Feasibility Electrical Stimulation Study for Visual Hallucinations

• ClinicalTrials.gov Identifier: NCT04870710
• Recruitment Status: Completed
• First Posted: May 3, 2021
• Last Update Posted: December 19, 2022
• Sponsor: Beth Israel Deaconess Medical Center
• Information provided by (Responsible Party): Paulo Lizano, Beth Israel Deaconess Medical Center

Study Description

Brief Summary:

The visual system has increasingly been recognized as an important site of injury in patients with schizophrenia and other psychoses. Visual system alterations manifest as visual perceptual aberrations, deficits in visual processing, and visual hallucinations. These visual symptoms are associated with worse symptoms, poorer outcome and resistance to treatment. A recent study using brain lesion mapping of visual hallucinations and identified a causal location in the part of the brain that processes visual information (visual cortex). The association between visual cortex activation and visual hallucinations suggests that this region could be targeted using noninvasive brain stimulation. Two case studies have found that brain stimulation to the visual cortex improved visual hallucinations in treatment resistant patients with psychosis. While promising it is unclear whether these symptom reductions resulted from activity changes in the visual cortex or not. Here we aim to answer the question whether noninvasive brain stimulation when optimally targeted to the visual cortex can improve brain activity, visual processing and visual hallucinations. The knowledge gained from this study will contribute to the field of vision by providing a marker for clinical response and by personalizing treatment for patients with psychosis suffering from visual symptoms. This grant will allow us to set the foundation for a larger more targeted study utilizing noninvasive brain stimulation to improve visual symptoms in patients with psychosis.

Condition or disease	Intervention/treatment	Phase
Schizophrenia; Schizoaffective Disorder; Bipolar Disorder	Device: transcranial electrical stimulation	Not Applicable

Detailed Description:

The visual system has increasingly been recognized as an important site of pathology in patients with schizophrenia and other psychoses. Visual system impairments manifest as visual perceptual aberrations, deficits in visual processing tasks, and visual hallucinations (VH). In psychosis spectrum disorders, increased visual aberrations are strongly correlated with worse hallucinations and delusions. It is also recognized that poorer performance on visual spatial working memory, visual integration, and velocity discrimination tasks are associated with greater negative symptoms (a major contributor to disability). VH are common in psychotic disorders (30-70% prevalence) and can be refractory to existing treatments. VH have been understudied in psychosis with much of the literature focusing on auditory hallucinations. Despite the neuroscientific and clinical significance of VH, the brain regions responsible are less clear.

Functional neuroimaging studies have identified neural correlates of VH across multiple brain regions (lingual, fusiform, cuneus, lateral geniculate nucleus, and occipital cortex) and support hypotheses that increased visual cortex activity and sensory cortex over-stimulation generate VH. However, whether these neuroimaging findings represented a cause, consequence or incidental correlate of VH was unclear until recently. Using a newly validated technique termed lesion network mapping, researchers demonstrated that focal brain lesions having a causal role in the development of VH can occur in different brain locations, both inside and outside sensory pathways, and that these lesions are functionally connected to the lateral geniculate nucleus, a major relay center for the visual pathway. They also found that 98% of the subcortical and cortical lesions were connected to the exact same location in the extrastriate visual cortex. Therefore, the association between extrastriate visual cortex activation and VH would suggest this region may be optimal for modulation via brain stimulation.

One method by which cortical excitability can be altered is through the use of transcranial electrical stimulation (tES), a non-invasive brain stimulation technique. High definition tES (HD-tES) is a refined version of tES 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. The effects of tES 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) (14,15). Studies have shown that tES can modulate visual cortical function in a polarity-dependent manner, where anodal stimulation can increase and cathodal stimulation can decrease the amplitude of the N70 component from the visual-evoked potential. While tES is a promising adjunctive treatment of auditory hallucinations and negative symptoms in schizophrenia, less is known about its role in treating VH. To date, two cases have been described where cathodal tES (i.e., outward current flow) over the occipital area was applied to patients experiencing treatment refractory VH, and this resulted in symptomatic improvement. Taken together, the recent lesion network mapping identifying the extrastriate visual cortex as a major source of VH in schizophrenia combined with these two single-patient case studies suggest that it may be possible to alleviate VH by designing a tES protocol that targets the extrastriate visual cortex bilaterally. Technological advances in noninvasive neuromodulation and electrical field modeling further allow us to create a tES protocol specifically guided by the results of lesion network mapping studies (i.e., using the exact Montreal Neurological Institute coordinates) with high spatial resolution (i.e., using HD-tES).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Improving Visual Hallucinations by Targeting the Visual Cortex With Electrical Stimulation: A Feasibility Study
• Actual Study Start Date: October 1, 2020
• Actual Primary Completion Date: January 1, 2022
• Actual Study Completion Date: January 2, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: cathodal transcranial direct current stimulation (tDCS); Two, twenty minute sessions of cathodal tDCS to the bilateral extrastriate visual cortex for 5 days (10 total sessions).	Device: transcranial electrical stimulation; Electrical stimulation to the extrastriate visual cortex.
Experimental: Anodal transcranial alternating current stimulation (tACS); Two, twenty minute sessions of anodal tACS delta phase aligned for 5 days (10 total sessions).	Device: transcranial electrical stimulation; Electrical stimulation to the extrastriate visual cortex.

Outcome Measures

Primary Outcome Measures :

1. Steady state visual evoked potential (ssVEP) [ Time Frame: Measured at day 5 compared to day 0 ]
   Measuring the average evoked response potential amplitude change
2. Steady state visual evoked potential (ssVEP) [ Time Frame: Measured at day 30 compared to day 0 and day 5 ]
   Measuring the average evoked response potential amplitude change
3. Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Measured at day 5 compared to day 0 ]
   Measuring total psychosis symptoms score
4. Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Measured at day 30 compared to day 0 and day 5 ]
   Measuring total psychosis symptoms score
5. Biological motion [ Time Frame: Measured at day 5 compared to day 0 ]
   Measuring the percent correct of detected motion
6. Biological motion [ Time Frame: Measured at day 30 compared to day 0 and day 5 ]
   Measuring the percent correct of detected motion

Secondary Outcome Measures :

1. International Affective Picture System (IAPS) task [ Time Frame: Measured at day 5 compared to day 0 ]
   Measuring the average evoked response potential amplitude change
2. International Affective Picture System (IAPS) task [ Time Frame: Measured at day 30 compared to day 0 and day 5 ]
   Measuring the average evoked response potential amplitude change.
3. Velocity Discrimination [ Time Frame: Measured at day 5 compared to day 0 ]
   Measuring the mean velocity threshold
4. Velocity Discrimination [ Time Frame: Measured at day 30 compared to day 0 and day 5 ]
   Measuring the mean velocity threshold
5. Visual spatial working memory [ Time Frame: Measured at day 5 compared to day 0 ]
   Measuring the mean performance score
6. Visual spatial working memory [ Time Frame: Measured at day 30 compared to day 0 and day 5 ]
   Measuring the mean performance score
7. Global assessment of function (GAF) [ Time Frame: Measured at day 5 compared to day 0 ]
   Measuring global functioning
8. Global assessment of function (GAF) [ Time Frame: Measured at day 30 compared to day 0 and day 5 ]
   Measuring global functioning
9. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Measured at day 5 compared to day 0 ]
   Measuring total depression scores
10. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Measured at day 30 compared to day 0 and day 5 ]
    Measuring total depression scores

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• meet diagnostic criteria for schizophrenia, schizoaffective disorder, or psychotic bipolar disorder as verified by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV TR) and consensus clinical diagnosis;
• had no changes to relevant anti-psychotic medications for a period of 1 month prior to participation;
• had a sufficient level of English to allow participation.

Exclusion Criteria:

• pregnant or breastfeeding women;
• Intelligence quotient <60
• any major medical or neurologic
• diagnosis of substance abuse positive urine drug screen
• history of moderate-to-severe visual impairment secondary to glaucoma, cataract or macular degeneration
• serious medical illness or instability requiring hospitalization within the next year
• relevant skin allergies; metallic or electronic implants (e.g. pacemakers, brain stimulators).

Contacts and Locations

Locations

United States, Massachusetts

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

Beth Israel Deaconess Medical Center

Investigators

• Principal Investigator: Paulo Lizano, MD,PhD; Staff Physician/Scientist

More Information

• Responsible Party: Paulo Lizano, Assistant Professor of Psychiatry, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT04870710
• Other Study ID Numbers: 2019P001016
• First Posted: May 3, 2021
• Last Update Posted: December 19, 2022
• Last Verified: December 2022

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

Additional relevant MeSH terms:

Hallucinations; Disease; Schizophrenia; Bipolar Disorder; Psychotic Disorders; Pathologic Processes; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Bipolar and Related Disorders; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases