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Models of Auditory Hallucination

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ClinicalTrials.gov Identifier: NCT04210557
Recruitment Status : Recruiting
First Posted : December 24, 2019
Last Update Posted : March 16, 2021
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Yale University

Brief Summary:
The purpose of this study is to address the shortcoming in clinical hallucination research by causally manipulating the neural loci of conditioned hallucination task behavior in-person in patients with psychosis using transcranial magnetic stimulation (TMS), tracking the impact of this manipulation on the number of times participants with hallucinations report hearing tones that were not presented. With such a causal intervention, the veracity of this explanation of hallucinations will be either validated or disconfirmed. If validated, the task can be further developed as a biomarker for predicting the hallucination onset, guiding, developing or tracking the effects of treatments for hallucinations.

Condition or disease Intervention/treatment Phase
Schizophrenia Schizo Affective Disorder Auditory Hallucination Device: Transcranial Magnetic Stimulation (TMS) Not Applicable

Detailed Description:

Hallucinations are percepts without stimulus. 70% of patients with schizophrenia suffer distressing auditory hallucinations. Their mere presence increases the risk of suicide. Most reach remission with D2 dopamine receptor blocking drugs after 1 year of adherence. However, 30% of patients have intractable hallucinations, and 50% are non-adherent to their medications, commonly because of unfavorable side-effects - those intractable and non-adherent patients continue to suffer. There is a clear need for a mechanistic understanding of hallucinations as a prelude to rational treatment design.

This study provides the initial steps towards the development of an interventional biomarker for clinical hallucinations, grounded in computational neuroscience.

Computational psychiatry involves harnessing the power of computational neuroscience to address the clinical needs of those suffering from serious mental illnesses. There has been much discussion of the promise of the approach. There have been few studies thus far and they have largely involved correlative methods like functional neuroimaging. This study will address this shortcoming by causally manipulating the neural loci of computational model parameters in-person in patients with psychosis using transcranial magnetic stimulation (TMS), tracking the impact of this manipulation on behavioral task performance . With such a causal intervention, the veracity of the model's explanation of hallucinations will be either validated or disconfirmed. If validated, the model can be further developed as a biomarker for predicting the hallucination onset, guiding, developing or tracking the effects of treatments for hallucinations. If disconfirmed, the model ought to be discarded and other alternatives should be pursued.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: The participant, the physician administering TMS, and the research psychologist will be blind to the condition. One research assistant will be unblinded to the condition. This unblinded research assistant is responsible for setting up the active TMS coils or the sham TMS coils and determining the protocol used, to maintain the blindness of other study staff and the participant.
Primary Purpose: Basic Science
Official Title: Models of Auditory Hallucination
Actual Study Start Date : February 27, 2020
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : June 30, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TMS to insula

This study will recruit 30 clinical voice hearers (P+H+). They will complete two parallel forms of the conditioned hallucinations task (with different visual and auditory stimuli) on two occasions, separated by a week.

TMS and sham will be delivered in a randomized counterbalanced order. Hypothesis: Inhibiting the insula will decrease prior over-weighting. If this computational perturbation is responsible for conditioned hallucinations, then ameliorating it with TMS that increases insula engagement will decrease conditioned hallucination responses. Furthermore, the prior weighting parameter will be reduced following active TMS compared with sham.

Device: Transcranial Magnetic Stimulation (TMS)
Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction. An electric pulse generator, or stimulator, is connected to a magnetic coil, which in turn is connected to the scalp. The stimulator generates a changing electric current within the coil which induces a magnetic field; this field then causes a second inductance of inverted electric charge within the brain itself.
Other Name: repetitive transcranial magnetic stimulation (rTMS)

