The articles listed on this page are from a variety of sources. 
1. The staff of DBS-STN often attends conferences or educational opportunities both nationally and internationally, and a brief understandable write-up of the information presented at the event will be provided for our readers to review. 
2. DBS-STN staff also identifies or writes various articles related to topics that are thought to be of interest for the reader of

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Neural Interfaces Workshop, August 2006

Dr. Jeffrey Wertheimer

Neural Interfaces Workshop, August 2006

National Institute of Health and the National Institute of Neurological Disorders and Stroke

In August 2006, The Parkinson Alliance attended the Neural Interfaces Workshop in Bethesda, Maryland, which was sponsored by the National Institute of Health (NIH) and the National Institute of Neurological Disorders and Stroke (NINDS). A significant portion of this conference was dedicated to presenting updates on and introducing recent research endeavors that help facilitate the understanding and enhancement of treatment for Parkinson's disease, as it relates to Deep Brain Stimulation (DBS) therapy. Specifically, topics that were presented related to (1) understanding the mechanisms behind DBS, (2) optimizing deep brain stimulation implantation and targeting, (3) enhancing computer imagery and analyses in DBS therapy, and (4) improving DBS management. Additionally, there was a presentation entitled "The Patient Perspective on Deep Brain Stimulation" of which the Parkinson Alliance assisted in the facilitation. Mrs. Margaret Tuchman, the President of The Parkinson Alliance, and Dr. David Heydrick, a neurologist, are two individuals with bilateral DBS-STN who presented during this panel discussion.

A round-table discussion about advancements and challenges in DBS therapy

To begin the conference, the staff of The Parkinson Alliance hosted a round-table dinner wherein some of the leaders in DBS research were in attendance. Some of the major topics discussed included:
  1. Standardizing DBS programming
  2. Means of increasing access to programmers
  3. Means of increasing the quality of DBS management
  4. Battery Change

Although standardization appears to be a rather large obstacle to overcome due to the individuality of each patient and the specific needs therein (among other reasons), there is hope, however, that clinicians will coalesce in the future. Moreover, through "designating" centers of excellence that have the "ideal multi-disciplinary treatment teams" and when treatment/interventions adhere to high standards (quality), common approaches may result across institutions [and the clinicians therein].

With regard to increasing the access to programmers, improvement in gaining access to programmers is currently in the works. Specifically, a curriculum for residents and movement disorder fellows in DBS management will hopefully be established in the academic setting permitting more clinicians to be knowledgeable about DBS management. Further, ongoing education about DBS to the community at large and increased resources to market DBS programmers will hopefully aid the management of DBS; it was agreed upon, though, that training our "new clinicians" during their residency will likely be one of the most efficacious means of improving access to and the quality of programming. In addition to these aforementioned points, there are several factors that were mentioned that can improve the quality of DBS management. These factors include: educating neurologist, ensuring appropriate patient selection, improvement in the hardware, and the use of a multi-disciplinary and an inter-disciplinary treatment team.

Some of the key factors related to the battery change include: (1) Prepare the patients: informing them about the estimated duration of the battery and educate them about signs that the battery is declining. (2) When the battery starts to fade, the PD symptoms may return in greater severity, and that is a clear indicator that the battery needs to be replaced soon. (3) After the battery change, start with slightly lower parameters. (4) Schedule a quick follow-up for programming after the battery change. (5) Maintain regular follow-ups.

Formal Presentations at the Neural Interface Conference

Some of the relevant presentations that occurred at the conference are discussed in the succeeding paragraphs.

"Mechanisms of Deep Brain Stimulation"

Joel Perlmutter, M.D. from Washington University provided a lecture on the mechanism of Deep Brain Stimulation. Dr. Perlmutter made an important point regarding the role of DBS from the bigger picture. He stated that we continue to approach PD with an emphasis on structures that are affected by the cause rather than aiming at the cause itself. It was opined that this approach is likely to focus on treatment first, to improve overall quality of life by managing the symptoms. It is important to mention that the major interventions that appear to the public's eye (in the clinical realm) are symptom specific. However, as pointed out in this conference, there is much research in existence that pertains to gaining a better understanding of the origins of PD and how we can intervene at that level. Moreover, although the "clinical force" emphasizes the management of PD symptoms, in the background or "back stage", scientists are investigating with great rigor how to assess for and ultimately prevent the cause of PD.

Some of Dr. Perlmutter's other points related to the complexity of target selection and the impact therein. He contended that there are many pathways that one could choose to stimulate, and understanding how the pathways carrying information toward and away from the site of stimulation are effected is critically important. For example, Hashimoto and colleagues (2006) found that activation of the subthalamic nucleus (STN; a structure in the brain that is often the identified target for DBS in patients with PD) impact the fibers going away from that structure and subsequently impact the function of other structures that play a major role in controlling "movement" (e.g., as it relates to movement disorders). Some of the challenges to DBS to date include finding the optimal site to stimulate, providing rationale for a particular target, clarification of key circuits surrounding the target, improved understanding of the cellular interactions during stimulation, and improved quantification of behavioral responses to stimulation. Fortunately, with many dedicated scientists, we are making steps in the right direction that will address some of these challenges.

"Cellular Mechanisms Underlying the Therapeutic Benefit of High-Frequency Stimulation of the Subthalamic Nucleus"

Mark Bevan, Ph.D. is an Associate Professor in the Department of Physiology at the Northwestern University School of Medicine. He facilitated a presentation on Cellular mechanisms underlying the therapeutic benefit of high frequency stimulation of the STN. Dr. Bevan stated that we continue to make advances in our ability to assess cellular physiology as it relates to DBS. Specifically, he stated that cellular physiology is now capable of standard single cell recordings that permit a better understanding about the blocking of the transmission of electrical activity between cells. These detailed cell recordings permit scientists to look more closely at structures in the brain and how they relate to increasing activity between one another. For example, Hallworth and Bevan (2005) found that there is a reciprocal connection between certain structures and fibers in the brain (e.g., the relationship between fibers and neurochemicals between the Globus Pallidus and the Subthalamic Nucleus) that generate pathological rhythmic burst firing in PD, causing the motor disturbance. The take home message appeared to be that we continue to advance our knowledge about the relationship between the Globus pallidus, STN, and cortex (surface of the brain) through enhanced ability to record activity in the brain, even at the single-cell level (e.g., Baufreton, et al., 2005; Magill et al., 2006).

"Computational Analysis of Deep Brain Stimulation for Parkinson's Disease"

Cameron McIntyre, Ph.D. is an Assistant Professor in the Cleveland Clinic Lerner College of Medicine and an Assistant Staff member in the Department of Biomedical Engineering at the Cleveland Clinic Foundation. One focus of Dr. McIntyre's lab is research on PD and technology. Dr. McIntyre attempted to answer 4 common questions as it relates to DBS in PD. Question one related to identifying the best target in the brain for stimulation to control symptoms of PD. He cited studies from his lab regarding the STN and surrounding fibers that connect to other areas in the brain, which he opined to be the best targets based on his research. Question two addressed the complicated aspects of finding the ideal parameters of the deep brain stimulator. He stated one of the projects his lab is working on involves building a specific computer generated model for each patient that allows a technician to better predict stimulator parameters so patients would not have to spend as long in programming after DBS surgery. This model is still in its infancy and needs to have clinical validation in humans. Question three addressed the need for clinical utility of the models that Dr. McIntyre proposed. He noted that large expensive computers in his lab can manage the program they have created easily but that this program needs to be transferred to the laptop computer that is commonly used in the physician's office so that more doctors can use this form of technology. They are not attempting to say with 100% certainty what the actual parameter settings are or to replace the need for human knowledge/training in the programming; their goal is to minimize the amount of time needed for programming by maximizing the efficiency of technology. Also, this technology will assist with decreasing the time it takes for surgical planning. The last question he addressed was related specifically to improving the stimulator itself. He noted as technology improves it will be important to continually evaluate and improve the tools used for this surgery.
At the end of Dr. McIntyre's talk there were a series of questions answered by the panel, two of which are included below:

Q: Will there be better electrode designs?

A: Yes. There are indeed many research projects that are currently underway that are looking to better electrode designs. However, there are some hurdles, such as getting FDA approval and limited competition in the stimulator industry.

Q: What are the microlesion effects?

A: (Microlesions are small lesions in the brain in the tissue near the electrode site produced by electrical stimulation. They typically are
Panel Discussion:"Optimizing Deep Brain Stimulation and Targeting"

Panel Members included Jean Saint-Cyr, Ph.D., Peter Konrad, M.D., Ph.D., and Jens Volkmann, M.D. and the moderator was Warren Grill, Ph.D.

Jean Saint-Cyr, Ph.D., a full professor at the University of Toronto's Department of Surgery, elaborated on the advancements of the understanding of DBS surgical procedures. He discussed some of the techniques in approaching surgical implantation of DBS (e.g. the MRI structural imaging, which appears to be the preferential approach in the United States; Ben's Gun approach - Tamma et al., 2002). He acknowledged that the STN is indeed a preferred target for many, and he discussed some ideal locations within the STN wherein stimulation appears to be optimal (e.g., in the top portion of the STN). Dr. Saint-Cyr also pointed out that when conducting surgical procedures, precision is of course important, but when it comes to the individual person, the goal is to provide the optimal placement, and he opined that for many the "general ball park" will suffice (once again, with some reasonable sense of precision).
Peter Konrad, M.D., Ph.D. is an Associate Professor in the Department of Neurological Surgery and Biomedical Engineering at Vanderbilt University Medical Center. Dr. Konrad facilitated a presentation entitled,"Optimizing DBS implantation and targeting: a neurosurgeon's perspective." He stated that the precise location of the stimulator is of great importance. In fact, he stated that less than one millimeter away from the ideal location can make "a huge difference in effectiveness." Dr. Konrad also stated that no programming can substitute for a poorly implanted stimulator; consequently the location of the stimulator can directly impact the outcome of the surgery. He indicated that a couple challenges in the treatment of PD - from a neurosurgeon's perspective - include: (1) more contacts and multiple "leads" are needed for optimal treatment, and (2) target selection is frequently based on symptomatic treatment rather than the disease process itself.

Jens Volkmann, M.D. is a neurologist and professor from Christian-Albrechts University in Germany. He posed the question, "Is it preferable to stimulate gray matter (e.g., the STN itself) or fibers directly related to the intended anatomical structure [in DBS]?" He stated that research on the mechanisms of DBS suggests that axons are a primary target (axons are a usually long process of a nerve fiber that conducts impulses away from the body of the nerve cell). He added that, ultimately, the optimal electrode placement appears to be wherever stimulation causes maximal symptomatic benefit with the lowest possible stimulation energy and with the fewest side-effects. Dr. Volkmann reiterated other opinions that [for Parkinson's Disease] the most effective contacts appear to be within the STN fiber tracts.

Panel Discussion: "The Patient Perspective on Deep Brain Stimulation"

Panel members included: Margaret Tuchman, M.A. and David Heydrick, M.D., and the moderator was Jeffrey Wertheimer, Ph.D.

For a detailed review of the content of this panel discussion, please visit the DBS-STN website, where Mrs. Tuchman, Dr. Heydrick, and Dr. Wertheimer have posted their speeches ( ). Suffice it to say in this overall summary of the conference, however, the audience was very receptive to the presentations and feedback "from the patient's perspective."


Baufreton, J., Atherton, J., Surbeier, D., & Bevan, M. (2005). Enhancement of excitatory synaptic integration by GABAergic inhibition in the subthalamic nucleus. Journal of Neuroscience, 14;25(37), 8505-17.

Hallworth, N. & Bevan, M. (2005). Globus pallidus neurons dynamically regulate the activity pattern of subthalamic nucleus neurons through the frequency-dependent activation of postsynaptic GABAA and GABAB receptors. Journal of Neuroscience, 6;25(27), 6304-15.

Hashimoto, T., Elder, C., Okun, M., Patrick, S., & Vitek, J. (2003). Stimulation of the subthalamic nucleus changes the firing pattern of pallidal neurons. Journal of Neuroscience, 1;23(5), 1916-23.

Magill, P., Sharott, A., Bolam, J., & Brown, P. (2006). Delayed synchronization of activity in cortex and subthalamic nucleus following cortical stimulation in the rat. Journal of Physiology, 574(Pt 3):929-46

Tamma, F., Caputo, E., Chiesa, V., Egidi, M., Locatelli, M., Rampini, P., Cinnante, C. (2002). Anatomo-clinical correlation of intraoperative stimulation-induced side-effects during HF-DBS of the subthalamic nucleus. Neurological Sciences, 23 (2), S109-10

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