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Parkinson Disease: HELP
Articles by Kelly D. Foote
Based on 60 articles published since 2010
(Why 60 articles?)
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Between 2010 and 2020, K. Foote wrote the following 60 articles about Parkinson Disease.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review Pedunculopontine Nucleus Region Deep Brain Stimulation in Parkinson Disease: Surgical Techniques, Side Effects, and Postoperative Imaging. 2016

Hamani, Clement / Lozano, Andres M / Mazzone, Paolo A M / Moro, Elena / Hutchison, William / Silburn, Peter A / Zrinzo, Ludvic / Alam, Mesbah / Goetz, Laurent / Pereira, Erlick / Rughani, Anand / Thevathasan, Wesley / Aziz, Tipu / Bloem, Bastiaan R / Brown, Peter / Chabardes, Stephan / Coyne, Terry / Foote, Kelly / Garcia-Rill, Edgar / Hirsch, Etienne C / Okun, Michael S / Krauss, Joachim K. ·Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ont., Canada. ·Stereotact Funct Neurosurg · Pubmed #27728909.

ABSTRACT: The pedunculopontine nucleus (PPN) region has received considerable attention in clinical studies as a target for deep brain stimulation (DBS) in Parkinson disease. These studies have yielded variable results with an overall impression of improvement in falls and freezing in many but not all patients treated. We evaluated the available data on the surgical anatomy and terminology of the PPN region in a companion paper. Here we focus on issues concerning surgical technique, imaging, and early side effects of surgery. The aim of this paper was to gain more insight into the reasoning for choosing specific techniques and to discuss shortcomings of available studies. Our data demonstrate the wide range in almost all fields which were investigated. There are a number of important challenges to be resolved, such as identification of the optimal target, the choice of the surgical approach to optimize electrode placement, the impact on the outcome of specific surgical techniques, the reliability of intraoperative confirmation of the target, and methodological differences in postoperative validation of the electrode position. There is considerable variability both within and across groups, the overall experience with PPN DBS is still limited, and there is a lack of controlled trials. Despite these challenges, the procedure seems to provide benefit to selected patients and appears to be relatively safe. One important limitation in comparing studies from different centers and analyzing outcomes is the great variability in targeting and surgical techniques, as shown in our paper. The challenges we identified will be of relevance when designing future studies to better address several controversial issues. We hope that the data we accumulated may facilitate the development of surgical protocols for PPN DBS.

2 Review Pedunculopontine Nucleus Region Deep Brain Stimulation in Parkinson Disease: Surgical Anatomy and Terminology. 2016

Hamani, Clement / Aziz, Tipu / Bloem, Bastiaan R / Brown, Peter / Chabardes, Stephan / Coyne, Terry / Foote, Kelly / Garcia-Rill, Edgar / Hirsch, Etienne C / Lozano, Andres M / Mazzone, Paolo A M / Okun, Michael S / Hutchison, William / Silburn, Peter / Zrinzo, Ludvic / Alam, Mesbah / Goetz, Laurent / Pereira, Erlick / Rughani, Anand / Thevathasan, Wesley / Moro, Elena / Krauss, Joachim K. ·Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ont., Canada. ·Stereotact Funct Neurosurg · Pubmed #27723662.

ABSTRACT: Several lines of evidence over the last few years have been important in ascertaining that the pedunculopontine nucleus (PPN) region could be considered as a potential target for deep brain stimulation (DBS) to treat freezing and other problems as part of a spectrum of gait disorders in Parkinson disease and other akinetic movement disorders. Since the introduction of PPN DBS, a variety of clinical studies have been published. Most indicate improvements in freezing and falls in patients who are severely affected by these problems. The results across patients, however, have been variable, perhaps reflecting patient selection, heterogeneity in target selection and differences in surgical methodology and stimulation settings. Here we outline both the accumulated knowledge and the domains of uncertainty in surgical anatomy and terminology. Specific topics were assigned to groups of experts, and this work was accumulated and reviewed by the executive committee of the working group. Areas of disagreement were discussed and modified accordingly until a consensus could be reached. We demonstrate that both the anatomy and the functional role of the PPN region need further study. The borders of the PPN and of adjacent nuclei differ when different brainstem atlases and atlas slices are compared. It is difficult to delineate precisely the PPN pars dissipata from the nucleus cuneiformis, as these structures partially overlap. This lack of clarity contributes to the difficulty in targeting and determining the exact localization of the electrodes implanted in patients with akinetic gait disorders. Future clinical studies need to consider these issues.

3 Review Proceedings of the Second Annual Deep Brain Stimulation Think Tank: What's in the Pipeline. 2015

Gunduz, Aysegul / Morita, Hokuto / Rossi, P Justin / Allen, William L / Alterman, Ron L / Bronte-Stewart, Helen / Butson, Christopher R / Charles, David / Deckers, Sjaak / de Hemptinne, Coralie / DeLong, Mahlon / Dougherty, Darin / Ellrich, Jens / Foote, Kelly D / Giordano, James / Goodman, Wayne / Greenberg, Benjamin D / Greene, David / Gross, Robert / Judy, Jack W / Karst, Edward / Kent, Alexander / Kopell, Brian / Lang, Anthony / Lozano, Andres / Lungu, Codrin / Lyons, Kelly E / Machado, Andre / Martens, Hubert / McIntyre, Cameron / Min, Hoon-Ki / Neimat, Joseph / Ostrem, Jill / Pannu, Sat / Ponce, Francisco / Pouratian, Nader / Reymers, Donnie / Schrock, Lauren / Sheth, Sameer / Shih, Ludy / Stanslaski, Scott / Steinke, G Karl / Stypulkowski, Paul / Tröster, Alexander I / Verhagen, Leo / Walker, Harrison / Okun, Michael S. ·University of Florida , Gainesville, FL , USA. ·Int J Neurosci · Pubmed #25526555.

ABSTRACT: 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 Parkinson's disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies.

4 Review Swallowing and deep brain stimulation in Parkinson's disease: a systematic review. 2013

Troche, Michelle S / Brandimore, Alexandra E / Foote, Kelly D / Okun, Michael S. ·Department of Speech, Language, & Hearing Sciences, University of Florida, Gainesville, FL, USA. ·Parkinsonism Relat Disord · Pubmed #23726461.

ABSTRACT: The purpose of this review is to assess the current state of the literature on the topic of deep brain stimulation (DBS) and its effects on swallowing function in Parkinson's disease (PD). Pubmed, Cochrane review, and web of science searches were completed on all articles addressing DBS that contained a swallowing outcome measure. Outcome measures included the penetration/aspiration scale, pharyngeal transit time, oropharyngeal residue, drooling, aspiration pneumonia, death, hyolaryngeal excursion, epiglottic inversion, UPDRS scores, and presence of coughing/throat clearing during meals. The search identified 13 studies specifically addressing the effects of DBS on swallowing. Critical assessment of the 13 identified peer-reviewed publications revealed nine studies employing an experimental design, (e.g. "on" vs. "off", pre- vs. post-DBS) and four case reports. None of the nine experimental studies were found to identify clinically significant improvement or decline in swallowing function with DBS. Despite these findings, several common threads were identified across experimental studies and will be examined in this review. Additionally, available data demonstrate that, although subthalamic nucleus (STN) stimulation has been considered to cause more impairment to swallowing function than globus pallidus internus (GPi) stimulation, there are no experimental studies directly comparing swallowing function in STN vs. GPi. Moreover, there has been no comparison of unilateral vs. bilateral DBS surgery and the coincident effects on swallowing function. This review includes a critical analysis of all experimental studies and discusses methodological issues that should be addressed in future studies.

