Application Of Deep Brain Stimulation Research Articles

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

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.

Expanding indications for deep brain stimulation.

It has been three decades since the first application of deep brain stimulation (DBS) for tremors was described by Benabid. Over the years, the indications for the performance of DBS have been expanding. There are now more than 1,50,000 patients around the world who have undergone DBS for various disorders. The main appeal of DBS is in its reversibility and titratability. Though the initial interest in DBS was for pain, the main indications for DBS have been movement disorders. Despite its wide appeal and "perceived" advantage, United States Food and Drug Administration, the nodal agency for approving therapies, has been cautious and guarded in providing approvals. Only two indications, i.e., Parkinson's disease and tremors, have been approved; the two other indications, i.e., dystonia and obsessive compulsive disorder (OCD), have been granted exemption under the humanitarian device usage. However, the European community has been more liberal and several of these indications have CE (Conformite Europeene) approval. Most of them will be reviewed in this article. There have been numerous indications for which DBS has been applied, which in turn has helped to change the lives of several patients. Unfortunately, due to the paucity of the number of procedures performed and the inherent difficulty in conducting "surgical" double blind randomized trials, Class 1 or Class 2 evidence for several of these indications is lacking. Hence, it is advisable that one does not embark on using each and any target for each and any indication without having the understanding or the team backup. It is cautionary that most of these therapies should be conducted in an institutional setting with an ethics and scientific committee backup and ably assisted by an experienced team.

Brain Trust

Deep brain stimulation: Deep brain stimulationFigureFigureSometimes it can seem as if the emergency department is the neurology waiting room. Many new technologies are being applied to neurologic disorders, but they may result in complications and an ED visit for the patient. Deep brain stimulation is one of them. Deep brain stimulation (DBS) consists of the implantation of electrodes that block electrical signals in certain target regions (subthalamic nucleus, the internal segment of the globus pallidus, or the ventral intermediate nucleus of the thalamus) that can dramatically alleviate symptoms such as tremor, slowed movement or bradykinesia, and altered muscle tone or dystonia. (Annu Rev Neurosci 2006;29:229.) DBS has proven to be remarkably successful in treating movement disorders such as Parkinson's disease (PD) or essential tremor over the past 25 years. The application of DBS in other neurologic and neuropsychiatric conditions like neuropathic pain, depression, and Tourette's syndrome has become the object of extensive research in recent years. (Front Hum Neurosci 2017;11:177; Ann Transl Med 2017;5[Suppl 1]:S1; Lancet Neurol 2017;16[8]:610.) The physiological mechanisms behind the varied uses of this treatment remain uncertain, but its use continues to increase. (Annu Rev Neurosci 2006;29:229.) The most extended use of DBS is, by far, in movement disorders such as PD. DBS has been proven to enable a significant reduction in dopaminergic medications and their side effects. (Annu Rev Neurosci 2006;29:229.) This is advantageous for patients, but we should expect to see some associated complications and understand how to identify them correctly. These conditions can be divided into perioperative and postoperative. The main perioperative complications are intracranial hemorrhage (including intracerebral, intraventricular, subdural, subarachnoid, and epidural), venous infarction, and air embolus. (Parkinsonism Relat Disord 2010;16[3]:153.) Symptoms of intracranial hemorrhage can include epileptic seizure, hemiparesis, or a reduced level of consciousness, and may be a consequence of venous infarction. Venous infarction may present progressively hours to days after surgery, and manifest with confusion and focal neurological symptoms. Air embolus is caused by the entry of air into the venous system during surgery, and usually has a benign clinical course. (Curr Neurol Neurosci Rep 2017;17[7]:51.) Postoperative complications can appear at any stage from the immediate perioperative phase to weeks or months after surgery. They can include neuroleptic-like malignant syndrome, dyskinetic storm, psychiatric complications (acute behavioral and cognitive changes, suicide attempt or ideation), and hardware-related complications (hardware infection, failure, accidental on/off), among others. All of them may present in the emergency department. Postoperative Complications Neuroleptic-like malignant syndrome, though rare in clinical practice, can be a consequence of postoperative withdrawal of dopaminergic agents used to evaluate the success of the procedure. It is defined by parkinsonism, high fever, rhabdomyolysis, and myoglobinuria. Treatment measures typically include hydration and respiratory support. (Curr Neurol Neurosci Rep 2017;17[7]:51.) Postoperative dyskinesias, in which a patient presents with involuntary movement, can sometimes acutely progress to dyskinetic storm, in which a patient presents with severe, uncontrollable, and often violent involuntary movement that can manifest with dyspnea and rhabdomyolysis in severe cases. (Parkinsonism Relat Disord 2010;16[3]:153.) Careful dose reduction of dopaminergic medications and administration of sedatives may help; ICU care is sometimes necessary. (Curr Neurol Neurosci Rep 2017;17[7]:51.) Psychiatric or neuropsychiatric complications such as cognitive and behavioral changes are common adverse events after DBS surgery. Though usually self-limited, these changes may become permanent in patients with cognitive alterations pre-surgery. Confusion and alterations in verbal fluency are the most common manifestations. Underlying causes such as hemorrhage or urinary tract infection can contribute to psychiatric changes. (Parkinsonism Relat Disord 2010;16[3]:153.) Suicide attempt or ideation may be more prevalent in DBS patients than in the general population, but not when compared with the PD population. (Neurology 2004;63[11]:2170.) Screening for suicide ideation following DBS and inpatient psychiatric treatment if suicidal thoughts are identified are recommended. (Parkinsonism Relat Disord 2010;16[3]:153.) Hardware complications can include infection, malfunction, and accidental on/off, among others. Infection following surgery is not uncommon, and can present with focal neurological deficits and fever. Abscess drainage and removal of infected pieces of hardware, along with antibiotics, are the main components of adequate treatment. (Parkinsonism Relat Disord 2010;16[3]:153.) Sudden loss of function in a previously satisfactory clinical course post-DBS might be due to hardware malfunction or accidental on/off. Adequate patient information, use of the DBS programming/interrogation device, and referral to a DBS specialist may be of help in these cases. (Curr Neurol Neurosci Rep 2017;17[7]:51.) Keeping these complications in mind when presented with a patient who has used DBS is key. A thorough patient history and physical examination, including a complete neurological examination, as well as careful listing of the patients' medications with special attention to past or present use of dopaminergic agents can point us in the right direction.

Target-specific deep brain stimulation of the ventral capsule/ventral striatum for the treatment of neuropsychiatric disease.

Deep brain stimulation (DBS) is a well-established therapy for Parkinson's disease and other movement disorders. An accumulating body of evidence supports the extension of DBS application for the treatment of refractory psychiatric disorders. The ventral capsule/ventral striatum (VC/VS) is the most common anatomical target for obsessive-compulsive disorder (OCD), addiction, and depression. However, no specific electrode is available for the clinical targeting of these areas for DBS. According to the anatomical features of the VC/VS, a novel electrode was developed for simultaneous and independently programmed stimulation of the nucleus accumbens (NAc) and the anterior limb of the internal capsule (ALIC). This VC/VS-specific electrode has the potential to enhance stimulus intensity, provide independent and flexible target stimulation.

Prefrontal Cortex Deep Brain Stimulation Improves Fear and Anxiety-Like Behavior and Reduces Basolateral Amygdala Activity in a Preclinical Model of Posttraumatic Stress Disorder.

Deep brain stimulation (DBS) is being investigated for a number of psychiatric indications, including posttraumatic stress disorder (PTSD). Preclinical studies continue to be a cornerstone for the development of new DBS applications. We investigate whether DBS delivered to the infralimbic cortex (IL), a region involved in mechanisms of stress resiliency, may counter behavioral abnormalities in rats that present persistent extinction deficits and long-term anxiety after exposure to fear conditioning. Rats undergoing fear conditioning/extinction were segregated into weak and strong extinction groups (WE >70% or SE <30% of freezing during extinction). Following 2 weeks of DBS, animals were exposed to novel recall sessions and tested in the open field, novelty-suppressed feeding, and elevated plus maze. zif268 expression was measured in structures involved in mechanisms of fear and stress. In vivo electrophysiology was used to record activity from the basolateral amygdala (BLA). We found that DBS improved extinction deficits and anxiety-like behavior in WE animals, having no significant effects in SE rats. No major differences in absolute zif268 levels were recorded across groups. However, correlation between zif268 expression in the IL and BLA was disrupted in WE animals, a deficit that was countered by DBS treatment. Electrophysiology experiments have shown that DBS reduced BLA firing of both putative principal cells and interneurons in WE rats, with no significant differences being detected between SE and SE DBS animals. In summary, IL DBS mitigated fear, partially improved anxiety-like behavior, reversed neurocircuitry abnormalities, and reduced BLA cell firing in a preclinical model of PTSD.

Refining the Deep Brain Stimulation Target within the Limbic Globus Pallidus Internus for Tourette Syndrome

Background: Deep brain stimulation (DBS) in patients with severe, refractory Tourette syndrome (TS) has demonstrated promising but variable results thus far. The thalamus and anteromedial globus pallidus internus (amGPi) have been the most commonly stimulated sites within the cortico-striato thalamic circuit, but an optimal target is yet to be elucidated. Objectives: This study of 15 patients with long-term amGPi DBS for severe TS investigated whether a specific anatomical site within the amGPi correlated with optimal clinical outcome for the measures of tics, obsessive compulsive behaviour (OCB), and mood. Methods: Validated clinical assessments were used to measure tics, OCB, quality of life, anxiety, and depression before DBS and at the latest follow-up (17-82 months). Electric field simulations were created for each patient using information on electrode location and individual stimulation parameters. A subsequent regression analysis correlated these patient-specific simulations to percentage changes in outcome measures in order to identify any significant voxels related to clinical improvement. Results: A region within the ventral limbic GPi, specifically on the medial medullary lamina in the pallidum at the level of the AC-PC, was significantly associated with improved tics but not mood or OCB outcome. Conclusions: This study adds further support to the application of DBS in a tic-related network, though factors such as patient sample size and clinical heterogeneity remain as limitations and replication is required.

What Have We Learned About Movement Disorders from Functional Neurosurgery?

Modern functional neurosurgery for movement disorders such as Parkinson's disease, tremor, and dystonia involves the placement of focal lesions or the application of deep brain stimulation (DBS) within circuits that modulate motor function. Precise targeting of these motor structures can be further refined by the use of electrophysiological approaches. In particular, microelectrode recordings enable the delineation of neuroanatomic structures. In the course of these operations, there is an opportunity not only to map basal ganglia structures but also to gain insights into how disturbances in neural activity produce movement disorders. In this review, we aim to highlight what the field has uncovered thus far about movement disorders through DBS. The work to date lays the foundation for future studies that will shed further light on dysfunctional circuits mediating diseases of the nervous system and how we might modulate these circuits therapeutically.

Deep brain stimulation in movement disorders: evidence and therapy standards

The deep brain stimulation (DBS) in movement disorders is well established and in many aspects evidence-based procedure. The treatment indications are very heterogeneous and very specific in their course and therapy. The deep brain stimulation plays very important, but usually not the central role in this conditions. The success in the application of DBS is essentially associated with the correct, appropriate and timely indication of the therapy in the course of these diseases. Thanks to the good standardization of the DBS procedure and sufficient published data, the recommendations for indication, diagnosis and operative procedures can be generated. The following article attempts to summarize the most important decision-making criteria and current therapy standards in this fairly comprehensive subject and to present them in close proximity to practice.

Tiefe Hirnstimulation bei Bewegungsstörungen: Evidenz und Therapiestandards

The deep brain stimulation (DBS) in movement disorders is well established and in many aspects evidence-based procedure. The treatment indications are very heterogeneous and very specific in their course and therapy. The deep brain stimulation plays very important, but usually not the central role in this conditions. The success in the application of DBS is essentially associated with the correct, appropriate and timely indication of the therapy in the course of these diseases. Thanks to the good standardization of the DBS procedure and sufficient published data, the recommendations for indication, diagnosis and operative procedures can be generated. The following article attempts to summarize the most important decision-making criteria and current therapy standards in this fairly comprehensive subject and to present them in close proximity to practice.

A proof-of-principle simulation for closed-loop control based on preexisting experimental thalamic DBS-enhanced instrumental learning

