Jay L. Alberts

Reversing cognitive–motor impairments in Parkinson’s disease patients using a computational modelling approach to deep brain stimulation programming

Deep brain stimulation in the subthalamic nucleus is an effective and safe surgical procedure that has been shown to reduce the motor dysfunction of patients with advanced Parkinsons disease. Bilateral subthalamic nucleus deep brain stimulation, however, has been associated with declines in cognitive and cognitive-motor functioning. It has been hypothesized that spread of current to nonmotor areas of the subthalamic nucleus may be responsible for declines in cognitive and cognitive-motor functioning. The aim of this study was to assess the cognitive-motor performance in advanced Parkinsons disease patients with subthalamic nucleus deep brain stimulation parameters determined clinically (Clinical) to settings derived from a patient-specific computational model (Model). Data were collected from 10 patients with advanced Parkinsons disease bilaterally implanted with subthalamic nucleus deep brain stimulation systems. These patients were assessed off medication and under three deep brain stimulation conditions: Off, Clinical or Model based stimulation. Clinical stimulation parameters had been determined based on clinical evaluations and were stable for at least 6 months prior to study participation. Model-based parameters were selected to minimize the spread of current to nonmotor portions of the subthalamic nucleus using Cicerone Deep Brain Stimulation software. For each stimulation condition, participants performed a working memory (n-back task) and motor task (force tracking) under single- and dual-task settings. During the dual-task, participants performed the n-back and force-tracking tasks simultaneously. Clinical and Model parameters were equally effective in improving the Unified Parkinsons disease Rating Scale III scores relative to Off deep brain stimulation scores. Single-task working memory declines, in the 2-back condition, were significantly less under Model compared with Clinical deep brain stimulation settings. Under dual-task conditions, force tracking was significantly better with Model compared with Clinical deep brain stimulation. In addition to better overall cognitive-motor performance associated with Model parameters, the amount of power consumed was on average less than half that used with the Clinical settings. These results indicate that the cognitive and cognitive-motor declines associated with bilateral subthalamic nucleus deep brain stimulation may be reversed, without compromising motor benefits, by using model-based stimulation parameters that minimize current spread into nonmotor regions of the subthalamic nucleus.

Quality-of-Life Change Associated With Robotic-Assisted Therapy to Improve Hand Motor Function in Patients With Subacute Stroke: A Randomized Clinical Trial

Background At 6 months poststroke, most patients cannot incorporate their affected hand into daily activities, which in turn is likely to reduce their perceived quality of life. Objective This preliminary study explored change in patient-reported, health-related quality of life associated with robotic-assisted therapy combined with reduced therapist-supervised training. Design and Setting A single-blind, multi-site, randomized clinical trial was conducted. Participants Seventeen individuals who were 3 to 9 months poststroke participated. Intervention Sixty hours of therapist-supervised repetitive task practice (RTP) was compared with 30 hours of RTP combined with 30 hours of robotic-assisted therapy. Measurements Participants completed the Stroke Impact Scale (SIS) at baseline, immediately postintervention, and 2 months postintervention. Change in SIS score domains was assessed in a mixed model analysis. Results The combined therapy group had a greater increase in rating of mood from preintervention to postintervention, and the RTP-only group had a greater increase in rating of social participation from preintervention to follow-up. Both groups had statistically significant improvement in activities of daily living and instrumental activities of daily living scores from preintervention to postintervention. Both groups reported significant improvement in hand function postintervention and at follow-up, and the magnitude of these changes suggested clinical significance. The combined therapy group had significant improvements in stroke recovery rating postintervention and at follow-up, which appeared clinically significant; this also was true for stroke recovery rating from preintervention to follow-up in the RTP-only group. Limitations Outcomes of 30 hours of RTP in the absence of robotic-assisted therapy remain unknown. Conclusion Robotic-assisted therapy may be an effective alternative or adjunct to the delivery of intensive task practice interventions to enhance hand function recovery in patients with stroke.

It is not about the bike, it is about the pedaling: forced exercise and Parkinson's disease.

Forced exercise has resulted in neuroprotective effects and improved motor function in animal studies. These promising results have not yet been translated fully to humans with Parkinsons disease (PD), as traditional exercise interventions have not yielded global improvements in function. A novel forced exercise intervention is described that has resulted in improved motor function and central nervous system function in PD patients.

The Effects of Constraint-Induced Therapy on Precision Grip: A Preliminary Study

Objective. This preliminary study examines the effects of a 2-week constraint-induced therapy (CIT) intervention on the force-producing capabilities of the hemiparetic hand during the performance of a functional dexterous manipulation task. Methods. A 6-degree-of-freedom force/torque transducer that was embedded into the handle of a key allowed for the quantification of grasping forces and torques produced during the performance of a functional key-turning task. Clinical and kinetic data were collected from 10 subacute patients (3-9 months poststroke) who were participating in an ongoing national clinical study (EXCITE trial) examining the effects of CIT on upper extremity motor performance. Investigators were blinded to treatment designation. Five patients receiving treatment immediately completed 2 weeks of intensive CIT, whereas a group randomized to treatment 1 year later did not receive any therapy during a similar 2-week span. Results .Results indicated that 4 of the 5 patients in the CIT group, compared to the delayed group, showed significant clinical improvements in hand function, increased maximum precision grip force, improved force and torque regulation, and reduced variability in rate of force production during task performance. Conclusions. Improved force control may be a mechanism contributing to the observed improvements in dexterous function in those patients undergoing CIT.

Improving Quality of Life and Depression After Stroke Through Telerehabilitation

OBJECTIVE The aim of this study was to determine the effects of home-based robot-assisted rehabilitation coupled with a home exercise program compared with a home exercise program alone on depression and quality of life in people after stroke. METHOD A multisite randomized controlled clinical trial was completed with 99 people<6 mo after stroke who had limited access to formal therapy. Participants were randomized into one of two groups, (1) a home exercise program or (2) a robot-assisted therapy+home exercise program, and participated in an 8-wk home intervention. RESULTS We observed statistically significant changes in all but one domain on the Stroke Impact Scale and the Center for Epidemiologic Studies Depression Scale for both groups. CONCLUSION A robot-assisted intervention coupled with a home exercise program and a home exercise program alone administered using a telerehabilitation model may be valuable approaches to improving quality of life and depression in people after stroke.

Changes in Serial Optical Topography and TMS during Task Performance after Constraint-Induced Movement Therapy in Stroke: A Case Study

The authors examined serial changes in optical topography in a stroke patient performing a functional task, as well as clinical and physiologic measures while undergoing constraint-induced therapy (CIT). A 73-year-old right hemiparetic patient, who had a subcortical stroke 4 months previously, received 2 weeks of CIT. During the therapy, daily optical topography imaging using nearinfrared light was measured serially while the participant performed a functional key-turning task. Clinical outcome measures included the Wolf Motor Function Test (WMFT), Motor Activity Log (MAL), and functional key grip test. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) were also used to map cortical areas and hemodynamic brain responses, respectively. Optical topography measurement showed an overall decrease in oxy-hemoglobin concentration in both hemispheres as therapy progressed and the laterality index increased toward the contralateral hemisphere. An increased TMS motor map area was observed in the contralateral cortex following treatment. Posttreatment fMRI showed bilateral primary motor cortex activation, although slightly greater in the contralateral hemisphere, during affected hand movement. Clinical scores revealed marked improvement in functional activities. In one patient who suffered a stroke, 2 weeks of CIT led to improved function and cortical reorganization in the hemisphere contralateral to the affected hand.

Are two leads always better than one: an emerging case for unilateral subthalamic deep brain stimulation in Parkinson's disease.

Bilateral subthalamic (STN) deep brain stimulation (DBS) provides significant symptom relief for the majority of well-screened patients suffering with Parkinsons disease (PD). Implantation of stimulating electrodes bilaterally in a single session has become standard in most operating theaters worldwide. There is, however, limited evidence-based support for this approach. Although bilateral surgical procedures have been shown, using standardized clinical ratings, to provide greater motor benefits compared to unilateral procedures, bilateral procedures are more likely to be associated with increased acute and long-term complications including post-operative confusion, speech difficulties and cognitive dysfunction. Unilateral stimulation has been shown to provide significant benefits for appendicular and axial symptoms. The relative benefit of implanting one versus two sides and whether the degree of benefit associated with the second side is worth the potential risk of doing so have not been examined systematically. The relative magnitude of benefit associated with unilateral versus bilateral procedures is likely to vary from patient to patient, particularly in those patients with asymmetric symptomatology. As such, there are likely subsets of patients who do not require and therefore should not be exposed to the potential complications associated with bilateral simultaneous implantation. This review and commentary will outline our current understanding of the benefits associated with unilateral and bilateral STN DBS and discuss the role of unilateral or staged unilateral procedures as an alternative surgical approach for patients with advanced PD.