5 Review Deep brain stimulation for Parkinson disease: an expert consensus and review of key issues. 2011

Bronstein, Jeff M / Tagliati, Michele / Alterman, Ron L / Lozano, Andres M / Volkmann, Jens / Stefani, Alessandro / Horak, Fay B / Okun, Michael S / Foote, Kelly D / Krack, Paul / Pahwa, Rajesh / Henderson, Jaimie M / Hariz, Marwan I / Bakay, Roy A / Rezai, Ali / Marks, William J / Moro, Elena / Vitek, Jerrold L / Weaver, Frances M / Gross, Robert E / DeLong, Mahlon R. ·University of California, Los Angeles, School of Medicine, Department of Neurology, 710 Westwood Plaza, Los Angeles, CA 90095, USA. jbronste@ucla.edu ·Arch Neurol · Pubmed #20937936.

ABSTRACT: OBJECTIVE: To provide recommendations to patients, physicians, and other health care providers on several issues involving deep brain stimulation (DBS) for Parkinson disease (PD). DATA SOURCES AND STUDY SELECTION: An international consortium of experts organized, reviewed the literature, and attended the workshop. Topics were introduced at the workshop, followed by group discussion. DATA EXTRACTION AND SYNTHESIS: A draft of a consensus statement was presented and further edited after plenary debate. The final statements were agreed on by all members. CONCLUSIONS: (1) Patients with PD without significant active cognitive or psychiatric problems who have medically intractable motor fluctuations, intractable tremor, or intolerance of medication adverse effects are good candidates for DBS. (2) Deep brain stimulation surgery is best performed by an experienced neurosurgeon with expertise in stereotactic neurosurgery who is working as part of a interprofessional team. (3) Surgical complication rates are extremely variable, with infection being the most commonly reported complication of DBS. (4) Deep brain stimulation programming is best accomplished by a highly trained clinician and can take 3 to 6 months to obtain optimal results. (5) Deep brain stimulation improves levodopa-responsive symptoms, dyskinesia, and tremor; benefits seem to be long-lasting in many motor domains. (6) Subthalamic nuclei DBS may be complicated by increased depression, apathy, impulsivity, worsened verbal fluency, and executive dysfunction in a subset of patients. (7) Both globus pallidus pars interna and subthalamic nuclei DBS have been shown to be effective in addressing the motor symptoms of PD. (8) Ablative therapy is still an effective alternative and should be considered in a select group of appropriate patients.

6 Review Parkinson’s disease DBS: what, when, who and why? The time has come to tailor DBS targets. 2010

Okun, Michael S / Foote, Kelly D. ·University of Florida Movement Disorders Center, McKnight Brain Institute, Gainesville, FL USA. okun@neurology.ufl.edu ·Expert Rev Neurother · Pubmed #21384698.

ABSTRACT: Deep brain stimulation (DBS) has recently been proven to be an effective therapy for medication refractory symptoms of Parkinson's disease. As the evidence base continues to evolve, many important issues have surfaced, including: what operation should be performed (brain target[s],unilateral vs bilateral, simultaneous vs staged); when to operate (how early is too early to intervene?), who should be operated on (disease duration, age, symptom profiles and the use of the interdisciplinary screening team); and finally, why to operate (the rationale of surgery vs medication/apomorphine pumps/duodopa pumps/stem cell trials/gene therapy trials). We will address each of these critical issues, as well make the argument that a tailored approach to DBS and DBS targeting will best serve each potential candidate. We will review the multiple peer reviewed studies and we will emphasize the recently available data from randomized DBS studies.We will argue that moving away from a single DBS target (e.g., subthalamic nucleus DBS) and a single approach to DBS methodology (e.g., bilateral simultaneous operations) is a reasonable next step for the Parkinson's disease community. Following careful interdisciplinary DBS screening, a physician-patient discussion has the potential to establish a patient-centered and symptom-specific outcome for each potential DBS candidate. The interdisciplinary DBS team can function together to formulate and to consider an optimal and tailored approach. A tailored approach will allow for the consideration of the complex and numerous variables that may contribute to a positive or negative overall DBS outcome. We will review and provide expert commentary on a potential interdisciplinary approach to selecting unilateral or alternatively bilateral subthalamic nucleus or globus pallidus internus DBS. Our approach is aimed to maximize benefit(s) and minimize risk(s) in order to best tailor therapy for an individual patient.

7 Review INPH and Parkinson disease: differentiation by levodopa response. 2010

Morishita, Takashi / Foote, Kelly D / Okun, Michael S. ·Department of Neurology, University of Florida College of Medicine, Shands Hospital, Movement Disorders Center, McKnight Brain Institute, 100 S. Newell Drive, Gainesville, FL 32610, USA. ·Nat Rev Neurol · Pubmed #20057498.

ABSTRACT: Differentiating between Parkinson disease (PD) and idiopathic normal pressure hydrocephalus (INPH) can be challenging for the practicing clinician. Patients with undiagnosed PD but with incidental ventriculomegaly run the risk of being subjected to unnecessary shunt surgery. Taking a family history of PD and establishing the presence of motor symptoms (tremor, rigidity, bradykinesia) and nonmotor symptoms could help to differentiate between the two disorders. For patients with parkinsonian features, a dopamine challenge test to exclude the possibility of idiopathic PD might be beneficial. In this article, we highlight the difficulty of accurately differentiating INPH from PD as illustrated by three clinical cases of patients referred for shunt surgery.

8 Clinical Trial Acute and Chronic Mood and Apathy Outcomes from a randomized study of unilateral STN and GPi DBS. 2014

Okun, Michael S / Wu, Samuel S / Fayad, Sarah / Ward, Herbert / Bowers, Dawn / Rosado, Christian / Bowen, Lauren / Jacobson, Charles / Butson, Christopher / Foote, Kelly D. ·Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Gainesville, FL, United States of America; Department of Neurosurgery, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Gainesville, FL, United States of America. · Department of Biostatistics, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Gainesville, FL, United States of America. · Department of Psychiatry, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Gainesville, FL, United States of America. · Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Gainesville, FL, United States of America; Department of Clinical and Health Psychology, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Gainesville, FL, United States of America. · Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Gainesville, FL, United States of America. · Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, United States of America. · Department of Neurosurgery, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Gainesville, FL, United States of America. ·PLoS One · Pubmed #25469706.

ABSTRACT: OBJECTIVE: To study mood and behavioral effects of unilateral and staged bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for Parkinson's disease (PD). BACKGROUND: There are numerous reports of mood changes following DBS, however, most have focused on bilateral simultaneous STN implants with rapid and aggressive post-operative medication reduction. METHODS: A standardized evaluation was applied to a subset of patients undergoing STN and GPi DBS and who were also enrolled in the NIH COMPARE study. The Unified Parkinson Disease Rating Scale (UPDRS III), the Hamilton depression (HAM-D) and anxiety rating scales (HAM-A), the Yale-Brown obsessive-compulsive rating scale (YBOCS), the Apathy Scale (AS), and the Young mania rating scale (YMRS) were used. The scales were repeated at acute and chronic intervals. A post-operative strategy of non-aggressive medication reduction was employed. RESULTS: Thirty patients were randomized and underwent unilateral DBS (16 STN, 14 GPi). There were no baseline differences. The GPi group had a higher mean dopaminergic dosage at 1-year, however the between group difference in changes from baseline to 1-year was not significant. There were no differences between groups in mood and motor outcomes. When combining STN and GPi groups, the HAM-A scores worsened at 2-months, 4-months, 6-months and 1-year when compared with baseline; the HAM-D and YMRS scores worsened at 4-months, 6-months and 1-year; and the UPDRS Motor scores improved at 4-months and 1-year. Psychiatric diagnoses (DSM-IV) did not change. No between group differences were observed in the cohort of bilateral cases. CONCLUSIONS: There were few changes in mood and behavior with STN or GPi DBS. The approach of staging STN or GPi DBS without aggressive medication reduction could be a viable option for managing PD surgical candidates. A study of bilateral DBS and of medication reduction will be required to better understand risks and benefits of a bilateral approach.

