Method for patient-specific finite element modeling and simulation of deep brain stimulation

Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease. Success of DBS is highly dependent on electrode location and electrical parameter settings. The aim of this study was to develop a general method for setting up patient-specific 3D computer models of DBS, based on magnetic resonance images, and to demonstrate the use of such models for assessing the position of the electrode contacts and the distribution of the electric field in relation to individual patient anatomy. A software tool was developed for creating finite element DBS-models. The electric field generated by DBS was simulated in one patient and the result was visualized with isolevels and glyphs. The result was evaluated and it corresponded well with reported effects and side effects of stimulation. It was demonstrated that patient-specific finite element models and simulations of DBS can be useful for increasing the understanding of the clinical outcome of DBS.     

Dose-titrated,double-blind,cross-over comparison of a selective beta-blocker and methyldopa in the treatment of hypertension

Summary The efficacy and toxicity of tolamolol and methyldopa in hypertensive patients has been compared by a dose-titrated, double-blind, cross-over study. Thirteen patients completed the trial. Within the dose ranges investigated (tolamolol — 300 mg/day — 900 mg/day; methyldopa — 750 mg/day — 2250 mg/day) both drugs produced significant falls in laying and standing, systolic and diastolic blood pressures. Although the hypotensive effects of methyldopa were more marked than tolamolol, these only achieved conventional (P<0.05) levels of significance for lying blood pressure. There were no objective changes in haematological or biochemical indices during treatment with either drug, but patients complained of tiredness, weak limbs and mouth dryness significantly more during methyldopa treatment, than during either placebo or tolamolol therapy.     

A gamma band specific role of the subthalamic nucleus in switching during verbal fluency tasks in Parkinson's disease

Objective

Decline in verbal fluency is the most consistent and persistent cognitive impairment documented after deep brain stimulation of the subthalamic nucleus in Parkinson's disease. The mechanisms of this deficit are unclear. We aimed to identify and characterise verbal fluency related processing within the subthalamic nucleus through analysis of local field potentials.

Methods

Local field potentials were recorded from deep brain stimulation electrodes implanted in the subthalamic nuclei of 8 patients (16 sides) with Parkinson's disease, when patients were on medication. Patients performed phonemic and semantic verbal fluency tasks and a control word repetition task to control for the motor output involved in response generation.

Results

Significant increases in local field potential Power (p ≤ 0.05) were seen across a broad gamma frequency band (30–95 Hz) during both verbal fluency tasks, after controlling for motor output. Increases in gamma local field potential Power of + 7.5% ± 2.3% (SEM) in the semantic fluency task and + 6.9% ± 2.0% in the phonemic fluency task were derived when averaging across all electrode contact pairs. Gamma changes recorded from contacts lying in the left hemisphere (dominant in verbal fluency) correlated with average number of correct responses generated (r = 0.81 p = 0.015) and measures of ‘switching’ (r = 0.79 p = 0.020) particularly strongly in the semantic fluency task.

Interpretation

Frequency specific power changes observed during task performance are consistent with involvement of the subthalamic nucleus in switching during verbal fluency. Antagonism of such task-related activity with high frequency stimulation of this nucleus may explain the impairments reported.     

Targeting of the pedunculopontine nucleus by an MRI-guided approach: a cadaver study

Laboratory evidence suggests that the pedunculopontine nucleus (PPN) plays a central role in the initiation and maintenance of gait. Translational research has led to reports on deep brain stimulation (DBS) of the rostral brainstem in parkinsonian patients. However, initial clinical results appear to be rather variable. Possible factors include patient selection and the wide variability in anatomical location of implanted electrodes. Clinical studies on PPN DBS efficacy would, therefore, benefit from an accurate and reproducible method of stereotactic localization of the nucleus. The present study evaluates the anatomical accuracy of a specific protocol for MRI-guided stereotactic targeting of the PPN in a human cadaver. Imaging at 1.5 and 9.4?T confirmed electrode location in the intended region as defined anatomically by the surrounding fiber tracts. The spatial relations of each electrode track to the nucleus were explored by subsequent histological examination. This confirmed that the neuropil surrounding each electrode track contained scattered large neurons morphologically consistent with those of the subnucleus dissipatus and compactus of the PPN. The results support the accuracy of the described specific MR imaging protocol.