Dopaminergic therapy in Parkinson's disease decreases cortical beta band coherence in the resting state and increases cortical beta band power during executive control.

It is not yet well understood how dopaminergic therapy improves cognitive and motor function in Parkinson's disease (PD). One possibility is that it reduces the pathological synchronization within and between the cortex and basal ganglia, thus improving neural communication. We tested this hypothesis by recording scalp electroencephalography (EEG) in PD patients when On and Off medication, during a brief resting state epoch (no task), and during performance of a stop signal task that is thought to engage two partially overlapping (or different) frontal-basal-ganglia circuits. For resting state EEG, we measured pair-wise coherence between scalp electrodes in several frequency bands. Consistent with previous studies, in the Off medication state, those patients with the greatest clinical impairment had the strongest coherence, especially in the beta band, indicating pathological over-synchronization. Dopaminergic medication reduced this coherence. For the stop signal task, On vs. Off medication increased beta band power over right frontal cortex for successful stopping and over bilateral sensorimotor cortex for going, especially for those patients who showed greater clinical improvement. Thus, medication reduced pathological coherence in beta band at rest and increased task related beta power for two potentially dissociable cortico-basal ganglia circuits. These results support the hypothesis that dopaminergic medication in PD improves neural communication both at rest and for executive and motor function.

The role of the right presupplementary motor area in stopping action: two studies with event-related transcranial magnetic stimulation.

Rapidly stopping action engages a network in the brain including the right presupplementary motor area (preSMA), the right inferior frontal gyrus, and the basal ganglia. Yet the functional role of these different regions within the overall network still remains unclear. Here we focused on the role of the right preSMA in behavioral stopping. We hypothesized that the underlying neurocognitive function of this region is one or more of setting up a stopping rule in advance, modulating response tendencies (e.g., slowing down in anticipation of stopping), and implementing stopping when the stop signal occurs. We performed two experiments with magnetic resonance imaging (MRI)-guided, event-related, transcranial magnetic stimulation(TMS), during the performance of variants of the stop signal task. In experiment 1 we show that stimulation of the right preSMA versus vertex (control site) slowed the implementation of stopping (measured via stop signal reaction time) but had no influence on modulation of response tendencies. In experiment 2, we showed that stimulation of the right preSMA slowed implementation of stopping in a mechanistically selective form of stopping but had no influence on setting up stopping rules. The results go beyond the replication of prior findings by showing that TMS of the right preSMA impairs stopping behavior (including a behaviorally selective form of stopping) through a specific disruption of the implementation of stopping. Future studies are required to establish whether this was due to stimulation of the right preSMA itself or because of remote effects on the wider stopping network.

Transcranial magnetic stimulation reveals dissociable mechanisms for global versus selective corticomotor suppression underlying the stopping of action.

Stopping an initiated response is an essential function, investigated in many studies with go/no-go and stop-signal paradigms. These standard tests require rapid action cancellation. This appears to be achieved by a suppression mechanism that has "global" effects on corticomotor excitability (i.e., affecting task-irrelevant muscles). By contrast, stopping action in everyday life may require selectivity (i.e., targeting a specific response tendency without affecting concurrent action). We hypothesized that while standard stopping engages global suppression, behaviorally selective stopping engages a selective suppression mechanism. Accordingly, we measured corticomotor excitability of the task-irrelevant leg using transcranial magnetic stimulation while subjects stopped the hand. Experiment 1 showed that for standard (i.e., nonselective) stopping, the task-irrelevant leg was suppressed. Experiment 2 showed that for behaviorally selective stopping, there was no mean leg suppression. Experiment 3 directly compared behaviorally nonselective and selective stopping. Leg suppression occurred only in the behaviorally nonselective condition. These results argue that global and selective suppression mechanisms are dissociable. Participants may use a global suppression mechanism when speed is stressed; however, they may recruit a more selective suppression mechanism when selective stopping is behaviorally necessary and preparatory information is available. We predict that different fronto-basal-ganglia pathways underpin these different suppression mechanisms.

Stimulating deep cortical structures with the batwing coil: how to determine the intensity for transcranial magnetic stimulation using coil-cortex distance.

