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

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

Balancing the Brain: Resting State Networks and Deep Brain Stimulation

Over the last three decades, large numbers of patients with otherwise treatment-resistant disorders have been helped by deep brain stimulation (DBS), yet a full scientific understanding of the underlying neural mechanisms is still missing. We have previously proposed that efficacious DBS works by restoring the balance of the brain's resting state networks. Here, we extend this proposal by reviewing how detailed investigations of the highly coherent functional and structural brain networks in health and disease (such as Parkinson's) have the potential not only to increase our understanding of fundamental brain function but of how best to modulate the balance. In particular, some of the newly identified hubs and connectors within and between resting state networks could become important new targets for DBS, including potentially in neuropsychiatric disorders. At the same time, it is of essence to consider the ethical implications of this perspective

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

Monitoring blood pressure variability via chaotic global metrics using local field potential oscillations

The intention was to associate blood pressure (BP) variability (BPV) measurements to Local field potentials (LFPs). Thus, assessing how LFPs can co-vary with BPV to permit implantable brain devices (via LFPs) to control output. Elevated BPV is a considerable cardiovascular disease risk factor. Often patients are resistant to pharmacotherapies. An alternative treatment is Deep Brain Stimulation (DBS). Mathematical techniques based on nonlinear dynamics assessed their correlation of BPV chaotic global metrics to LFPs. Chaos Forward Parameter (CFP6) was computed for LFPs, at three electrode depths in the mid-brain and sensory thalamus. Mean, root mean square of the successive differences (RMSSD) and the chaotic global metrics (CFP1 to CFP7) were computed for the BP signal. The right ventroposterolateral (RVPL) nucleus provided a substantial correlation via CFP6 for BP with R-squared up to approximately 79% by means of LFP gamma oscillations. Investigation of BPV via LFPs as a proxy marker might allow therapies to be attuned in a closed-loop system. Whilst all patients were chronic pain patients the chaotic global relationship should be unperturbed. LFPs correlation does not unconditionally predict its causation. There is no certainty DBS in these locations would be therapeutic but can be used as an assessment tool

A block to pre-prepared movement in gait freezing, relieved by pedunculopontine nucleus stimulation

Gait freezing and postural instability are disabling features of Parkinsonian disorders, treatable with pedunculopontine nucleus stimulation. Both features are considered deficits of proximal and axial musculature, innervated predominantly by reticulospinal pathways and tend to manifest when gait and posture require adjustment. Adjustments to gait and posture are amenable to pre-preparation and rapid triggered release. Experimentally, such accelerated release can be elicited by loud auditory stimuli—a phenomenon known as ‘StartReact’. We observed StartReact in healthy and Parkinsonian controls. However, StartReact was absent in Parkinsonian patients with severe gait freezing and postural instability. Pedunculopontine nucleus stimulation restored StartReact proximally and proximal reaction times to loud stimuli correlated with gait and postural disturbance. These findings suggest a relative block to triggered, pre-prepared movement in gait freezing and postural instability, relieved by pedunculopontine nucleus stimulation

Alpha oscillations in the pedunculopontine nucleus correlate with gait performance in parkinsonism

The pedunculopontine nucleus, a component of the reticular formation, is topographically organized in animal models and implicated in locomotor control. In Parkinson's disease, pedunculopontine nucleus stimulation is an emerging treatment for gait freezing. Local field potentials recorded from pedunculopontine nucleus electrodes in such patients have demonstrated oscillations in the alpha and beta frequency bands, reactive to self-paced movement. Whether these oscillations are topographically organized or relevant to locomotion is unknown. Here, we recorded local field potentials from the pedunculopontine nucleus in parkinsonian patients during rest and unconstrained walking. Relative gait speed was assessed with trunk accelerometry. Peaks of alpha power were present at rest and during gait, when they correlated with gait speed. Gait freezing was associated with attenuation of alpha activity. Beta peaks were less consistently observed across rest and gait, and did not correlate with gait speed. Alpha power was maximal in the caudal pedunculopontine nucleus region and beta power was maximal rostrally. These results indicate a topographic distribution of neuronal activity in the pedunculopontine nucleus region and concur with animal data suggesting that the caudal subregion has particular relevance to gait. Alpha synchronization, proposed to suppress ‘task irrelevant’ distraction, has previously been demonstrated to correlate with performance of cognitive tasks. Here, we demonstrate a correlation between alpha oscillations and improved gait performance. The results raise the possibility that stimulation of caudal and rostral pedunculopontine nucleus regions may differ in their clinical effects