Impact of an Interdisciplinary Deep Brain Stimulation Screening Model on Post-Surgical Complications in Essential Tremor Patients

Objective

To investigate the relationship of our interdisciplinary screening process on post-operative unintended hospitalizations and quality of life.

Background

There are currently no standardized criteria for selection of appropriate Deep Brain Stimulation candidates and little hard data exists to support the use of any singular method.

Methods

An Essential Tremor cohort was selected from our institutional Deep Brain Stimulation database. The interdisciplinary model utilized seven specialties who pre-operatively screened all potential Deep Brain Stimulation candidates. Concerns for surgery raised by each specialty were documented and classified as none, minor, or major. Charts were reviewed to identify unintended hospitalizations and quality of life measurements at 1 year post-surgery.

Results

Eighty-six percent (44/51) of the potential screened candidates were approved for Deep Brain Stimulation. Eight (18%) patients had an unintended hospitalization during the follow-up period. Patients with minor or major concerns raised by any specialty service had significantly more unintended hospitalizations when compared to patients without concerns (75% vs. 25%, p < 0.005). The rate of hospitalization revealed a direct relationship to the “level of concern”; ranging from 100% if major concerns, 42% if minor concerns, and 7% if no concerns raised, p = 0.001. Quality of life scores significantly worsened in patients with unintended hospitalizations at 6 (p = 0.046) and 12 months (p = 0.027) when compared to baseline scores. No significant differences in tremor scores between unintended and non-unintended hospitalizations were observed.

Conclusions

The number and level of concerns raised during interdisciplinary Deep Brain Stimulation screenings were significantly related to unintended hospitalizations and to a reduced quality of life. The interdisciplinary evaluation may help to stratify risk for these complications. However, data should be interpreted with caution due to the limitations of our study. Further prospective comparative and larger studies are required to confirm our results.     

Capitalizing on deep brain stimulation: thalamus as a language monitor

In this issue of Neuron, Wahl et al. demonstrate via invasive recordings from Deep Brain Stimulation leads that the thalamus (but not basal ganglia) is sensitive to certain linguistic violations, consistent with a subcortical role in selective recruitment of language-related cortical areas.     

The epigenetic component of the brain response to electromagnetic stimulation in Parkinson's Disease patients: A literature overview

Modulations of epigenetic machinery, namely DNA methylation pattern, histone modification, and non‐coding RNAs expression, have been recently included among the key determinants contributing to Parkinson's Disease (PD) aetiopathogenesis and response to therapy. Along this line of reasoning, a set of experimental findings are highlighting the epigenetic‐based response to electromagnetic (EM) therapies used to alleviate PD symptomatology, mainly Deep Brain Stimulation (DBS) and Transcranial Magnetic Stimulation (TMS). Notwithstanding the proven efficacy of EM therapies, the precise molecular mechanisms underlying the brain response to these types of stimulations are still far from being elucidated. In this review we provide an overview of the epigenetic changes triggered by DBS and TMS in both PD patients and neurons from different experimental animal models. Furthermore, we also propose a critical overview of the exposure modalities currently applied, in order to evaluate the technical robustness and dosimetric control of the stimulation, which are key issues to be carefully assessed when new molecular findings emerge from experimental studies. Bioelectromagnetics. 39:3–14, 2018. © 2017 Wiley Periodicals, Inc.     

Effects of Deep Brain Stimulation on the Lived Experience of Obsessive-Compulsive Disorder Patients: In-Depth Interviews with 18 Patients

Deep Brain Stimulation (DBS) is a relatively new, experimental treatment for patients suffering from treatment-refractory Obsessive Compulsive Disorder (OCD). The effects of treatment are typically assessed with psychopathological scales that measure the amount of symptoms. However, clinical experience indicates that the effects of DBS are not limited to symptoms only: patients for instance report changes in perception, feeling stronger and more confident, and doing things unreflectively. Our aim is to get a better overview of the whole variety of changes that OCD patients experience during DBS treatment. For that purpose we conducted in-depth, semi-structured interviews with 18 OCD patients. In this paper, we present the results from this qualitative study. We list the changes grouped in four domains: with regard to (a) person, (b) (social) world, (c) characteristics of person-world interactions, and (d) existential stance. We subsequently provide an interpretation of these results. In particular, we suggest that many of these changes can be seen as different expressions of the same process; namely that the experience of anxiety and tension gives way to an increased basic trust and increased reliance on one’s abilities. We then discuss the clinical implications of our findings, especially with regard to properly informing patients of what they can expect from treatment, the usefulness of including CBT in treatment, and the limitations of current measures of treatment success. We end by making several concrete suggestions for further research.     

