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Safety and proof of principle study of cerebellar vermal theta burst stimulation in refractory schizophrenia
Open accessAbstract
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.
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“as prior work suggested that improvement could occur even in patients with low baseline symptoms (Demirtas-Tatlidede et al., 2010)”
From A double-blind, randomized, sham-controlled clinical trial of cerebellar intermittent theta burst stimulation for bipolar disorder: Safety, tolerability, mood and cognitive effects (2025) · cites this paper as Demirtas-Tatlidede et al., 2010
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“In subjects with schizophrenia, CBM-iTBS can alter brain metabolism and cerebellar-frontal functional connectivity (Basavaraju et al., 2021; Brady et al., 2019; Cho et al., 2012; Halko et al., 2014; Singh et al., 2019), as well as positively impact affective and cognitive symptoms (Basavaraju et al., 2021; Demirtas-Tatlidede et al., 2010; Garg et al., 2016; Shinn et al., 2023; Zhu et al., 2021).”
From A double-blind, randomized, sham-controlled clinical trial of cerebellar intermittent theta burst stimulation for bipolar disorder: Safety, tolerability, mood and cognitive effects (2025) · cites this paper as Demirtas-Tatlidede et al., 2010
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“Specifically, a protocol of ten sessions of CBM-iTBS (delivered over 1–2 weeks) in patients with schizophrenia has demonstrated safety and tolerability (Demirtas-Tatlidede et al., 2010), reduced negative symptoms, improvements in mood, and improvements in cognitive functioning (Garg et al., 2016), with significant findings up to 24 weeks following treatment in controlled trials (Zhu et al., 2021).”
From A double-blind, randomized, sham-controlled clinical trial of cerebellar intermittent theta burst stimulation for bipolar disorder: Safety, tolerability, mood and cognitive effects (2025) · cites this paper as Demirtas-Tatlidede et al., 2010
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Schmahmann, J. D. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2018.07.005 · Cited by 1,625
Self-citationConsensus Paper: The Cerebellum's Role in Movement and Cognition
Koziol, L. F., Budding, D. E., Andreasen, N. C., D’Arrigo, S., Bulgheroni, S., Imamizu, H., Ito, M., Manto, M. U., Marvel, C. L., Parker, K. L., et al. (2013) · The Cerebellum · doi:10.1007/s12311-013-0511-x · Cited by 1,193
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Schmahmann, J. D., Guell, X., Stoodley, C. J., & Halko, M. A. (2019) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-070918-050258 · Cited by 587
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Metadata
- Authors
- Demirtas-Tatlidede, A., Freitas, C., Cromer, J. R., Safar, L., Ongur, D., Stone, W. S., Seidman, L. J., Schmahmann, J. D., & Pascual-Leone, A.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Harvard University (US)
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 124
- Issue
- 1-3
- Pages
- 91-100
- ISSN
- 0920-9964 (ISSN-L)
- PMC
- PMC3268232
- OpenAlex
- W2129217681
- Cited by
- 185
- References
- 101
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 14 · 2023: 6 · 2022: 14 · 2021: 18 · 2020: 10 · 2019: 15 · 2018: 10 · 2017: 11 · 2016: 13 · 2015: 8 · 2014: 12 · 2013: 11 · 2012: 11
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Schizophrenia Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Center for Research Resources (K24RR018875, UL1RR025758)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Keywords
- theta burst stimulation, cerebellar vermis
- MeSH terms
- Adult, Blood Pressure, Cerebellum, Cognition, Emotions, Female, Follow-Up Studies, Happiness, Headache, Humans, Magnetic Resonance Imaging, Male, Memory, Short-Term, Middle Aged, Neuropsychological Tests, Psychiatric Status Rating Scales, Schizophrenia, Schizophrenic Psychology, Theta Rhythm, Treatment Outcome, Neck Pain, Transcranial Magnetic Stimulation
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