Synchronizing theta oscillations with direct-current stimulation strengthens adaptive control in the human brain

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 medialfrontal 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.oscillations | neural synchrony | adaptive control | schizophrenia | transcranial direct current stimulation N etworks involving frontal cortex allow us to adapt our actions to dynamic environments and adjust information processing following errors (1). This adaptive control is a hallmark of healthy goal-directed behavior, but it is dysfunctional in a variety of psychiatric and neurological disorders (2-4). In particular, the adaptive-control deficits that are a central feature of schizophrenia are highly predictive of poor functioning in daily life (5). In the laboratory, a canonical signature of adaptive control is the magnitude of posterror slowing of reaction time (RT), in which healthy subjects respond more slowly after making an error (6, 7). Patients with schizophrenia show an impaired ability to slow down their responses after errors (4, 8-13, but also 14, 15), providing a laboratory index that captures the rigid, perseverative, and maladaptive behavior that is characteristic of the disorder (8, 16).Adaptive control in the healthy brain is hypothesized to depend partly on the low-frequency EEG oscillations measured over medial-frontal cortex. The low-frequency oscillations are thought to reflect coordinated activity across the diverse set of brain areas recruited to perform a task (1,(17)(18)(19)(20)(21)(22). In addition, medial-frontal theta (4-8 Hz) oscillations appear to signal the need for adaptive control across a variety of tasks and situations. Situations that call for adaptive control include stimulus novelty, response conflict, negative feedback, and behavioral errors, with all of these situations sharing a common medial-frontal spectral signature in the theta band (21). However, the functional significance of medial-frontal theta may be much broader than simply ...

Stimulating cognition in schizophrenia: A controlled pilot study of the effects of prefrontal transcranial direct current stimulation upon memory and learning

“…Interestingly, in schizophrenia a delayed improvement in WM has been observed after online stimulation, [33,34]; wherein the effects of anodal tDCS to the left MFG improved performance after consolidation of 20 and 40 minutes [33,34]; whereas immediate effects were observed on a top-signal task investigating executive control [35,36]. However, to date no work has investigated the effects of online tDCS on the brain's neurophysiological response in individuals with schizophrenia.…”

“…In this study, we examined the effects of tDCS on two tasks, a previously trained WM and a novel EF task, and the related brain response in schizophrenia using fMRI; we hypothesized that the online administration of tDCS will only impact EF performance, and not impact the immediate behavioral performance on a WM task, as earlier studies have noted differential improvements in these domains [34,36]. However, we anticipated increased activation beneath the anode during WM and EF in the real tDCS group; in the former task activation change would correlate with task performance after consolidation [37,38].…”

Rectifying disordered brain dynamics to improve cognition in schizophrenia

“…Impaired cognition is largely unresponsive to antipsychotic treatment, and despite a very significant investment by the pharmaceutical industry for over a decade, no proven pharmacological treatments have been found for this disabling aspect of the illness. The study by Reinhart et al (2) in PNAS takes a cognitive neuroscience approach to pursue an entirely new avenue for the treatment of impaired cognition and associated functional disability in schizophrenia.…”

“…As one aspect of their cognitive control deficit, individuals with schizophrenia show impaired dynamic control as indexed by reduced error and conflict-related activity in the medial PFC during errors, along with altered behavioral adjustments in some but not all studies (6). Reinhart et al (2) apply very low doses of electric current to the scalp in the region overlying the medial PFC to test the hypothesis that they can enhance the function of the adaptive control system in the brain in patients with schizophrenia, predicting that the effects will be mediated by increased theta synchrony measured using EEG (Fig. 1).…”

“…Instead, neural activity can be modulated using noninvasive stimulation, including the more established repetitive transcranial magnetic stimulation technique, as well as the more recently and increasingly widely implemented transcranial direct current stimulation (tDCS)-based approach used in the present study (2). What distinguishes this study, and hopefully future ones that follow, is that the functional neural circuit being targeted has been extensively characterized in healthy subjects and a substantial body of evidence has suggested that reductions in its activity were associated with impaired dynamic control in schizophrenia.…”