The Dynamic Duo: Combining noninvasive brain stimulation with cognitive interventions

Pharmacotherapy, psychotherapy, and non-invasive brain stimulation (NIBS)(1) each show efficacy in the treat-ment of psychiatric disorders; however, more efficacious interventions are needed as reflected by an overall unmet need in mental health care. While each modality has typically been studied and developed as a mono-therapy, in practice they are typically used in combination. Research has begun to emerge studying the potential synergistic actions of multi-modal, combination therapies. For example, NIBS combined with rehabilitation strategies have demonstrated some success for speech and motor rehabilitation in stroke patients. In this review we present evidence suggesting that combining NIBS with targeted, cognitive interventions offers a potentially powerful new approach to treating neuropsychiatric disorders. Here we focus on NIBS studies using transcranial direct current stimulation (tDCS)(2)` and transcranial magnetic stimulation (TMS)(3) given that these modalities are relatively safe, noninvasive, and can be performed simultaneously with neurocognitive interventions. We review the concept of "state dependent" effects of NIBS and highlight how simultaneous or sequential cognitive in-terventions could help optimize NIBS therapy by providing further control of ongoing neural activity in targeted neural networks. This review spans a range of neuropsychiatric disorders including major depressive disorder, schizophrenia, generalized anxiety, and autism. For each disorder, we emphasize neuroanatomical circuitry that could be engaged with combination therapy and critically discuss the literature that has begun to emerge. Finally, we present possible underlying mechanisms and propose future research strategies that may further refine the potential of combination therapies.