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 how it changes cognition. In particular, the challenge of how learning, or training, in one domain generalizes to unlearned or unpracticed domains has long been a focus of educational psychology. TDCS may have a critical role to play in generalization, previous studies have found: (i) Right prefrontal anodal tDCS with concurrent cognitive training enhances generalization of training in healthy controls that endures as much as 3-months later, (ii) Left prefrontal tDCS with concurrent cognitive training enhanced generalization of training in patients with schizophrenia compared to sham. Understanding how tDCS affects brain circuitry is critical to the design and application of effective interventions, especially if the effects are different for healthy vs. psychiatric populations. The premise of this proposal is that improvements in thalamocortical FC are associated with the generalization of cognitive training, and tDCS facilitates these improvements. The overarching goal of this proposal is to deploy neuroimaging and cognitive testing to understand how tDCS with cognitive training affects thalamocortical circuitry in individuals with and without psychopathology. Study 1 will compare right frontal, left frontal and sham tDCS during concurrent cognitive training over 10 weeks in 75 healthy controls (HC). Study 2 will be similar in all respects but will examine 75 patients with schizophrenia and include clinical assessments. Measures of learning rate, generalization and durability will be collected at regular intervals during the intervention period, including a mid-training scanning session and a 12-week follow-up assessment. These two studies will allow us to address the following specific aims: SA1. Compare the effect of right active-tDCS, left active-tDCS and sham (hemisphere), length of treatment and measured dosage on brain circuitry. In both HC and SZ, greater ipsilateral thalamocortical (prefrontal) FC increases are driven by H1.1 active tDCS in the ipsilateral hemisphere; H1.2 a longer length of treatment; and H1.3 higher modeled dosage. SA2. Establish the effects of hemisphere, length of treatment and modeled dosage on generalization and durability. In both HC and SZ, greater generalization and durability are driven H2.1 more by right tDCS compared to left tDCS or sham; H2.2 by a longer length of treatment; and H2.3 by higher modeled dosage. SA3. Examine how changes in thalamocortical FC in both hemispheres affect generalization and durability. In both HC and SZ, greater thalamocortical FC drives H3.1 greater generalization; and H3.2 greater durability. Impact. We propose the first experiments to examine tDCS-augmented cognitive training effects on brain circuitry and generalization in both health and psychosis, providing crucial information about location of stimulation, length of treatment, modeled dosage, trajectory and durability needed to guide future research and interventions for cognitive impairments.