9 Clinical Trial Selection of deep brain stimulation candidates in private neurology practices: referral may be simpler than a computerized triage system. 2012

Oyama, Genko / Rodriguez, Ramon L / Jones, Jacob D / Swartz, Camille / Merritt, Stacy / Unger, Richard / Hubmann, Monica / Delgado, Alain / Simon, Ely / Doniger, Glen M / Bowers, Dawn / Foote, Kelly D / Fernandez, Hubert H / Okun, Michael S. ·Department of Neurology, University of Florida, Center for Movement Disorders and Neurorestoration, McKnight Brain Institute, Gainesville, FL 32610, USA. ·Neuromodulation · Pubmed #22376158.

ABSTRACT: OBJECTIVE: The objective of this study is to compare a computerized deep brain stimulation (DBS) screening module (Comparing Private Practice vs. Academic Centers in Selection of DBS Candidates [COMPRESS], NeuroTrax Corp., Bellaire, TX, USA) with traditional triage by a movement disorders specialized neurologist as the gold standard. METHODS: The COMPRESS consists of a combination of the Florida Surgical Questionnaire for Parkinson disease (FLASQ-PD), a cognitive assessment battery provided by MindStreams® (NeuroTrax Corp.), and the Geriatric Depression Scale and the Zung Anxiety Self-Assessment Scale. COMPRESS resulted in the classification of patients into three categories: "optimal candidate,""probable candidate," and "not a good candidate." Similar categorical ratings made by a referring private practice neurologist and by a trained movement disorders specialist were compared with the ratings generated by COMPRESS. RESULTS: A total of 19 subjects with Parkinson's disease were enrolled from five private neurological practices. The clinical impressions of the private practice neurologist vs. those of the movement disorders specialist were in agreement approximately half the time (10/19 cases). The movement disorders specialist and COMPRESS agreed on 15/19 cases. A further comparison between outcomes from the entire COMPRESS module and the FLASQ-PD questionnaire by itself resulted in high agreement (18/19 cases in agreement). CONCLUSIONS: The COMPRESS agreed with an in-person evaluation by a movement disorders neurologist approximately 80% of the time. The computerized COMPRESS did not provide any screening advantage over the short FLASQ-PD paper questionnaire. Larger studies will be needed to assess the utility and cost effectiveness of this computerized triage method for DBS.

10 Clinical Trial A closer look at unilateral versus bilateral deep brain stimulation: results of the National Institutes of Health COMPARE cohort. 2010

Taba, Houtan A / Wu, Samuel S / Foote, Kelly D / Hass, Chris J / Fernandez, Hubert H / Malaty, Irene A / Rodriguez, Ramon L / Dai, Yunfeng / Zeilman, Pamela R / Jacobson, Charles E / Okun, Michael S. ·Department of Neurology, University of Forlida Movement Disorders Center, College of Medicine, University of Florida, Gainesville, FL 32611, USA. ·J Neurosurg · Pubmed #20849215.

ABSTRACT: OBJECT: In this paper, the authors' aim was to examine reasons underpinning decisions to undergo, or alternatively forgo, a second-sided deep brain stimulation (DBS) implantation in patients with Parkinson disease (PD). METHODS: Fifty-two patients with Parkinson disease (PD) were randomized to receive DBS to the subthalamic nucleus or globus pallidus internus (GPi) as part of the COMPARE trial. Forty-four patients had complete data sets. All patients were offered a choice at 6 months after unilateral implantation whether to receive a contralateral DBS implant. All patients had advanced PD. The mean patient age was 59.8 years (range 43-76 years), and the mean duration of disease was 12.2 years (range 5-21 years). The mean baseline Unified Parkinson's Disease Rating Scale (UPDRS)-III motor score was 42.7. The main outcome measures used in this study were the UPDRS-III Motor Scale and the UPDRS-IV Dyskinesia Scale. RESULTS: Twenty-one (48%) of the 44 patients in the cohort did not undergo bilateral implantation and have been successfully treated for an average of 3.5 years; of these, 14 (67%) had a GPi target. The most common reason for adding a second side was inadequacy to address motor symptoms. Patient satisfaction with motor outcomes after unilateral DBS implantation was the most common reason for not undergoing bilateral implantation. Those who chose a second DBS procedure had significantly higher baseline UPDRS-III motor and ipsilateral UPDRS-III scores, and a significantly lower asymmetrical index. The logistic regression analysis revealed that the odds of proceeding to bilateral DBS was 5.2 times higher for STN than for GPi DBS. For every 1% increase in asymmetry, the odds of bilateral DBS decreased [corrected] by 0.96. CONCLUSIONS: Unilateral DBS is an effective treatment for a subset of patients with PD. Baseline asymmetry is an important factor in the effectiveness and decision-making process between unilateral and bilateral DBS. Patients with GPi DBS in this cohort were more likely to choose to remain with unilateral implantation.

11 Article Square Biphasic Pulse Deep Brain Stimulation for Parkinson's Disease: The BiP-PD Study. 2019

De Jesus, Sol / Okun, Michael S / Foote, Kelly D / Martinez-Ramirez, Daniel / Roper, Jaimie A / Hass, Chris J / Shahgholi, Leili / Akbar, Umer / Wagle Shukla, Aparna / Raike, Robert S / Almeida, Leonardo. ·Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, United States. · Department of Neurology, Penn State Milton S. Hershey Medical Center, Hershey, PA, United States. · Department of Neurosurgery, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, United States. · Tecnologico de Monterrey, Escuela de Medicina Ignacio A. Santos, Monterrey, Mexico. · Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, United States. · Department of Neurology, Brown University, Providence, RI, United States. · Restorative Therapies Group Implantables, Research and Core Technology, Medtronic, Minneapolis, MN, United States. ·Front Hum Neurosci · Pubmed #31680918.

ABSTRACT: Background: Conventional Parkinson's disease (PD) deep brain stimulation (DBS) utilizes a pulse with an active phase and a passive charge-balancing phase. A pulse-shaping strategy that eliminates the passive phase may be a promising approach to addressing movement disorders. Objectives: The current study assessed the safety and tolerability of square biphasic pulse shaping (sqBIP) DBS for use in PD. Methods: This small pilot safety and tolerability study compared sqBiP versus conventional DBS. Nine were enrolled. The safety and tolerability were assessed over a 3-h period on sqBiP. Friedman's test compared blinded assessments at baseline, washout, and 30 min, 1 h, 2 h, and 3 h post sqBIP. Results: Biphasic pulses were safe and well tolerated by all participants. SqBiP performed as well as conventional DBS without significant differences in motor scores nor accelerometer or gait measures. Conclusion: Biphasic pulses were well-tolerated and provided similar benefit to conventional DBS. Further studies should address effectiveness of sqBIP in select PD patients.