Transcranial magnetic stimulation (TMS) is increasingly used in cognitive neuroscience to probe non-motor cortical regions. A key question for such studies is the choice of stimulation intensity. Early studies used a simple metric such as 115% of motor threshold (MT) for non-motor regions; where MT is the stimulation intensity required to elicit a particular amplitude of motor evoked potential or visible muscle twitch when the coil is placed over primary motor cortex. Recently, however, it was demonstrated that this simple metric for stimulation of non-motor regions is inadequate - it could lead to over or under-stimulation depending on the distance between the coil and the cortex. Instead, a method was developed to scale the motor threshold based on coil-cortex distance, at least for standard figure-of-eight stimulating coils. Here we validate the same method for a 'batwing coil', which is designed to stimulate deeper cortical structures such as the medial frontal cortex. We modulated coil-cortex distance within-participant by inserting spacers of different thickness between coil and scalp. We then measured MT at each spacer. We show that for every millimeter between coil and scalp an additional 1.4% of TMS output is required to induce an equivalent level of brain stimulation at the motor cortex. Using this parameter we describe a linear function to adjust MT for future studies of non-motor regions-of-interest using the batwing coil. This is the first study to demonstrate the effects of coil-cortical distance on stimulation efficiency via a monophasic system using a batwing coil.

Roles for the pre-supplementary motor area and the right inferior frontal gyrus in stopping action: electrophysiological responses and functional and structural connectivity.

Both the pre-supplementary motor area (preSMA) and the right inferior frontal gyrus (rIFG) are important for stopping action outright. These regions are also engaged when preparing to stop. We aimed to elucidate the roles of these regions by harnessing the high spatio-temporal resolution of electrocorticography (ECoG), and by using a task that engages both preparing to stop and stopping outright. First, we validated the task using fMRI in 16 healthy control participants to confirm that both the preSMA and the rIFG were active. Next, we studied a rare patient with intracranial grid coverage of both these regions, using macrostimulation, diffusion tractography, cortico-cortical evoked potentials (CCEPs) and task-based ECoG. Macrostimulation of the preSMA induced behavioral motor arrest. Diffusion tractography revealed a structural connection between the preSMA and rIFG. CCEP analysis showed that stimulation of the preSMA evoked strong local field potentials within 30 ms in rIFG. During the task, when preparing to stop, there was increased high gamma amplitude (~70-250 Hz) in both regions, with preSMA preceding rIFG by ~750 ms. For outright stopping there was also a high gamma amplitude increase in both regions, again with preSMA preceding rIFG. Further, at the time of stopping, there was an increase in beta band activity (~16 Hz) in both regions, with significantly stronger inter-regional coherence for successful vs. unsuccessful stop trials. The results complement earlier reports of a structural/functional action control network between the preSMA and rIFG. They go further by revealing between-region timing differences in the high gamma band when preparing to stop and stopping outright. They also reveal strong between-region coherence in the beta band when stopping is successful. Implications for theories of action control are discussed.

Deep brain stimulation of the subthalamic nucleus alters the cortical profile of response inhibition in the beta frequency band: a scalp EEG study in Parkinson's disease.

Stopping an initiated response could be implemented by a fronto-basal-ganglia circuit, including the right inferior frontal cortex (rIFC) and the subthalamic nucleus (STN). Intracranial recording studies in humans reveal an increase in beta-band power (approximately 16-20 Hz) within the rIFC and STN when a response is stopped. This suggests that the beta-band could be important for communication in this network. If this is the case, then altering one region should affect the electrophysiological response at the other. We addressed this hypothesis by recording scalp EEG during a stop task while modulating STN activity with deep brain stimulation. We studied 15 human patients with Parkinson's disease and 15 matched healthy control subjects. Behaviorally, patients OFF stimulation were slower than controls to stop their response. Moreover, stopping speed was improved for ON compared to OFF stimulation. For scalp EEG, there was greater beta power, around the time of stopping, for patients ON compared to OFF stimulation. This effect was stronger over the right compared to left frontal cortex, consistent with the putative right lateralization of the stopping network. Thus, deep brain stimulation of the STN improved behavioral stopping performance and increased the beta-band response over the right frontal cortex. These results complement other evidence for a structurally connected functional circuit between right frontal cortex and the basal ganglia. The results also suggest that deep brain stimulation of the STN may improve task performance by increasing the fidelity of information transfer within a fronto-basal-ganglia circuit.