Cerebellar transcranial magnetic stimulation in psychotic disorders: intermittent, continuous, and sham theta-burst stimulation on time perception and symptom severity

Abstract

Background: The cerebellum contributes to the precise timing of non-motor and motor functions, and cerebellum abnormalities have been implicated in psychosis pathophysiology. In this study, we explored the effects of cerebellar theta burst stimulation (TBS), an efficient transcranial magnetic stimulation protocol, on temporal discrimination and self-reported mood and psychotic symptoms.

Methods: We conducted a case-crossover study in which patients with psychosis (schizophrenias, schizoaffective disorders, or bipolar disorders with psychotic features) were assigned to three sessions of TBS to the cerebellar vermis: one session each of intermittent (iTBS), continuous (cTBS), and sham TBS. Of 28 enrolled patients, 26 underwent at least one TBS session, and 20 completed all three. Before and immediately following TBS, participants rated their mood and psychotic symptoms and performed a time interval discrimination task (IDT). We hypothesized that cerebellar iTBS and cTBS would modulate these measures in opposing directions, with iTBS being adaptive and cTBS maladaptive.

Results: Reaction time (RT) in the IDT decreased significantly after iTBS vs. Sham (LS-mean difference = -73.3, p = 0.0001, Cohen's d = 1.62), after iTBS vs. cTBS (LS-mean difference = -137.6, p < 0.0001, d = 2.03), and after Sham vs. cTBS (LS-mean difference = -64.4, p < 0.0001, d = 1.33). We found no effect on IDT accuracy. We did not observe any effects on symptom severity after correcting for multiple comparisons.

Conclusion: We observed a frequency-dependent dissociation between the effects of iTBS vs. cTBS to the cerebellar midline on the reaction time of interval discrimination in patients with psychosis. iTBS showed improved (adaptive) while cTBS led to worsening (maladaptive) speed of response. These results demonstrate behavioral target engagement in a cognitive dimension of relevance to patients with psychosis and generate testable hypotheses about the potential therapeutic role of cerebellar iTBS in this clinical population.

Clinical trial registration: clinicaltrials.gov, identifier NCT02642029.

Keywords: bipolar disorder; cerebellum; interval discrimination task; neuromodulation; schizophrenia.