Increased Thalamic Gamma Band Activity Correlates with Symptom Relief following Deep Brain Stimulation in Humans with Tourette’s Syndrome

<div><p>Tourette syndrome (TS) is an idiopathic, childhood-onset neuropsychiatric disorder, which is marked by persistent multiple motor and phonic tics. The disorder is highly disruptive and in some cases completely debilitating. For those with severe, treatment-refractory TS, deep brain stimulation (DBS) has emerged as a possible option, although its mechanism of action is not fully understood. We performed a longitudinal study of the effects of DBS on TS symptomatology while concomitantly examining neurophysiological dynamics. We present the first report of the clinical correlation between the presence of gamma band activity and decreased tic severity. Local field potential recordings from five subjects implanted in the centromedian nucleus (CM) of the thalamus revealed a temporal correlation between the power of gamma band activity and the clinical metrics of symptomatology as measured by the Yale Global Tic Severity Scale and the Modified Rush Tic Rating Scale. Additional studies utilizing short-term stimulation also produced increases in gamma power. Our results suggest that modulation of gamma band activity in both long-term and short-term DBS of the CM is a key factor in mitigating the pathophysiology associated with TS.</p> </div

MaDoPO: Magnetic Detection of Positions and Orientations of Segmented Deep Brain Stimulation Electrodes: A Radiation-Free Method Based on Magnetoencephalography

Background: Current approaches to detect the positions and orientations of directional deep brain stimulation (DBS) electrodes rely on radiative imaging data. In this study, we aim to present an improved version of a radiation-free method for magnetic detection of the position and the orientation (MaDoPO) of directional electrodes based on a series of magnetoencephalography (MEG) measurements and a possible future solution for optimized results using emerging on-scalp MEG systems. Methods: A directional DBS system was positioned into a realistic head&ndash;torso phantom and placed in the MEG scanner. A total of 24 measurements of 180 s each were performed with different predefined electrode configurations. Finite element modeling and model fitting were used to determine the position and orientation of the electrode in the phantom. Related measurements were fitted simultaneously, constraining solutions to the a priori known geometry of the electrode. Results were compared with the results of the high-quality CT imaging of the phantom. Results: The accuracy in electrode localization and orientation detection depended on the number of combined measurements. The localization error was minimized to 2.02 mm by considering six measurements with different non-directional bipolar electrode configurations. Another six measurements with directional bipolar stimulations minimized the orientation error to 4&deg;. These values are mainly limited due to the spatial resolution of the MEG. Moreover, accuracies were investigated as a function of measurement time, number of sensors, and measurement direction of the sensors in order to define an optimized MEG device for this application. Conclusion: Although MEG introduces inaccuracies in the detection of the position and orientation of the electrode, these can be accepted when evaluating the benefits of a radiation-free method. Inaccuracies can be further reduced by the use of on-scalp MEG sensor arrays, which may find their way into clinics in the foreseeable future

Modeling of Electric Fields in Individual Imaging Atlas for Capsular Threshold Prediction of Deep Brain Stimulation in Parkinson's Disease: A Pilot Study.

Background: Modeling of deep brain stimulation electric fields and anatomy-based software might improve post-operative management of patients with Parkinson's disease (PD) who have benefitted from subthalamic nucleus deep brain stimulation (STN-DBS). Objective: We compared clinical and software-guided determination of the thresholds for current diffusion to the pyramidal tract, the most frequent limiting side effect in post-operative management of STN-DBS PD patients. Methods: We assessed monopolar reviews in 16 consecutive STN-DBS PD patients and retrospectively compared clinical capsular thresholds, which had been assessed according to standard clinical practice, to those predicted by volume of tissue activated (VTA) model software. All the modeling steps were performed blinded from patients' clinical evaluations. Results: At the group level, we found a significant correlation (p = 0.0001) when performing statistical analysis on the z-scored capsular thresholds, but with a low regression coefficient (r = 0.2445). When considering intra-patient analysis, we found significant correlations (p < 0.05) between capsular threshold as modeled with the software and capsular threshold as determined clinically in five patients (31.2%). Conclusions: In this pilot study, the VTA model software was of limited assistance in identifying capsular thresholds for the whole cohort due to a large inter-patient variability. Clinical testing remains the gold standard in selecting stimulation parameters for STN-DBS in PD

Subject demographics.

<p>Components from this table have been reproduced with permission from Okun (Archives of Neurology Express, 2012) and have been published with the original NIH supported FDA clinical trial (clinicaltrials.gov).</p

Electrode configuration and representative spectra.

<p>A) Subjects were either implanted with one stimulator controlling bilateral leads or B) two simulators each controlling one ipsilateral lead. LFPs were recorded across contact pairs as indicated. For stimulators serving bilateral leads, channels 1 & 2 represent distal and proximal LFPs in one hemisphere. Channels 3 & 4 represent distal and proximal LFPs from the opposite hemisphere. For stimulators serving unilateral leads, channels 1–3 represent consecutive contact pairs. Channel 4 represents a wider field LFP between contacts 1 & 4. C) Representative spectra from four channels recorded from a unilateral stimulator are shown.</p

Changes in theta, gamma, and YGTSS over the six-month study.

<p>Note *TS2 exhibited optimal benefit and maximum gamma on month 5 (benefit at month 6 was 18% compared to pre-op value). Value (⧫) in gamma increase corresponds to robust drop in the YGTSS score for month 5.</p