Kinematic optimization of deep brain stimulation across multiple motor symptoms in Parkinson's disease.

Parkinsons disease (PD) is a neurodegenerative disorder characterized by motor symptoms including tremor and bradykinesia (slowness of movement). Drug treatment, although capable of controlling these symptoms over a number of years, becomes less effective as the disease progresses and leads to motor complications such as drug-induced dyskinesia (involuntary abnormal movements). Deep brain stimulation (DBS) provides an alternative means of controlling motor symptoms in these patients, and while DBS has been effective in improving motor symptoms, these improvements are largely based on accurate placement of the lead and the ability of medical personnel to adequately program the DBS device following implantation. While guidelines exist for DBS programming, selection of stimulation parameters and patient outcome is greatly dependent on subjective clinical assessments and the experience of the medical personnel performing the programming. The aim of this project was to assess the feasibility of using a quantitative and objective approach to programming. Two subjects underwent standard procedures for DBS programming while wearing a small, compact motion sensor. Kinematic data were collected from subjects as they completed motor tasks to evaluate DBS efficacy. Quantitative variables characterizing tremor and bradykinesia were related to stimulation parameters. Results indicated different stimulation settings might be required for optimal improvement of different motor symptoms. A standardized method of programming DBS parameters utilizing motion analysis may provide an objective method of assessment that the programmer can use to better identify stimulation parameters to achieve optimal improvement across multiple motor symptoms.

Combined Use of Repetitive Task Practice and an Assistive Robotic Device in a Patient With Subacute Stroke

Background and Purpose. This case report describes a training program comprising repetitive task practice (RTP) and robotic therapy for a patient with subacute stroke and resultant impaired upper-extremity function. Case Description. A 63-year-old man with right-sided hemiplegia resulting from a hemorrhagic stroke received a combined intervention of RTP and robotic therapy for 4 hours per day for 3 weeks. Clinical and kinetic evaluations were performed before and after intervention. Outcomes. Following the combined intervention, clinical improvements in hand function were observed, maximum grip force decreased slightly, and interlimb coupling decreased. Discussion. An intervention of RTP with robotic therapy may be an effective method to improve upper-extremity function following stroke. Furthermore, the case suggests that improvements in strength are not necessary for improved dexterous function, provided that a minimal level of strength is present.

The Persistent Effects of Unilateral Pallidal and Subthalamic Deep Brain Stimulation on Force Control in advanced Parkinson’s patients

The persistent effects of unilateral deep brain stimulation (DBS) of the globus pallidus interna (GPi) or subthalamic nucleus (STN) on specific movement parameters produced by Parkinsons disease (PD) patients are poorly understood. The aim of this study was to determine the effects of unilateral GPi and STN DBS on the force-producing capabilities of PD patients during maximal efforts and functional bimanual dexterity. Clinical and biomechanical data were collected from 14 unilaterally implanted patients (GPi=7; STN=7), at least 13 months post-DBS surgery, during On and Off stimulation in the absence of medication. Unilateral DBS of either location produced a 33% improvement in UPDRS motor scores. Significant gains in maximum force production were present in both limbs during unimanual efforts. The greatest increase in maximum force, for both limbs, was under bimanual conditions. Force in the contralateral limb increased more than 30% during bimanual efforts while ipsilateral force increased by 25%. Unilateral DBS improved grasping force control and consistency of digit placement during the performance of a bimanual dexterity task. The clinical and biomechanical data indicate that unilateral DBS of GPi or STN results in persistent improvements in the control and coordination of grasping forces during maximal efforts and functional dexterous actions. Unilateral DBS implantation of either site should be considered an option for those patients in which bilateral procedures are contraindicated.