Experimental: TMS to cerebellum
This study will recruit a further 70 clinical voice hearers. Again, they will complete parallel forms of the conditioned hallucinations task on two occasions, separated by a week. They will receive excitatory TMS over the cerebellum (and sham on the other occasion, in a randomized counterbalanced order). Hypotheses: Exciting the cerebellum will increase belief-updating. If poor belief-updating contributes to conditioned hallucinations, increasing cerebellum engagement should decrease conditioned hallucinations and alter the belief-updating model parameter compared with sham TMS.
Device: Transcranial Magnetic Stimulation (TMS)
Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction. An electric pulse generator, or stimulator, is connected to a magnetic coil, which in turn is connected to the scalp. The stimulator generates a changing electric current within the coil which induces a magnetic field; this field then causes a second inductance of inverted electric charge within the brain itself.
Other Name: repetitive transcranial magnetic stimulation (rTMS)




Primary Outcome Measures :
  1. Conditioned Hallucinations task performance [ Time Frame: 18 months ]
    The primary outcome measure is the number of times participants report hearing tones that were not presented. There are 360 total trials. There are 120 no tone trials. People who hear voices typically report hearing tones on 30% of the no tone trials (approximately 36 times, as compared to 12 times in people who do not hear voices). The investigators anticipate fewer conditioned hallucinations (fewer than 36 reports of tones when none were presented) in the active TMS conditions as compared to the sham.



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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged 18 - 45 years
  • Voice hearing patients
  • Meet diagnostic criteria for DSM-V schizophrenia or schizophreniform disorder
  • Report hearing voices at least once a day
  • Score > 3 on PANSS P3 (hallucinations item)

Exclusion Criteria:

  • DSM-V substance use disorder within the past 6 months
  • Previous head injury with neurological symptoms and/or unconsciousness
  • Intellectual disability (IQ < 70)
  • Non-English speaker
  • Contraindications for TMS, including:

    • History of seizures
    • Metallic implants
    • Pacemaker
    • Pregnancy
  • Less than 6 weeks of a stable dose of psychotropic medication(s)
  • Comorbid mood or anxiety diagnosis
  • Clinically/behaviorally instability and unable to cooperate with TMS procedures
  • Clinically significant medical condition(s)
  • Unstable medical condition(s) based on EKG, medical history, physical examination, and routine lab work
  • Personal history of stroke
  • Family history of seizures

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04210557


Contacts
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Contact: Ramone Brown, BA 203 974 7866 belieflab@yale.edu

Locations
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United States, Connecticut
Connecticut Mental Health Center (CMHC) Recruiting
New Haven, Connecticut, United States, 06519
Contact: Kyle Pedersen, MAR    203-974-7089    kyle.pedersen@yale.edu   
Contact: Norma Gibson, MEd    (203)974-7089    norma.gibson@yale.edu   
Sub-Investigator: Al Powers, PhD, MD         
Sponsors and Collaborators
Yale University
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: Philip R Corlett, PhD Yale School of Medicine
Publications:
Helmholtz, H., & Southall, J. P. C. (1924). Helmholtz's treatise on physiological optics. Rochester, N.Y.: Optical Society of America.
Bayes T. (1958). An Essay Towards Solving a Problem in the Doctrine of Chances. Biometrika. 45(3-4): 296-315.
Friston, K. (2005). Hallucinations and perceptual inference. Behavioral and Brain Sciences, 28(6), 764-766. doi:10.1017/S0140525X05290131
G. Ellson, D. (1941). Hallucinations produced by sensory conditioning. Journal of Experimental Psychology. 28. 1-20. 10.1037/h0054167.
Stromer R, McIlvane W.J, Serna R.W. Complex stimulus control and equivalence. The Psychological Record. 1993;43:585-598.
Rosner, B. Fundamentals of biostatistics. 1995. Duxbury Press: New York.
Bohning, D. E. (2000). Introduction and overview of TMS physics. Transcranial magnetic stimulation in neuropsychiatry, 13-44.

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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT04210557    
Other Study ID Numbers: 2000023640
First Posted: December 24, 2019    Key Record Dates
Last Update Posted: March 16, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Yale University:
TMS
Transcranial Magnetic Stimulation
Additional relevant MeSH terms:
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Hallucinations
Schizophrenia
Mood Disorders
Psychotic Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Perceptual Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases