Electric and magnetic stimulation of the human brain can be used to excite or inhibit neurons. Numerous methods have been designed over the years for this purpose with various advantages and disadvantages that are the topic of this review. Deep brain stimulation (DBS) is the most direct and focal application of electric impulses to brain tissue. Electrodes are placed in the brain in order to modulate neural activity and to correct parameters of pathological oscillation in brain circuits such as their amplitude or frequency. Transcranial magnetic stimulation (TMS) is a non-invasive alternative with the stimulator generating a magnetic field in a coil over the scalp that induces an electric field in the brain which, in turn, interacts with ongoing brain activity. Depending upon stimulation parameters, excitation and inhibition can be achieved. Transcranial electric stimulation (tES) applies electric fields to the scalp that spread along the skull in order to reach the brain, thus, limiting current strength to avoid skin sensations and cranial muscle pain. Therefore, tES can only modulate brain activity and is considered subthreshold, i.e., it does not directly elicit neuronal action potentials. In this review, we collect hints for neuroplastic changes such as modulation of behavior, the electric activity of the brain, or the evolution of clinical signs and symptoms in response to stimulation. Possible mechanisms are discussed, and future paradigms are suggested.

Adaptive control has been studied in Parkinson’s disease mainly in the context of proactive control and with mixed results. We compared reactive- and proactive control in 30 participants with Parkinson’s disease to 30 age matched healthy control participants. The electroencephalographic activity of the participants was recorded over 128 channels while they performed a numerical Stroop task, in which we controlled for confounding stimulus-response learning. We assessed effects of reactive- and proactive control on reaction time-, accuracy- and electroencephalographic time-frequency data. Behavioural results show distinct impairments of proactive- and reactive control in participants with Parkinson’s disease, when tested on their usual medication. Compared to healthy control participants, participants with Parkinson’s disease were impaired in their ability to adapt cognitive control proactively and were less effective to resolve conflict using reactive control. Successful reactive and proactive control in the healthy control group was accompanied by a reduced conflict effect between congruent and incongruent items in midline-frontal theta power. Our findings provide evidence for a general impairment of proactive control in Parkinson’s disease and highlight the importance of controlling for the effects of S-R learning when studying adaptive control. Evidence concerning reactive control was inconclusive, but we found that participants with Parkinson’s disease were less effective than healthy control participants in resolving conflict during the reactive control task.

High-frequency deep brain stimulation of the subthalamic nucleus is used to treat motor symptoms in patients with Parkinson’s disease. There is evidence that low-frequency stimulation in the range of 4–10 Hz may improve cognitive functions. This study investigates whether low-frequency deep brain stimulation of the subthalamic nucleus in the beta band (20 Hz) frequency can improve response inhibition in patients with Parkinson’s disease. In a double-blind crossover design, N = 17 participants with Parkinson’s disease performed four neuropsychological experiments, while on their usual dopaminergic medication, under no, standard high-frequency and 20 Hz beta low-frequency deep brain stimulation. The experiments consisted of a response selection task (response execution), a flanker task (conflict monitoring), a Go-NoGo task (automatic inhibition) and a stop-change task (controlled inhibition). Reaction time and response accuracy were analysed using Bayesian mixed-effect models. Participants responded [m = 33.6 ms, Bayes factor (BF) = 129.6] slower and [m = 6.0%, BF > 1000] more accurately under low-frequency than high-frequency stimulation but not under no stimulation during the response selection task. In the flanker task, participants responded slower under low-frequency than high-frequency stimulation [m = 77.0 ms, BF > 1000] but not under no stimulation [m = 18.3 ms, BF = 0.1]. We found no performance differences by the stimulation condition of the congruency effect. In the Go-NoGo task, we found low-frequency stimulation slowed responses on uncertain Go trials compared to no stimulation [m = 136.8 ms, BF = 30.3] and high-frequency stimulation [m = 105.2 ms, BF = 2.5]. Additionally, participants committed fewer errors under low-frequency stimulation than under no and high-frequency stimulation, suggesting that 20 Hz subthalamic nucleus stimulation may improve automatic inhibition. Lastly, in the stop-change task, we found no performance modulation by low-frequency stimulation compared to no and high-frequency stimulation. Our results show that low-frequency beta stimulation may improve aspects of automatic response inhibition in patients with Parkinson’s disease.

The dual mechanisms of control (DMC) framework distinguishes between proactive (anticipatory) and reactive (post-conflict) adaptive cognitive control mechanisms. Evidence for proactive deficits in Parkinsons disease (PD) is inconsistent, and the neurophysiological underpinnings remain poorly understood. We investigated adaptive control in 30 PD patients and 30 demographically similar healthy controls. Adaptive cognitive control was tested using a numerical Stroop test that included manipulations sensitive to proactive and reactive control. In both behavioral and EEG analyses, inducer items that trigger control adaptation were distinguished from diagnostic items, allowing adaptation to be assessed independently of learning effects. Event-related potentials (ERPs) derived from electroencephalography (EEG) captured signatures of proactive (N450) and reactive (Late Positive Complex, LPC) control. The HC group showed robust proactive control with faster responses compared to reaction times to reactive control condition, whereas PD revealed reduced proactive control, particularly for diagnostic items. ERP analysis indicated a clear N450 in the HC group, whereas the N450 was absent in the PD group. Both groups displayed LPC activity during reactive control, but PD also showed LPC activity in the adaptive proactive control condition, suggesting compensatory reliance on reactive mechanisms. Both, behavioural and ERP analyses provide insights into the dissociation of reactive and proactive control processes in PD. Our findings indicate selective impairments in proactive control, along with preserved reactive control, in patients with PD. Moreover, the presence of the LPC during proactive control trials suggests that the recruitment of reactive control mechanisms may compensate deficits in proactive control in PD.

Adaptive control has been studied in Parkinson’s disease (PD) mainly in the context of proactive control and with mixed results. We compared reactive- and proactive control in 30 participants with Parkinson’s disease (PD) to 30 age matched healthy control participants (HC). The electroencephalographic (EEG) activity of the participants was recorded over 128 channels while they performed a numerical Stroop task, in which we controlled for confounding stimulus-response learning. We assessed effects of reactive- and proactive control on reaction time-, accuracy- and EEG time-frequency data. Behavioral results show distinct impairments of proactive-reactive control in participants with PD, when tested on their usual medication. Participants with PD were unable to adapt cognitive control proactively and were less effective to resolve conflict using reactive control. Successful reactive and proactive control in the HC group was accompanied by a reduced conflict effect between congruent and incongruent items in midline-frontal theta power. Our findings provide evidence for a general impairment of proactive control in PD and suggest that the same may be the case for reactive control.