Clinical applications of neurochemical and electrophysiological measurements for closed-loop neurostimulation.

The development of closed-loop deep brain stimulation (DBS) systems represents a significant opportunity for innovation in the clinical application of neurostimulation therapies. Despite the highly dynamic nature of neurological diseases, open-loop DBS applications are incapable of modifying parameters in real time to react to fluctuations in disease states. Thus, current practice for the designation of stimulation parameters, such as duration, amplitude, and pulse frequency, is an algorithmic process. Ideal stimulation parameters are highly individualized and must reflect both the specific disease presentation and the unique pathophysiology presented by the individual. Stimulation parameters currently require a lengthy trial-and-error process to achieve the maximal therapeutic effect and can only be modified during clinical visits. The major impediment to the development of automated, adaptive closed-loop systems involves the selection of highly specific disease-related biomarkers to provide feedback for the stimulation platform. This review explores the disease relevance of neurochemical and electrophysiological biomarkers for the development of closed-loop neurostimulation technologies. Electrophysiological biomarkers, such as local field potentials, have been used to monitor disease states. Real-time measurement of neurochemical substances may be similarly useful for disease characterization. Thus, the introduction of measurable neurochemical analytes has significantly expanded biomarker options for feedback-sensitive neuromodulation systems. The potential use of biomarker monitoring to advance neurostimulation approaches for treatment of Parkinson's disease, essential tremor, epilepsy, Tourette syndrome, obsessive-compulsive disorder, chronic pain, and depression is examined. Further, challenges and advances in the development of closed-loop neurostimulation technology are reviewed, as well as opportunities for next-generation closed-loop platforms.

Conflicts of interest and industry professional relationships in psychiatric neurosurgery: a comparative literature review.

OBJECTIVE The research required to establish that psychiatric treatments are effective often depends on collaboration between academic clinical researchers and industry. Some of the goals of clinical practice and those of commercial developers of psychiatric therapies overlap, such as developing safe and effective treatments. However, there might also be incompatible goals; physicians aim to provide the best care they can to their patients, whereas the medical industry ultimately aims to develop therapies that are commercially successful. In some cases, however, clinical research may be aiming both at improved patient care and commercial success. It is in these cases that a conflict of interest (COI) arises. The goal of this study was to identify differences and commonalities regarding COIs between 2 kinds of somatic psychiatric interventions: pharmacological and neurosurgical. METHODS The authors conducted a study focused on professional concerns regarding pharmacological and neurosurgical psychiatric interventions. They used medical and bioethics journal articles as an indicator of professionals' concerns and carried out a thematic content analysis of peer-reviewed articles published between 1960 and 2015, using PubMed and Google Scholar. RESULTS One hundred thirty-seven relevant articles were identified, of which 86 papers focused primarily on psychopharmacology and 51 on neurosurgery. The intervention most discussed in the psychiatric neurosurgery data set was deep brain stimulation (n = 42). While there were no significant differences at the level of categories, pharmacological and neurosurgical interventions differ in the underlying themes discussed. Two issues widely discussed in the articles on pharmaceutical interventions, but largely neglected in the neurosurgery articles, were medical professional issues and industry involvement. CONCLUSIONS COIs are a neglected issue in the discussion of ethics concerns regarding medical devices in psychiatry. Yet as these interventions become more common, it is important to address them in part through learning from the discussion regarding COIs in the pharmaceutical industry and by developing approaches to address those aspects of COIs that are unique to the medical device industry.

Deep brain stimulation for appetite disorders: a review.

The mechanisms of appetite disorders, such as refractory obesity and anorexia nervosa, have been vigorously studied over the last century, and these studies have shown that the central nervous system has significant involvement with, and responsibility for, the pathology associated with these diseases. Because deep brain stimulation has been shown to be a safe, efficacious, and adjustable treatment modality for a variety of other neurological disorders, it has also been studied as a possible treatment for appetite disorders. In studies of refractory obesity in animal models, the ventromedial hypothalamus, the lateral hypothalamus, and the nucleus accumbens have all demonstrated elements of success as deep brain stimulation targets. Multiple targets for deep brain stimulation have been proposed for anorexia nervosa, with research predominantly focusing on the subcallosal cingulate, the nucleus accumbens, and the stria terminalis and medial forebrain bundle. Human deep brain stimulation studies that focus specifically on refractory obesity and anorexia nervosa have been performed but with limited numbers of patients. In these studies, the target for refractory obesity has been the lateral hypothalamus, ventromedial hypothalamus, and nucleus accumbens, and the target for anorexia nervosa has been the subcallosal cingulate. These studies have shown promising findings, but further research is needed to elucidate the long-term efficacy of deep brain stimulation for the treatment of appetite disorders.

