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Molecular Psychiatry (2017) 22, 647–655; doi:10.1038/mp.2017.50 published online 28 March 2017

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

K L Parker1, Y C Kim2, R M Kelley2, A J Nessler1, K-H Chen3, V A Muller-Ewald4, N C Andreasen1 and N S Narayanan2

  1. 1Department of Psychiatry, The University of Iowa, Iowa City, IA, USA
  2. 2Department of Neurology, The University of Iowa, Iowa City, IA, USA
  3. 3Institute of Personality and Social Research, University of California, Berkeley, Berkeley, CA, USA
  4. 4Department of Psychology, The University of Iowa, Iowa City, IA, USA

Correspondence: Dr N Narayanan, Department of Neurology, The University of Iowa, 169 Newton Road, Iowa City, IA 52242, USA. E-mail: Nandakumar-narayanan@uiowa.edu

Received 18 September 2016; Revised 15 January 2017; Accepted 18 January 2017
Advance online publication 28 March 2017

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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 1–4Hz 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.