title: Safety and proof of principle study of cerebellar vermal theta burst stimulation in refractory schizophrenia.
abstract: BACKGROUND
  Early invasive electrical stimulation studies suggested that enhancement of cerebellar vermal activity might prove valuable in symptomatic treatment of refractory neuropsychiatric diseases via modulation of emotion and affect. This proof of principle study aimed to test this hypothesis using noninvasive brain stimulation, and to explore the safety of this protocol in schizophrenia.
  
  
  METHODS
  Eight treatment-refractory patients with schizophrenia underwent ten sessions of intermittent theta burst stimulation (TBS) to the cerebellar vermis using MRI-guided transcranial magnetic stimulation (TMS). Assessments included side effect questionnaires, cardiovascular monitoring, psychiatric evaluations and comprehensive neuropsychological testing before and after TBS and at one-week follow-up.
  
  
  RESULTS
  Overall, TBS was tolerated well with mild side effects primarily comprising neck pain and headache. No serious adverse events occurred. Diastolic blood pressure (BP) showed mild decreases for five minutes post-TBS; no significant changes were detected for systolic BP or pulse. PANSS negative subscale showed significant improvements following TBS and during the follow-up. Calgary Depression Scale and self-report visual analog scales for Happiness and Sadness pointed to significant mood elevation. Neuropsychological testing revealed significantly fewer omissions in working memory and interference conditions of a Continuous Performance Test, a longer spatial span and better delay organization on the Rey-Osterrieth Complex Figure during follow-up. No significant worsening in psychiatric or neuropsychological measures was detected.
  
  
  CONCLUSIONS
  Theta burst stimulation of the cerebellar vermis is safe and well-tolerated, while offering the potential to modulate affect, emotion and cognition in schizophrenia. Future randomized, sham-stimulation controlled studies are warranted to support the clinical efficacy of this technique.
authors.affiliation: Harvard Medical School, Boston, MA, United States.
authors.forename: Asli
authors.initials: A
authors.lastname: Demirtas-Tatlidede
authors.forename: Catarina
authors.initials: C
authors.lastname: Freitas
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Cromer
authors.forename: Laura
authors.initials: L
authors.lastname: Safar
authors.forename: Dost
authors.initials: D
authors.lastname: Ongur
authors.forename: William S
authors.initials: WS
authors.lastname: Stone
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Schmahmann
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pascual-Leone
mesh_terms: D000328:Adult; D001794:Blood Pressure; D002531:Cerebellum / Q000503:physiopathology*; D003071:Cognition; D004644:Emotions; D005260:Female; D005500:Follow-Up Studies; D006240:Happiness; D006261:Headache / Q000209:etiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term; D008875:Middle Aged; D019547:Neck Pain / Q000209:etiology; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D012565:Schizophrenic Psychology; D013826:Theta Rhythm; D050781:Transcranial Magnetic Stimulation / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome
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