Using Transcranial Magnetic Stimulation (TMS) to Understand Hallucinations in Schizophrenia

Schizophrenia Clinical Trial

Official title:

Empirical Validation of a Cerebellar-cortical Hallucination Circuit

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05343598
• Other study ID #: 2021P002459
• Secondary ID: R01MH126000
• Status: Recruiting
• Phase: N/A
• Start date: October 13, 2021
• Est. completion date: October 31, 2026

Study information

• Verified date: March 2024
• Source: Mclean Hospital
• Contact: Mark Halko, PhD
• Email: mhalko[@]mclean.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study uses a noninvasive technique called transcranial magnetic stimulation (TMS) to study how hallucinations work in schizophrenia.

TMS is a noninvasive way of stimulating the brain, using a magnetic field to change activity in the brain. The magnetic field is produced by a coil that is held next to the scalp. In this study the investigators will be stimulating the brain to learn more about how TMS might improve these symptoms of schizophrenia.

Description:

This study tests the hypothesis that hallucinations in schizophrenia are mediated by network pathophysiology, and that network pathophysiology can be quantified by the functional connectivity of a cerebellar-thalamo-cortical circuit. To accomplish this, participants will be recruited who are diagnosed with schizophrenia or schizoaffective disorder who experience auditory hallucinations.

Participants will undergo an initial screening session to complete informed consent and undergo baseline assessments of schizophrenia symptom severity. These assessments include reporter-based measures such as the Positive and Negative Syndrome Scale (PANSS).

Participants will then undergo an MRI scan that includes structural and resting-state functional magnetic resonance imaging (rsfMRI). These rsfMRI imagines will be used to isolate individual resting state networks for targeting of rTMS modulation.

Participants will then undergo five days of twice daily rTMS sessions.

One week after the last rTMS session, participants will undergo follow-up MRI imaging and the same study assessments.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 68
• Est. completion date: October 31, 2026
• Est. primary completion date: October 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Diagnosis of schizophrenia or schizoaffective disorder

Exclusion Criteria:

• substance use disorder in past 3 months

• ambidexterity

• contraindications for TMS or MRI including :

• history of neurological disorder

• history of head trauma resulting in loss of consciousness

• history of seizures or diagnosis of epilepsy or first degree relative family history of epilepsy

• metal in brain or skull

• implanted devices such as a pacemaker, medication pump, nerve stimulator or ventriculoperitoneal shunt

• claustrophobic in MRI

Related Conditions & MeSH terms

• Hallucinations
• Mood Disorders
• Psychotic Disorders
• Schizo Affective Disorder
• Schizophrenia

Intervention

Device:
• Repetitive Transcranial Magnetic Stimulation (rTMS)
rTMS is a technique of TMS that allows for selective external manipulation of neural activity in a non-invasive manner. During rTMS a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field, which in turn induces electrical current in neurons and allows for modulation of neural circuitry. The rTMS pulses will be delivered in a pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz every 10s for 600 total pulses.
• Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
rTMS is a technique of TMS that allows for selective external manipulation of neural activity in a non-invasive manner. During rTMS a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field, which in turn induces electrical current in neurons and allows for modulation of neural circuitry. The rTMS pulses will be delivered in a pattern consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz every 10s for 600 total pulses. Sham is achieved by using a coil with a magnetic shield preventing magnetic field from reaching the head.

Locations

Country	Name	City	State
United States	McLean Hospital	Belmont	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Mclean Hospital	Beth Israel Deaconess Medical Center, National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (8)

Basavaraju R, Ithal D, Thanki MV, Ramalingaiah AH, Thirthalli J, Reddy RP, Brady RO Jr, Halko MA, Bolo NR, Keshavan MS, Pascual-Leone A, Mehta UM, Kesavan M. Intermittent theta burst stimulation of cerebellar vermis enhances fronto-cerebellar resting state functional connectivity in schizophrenia with predominant negative symptoms: A randomized controlled trial. Schizophr Res. 2021 Dec;238:108-120. doi: 10.1016/j.schres.2021.10.005. Epub 2021 Oct 12. — View Citation

Brady RO Jr, Beermann A, Nye M, Eack SM, Mesholam-Gately R, Keshavan MS, Lewandowski KE. Cerebellar-Cortical Connectivity Is Linked to Social Cognition Trans-Diagnostically. Front Psychiatry. 2020 Nov 4;11:573002. doi: 10.3389/fpsyt.2020.573002. eCollection 2020. — View Citation

Brady RO Jr, Gonsalvez I, Lee I, Ongur D, Seidman LJ, Schmahmann JD, Eack SM, Keshavan MS, Pascual-Leone A, Halko MA. Cerebellar-Prefrontal Network Connectivity and Negative Symptoms in Schizophrenia. Am J Psychiatry. 2019 Jul 1;176(7):512-520. doi: 10.1176/appi.ajp.2018.18040429. Epub 2019 Jan 30. — View Citation

Halko MA, Farzan F, Eldaief MC, Schmahmann JD, Pascual-Leone A. Intermittent theta-burst stimulation of the lateral cerebellum increases functional connectivity of the default network. J Neurosci. 2014 Sep 3;34(36):12049-56. doi: 10.1523/JNEUROSCI.1776-14.2014. — View Citation

Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201-6. doi: 10.1016/j.neuron.2004.12.033. — View Citation

Hwang M, Roh YS, Talero J, Cohen BM, Baker JT, Brady RO, Ongur D, Shinn AK. Auditory hallucinations across the psychosis spectrum: Evidence of dysconnectivity involving cerebellar and temporal lobe regions. Neuroimage Clin. 2021;32:102893. doi: 10.1016/j.nicl.2021.102893. Epub 2021 Nov 24. — View Citation

Nawaz U, Lee I, Beermann A, Eack S, Keshavan M, Brady R. Individual Variation in Functional Brain Network Topography is Linked to Schizophrenia Symptomatology. Schizophr Bull. 2021 Jan 23;47(1):180-188. doi: 10.1093/schbul/sbaa088. — View Citation

Ward HB, Brady RO Jr, Halko MA. Bridging the Gap: Strategies to Make Psychiatric Neuroimaging Clinically Relevant. Harv Rev Psychiatry. 2021 May-Jun 01;29(3):185-187. doi: 10.1097/HRP.0000000000000295. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	functional connectivity	change in functional connectivity of a putative cerebellar-thalamic-cortical hallucination circuit (cerebellum to thalamus) will be assessed before and after (1 week followup) TMS stimulation.	baseline, 1 week after TMS
Primary	Positive and Negative Syndrome Scale (PANSS)	The PANSS is clinical rating scale of symptom severity . Each descriptor is rated on a 7 point scale from 1=(absence of any symptom) to 7=(extremely severe symptoms).	baseline
Primary	Scale for the Assessment of Positive Symptoms (SAPS)	The SAPS is clinical rating scale of symptom severity . Each descriptor is rated on a 5 point scale from 1=(absence of any symptom) to 5=(extremely severe symptoms).	baseline
Primary	Auditory Hallucination Rating Scale (AHRS) Scale (AHRS)	The AHRS is a 7-item clinical rating scale used to assess auditory hallucinations.	baseline