Improving Visual Hallucinations by Targeting the Visual Cortex With Electrical Stimulation: A Feasibility Study
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Schizophrenia
- Sponsor
- Beth Israel Deaconess Medical Center
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Positive and Negative Syndrome Scale (PANSS)
- Status
- Completed
- Last Updated
- 10 months ago
Overview
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).
Investigators
Paulo Lizano
Assistant Professor of Psychiatry
Beth Israel Deaconess Medical Center
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).
Outcomes
Primary Outcomes
Positive and Negative Syndrome Scale (PANSS)
Time Frame: Measured at day 30 compared to day 0 and day 5
Measuring total psychosis symptoms score. PANSS is a clinician administered instrument which has 30 items measuring a range of symptoms which are rated on a 7-point scale (1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate severe, 6=severe, and 7=extreme). A total score ranges from 30-210 with higher scores indicate worsen symptoms. Subscales include, general, negative and positive symptom categories with higher scores indicate worsen symptoms. The range for the positive and negative Scales is 7-49, and the range for the general Psychopathology Scale is 16-112.
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 for P100 at Baseline, 5 day and 1 month visits. ssVEP was utilized to measure changes in electrical biomarkers of the early visual response. Stimuli consisted of 50 trials of a black and white square oscillating at 18.75 Hz in the subject's central, bilateral, left, or right visual field for 2000 ms (200 total trials pseudorandomly interleaved) with inter-trial intervals of 2.5 seconds.
Biological Motion
Time Frame: Measured at day 30 compared to day 0 and day 5
Measuring the percent correct of detected motion. Biological motion perception was assessed using point-light animations (12 dots on the head and major joints of the body) walking either rightward or leftward. The target animation was embedded in a number of random-moving noise dots (24, 48, or 72) to manipulate the difficulty level of the task. Participants were asked to indicate the direction that the animation was walking towards. The task lasted for about 4 minutes.
Secondary Outcomes
- Visual Spatial Working Memory(Measured at day 30 compared to day 0 and day 5)
- Velocity Discrimination(Measured at day 30 compared to day 0 and day 5)
- Montgomery-Asberg Depression Rating Scale (MADRS)(Measured at day 30 compared to day 0 and day 5)
- International Affective Picture System (IAPS) Task(Measured at day 30 compared to day 0 and day 5)
- Global Assessment of Function (GAF)(Measured at day 30 compared to day 0 and day 5)