The Moral Obligation to Prioritize Research Into Deep Brain Stimulation Over Brain Lesioning Procedures for Severe Enduring Anorexia Nervosa

Deep Brain Stimulation is currently being investigated as an experimental treatment for patients suffering from treatment-refractory AN, with an increasing number of case reports and small-scale trials published. Although still at an exploratory and experimental stage, initial results have been promising. Despite the risks associated with an invasive neurosurgical procedure and the long-term implantation of a foreign body, DBS has a number of advantageous features for patients with SE-AN. Stimulation can be fine-tuned to the specific needs of the particular patient, is relatively reversible, and the technique also allows for the crucial issue of investigating and comparing the effects of different neural targets. However, at a time when DBS is emerging as a promising investigational treatment modality for AN, lesioning procedures in psychiatry are having a renaissance. Of concern it has been argued that the two kinds of interventions should instead be understood as rivaling, yet “mutually enriching paradigms” despite the fact that lesioning the brain is irreversible and there is no evidence base for an effective target in AN. We argue that lesioning procedures in AN are unethical at this stage of knowledge and seriously problematic for this patient group, for whom self-control is particularly central to wellbeing. They pose a greater risk of major harms that cannot justify ethical equipoise, despite the apparent superiority in reduced short term surgical harms and lower cost

Closed-loop deep brain stimulation based on a stream-clustering system

Idiopathic Parkinsons disease (PD) is currently the second most important neurodegenerative disease in incidence. Deep brain stimulation (DBS) constitutes a successful and necessary therapy; however, the continuous stimulation it provides can be associated with multiple side effects. DBS uses an implanted pulse generator that delivers, through a set of electrodes, electrical stimulation to the target area, normally the Sub Thalamic Nucleus. Recently, Closed-loop DBS has emerged as a promising new strategy, where the device stimulates only when necessary, thereby reducing any adverse effects. Here, we present a Closed-loop DBS system for PD, which is able to recognize, with 100% accuracy, when the patient is going to enter into the tremor phase, thus allowing the device to stimulate only in such cases. The expert system has been designed and implemented within the data stream mining paradigm, suitable for our scenario since it can cope with continuous data of a theoretical infinite length and with a certain variability, which uses the synchronization among the neural population within the Sub Thalamic Nucleus as the continuous data stream input to the system.Depto. de Psicología Experimental, Procesos Cognitivos y LogopediaDepto. de MedicinaFac. de PsicologíaFac. de MedicinaTRUEpu

Non-linear dynamical analysis of resting tremor for demand-driven deep brain stimulation.

Parkinson's Disease (PD) is currently the second most common neurodegenerative disease. One of the most characteristic symptoms of PD is resting tremor. Local Field Potentials (LFPs) have been widely studied to investigate deviations from the typical patterns of healthy brain activity. However, the inherent dynamics of the Sub-Thalamic Nucleus (STN) LFPs and their spatiotemporal dynamics have not been well characterized. In this work, we study the non-linear dynamical behaviour of STN-LFPs of Parkinsonian patients using ε -recurrence networks. RNs are a non-linear analysis tool that encodes the geometric information of the underlying system, which can be characterised (for example, using graph theoretical measures) to extract information on the geometric properties of the attractor. Results show that the activity of the STN becomes more non-linear during the tremor episodes and that ε -recurrence network analysis is a suitable method to distinguish the transitions between movement conditions, anticipating the onset of the tremor, with the potential for application in a demand-driven deep brain stimulation system

A torque-based method demonstrates increased rigidity in Parkinson’s disease during low-frequency stimulation

Low-frequency oscillations in the basal ganglia are prominent in patients with Parkinson's disease off medication. Correlative and more recent interventional studies potentially implicate these rhythms in the pathophysiology of Parkinson's disease. However, effect sizes have generally been small and limited to bradykinesia. In this study, we investigate whether these effects extend to rigidity and are maintained in the on-medication state. We studied 24 sides in 12 patients on levodopa during bilateral stimulation of the STN at 5, 10, 20, 50, 130 Hz and in the off-stimulation state. Passive rigidity at the wrist was assessed clinically and with a torque-based mechanical device. Low-frequency stimulation at ≤20 Hz increased rigidity by 24 % overall (p = 0.035), whereas high-frequency stimulation (130 Hz) reduced rigidity by 18 % (p = 0.033). The effects of low-frequency stimulation (5, 10 and 20 Hz) were well correlated with each other for both flexion and extension (r = 0.725 ± SEM 0.016 and 0.568 ± 0.009, respectively). Clinical assessments were unable to show an effect of low-frequency stimulation but did show a significant effect at 130 Hz (p = 0.002). This study provides evidence consistent with a mechanistic link between oscillatory activity at low frequency and Parkinsonian rigidity and, in addition, validates a new method for rigidity quantification at the wrist

Deep Brain Stimulation (DBS) Applications

The issue is dedicated to applications of Deep Brain Stimulation and, in this issue, we would like to highlight the new developments that are taking place in the field. These include the application of new technology to existing indications, as well as ‘new’ indications. We would also like to highlight the most recent clinical evidence from international multicentre trials. The issue will include articles relating to movement disorders, pain, psychiatric indications, as well as emerging indications that are not yet accompanied by clinical evidence. We look forward to your expert contribution to this exciting issue

Molybdenum Cofactor Deficiency Causing Neonatal Seizures and Global Developmental Delay

ABSTRACT: Molybdenum cofactor deficiency is a rare degenerative brain disorder with autosomal recessive inheritance. It presents early in neonatal life with seizures, feeding difficulty and spasticity, sometimes misdiagnosed as neonatal hypoxic ischemic encephalopathy. Neuroimaging findings are consistent with loss of white matter and volume along with cystic encephalomalacic changes. Most of the patients have mutations in the MOCS1 and MOCS2 genes causing imbalance in the sulfur-containing amino acid metabolism leading to progressive neurological damage and early childhood death in majority of cases. We report a case of a 7 months old child, product of non-consanguineous marriage with history of neonatal seizures and global developmental delay. Examination showed facial dysmorphism and spasticity with neuroimaging showing marked cortical atrophy and agenesis of corpus callosum

Beta oscillations and urinary voiding in Parkinson disease

Objectives To investigate the role of beta oscillations in urinary voiding and their association with lower urinary tract symptoms in Parkinson disease (PD). Methods We used surgically implanted deep brain stimulation electrodes to record local field potential signals from the subthalamic nucleus (STN) and globus pallidus interna (GPi) of patients with PD during urinary voiding. Five patients with STN electrodes and 5 patients with GPi electrodes were tested. We also explored correlations between beta oscillatory power and urinary symptoms assessed by the International Consultation on Incontinence Lower Urinary Tract Symptoms questionnaire. Results Beta suppression occurred during urinary voiding in the GPi (p ≺ 0.05) but not the STN. Furthermore, the beta signal in the GPi during voiding correlated significantly with severity of incontinence and urinary frequency (p ≺ 0.05). Conclusions In this study, we have demonstrated that local field potentials can provide information about the neural control of the bladder. Our findings suggest that the GPi is implicated in the process of urinary voiding and that its mechanism of action is linked to signals in the beta frequency band. Moreover, our correlational analyses show that beta oscillations may be implicated more generally in the pathophysiology of lower urinary tract symptoms in PD

A Fuzzy Inference System for Closed-Loop Deep Brain Stimulation in Parkinson’s Disease

Parkinsons disease is a complex neurodegenerative disorder for which patients present many symptoms, tremor being the main one. In advanced stages of the disease, Deep Brain Stimulation is a generalized therapy which can significantly improve the motor symptoms. However despite its beneficial effects on treating the symptomatology, the technique can be improved. One of its main limitations is that the parameters are fixed, and the stimulation is provided uninterruptedly, not taking into account any fluctuation in the patients state. A closed-loop system which provides stimulation by demand would adjust the stimulation to the variations in the state of the patient, stimulating only when it is necessary. It would not only perform a more intelligent stimulation, capable of adapting to the changes in real time, but also extending the devices battery life, thereby avoiding surgical interventions. In this work we design a tool that learns to recognize the principal symptom of Parkinsons disease and particularly the tremor. The goal of the designed system is to detect the moments the patient is suffering from a tremor episode and consequently to decide whether stimulation is needed or not. For that, local field potentials were recorded in the subthalamic nucleus of ten Parkinsonian patients, who were diagnosed with tremor-dominant Parkinsons disease and who underwent surgery for the implantation of a neurostimulator. Electromyographic activity in the forearm was simultaneously recorded, and the relation between both signals was evaluated using two different synchronization measures. The results of evaluating the synchronization indexes on each moment represent the inputs to the designed system. Finally, a fuzzy inference system was applied with the goal of identifying tremor episodes. Results are favourable, reaching accuracies of higher 98.7 % in 70 % of the patients.Centro de Investigación Biomédica en RedDepto. de Psicología Experimental, Procesos Cognitivos y LogopediaDepto. de Radiología, Rehabilitación y FisioterapiaFac. de PsicologíaFac. de MedicinaTRUEpu

Oscillatory neural representations in the sensory thalamus predict neuropathic pain relief by deep brain stimulation

Objective Understanding the function of sensory thalamic neural activity is essential for developing and improving interventions for neuropathic pain. However, there is a lack of investigation of the relationship between sensory thalamic oscillations and pain relief in patients with neuropathic pain. This study aims to identify the oscillatory neural characteristics correlated with pain relief induced by deep brain stimulation (DBS), and develop a quantitative model to predict pain relief by integrating characteristic measures of the neural oscillations. Approach Measures of sensory thalamic local field potentials (LFPs) in thirteen patients with neuropathic pain were screened in three dimensional feature space according to the rhythm, balancing, and coupling neural behaviours, and correlated with pain relief. An integrated approach based on principal component analysis (PCA) and multiple regression analysis is proposed to integrate the multiple measures and provide a predictive model. Main results This study reveals distinct thalamic rhythms of theta, alpha, high beta and high gamma oscillations correlating with pain relief. The balancing and coupling measures between these neural oscillations were also significantly correlated with pain relief. Significance The study enriches the series research on the function of thalamic neural oscillations in neuropathic pain and relief, and provides a quantitative approach for predicting pain relief by DBS using thalamic neural oscillations