Feasibility Electrical Stimulation Study for Visual Hallucinations
Condition: Schizophrenia; Schizoaffective Disorder; Bipolar Disorder
MeSH terms: Hallucinations; Schizophrenia; Bipolar Disorder; Psychotic Disorders
Study type: Interventional

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).
    

Intervention name(s): transcranial electrical stimulation
Intervention type(s): Device
Intervention description(s): Electrical stimulation to the extrastriate visual cortex.
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment