The ability to exert control over our behavior is fundamental to human cognition, and is impaired in many neuropsychiatric disorders. Here, we show evidence for the neural mechanisms of adaptive control that distinguish healthy people from people who have schizophrenia. We found that the noninvasive electrical stimulation phase aligns low-frequency brain rhythms and enhances functional connectivity. This brain stimulation modulated the temporal structure of low-frequency oscillations and synchrony, improving adaptive control. Moreover, we found that causal changes in the low-frequency oscillations improved behavioral responses to errors and long-range connectivity at the single-trial level. These results implicate theories of executive control and cortical dysconnectivity, and point to the possible development of nonpharmacological treatment alternatives for neuropsychiatric conditions.Abstract
Executive control and flexible adjustment of behavior following errors are essential to adaptive functioning. Loss of adaptive control may be a biomarker of a wide range of neuropsychiatric disorders, particularly in the schizophrenia spectrum. Here, we provide support for the view that oscillatory activity in the frontal cortex underlies adaptive adjustments in cognitive processing following errors. Compared with healthy subjects, patients with schizophrenia exhibited low frequency oscillations with abnormal temporal structure and an absence of synchrony over medial-frontal and lateral-prefrontal cortex following errors. To demonstrate that these abnormal oscillations were the origin of the impaired adaptive control in patients with schizophrenia, we applied noninvasive dc electrical stimulation over the medial-frontal cortex. This noninvasive stimulation descrambled the phase of the low-frequency neural oscillations that synchronize activity across cortical regions. Following stimulation, the behavioral index of adaptive control was improved such that patients were indistinguishable from healthy control subjects. These results provide unique causal evidence for theories of executive control and cortical dysconnectivity in schizophrenia.