Maximizing the Impact of Neuroplasticity Using Transcranial Electrical Stimulation Study 2

Increased Thalamocortical Connectivity in Tdcs-potentiated Generalization of Cognitive Training

Non-invasive neuromodulation, such as transcranial direct current stimulation ( tDCS) , is emerging as an important therapeutic tool with documented effects on brain circuitry, yet little is understood about h ow it changes cognition. In particular, tDCS may have a critical role to play in generalization, that is how training in one domain generalizes to unlearned or unpracticed domains. This problem has resonance for disorders with cognitive deficits, such as schizophrenia.

Understanding how tDCS affects brain circuity is critical to the design and application of effective interventions, especially if the effects are different for healthy vs. psychiatric populations. In previous research, one clue to the mechanism underlying increased learning and generalization with tDCS was provided by neuroimaging data from subjects with schizophrenia undergoing cognitive training where increases in thalamocortical (prefrontal) functional connectivity (FC) predicted greater generalization.

The premise of this proposal is that increases in thalamocortical FC are associated with the generalization of cognitive training, and tDCS facilitates these increases. The overarching goals of this proposal are to deploy neuroimaging and cognitive testing to understand how tDCS with cognitive training affect thalamocortical circuitry in individuals with and without psychosis and to examine variability in response within both groups.

Study 1(NCT03896425) will compare right prefrontal, left prefrontal and sham tDCS during concurrent cognitive training over 12 weeks in 90 healthy controls. Study 2 will be similar in all aspects but will examine 90 patients with schizophrenia or schizoaffective disorder and include clinical assessments. Results of the study will provide crucial information about location of stimulation, length of treatment, modeled dosage, trajectory and durability needed to guide future research and interventions for cognitive impairments.

Inclusion Criteria:

1. Ability to provide consent and comply with study procedures.
2. Age 18 - 60 years old.
3. Estimated IQ range within the range: 70 ≤ IQ ≤ 115.
4. Schizophrenia or schizoaffective disorder as assessed by the MINI (Mini International Neuropsychiatric Interview)(Sheehan et al., 1998).
5. Not having a current addictive disorder as measured by MINI (Mini International Neuropsychiatric Interview), or a sleep disorder.
6. Ability to participate in three weekly 45' training sessions over 12 weeks and participate in four assessments.
7. Clinically stable and on stable medications for at least one month before start of study.

Exclusion Criteria:

1. Any medical condition or treatment with neurological sequelae (e.g. stroke, tumor, loss of consciousness > 30 min, HIV).
2. Contraindications for tDCS or MRI scanning (tDCS contraindication: history of seizures; MRI contraindications: The research team will utilize the CMRR Center's screening tools and adhere to the screening SOP during enrollment of all research participants in this protocol. The CMRR Center's screening tools and SOP are IRB approved under the CMRR Center Grant (HSC# 1406M51205) and information regarding screening procedures is publicly available on the CMRR website (CMRR Policies / Procedures).