Temporally optimized patterned stimulation (TOPS®) as a therapy to personalize deep brain stimulation treatment of Parkinson's disease.

Deep brain stimulation (DBS) is a well-established therapy for the motor symptoms of Parkinson's disease (PD), but there remains an opportunity to improve symptom relief. The temporal pattern of stimulation is a new parameter to consider in DBS therapy, and we compared the effectiveness of Temporally Optimized Patterned Stimulation (TOPS) to standard DBS at reducing the motor symptoms of PD. Twenty-six subjects with DBS for PD received three different patterns of stimulation (two TOPS and standard) while on medication and using stimulation parameters optimized for standard DBS. Side effects and motor symptoms were assessed after 30 min of stimulation with each pattern. Subjects experienced similar types of side effects with TOPS and standard DBS, and TOPS were well-tolerated by a majority of the subjects. On average, the most effective TOPS was as effective as standard DBS at reducing the motor symptoms of PD. In some subjects a TOPS pattern was the most effective pattern. Finally, the TOPS pattern with low average frequency was found to be as effective or more effective in about half the subjects while substantially reducing estimated stimulation energy use. TOPS DBS may provide a new programing option to improve DBS therapy for PD by improving symptom reduction and/or increasing energy efficiency. Optimizing stimulation parameters specifically for TOPS DBS may demonstrate further clinical benefit of TOPS DBS in treating the motor symptoms of Parkinson's disease.

Local Fields in Human Subthalamic Nucleus Track the Lead-up to Impulsive Choices.

The ability to adaptively minimize not only motor but cognitive symptoms of neurological diseases, such as Parkinson's Disease (PD) and obsessive-compulsive disorder (OCD), is a primary goal of next-generation deep brain stimulation (DBS) devices. On the basis of studies demonstrating a link between beta-band synchronization and severity of motor symptoms in PD, the minimization of beta band activity has been proposed as a potential training target for closed-loop DBS. At present, no comparable signal is known for the impulsive side effects of PD, though multiple studies have implicated theta band activity within the subthalamic nucleus (STN), the site of DBS treatment, in processes of conflict monitoring and countermanding. Here, we address this challenge by recording from multiple independent channels within the STN in a self-paced decision task to test whether these signals carry information sufficient to predict stopping behavior on a trial-by-trial basis. As in previous studies, we found that local field potentials (LFPs) exhibited modulations preceding self-initiated movements, with power ramping across multiple frequencies during the deliberation period. In addition, signals showed phasic changes in power around the time of decision. However, a prospective model that attempted to use these signals to predict decision times showed effects of risk level did not improve with the addition of LFPs as regressors. These findings suggest information tracking the lead-up to impulsive choices is distributed across multiple frequency scales in STN, though current techniques may not possess sufficient signal-to-noise ratios to predict-and thus curb-impulsive behavior on a moment-to-moment basis.

Dopamine Transporter Imaging has no Impact on Functional Outcomes in de Novo Probable Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is among the most prevalent neurodegenerative conditions. While motor and non-motor aspects of this disease have been well characterized, no objective biomarker exists to support an accurate clinical diagnosis. However, newer imaging techniques, including [123I]-FP-CIT (DaTSCAN), have demonstrated utility in differentiating between PD and non-neurodegenerative tremor disorders. OBJECTIVE: DaTSCAN has been primarily investigated in situations where diagnostic confusion exists, and in these instances has been shown to significantly impact clinical management. The goal of this pilot study was to evaluate the impact of DaTSCAN on the clinical management of patients with early probable PD, where no diagnostic uncertainty exists. METHODS: This was a prospective, 54-week, comparative pilot study, in which twenty subjects with de novo PD were randomly assigned to DaTSCAN either immediately upon diagnosis (and again at 6 and 12 months) or delayed to 6 months (and again at 12 months). The primary outcome measure was the frequency of deviation from the initial treatment plan from baseline to 54 weeks between the two groups. Secondary outcomes included motor and non-motor assessments. RESULTS: There was no significant difference in the number of treatment changes over the course of the study between the two groups: initial imaging group = 4.2 (SD:2.74) vs. delayed imaging group = 2.3 (SD:2.0, p = 0.11). In addition, there were no group differences in medication requirements, motor performance, or patient expectations of disease. CONCLUSIONS: In patients with early, probable PD, DaTSCAN contributes no additional impact on clinical management or functional outcomes when added to the diagnostic algorithm.

Effects of repetitive transcranial magnetic stimulation on motor symptoms in Parkinson disease: a systematic review and meta-analysis.

IMPORTANCE: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that has been closely examined as a possible treatment for Parkinson disease (PD). However, results evaluating the effectiveness of rTMS in PD are mixed, mostly owing to low statistical power or variety in individual rTMS protocols. OBJECTIVES: To determine the rTMS effects on motor dysfunction in patients with PD and to examine potential factors that modulate the rTMS effects. DATA SOURCES: Databases searched included PubMed, EMBASE, Web of Knowledge, Scopus, and the Cochrane Library from inception to June 30, 2014. STUDY SELECTION: Eligible studies included sham-controlled, randomized clinical trials of rTMS intervention for motor dysfunction in patients with PD. DATA EXTRACTION AND SYNTHESIS: Relevant measures were extracted independently by 2 investigators. Standardized mean differences (SMDs) were calculated with random-effects models. MAIN OUTCOMES AND MEASURES: Motor examination of the Unified Parkinson's Disease Rating Scale. RESULTS: Twenty studies with a total of 470 patients were included. Random-effects analysis revealed a pooled SMD of 0.46 (95% CI, 0.29-0.64), indicating an overall medium effect size favoring active rTMS over sham rTMS in the reduction of motor symptoms (P<.001). Subgroup analysis showed that the effect sizes estimated from high-frequency rTMS targeting the primary motor cortex (SMD, 0.77; 95% CI, 0.46-1.08; P<.001) and low-frequency rTMS applied over other frontal regions (SMD, 0.50; 95% CI, 0.13-0.87; P=.008) were significant. The effect sizes obtained from the other 2 combinations of rTMS frequency and rTMS site (ie, high-frequency rTMS at other frontal regions: SMD, 0.23; 95% CI, -0.02 to 0.48, and low primary motor cortex: SMD, 0.28; 95% CI, -0.23 to 0.78) were not significant. Meta-regression revealed that a greater number of pulses per session or across sessions is associated with larger rTMS effects. Using the Grading of Recommendations, Assessment, Development, and Evaluation criteria, we characterized the quality of evidence presented in this meta-analysis as moderate quality. CONCLUSIONS AND RELEVANCE: The pooled evidence suggests that rTMS improves motor symptoms for patients with PD. Combinations of rTMS site and frequency as well as the number of rTMS pulses are key modulators of rTMS effects. The findings of our meta-analysis may guide treatment decisions and inform future research.