Disruption and rescue of interareal theta phase coupling and adaptive behavior

Rescuing executive functions in people with neurological and neuropsychiatric disorders has been a major goal of psychology and neuroscience for decades. Innovative computer-training regimes for executive functions have made tremendous inroads, yet the positive effects of training have not always translated into improved cognitive functioning and often take many days to emerge. In the present study, we asked whether it was possible to immediately change components of executive function by directly manipulating neural activity using a stimulation technology called high-definition transcranial alternating current stimulation (HD-tACS). Twenty minutes of inphase stimulation over medial frontal cortex (MFC) and right lateral prefrontal cortex (lPFC) synchronized theta (∼6 Hz) rhythms between these regions in a frequency and spatially specific manner and rapidly improved adaptive behavior with effects lasting longer than 40 min. In contrast, antiphase stimulation in the same individuals desynchronized MFC-lPFC theta phase coupling and impaired adaptive behavior. Surprisingly, the exogenously driven impairments in performance could be instantly rescued by reversing the phase angle of alternating current. The results suggest executive functions can be rapidly up- or down-regulated by modulating theta phase coupling of distant frontal cortical areas and can contribute to the development of tools for potentially normalizing executive dysfunction in patient populations.