrenia-related frontal dysfunction. These data provide insight into how the cerebellum influences medial frontal networks and the role of the cerebellum in cognitive processing.
 Nervous System behavioral disciplines and activities Article

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