Rene Molina

Proceedings of the Third Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies

The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tanks contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies.

Thalamocortical network activity enables chronic tic detection in humans with Tourette syndrome

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by multiple motor and vocal tics. Deep brain stimulation (DBS) is an emerging therapy for severe cases of TS. We studied two patients with TS implanted with bilateral Medtronic Activa PC + S DBS devices, capable of chronic recordings, with depth leads in the thalamic centromedian–parafascicular complex (CM-PF) and subdural strips over the precentral gyrus. Low-frequency (1–10 Hz) CM-PF activity was observed during tics, as well as modulations in beta rhythms over the motor cortex. Tics were divided into three categories: long complex, complex, and simple. Long complex tics, tics involving multiple body regions and lasting longer than 5 s, were concurrent with a highly detectable thalamocortical signature (average recall [sensitivity] 88.6%, average precision 96.3%). Complex tics were detected with an average recall of 63.9% and precision of 36.6% and simple tics an average recall of 39.3% and precision of 37.9%. The detections were determined using data from both patients.

Report of a patient undergoing chronic responsive deep brain stimulation for Tourette syndrome: proof of concept

Deep brain stimulation (DBS) has emerged as a promising intervention for the treatment of select movement and neuropsychiatric disorders. Current DBS therapies deliver electrical stimulation continuously and are not designed to adapt to a patients symptoms. Continuous DBS can lead to rapid battery depletion, which necessitates frequent surgery for battery replacement. Next-generation neurostimulation devices can monitor neural signals from implanted DBS leads, where stimulation can be delivered responsively, moving the field of neuromodulation away from continuous paradigms. To this end, the authors designed and chronically implemented a responsive stimulation paradigm in a patient with medically refractory Tourette syndrome. The patient underwent implantation of a responsive neurostimulator, which is capable of responsive DBS, with bilateral leads in the centromedian-parafascicular (Cm-Pf) region of the thalamus. A spectral feature in the 5- to 15-Hz band was identified as the control signal. Clinical data collected prior to and after 12 months of responsive therapy revealed improvements from baseline scores in both Modified Rush Tic Rating Scale and Yale Global Tic Severity Scale scores (64% and 48% improvement, respectively). The effectiveness of responsive stimulation (p = 0.16) was statistically identical to that of scheduled duty cycle stimulation (p = 0.33; 2-sided Wilcoxon unpaired rank-sum t-test). Overall, responsive stimulation resulted in a 63.3% improvement in the neurostimulators projected mean battery life. Herein, to their knowledge, the authors present the first proof of concept for responsive stimulation in a patient with Tourette syndrome.

Current Practice and the Future of Deep Brain Stimulation Therapy in Parkinson's Disease

Deep brain stimulation (DBS) is an effective therapy for Parkinsons disease patients experiencing motor fluctuations, medication-resistant tremor, and/or dyskinesia. Currently, the subthalamic nucleus and the globus pallidus internus are the two most widely used targets, with individual advantages and disadvantages influencing patient selection. Potential DBS patients are selected using the few existing guidelines and the available DBS literature, and many centers employ an interdisciplinary team review of the individuals risk-benefit profile. Programmed settings vary based on institution- or physician-specific protocols designed to maximize benefits and limit adverse effects. Expectations should be realistic and clearly defined during the evaluation process, and each bothersome symptom should be addressed in the context of building the risk-benefit profile. Current DBS research is focused on improved symptom control, the development of newer technologies, and the improved efficiency of stimulation delivery. Techniques deliver stimulation in a more personalized way, and methods of adaptive DBS such as closed-loop approaches are already on the horizon.

Impulsivity in Parkinson’s disease is associated with altered subthalamic but not globus pallidus internus activity

Background A significant subset of patients with Parkinson’s disease (PD) suffer from impulse control disorders (ICDs). A hallmark feature of many ICDs is the pursuit of rewarding behaviours despite negative consequences. Recent evidence implicates the subthalamic nucleus (STN) and globus pallidus internus (GPi) in reward and punishment processing, and deep brain stimulation (DBS) of these structures has been associated with changes in ICD symptoms. Methods We tested the hypothesis that in patients with PD diagnosed with ICD, neurons in the STN and GPi would be more responsive to reward-related stimuli and less responsive to loss-related stimuli. We studied a cohort of 43 patients with PD (12 with an ICD and 31 without) undergoing DBS electrode placement surgery. Patients performed a behavioural task in which their action choices were motivated by the potential for either a monetary reward or a monetary loss. During task performance, the activity of individual neurons was recorded in either the STN (n=100) or the GPi (n=100). Results The presence of an ICD was associated with significantly greater proportions of reward responsive neurons (p<0.01) and significantly lower proportions of loss responsive neurons (p<0.05) in the STN, but not in the GPi. Conclusions These findings provide further evidence of STN involvement in impulsive behaviour in the PD population.