12 Article Proceedings of the Sixth Deep Brain Stimulation Think Tank Modulation of Brain Networks and Application of Advanced Neuroimaging, Neurophysiology, and Optogenetics. 2019

Ramirez-Zamora, Adolfo / Giordano, James / Boyden, Edward S / Gradinaru, Viviana / Gunduz, Aysegul / Starr, Philip A / Sheth, Sameer A / McIntyre, Cameron C / Fox, Michael D / Vitek, Jerrold / Vedam-Mai, Vinata / Akbar, Umer / Almeida, Leonardo / Bronte-Stewart, Helen M / Mayberg, Helen S / Pouratian, Nader / Gittis, Aryn H / Singer, Annabelle C / Creed, Meaghan C / Lazaro-Munoz, Gabriel / Richardson, Mark / Rossi, Marvin A / Cendejas-Zaragoza, Leopoldo / D'Haese, Pierre-Francois / Chiong, Winston / Gilron, Ro'ee / Chizeck, Howard / Ko, Andrew / Baker, Kenneth B / Wagenaar, Joost / Harel, Noam / Deeb, Wissam / Foote, Kelly D / Okun, Michael S. ·Department of Neurology, Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, United States. · Neuroethics Studies Program, Department of Neurology and Department of Biochemistry, Georgetown University Medical Center, Washington, DC, United States. · Media Laboratory, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States. · Center for Neurobiological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States. · Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, United States. · Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, United States. · Department of Neuroscience and Department of Biomedical Engineering and Department of Neurology, Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, United States. · Graduate Program in Neuroscience, Department of Neurological Surgery, Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA, United States. · Department of Neurological Surgery, Baylor College of Medicine, Houston, TX, United States. · Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States. · Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States. · Department of Neurology, University of Minnesota, Minneapolis, MN, United States. · Department of Neurosurgery, Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, United States. · Center for Neurorestoration and Neurotechnology, Rehabilitation R&D Service, Veterans Affairs Medical Center, Brown Institute for Brain Science, Brown University, Providence, RI, United States. · Department of Neurology and Department of Neurological Sciences and Department of Neurosurgery, Stanford University, Stanford, CA, United States. · Department of Neurology and Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, United States. · Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States. · Biological Sciences and Center for Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, PA, United States. · Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University School of Medicine, Atlanta, GA, United States. · Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, United States. · Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, TX, United States. · Center for the Neural Basis of Cognition, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States. · Department of Diagnostic Radiology and Nuclear Medicine, Rush University Medical Center, Chicago, IL, United States. · Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, United States. · Electrical Engineering, Vanderbilt University, Nashville, TN, United States. · Department of Neurology, University of California, San Francisco, San Francisco, CA, United States. · Graduate Program in Neuroscience, Department of Electrical Engineering, University of Washington, Seattle, WA, United States. · Department of Neurological Surgery, University of Washington, Seattle, WA, United States. · Movement Disorders Program, Cleveland Clinic Foundation, Cleveland, OH, United States. · Department of Neurology, Center for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia, PA, United States. · Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States. ·Front Neurosci · Pubmed #31572109.

ABSTRACT: The annual deep brain stimulation (DBS) Think Tank aims to create an opportunity for a multidisciplinary discussion in the field of neuromodulation to examine developments, opportunities and challenges in the field. The proceedings of the Sixth Annual Think Tank recapitulate progress in applications of neurotechnology, neurophysiology, and emerging techniques for the treatment of a range of psychiatric and neurological conditions including Parkinson's disease, essential tremor, Tourette syndrome, epilepsy, cognitive disorders, and addiction. Each section of this overview provides insight about the understanding of neuromodulation for specific disease and discusses current challenges and future directions. This year's report addresses key issues in implementing advanced neurophysiological techniques, evolving use of novel modulation techniques to deliver DBS, ans improved neuroimaging techniques. The proceedings also offer insights into the new era of brain network neuromodulation and connectomic DBS to define and target dysfunctional brain networks. The proceedings also focused on innovations in applications and understanding of adaptive DBS (closed-loop systems), the use and applications of optogenetics in the field of neurostimulation and the need to develop databases for DBS indications. Finally, updates on neuroethical, legal, social, and policy issues relevant to DBS research are discussed.

13 Article Postmortem Dissections of Common Targets for Lesion and Deep Brain Stimulation Surgeries. 2019

Holanda, Vanessa M / Okun, Michael S / Middlebrooks, Erik H / Gungor, Abuzer / Barry, Margaret E / Forder, John / Foote, Kelly D. ·Fixel Institute for Neurological Diseases, Department of Neurosurgery, University of Florida, Gainesville, Florida. · Center of Neurology and Neurosurgery Associates (NeuroCENNA), BP - A Beneficência Portuguesa de São Paulo, São Paulo SP, Brazil. · Department of Neurosurgery, Mayo Clinic College of Medicine, Jacksonville, Florida. · Fixel Institute for Neurological Diseases, Department of Neurology, University of Florida, Gainesville, Florida. · Department of Radiology, Mayo Clinic College of Medicine, Jacksonville, Florida. · Department of Neurosurgery, Acιbadem Mehmet Ali Aydinlar University, Istanbul, Turkey. · Department of Radiology, University of Florida, Gainesville, Florida. ·Neurosurgery · Pubmed #31504849.

ABSTRACT: BACKGROUND: The subthalamic nucleus (STN), globus pallidus internus (GPi), and pedunculopontine nucleus (PPN) are effective targets for deep brain stimulation (DBS) in many pathological conditions. Previous literature has focused on appropriate stimulation targets and their relationships with functional neuroanatomic pathways; however, comprehensive anatomic dissections illustrating these nuclei and their connections are lacking. This information will provide insight into the anatomic basis of stimulation-induced DBS benefits and side effects. OBJECTIVE: To combine advanced cadaveric dissection techniques and ultrahigh field magnetic resonance imaging (MRI) to explore the anatomy of the STN, GPi, and PPN with their associated fiber pathways. METHODS: A total of 10 cadaveric human brains and 2 hemispheres of a cadaveric head were examined using fiber dissection techniques. The anatomic dissections were compared with 11.1 Tesla (T) structural MRI and 4.7 T MRI fiber tractography. RESULTS: The extensive connections of the STN (caudate nucleus, putamen, medial frontal cortex, substantia innominata, substantia nigra, PPN, globus pallidus externus (GPe), GPi, olfactory tubercle, hypothalamus, and mammillary body) were demonstrated. The connections of GPi to the thalamus, substantia nigra, STN, amygdala, putamen, PPN, and GPe were also illustrated. The PPN was shown to connect to the STN and GPi anteriorly, to the cerebellum inferiorly, and to the substantia nigra anteriorly and superiorly. CONCLUSION: This study demonstrates connections using combined anatomic microdissections, ultrahigh field MRI, and MRI tractography. The anatomic findings are analyzed in relation to various stimulation-induced clinical effects. Precise knowledge of neuroanatomy, anatomic relationships, and fiber connections of the STN, GPi, PPN will likely enable more effective targeting and improved DBS outcomes.

14 Article Microsurgical anatomy of the subthalamic nucleus: correlating fiber dissection results with 3-T magnetic resonance imaging using neuronavigation. 2018

Güngör, Abuzer / Baydın, Şevki Serhat / Holanda, Vanessa M / Middlebrooks, Erik H / Isler, Cihan / Tugcu, Bekir / Foote, Kelly / Tanriover, Necmettin. ·1Department of Neurosurgery, Acıbadem University. · 2Department of Neurosurgery, Bakirkoy Research & Training Hospital for Psychiatry, Neurology, and Neurosurgery. · 3Department of Neurosurgery, Kanuni Sultan Süleyman Research & Training Hospital. · 4Department of Neurosurgery, University of Florida, Gainesville, Florida; and. · 5Department of Radiology, University of Alabama, Birmingham, Alabama. · 6Department of Neurosurgery, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey. ·J Neurosurg · Pubmed #29726781.

ABSTRACT: OBJECTIVE: Despite the extensive use of the subthalamic nucleus (STN) as a deep brain stimulation (DBS) target, unveiling the extensive functional connectivity of the nucleus, relating its structural connectivity to the stimulation-induced adverse effects, and thus optimizing the STN targeting still remain challenging. Mastering the 3D anatomy of the STN region should be the fundamental goal to achieve ideal surgical results, due to the deep-seated and obscure position of the nucleus, variable shape and relatively small size, oblique orientation, and extensive structural connectivity. In the present study, the authors aimed to delineate the 3D anatomy of the STN and unveil the complex relationship between the anatomical structures within the STN region using fiber dissection technique, 3D reconstructions of high-resolution MRI, and fiber tracking using diffusion tractography utilizing a generalized q-sampling imaging (GQI) model. METHODS: Fiber dissection was performed in 20 hemispheres and 3 cadaveric heads using the Klingler method. Fiber dissections of the brain were performed from all orientations in a stepwise manner to reveal the 3D anatomy of the STN. In addition, 3 brains were cut into 5-mm coronal, axial, and sagittal slices to show the sectional anatomy. GQI data were also used to elucidate the connections among hubs within the STN region. RESULTS: The study correlated the results of STN fiber dissection with those of 3D MRI reconstruction and tractography using neuronavigation. A 3D terrain model of the subthalamic area encircling the STN was built to clarify its anatomical relations with the putamen, globus pallidus internus, globus pallidus externus, internal capsule, caudate nucleus laterally, substantia nigra inferiorly, zona incerta superiorly, and red nucleus medially. The authors also describe the relationship of the medial lemniscus, oculomotor nerve fibers, and the medial forebrain bundle with the STN using tractography with a 3D STN model. CONCLUSIONS: This study examines the complex 3D anatomy of the STN and peri-subthalamic area. In comparison with previous clinical data on STN targeting, the results of this study promise further understanding of the structural connections of the STN, the exact location of the fiber compositions within the region, and clinical applications such as stimulation-induced adverse effects during DBS targeting.

15 Article Segmentation of the Globus Pallidus Internus Using Probabilistic Diffusion Tractography for Deep Brain Stimulation Targeting in Parkinson Disease. 2018

Middlebrooks, E H / Tuna, I S / Grewal, S S / Almeida, L / Heckman, M G / Lesser, E R / Foote, K D / Okun, M S / Holanda, V M. ·From the Departments of Radiology (E.H.M.) Middlebrooks.Erik@mayo.edu. · Departments of Radiology (I.S.T.). · Neurosurgery (S.S.G.). · Neurology (L.A., M.S.O.). · Division of Biomedical Statistics and Informatics (M.G.H., E.R.L.), Mayo Clinic, Jacksonville, Florida. · Neurosurgery (K.D.F.), University of Florida, Gainesville, Florida. · Center of Neurology and Neurosurgery Associates (V.M.H.), BP-A Beneficência Portuguesa de São Paulo, São Paulo, Brazil. ·AJNR Am J Neuroradiol · Pubmed #29700048.

ABSTRACT: BACKGROUND AND PURPOSE: Although globus pallidus internus deep brain stimulation is a widely accepted treatment for Parkinson disease, there is persistent variability in outcomes that is not yet fully understood. In this pilot study, we aimed to investigate the potential role of globus pallidus internus segmentation using probabilistic tractography as a supplement to traditional targeting methods. MATERIALS AND METHODS: Eleven patients undergoing globus pallidus internus deep brain stimulation were included in this retrospective analysis. Using multidirection diffusion-weighted MR imaging, we performed probabilistic tractography at all individual globus pallidus internus voxels. Each globus pallidus internus voxel was then assigned to the 1 ROI with the greatest number of propagated paths. On the basis of deep brain stimulation programming settings, the volume of tissue activated was generated for each patient using a finite element method solution. For each patient, the volume of tissue activated within each of the 10 segmented globus pallidus internus regions was calculated and examined for association with a change in the Unified Parkinson Disease Rating Scale, Part III score before and after treatment. RESULTS: Increasing volume of tissue activated was most strongly correlated with a change in the Unified Parkinson Disease Rating Scale, Part III score for the primary motor region (Spearman CONCLUSIONS: In this pilot study, we assessed a novel method of segmentation of the globus pallidus internus based on probabilistic tractography as a supplement to traditional targeting methods. Our results suggest that our method may be an independent predictor of deep brain stimulation outcome, and evaluation of a larger cohort or prospective study is warranted to validate these findings.

16 Article Deep Brain Stimulation associated gliosis: A post-mortem study. 2018

Vedam-Mai, Vinata / Rodgers, Cooper / Gureck, Ashley / Vincent, Michael / Ippolito, Gianna / Elkouzi, Ahmad / Yachnis, Anthony T / Foote, Kelly D / Okun, Michael S. ·Department of Neurosurgery, McKnight Brain Institute, University of FL, Gainesville, FL 32610-0015, United States; Department of Neurology, UF Center for Movement Disorders and Restoration, Gainesville, FL, United States. Electronic address: vinved@neurosurgery.ufl.edu. · Department of Neurosurgery, McKnight Brain Institute, University of FL, Gainesville, FL 32610-0015, United States. · Department of Neurology, UF Center for Movement Disorders and Restoration, Gainesville, FL, United States. · Department of Pathology and Immunology, University of FL, Gainesville, FL 32610-0015, United States. ·Parkinsonism Relat Disord · Pubmed #29653910.

ABSTRACT: BACKGROUND: DBS is a well-established therapy for patients with PD and is an emerging therapy for other neuropsychiatric disorders. Despite the rise in DBS usage, relatively little is known about the tissue and cellular responses to DBS. PURPOSE: To examine post-mortem effects of DBS leads by objectively quantifying gliosis around the distal DBS lead tip. METHODS: The UF DBS Brain Bank repository currently has 64 brains, of which 18 cases met criteria for this study. RESULTS: The average patient age was 54.88 ± 13.43 years (mean ± SD), male:female ratio was 3:1, average disease duration was 20.70 ± 6.36 years and average DBS duration was 7.26 ± 6.36 years. Microscopic evaluation revealed tissue reaction and astrocytic responses to the lead. Significant fibrosis was seen in n = 2 brains and prominent microglial response in n = 1. Mean gliotic collar measured from H&E and GFAP staining was 122.5 μm and 162.5 μm, respectively. Mean gliotic thickness at the DBS electrode lead tip was 119.13 ± 64.29 μm for patients receiving DBS for 0-5 years, 127.85 ± 94.34 μm for 5-10 years and 111.73 ± 114.18 μm for patients with DBS >10 years. Kruskal-Wallis one-way analysis of variance (ANOVA) revealed no statistically significant differences between DBS duration and amount of gliosis. CONCLUSIONS: This study revealed that approximately three out of four post-mortem DBS cases exhibited pathological evidence of a glial collar or scar present at the ventral DBS lead tip. The amount of gliosis was not significantly associated with duration of DBS. Future studies should include serial sectioning across all DBS contacts with correlation to the volume of tissue activation and to the clinical outcome.

17 Article Evolving Applications, Technological Challenges and Future Opportunities in Neuromodulation: Proceedings of the Fifth Annual Deep Brain Stimulation Think Tank. 2017

