The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease (PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.

Subthalamic Nucleus Deep Brain Stimulation (STN DBS) is a well-established and effective treatment modality for selected patients with Parkinson’s disease (PD). Since its advent, systematic exploration of the effect of stimulation parameters including the stimulation intensity, frequency, and pulse width have been carried out to establish optimal therapeutic ranges. This review examines published data on these stimulation parameters in terms of efficacy of treatment and adverse effects. Altering stimulation intensity is the mainstay of titration in DBS programming via alterations in voltage or current settings, and is characterised by a lower efficacy threshold and a higher side effect threshold which define the therapeutic window. In addition, much work has been done in exploring the effects of frequency modulation, which may help patients with gait freezing and other axial symptoms. However, there is a paucity of data on the use of ultra-short pulse width settings which are now possible with technological advances. We also discuss current evidence for the use of novel programming techniques including directional and adaptive stimulation, and highlight areas for future research.

Background Subthalamic nucleus deep brain stimulation (STN‐DBS) is an effective therapy for selected Parkinson's disease patients with motor fluctuations, but can adversely affect speech and axial symptoms. The use of short pulse width (PW) has been shown to expand the therapeutic window acutely, but its utility in reducing side effects in chronic STN‐DBS patients has not been evaluated. Objective To compare the effect of short PW settings using 30‐μs with conventional 60‐μs settings on stimulation‐induced dysarthria in Parkinson's disease patients with previously implanted STN‐DBS systems. Methods In this single‐center, double‐blind, randomized crossover trial, we assigned 16 Parkinson's disease patients who had been on STN‐DBS for a mean of 6.5 years and exhibited moderate dysarthria to 30‐μs or 60‐μs settings for 4 weeks followed by the alternative PW setting for a further 4 weeks. The primary outcome was difference in dysarthric speech measured by the Sentence Intelligibility Test between study baseline and the 2 PW conditions. Secondary outcomes included motor, nonmotor, and quality of life measures. Results There was no difference in the Sentence Intelligibility Test scores between baseline and the 2 treatment conditions (P = 0.25). There were also no differences noted in motor, nonmotor, or quality of life scores. The 30‐μs settings were well tolerated, and adverse event rates were similar to those at conventional PW settings. Post hoc analysis indicated that patients with dysarthria and a shorter duration of DBS may be improved by short PW stimulation. Conclusions Short PW settings using 30 μs did not alter dysarthric speech in chronic STN‐DBS patients. A future study should evaluate whether patients with shorter duration of DBS may be helped by short PW settings. © 2019 International Parkinson and Movement Disorder Society

BACKGROUND:Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for selected Parkinson's disease (PD) patients, but therapy is often limited by side effects. Previous studies indicate an inverse relationship of the therapeutic window (TW) to pulse width (PW) settings down to 60µs, but there is limited data available on the effect of shorter PWs.

A BS TRACT: Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is a widely used treatment for Parkinsonʼs disease (PD) patients with motor complications, but can result in adverse effects (AEs) in a significant proportion of treated patients. The use of novel programming features including short pulse width (PW) and directional steering in alleviating stimulationinduced AEs has not been explored. Objective: To determine if programming with short PW, directional steering, or the combination of these novel techniques can improve stimulation-induced dysarthria, dyskinesia, and pyramidal AEs. Methods: Thirty-two consecutive PD patients who experienced reversible AEs of STN-DBS had optimization of their settings using either short PW, directional steering, or the combination, while ensuring equivalent control of motor symptoms. Pairwise comparisons of pre-and post-optimization adverse effect ratings were made. Patients were left on the alternative setting with the greatest benefit and followed up at 6 months. Modeling of volume of tissue activated (VTA) and charge per pulse (Qp) calculations were used to explore potential underlying mechanisms of any differences found. Results: There were significant improvements in stimulation-induced dysarthria, dyskinesia, and pyramidal side effects after optimization. At 6 months, mean AE ratings remained significantly improved compared to preoptimization ratings. Different patterns of shift in VTA for each AE, and Qp could be used to explain improvements using novel techniques. Conclusions: Stimulation-induced dysarthria, dyskinesia, and pyramidal AEs induced by STN-DBS can be improved by using novel programming techniques. These represent additional tools to conventional methods that can be used to address these AEs.