Models of Auditory Hallucination
- Conditions
- Schizo Affective DisorderAuditory HallucinationSchizophrenia
- Interventions
- Device: Transcranial Magnetic Stimulation (TMS)
- 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
- 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)
-
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
- Arm && Interventions
Group Intervention Description TMS to insula Transcranial Magnetic Stimulation (TMS) 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. TMS to cerebellum Transcranial Magnetic Stimulation (TMS) 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.
- 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