Improving Hallucinations by Targeting the rSTS With tES

• ClinicalTrials.gov Identifier: NCT05165654
• Recruitment Status: Recruiting
• First Posted: December 21, 2021
• Last Update Posted: December 21, 2021
• Sponsor: Beth Israel Deaconess Medical Center
• Information provided by (Responsible Party): Paulo Lizano, Beth Israel Deaconess Medical Center

Study Description

Brief Summary:

Hallucinations are a core diagnostic feature of psychotic disorders. They involve different sensory modalities, including auditory, visual, olfactory, tactile, and gustatory hallucinations, among others. Hallucinations occur in multiple different neurological and psychiatric illnesses and can be refractory to existing treatments. Auditory hallucinations and visual hallucinations are found across diagnostic categories of psychotic disorders (schizophrenia, schizoaffective, bipolar disorder). Despite visual hallucinations being approximately half as frequent as auditory hallucinations, they almost always co-occur with auditory hallucinations, and are linked to a more severe psychopathological profile. Auditory and visual hallucinations at baseline also predict higher disability, risk of relapse and duration of psychosis after 1 and 2 years, especially when they occur in combination. Using a newly validated technique termed lesion network mapping, researchers demonstrated that focal brain lesions connected to the right superior temporal sulcus (rSTS) plays a causal role in the development of hallucinations. The rSTS receives convergent somatosensory, auditory, and visual inputs, and is regarded as a site for multimodal sensory integration. Here the investigators aim to answer the question whether noninvasive brain stimulation when optimally targeted to the rSTS can improve brain activity, sensory integration, and hallucinations.

Condition or disease	Intervention/treatment	Phase
Hallucinations, Auditory; Psychosis	Device: Transcranial Electrical Stimulation	Not Applicable

Detailed Description:

Functional neuroimaging studies have identified neural correlates of hallucinations across multiple brain regions. Some studies suggest a common neuroanatomical substrate independent of the sensory modality, while others suggest different neural correlates for different types of hallucinations. However, whether these neuroimaging findings represented a cause, consequence or epiphenomenon of hallucinations was unclear until recently. Using lesion network mapping, researchers demonstrated that focal brain lesions play a causal role in the development of hallucinations and can occur in different brain locations, both inside and outside sensory pathway, and that greater than 90% of lesion locations causing hallucinations are negatively connected to the right superior temporal sulcus (rSTS). The rSTS is known to play a role in social cognition, biological motion, audiovisual integration, and speech. Hence, when spontaneous activity decreases at lesion locations causing hallucinations, spontaneous activity in the rSTS increases, the exact pattern thought to predispose to hallucinations. Additionally, functional connectivity within this region is abnormal in patients with visual and auditory hallucinations. Therefore, the association between rSTS connectivity and hallucinations would suggest this region may be optimal for modulation via non-invasive brain stimulation.

One method by which cortical excitability can be altered is with transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique. High definition tDCS (HD-tDCS) is a refined version of tDCS with improved spatial precision of cortical stimulation. This involves the application of a weak electrical current (1-2 mA) delivered to the brain via scalp electrodes. tDCS can modulate cortical excitability, where anodal stimulation tends to increase (i.e. the resting potential becomes less negative) and cathodal stimulation tends to decrease the underlying membrane potential (i.e. the resting potential becomes more negative). While tDCS is a promising adjunctive treatment of auditory hallucinations and negative symptoms in schizophrenia, less is known about its role in treating hallucinations overall. To date, no study has non-invasively stimulated the rSTS with tDCS in psychosis and examined its effects on hallucinations. However, there are studies in healthy volunteers showing that anodal stimulation to the STS resulted in increased auditory false perceptions, while cathodal stimulation decreased false perceptions and was lower than the sham condition. Taken together, the recent lesion network mapping identifying the rSTS as a major source of hallucinations combined with prior studies showing that the rSTS is associated with hallucinations suggest that it may be possible to alleviate hallucinations by designing a tDCS protocol that targets the rSTS with cathodal stimulation. Technological advances in noninvasive neuromodulation and electrical field modeling further allow us to create a tDCS protocol specifically guided by the results of lesion network mapping studies with high spatial resolution.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Double Blinded
• Primary Purpose: Treatment
• Official Title: Improving Hallucinations by Targeting the Right Superior Temporal Sulcus With Electrical Stimulation
• Actual Study Start Date: November 1, 2021
• Estimated Primary Completion Date: October 1, 2022
• Estimated Study Completion Date: November 1, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Active Stimulation with TDCS; 10 tDCS; Two, twenty-minute sessions of tDCS to the rSTS for 5 days (10 total sessions).	Device: Transcranial Electrical Stimulation; Transcranial electrical stimulation
Sham Comparator: SHAM Stimulation; 10 passive sham control; Two, twenty-minute sessions of passive sham control to the rSTS for a 30 second ramped up and down at the beginning and end of the 20 min period for 5 days (10 total sessions).	Device: Transcranial Electrical Stimulation; Transcranial electrical stimulation

