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The effect of deep brain stimulation randomized by site on balance in Parkinson's disease.

ABSTRACT: The effect of the surgical site of DBS on balance and gait in Parkinson's Disease (PD) is uncertain. This is the first double-blind study of subjects randomized to either the STN (N = 14) or GPi (N = 14) who were assessed on a range of clinical balance measures.Balance testing occurred before and 6 months postsurgery. A control PD group was tested over the same period without surgery (N = 9). All subjects were tested on and off medication and DBS subjects were also tested on and off DBS. The Postural Instability and Gait Disability items of the UPDRS and additional functional tests, which we call the Balance and Gait scale, were assessed. Activities of Balance Confidence and Activities of Daily Living questionnaires were also recorded.Balance was not different between the best-treated states before and after DBS surgery for both sites. Switching DBS on improved balance scores, and scores further improved with medication, compared to the off state. The GPi group showed improved performance in the postsurgery off state and better ratings of balance confidence after surgery, compared to the STN group.Clinical measures of balance function for both the STN and GPi sites showed that balance did not improve beyond the best medically treated state before surgery. Both clinical balance testing in the off/off state and self-reported balance confidence after surgery showed better performance in the GPi than the STN group.

SUBMITTER: St George RJ

PROVIDER: S-EPMC4057940 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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The effect of deep brain stimulation randomized by site on balance in Parkinson's disease.

St George Rebecca J RJ Carlson-Kuhta Patricia P Nutt John G JG Hogarth Penelope P Burchiel Kim J KJ Horak Fay B FB

Movement disorders : official journal of the Movement Disorder Society 20140214 7

<h4>Background</h4>The effect of the surgical site of DBS on balance and gait in Parkinson's Disease (PD) is uncertain. This is the first double-blind study of subjects randomized to either the STN (N = 14) or GPi (N = 14) who were assessed on a range of clinical balance measures.<h4>Methods</h4>Balance testing occurred before and 6 months postsurgery. A control PD group was tested over the same period without surgery (N = 9). All subjects were tested on and off medication and DBS subjects were ...[more]

PMID: 24532106

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Project description:Deep brain stimulation of the subthalamic nucleus for Parkinson's disease is an established advanced therapy that addresses motor symptoms and improves quality of life. However, it has also been associated with neuropsychiatric symptoms such as impulsivity and hypomania. When significant, these symptoms can be distressing, necessitating psychiatric intervention. However, a comprehensive analysis of neurocognitive and neuropsychiatric outcomes with reference to the site of subthalamic stimulation has not been undertaken. We examined this matter in a consecutive sample of 64 persons with Parkinson's disease undertaking subthalamic deep brain stimulation. Participants were assessed with a battery of neuropsychiatric instruments at baseline and at repeated postoperative intervals. A psychiatrist identified patients with emergent, clinically-significant symptoms due to stimulation. The site of the active electrode contact and a simulated volume of activated tissue were evaluated with reference to putative limbic, associative and motor subregions of the subthalamic nucleus. We studied anatomical correlates of longitudinal neuropsychiatric change and delineated specific subthalamic regions associated with neuropsychiatric impairment. We tested the ability of these data to predict clinically-significant symptoms. Subthalamic stimulation within the right associative subregion was associated with inhibitory errors on the Excluded Letter Fluency task at 6-weeks (p = 0.023) and 13-weeks postoperatively (p = 0.0017). A cluster of subthalamic voxels associated with inhibitory errors was identified in the right associative and motor subregions. At 6-weeks, clinically-significant neuropsychiatric symptoms were associated with the distance of the active contact to the right associative subregion (p = 0.0026) and stimulation within the right associative subregion (p = 0.0009). At 13-weeks, clinically-significant symptoms were associated with the distance to the right (p = 0.0027) and left (p = 0.0084) associative subregions and stimulation within the right associative subregion (p = 0.0026). Discrete clusters of subthalamic voxels associated with high and low likelihood of postoperative neuropsychiatric symptoms were identified in ventromedial and dorsolateral zones, respectively. When a classifier was trained on these data, clinically-significant symptoms were predicted with an accuracy of 79%. These data underscore the importance of accurate electrode targeting, contact selection and device programming to reduce postoperative neuropsychiatric impairment. The ability to predict neuropsychiatric symptoms based on subthalamic data may permit anticipation and prevention of these occurrences, improving safety and tolerability.

Project description:Objective: The objective of this study was to use functional connectivity and graphic indicators to investigate the abnormal brain network topological characteristics caused by Parkinson's disease (PD) and the effect of acute deep brain stimulation (DBS) on those characteristics in patients with PD. Methods: We recorded high-density EEG (256 channels) data from 21 healthy controls (HC) and 20 patients with PD who were in the DBS-OFF state and DBS-ON state during the resting state with eyes closed. A high-density EEG source connectivity method was used to identify functional brain networks. Power spectral density (PSD) analysis was compared between the groups. Functional connectivity was calculated for 68 brain regions in the theta (4-8 Hz), alpha (8-13 Hz), beta1 (13-20 Hz), and beta2 (20-30 Hz) frequency bands. Network estimates were measured at both the global (network topology) and local (inter-regional connection) levels. Results: Compared with HC, PSD was significantly increased in the theta (p = 0.003) frequency band and was decreased in the beta1 (p = 0.009) and beta2 (p = 0.04) frequency bands in patients with PD. However, there were no differences in any frequency bands between patients with PD with DBS-OFF and DBS-ON. The clustering coefficient and local efficiency of patients with PD showed a significant decrease in the alpha, beta1, and beta2 frequency bands (p < 0.001). In addition, edgewise statistics showed a significant difference between the HC and patients with PD in all analyzed frequency bands (p < 0.005). However, there were no significant differences between the DBS-OFF state and DBS-ON state in the brain network, except for the functional connectivity in the beta2 frequency band (p < 0.05). Conclusion: Compared with HC, patients with PD showed the following characteristics: slowed EEG background activity, decreased clustering coefficient and local efficiency of the brain network, as well as both increased and decreased functional connectivity between different brain areas. Acute DBS induces a local response of the brain network in patients with PD, mainly showing decreased functional connectivity in a few brain regions in the beta2 frequency band.

Project description:Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson's disease, elevations in beta activity (13-35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson's disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this approach could be more efficacious than conventional continuous deep brain stimulation in the treatment of Parkinson's disease, and helps inform how adaptive deep brain stimulation might best be delivered.

Dataset Information

The effect of deep brain stimulation randomized by site on balance in Parkinson's disease.

Publications

The effect of deep brain stimulation randomized by site on balance in Parkinson's disease.

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