Hemmings Wu

Deep-Brain Stimulation for Anorexia Nervosa

OBJECTIVE Anorexia nervosa (AN) is a complex and severe, sometimes life-threatening, psychiatric disorder with high relapse rates under standard treatment. After decades of brain-lesioning procedures offered as a last resort, deep-brain stimulation (DBS) has come under investigation in the last few years as a treatment option for severe and refractory AN. METHODS AND RESULTS In this jointly written article, Sun et al. (the Shanghai group) report an average of 65% increase in body weight in four severe and refractory patients with AN after they underwent the DBS procedure (average follow-up: 38 months). All patients weighed greater than 85% of expected body weight and thus no longer met the diagnostic criteria of AN at last follow-up. Nuttin et al. (the Leuven group) describe other clinical studies that provide evidence for the use of DBS for AN and further discuss patient selection criteria, target selection, and adverse event of this evolving therapy. CONCLUSION Preliminary results from the Shanghai group and other clinical centers showed that the use of DBS to treat AN may be a valuable option for weight restoration in otherwise-refractory and life-threatening cases. The nature of this procedure, however, remains investigational and should not be viewed as a standard clinical treatment option. Further scientific investigation is essential to warrant the long-term efficacy and safety of DBS for AN.

Consensus on guidelines for stereotactic neurosurgery for psychiatric disorders

Background For patients with psychiatric illnesses remaining refractory to ‘standard’ therapies, neurosurgical procedures may be considered. Guidelines for safe and ethical conduct of such procedures have previously and independently been proposed by various local and regional expert groups. Methods To expand on these earlier documents, representative members of continental and international psychiatric and neurosurgical societies, joined efforts to further elaborate and adopt a pragmatic worldwide set of guidelines. These are intended to address a broad range of neuropsychiatric disorders, brain targets and neurosurgical techniques, taking into account cultural and social heterogeneities of healthcare environments. Findings The proposed consensus document highlights that, while stereotactic ablative procedures such as cingulotomy and capsulotomy for depression and obsessive-compulsive disorder are considered ‘established’ in some countries, they still lack level I evidence. Further, it is noted that deep brain stimulation in any brain target hitherto tried, and for any psychiatric or behavioural disorder, still remains at an investigational stage. Researchers are encouraged to design randomised controlled trials, based on scientific and data-driven rationales for disease and brain target selection. Experienced multidisciplinary teams are a mandatory requirement for the safe and ethical conduct of any psychiatric neurosurgery, ensuring documented refractoriness of patients, proper consent procedures that respect patients capacity and autonomy, multifaceted preoperative as well as postoperative long-term follow-up evaluation, and reporting of effects and side effects for all patients. Interpretation This consensus document on ethical and scientific conduct of psychiatric surgery worldwide is designed to enhance patient safety.

Targeting Bed Nucleus of the Stria Terminalis for Severe Obsessive-Compulsive Disorder: More Unexpected Lead Placement in Obsessive-Compulsive Disorder than in Surgery for Movement Disorders

BACKGROUND In preparation for a multicenter study, a protocol was written on how to perform surgical targeting of the bed nucleus of the stria terminalis, based on the lead implantation experience in patients with treatment-refractory obsessive-compulsive disorder (OCD) at the Universitaire Ziekenhuizen Leuven (UZ Leuven). When analyzing the postoperative images, we were struck by the fact that the difference between the postoperative position of the leads and the planned position seemed larger than expected. METHODS The precision of targeting in four patients with severe OCD who received bilateral model 3391 leads (Medtronic) was compared with the precision of targeting in the last seven patients who underwent surgery at UZ Leuven for movement disorders (four with Parkinson disease and three with essential tremor; all received bilateral leads). Because the leads implanted in six of the seven patients with movement disorders were model 3387 leads (Medtronic), targeting precision was also analyzed in four patients with OCD in whom model 3387 leads were implanted in the same target as the other patients with OCD. RESULTS In the patients with OCD, every implanted lead deviated at least 1.3 mm from its intended position in at least one of three directions (lateral, anteroposterior, and depth), whereas in the patients with movement disorders, the maximal deviation of any of all implanted leads was 1.3 mm. The deviations in lead placement were comparable in patients with OCD who received a model 3387 implant and patients who received a model 3391 implant. In the patients with OCD, all leads were implanted more posteriorly than planned. CONCLUSIONS The cause of the posterior deviation could not be determined with certainty. The most likely cause was an increased mechanical resistance of the brain tissue along the trajectory when following the targeting protocol compared with the trajectories classically used for subthalamic nucleus or ventral intermediate nucleus of the thalamus stimulation.

Conceptualization and validation of an open-source closed-loop deep brain stimulation system in rat

Conventional deep brain stimulation (DBS) applies constant electrical stimulation to specific brain regions to treat neurological disorders. Closed-loop DBS with real-time feedback is gaining attention in recent years, after proved more effective than conventional DBS in terms of pathological symptom control clinically. Here we demonstrate the conceptualization and validation of a closed-loop DBS system using open-source hardware. We used hippocampal theta oscillations as system input and electrical stimulation in the mesencephalic reticular formation (mRt) as controller output. It is well documented that hippocampal theta oscillations are highly related to locomotion, while electrical stimulation in the mRt induces freezing. We used an Arduino open-source microcontroller between input and output sources. This allowed us to use hippocampal local field potentials (LFPs) to steer electrical stimulation in the mRt. Our results showed that closed-loop DBS significantly suppressed locomotion compared to no stimulation and required on average only 56% of the stimulation used in open-loop DBS to reach similar effects. The main advantages of open-source hardware include wide selection and availability, high customizability and affordability. Our open-source closed-loop DBS system is effective and warrants further research using open-source hardware for closed-loop neuromodulation.

Rethinking Food Anticipatory Activity in the Activity-Based Anorexia Rat Model

When a rat is on a limited fixed-time food schedule with full access to a running wheel (activity-based anorexia model, ABA), its activity level will increase hours prior to the feeding period. This activity, called food-anticipatory activity (FAA), is a hypothesized parallel to the hyperactivity symptom in human anorexia nervosa. To investigate in depth the characteristics of FAA, we retrospectively analyzed the level of FAA and activities during other periods in ABA rats. To our surprise, rats with the most body weight loss have the lowest level of FAA, which contradicts the previously established link between FAA and the severity of ABA symptoms. On the contrary, our study shows that postprandial activities are more directly related to weight loss. We conclude that FAA alone may not be sufficient to reflect model severity, and activities during other periods may be of potential value in studies using ABA model.

Neurosurgery for Psychiatric Disorders in the People's Republic of China—Responsibilities of International Societies

The Ministry of Health of the Peoples Republic of China issued in April 2008 the regulation “Notification Regarding Improvement of Management and Related Issues in Neurosurgery for Psychiatric Disorders from General Office of Ministry of Health,” in order to ensure medical health care quality and to protect peoples safety. This notification consists of three major regulations: specific requirements for hospitals to perform neurosurgery for psychiatric disorders, rigorously defined indication for neurosurgery for psychiatric disorders, and improved management of clinical research in neurosurgery for psychiatric disorders. The development of this notification is undoubtedly a step forward in neurosurgery for psychiatric disorders in China. However, it was only published in Chinese to our knowledge, and therefore remained incomprehensible to non-Chinese-speaking communities. Today an English version of this notification, translated by one of the authors, sheds a light on the perspective of the Chinese government on neurosurgery for psychiatric disorders. Moreover, the authors emphasize the important role of guidelines, endorsed by world societies involved in neurosurgery for psychiatric disorders, to guide the future of this field in the right direction.

Field Potential Oscillations in the Bed Nucleus of the Stria Terminalis Correlate with Compulsion in a Rat Model of Obsessive-Compulsive Disorder

The bed nucleus of the stria terminalis (BNST) is implicated in anxiety and reward processing, both of which are associated with obsessive-compulsive disorder (OCD). Specific neuronal groups in the BNST related to anxiety and reward have been identified, but quantitative data about the information carried by local field potential (LFP) signals in this area during obsession/compulsion are lacking. Here we investigate the BNST LFP in the schedule-induced polydipsia, an animal model of OCD. We implanted electrodes bilaterally in the BNST and random control brain regions in 32 male Wistar rats, and recorded corresponding LFP during compulsive and noncompulsive behavior. We first applied high-frequency (100 Hz) electrical stimulation through the implanted electrodes and analyzed its effects on compulsive behavior. We then performed time-frequency analysis of LFPs and statistically compared the normalized power of δ (1–4 Hz), θ (4–8 Hz), α (8–12 Hz), β (12–30 Hz), and lower γ (30–45 Hz) bands between different groups. Our data showed that the normalized δ, β, and γ powers in the right BNST were specifically correlated with compulsive behaviors. δ and γ oscillations increased and decreased during the initiation phase of compulsion, respectively, whereas β increased after compulsion stopped. Moreover, the effect of BNST electrical stimulation, in terms of suppression of compulsion, was significantly correlated with the percentage change of these bands during compulsion. Our research reveals potential biomarkers and underlying neurophysiological mechanisms of compulsion and warrants further assessment of the use of LFP for closed-loop neuromodulation in OCD. SIGNIFICANCE STATEMENT Although specific neuronal groups in the bed nucleus of the stria terminalis (BNST) related to anxiety and reward circuitries have been identified, psychopathological information carried by local field potentials in the BNST has not yet been described. We discovered that normalized powers of the right BNST δ, β, and γ oscillations were highly correlated with compulsion. Specifically, δ and γ oscillations increased and decreased during the initiation phase of compulsion, respectively, whereas β increased after compulsion stopped. Such correlations were not found in other parts of the brain during compulsion, or in the BNST during noncompulsive behavior. Current findings reveal real-time neurophysiological biomarkers of compulsion and warrant further assessment of the use of local field potentials for closed-loop neuromodulation for OCD.

Preoperative Evaluation and Postoperative Follow-up of Deep Brain Stimulation for Psychiatric Disorders

Deep brain stimulation (DBS) is under investigation as a new treatment for an increasing number of psychiatric conditions. Candidates for DBS are treatment refractory, severely incapacitated and have a very low quality of life. Patient selection should identify candidates that obtain and retain the greatest benefit. In psychiatric care, it is evident that a psychiatric disorder does not affect patients alone, but has a profound and devastating impact on those around them. These caregivers cannot be neglected in the follow-up process, since the impact of DBS on the psychiatric symptoms of the patient will reflect on the relationships. After surgery, the search for adequate stimulation parameters and the optimization process with fluctuations in symptom severity may be burdensome. Patients may not be abandoned once the DBS procedure is performed. With improvement of symptoms, patients are less stuck in their chronic psychiatric disorder and may need help in the definition of new goals and new purposes in life.