Deep brain stimulation for the treatment of drug addiction.

Drug addiction represents a significant public health concern that has high rates of relapse despite optimal medical therapy and rehabilitation support. New therapies are needed, and deep brain stimulation (DBS) may be an effective treatment. The past 15 years have seen numerous animal DBS studies for addiction to various drugs of abuse, with most reporting decreases in drug-seeking behavior with stimulation. The most common target for stimulation has been the nucleus accumbens, a key structure in the mesolimbic reward pathway. In addiction, the mesolimbic reward pathway undergoes a series of neuroplastic changes. Chief among them is a relative hypofunctioning of the prefrontal cortex, which is thought to lead to the diminished impulse control that is characteristic of drug addiction. The prefrontal cortex, as well as other targets involved in drug addiction such as the lateral habenula, hypothalamus, insula, and subthalamic nucleus have also been stimulated in animals, with encouraging results. Although animal studies have largely shown promising results, current DBS studies for drug addiction primarily use stimulation during active drug use. More data are needed on the effect of DBS during withdrawal in preventing future relapse. The published human experience for DBS for drug addiction is currently limited to several promising case series or case reports that are not controlled. Further animal and human work is needed to determine what role DBS can play in the treatment of drug addiction.

Therapeutic potential of deep brain stimulation of the nucleus accumbens in morbid obesity.

OBJECTIVE Morbid obesity is a growing problem worldwide. The current treatment options have limitations regarding effectiveness and complication rates. New treatment modalities are therefore warranted. One of the options is deep brain stimulation (DBS) of the nucleus accumbens (NAC). This review aims to summarize the current knowledge on NAC-DBS for the treatment of morbid obesity. METHODS Studies were obtained from multiple electronic bibliographic databases, supplemented with searches of reference lists. All animal and human studies reporting on the effects of NAC-DBS on body weight in morbidly obese patients were included. Articles found during the search were screened by 2 reviewers, and when deemed applicable, the relevant data were extracted. RESULTS Five relevant animal experimental papers were identified, pointing toward a beneficial effect of high-frequency stimulation of the lateral shell of the NAC. Three human case reports show a beneficial effect of NAC-DBS on body weight in morbidly obese patients. CONCLUSIONS The available literature supports NAC-DBS to treat morbid obesity. The number of well-conducted animal studies, however, is very limited. Also, the optimal anatomical position of the DBS electrode within the NAC, as well as the optimal stimulation parameters, has not yet been established. These matters need to be addressed before this strategy can be considered for human clinical trials.

High-intensity focused ultrasound: past, present, and future in neurosurgery.

Since Lynn and colleagues first described the use of focused ultrasound (FUS) waves for intracranial ablation in 1942, many strides have been made toward the treatment of several brain pathologies using this novel technology. In the modern era of minimal invasiveness, high-intensity focused ultrasound (HIFU) promises therapeutic utility for multiple neurosurgical applications, including treatment of tumors, stroke, epilepsy, and functional disorders. Although the use of HIFU as a potential therapeutic modality in the brain has been under study for several decades, relatively few neuroscientists, neurologists, or even neurosurgeons are familiar with it. In this extensive review, the authors intend to shed light on the current use of HIFU in different neurosurgical avenues and its mechanism of action, as well as provide an update on the outcome of various trials and advances expected from various preclinical studies in the near future. Although the initial technical challenges have been overcome and the technology has been improved, only very few clinical trials have thus far been carried out. The number of clinical trials related to neurological disorders is expected to increase in the coming years, as this novel therapeutic device appears to have a substantial expansive potential. There is great opportunity to expand the use of HIFU across various medical and surgical disciplines for the treatment of different pathologies. As this technology gains recognition, it will open the door for further research opportunities and innovation.

Psychosurgery, ethics, and media: a history of Walter Freeman and the lobotomy.

