Non-invasive Brain Stimulation Using Tdcs of the Third (of Many) Visual Pathways

Sensory Contributions to Third Visual Pathway Dysfunction in Schizophrenia: Correlation and Causation

This study investigates the ability of transcranial direct current stimulation (tDCS) applied over the motion processing area of the brain (area MT) to improve face emotion recognition (FER) ability. tDCS is a type of non-invasive brain stimulation in which low level currents are applied over the scalp to influence underlying brain function. In schizophrenia, impaired ability to detect facial motion has been shown to contribute to impaired FER, which, in turn, leads to difficulties in social cognition and poor social outcome. The study will use both fMRI and EEG to measure brain function while participants view moving dot and dynamic face stimuli. Analyses will compare changes in fMRI and EEG activity in individuals receiving active vs. sham stimulation.

The studey involves a randomized, parallel group comparison of personalized, MR-guided, cathodal HD-tDCS vs. sham targeting the middle temporal motion-sensitive region (HCP MMP1.0-atlas area MT+ complex) for the reversal of physiological impairments in Sz related to motion processing and social cognitive dysfunction. RDoC constructs to be tested include face emotion recognition (FER) and Understanding Mental State (UMS), which has also been termed Theory of Mind (ToM) or mentalizing. The overall goals of the study are to determine whether tDCS applied over MT+ can ameliorate 1) motion-processing deficits in Sz and 2) deficits in activation of other TVP regions. Key outcome measures include 1) activation of MT+, pSTS and mSTS regions to motion and dynamic FER stimuli and 2) fractional occupancy (FO) of the CAP state corresponding to the TVP structure. Behavioral outcomes will include scores on motion discrimination, FER to dynamic faces, and TASIT sarcasm (UMS).

Participants will include 120 individuals with Sz and 30 healthy controls (HC). Sz individuals will be evaluated both cross-sectionally and during blinded, randomized active (cathodal) or sham pHD-tDCS targeted to MTC. HC will be evaluated cross-sectionally only. All participants will first undergo baseline assessment (Visit 1) and baseline physiological assessments (Visit 2). Each Sz participant will then be assigned to blinded intervention with either active or sham tDCS and will participate in one ERP (Visit 3) and one fMRI session (Visit 4) involving up to 40-min stimulation each. The two tDCS sessions will be conducted at least 1 week apart and may occur in either order. For each participant, the same randomized treatment (active vs. sham tDCS) will be used in both the ERP and fMRI sessions (Visits 3 and 4). Behavior is obtained during the ERP session (Visit 3). Comparisons will focus on correlations among the fMRI, ERP and behavioral outcome measures within participants as well as the effects of active vs. sham tDCS across participants.

Inclusion Criteria:

1. Male or female subject, age 18-55
2. Competent and willing to sign informed consent
3. No more than moderately ill
4. SCID DSM-5 diagnosis of Sz/SzAff
5. WAIS IQ >70
6. Does not meet current criteria for DSM-5 defined substance abuse or dependence or have a history of diagnosis within past 6 months
7. On medication within clinically approved range
8. Does not meet criteria for another DSM-5 disorder other than those judged to be minor (e.g. simple phobia)

Exclusion Criteria:

1. Significant neurological illness or history of significant head trauma
2. Unstable physical illness or significant auditory/visual deficits that might interfer
3. Contraindication to MRI (e.g. metal implants, claustrophobia, pregnancy)
4. Contraindications to tDCS including metal implant, pacemaker, history of seizure, traumatic brain injury or stroke
5. Significant risk for suicide
6. Has a history of an illness, disease, condition injury, or disability which, in the opinion of the principal investigator, may interfere with the completion of all study requirements per protocol, impact the quality of the data, or the validity of the study results, including unstable physical illness, significant neurological illness, significant head trauma
7. Moderate or greater DSM-5 current substance use disorder, defined based on the presence of 4 or more of 11 substance use criteria within the past 12 months. In addition, individuals for whom substance use leads to not being able to perform work, home or school activities