Deep brain stimulation (DBS) has been applied as an effective therapy for treating Parkinson's disease or essential tremor. Several open-loop DBS control strategies have been developed for clinical experiments, but they are limited by short battery life and inefficient therapy. Therefore, many closed-loop DBS control systems have been designed to tackle these problems by automatically adjusting the stimulation parameters via feedback from neural signals, which has been reported to reduce the power consumption. However, when the association between the biomarkers of the model and stimulation is unclear, it is difficult to develop an optimal control scheme for other DBS applications, i.e., DBS-enhanced instrumental learning. Furthermore, few studies have investigated the effect of closed-loop DBS control for cognition function, such as instrumental skill learning, and have been implemented in simulation environments. In this paper, we proposed a proof-of-principle design for a closed-loop DBS system, cognitive-enhancing DBS (ceDBS), which enhanced skill learning based on in vivo experimental data. The ceDBS acquired local field potential (LFP) signal from the thalamic central lateral (CL) nuclei of animals through a neural signal processing system. A strong coupling of the theta oscillation (4–7 Hz) and the learning period was found in the water reward-related lever-pressing learning task. Therefore, the theta-band power ratio, which was the averaged theta band to averaged total band (1–55 Hz) power ratio, could be used as a physiological marker for enhancement of instrumental skill learning. The on-line extraction of the theta-band power ratio was implemented on a field-programmable gate array (FPGA). An autoregressive with exogenous inputs (ARX)-based predictor was designed to construct a CL-thalamic DBS model and forecast the future physiological marker according to the past physiological marker and applied DBS. The prediction could further assist the design of a closed-loop DBS controller. A DBS controller based on a fuzzy expert system was devised to automatically control DBS according to the predicted physiological marker via a set of rules. The simulated experimental results demonstrate that the ceDBS based on the closed-loop control architecture not only reduced power consumption using the predictive physiological marker, but also achieved a desired level of physiological marker through the DBS controller.

Clinical analysis and treatment of symptomatic intracranial hemorrhage after deep brain stimulation surgery

Background: Symptomatic intracranial hemorrhage (ICH) may lead to permanent neurological disability of patients and has impeded the extensive clinical application of deep brain stimulation (DBS). The present study was conducted to discuss the incidence, prevention, and treatment of symptomatic ICH after DBS surgery.Methods: From January 2009 to December 2014, 396 patients underwent DBS with a total of 691 implanted leads. In all, 10 patients had symptomatic ICH. We analyzed these cases’ clinical characteristics, including comorbid diagnoses and coagulation profile. We described the onset of ICH, imaging features, clinical manifestations, treatment, neurological impairment, and outcome of DBS.Results: Of the 10 patients with symptomatic ICH, 2 had hypertension. Three cases of ICH occurred within 12 h of the procedure; four cases within 24 h. Five experienced grand mal seizures concurrently with hemorrhage. Unilateral frontal lobe hemorrhage occurred in all cases. In seven cases, hematomas occurred around the electrodes. Some hematomas were not well-circumscribed and had perihematomal edema. Conservative therapy was administered to 8 patients, and 2 patients underwent craniotomy and hematoma evacuation. All electrodes were successfully preserved. Neurological dysfunction in all patients gradually improved. Nine patients ultimately experienced effective symptom relief of Parkinson’s disease with DBS.Conclusions: Symptomatic ICH should be identified as soon as possible after implantation surgery and treated effectively to limit neurological deficit and preserve DBS leads.

EP 39. Clinical experience with deep brain stimulation in Huntington’s disease

Introduction Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) are well-established standard procedures for various movement disorders, e.g. Parkinson’s disease or dystonia. Until now, application of DBS in Huntington’s disease (HD) has been performed only as an individual and experimental treatment option reported in a few cases. Objective We present a prospective controlled case series of six patients with HD and bilateral DBS of the GPi. Material and Methods Indication for DBS was stated in six patients with severe, treatment-refractory chorea. The procedure was performed in general, intravenous anaesthesia. Bilateral lead placement in the GPi was achieved with stereotactic MRI-coordinates and intraoperative microrecordings. Stereotactic coordinates were as follows: (x) 19–20 mm lateral the midline of the intercommissural line, (y) 3 mm anterior and (z) 2–3 mm inferior the midpoint of the intercommissural line. Also intraoperative stimulation via the implanted leads was performed to evaluate stimulation induced-side effects like dystonic movements, eye movements etc. After insertion of the leads a second stereotactic MRI was performed to rule out any intracerebral complications and to document the definite position of the lead. Clinical evaluation included the motor score of the Unified Huntington‘s disease rating scale (UHDRS), Total Functional Capacity score (TFC), the Functional Assessment score (FA) and the 26-item version of the World Health Organisation questionnaire (WHO Bref) preoperatively and six months postoperatively. Results In all 6 patients leads were successfully implanted bilaterally in general anaesthesia. In one case one lead needed to be revised due to dislocation detected in the control, second MRI. Also in one case, second MRI revealed a small local haemorrhage in the course of one lead, but no clinical neurological deficits were observed in the patient postoperatively. Standard stimulation parameters were programmed and adjusted individually (mono- or bipolar mode, 30–130 hertz, 50–100 microseconds, amplitude 2–5.0 milliampere). The chorea subscore of the UHDRS motor score improved by 47% (range 21–86%; p Conclusion DBS of the GPi is an additional invasive treatment option for well-selected patients with HD. Risks and complications of the procedure and related to the implanted materials are low and acceptable. Continuous clinical experience and long-term follow-up of these patients are needed to evaluate the significance and evidence of DBS in HD.

EP 17. Preserved frontoparietal brain morphology correlates with beneficial response to deep brain stimulation of the Nucleus basalis of Meynert in patients with Alzheimer’s disease

Question First reports on the application of deep brain stimulation of the Nucleus basalis of Meynert reported feasibility and safety of the intervention in patients with Alzheimer’s disease. However, clinical effects vary and the mechanisms of actions are still not well understood. Methods We studied preoperative T1-weighted MR images of ten patients with Alzheimer’s disease and correlated the clinical outcome with volumetric differences in a vertex-based analysis, controlling for age, sex and the total intracranial volume. Clinical assessments, 12 months after the intervention, included the Alzheimer’s Disease Assessment Scale with its subitems for cognition and memory as well as the mini mental status examination. Results A fronto-parietal pattern including significant clusters covering the inferior and superior parietal gyrus, the precuneus, the superior and middle frontal gyrus were found to be correlated with a beneficial outcome. Conclusion Our results support the assumption, that patients with less advanced morphological changes may benefit more from deep brain stimulation of the Nucleus basalis of Meynert. Furthermore, we conclude that positive effects are mediated by a preserved fronto-parietal interplay.

Deep brain stimulation for prolonged disorders of consciousness

Deep brain stimulation has emerged as a “last resort” therapy for patients with prolonged disorders of consciousness. The latter encompasses a range of conditions including minimal conscious state and persistent vegetative state. Functional neuroimaging studies have shown that minimal conscious state and persistent vegetative state have different patterns of residual brain function and may therefore respond differently to deep brain stimulation. The failure to distinguish between the two conditions in this context can give rise to false expectation, misunderstanding and ill-guided treatment. As a halfway technology for prolonged disorders of consciousness, deep brain stimulation could also produce improvement in awareness that is in fact harm, and its impact may involve a wide range of public interests. This paper will discuss related ethical and legal issues with an emphasis on the distinction between minimal conscious state and persistent vegetative state in the application of deep brain stimulation.

Multimodal 7T Imaging of Thalamic Nuclei for Preclinical Deep Brain Stimulation Applications.

Precise neurosurgical targeting of electrode arrays within the brain is essential to the successful treatment of a range of brain disorders with deep brain stimulation (DBS) therapy. Here, we describe a set of computational tools to generate in vivo, subject-specific atlases of individual thalamic nuclei thus improving the ability to visualize thalamic targets for preclinical DBS applications on a subject-specific basis. A sequential nonlinear atlas warping technique and a Bayesian estimation technique for probabilistic crossing fiber tractography were applied to high field (7T) susceptibility-weighted and diffusion-weighted imaging, respectively, in seven rhesus macaques. Image contrast, including contrast within thalamus from the susceptibility-weighted images, informed the atlas warping process and guided the seed point placement for fiber tractography. The susceptibility-weighted imaging resulted in relative hyperintensity of the intralaminar nuclei and relative hypointensity in the medial dorsal nucleus, pulvinar, and the medial/ventral border of the ventral posterior nuclei, providing context to demarcate borders of the ventral nuclei of thalamus, which are often targeted for DBS applications. Additionally, ascending fiber tractography of the medial lemniscus, superior cerebellar peduncle, and pallidofugal pathways into thalamus provided structural demarcation of the ventral nuclei of thalamus. The thalamic substructure boundaries were validated through in vivo electrophysiological recordings and post-mortem blockface tissue sectioning. Together, these imaging tools for visualizing and segmenting thalamus have the potential to improve the neurosurgical targeting of DBS implants and enhance the selection of stimulation settings through more accurate computational models of DBS.

Mavridis’ Area Targeting for Deep Brain Stimulation in Psychiatric Disorders: Stereotactic Microanatomy and Technical Aspects

Context: The human Nucleus Accumbens (NA) constitutes nowadays a target of deep brain stimulation (DBS) for selected patients mainly suffering from some psychiatric disorders. Mavridis’ Area (MA) of the human brain is the most reliable stereotactically standard part of the NA, regardless of side or gender. Primary purpose of this review article was to discuss the MA as a stereotactic microanatomic target for NA DBS application, emphasizing on technical aspects of targeting the MA. Evidence Acquisition: A detailed search of the current literature regarding MA was applied. The critically reviewed literature was then used to discuss the MA as a stereotactic microanatomic target for NA DBS application, emphasizing on technical aspects of targeting the MA. The suggestion of future research directions was also aimed. Results: Following the currently used trajectory through the anterior limb of the internal capsule (ALIC) in combination with the principles of the ‘port model’, a DBS electrode placement within the NA, targeting the MA, is feasible. MA could be the target area of one, only, of the electrode contacts, preferably contact 1 or 2. It could be also the target area for contact 0 in ALIC DBS and even the target for a combined NA-ALIC DBS. MA is the first and most representative example of the evolution of stereotactic anatomy into stereotactic microanatomy, in order to serve the development of the field of stereotactic microneurosurgery. Conclusions: MA is nowadays the most accurate stereotactic anatomic guide for targeting the human NA. It is a representative example of how stereotactic microanatomy could serve the development of stereotactic microneurosurgery. Following the currently used trajectory through the ALIC, a DBS electrode placement within the NA, targeting the MA, is feasible, allowing either NA or ALIC stimulation. Simultaneous stimulation of the NA and ALIC is also possible with this application.

Carbon Nanofiber Nanoelectrodes for Neural Stimulation and Chemical Detection: The Era of "Smart" Deep Brain Stimulation

A sensor platform based on vertically aligned carbon nanofibers (CNFs) has been developed. Their inherent nanometer scale, high conductivity, wide potential window, good biocompatibility and well-defined surface chemistry make them ideal candidates as biosensor electrodes. Here, we report two studies using vertically aligned CNF nanoelectrodes for biomedical applications. CNF arrays are investigated as neural stimulation and neurotransmitter recording electrodes for application in deep brain stimulation (DBS). Polypyrrole coated CNF nanoelectrodes have shown great promise as stimulating electrodes due to their large surface area, low impedance, biocompatibility and capacity for highly localized stimulation. CNFs embedded in SiO2 have been used as sensing electrodes for neurotransmitter detection. Our approach combines a multiplexed CNF electrode chip, developed at NASA Ames Research Center, with the Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS) system, developed at the Mayo Clinic. Preliminary results indicate that the CNF nanoelectrode arrays are easily integrated with WINCS for neurotransmitter detection in a multiplexed array format. In the future, combining CNF based stimulating and recording electrodes with WINCS may lay the foundation for an implantable “smart” therapeutic system that utilizes neurochemical feedback control while likely resulting in increased DBS application in various neuropsychiatric disorders. In total, our goal is to take advantage of the nanostructure of CNF arrays for biosensing studies requiring ultrahigh sensitivity, high-degree of miniaturization, and selective biofunctionalization.

Manic episode following deep brain stimulation

Deep brain stimulation (DBS) of subthalamic nucleus is an effective treatment method for palliating Parkinson’s disease. But this treatment has some psychiatric side effects. Mania, depression, suicide attempt and cognitive problems can be seen as side effects of deep brain stimulation. The mechanism of emerging these side effects is not well understood. In this article, in order to attract attention to multidisciplinary approach of DBS application in Parkinson’s disease treatment, it is discussed that clinic and treatment of mania developed after DBS treatment of a Parkinson’s disease patient who is 73 years old and has not any psychiatric disease in the past.

Commentary: Tractography-Activation Models Applied to Subcallosal Cingulate Deep Brain Stimulation.

Commentary: Tractography-Activation Models Applied to Subcallosal Cingulate Deep Brain Stimulation.

Research progress of deep brain stimulation for the treatment of drug addiction

Drug addiction is a serious problem all over the world involving both medical and social issues. The treatment strategy lies in two aspects, promoting detoxification and preventing relapse. The latter is the key for successful treatment. Although surgical measures, like stereotactic ablation of nucleusaccumbens (NAc), had already been proven to be effective for relapse prevention clinically, the application was restricted because of the damage to brain tissues. Deep brain stimulation (DBS), which had been successfully applied in movement disorders, was recently performed in addiction studies on both animals and humankind. Among numbers of brain areas related to addiction, NAc is the hottest target studied and may bring better clinical effect. In addition, combining stimulation of multiple brain targets is currently performed for relapse prevention. The mechanism of DBS for treatment of addiction remains unclear right now, however, DBS may be an experimental method to treat refractory addictive patients. Certainly, lots of problems need to be solved in large sample study before the wide application of DBS for addiction treatment, such as the setting of stimulation parameters, recognition of objective treatment feedback and ethical issues. DOI: 10.3969/j.issn.1672-6731.2015.10.004