At the peak of his career, Walter J. Freeman II was a celebrated physician and scientist. He served as the first chairman of the Department of Neurology at George Washington University and was a tireless advocate of surgical treatment for mental illness. His eccentric appearance, engaging personality during interviews, and theatrical demonstrations of his surgical techniques gained him substantial popularity with local and national media, and he performed more than 3000 prefrontal and transorbital lobotomies between 1930 and 1960. However, poor patient outcomes, unfavorable portrayals of the lobotomy in literature and film, and increased regulatory scrutiny contributed to the lobotomy's decline in popularity. The development of antipsychotic medications eventually relegated the lobotomy to rare circumstances, and Freeman's reputation deteriorated. Today, despite significant advancements in technique, oversight, and ethical scrutiny, neurosurgical treatment of mental illness still carries a degree of social stigma. This review presents a historical account of Walter Freeman's life and career, and the popularization of the lobotomy in the US. Additionally, the authors pay special attention to the influence of popular literature and film on the public's perception of psychosurgery. Aided by an understanding of this pivotal period in medical history, neurosurgeons are poised to confront the ethical and sociological questions facing psychosurgery as it continues to evolve.

History of psychosurgery at Sainte-Anne Hospital, Paris, France, through translational interactions between psychiatrists and neurosurgeons.

Sainte-Anne Hospital is the largest psychiatric hospital in Paris. Its long and fascinating history began in the 18th century. In 1952, it was at Sainte-Anne Hospital that Jean Delay and Pierre Deniker used the first neuroleptic, chlorpromazine, to cure psychiatric patients, putting an end to the expansion of psychosurgery. The Department of Neuro-psychosurgery was created in 1941. The works of successive heads of the Neurosurgery Department at Sainte-Anne Hospital summarized the history of psychosurgery in France. Pierre Puech defined psychosurgery as the necessary cooperation between neurosurgeons and psychiatrists to treat the conditions causing psychiatric symptoms, from brain tumors to mental health disorders. He reported the results of his series of 369 cases and underlined the necessity for proper follow-up and postoperative re-education, illustrating the relative caution of French neurosurgeons concerning psychosurgery. Marcel David and his assistants tried to follow their patients closely postoperatively; this resulted in numerous publications with significant follow-up and conclusions. As early as 1955, David reported intellectual degradation 2 years after prefrontal leucotomies. Jean Talairach, a psychiatrist who eventually trained as a neurosurgeon, was the first to describe anterior capsulotomy in 1949. He operated in several hospitals outside of Paris, including the Sarthe Psychiatric Hospital and the Public Institution of Mental Health in the Lille region. He developed stereotactic surgery, notably stereo-electroencephalography, for epilepsy surgery but also to treat psychiatric patients using stereotactic lesioning with radiofrequency ablation or radioactive seeds of yttrium-90. The evolution of functional neurosurgery has been marked by the development of deep brain stimulation, in particular for obsessive-compulsive disorder, replacing the former lesional stereotactic procedures. The history of Sainte-Anne Hospital's Neurosurgery Department sheds light on the initiation-yet fast reconsideration-of psychosurgery in France. This relatively more prudent attitude toward the practice of psychosurgery compared with other countries was probably due to the historically strong collaboration between psychiatrists and neurosurgeons in France.

A brief note on the history of psychosurgery in Japan.

In Japan, there has been no neurosurgical treatment for psychiatric disorders since the 1970s. Even deep brain stimulation (DBS) has not been studied or used for psychiatric disorders. Neurosurgery for psychiatric disorders has been thwarted by social taboos for many years, and psychiatrists today seem to simply ignore modern developments and therapies offered by neurosurgery such as DBS. As a result, most patients and their families do not know such "last-resort" options exist. Historically, as in other countries, frontal lobotomies were widely performed in Japan in the 1940s and 1950s, and some Japanese neurosurgeons used stereotactic methods for the treatment of psychiatric disorders until the 1960s. However, in the 1960s and 1970s such surgical treatments began to receive condemnation based on political judgment, rather than on medical and scientific evaluation. Protest campaigns at the time hinged on the prevailing political beliefs, forming a part of the new "left" movement against leading authorities across a wide range of societal institutions including medical schools. Finally, the Japanese Society for Psychiatry and Neurology banned the surgical treatment for psychiatric disorders in 1975. Even today, Japan's dark history continues to exert an enormous negative influence on neurosurgery for psychiatric disorders.

The origins and persistence of psychosurgery in the state of Iowa.

Neurosurgery for the treatment of psychological disorders has a checkered history in the United States. Prior to the advent of antipsychotic medications, individuals with severe mental illness were institutionalized and subjected to extreme therapies in an attempt to palliate their symptoms. Psychiatrist Walter Freeman first introduced psychosurgery, in the form of frontal lobotomy, as an intervention that could offer some hope to those patients in whom all other treatments had failed. Since that time, however, the use of psychosurgery in the United States has waxed and waned significantly, though literature describing its use is relatively sparse. In an effort to contribute to a better understanding of the evolution of psychosurgery, the authors describe the history of psychosurgery in the state of Iowa and particularly at the University of Iowa Department of Neurosurgery. An interesting aspect of psychosurgery at the University of Iowa is that these procedures have been nearly continuously active since Freeman introduced the lobotomy in the 1930s. Frontal lobotomies and transorbital leukotomies were performed by physicians in the state mental health institutions as well as by neurosurgeons at the University of Iowa Hospitals and Clinics (formerly known as the State University of Iowa Hospital). Though the early technique of frontal lobotomy quickly fell out of favor, the use of neurosurgery to treat select cases of intractable mental illness persisted as a collaborative treatment effort between psychiatrists and neurosurgeons at Iowa. Frontal lobotomies gave way to more targeted lesions such as anterior cingulotomies and to neuromodulation through deep brain stimulation. As knowledge of brain circuits and the pathophysiology underlying mental illness continues to grow, surgical intervention for psychiatric pathologies is likely to persist as a viable treatment option for select patients at the University of Iowa and in the larger medical community.

Deep brain stimulation for the obsessive-compulsive and Tourette-like symptoms of Kleefstra syndrome.

Deep brain stimulation (DBS) has been reported to have beneficial effects in severe, treatment-refractory cases of obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). In this report, the authors present the first case in which DBS was used to treat the neuropsychiatric symptoms of Kleefstra syndrome, a rare genetic disorder characterized by childhood hypotonia, intellectual disability, distinctive facial features, and myriad psychiatric and behavioral disturbances. A 24-year-old female patient with childhood hypotonia, developmental delay, and diagnoses of autism spectrum disorder, OCD, and TS refractory to medical management underwent the placement of bilateral ventral capsule/ventral striatum (VC/VS) DBS leads, with clinical improvement. Medical providers and family observed gradual and progressive improvement in the patient's compulsive behaviors, coprolalia, speech, and social interaction. Symptoms recurred when both DBS electrodes failed because of lead fracture and dislodgement, although the clinical benefits were restored by lead replacement. The symptomatic and functional improvements observed in this case of VC/VS DBS for Kleefstra syndrome suggest a novel indication for DBS worthy of further investigation.

Deep brain stimulation for severe autism: from pathophysiology to procedure.

Autism is a heterogeneous neurodevelopmental disorder characterized by early-onset impairment in social interaction and communication and by repetitive, restricted behaviors and interests. Because the degree of impairment may vary, a spectrum of clinical manifestations exists. Severe autism is characterized by complete lack of language development and potentially life-threatening self-injurious behavior, the latter of which may be refractory to medical therapy and devastating for affected individuals and their caretakers. New treatment strategies are therefore needed. Here, the authors propose deep brain stimulation (DBS) of the basolateral nucleus of the amygdala (BLA) as a therapeutic intervention to treat severe autism. The authors review recent developments in the understanding of the pathophysiology of autism. Specifically, they describe the genetic and environmental alterations that affect neurodevelopment. The authors also highlight the resultant microstructural, macrostructural, and functional abnormalities that emerge during brain development, which create a pattern of dysfunctional neural networks involved in socioemotional processing. They then discuss how these findings implicate the BLA as a key node in the pathophysiology of autism and review a reported case of BLA DBS for treatment of severe autism. Much progress has been made in recent years in understanding the pathophysiology of autism. The BLA represents a logical neurosurgical target for treating severe autism. Further study is needed that considers mechanistic and operative challenges.

Deep brain stimulation for obesity: rationale and approach to trial design.

Obesity is one of the most serious public health concerns in the US. While bariatric surgery has been shown to be successful for treatment of morbid obesity for those who have undergone unsuccessful behavioral modification, its associated risks and rates of relapse are not insignificant. There exists a neurological basis for the binge-like feeding behavior observed in morbid obesity that is believed to be due to dysregulation of the reward circuitry. The authors present a review of the evidence of the neuroanatomical basis for obesity, the potential neural targets for deep brain stimulation (DBS), as well as a rationale for DBS and future trial design. Identification of an appropriate patient population that would most likely benefit from this type of therapy is essential. There are also significant cost and ethical considerations for such a neuromodulatory intervention designed to alter maladaptive behavior. Finally, the authors present a consolidated set of inclusion criteria and study end points that should serve as the basis for any trial of DBS for obesity.

