Models of Auditory Hallucination

Not Applicable

Terminated

Conditions: Schizo Affective Disorder
Auditory Hallucination
Schizophrenia

Registration Number: NCT04210557

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Conditioned Hallucinations Task Performance	approximately 13 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.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (1): Connecticut Mental Health Center (CMHC)
🇺🇸
New Haven, Connecticut, United States
Connecticut Mental Health Center (CMHC)
🇺🇸New Haven, Connecticut, United States