Cerebellar stimulation modulates working memory performance and anterior cerebellum-thalamic-cortical network connectivity in a subgroup of individuals with early course psychosis

Psychosis onset and clinical course are predicted by abnormalities in both cerebellar connectivity and verbal working memory that contribute to functional impairment. Transcranial direct current stimulation (tDCS) of the cerebellum may provide a viable treatment option to address verbal working memory deficits in psychosis. In this double-blind, randomized, crossover-controlled trial, twenty-seven individuals with an early course psychosis (ECP) diagnosis received anodal cerebellar stimulation or sham tDCS before a verbal working memory fMRI task then returned a week later for a counterbalanced session of sham or stimulation.

An additional healthy control comparison group (n = 36) received only sham. The tDCS intervention was well-tolerated (90% retention). In the sham stimulation condition, the ECP showed a verbal working memory deficit (p = 0.006).

During stimulation, verbal working memory improved (d = 0.016), though not significantly more than their own sham performance (p = 0.66). Among the ECP group there was a clear “responder” subgroup (n = 14) defined by a significant within-group verbal working memory improvement between conditions (d = 0.586), and between-group difference (d = −0.580) compared to non-responders (n = 11; p sham)- greater extrinsic connectivity in an anterior cerebello-thalamo-cortical network. These preliminary results suggest cerebellar tDCS may be a treatment option for a specific subgroup to address verbal working memory deficits and underscores the value of precision medicine.

This work was supported by the Brain Behavior Research Foundation (NARSAD) Independent Investigator Award to VAM. Department of Psychology, School of Brain and Behavioral Sciences, University of Texas -Dallas, Richardson, TX, USA Center for Vital Longevity, School of Brain and Behavioral Sciences, University of Texas -Dallas, Dallas, TX, USA Center for Brain Health, School of Brain and Behavioral Sciences, University of Texas -Dallas, Dallas, TX, USA Katherine S. Calhoun Department of Psychology, Northwestern University, Evanston, IL, USA Department of Psychiatry, Northwestern University, Chicago, IL, USA School of Education and Social Policy, Northwestern University, Evanston, IL, USA Medical Social Sciences, Northwestern University, Chicago, IL, USA Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, Atlanta Georgia, GA, USA Department of Psychology, University of California at Irvine, Irvine, CA, USA Department of Psychological and Brain Sciences, Texas A&M University, 4235 TAMU, College Station, TX, USA Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX, USA Institute for Innovations in Developmental Sciences (DevSci), Northwestern University, Evanston and Chicago, IL, USA Institute for Policy Research (IPR), Northwestern University, Chicago, IL, USA Correspondence to Katherine S.

The authors declare no competing interests. The study is a double-blind crossover randomized control trial design, treatment of subjects related to the study discussed in the attached manuscript was in accordance with the ethical guidelines of the APA and the Northwestern University’s Internal Review Board. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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