Deep brain stimulation for obesity: past, present, and future targets.

The authors review the history of deep brain stimulation (DBS) in patients for treating obesity, describe current DBS targets in the brain, and discuss potential DBS targets and nontraditional stimulation parameters that may improve the effectiveness of DBS for ameliorating obesity. Deep brain stimulation for treating obesity has been performed both in animals and in humans with intriguing preliminary results. The brain is an attractive target for addressing obesity because modulating brain activity may permit influencing both sides of the energy equation--caloric intake and energy expenditure.

Deep brain stimulation for psychiatric disorders: where we are now.

Fossil records showing trephination in the Stone Age provide evidence that humans have sought to influence the mind through physical means since before the historical record. Attempts to treat psychiatric disease via neurosurgical means in the 20th century provided some intriguing initial results. However, the indiscriminate application of these treatments, lack of rigorous evaluation of the results, and the side effects of ablative, irreversible procedures resulted in a backlash against brain surgery for psychiatric disorders that continues to this day. With the advent of psychotropic medications, interest in invasive procedures for organic brain disease waned. Diagnosis and classification of psychiatric diseases has improved, due to a better understanding of psychiatric patho-physiology and the development of disease and treatment biomarkers. Meanwhile, a significant percentage of patients remain refractory to multiple modes of treatment, and psychiatric disease remains the number one cause of disability in the world. These data, along with the safe and efficacious application of deep brain stimulation (DBS) for movement disorders, in principle a reversible process, is rekindling interest in the surgical treatment of psychiatric disorders with stimulation of deep brain sites involved in emotional and behavioral circuitry. This review presents a brief history of psychosurgery and summarizes the development of DBS for psychiatric disease, reviewing the available evidence for the current application of DBS for disorders of the mind.

Anterior capsulotomy for obsessive-compulsive disorder: a review of old and new literature.

Over the last two decades, deep brain stimulation (DBS) has gained popularity as a treatment of severe and medically refractory obsessive-compulsive disorder (OCD), often using brain targets informed by historical lesional neurosurgical procedures. Paradoxically, the use of DBS in OCD has led some multidisciplinary teams to revisit the use of lesional procedures, especially anterior capsulotomy (AC), although significant aversion still exists toward the use of lesional neurosurgery for psychiatric disorders. This paper aims to review all literature on the use of AC for OCD to examine its effectiveness and safety profile.All publications on AC for OCD were searched. In total 512 patients were identified in 25 publications spanning 1961-2018. In papers where a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score was available, 73% of patients had a clinical response (i.e., > 35% improvement in Y-BOCS score) and 24% patients went into remission (Y-BOCS score < 8). In the older publications, published when the Y-BOCS was not yet available, 90% of patients were deemed to have had a significant clinical response and 39% of patients were considered symptom free. The rate of serious complications was low.In summary, AC is a safe, well-tolerated, and efficacious therapy. Its underuse is likely a result of historical prejudice rather than lack of clinical effectiveness.

A multicenter, open-label, controlled trial on acceptance, convenience, and complications of rechargeable internal pulse generators for deep brain stimulation: the Multi Recharge Trial.

OBJECTIVE: Rechargeable neurostimulators for deep brain stimulation have been available since 2008, promising longer battery life and fewer replacement surgeries compared to non-rechargeable systems. Long-term data on how recharging affects movement disorder patients are sparse. This is the first multicenter, patient-focused, industry-independent study on rechargeable neurostimulators. METHODS: Four neurosurgical centers sent a questionnaire to all adult movement disorder patients with a rechargeable neurostimulator implanted at the time of the trial. The primary endpoint was the convenience of the recharging process rated on an ordinal scale from "very hard" (1) to "very easy" (5). Secondary endpoints were charge burden (time spent per week on recharging), user confidence, and complication rates. Endpoints were compared for several subgroups. RESULTS: Datasets of 195 movement disorder patients (66.1% of sent questionnaires) with Parkinson's disease (PD), tremor, or dystonia were returned and included in the analysis. Patients had a mean age of 61.3 years and the device was implanted for a mean of 40.3 months. The overall convenience of recharging was rated as "easy" (4). The mean charge burden was 122 min/wk and showed a positive correlation with duration of therapy; 93.8% of users felt confident recharging the device. The rate of surgical revisions was 4.1%, and the infection rate was 2.1%. Failed recharges occurred in 8.7% of patients, and 3.6% of patients experienced an interruption of therapy because of a failed recharge. Convenience ratings by PD patients were significantly worse than ratings by dystonia patients. Caregivers recharged the device for the patient in 12.3% of cases. Patients who switched from a non-rechargeable to a rechargeable neurostimulator found recharging to be significantly less convenient at a higher charge burden than did patients whose primary implant was rechargeable. Age did not have a significant impact on any endpoint. CONCLUSIONS: Overall, patients with movement disorders rated recharging as easy, with low complication rates and acceptable charge burden.

Pallidal deep brain stimulation combined with capsulotomy for Tourette's syndrome with psychiatric comorbidity.

OBJECTIVE: A current challenge is finding an effective and safe treatment for severely disabled patients with Tourette's syndrome (TS) and comorbid psychiatric disorders, in whom conventional treatments have failed. The authors aimed to evaluate the utility of globus pallidus internus deep brain stimulation (GPi-DBS) combined with bilateral anterior capsulotomy in treating these clinically challenging patients. METHODS: The authors conducted a retrospective review of the clinical history and outcomes of 10 severely disabled patients with treatment-refractory TS and a psychiatric comorbidity, who had undergone GPi-DBS combined with bilateral anterior capsulotomy in their hospital. At the time of surgery, patients presented mainly with obsessive-compulsive disorder and affective disorders. Clinical outcome assessments of tic and psychiatric symptoms, as well as of general adaptive functioning and quality of life, were performed at the time of surgery and at 6, 12, and between 24 and 96 months postsurgery. RESULTS: After surgery, all patients showed significant progressive improvements in tic and psychiatric symptoms, along with improvements in general adaptive functioning and quality of life. Tic alleviation reached 64% at 12 months and 77% at the last follow-up on the Yale Global Tic Severity Scale. At the final follow-up, patients had functionally recovered and displayed no or only mild tic and psychiatric symptoms. All patients tolerated treatment reasonably well, with no serious side effects. CONCLUSIONS: GPi-DBS combined with bilateral anterior capsulotomy seems to offer major clinical benefits to severely disabled patients with otherwise treatment-refractory TS and psychiatric comorbidities.

Current and future directions of deep brain stimulation for neurological and psychiatric disorders.

Deep brain stimulation (DBS) has evolved considerably over the past 4 decades. Although it has primarily been used to treat movement disorders such as Parkinson's disease, essential tremor, and dystonia, recently it has been approved to treat obsessive-compulsive disorder and epilepsy. Novel potential indications in both neurological and psychiatric disorders are undergoing active study. There have been significant advances in DBS technology, including preoperative and intraoperative imaging, surgical approaches and techniques, and device improvements. In addition to providing significant clinical benefits and improving quality of life, DBS has also increased the understanding of human electrophysiology and network interactions. Despite the value of DBS, future developments should be aimed at developing less invasive techniques and attaining not just symptom improvement but curative disease modification.

Deep brain stimulation for Tourette syndrome: a single-center series.

OBJECTIVE Tourette syndrome (TS) is a complex neuropsychiatric disorder characterized by multiple motor and phonic tics. While pharmacological and behavioral therapy can be effective in most patients, a subset of patients remains refractory to treatment. Increasing clinical evidence from multiple centers suggests that deep brain stimulation (DBS) of the medial thalamus can be effective in many cases of refractory TS. METHODS The authors retrospectively reviewed outcomes in 13 patients with refractory TS who underwent medial thalamic DBS performed by their team over a 7-year period. Patients were evaluated by a multidisciplinary team, and preoperative objective assessments were performed using the Yale Global Tic Severity Scale (YGTSS) and Yale-Brown Obsessive Compulsive Scale. YGTSS scores were calculated at visits immediately postoperatively and at the most recent follow-up in patients with a minimum of 6 months of postoperative follow-up. Coordinates of the active DBS contacts were calculated and projected onto each patient's pre- and postoperative images. RESULTS Patients showed an average decrease of 37% (p = 0.0063) in the total tic severity at their first postoperative visit. At their latest visit, their scores achieved significance, decreasing from preoperative scores by an average of 50% (p = 0.0014). The average position of the active contact was noted to be at the junction of the posterior ventralis oralis internus/centromedian-parafascicular nuclei. Device-related complications occurred in 2 patients, necessitating additional surgeries. All patients continued to use the system at last follow-up. CONCLUSIONS The authors' data are consistent with the small but growing body of literature supporting DBS of the ventralis oralis internus/centromedian-parafascicular thalamus as an effective and relatively safe treatment for severe, refractory TS.