Chencheng Zhang

A Remote and Wireless Deep Brain Stimulation Programming System.

To the Editor: The success of deep brain stimulation generally depends on a good grasp of surgical indications, precise implantation of electrodes, and the optimal adjustment of programmable parameters (1). Programming settings are modified through contact selection, pulse width, frequency, and amplitude, to achieve optimal control of clinical symptoms with minimal stimulation parameters. Hence, programming is a crucial aspect of DBS, which directly influences its therapeutic efficacy (2). DBS patients are typically required to undergo three stages of programming: intraoperative, initial postoperative, and follow-up postoperative. Intraoperative programming is intended to test the physical connectivity (impedance) of the DBS system and the clinical efficacy of DBS, thereby providing indirect evidence of accurate electrode placement (3,4). The goal of initial postoperative programming is to identify the minimal stimulation parameters needed to achieve optimal control of clinical symptoms. The purpose of followup postoperative programming is to perform appropriate adjustments to stimulation parameters according to changes in the patient’s condition, including disease progression and suboptimal symptom control due to medication adjustments. Different programming requirements exist at different programming stages. Intraoperative programming time should be minimized to reduce total operation time, while the surgical procedure should be adapted to minimize risk of infection caused by programming. For initial postoperative programming, the time needed to ascertain optimum stimulation parameters should also be minimized, and reasonable arrangement of numerous patients’ programming schedules must be organized. Finally, follow-up postoperative programming should maximize patient convenience by reducing the time and financial cost of travelling between the patient’s home and the hospital. There are a number of inadequacies in conventional programming methods. First, the programming probe must come into close contact with the implantable pulse generator (IPG) and test stimulator to complete programming. However, the probe is not sterile during intraoperative programming and must therefore be wrapped in a sterile plastic bag before it can be attached to the IPG. Furthermore, when measuring the physical connectivity of the DBS product, the surgeon must pause the surgery and make room for the attachment between the programming probe and IPG. During initial postoperative programming, only the parameters of one patient can be ascertained. In addition, the same frequency is typically used in the left and right brain for dual channel IPG. During follow-up postoperative programming, the patient must repeatedly travel between their home and the hospital, leading to increased time and expense. An ideal solution to the outlined issues lies in wireless and remote programming technology. With this technology, the need for an additional probe is eliminated, as is the need for close contact, thus significantly reducing the risk of infection. Furthermore, all patients awaiting programming can be simultaneously identified, and programming a single patient only requires switching within the patient list. Data from multiple groups can also be stored. In addition, the technology offers remote follow-up capabilities. It is therefore convenient, time-saving, and economical for patients. To address the outlined issues, we developed the SceneRay wireless and remote DBS system. This system has significant advantages across all three stages of programming compared to conventional programming methods. Patient convenience is markedly improved, while risk of infection and total treatment time are minimized, thereby leading to an overall benefit for doctors and patients alike.

Remotely Programmed Deep Brain Stimulation of the Bilateral Subthalamic Nucleus for the Treatment of Primary Parkinson Disease: A Randomized Controlled Trial Investigating the Safety and Efficacy of a Novel Deep Brain Stimulation System.

Background: Deep brain stimulation (DBS) is the most commonly performed surgery for the debilitating symptoms of Parkinson disease (PD). However, DBS systems remain largely unaffordable to patients in developing countries, warranting the development of a safe, economically viable, and functionally comparable alternative. Objective: To investigate the efficacy and safety of wirelessly programmed DBS of bilateral subthalamic nucleus (STN) in patients with primary PD. Methods: Sixty-four patients with primary PD were randomly divided into test and control groups (1:1), where DBS was initiated at either 1 month or 3 months, respectively, after surgery. Safety and efficacy of the treatment were compared between on- and off-medication states 3 months after surgery. Outcome measures included analysis of Unified Parkinsons Disease Rating Scale (UPDRS) scores, duration of “on” periods, and daily equivalent doses of levodopa. All patients were followed up both 6 and 12 months after surgery. Results: Three months after surgery, significant decrease in the UPDRS motor scores were observed for the test group in the off-medication state (25.08 ± 1.00) versus the control group (4.20 ± 1.99). Conclusions: Bilateral wireless programming STN-DBS is safe and effective for patients with primary PD in whom medical management has failed to restore motor function.

Effects of Anterior Capsulotomy on Decision Making in Patients with Refractory Obsessive–Compulsive Disorder

Despite various lines of evidence implicating impaired decision-making ability in individuals with obsessive–compulsive disorder (OCD), neuropsychological investigation has generated inconsistent findings. Although the cortico-striato-thalamo-cortical (CSTC) circuitry has been suggested, the involvement of the cortex has not yet been fully demonstrated. Moreover, it is unknown whether surgical intervention on the CSTC circuitry results in a predicted improvement of decision-making ability of OCD. Here we present a study of decision making based on the Iowa Gambling Task (IGT) to investigate decision making in a large sample of individuals with treatment-resistant OCD with and without anterior capsulotomy (AC). Task performance was evaluated in healthy subjects, individuals with OCD that had not undergone surgery, and postsurgical OCD patients with AC. The latter group was further divided into a short-term postsurgical group and a long-term postsurgical group. We found that the OCD patients without surgery performed significantly worse than the healthy controls on the IGT. There were no significant differences in decision-making between the presurgical OCD patients and those at the short-term postsurgical follow-up. Decision-making ability of the long-term postsurgical OCD patients was improved to the level comparable to that of healthy controls. All clinical symptoms (OCD, depression, and anxiety) assessed by psychiatric rating scales were significantly alleviated post-surgically, but exhibited no correlation with their IGT task performance. Our findings provide strong evidence that OCD is linked to impairments in decision-making ability; that impaired CSTC circuitry function is directly involved in the manifestation of OCD; and that AC related improvements in cognitive functions are caused by long-term plasticity in the brain circuitry.

The safety issues and hardware-related complications of deep brain stimulation therapy: a single-center retrospective analysis of 478 patients with Parkinson’s disease

Introduction Deep brain stimulation (DBS) is a well-established therapy for the treatment of advanced Parkinson’s disease (PD) in patients experiencing motor fluctuations and medication-refractory tremor. Despite the relative tolerability and safety of this procedure, associated complications and unnatural deaths are still unavoidable. Methods In this study, hardware-related complications and the causes of unnatural death were retrospectively analyzed in 478 patients with PD who were treated with DBS. Results The results showed a 3-year survival rate of 98.6% and a 5-year survival rate of 96.4% for patients with PD who underwent DBS treatment at the study center. Pneumonia was the cause of death with the highest frequency. Prophylactic antibiotics and steroids or antihistamine drugs were adopted to reduce the risk of infection. Twenty-two patients (4.6%) experienced hardware-related complications. Conclusion Deaths of PD patients who receive DBS are typically unrelated to the disease itself or complications associated with the surgery. Pneumonia, malignant tumors, asphyxia, and multiple-organ failure are the common causes of death. Swallowing-related problems may be the most important clinical symptom in late-stage PD, as they cannot be stabilized or improved by DBS alone, and are potentially lethal. Although prophylactic antibiotics and steroids or antihistamine drugs may reduce the risk of infection, it is imperative to identify high-risk patients for whom a therapeutic approach not requiring an implantable device is more suitable, for example, pallidotomy and potentially transcranial ultrasound.

High-angular diffusion MRI in reward-based psychiatric disorders

The structural mapping of the complex brain networks under healthy and diseased states is of great importance to understand the working mechanism of the brain function. Diffusion weighted magnetic resonance imaging and its derivative methods are currently the only way to measure macroscopic axonal organization in nervous system tissues, in vivo and non-invasively. Nevertheless, it has revealed tremendous unprecedented details about the brain architecture and inspired unlimited expectation on its future development. In this chapter, we first explain the basic principles of diffusion tensor imaging (DTI) , and then discuss the strategies for resolving multiple fibers within one voxel, in particular on the diffusion spectrum imaging (DSI) method. We further introduce the pipeline of data analysis including quantification of whole brain white matter and visualization of specific microstructural tracts, and conclude with their recent applications in psychiatric disorders.

Effect of Bilateral Anterior Cingulotomy on Chronic Neuropathic Pain with Severe Depression

BACKGROUND The presence of neuropathic pain can severely impinge on emotional regulation and activities of daily living including social activities, resulting in diminished life satisfaction. Unfortunately, the majority of patients with neuropathic pain do not experience an amelioration of symptoms from conventional therapies, even when multimodal therapies are used. Chronic refractory neuropathic pain is usually accompanied by severe depression that is prone to incur suicidal events; thus clinical management of chronic neuropathic pain and depression presents a serious challenge for clinicians and patients. CASE DESCRIPTION Two patients presented at our institution with neuropathic pain and severe depression. The patients had different pain symptoms emerging a few months after central or peripheral nervous system impairment. These symptoms were associated with the development of severe depression, social isolation, and a gradual inability to perform daily activities. Both patients were referred to our treatment center for bilateral anterior cingulotomy. After surgery, both patients showed significant progressive improvements in perceived pain, mental health status, and daily functioning. CONCLUSIONS Bilateral anterior cingulotomy may serve as an alternative treatment for medically refractory neuropathic pain, especially for patients who also experience depression.

Spinal Cord Stimulation Combined with Anterior Cingulotomy to Manage Refractory Phantom Limb Pain

Background: Phantom limb pain (PLP) is an intractable and debilitating disease without satisfactory treatment options presently available. Central reorganization, peripheral changes, and psychiatric factors contribute to its development; thus, a neuropsychiatry-orientated combined therapy could be promising. Objectives: We used a combined strategy with the aims of demonstrating its therapeutic outcomes on PLP. Methods: The patient initially received spinal cord stimulation (SCS) implantation and then anterior cingulotomy (ACING) 2 years later. We administered the Hamilton Depression Scale-24, Hamilton Anxiety Scale, Pain Rating Index, Numerical Pain Rating Scale, and the Short Form (36) Health Survey to assess its outcomes at 5 time points, namely the time before performing SCS implantation, 1 year and 2 years after SCS implantation, and 1 year and 2 years after SCS combined with ACING. Results: Excellent pain relief and significant improvement in depression symptoms were observed in this patient with PLP who underwent SCS combined with ACING. Conclusions: This report suggests that SCS combined with ACING is efficacious for PLP. However, further studies are warranted.

Subthalamic deep brain stimulation in patients with primary dystonia: A ten-year follow-up study

BACKGROUND Subthalamic deep brain stimulation (STN-DBS) is a promising intervention for primary dystonia; however, evidence regarding its efficacy is lacking. Thus, a long-term follow-up is indispensable. OBJECTIVE This trial was designed to examine the efficacy and consistency of subthalamic deep brain stimulation in patients with primary dystonia over the long term. METHOD This was a retrospective study involving 14 patients with primary dystonia who underwent STN-DBS and consented to a follow-up of at least 10 years. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and 36-item Short-Form General Health Survey were employed, at five time points (pre-operation [baseline], 1 month post-operation, 1 year post-operation, 5 years post-operation, and last follow-up), to assess improvement of dystonic symptoms and changes in quality of life. OUTCOMES All patients gained extensive clinical benefits from STN-DBS therapy, without experiencing serious adverse effects. Improvements of 59.0% at 1 month, 85.0% at 1 year, and 90.8% at 5 years after the operation, and up to 91.4% at the last follow-up, were demonstrated by movement evaluation with the BFMDRS. All patients achieved a substantial improvement in quality of life. CONCLUSION Subthalamic deep brain stimulation is an effective and persisting alternative to pallidal deep brain stimulation, and importantly, it is very safe even with extremely long-term chronic stimulation.

Functional Connectivity-Based Modelling Simulates Subject-Specific Network Spreading Effects of Focal Brain Stimulation

Neurostimulation remarkably alleviates the symptoms in a variety of brain disorders by modulating the brain-wide network. However, how brain-wide effects on the direct and indirect pathways evoked by focal neurostimulation elicit therapeutic effects in an individual patient is unknown. Understanding this remains crucial for advancing neural circuit-based guidance to optimize candidate patient screening, pre-surgical target selection, and post-surgical parameter tuning. To address this issue, we propose a functional brain connectome-based modeling approach that simulates the spreading effects of stimulating different brain regions and quantifies the rectification of abnormal network topology in silico. We validated these analyses by pinpointing nuclei in the basal ganglia circuits as top-ranked targets for 43 local patients with Parkinson’s disease and 90 patients from a public database. Individual connectome-based analysis demonstrated that the globus pallidus was the best choice for 21.1% and the subthalamic nucleus for 19.5% of patients. Down-regulation of functional connectivity (up to 12%) at these prioritized targets optimally maximized the therapeutic effects. Notably, the priority rank of the subthalamic nucleus significantly correlated with motor symptom severity (Unified Parkinson’s Disease Rating Scale III) in the local cohort. These findings underscore the potential of neural network modeling for advancing personalized brain stimulation therapy, and warrant future experimental investigation to validate its clinical utility.

Deep Brain Stimulation of the Internal Globus Pallidus Improves Response Initiation and Proactive Inhibition in Patients With Parkinson’s Disease

Background: Impulse control disorder is not uncommon in patients with Parkinson’s disease (PD) who are treated with dopamine replacement therapy and subthalamic deep brain stimulation (DBS). Internal globus pallidus (GPi)-DBS is increasingly used, but its role in inhibitory control has rarely been explored. In this study, we evaluated the effect of GPi-DBS on inhibitory control in PD patients. Methods: A stop-signal paradigm was used to test response initiation, proactive inhibition, and reactive inhibition. The subjects enrolled in the experiment were 27 patients with PD, of whom 13 had received only drug treatment and 14 had received bilateral GPi-DBS in addition to conventional medical treatment and 15 healthy individuals. Results: Our results revealed that with GPi-DBS on, patients with PD showed significantly faster responses than the other groups in trials where it was certain that no stop signal would be presented. Proactive inhibition was significantly different in the surgical patients with GPi-DBS on versus when GPi-DBS was off, in surgical patients with GPi-DBS on versus drug-treated patients, and in healthy controls versus drug-treated patients. Correlation analyses revealed that when GPi-DBS was on, there was a statistically significant moderate positive relationship between proactive inhibition and dopaminergic medication. Conclusion: GPi-DBS may lead to an increase in response initiation speed and improve the dysfunctional proactive inhibitory control observed in PD patients. Our results may help us to understand the role of the GPi in cortical-basal ganglia circuits.