Targeting Cerebellum to Treat Psychosis: a Transcranial Magnetic Stimulation (TMS) Study
Condition: Schizophrenia; Schizoaffective Disorder; Bipolar Disorder I
MeSH terms: Schizophrenia; Bipolar Disorder; Psychotic Disorders
Study type: Interventional

Summary: 
      The goal of this study is to use transcranial magnetic stimulation (TMS) to investigate the
      impact of modulating cerebellar activity on time perception, executive function, and mood and
      psychotic symptoms in psychosis patients (i.e., schizophrenia, schizoaffective disorder, and
      bipolar disorder with psychotic features). The investigators hypothesize that abnormally
      reduced activity in the cerebellum contributes to the abnormalities in patients, that
      cerebellum-mediated disruptions in time perception may partially underlie executive
      dysfunction and symptoms, and that cerebellar stimulation will normalize disease-relevant
      outcome measures.
    

Detailed description: 
      The cerebellum plays a major role in integrative processing of higher order cognitive and
      affective functions, but it has not been considered a major treatment target for psychotic
      disorders. The goal of this study is to administer three different conditions of transcranial
      magnetic stimulation (TMS)-- excitatory, inhibitory, and sham TMS-- in a cross-over design in
      psychosis patients (i.e., schizophrenia, schizoaffective disorder, and bipolar disorder with
      psychotic features) to investigate with causal explanatory power the role of the cerebellum
      as a treatment target for psychotic disorders. More specifically, the investigators will
      measure the effects of cerebellar excitation and inhibition on time perception, executive
      function, and symptomatology. TMS will be administered using a theta-burst stimulation (TBS)
      protocol applied to the posterior cerebellar vermis. Participants will undergo three study
      sessions, one for each of the three TMS conditions. During each session, the investigators
      will administer validated cognitive paradigms and clinical measures immediately before and
      after TMS.

      The specific aims are to:

      1: Investigate the role of the cerebellum in abnormalities of time perception, executive
      function, and mood and psychotic symptoms by evaluating these functions before and
      immediately after excitatory, inhibitory, or sham TMS applied to the cerebellar vermis in
      patients with psychosis.

      (1a) Time perception hypothesis: Patients with psychotic disorders will have impaired timing
      perception, i.e., higher number of errors and/or greater inter-trial variability in an
      interval discrimination task both at baseline and after sham TMS. The investigators predict
      that the abnormalities in patients will improve after excitatory but not inhibitory TMS.

      (1b) Executive function hypothesis: Patients will show a higher number of errors and longer
      reaction times on the N-back working memory task, both at baseline and after sham TMS. The
      investigators predict that these deficits in patients will improve after excitatory but not
      inhibitory TMS.

      (1c) Symptom hypothesis: Symptom ratings using visual analog scales will improve in the
      period immediately after excitatory but not inhibitory TMS, and show no significant change
      after sham TMS.

      2: Investigate the relationship between time perception and symptomatology in patients with
      psychotic disorders. Hypothesis: The investigators predict that performance on the time
      perception task will correlate with performance on a working memory task as well as with mood
      and psychotic symptoms.

      This study may improve understanding about the role of the cerebellum in the pathophysiology
      of psychotic disorders. Such knowledge can potentially guide the development of cerebellar
      TMS as a therapeutic intervention for psychosis.
    

Intervention name(s): Excitatory TMS; Inhibitory TMS; Sham TMS
Intervention type(s): Device; Device; Device
Intervention description(s): Single session of intermittent theta-burst stimulation (600 pulses in blocks of 2s, separated by 8s of pause) to cerebellar vermis.; Single session of continuous theta-burst stimulation of 600 pulses to cerebellar vermis.; Single session, using the exact same procedures as the active arms but with a sham coil, which is designed to induce the same nonspecific sensory effects of TMS (auditory and somatosensory activation) without inducing the neuromodulatory magnetic fields.
Other intervention name(s): iTBS; cTBS; shamTBS
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: time perception; executive function; psychosis; mood symptoms