Characterizing Deep Brain Stimulation effects in computationally efficient neural network models

Background  

Recent studies on the medical treatment of Parkinson's disease (PD) led to the introduction of the so called Deep Brain Stimulation (DBS) technique. This particular therapy allows to contrast actively the pathological activity of various Deep Brain structures, responsible for the well known PD symptoms. This technique, frequently joined to dopaminergic drugs administration, replaces the surgical interventions implemented to contrast the activity of specific brain nuclei, called Basal Ganglia (BG). This clinical protocol gave the possibility to analyse and inspect signals measured from the electrodes implanted into the deep brain regions. The analysis of these signals led to the possibility to study the PD as a specific case of dynamical synchronization in biological neural networks, with the advantage to apply the theoretical analysis developed in such scientific field to find efficient treatments to face with this important disease. Experimental results in fact show that the PD neurological diseases are characterized by a pathological signal synchronization in BG. Parkinsonian tremor, for example, is ascribed to be caused by neuron populations of the Thalamic and Striatal structures that undergo an abnormal synchronization. On the contrary, in normal conditions, the activity of the same neuron populations do not appear to be correlated and synchronized.     

Ethical concerns regarding commercialization of deep brain stimulation for obsessive compulsive disorder

The United States Food and Drug Administration's recent approval of the commercial use of Deep Brain Stimulation (DBS) as a treatment for Obsessive Compulsive Disorder (OCD) will be discussed within the context of the existing USA regulatory framework. The purpose will be to illustrate the current lack of regulation and oversight of the DBS market, which has resulted in the violation of basic ethical norms. The discussion will focus on: 1) the lack of available evidence on procedural safety and efficacy, 2) the numerous conflicts of interest held by research investigators, and 3) the ambiguity of both aforementioned categories due to an inherent lack of transparency in the research. It is argued that in order to address these issues, ethical analyses of DBS for psychiatric disorders must include the role of the industry forces that have become the primary impetus for this research. As such, DBS for OCD serves as an important case example in studies of neurotechnology and innovative surgery.     

BRAIN,MIND AND MACHINE: WHAT ARE THE IMPLICATIONS OF DEEP BRAIN STIMULATION FOR PERCEPTIONS OF PERSONAL IDENTITY,AGENCY AND FREE WILL?

Brain implants, such as Deep Brain Stimulation (DBS), which are designed to improve motor, mood and behavioural pathology, present unique challenges to our understanding of identity, agency and free will. This is because these devices can have visible effects on persons' physical and psychological properties yet are essentially undetectable when operating correctly. They can supplement and compensate for one's inherent abilities and faculties when they are compromised by neuropsychiatric disorders. Further, unlike talk therapy or pharmacological treatments, patients need not ‘do’ anything for the treatment to take effect. If one accepts, as we argue here, that brain implants are unique among implantable types of devices, then this can have significant implications for what it means to persist as the same person and be the source of one's thoughts and actions. By examining two of the most common indications for DBS in current use, namely in the motor (Parkinson's Disease) and psychiatric (Major Depression) domains, we further argue that although DBS, as it is currently applied, does not necessarily represent a unique threat to personal identity and agency per se, it introduces an unprecedented ‘third party’ into the debate on these concepts. In this way, DBS can be used as a tool to begin probing, both conceptually and empirically, some of philosophy's most perennial metaphysical questions.     

A population level computational model of the basal ganglia that generates parkinsonian local field potential activity

Recordings from the basal ganglia’s subthalamic nucleus are acquired via microelectrodes immediately prior to the application of Deep Brain Stimulation (DBS) treatment for Parkinson’s Disease (PD) to assist in the selection of the final point for the implantation of the DBS electrode. The acquired recordings reveal a persistent characteristic beta band peak in the power spectral density function of the Local Field Potential (LFP) signals. This peak is considered to lie at the core of the causality–effect relationships of the parkinsonian pathophysiology. Based on LFPs acquired from human subjects during DBS for PD, we constructed a computational model of the basal ganglia on the population level that generates LFPs to identify the critical pathophysiological alterations that lead to the expression of the beta band peak. To this end, we used experimental data reporting that the strengths of the synaptic connections are modified under dopamine depletion. The hypothesis that the altered dopaminergic modulation may affect both the amplitude and the time course of the postsynaptic potentials is validated by the model. The results suggest a pivotal role of both of these parameters to the pathophysiology of PD.     

Stochastic Modeling of Mouse Motor Activity under Deep Brain Stimulation: The Extraction of Arousal Information

In the present paper, we quantify, with a rigorous approach, the nature of motor activity in response to Deep Brain Stimulation (DBS), in the mouse. DBS is currently being used in the treatment of a broad range of diseases, but its underlying principles are still unclear. Because mouse movement involves rapidly repeated starting and stopping, one must statistically verify that the movement at a given stimulation time was not just coincidental, endogenously-driven movement. Moreover, the amount of activity changes significantly over the circadian rhythm, and hence the means, variances and autocorrelations are all time varying. A new methodology is presented. For example, to discern what is and what is not impacted by stimulation, velocity is classified (in a time-evolving manner) as being zero-, one- and two-dimensional movement. The most important conclusions of the paper are: (1) (DBS) stimulation is proven to be truly effective; (2) it is two-dimensional (2-D) movement that strongly differs between light and dark and responds to stimulation; and, (3) stimulation in the light initiates a manner of movement, 2-D movement, that is more commonly seen in the (non-stimulated) dark. Based upon these conclusions, it is conjectured that the above patterns of 2-D movement could be a straightforward, easy to calculate correlate of arousal. The above conclusions will aid in the systematic evaluation and understanding of how DBS in CNS arousal pathways leads to the activation of behavior.     

Reflections on a giant of brain science

Walter J. Freeman was a giant of the field of neuroscience whose visionary work contributed various experimental and theoretical breakthroughs to brain research in the past 60 years. He has pioneered a number of Electroencephalogram and Electrocorticogram tools and approaches that shaped the field, while “Freeman Neurodynamics” is a theoretical concept that is widely known, used, and respected among neuroscientists all over the world. His recent death is a profound loss to neuroscience and biomedical engineering. Many of his revolutionary ideas on brain dynamics have been ahead of their time by decades. We summarize his following groundbreaking achievements: (1) Mass Action in the Nervous System, from microscopic (single cell) recordings, through mesoscopic populations, to large-scale collective brain patterns underlying cognition; (2) Freeman–Kachalsky model of multi-scale, modular brain dynamics; (3) cinematic theory of cognitive dynamics; (4) phase transitions in cortical dynamics modeled with random graphs and quantum field theory; (5) philosophical aspects of intentionality, consciousness, and the unity of brain–mind–body. His work has been admired by many of his neuroscientist colleagues and followers. At the same time, his multidisciplinary approach combining advanced concepts of control theory and the mathematics of nonlinear systems and chaos, poses significant challenges to those who wish to thoroughly understand his message. The goal of this commemorative paper is to review key aspects of Freeman’s neurodynamics and to provide some handles to gain better understanding about Freeman’s extraordinary intellectual achievement.     

Increased bradykinesia in Parkinson’s disease with increased movement complexity: elbow flexion–extension movements

The present research investigates factors contributing to bradykinesia in the control of simple and complex voluntary limb movement in Parkinson’s disease (PD) patients. The functional scheme of the basal ganglia (BG)–thalamocortical circuit was described by a mathematical model based on the mean firing rates of BG nuclei. PD was simulated as a reduction in dopamine levels, and a loss of functional segregation between two competing motor modules. In order to compare model simulations with performed movements, flexion and extension at the elbow joint is taken as a test case. Results indicated that loss of segregation contributed to bradykinesia due to interference between competing modules and a reduced ability to suppress unwanted movements. Additionally, excessive neurotransmitter depletion is predicted as a possible mechanism for the increased difficulty in performing complex movements. The simulation results showed that the model is in qualitative agreement with the results from movement experiments on PD patients and healthy subjects. Furthermore, based on changes in the firing rate of BG nuclei, the model demonstrated that the effective mechanism of Deep Brain Stimulation (DBS) in STN may result from stimulation induced inhibition of STN, partial synaptic failure of efferent projections, or excitation of inhibitory afferent axons even though the underlying methods of action may be quite different for the different mechanisms.     

Psychosurgery; present indications and future prospects

Although the advent and widespread use of ataractic drugs has more or less eclipsed lobotomy as a method of dealing with severe psychotic states, variations and adaptations of the operation still can be used with benefit in certain pretty well defined circumstances."Chemical lobotomy" and regressive electroshock bring about alterations in behavior superficially resembling those of lobotomy, but without the changes in personality that are the object of lobotomy. These desirable changes consist in increased extraversion, decreased preoccupation with self and decreased sensitivity to the opinions of others. With restricted operations, undesirable changes-the "frontal lobe syndrome"-do not occur. OPERATIVE FAILURES ARE DUE TO THREE MAIN CAUSES: (a) Preoperative emotional deterioration; (b) progress of the underlying disease; (c) relapse, possibly due to inadequate operation. Lobotomy is advisable if the patient does not show sustained improvement after a year of active treatment by other indicated means. The operation often represents the turning point in effective treatment. After the first year of ineffective treatment valuable time is being lost, with danger of fixation and deterioration. Then it is safer to operate than to wait. The future of psychosurgery lies in prompt application, in favorable patients, of selective operations that will reverse the trend of illness. There is particular need for further exploration of the temporal lobes in the hope of finding some procedure that will suppress hallucinations. Some 90 per cent of patients remaining in hospitals after psychosurgery are experiencing hallucinations. If these phenomena can be eliminated without producing serious personality defects, another large field for the application of psychosurgery will be opened.     

Impulsivities and Parkinson's Disease: Delay Aversion Is Not Worsened by Deep Brain Stimulation of the Subthalamic Nucleus

Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN) improves motor symptoms in Parkinson''s disease (PD), but can exert detrimental effects on impulsivity. These effects are especially related to the inability to slow down when high-conflict choices have to be made. However, the influence that DBS has on delay aversion is still under-investigated. Here, we tested a group of 21 PD patients on and off stimulation (off medication) by using the Cambridge Gamble Task (CGT), a computerized task that allows the investigation of risk-related behaviours and delay aversion, and psychological questionnaires such as the Barratt Impulsiveness Scale (BIS), the Sensitivity to Punishment and to Reward Questionnaire (SPSRQ), and the Quick Delay Questionnaire (QDQ). We found that delay aversion scores on the CGT were no higher when patients were on stimulation as compared to when they were off stimulation. In contrast, PD patients reported feeling more impulsive in the off stimulation state, as revealed by significantly higher scores on the BIS. Higher scores on the sensitivity to punishment subscale of the SPSRQ highlighted that possible punishments influence patients'' behaviours more than possible rewards. Significant correlations between delay aversion scores on the CGT and QDQ delay aversion subscale suggest that these two instruments can be used in synergy to reach a convergent validity. In conclusion, our results show that not all impulsivities are detrimentally affected by DBS of the STN and that the joint use of experimental paradigms and psychological questionnaires can provide useful insights in the study of impulsivity.     

PSYCHOSURGERY—Present Indications and Future Prospects

Although the advent and widespread use of ataractic drugs has more or less eclipsed lobotomy as a method of dealing with severe psychotic states, variations and adaptations of the operation still can be used with benefit in certain pretty well defined circumstances.“Chemical lobotomy” and regressive electroshock bring about alterations in behavior superficially resembling those of lobotomy, but without the changes in personality that are the object of lobotomy. These desirable changes consist in increased extraversion, decreased preoccupation with self and decreased sensitivity to the opinions of others. With restricted operations, undesirable changes—the “frontal lobe syndrome”—do not occur.Operative failures are due to three main causes: (a) Preoperative emotional deterioration; (b) progress of the underlying disease; (c) relapse, possibly due to inadequate operation.Lobotomy is advisable if the patient does not show sustained improvement after a year of active treatment by other indicated means. The operation often represents the turning point in effective treatment. After the first year of ineffective treatment valuable time is being lost, with danger of fixation and deterioration. Then it is safer to operate than to wait.The future of psychosurgery lies in prompt application, in favorable patients, of selective operations that will reverse the trend of illness.There is particular need for further exploration of the temporal lobes in the hope of finding some procedure that will suppress hallucinations. Some 90 per cent of patients remaining in hospitals after psychosurgery are experiencing hallucinations. If these phenomena can be eliminated without producing serious personality defects, another large field for the application of psychosurgery will be opened.     

A Simple Stimulatory Device for Evoking Point-like Tactile Stimuli: A Searchlight for LFP to Spike Transitions

Current neurophysiological research has the aim to develop methodologies to investigate the signal route from neuron to neuron, namely in the transitions from spikes to Local Field Potentials (LFPs) and from LFPs to spikes.LFPs have a complex dependence on spike activity and their relation is still poorly understood¹. The elucidation of these signal relations would be helpful both for clinical diagnostics (e.g. stimulation paradigms for Deep Brain Stimulation) and for a deeper comprehension of neural coding strategies in normal and pathological conditions (e.g. epilepsy, Parkinson disease, chronic pain). To this aim, one has to solve technical issues related to stimulation devices, stimulation paradigms and computational analyses. Therefore, a custom-made stimulation device was developed in order to deliver stimuli well regulated in space and time that does not incur in mechanical resonance. Subsequently, as an exemplification, a set of reliable LFP-spike relationships was extracted.The performance of the device was investigated by extracellular recordings, jointly spikes and LFP responses to the applied stimuli, from the rat Primary Somatosensory cortex. Then, by means of a multi-objective optimization strategy, a predictive model for spike occurrence based on LFPs was estimated.The application of this paradigm shows that the device is adequately suited to deliver high frequency tactile stimulation, outperforming common piezoelectric actuators. As a proof of the efficacy of the device, the following results were presented: 1) the timing and reliability of LFP responses well match the spike responses, 2) LFPs are sensitive to the stimulation history and capture not only the average response but also the trial-to-trial fluctuations in the spike activity and, finally, 3) by using the LFP signal it is possible to estimate a range of predictive models that capture different aspects of the spike activity.     

Investigating the effects of subthalamic Nucleus–Deep brain stimulation on the voice quality

Abstract

Introduction: Deep brain stimulation (DBS) is a standard surgical treatment method which is generally applied to subthalamic nucleus in Parkinson’s patients in cases where medical treatment is insufficient in treating the motor symptoms. It is known that Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) treats many motor symptoms. However, the results of studies on speech and voice vary. The aim of the study is analysing the effect of STN-DBS on the characteristics of voice.

Materials/methods: A total of 12 patients, (8 male–4 female) with an age average of 58.8?±?9.6, who have been applied DBS surgery on STN included in the study. The voice recordings of the patients have been done prior to surgery and 6?months after the surgery. The evaluation of voice has been carried out through the instrumental method. The patients’ voice recordings of the /a,e,i/ vowels have been done. The obtained recordings were evaluated by the Praat programme and the effects on jhitter, shimmer, fundamental frequency (F0) and noise harmonic rate (NHR) were analysed.

Results: Numerical values of F0 of all female participants have been decreased for all of the vowels postoperatively. In the females; jhitter and fraction parameters were found to be significantly different (0.056 and 0.017, perspectively) for the vowel /e/. In addition, p values in the shimmer for vowels /e,i/ were thought to be clinically significant (.087, .079 and .076) respectively. All these changes in second measurements were found to indicate worsening vocal quality after the DBS in females. In males, there is not any significant difference observed between two measures in any of the parameters of any vowels.

Conclusions: Acoustic voice quality deteriorated after STN-DBS predominantly for females however this deterioration was not prominent audio-perceptually. This finding commented as a result of the fact that that voice quality deviance of the participants was not severe.     

Natural deep eutectic solvents for lignocellulosic biomass pretreatment: Recent developments,challenges and novel opportunities

Conversion of lignocellulosic biomass to fuels and chemicals has attracted immense research and development around the world. Lowering recalcitrance of biomass in a cost-effective manner is a challenge to commercialize biomass-based technologies. Deep eutectic solvents (DESs) are new ‘green' solvents that have a high potential for biomass processing because of their low cost, low toxicity, biodegradability, easy recycling and reuse. This article discusses the properties of DESs and recent advances in their application for lignocellulosic biomass processing. The effectiveness of DESs in hydrolyzing lignin-carbohydrate complexes, removing lignin/hemicellulose from biomass as well as their effect on biomass deconstruction, crystallinity and enzymatic digestibility have been discussed. Moreover, this review presents recent findings on the compatibility of natural DESs with enzymes and microorganisms.     

Conochironomus Freeman: an Afro-Australian Chironomini genus revised (Diptera: Chironomidae)

The chironomid genus Conochironomus is revised, with diagnoses provided for both sexes of adults and, for the first time, the immature stages. The Afrotropical genotype C.acutistilus Freeman and the newly described Australian species C.australiensis (for misidentified acutistilus in Australia), C.cygnus and C.kakadu are described in all stages. C.avicula Freeman is redescribed from the male, and C.deemingi is described as new from the male alone, both from the Afrotropical Region. The Australian species C.cervus is described as new, based on the pupa alone. Comments are made on the ecology and distribution. A previously little-recognized 'tropical' Gondwanan biogeographic explanation for Conochironomus distribution is postulated.     

Brain/MINDS: brain-mapping project in Japan

There is an emerging interest in brain-mapping projects in countries across the world, including the USA, Europe, Australia and China. In 2014, Japan started a brain-mapping project called Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS). Brain/MINDS aims to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain, and takes advantage of a unique non-human primate animal model, the common marmoset (Callithrix jacchus). In Brain/MINDS, the RIKEN Brain Science Institute acts as a central institute. The objectives of Brain/MINDS can be categorized into the following three major subject areas: (i) structure and functional mapping of a non-human primate brain (the marmoset brain); (ii) development of innovative neurotechnologies for brain mapping; and (iii) human brain mapping; and clinical research. Brain/MINDS researchers are highly motivated to identify the neuronal circuits responsible for the phenotype of neurological and psychiatric disorders, and to understand the development of these devastating disorders through the integration of these three subject areas.