Improving Hallucinations by Targeting the rSTS With tES

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.

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.

10 passive sham control; Two, twenty-minute sessions of passive sham control to the rSTS for a 30 second ramped up and down at the beginning and end of the 20 min period for 5 days (10 total sessions).

Measuring total psychosis symptoms score (Total score minimum = 30, maximum = 210); General symptoms (minimum score = 16, maximum score = 112); Negative Symptoms (minimum score = 16, maximum score = 112); and Positive Symptoms (minimum score = 16, maximum score = 112); higher scores represent higher severity of symptoms

Measuring total psychosis symptoms score (Total score minimum = 30, maximum = 210); General symptoms (minimum score = 16, maximum score = 112); Negative Symptoms (minimum score = 16, maximum score = 112); and Positive Symptoms (minimum score = 16, maximum score = 112); higher scores represent higher severity of symptoms

Measuring severity and duration of hallucinations; 20-item questionnaire to be used as a screening instrument to assess hallucinations (6 quantitative and 14 qualitative items); higher scores represent higher severity of symptoms

Measuring severity and duration of hallucinations; 20-item questionnaire to be used as a screening instrument to assess hallucinations (6 quantitative and 14 qualitative items); higher scores represent higher severity of symptoms

Measuring severity and duration of hallucinations; severity for each item is rated on a 7-point scale; higher scores represent higher severity of symptoms

Measuring severity and duration of hallucinations; severity for each item is rated on a 7-point scale; higher scores represent higher severity of symptoms

Measuring the average evoked response potential amplitude change to a combined auditory and visual stimulus

Measuring the average evoked response potential amplitude change to a combined auditory and visual stimulus

Measuring the percent correct of detected motion by presenting a simulated walker; difficulty is increased by the level of random noise around stimuli

Measuring the percent correct of detected motion by presenting a simulated walker; difficulty is increased by the level of random noise around stimuli

Measuring the percent correct of auditory and visual integration; auditory stimuli partners are matched to visual stimuli; difficulty is increased with more complex patterns

Measuring the percent correct of auditory and visual integration; auditory stimuli partners are matched to visual stimuli; difficulty is increased with more complex patterns

Measuring global functioning; severity of symptoms related to day-to-day life on a scale of 0 to 100; higher scores represent higher severity of symptoms

Measuring global functioning; severity of symptoms related to day-to-day life on a scale of 0 to 100; higher scores represent higher severity of symptoms

Measuring total depression scores; 10 item scale related to depressive episodes (total score 0-60); higher scores represent higher severity of symptoms

Measuring total depression scores; 10 item scale related to depressive episodes (total score 0-60); higher scores represent higher severity of symptoms

Measuring total Mania scores; 11 items used to access severity of mania (total score 0-60); higher scores represent higher severity of symptoms

Measuring total Mania scores; 11 items used to access severity of mania (total score 0-60); higher scores represent higher severity of symptoms

Measuring cognition; cognitive domains assessed include memory, working memory, processing speed, executive functions and verbal fluency

Measuring cognition; cognitive domains assessed include memory, working memory, processing speed, executive functions and verbal fluency

Measuring total psychiatric symptoms; 90 symptoms and evaluates nine symptomatic dimensions; higher scores represent higher severity of symptoms

Measuring total psychiatric symptoms; 90 symptoms and evaluates nine symptomatic dimensions; higher scores represent higher severity of symptoms

Inclusion Criteria: Aged 18-50 years of age Proficient in English Able to give informed consent Actively experiencing hallucinations (tactile, auditory, visual, etc.) Has not recently participated in tES/TMS treatments Exclusion Criteria: Substance abuse or dependence (w/in past 6 months) Those who are pregnant/breastfeeding History of head injury with > 15 minutes of loss of consciousness/mal sequelae DSM-V intellectual disability Having a non-removable ferromagnetic metal within the body (particularly in the head) History of seizures