Clinical trial NCT04870710: Feasibility Electrical Stimulation Study for Visual Hallucinations
Official title: Improving Visual Hallucinations by Targeting the Visual Cortex With Electrical Stimulation: A Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Schizoaffective Disorder
Bipolar Disorder
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: National Center for Advancing Translational Sciences (NCATS)
First posted: 2021-05-03
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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).

Eligibility 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).

Primary outcomes:
measure: Steady State Visual Evoked Potential (ssVEP)
timeFrame: Measured at day 5 compared to day 0
measure: Steady State Visual Evoked Potential (ssVEP)
timeFrame: Measured at day 30 compared to day 0 and day 5
measure: Positive and Negative Syndrome Scale (PANSS)
timeFrame: Measured at day 5 compared to day 0
measure: Positive and Negative Syndrome Scale (PANSS)
timeFrame: Measured at day 30 compared to day 0 and day 5
measure: Biological Motion
timeFrame: Measured at day 5 compared to day 0
measure: Biological Motion
timeFrame: Measured at day 30 compared to day 0 and day 5
Secondary outcomes:
measure: International Affective Picture System (IAPS) Task
timeFrame: Measured at day 5 compared to day 0
measure: International Affective Picture System (IAPS) Task
timeFrame: Measured at day 30 compared to day 0 and day 5
measure: Velocity Discrimination
timeFrame: Measured at day 5 compared to day 0
measure: Velocity Discrimination
timeFrame: Measured at day 30 compared to day 0 and day 5
measure: Visual Spatial Working Memory
timeFrame: Measured at day 5 compared to day 0
measure: Visual Spatial Working Memory
timeFrame: Measured at day 30 compared to day 0 and day 5
measure: Global Assessment of Function (GAF)
timeFrame: Measured at day 5 compared to day 0
measure: Global Assessment of Function (GAF)
timeFrame: Measured at day 30 compared to day 0 and day 5
measure: Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Measured at day 5 compared to day 0
measure: Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Measured at day 30 compared to day 0 and day 5
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Staff Physician/Scientist
name: Paulo Lizano, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: