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.

Impact of Isolation During the COVID-19 Pandemic on the Patient Burden of Parkinson's Disease: A PMD Alliance Survey.

Purpose: As the COVID-19 pandemic resulted in social restrictions around the globe, this cross-sectional survey aimed to assess the impact of social isolation on self- or proxy-reported symptoms of Parkinson's disease (PD) during the pandemic. Patients and Methods: The survey was distributed among 7109 subscribers of the Parkinson and Movement Disorders Alliance (PMD Alliance) News and Information list and was open only to people with PD (PwP) and care partners (CP, defined as main caregivers of PwP and serving as proxy respondents). No attempt was made to identify PwP and CP pairs. The survey was distributed online using Survey Monkey between 01/06/2021 and 02/27/2021. Respondents were grouped by level of social support from outside of their household during the pandemic (decreased or maintained [ie, the same as pre-pandemic or increased]). Results: Of 7109 invited participants, 718 responded to the survey (response rate 10.1%). PwP (self-reports) accounted for 70.6% of respondents and CP (proxy reports) for 29.4%. Decreased social support from outside of the household during the COVID-19 pandemic (58.5% of all responses) was significantly associated with increases in sadness/depression and anxiety, compared with maintained levels of social support (p < 0.0001 for both comparisons). It was also associated with increased burden of several non-motor (decline in memory, problem solving, or communication, p = 0.0009; new or worsening confusion, p < 0.0001; new or worsening delusions, p = 0.018) and motor PD symptoms. Conclusion: Decline in social support from outside of the household during the COVID-19 pandemic showed a statistically significant and negative association with the burden of mood and non-motor symptoms of PD. These results call for increased vigilance towards non-motor symptoms in PwP experiencing social isolation and highlight the need for stronger provider focus on encouraging PwP and their CPs to build and maintain social connections and engagements.

Combined accelerometer and genetic analysis to differentiate essential tremor from Parkinson's disease.

Essential tremor (ET) and Parkinson's disease (PD) are among the most common adult-onset tremor disorders. Clinical and pathological studies suggest that misdiagnosis of PD for ET, and vice versa, occur in anywhere from 15% to 35% of cases. Complex diagnostic procedures, such as dopamine transporter imaging, can be powerful diagnostic aids but are lengthy and expensive procedures that are not widely available. Preliminary studies suggest that monitoring of tremor characteristics with consumer grade accelerometer devices could be a more accessible approach to the discrimination of PD from ET, but these studies have been performed in well-controlled clinical settings requiring multiple maneuvers and oversight from clinical or research staff, and thus may not be representative of at-home monitoring in the community setting. Therefore, we set out to determine whether discrimination of PD vs. ET diagnosis could be achieved by monitoring research subject movements at home using consumer grade devices, and whether discrimination could be improved with the addition of genetic profiling of the type that is readily available through direct-to-consumer genetic testing services. Forty subjects with PD and 27 patients with ET were genetically profiled and had their movements characterized three-times a day for two weeks through a simple procedure meant to induce rest tremors. We found that tremor characteristics could be used to predict diagnosis status (sensitivity = 76%, specificity = 65%, area under the curve (AUC) = 0.75), but that the addition of genetic risk information, via a PD polygenic risk score, did not improve discriminatory power (sensitivity = 80%, specificity = 65%, AUC = 0.73).

Stimulation of contacts in ventral but not dorsal subthalamic nucleus normalizes response switching in Parkinson's disease.

Switching between responses is a key executive function known to rely on the frontal cortex and the basal ganglia. Here we aimed to establish with greater anatomical specificity whether such switching could be mediated via different possible frontal-basal-ganglia circuits. Accordingly, we stimulated dorsal vs. ventral contacts of electrodes in the subthalamic nucleus (STN) in Parkinson's patients during switching performance, and also studied matched controls. The patients underwent three sessions: once with bilateral dorsal contact stimulation, once with bilateral ventral contact stimulation, and once Off stimulation. Patients Off stimulation showed abnormal patterns of switching, and stimulation of the ventral contacts but not the dorsal contacts normalized the pattern of behavior relative to controls. This provides some of the first evidence in humans that stimulation of dorsal vs. ventral STN DBS contacts has differential effects on executive function. As response switching is an executive function known to rely on prefrontal cortex, these results suggest that ventral contact stimulation affected an executive/associative cortico-basal ganglia circuit.

Stimulation at dorsal and ventral electrode contacts targeted at the subthalamic nucleus has different effects on motor and emotion functions in Parkinson's disease.

Motor and emotion processing depend on different fronto-basal ganglia circuits. Distinct sub-regions of the subthalamic nucleus (STN) may modulate these circuits. We evaluated whether stimulation targeted at separate territories in the STN region would differentially affect motor and emotion function. In a double-blind design, we studied twenty Parkinson's disease patients who had deep brain stimulation (DBS) electrodes implanted bilaterally in the STN. We stimulated either dorsal or ventral contacts of the STN electrodes on separate days in each patient and acquired behavioral measures. Dorsal contact stimulation improved motor function by reducing scores on the Unified Parkinson's Disease Rating Scale and by reducing both reaction time and reaction time variability compared to ventral contact stimulation. By contrast, ventral contact stimulation led to an increase in positive emotion compared to dorsal contact stimulation. These results support the hypothesis that different territories within the STN region implement motor and emotion functions.