Outcome Measures

Primary Outcome Measures :

1. Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Change from baseline to day 5 ]
   Measuring total psychosis symptoms score (Total score minimum = 30, maximum = 210); General symptoms (minimum score = 16, maximum score = 112); Negative Symptoms (minimum score = 16, maximum score = 112); and Positive Symptoms (minimum score = 16, maximum score = 112); higher scores represent higher severity of symptoms
2. Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Change from baseline to month follow-up ]
   Measuring total psychosis symptoms score (Total score minimum = 30, maximum = 210); General symptoms (minimum score = 16, maximum score = 112); Negative Symptoms (minimum score = 16, maximum score = 112); and Positive Symptoms (minimum score = 16, maximum score = 112); higher scores represent higher severity of symptoms
3. University of Miami Parkinson's Disease Hallucinations Questionnaire (UM-PDHQ) [ Time Frame: Change from baseline to day 5 ]
   Measuring severity and duration of hallucinations; 20-item questionnaire to be used as a screening instrument to assess hallucinations (6 quantitative and 14 qualitative items); higher scores represent higher severity of symptoms
4. University of Miami Parkinson's Disease Hallucinations Questionnaire (UM-PDHQ) [ Time Frame: Change from baseline to month follow-up ]
   Measuring severity and duration of hallucinations; 20-item questionnaire to be used as a screening instrument to assess hallucinations (6 quantitative and 14 qualitative items); higher scores represent higher severity of symptoms
5. 7-item Auditory Hallucinations Rating Scale (AHRS) [ Time Frame: Change from baseline to day 5 ]
   Measuring severity and duration of hallucinations; severity for each item is rated on a 7-point scale; higher scores represent higher severity of symptoms
6. 7-item Auditory Hallucinations Rating Scale (AHRS) [ Time Frame: Change from baseline to month follow-up ]
   Measuring severity and duration of hallucinations; severity for each item is rated on a 7-point scale; higher scores represent higher severity of symptoms

Secondary Outcome Measures :

1. Auditory Steady state evoked potential [ Time Frame: Change from baseline to day 5 ]
   Measuring the average evoked response potential amplitude change to an auditory stimulus
2. Auditory Steady state evoked potential [ Time Frame: Change from baseline to month follow-up ]
   Measuring the average evoked response potential amplitude change to an auditory stimulus
3. Steady state visual evoked potential [ Time Frame: Change from baseline to day 5 ]
   Measuring the average evoked response potential amplitude change to a visual stimulus
4. Steady state visual evoked potential [ Time Frame: Change from baseline to month follow-up ]
   Measuring the average evoked response potential amplitude change to a visual stimulus
5. Cross Modal Steady state evoked potential [ Time Frame: Change from baseline to day 5 ]
   Measuring the average evoked response potential amplitude change to a combined auditory and visual stimulus
6. Cross Modal Steady state evoked potential [ Time Frame: Change from baseline to month follow-up ]
   Measuring the average evoked response potential amplitude change to a combined auditory and visual stimulus
7. Resting State EEG [ Time Frame: Change from baseline to 5 day ]
   Measuring neural activity at rest and connectivity
8. Resting State EEG [ Time Frame: Change from baseline to month follow-up ]
   Measuring neural activity at rest and connectivity
9. Biological motion [ Time Frame: Change from baseline to 5 day ]
   Measuring the percent correct of detected motion by presenting a simulated walker; difficulty is increased by the level of random noise around stimuli
10. Biological motion [ Time Frame: Change from baseline to month follow-up ]
    Measuring the percent correct of detected motion by presenting a simulated walker; difficulty is increased by the level of random noise around stimuli
11. Neurological Evaluation Scale; Sensory Integration [ Time Frame: Change from baseline to 5 day ]
    Measuring the percent correct of auditory and visual integration; auditory stimuli partners are matched to visual stimuli; difficulty is increased with more complex patterns
12. Neurological Evaluation Scale; Sensory Integration [ Time Frame: Change from baseline to month follow-up ]
    Measuring the percent correct of auditory and visual integration; auditory stimuli partners are matched to visual stimuli; difficulty is increased with more complex patterns
13. Global assessment of function (GAF) [ Time Frame: Change from baseline to day 5 ]
    Measuring global functioning; severity of symptoms related to day-to-day life on a scale of 0 to 100; higher scores represent higher severity of symptoms
14. Global assessment of function (GAF) [ Time Frame: Change from baseline to month follow-up ]
    Measuring global functioning; severity of symptoms related to day-to-day life on a scale of 0 to 100; higher scores represent higher severity of symptoms
15. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Change from baseline to 5 day ]
    Measuring total depression scores; 10 item scale related to depressive episodes (total score 0-60); higher scores represent higher severity of symptoms
16. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Change from baseline to month follow-up ]
    Measuring total depression scores; 10 item scale related to depressive episodes (total score 0-60); higher scores represent higher severity of symptoms
17. Young Mania Rating Scale (YMRS) [ Time Frame: Change from baseline to 5 day ]
    Measuring total Mania scores; 11 items used to access severity of mania (total score 0-60); higher scores represent higher severity of symptoms
18. Young Mania Rating Scale (YMRS) [ Time Frame: Change from baseline to month follow-up ]
    Measuring total Mania scores; 11 items used to access severity of mania (total score 0-60); higher scores represent higher severity of symptoms
19. Brief Assessment of Cognition (BACS) [ Time Frame: Change from baseline to 5 day ]
    Measuring cognition; cognitive domains assessed include memory, working memory, processing speed, executive functions and verbal fluency
20. Brief Assessment of Cognition (BACS) [ Time Frame: Change from baseline to month follow-up ]
    Measuring cognition; cognitive domains assessed include memory, working memory, processing speed, executive functions and verbal fluency
21. Symptom Checklist-90 [ Time Frame: Change from baseline to 5 day ]
    Measuring total psychiatric symptoms; 90 symptoms and evaluates nine symptomatic dimensions; higher scores represent higher severity of symptoms
22. Symptom Checklist-90 [ Time Frame: Change from baseline to month follow-up ]
    Measuring total psychiatric symptoms; 90 symptoms and evaluates nine symptomatic dimensions; higher scores represent higher severity of symptoms

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Aged 18-50 years of age
2. Proficient in English
3. Able to give informed consent
4. Actively experiencing hallucinations (tactile, auditory, visual, etc.)
5. Has not recently participated in tES/TMS treatments

Exclusion Criteria:

1. Substance abuse or dependence (w/in past 6 months)
2. Those who are pregnant/breastfeeding
3. History of head injury with > 15 minutes of loss of consciousness/mal sequelae
4. DSM-V intellectual disability
5. Having a non-removable ferromagnetic metal within the body (particularly in the head)
6. History of seizures

Contacts and Locations

Contacts

Contact: Paulo Lizano, MD, PhD; (617) 754-1227; plizano@bidmc.harvard.edu

Locations

United States, Massachusetts

Beth Israel Deaconess Medical Center; Recruiting

Boston, Massachusetts, United States, 02215

Contact: Paulo Lizano, MD, PhD 617-754-1227 plizano@bidmc.harvard.edu

Sponsors and Collaborators

Beth Israel Deaconess Medical Center

More Information

• Responsible Party: Paulo Lizano, Assistant Professor, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT05165654
• Other Study ID Numbers: 2019P001016X
• First Posted: December 21, 2021
• Last Update Posted: December 21, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Paulo Lizano, Beth Israel Deaconess Medical Center:

Transcranial Electrical Stimulation; Electroencephalography

Additional relevant MeSH terms:

Hallucinations; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases