Clinical trial NCT05165654: Improving Hallucinations by Targeting the RSTS with TES
Official title: Improving Hallucinations by Targeting the Right Superior Temporal Sulcus with Electrical Stimulation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hallucinations, Auditory
Psychosis
Keywords: Transcranial Electrical Stimulation
Electroencephalography
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
First posted: 2021-12-21
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Positive and Negative Syndrome Scale (PANSS)
timeFrame: Change from baseline to day 5
measure: Positive and Negative Syndrome Scale (PANSS)
timeFrame: Change from baseline to month follow-up
measure: University of Miami Parkinson's Disease Hallucinations Questionnaire (UM-PDHQ)
timeFrame: Change from baseline to day 5
measure: University of Miami Parkinson's Disease Hallucinations Questionnaire (UM-PDHQ)
timeFrame: Change from baseline to month follow-up
measure: 7-item Auditory Hallucinations Rating Scale (AHRS)
timeFrame: Change from baseline to day 5
measure: 7-item Auditory Hallucinations Rating Scale (AHRS)
timeFrame: Change from baseline to month follow-up
Secondary outcomes:
measure: Auditory Steady state evoked potential
timeFrame: Change from baseline to day 5
measure: Auditory Steady state evoked potential
timeFrame: Change from baseline to month follow-up
measure: Steady state visual evoked potential
timeFrame: Change from baseline to day 5
measure: Steady state visual evoked potential
timeFrame: Change from baseline to month follow-up
measure: Cross Modal Steady state evoked potential
timeFrame: Change from baseline to day 5
measure: Cross Modal Steady state evoked potential
timeFrame: Change from baseline to month follow-up
measure: Resting State EEG
timeFrame: Change from baseline to 5 day
measure: Resting State EEG
timeFrame: Change from baseline to month follow-up
measure: Biological motion
timeFrame: Change from baseline to 5 day
measure: Biological motion
timeFrame: Change from baseline to month follow-up
measure: Neurological Evaluation Scale; Sensory Integration
timeFrame: Change from baseline to 5 day
measure: Neurological Evaluation Scale; Sensory Integration
timeFrame: Change from baseline to month follow-up
measure: Global assessment of function (GAF)
timeFrame: Change from baseline to day 5
measure: Global assessment of function (GAF)
timeFrame: Change from baseline to month follow-up
measure: Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Change from baseline to 5 day
measure: Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Change from baseline to month follow-up
measure: Young Mania Rating Scale (YMRS)
timeFrame: Change from baseline to 5 day
measure: Young Mania Rating Scale (YMRS)
timeFrame: Change from baseline to month follow-up
measure: Brief Assessment of Cognition (BACS)
timeFrame: Change from baseline to 5 day
measure: Brief Assessment of Cognition (BACS)
timeFrame: Change from baseline to month follow-up
measure: Symptom Checklist-90
timeFrame: Change from baseline to 5 day
measure: Symptom Checklist-90
timeFrame: Change from baseline to month follow-up
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Paulo Lizano, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: