P. Justin Rossi

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.

The Subthalamic Nucleus, Limbic Function, and Impulse Control

It has been well documented that deep brain stimulation (DBS) of the subthalamic nucleus (STN) to address some of the disabling motor symptoms of Parkinson’s disease (PD) can evoke unintended effects, especially on non-motor behavior. This observation has catalyzed more than a decade of research concentrated on establishing trends and identifying potential mechanisms for these non-motor effects. While many issues remain unresolved, the collective result of many research studies and clinical observations has been a general recognition of the role of the STN in mediating limbic function. In particular, the STN has been implicated in impulse control and the related construct of valence processing. A better understanding of STN involvement in these phenomena could have important implications for treating impulse control disorders (ICDs). ICDs affect up to 40% of PD patients on dopamine agonist therapy and approximately 15% of PD patients overall. ICDs have been reported to be associated with STN DBS. In this paper we will focus on impulse control and review pre-clinical, clinical, behavioral, imaging, and electrophysiological studies pertaining to the limbic function of the STN.

Translational Imperatives in Deep Brain Stimulation Research: Addressing Neuroethical Issues of Consequences and Continuity of Clinical Care

For the nonrelativist, what makes IVF morally acceptable is that there are no good reasons against it, and many good reasons in favor of it. While the cultural relativist concludes that the negative moral attitudes toward IVF in 1978 are appropriate, the nonrelativist can give reasons for why we ought to reject the 1978 attitudes as arbitrary or confused. For example, the feature of IVF that critics seem to object to is not the intentional fertilization involved, but the location of said fertilization. To paraphrase Rachels (1979), the spatial location of the fertilization hardly seems a relevant consideration. It is uncontroversially true that different cultures have different moral beliefs, and that the moral beliefs an individual or culture holds can change over time. However, the same can be said for medical beliefs and scientific beliefs, yet few medical professionals or scientists are willing to accept medical relativism or scientific relativism. Nor should they. By claiming that the bioethical concerns regarding DBS are contingent upon both the current state of DBS technology and current moral attitudes about DBS, the authors commit themselves to a troubling relativism that is wildly inconsistent with our use of moral terms, and our commonsense moral beliefs. Whether DBS is morally acceptable has nothing to do with the moral attitudes someone expressed about DBS; rather, it has to do with facts about the technology and what reasons we have for or against the implementation of that technology. CONCLUSION

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.

Proceedings of the second annual deep brain stimulation think tank: What's in the pipeline

The proceedings of the 2nd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of 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 advocacy for DBS, improving clinical outcomes, innovations in computational models of DBS, understanding of the neurophysiology of Parkinsons disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies.

The Problem of Funding Off-label Deep Brain Stimulation: Bait-and-Switch Tactics and the Need for Policy Reform

Deep brain stimulation (DBS) is currently approved by the US Food and Drug Administration to treat Parkinson disease, essential tremor, and dystonia. However, so-called off-label use of DBS may be permissible under research-based or compassionate use guidelines to treat severe, medication-refractory cases of other neurological and psychiatric disorders such as Tourette syndrome and obsessive-compulsive disorder. While affording promising outcomes, DBS surgery and its associated postoperative care is expensive. Mean initial surgical costs are US

Scheduled, intermittent stimulation of the thalamus reduces tics in Tourette syndrome

65 000 per patient, and battery replacements can add an additional

Medicare Coverage of Investigational Devices: The Troubled Path Forward for Deep Brain Stimulation

10 000 to

Measures of impulsivity in Parkinson's disease decrease after DBS in the setting of stable dopamine therapy

20 000 in costs during the first 36 months postimplantation (depending on brain target and amount of electricity required).1 These costs can be daunting because governmental and commercial insurance providers are reluctant to subsidize off-label therapies. Coverage depends on preauthorization requests that require exhaustive documentation of a patient’s medical history and peer-to-peer review with an insurance provider’s medical director. Yet, even when medical necessity has been documented and coverage preapproved, third-party payers often refuse to reimburse the costs of off-label DBS, and notification of nonpayment frequently occurs after the procedure has been implemented. Most commonly, payers deny reimbursement by referring to the terms and conditions of the policy: most policies in the United States stipulate that coverage of humanitarian or investigational therapies is provisional and may be covered on a discretionary basis. To further investigate this trend, we conducted a retrospective review of claims data for all DBS procedures performed at our university-based movement disorders center over a 10-year period (January 2005 to December 2014). During this time, 18 DBS lead implantation procedures and 56 implantable pulse generator or battery-replacement procedures were performed on 26 individual patients for non–US Food and Drug Administration–approved indications. Seven patients were treated for Tourette syndrome, 5 were treated for Alzheimer disease, and 14 were treated for obsessivecompulsive disorder. The costs of 7 lead implantations and 16 implantable pulse generator/battery surgeries were covered via dedicated research grants. Of the remaining procedures requiring third-party coverage, 8 of 11 lead implantations (72%) and 25 of 40 implantable pulse generator procedures (62.5%) were not reimbursed, despite preapproval of all cases. A depiction of coverage by diagnosis is shown in Figure, A. A striking finding of our review was that greater than half of nonreimbursed procedures could be attributed to a government insurance provider’s failure to pay (Figure, B). The so-called preapproval and subsequent denial of coverage could be regarded as a bait-and-switch tactic. Physicians (and patients) are baited to believe that coverage will be provided and then when the decision to subsidize switches and payment is denied, physicians must explain to patients and their families that coverage was refused and explain why. This financial uncertainty can impose additional stress on patients that can compromise therapeutic outcomes,2 and physicians may be obliged to draw on limited research funds to help patients cover expenses. This vexing issue imposes undue burdens on patients, families, and physicians. As a result, physicians may be less likely to perform off-label DBS procedures.3 This would incur decreased enrollment in clinical studies and hinder collection of evidence necessary to determine procedural efficacy, thereby further impeding clinical benefits and ongoing research. Because we only provide data from our center, it is difficult to determine the extent to which the findings are generalizable, particularly given that in the United States, third-party payers and their policies can vary from region to region (and even within a state). However, our finding that federal government insurance providers were among those that failed to reimburse preapproved off-label care suggests that our experience may represent a national trend. Furthermore, postures toward cost reduction and benefit restriction are becoming increasingly common on the national stage and are likely to incur more widespread constraints on third-party support for DBS and other neurotechnological interventions. Simply, we do not view the system and model of third-party support as viable. We argue that given calls for the translation of advanced neurotechnologies to clinical practice,4 limiting off-label DBS therapy only to those patients capable of self-subsidizing the procedure and its attendant postsurgical care would be inconsistent with the goals and objectives of federal directives, inequitable, impractical, and somewhat disingenuous. Ideally, insurance preapproval standards and policies for off-label procedures should be more transparent, uniformly honored by third-party payers, and enforced by law. However, we acknowledge that if reforms VIEWPOINT