Michael T. Barbe

Dissociation of decision-making under ambiguity and decision-making under risk in patients with Parkinson's disease: A neuropsychological and psychophysiological study

Decision-making impairments in Parkinsons disease (PD) are most likely associated with dysfunctions in fronto-striatal loops. Recent studies examined decision-making in PD either in ambiguous situations with implicit rules, using the Iowa Gambling Task (IGT), or in risky situations with explicit rules, using the Game of Dice Task (GDT). Both tasks have been associated with the limbic-orbitofrontal-striatal loop, involved in emotional processing. However, the GDT has additionally been highly associated with the dorsolateral prefrontal-striatal loop, being involved in executive functions. The present study is the first one which examined decision-making in PD patients with both, IGT and GDT. We studied 21 non-demented PD patients on dopaminergic medication and 23 healthy controls with both tasks and a neuropsychological test battery with focus on executive functions. To analyse possible abnormalities in emotional processing, electrodermal responses (EDRs) were assessed while performing the tasks. We found that PD patients were significantly impaired in the GDT, but not in the IGT. Executive dysfunctions correlated with GDT but not with IGT performance. In both tasks, PD patients showed significantly reduced feedback EDRs after losses, but not after gains, indicating a primary decline of sensitivity to negative feedback. Our behavioural data suggest that dysfunctions in the dorsolateral prefrontal loop might be stronger than in the limbic loop, resulting in deficits in executive functions and GDT performance but unimpaired IGT performance. Reduced sensitivity to negative feedback is discussed with regard to dysfunctions in the limbic loop, which may result from pathology of limbic structures or dopaminergic medication.

Multiple-source current steering in subthalamic nucleus deep brain stimulation for Parkinson's disease (the VANTAGE study): a non-randomised, prospective, multicentre, open-label study

BACKGROUND High-frequency deep brain stimulation (DBS) with a single electrical source is effective for motor symptom relief in patients with Parkinsons disease. We postulated that a multiple-source, constant-current device that permits well defined distribution of current would lead to motor improvement in patients with Parkinsons disease. METHODS We did a prospective, multicentre, non-randomised, open-label intervention study of an implantable DBS device (the VANTAGE study) at six specialist DBS centres at universities in six European countries. Patients were judged eligible if they were aged 21-75 years, had been diagnosed with bilateral idiopathic Parkinsons disease with motor symptoms for more than 5 years, had a Hoehn and Yahr score of 2 or greater, and had a Unified Parkinsons disease rating scale part III (UPDRS III) score in the medication-off state of more than 30, which improved by 33% or more after a levodopa challenge. Participants underwent bilateral implantation in the subthalamic nucleus of a multiple-source, constant-current, eight-contact, rechargeable DBS system, and were assessed 12, 26, and 52 weeks after implantation. The primary endpoint was the mean change in UPDRS III scores (assessed by site investigators who were aware of the treatment assignment) from baseline (medication-off state) to 26 weeks after first lead implantation (stimulation-on, medication-off state). This study is registered with ClinicalTrials.gov, number NCT01221948. FINDINGS Of 53 patients enrolled in the study, 40 received a bilateral implant in the subthalamic nucleus and their data contributed to the primary endpoint analysis. Improvement was noted in the UPDRS III motor score 6 months after first lead implantation (mean 13·5 [SD 6·8], 95% CI 11·3-15·7) compared with baseline (37·4 [8·9], 34·5-40·2), with a mean difference of 23·8 (SD 10·6; 95% CI 20·3-27·3; p<0·0001). One patient died of pneumonia 24 weeks after implantation, which was judged to be unrelated to the procedure. 125 adverse events were reported, the most frequent of which were dystonia, speech disorder, and apathy. 18 serious adverse events were recorded, three of which were attributed to the device or procedure (one case each of infection, migration, and respiratory depression). All serious adverse events resolved without residual effects and stimulation remained on during the study. INTERPRETATION The multiple-source, constant-current, eight-contact DBS system suppressed motor symptoms effectively in patients with Parkinsons disease, with an acceptable safety profile. Future trials are needed to investigate systematically the potential benefits of this system on postoperative outcome and its side-effects. FUNDING Boston Scientific.

Dopaminergic modulation of motor network dynamics in Parkinson’s disease

Using connectivity analyses based on functional MRI, Michely et al. investigate dopaminergic modulation of neural network dynamics involved in motor control in Parkinson’s disease. The findings provide insights into the pathophysiology underlying bradykinesia and deficits in executive function, and help to explain why dopaminergic treatments have a greater effect on the former.

Individualized current-shaping reduces DBS-induced dysarthria in patients with essential tremor

Objective: To investigate in patients with essential tremor (ET) treated with thalamic/subthalamic deep brain stimulation (DBS) whether stimulation-induced dysarthria (SID) can be diminished by individualized current-shaping with interleaving stimulation (cs-ILS) while maintaining tremor suppression (TS). Methods: Of 26 patients screened, 10 reported SID and were invited for testing. TS was assessed by the Tremor Rating Scale and kinematic analysis of postural and action tremor. SID was assessed by phonetic and logopedic means. Additionally, patients rated their dysarthria on a visual analog scale. Results: In 6 of the 10 patients with ET, DBS-ON (relative to DBS-OFF) led to SID while tremor was successfully reduced. When comparing individualized cs-ILS with a non–current-shaped interleaving stimulation (ILS) in these patients, there was no difference in TS while 4 of the 6 patients showed subjective improvement of speech during cs-ILS. Phonetic analysis (ILS vs cs-ILS) revealed that during cs-ILS there was a reduction of voicing during the production of voiceless stop consonants and also a trend toward an improvement in oral diadochokinetic rate, reflecting less dysarthria. Logopedic rating showed a trend toward deterioration in the diadochokinesis task when comparing ON with OFF but no difference between ILS and cs-ILS. Conclusion: This is a proof-of-principle evaluation of current-shaping in patients with ET treated with thalamic/subthalamic DBS and experiencing SID. Data suggest a benefit on SID from individual shaping of current spread while TS is preserved. Classification of evidence: This study provides Class IV evidence that in patients with ET treated with DBS with SID, individualized cs-ILS reduces dysarthria while maintaining tremor control.

Task-specific modulation of effective connectivity during two simple unimanual motor tasks: A 122-channel EEG study

Neural oscillations are thought to underlie coupling of spatially remote neurons and gating of information within the human sensorimotor system. Here we tested the hypothesis that different unimanual motor tasks are specifically associated with distinct patterns of oscillatory coupling in human sensorimotor cortical areas. In 13 healthy, right-handed subjects, we recorded task-induced neural activity with 122-channel electroencephalography (EEG) while subjects performed fast self-paced extension-flexion movements with the right index finger and an isometric contraction of the right forearm. Task-related modulations of inter-regional coupling within a core motor network comprising the left primary motor cortex (M1), lateral premotor cortex (lPM) and supplementary motor area (SMA) were then modeled using dynamic causal modeling (DCM). A network model postulating coupling both within and across frequencies best captured observed spectral responses according to Bayesian model selection. DCM revealed dominant coupling within the β-band (13-30 Hz) between M1 and SMA during isometric contraction of the forearm, whereas fast repetitive finger movements were characterized by strong coupling within the γ-band (31-48 Hz) and between the θ- (4-7 Hz) and the γ-band. This coupling pattern was mainly expressed in connections from lPM to SMA and from lPM to M1. We infer that human manual motor control involves task-specific modulation of inter-regional oscillatory coupling both within and across distinct frequency bands. The results highlight the potential of DCM to characterize context-specific changes in coupling within functional brain networks.

A new rechargeable device for deep brain stimulation: a prospective patient satisfaction survey.

Background: Deep brain stimulation (DBS) is highly successful in treating Parkinson’s disease (PD), dystonia, and essential tremor (ET). Until recently implantable neurostimulators were nonrechargeable, battery-driven devices, with a lifetime of about 3–5 years. This relatively short duration causes problems for patients (e.g. programming and device-use limitations, unpredictable expiration, surgeries to replace depleted batteries). Additionally, these batteries (relatively large with considerable weight) may cause discomfort. To overcome these issues, the first rechargeable DBS device was introduced: smaller, lighter and intended to function for 9 years. Methods: Of 35 patients implanted with the rechargeable device, 21 (including 8 PD, 10 dystonia, 2 ET) were followed before and 3 months after surgery and completed a systematic survey of satisfaction with the rechargeable device. Results: Overall patient satisfaction was high (83.3 ± 18.3). Dystonia patients tended to have lower satisfaction values for fit and comfort of the system than PD patients. Age was significantly negatively correlated with satisfaction regarding process of battery recharging. Conclusions: Dystonia patients (generally high-energy consumption, severe problems at the DBS device end-of-life) are good, reliable candidates for a rechargeable DBS system. In PD, younger patients, without signs of dementia and good technical understanding, might have highest benefit.

Dopamine Replacement Modulates Oscillatory Coupling Between Premotor and Motor Cortical Areas in Parkinson's Disease

Efficient neural communication between premotor and motor cortical areas is critical for manual motor control. Here, we used high-density electroencephalography to study cortical connectivity in patients with Parkinsons disease (PD) and age-matched healthy controls while they performed repetitive movements of the right index finger at maximal repetition rate. Multiple source beamformer analysis and dynamic causal modeling were used to assess oscillatory coupling between the lateral premotor cortex (lPM), supplementary motor area (SMA), and primary motor cortex (M1) in the contralateral hemisphere. Elderly healthy controls showed task-related modulation in connections from lPM to SMA and M1, mainly within the γ-band (>30 Hz). Nonmedicated PD patients also showed task-related γ-γ coupling from lPM to M1, but γ coupling from lPM to SMA was absent. Levodopa reinstated physiological γ-γ coupling from lPM to SMA and significantly strengthened coupling in the feedback connection from M1 to lPM expressed as β-β as well as θ-β coupling. Enhancement in cross-frequency θ-β coupling from M1 to lPM was correlated with levodopa-induced improvement in motor function. The results show that PD is associated with an altered neural communication between premotor and motor cortical areas, which can be modulated by dopamine replacement.

Impaired self-awareness of motor deficits in Parkinson's disease: association with motor asymmetry and motor phenotypes.

This study investigated impaired self‐awareness of motor deficits in nondemented, nondepressed Parkinsons disease (PD) patients during a defined clinical on state.

Multiple source current steering – A novel deep brain stimulation concept for customized programming in a Parkinson's disease patient ☆

1353-8020/

Directional DBS increases side‐effect thresholds—A prospective, double‐blind trial

– see front matter http://dx.doi.org/10.1016/j.parkreldis.2013.07.021 This case report is in accordance with the Declaration of Helsinki. Deep brain stimulationwas carried out with the adequate understanding and written consent of the patient involved and with the ethical approval of the authors’ institutional review board. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a safe and effective treatment for Parkinson’s disease (PD). However, small variations in stimulation current can cause excessive neural activation of neighboring anatomical structures or the non-motor portions of the STN which might induce unintended side effects. Therefore, in a number of patients, this leads to the dilemma of choosing suboptimal stimulation parameters to avoid side effects at the cost of suboptimal suppression of motor symptoms. In conventional, single-source DBS systems (voltageand current-control systems), precision and stability of therapy delivery may be limited since each contact cannot be controlled independently. In contrast, simulation models of DBS indicate that current steeringwithmultiple stimulation sourcesmight be able to transfer current more precisely and more constant over time [1,2]. In principle this approach might be a helpful tool for the clinician to control side effects thereby improving the overall outcome of DBS. Here, we report of our experience with a novel DBS-system capable of multiple source current steering and describe how this novel programming capability added to a more customized DBS-programming in a PD patient treated with bilateral STNDBS. This case report is in accordance with the Declaration of Helsinki. Deep brain stimulation was carried out with the adequate understanding and written consent of the patient involved and with the ethical approval of the authors’ institutional review board. A 60 year old male diagnosed with PD for 13 years presented at our clinic. He suffered from severe parkinsonism, resting and postural tremor more dominant on the left side, and a history of depressive symptoms. Dopaminergic drugs induced severe sleep apnea and day-time sleepiness. The patient experienced offtime freezing of gait episodes and severe dyskinesia, limiting his daily activities and quality of life. The patient reported