Ramirez-Zamora, Adolfo / Giordano, James J / Gunduz, Aysegul / Brown, Peter / Sanchez, Justin C / Foote, Kelly D / Almeida, Leonardo / Starr, Philip A / Bronte-Stewart, Helen M / Hu, Wei / McIntyre, Cameron / Goodman, Wayne / Kumsa, Doe / Grill, Warren M / Walker, Harrison C / Johnson, Matthew D / Vitek, Jerrold L / Greene, David / Rizzuto, Daniel S / Song, Dong / Berger, Theodore W / Hampson, Robert E / Deadwyler, Sam A / Hochberg, Leigh R / Schiff, Nicholas D / Stypulkowski, Paul / Worrell, Greg / Tiruvadi, Vineet / Mayberg, Helen S / Jimenez-Shahed, Joohi / Nanda, Pranav / Sheth, Sameer A / Gross, Robert E / Lempka, Scott F / Li, Luming / Deeb, Wissam / Okun, Michael S. ·Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, United States. · Department of Neurology, Pellegrino Center for Clinical Bioethics, Georgetown University Medical Center, Washington, DC, United States. · J. Crayton Pruitt Family Department of Biomedical Engineering, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, United States. · Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom. · Biological Technologies Office, Defense Advanced Research Projects Agency, Arlington, VA, United States. · Department of Neurosurgery, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, United States. · Department of Neurological Surgery, Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA, United States. · Departments of Neurology and Neurological Sciences and Neurosurgery, Stanford University, Stanford, CA, United States. · Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States. · Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States. · Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States. · Division of Biomedical Physics, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, United States Food and Drug Administration, White Oak Federal Research Center, Silver Spring, MD, United States. · Department of Biomedical Engineering, Duke University, Durham, NC, United States. · Division of Movement Disorders, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, United States. · Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, United States. · Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, United States. · Department of Neurology, University of Minnesota, Minneapolis, MN, United States. · NeuroPace, Inc., Mountain View, CA, United States. · Department of Psychology, University of Pennsylvania, Philadelphia, PA, United States. · Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, United States. · Physiology and Pharmacology, Wake Forest University School of Medicine, Wake Forest University, Winston-Salem, NC, United States. · Department of Neurology, Center for Neurotechnology and Neurorecovery, Massachusetts General Hospital, Harvard Medical School, Harvard University, Boston, MA, United States. · Center for Neurorestoration and Neurotechnology, Rehabilitation R and D Service, Veterans Affairs Medical Center, Providence, RI, United States. · School of Engineering and Brown Institute for Brain Science, Brown University, Providence, RI, United States. · Laboratory of Cognitive Neuromodulation, Feil Family Brain Mind Research Institute, Weill Cornell Medicine, New York, NY, United States. · Medtronic Neuromodulation, Minneapolis, MN, United States. · Department of Neurology, Mayo Clinic, Rochester, MN, United States. · Department of Biomedical Engineering, Georgia Institute of Technology, Emory University School of Medicine, Emory University, Atlanta, GA, United States. · Departments of Psychiatry, Neurology, and Radiology, Emory University School of Medicine, Emory University, Atlanta, GA, United States. · Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, United States. · Department of Neurological Surgery, The Neurological Institute, Columbia University Herbert and Florence Irving Medical Center, Colombia University, New York, NY, United States. · Department of Neurosurgery, Emory University, Atlanta, GA, United States. · Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States. · National Engineering Laboratory for Neuromodulation, School of Aerospace Engineering, Tsinghua University, Beijing, China. · Precision Medicine and Healthcare Research Center, Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Beijing, China. · Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing, China. ·Front Neurosci · Pubmed #29416498.

ABSTRACT: The annual Deep Brain Stimulation (DBS) Think Tank provides a focal opportunity for a multidisciplinary ensemble of experts in the field of neuromodulation to discuss advancements and forthcoming opportunities and challenges in the field. The proceedings of the fifth Think Tank summarize progress in neuromodulation neurotechnology and techniques for the treatment of a range of neuropsychiatric conditions including Parkinson's disease, dystonia, essential tremor, Tourette syndrome, obsessive compulsive disorder, epilepsy and cognitive, and motor disorders. Each section of this overview of the meeting provides insight to the critical elements of discussion, current challenges, and identified future directions of scientific and technological development and application. The report addresses key issues in developing, and emphasizes major innovations that have occurred during the past year. Specifically, this year's meeting focused on technical developments in DBS, design considerations for DBS electrodes, improved sensors, neuronal signal processing, advancements in development and uses of responsive DBS (closed-loop systems), updates on National Institutes of Health and DARPA DBS programs of the BRAIN initiative, and neuroethical and policy issues arising in and from DBS research and applications in practice.

18 Article Postoperative lead migration in deep brain stimulation surgery: Incidence, risk factors, and clinical impact. 2017

Morishita, Takashi / Hilliard, Justin D / Okun, Michael S / Neal, Dan / Nestor, Kelsey A / Peace, David / Hozouri, Alden A / Davidson, Mark R / Bova, Francis J / Sporrer, Justin M / Oyama, Genko / Foote, Kelly D. ·Department of Neurosurgery, Fukuoka University, Fukuoka, Japan. · Department of Neurosurgery, University of Florida, Center for Movement Disorders and Neurorestoration, Gainesville, Florida, United States of America. · Department of Neurology, University of Florida, Center for Movement Disorders and Neurorestoration, Gainesville, Florida, United States of America. · Department of Materials Science and Engineering, University of Florida, Gainesville, Florida, United States of America. · Department of Neurology, Juntendo University, Tokyo, Japan. ·PLoS One · Pubmed #28902876.

ABSTRACT: INTRODUCTION: Deep brain stimulation (DBS) is an effective treatment for multiple movement disorders and shows substantial promise for the treatment of some neuropsychiatric and other disorders of brain neurocircuitry. Optimal neuroanatomical lead position is a critical determinant of clinical outcomes in DBS surgery. Lead migration, defined as an unintended post-operative displacement of the DBS lead, has been previously reported. Despite several reports, however, there have been no systematic investigations of this issue. This study aimed to: 1) quantify the incidence of lead migration in a large series of DBS patients, 2) identify potential risk factors contributing to DBS lead migration, and 3) investigate the practical importance of this complication by correlating its occurrence with clinical outcomes. METHODS: A database of all DBS procedures performed at UF was queried for patients who had undergone multiple post-operative DBS lead localization imaging studies separated by at least two months. Bilateral DBS implantation has commonly been performed as a staged procedure at UF, with an interval of six or more months between sides. To localize the position of each DBS lead, a head CT is acquired ~4 weeks after lead implantation and fused to the pre-operative targeting MRI. The fused targeting images (MR + stereotactic CT) acquired in preparation for the delayed second side lead implantation provide an opportunity to repeat the localization of the first implanted lead. This paradigm offers an ideal patient population for the study of delayed DBS lead migration because it provides a large cohort of patients with localization of the same implanted DBS lead at two time points. The position of the tip of each implanted DBS lead was measured on both the initial post-operative lead localization CT and the delayed CT. Lead tip displacement, intracranial lead length, and ventricular indices were collected and analyzed. Clinical outcomes were characterized with validated rating scales for all cases, and a comparison was made between outcomes of cases with lead migration versus those where migration of the lead did not occur. RESULTS: Data from 138 leads in 132 patients with initial and delayed lead localization CT scans were analyzed. The mean distance between initial and delayed DBS lead tip position was 2.2 mm and the mean change in intracranial lead length was 0.45 mm. Significant delayed migration (>3 mm) was observed in 17 leads in 16 patients (12.3% of leads, 12.1% of patients). Factors associated with lead migration were: technical error, repetitive dystonic head movement, and twiddler's syndrome. Outcomes were worse in dystonia patients with lead migration (p = 0.035). In the PD group, worse clinical outcomes trended in cases with lead migration. CONCLUSIONS: Over 10% of DBS leads in this large single center cohort were displaced by greater than 3 mm on delayed measurement, adversely affecting outcomes. Multiple risk factors emerged, including technical error during implantation of the DBS pulse generator and failure of lead fixation at the burr hole site. We hypothesize that a change in surgical technique and a more effective lead fixation device might mitigate this problem.

19 Article Measures of impulsivity in Parkinson's disease decrease after DBS in the setting of stable dopamine therapy. 2017

Rossi, P Justin / De Jesus, Sol / Hess, Christopher W / Martinez-Ramirez, Daniel / Foote, Kelly D / Gunduz, Aysegul / Okun, Michael S. ·Center for Movement Disorders and Neurorestoration, University of Florida, 3450 Hull Road, Gainesville, FL 32607, USA. Electronic address: pjrossi@ufl.edu. · Center for Movement Disorders and Neurorestoration, University of Florida, 3450 Hull Road, Gainesville, FL 32607, USA. · J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, 1275 Center Drive, Gainesville, FL 32610, USA. ·Parkinsonism Relat Disord · Pubmed #28827010.

ABSTRACT: INTRODUCTION: Recent evidence suggests deep brain stimulation can alter impulse control. Our objective was to prospectively evaluate the effects of subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation on impulse control disorders (ICDs) in the setting of a conservative dopamine reduction strategy. METHODS: Patients (n = 37) undergoing de novo, unilateral STN or GPi DBS lead implantation were evaluated pre-operatively and 6-12 months post-operatively for the presence of ICDs using the Questionnaire for Impulsivity in Parkinson's disease (QUIP) and by clinical interview. RESULTS: Of the patients enrolled, 23 underwent electrode implantation in the globus pallidus internus and 14 were implanted in the subthalamic nucleus. Mean time to long term follow-up was 9.7 ± 2.4 months. Post-operative LEDD was not significantly lower than pre-operative LEDD (pre-op: 1238.53 ± 128.47 vs. post-op: 1178.18 ± 126.43, p = 0.2972, paired t-test). Mean QUIP scores were significantly lower at follow up compared to pre-operative baseline (1.51 ± 0.45 vs. 2.51 ± 0.58, p = 0.0447, paired t-test). Patients with ICDs pre-operatively (n = 14, 37.8%) had significant improvement in QUIP scores at follow-up (6.00 ± 0.94 vs. 2.64 ± 0.98, p = 0.0014, paired t-test). Improvement was not uniform across the cohort: 1 patient with ICD at baseline developed worsening symptoms, and 4 patients with no ICD pre-operatively developed clinically significant ICDs post-operatively. CONCLUSION: When LEDD is relatively unchanged following STN or GPi DBS for PD, ICD symptoms tend toward improvement, although worsening and emergence of new ICDs can occur. In the setting of stable LEDD, these findings suggest that the intrinsic effects of DBS may play a significant role in altering impulsive behavior.

20 Article Impulsivity in Parkinson's disease is associated with altered subthalamic but not globus pallidus internus activity. 2017

Rossi, Peter Justin / Shute, Jonathan B / Opri, Enrico / Molina, Rene / Peden, Corinna / Castellanos, Oscar / Foote, Kelly D / Gunduz, Aysegul / Okun, Michael S. ·Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, USA. · Department of Biomedical Engineering, University of Florida, Gainesville, USA. ·J Neurol Neurosurg Psychiatry · Pubmed #28822983.

ABSTRACT: 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.

21 Article Motor subtype changes in early Parkinson's disease. 2017

Eisinger, Robert S / Hess, Christopher W / Martinez-Ramirez, Daniel / Almeida, Leonardo / Foote, Kelly D / Okun, Michael S / Gunduz, Aysegul. ·Department of Neuroscience, Center for Movement Disorders and Neurorestoration, 3450 Hull Road, University of Florida, Gainesville, FL 32607, United States. Electronic address: eisinger@ufl.edu. · Department of Neurology, Center for Movement Disorders and Neurorestoration, 3450 Hull Road, University of Florida, Gainesville, FL 32607, United States. Electronic address: christopher.hess@neurology.ufl.edu. · Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, United States. Electronic address: daniel.martinez-ramirez@neurology.ufl.edu. · Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, United States. Electronic address: leonardo.britodalmeida@neurology.ufl.edu. · Department of Neurosurgery, Center for Movement Disorders and Neurorestoration, McKnight Brain Institute, 3rd Floor, University of Florida, Gainesville, FL 32611, United States. Electronic address: foote@neurosurgery.ufl.edu. · Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, United States. Electronic address: okun@neurology.ufl.edu. · J. Crayton Pruitt Family Department of Biomedical Engineering, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, United States. Electronic address: agunduz@bme.ufl.edu. ·Parkinsonism Relat Disord · Pubmed #28754232.

ABSTRACT: INTRODUCTION: Distinct motor subtypes of Parkinson's disease (PD) have been described through both clinical observation and through data-driven approaches. However, the extent to which motor subtypes change during disease progression remains unknown. Our objective was to determine motor subtypes of PD using an unsupervised clustering methodology and evaluate subtype changes with disease duration. METHODS: The Parkinson's Progression Markers Initiative database of 423 newly diagnosed PD patients was utilized to retrospectively identify unique motor subtypes through a data-driven, hierarchical correlational clustering approach. For each patient, we assigned a subtype to each motor assessment at each follow-up visit (time points) and by using published criteria. We examined changes in PD subtype with disease duration using both qualitative and quantitative methods. RESULTS: Five distinct motor subtypes were identified based on the motor assessment items and these included: Tremor Dominant (TD), Axial Dominant, Appendicular Dominant, Rigidity Dominant, and Postural and Instability Gait Disorder Dominant. About half of the patients had consistent subtypes at all time points. Most patients met criteria for TD subtype soon after diagnosis. For patients with inconsistent subtypes, there was an overall trend to shift away from a TD phenotype with disease duration, as shown by chi-squared test, p < 0.001, and linear regression analysis, p < 0.05. CONCLUSION: These results strongly suggest that classification of motor subtypes in PD can shift with increasing disease duration. Shifting subtypes is a factor that should be accounted for in clinical practice or in clinical trials.

22 Article The human subthalamic nucleus and globus pallidus internus differentially encode reward during action control. 2017

Justin Rossi, Peter / Peden, Corinna / Castellanos, Oscar / Foote, Kelly D / Gunduz, Aysegul / Okun, Michael S. ·Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, Florida. · J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida. ·Hum Brain Mapp · Pubmed #28130916.

ABSTRACT: The subthalamic nucleus (STN) and globus pallidus internus (GPi) have recently been shown to encode reward, but few studies have been performed in humans. We investigated STN and GPi encoding of reward and loss (i.e., valence) in humans with Parkinson's disease. To test the hypothesis that STN and GPi neurons would change their firing rate in response to reward- and loss-related stimuli, we recorded the activity of individual neurons while participants performed a behavioral task. In the task, action choices were associated with potential rewarding, punitive, or neutral outcomes. We found that STN and GPi neurons encode valence-related information during action control, but the proportion of valence-responsive neurons was greater in the STN compared to the GPi. In the STN, reward-related stimuli mobilized a greater proportion of neurons than loss-related stimuli. We also found surprising limbic overlap with the sensorimotor regions in both the STN and GPi, and this overlap was greater than has been previously reported. These findings may help to explain alterations in limbic function that have been observed following deep brain stimulation therapy of the STN and GPi. Hum Brain Mapp 38:1952-1964, 2017. © 2017 Wiley Periodicals, Inc.

23 Article Proceedings of the Fourth Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies. 2016

Deeb, Wissam / Giordano, James J / Rossi, Peter J / Mogilner, Alon Y / Gunduz, Aysegul / Judy, Jack W / Klassen, Bryan T / Butson, Christopher R / Van Horne, Craig / Deny, Damiaan / Dougherty, Darin D / Rowell, David / Gerhardt, Greg A / Smith, Gwenn S / Ponce, Francisco A / Walker, Harrison C / Bronte-Stewart, Helen M / Mayberg, Helen S / Chizeck, Howard J / Langevin, Jean-Philippe / Volkmann, Jens / Ostrem, Jill L / Shute, Jonathan B / Jimenez-Shahed, Joohi / Foote, Kelly D / Wagle Shukla, Aparna / Rossi, Marvin A / Oh, Michael / Pourfar, Michael / Rosenberg, Paul B / Silburn, Peter A / de Hemptine, Coralie / Starr, Philip A / Denison, Timothy / Akbar, Umer / Grill, Warren M / Okun, Michael S. ·Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida Gainesville, FL, USA. · Department of Neurology, and Neuroethics Studies Program, Pellegrino Center for Clinical Bioethics, Georgetown University Medical Center Washington, DC, USA. · Department of Neurosurgery, Center for Neuromodulation, New York University Langone Medical Center New York, NY, USA. · Department of Neurology, Center for Movement Disorders and Neurorestoration, University of FloridaGainesville, FL, USA; J. Crayton Pruitt Family Department of Biomedical Engineering, University of FloridaGainesville, FL, USA. · Department of Neurology, Mayo Clinic Rochester, MN, USA. · Department of Bioengineering, Scientific Computing and Imaging Institute, University of Utah Salt Lake City, UT, USA. · Department of Neurosurgery, University of Kentucky Chandler Medical Center Lexington, KY, USA. · Department of Psychiatry, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands. · Department of Psychiatry, Massachusetts General Hospital Boston, MA, USA. · Asia Pacific Centre for Neuromodulation, Queensland Brain Institute, The University of Queensland Brisbane, QLD, Australia. · Department of Anatomy and Neurobiology, University of Kentucky Chandler Medical Center Lexington, KY, USA. · Departments of Psychiatry and Behavioral Sciences and Radiology and Radiological Sciences, Johns Hopkins University School of Medicine Baltimore, MD, USA. · Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center Phoenix Arizona, AZ, USA. · Department of Neurology and Department of Biomedical Engineering, University of Alabama at Birmingham Birmingham, AL, USA. · Departments of Neurology and Neurological Sciences and Neurosurgery, Stanford University Stanford, CA, USA. · Department of Psychiatry, Emory University School of Medicine Atlanta, GA, USA. · Electrical Engineering Department, University of WashingtonSeattle, WA, USA; NSF Engineering Research Center for Sensorimotor Neural EngineeringSeattle, WA, USA. · Department of Neurosurgery, VA Greater Los Angeles Healthcare System Los Angeles, CA, USA. · Department of Neurology, University Clinic of Würzburg Würzburg, Germany. · Department of Neurology, University of California San Francisco San Francisco, CA, USA. · J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida Gainesville, FL, USA. · Department of Neurology, Baylor College of Medicine Houston, TX, USA. · Department of Neurology, Center for Movement Disorders and Neurorestoration, University of FloridaGainesville, FL, USA; Department of Neurological Sciences, University of FloridaGainesville, FL, USA. · Departments of Neurological Sciences, Diagnostic Radiology, and Nuclear Medicine, Rush University Medical Center Chicago, IL, USA. · Division of Functional Neurosurgery, Department of Neurosurgery, Allegheny General Hospital Pittsburgh, PA, USA. · Department of Neurology, New York University Langone Medical Center New York, NY, USA. · Psychiatry and Behavioral Sciences, Johns Hopkins Bayview Medical Center, Johns Hopkins School of Medicine Baltimore, MD, USA. · Graduate Program in Neuroscience, Department of Neurological Surgery, Kavli Institute for Fundamental Neuroscience, University of California, San Francisco San Francisco, CA, USA. · Medtronic Modulation Minneapolis, MN, USA. · Movement Disorders Program, Department of Neurology, Alpert Medical School, Rhode Island Hospital, Brown University Providence, RI, USA. · Department of Biomedical Engineering, Duke University Durham, NC, USA. ·Front Integr Neurosci · Pubmed #27920671.

ABSTRACT: 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.

24 Article Tailored deep brain stimulation optimization for improved airway protective outcomes in Parkinson's disease. 2016

Troche, Michelle S / Brandimore, Alexandra E / Hegland, Karen W / Zeilman, Pamela R / Foote, Kelly D / Okun, Michael S. ·Center for Movement Disorders and Neurorestoration, University of Florida, 3450 Hull Rd, Gainesville, FL 32607, USA; Laboratory for the Study of Upper Airway Dysfunction, Teachers College, Columbia University, 525 West 120 Street, New York, NY 10027, USA. · Center for Movement Disorders and Neurorestoration, University of Florida, 3450 Hull Rd, Gainesville, FL 32607, USA. ·Interdiscip Neurosurg · Pubmed #27795943.

ABSTRACT: There is no consensus regarding the effects of deep brain stimulation (DBS) surgery on swallowing outcomes in Parkinson's disease (PD). No prospective studies have compared airway protective outcomes following DBS to the subthalamic nucleus (STN) versus globus pallidus interna (GPi). A recent retrospective study described swallowing outcomes pre- and post-STN vs. GPi DBS in a cohort of 34 patients with PD. The results revealed that the patients who received GPi DBS maintained their swallowing function post-DBS, while those in the STN group significantly worsened in swallowing safety. As DBS surgery becomes a common management option in PD it is important to understand the impact of DBS on airway protective outcomes; especially given that aspiration pneumonia is the leading cause of death in this population. We present a case report in which optimizing DBS settings with the goal of improving laryngeal function resulted in immediate improvements to swallowing safety.

25 Article Interdisciplinary Parkinson's Disease Deep Brain Stimulation Screening and the Relationship to Unintended Hospitalizations and Quality of Life. 2016

Higuchi, Masa-Aki / Martinez-Ramirez, Daniel / Morita, Hokuto / Topiol, Dan / Bowers, Dawn / Ward, Herbert / Warren, Lisa / DeFranco, Meredith / Hicks, Julie A / Hegland, Karen W / Troche, Michelle S / Kulkarni, Shankar / Hastings, Erin / Foote, Kelly D / Okun, Michael S. ·Department of Neurology, University of Florida College of Medicine, Center for Movement Disorders and Neurorestoration, Gainesville, Florida, United States of America. · Department of Clinical and Health Psychology, University of Florida College of Public Health and Health Professions, Gainesville, Florida, United States of America. · Department of Psychiatry, University of Florida College of Medicine, Gainesville, Florida, United States of America. · Rehabilitation Services, University Florida Center for Movement Disorders and Neurorestoration, Gainesville, Florida, United States of America. · Department of Speech, Language, and Hearing Sciences, University of Florida College of Public Health and Health Professions, Gainesville, Florida, United States of America. · Department of Neurosurgery, University of Florida College of Medicine, Gainesville, Florida, United States of America. ·PLoS One · Pubmed #27159519.

ABSTRACT: OBJECTIVE: To investigate the impact of pre-operative deep brain stimulation (DBS) interdisciplinary assessments on post-operative hospitalizations and quality of life (QoL). BACKGROUND: DBS has been utilized successfully in Parkinson's disease (PD) for the treatment of tremor, rigidity, bradykinesia, off time, and motor fluctuations. Although DBS is becoming a more common management approach there are no standardized criteria for selection of DBS candidates, and sparse data exist to guide the use of interdisciplinary evaluations for DBS screening. We reviewed the outcomes of the use of an interdisciplinary model which utilized seven specialties to pre-operatively evaluate potential DBS candidates. METHODS: The University of Florida (UF) INFORM database was queried for PD patients who had DBS implantations performed at UF between January 2011 and February 2013. Records were reviewed to identify unintended hospitalizations, falls, and infections. Minor and major concerns or reservations from each specialty were previously documented and quantified. Clinical outcomes were assessed through the use of the Parkinson disease quality of life questionnaire (PDQ-39), and the Unified Parkinson's Disease Rating Score (UPDRS) Part III. RESULTS: A total of 164 cases were evaluated for possible DBS candidacy. There were 133 subjects who were approved for DBS surgery (81%) following interdisciplinary screening. There were 28 cases (21%) who experienced an unintended hospitalization within the first 12 months following the DBS operation. The patients identified during interdisciplinary evaluation with major or minor concerns from any specialty service had more unintended hospitalizations (93%) when compared to those without concerns (7%). When the preoperative "concern" shifted from "major" to "minor" to "no concerns," the rate of hospitalization decreased from 89% to 33% to 3%. A strong relationship was uncovered between worsened PDQ-39 at 12 months and increased hospitalization. CONCLUSIONS: Unintended hospitalizations and worsened QOL scores correlated with the number and severity of concerns raised by interdisciplinary DBS evaluations. The data suggest that detailed screenings by interdisciplinary teams may be useful for more than just patient selection. These evaluations may help to stratify risk for post-operative hospitalization and QoL outcomes.

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