Deep brain stimulation (DBS) may improve disabling tics in severely affected medication and behaviorally resistant Tourette syndrome (TS). Here we review all reported cases of TS DBS and provide updated recommendations for selection, assessment, and management of potential TS DBS cases based on the literature and implantation experience. Candidates should have a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM V) diagnosis of TS with severe motor and vocal tics, which despite exhaustive medical and behavioral treatment trials result in significant impairment. Deep brain stimulation should be offered to patients only by experienced DBS centers after evaluation by a multidisciplinary team. Rigorous preoperative and postoperative outcome measures of tics and associated comorbidities should be used. Tics and comorbid neuropsychiatric conditions should be optimally treated per current expert standards, and tics should be the major cause of disability. Psychogenic tics, embellishment, and malingering should be recognized and addressed. We have removed the previously suggested 25-year-old age limit, with the specification that a multidisciplinary team approach for screening is employed. A local ethics committee or institutional review board should be consulted for consideration of cases involving persons younger than 18 years of age, as well as in cases with urgent indications. Tourette syndrome patients represent a unique and complex population, and studies reveal a higher risk for post-DBS complications. Successes and failures have been reported for multiple brain targets; however, the optimal surgical approach remains unknown. Tourette syndrome DBS, though still evolving, is a promising approach for a subset of medication refractory and severely affected patients.

Background Subthalamic deep brain stimulation is superior to medical therapy for the motor symptoms of advanced Parkinson’s disease, and additional evidence suggests that it improves refractory symptoms of essential tremor, primary generalized dystonia, and obsessive-compulsive disorder. Despite this, its therapeutic mechanism is unknown. We hypothesized that subthalamic stimulation activates cerebral cortex at short latencies after stimulus onset during clinically effective stimulation for Parkinson disease. Methods In 5 subjects (6 hemispheres) electroencephalography measured the response of cortex to subthalamic stimulation across a range of stimulation voltages and frequencies. Novel analytical techniques reversed the anode and cathode electrode contacts and summed the resulting pair of event related potentials to suppress the stimulation artifact. Results Subthalamic brain stimulation at 20 Hertz activates somatosensory cortex at discrete latencies (mean latencies 1.0 ± 0.4, 5.7 ± 1.1, and 22.2 ± 1.8 milliseconds, denoted R1, R2, and R3, respectively). The amplitude of the short latency peak (R1) during clinically effective high frequency stimulation is nonlinearly dependent on stimulation voltage (p < 0.001, repeated measures analysis of variance), and its latency is less variable than that of R3 (1.02 versus 19.46 milliseconds, p < 0.001, Levene’s test). Conclusions Clinically effective subthalamic brain stimulation in humans with Parkinson disease activates cerebral cortex at one millisecond after stimulus onset, most likely by antidromic activation. Our findings suggest that alteration of the precise timing of action potentials in cortical neurons with axonal projections to the subthalamic region is an important component of the therapeutic mechanism of subthalamic brain stimulation.

Considering the bilateral effects and tolerability of unilateral STN DBS, unilateral stimulation followed by a contralateral procedure later, if necessary, is a reasonable option for patients with advanced Parkinson's disease, especially with prominent asymmetry.

Multiple studies have shown bilateral improvement in motor symptoms in Parkinson disease (PD) following unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) and internal segment of the globus pallidus, yet the mechanism(s) underlying this phenomenon are poorly understood. We hypothesized that STN neuronal activity is altered by contralateral STN DBS. This hypothesis was tested intraoperatively in humans with advanced PD using microelectrode recordings of the STN during contralateral STN DBS. We demonstrate alterations in the discharge pattern of STN neurons in response to contralateral STN DBS including short latency, temporally precise, stimulation frequency-independent responses consistent with antidromic activation. Furthermore, the total discharge frequency during contralateral high frequency stimulation (160 Hz) was greater than during low frequency stimulation (30 Hz) and the resting state. These findings demonstrate complex responses to DBS and imply that output activation throughout the basal ganglia-thalamic-cortical network rather than local inhibition is a therapeutic mechanism of DBS.

Deep brain stimulation relieves disabling symptoms of neurologic and psychiatric diseases when medical treatments fail, yet its therapeutic mechanism is unknown. We hypothesized that ventral intermediate nucleus stimulation for essential tremor activates cortex at short latencies and that this potential is related to suppression of tremor in the contralateral arm. We measured cortical activity with electroencephalography in 5 subjects (7 brain hemispheres) across a range of stimulator settings, and reversal of the anode and cathode electrode contacts minimized the stimulus artifact, allowing visualization of brain activity. Regression quantified the relationship between stimulation parameters and both the peak of the short latency potential and tremor suppression. Stimulation generated a polyphasic event related potential in ipsilateral sensorimotor cortex with peaks at discrete latencies beginning less than one millisecond after stimulus onset (mean latencies 0.9±0.2, 5.6±0.7, and 13.9±1.4 milliseconds, denoted R1, R2, and R3, respectively). R1 showed more fixed timing than the subsequent peaks in the response (p<0.0001, Levene’s test), and R1 amplitude and frequency were both closely associated with tremor suppression (p<0.0001, respectively). These findings demonstrate that effective ventral intermediate nucleus thalamic stimulation for essential tremor activates cerebral cortex at approximately one millisecond after the stimulus pulse. The association between this short latency potential and tremor suppression suggests that deep brain stimulation may improve tremor by synchronizing the precise timing of discharges in nearby axons, and by extension the distributed motor network, to the stimulation frequency or one of its subharmonics.

These data provide low incidences for adverse events in a large series of DBS surgeries for movement disorders at up to 10 years follow-up. Accurate estimates of adverse events will better inform patients and caregivers about the potential risks and benefits of surgery and provide normative data for process improvement.

This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson's disease, essential tremor, Alzheimer's disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year's international Think Tank, with a view toward current and near future advancement of the field.

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