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Recruiting NCT05343598

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

No phase Interventional Schizophrenia Schizo Affective Disorder

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Repetitive Transcranial Magnetic Stimulation (rTMS), Sham Repetitive Transcranial Magnetic Stimulation (rTMS).
Who it may be relevant to
Registry conditions: Schizophrenia, Schizo Affective Disorder. Basic parameters: 18 years — 55 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Official title

Empirical Validation of a Cerebellar-cortical Hallucination Circuit

Overview

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.

Detailed 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.

Interventions

  • 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 p
  • Device 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 p

Primary outcome measures

  • functional connectivity [Time frame: baseline, 1 week after TMS]
  • Positive and Negative Syndrome Scale (PANSS) [Time frame: baseline]
  • Scale for the Assessment of Positive Symptoms (SAPS) [Time frame: baseline]
  • Auditory Hallucination Rating Scale (AHRS) Scale (AHRS) [Time frame: baseline]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Quadruple blind
Primary purpose
Basic science

Study locations

United States · 1 center
  • McLean Hospital — Belmont

Publications

  • 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. PMID 30696271
  • 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 PMID 34653740
  • 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. PMID 32648915
  • 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. PMID 34911197
  • 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. PMID 33329111
  • 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. PMID 33882534
  • 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. PMID 25186750
  • 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. PMID 15664172

Identifiers

NCT: NCT05343598 · 2021P002459 · R01MH126000

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