Hyperdirect projections from the supplementary motor area mediate subthalamic stimulation effects on movement initiation and inhibition in Parkinson’s disease

Subthalamic stimulation modulates working memory-related cortical dynamics in Parkinson’s disease

Abstract The dynamic modulation of large-scale network activity, which is inherent to cognitive processes, is disrupted in Parkinson’s disease. Subthalamic deep brain stimulation can either improve or deteriorate cognition, particularly executive function, with these effects often going unnoticed during acute parameter optimization. This highlights the need for longer stimulation periods and more focused research on the underlying cortical mechanisms, which remain underexplored. This study was a prospective clinical trial involving nineteen people with Parkinson’s disease, who were evaluated off their medication at preoperative baseline and 6 months after deep brain stimulation implantation. Brain activity related to verbal and visuospatial working memory tasks was recorded using electroencephalography at both baseline and during follow-up evaluations conducted under stimulation. The follow-up assessments were carried out following 3-week periods of either omnidirectional or directional stimulation, applied in a randomized, double-blind, crossover design. Average postoperative working memory performance remained stable at the group level regardless of the stimulation condition for both verbal and visuospatial working memory tasks. However, at the individual level, higher alpha and beta power at baseline was associated with slower visuospatial working memory reaction time at follow-up. Additionally, reductions in theta and beta power during stimulation at follow-up correlated with better verbal working memory accuracy during the task and compared with baseline, respectively. These findings suggest that task-related electroencephalography may provide candidate physiological markers of individual working memory trajectories after subthalamic deep brain stimulation. Oscillatory brain activity may help to characterize stimulation-related cognitive variability beyond motor outcomes, but these exploratory findings require validation in larger cohorts before they can inform stimulation programming or closed-loop treatment strategies. Registration: ClinicalTrials.gov: NCT03548506

Behavioral changes preceded by subthalamic nucleus activity alterations in a progressive macaque model of Parkinson’s disease

A temporal relationship between STN dysfunction and symptom onset is revealed and site- and frequency-specific stimulation strategies to address motor and non-motor symptoms in PD are supported.

From thalamic pathology to suppression stimulation of the subthalamic nucleus in Parkinson's disease: effects of variation in stimulation parameters

Pre-Supplementary Motor Area Theta Burst Stimulation Alters Corticomotor Facilitation and Action Reinitiation Without Impairing Response Inhibition

Background The pre-supplementary motor area (preSMA) is increasingly being explored as a neuromodulation target for impulsive behaviour in several clinical populations. Treatment effects are generally interpreted as improvements in inhibitory control. However, healthy studies report improved/impaired/unchanged inhibitory control following identical preSMA stimulation protocols, and few studies examine accompanying neurophysiological changes. We therefore investigated whether preSMA stimulation influences downstream corticomotor excitability to modify a general stopping mechanism, other components of action control, or wider cue-dependent attentional processes relevant to impulsive behaviour. Methods In a preregistered, double-blind crossover study, 18 healthy adults received active and sham continuous theta burst stimulation (cTBS) over right preSMA. Motor-evoked potentials (MEPs), anticipatory response inhibition task measures, and alcohol dot-probe reaction times were collected before and after stimulation and analysed with linear mixed models. Results MEPs increased during sham (p = .028) but not after active cTBS (p = .741). Active cTBS did not affect complete or partial stopping on the response inhibition task. Instead, active cTBS slowed the continuing response after partial stopping (p < .001) whereas response execution sped up across the sham session (p < .001). No alcohol attentional bias or stimulation effect was detected. Conclusions PreSMA cTBS did not impair general inhibitory or attentional control. Instead, it attenuated session-related corticomotor facilitation and selectively slowed reinitiation of a partially inhibited action. These findings suggest that clinical effects to impulsive behaviour from preSMA neuromodulation are primarily rooted in changes to motor preparation and action updating rather than a unitary stopping mechanism.

Beta transcranial alternating current stimulation over the dorsal premotor area impairs response initiation but not inhibition in humans.

BACKGROUND Response initiation and inhibition are core components of movement control, supported by a distributed frontal network including the dorsal premotor cortex (PMd) and inferior frontal gyrus (IFG). Converging evidence suggests that neural oscillations, particularly in the β- and γ bands, contribute to both response initiation and inhibitory control. Transcranial alternating current stimulation (tACS) enables non-invasive, frequency-specific modulation of cortical oscillations, offering a tool to causally probe these mechanisms. This study investigated whether β- and γ-tACS applied over PMd or IFG affect response initiation and inhibition in healthy participants. MATERIALS AND METHODS Twenty healthy right-handed participants performed a Stop Signal Task (SST) during online β (20 Hz) and γ (70 Hz) tACS applied bilaterally, over either the PMd or IFG, in randomised, separate sessions. Behavioural measures of response initiation included accuracy, reaction times (RTs) and RT variability. Response inhibition was measured using the probability of responding on Stop trials (p[R]) and stop-signal reaction time (SSRT). RESULTS β-tACS, but not γ-tACS, over the PMd but not over the IFG, significantly reduced response accuracy, suggesting a disruption of response initiation processes. For response inhibition, neither β- nor γ-tACS over IFG or PMd significantly modulated p[R] or SSRT. CONCLUSIONS PMd β-tACS selectively deteriorated response initiation in healthy participants. This finding implies that β-oscillations would play a key physiological role in response initiation. SIGNIFICANCE Applying β-tACS over the PMd selectively deteriorated response initiation, but not inhibition, in healthy humans.

Movement-responsive deep brain stimulation reinforces motor circuits in Parkinson's disease

Deep brain stimulation is an established treatment for Parkinson's disease but does not adapt to dynamic changes in brain state. Here, in four patients with sensing-enabled DBS systems, we evaluated a movement-responsive DBS (mDBS) paradigm that modulated subthalamic stimulation based on volitional motion decoded from cortical activity. During structured motor tasks, mDBS improved average forearm speed and mitigated the progressive bradykinetic slowing observed under constant-amplitude DBS (cDBS), accompanied by a cumulative increase in sensorimotor cortical beta activity and connectivity. In unconstrained, daily activities, mDBS lowered average bradykinesia severity and demonstrated progressive symptom reduction over hours of therapy, which gradually reversed upon switching to cDBS. These findings highlight the enhanced therapeutic benefit of mDBS and its potential to reinforce functional motor circuits in disorders of movement.