Edge detections of MER Signals of STN with DBS micro electrode local field potential acquisitions in Parkinson`s

Deep brain stimulation of the subthalamic nucleus (STN) is a highly effective treatment for motor symptoms of Parkinson’s disease. Sub thalamic nucleus deep brain stimulation (STN-DBS) is a therapeutic surgical procedure for reducing the symptoms Parkinson’s and restoring and increasing the motor functioning. However, precise intraoperative edge or perimeter detection of STN remains a procedural challenge. In this study, we present the micro electrode signals recordings (MER) of STNs and local field potentials (LFPs) were acquired from deep brain stimulation macro electrodes during trajectory towards STN, in Parkinson patients. The frequency versus intensity atlas of field potential activity was obtained and further than investigated in distinct sub band’s, to explore whether field potentials activity can be employed for STN edge detection. STN perimeter detections by means of L F Ps were evaluated to edge predictions by way of the functional stereotactic DBS neurosurgeon, based on micro electrode derived, single unit recordings (M E R – S N A of S T Ns). The findings show variation amongst M E R – S N A and macro electrode L F P-signals gathering through MER-system pertaining to the d o r s a l S T N b o r d e r of -1.00±0.85mm plus -0.42±1.08 mm in the and frequencies, correspondingly. For these sub band`s, root mean square of the voids was found to be 1.27milli meters and 1.07milli meters. The Assessment of other sub band`s didn`t set a limit for differentiating the posterior (c a u d a l) point of sub-thalamic nuclei. We may infer that In conclusion, macro electrode signal acquisitions of STNs derived L F P gatherings might offer an unconventional methodology in the direction of m e r – s n a, for detecting the aimed target subthalamic nucleus borders during DBS-surgery.

The Placebo Response in Double-Blind Randomised Trials Evaluating Regenerative Therapies for Parkinson’s Disease: A Systematic Review and Meta-Analysis

In the field of stem cell technologies, exciting advances are taking place leading to translational research to develop cell-based therapies which may replace dopamine releasing neurons lost in patients with Parkinson’s disease (PD). A major influence on trial design has been the assumption that the use of sham operated comparator groups is required in the implementation of randomised double-blind trials to evaluate the placebo response and effects associated with the surgical implantation of cells. The aim of the present review is to identify the improvements in motor functioning and striatal dopamine release in patients with PD who have undergone sham surgery. Of the nine published trials, there was at the designated endpoints, a pooled average improvement of 4.3 units, with 95% confidence interval of 3.1 to 5.6 on the motor subscale of the Unified Parkinson’s Disease Scale in the ‘OFF’ state. This effect size indicates a moderate degree of improvement in the motor functioning of the patients in the sham surgical arms of the trials. Four of the nine trials reported the results of 18 F-fluorodopa PET scans, indicating no improvements of dopaminergic nigrostriatal neurones following sham surgery. Therefore, while the initial randomised trials relying on the use of sham operated controls were justified on methodological grounds, we suggest that the analysis of the evidence generated by the completed and published trials indicates that placebo controlled trials are not necessary to advance and evaluate the safety and efficacy of emerging regenerative therapies for PD.

Rhythm and timing as vulnerabilities in neurodevelopmental disorders

Millions of children are impacted by neurodevelopmental disorders (NDDs), which unfold early in life, have varying genetic etiologies and can involve a variety of specific or generalized impairments in social, cognitive and motor functioning requiring potentially lifelong specialized supports. While specific disorders vary in their domain of primary deficit (e.g. autism spectrum disorder (social), attention-deficit/hyperactivity disorder (attention), developmental coordination disorder (motor) and developmental language disorder (language)), comorbidities between NDDs are common. Intriguingly, many NDDs are associated with difficulties in skills related to rhythm, timing and synchrony though specific profiles of rhythm/timing impairments vary across disorders. Impairments in rhythm/timing may instantiate vulnerabilities for a variety of NDDs and may contribute to both the primary symptoms of each disorder as well as the high levels of comorbidities across disorders. Drawing upon genetic, neural, behavioural and interpersonal constructs across disorders, we consider how disrupted rhythm and timing skills early in life may contribute to atypical developmental cascades that involve overlapping symptoms within the context of a disorder's primary deficits. Consideration of the developmental context, as well as common and unique aspects of the phenotypes of different NDDs, will inform experimental designs to test this hypothesis including via potential mechanistic intervention approaches. This article is part of the theme issue ‘Synchrony and rhythm interaction: from the brain to behavioural ecology’.

Neuropsychological rehabilitation, neuroimaging and neuroplasticity: A clinical commentary

Initial brain imaging studies on recovery of motor functioning after stroke suggested their potential prognostic value in neurorehabilitation. However, the value of brain imaging in documenting brain changes associated with cognitive and behavioral treatment effects seem less likely. Also, neuroimaging studies at that time seem to have little, if any, value for treatment planning. Advances in neuroimaging technology are beginning to challenge these initial impressions. In this clinical commentary, we propose that advances in the field of neuroimaging have relevance for the future development of neuropsychological rehabilitation. Neuropsychological rehabilitation is entering a new era which involves collaboration with neuroimaging and associated studies on neuroplasticity. We recognize that this may seem “aspirational” rather than practical in most rehabilitation settings. However, we provide examples of how this can be achieved as illustrated by collaborative efforts of clinicians and scientists in the SARAH Network of Rehabilitation Hospitals in Brazil. We also review selective papers on neuroplasticity, spontaneous recovery and diaschisis that have relevance for research which will expand and further develop the field of neuropsychological rehabilitation.

Neurocognitive outcomes of HIV-associated tuberculous meningitis

Background: The toll of tuberculous meningitis (TBM) in both mortality and disability is considerable, but advancements in rehabilitation have the potential to improve the functional abilities and the quality of survivors’ lives. However, the typical phenotype of neurocognitive impairment in TBM survivors remains unstudied in HIV-predominant populations in sub-Saharan Africa. Methods: We tested 36 survivors of TBM in Uganda with a comprehensive battery of neurocognitive assessments at 8 and 24 weeks after diagnosis, and compared results to a representative cohort of HIV-uninfected Ugandans. Results: While participants had a broad range of impairments at eight weeks, there was marked improvement by 24 weeks, when a phenotype of impairment including deficits in motor functioning, verbal learning and memory, processing speed, and executive function emerged. These deficits were present despite good clinician-rated functional status. The majority (23/27, 85%) had evidence of moderate to severe depression at week 8, and at week 24 (18/24, 75%). Conclusion: These findings highlight the need for more comprehensive neurocognitive assessment in the survivors of TBM, and further investment in and study of rehabilitation, including management of depression, to improve long-term outcomes in this population.

Association of Proportional Recovery After Stroke With Health-Related Quality of Life

Background and Purpose: No data exists on whether proportional recovery (PR) is associated with health-related quality of life (HRQOL) domains. We evaluated whether PR was associated with domain-specific HRQOL scores at 3 months after ischemic stroke. Methods: This prospective cohort study enrolled patients with ischemic stroke between January 2017 and June 2018. Impaired strength was assessed using the Fugl-Meyer Upper Extremity (range, 0–66 points) and Motricity Index (range, 0–100 points) during index hospitalization and 3 months. Both measures are well-validated and reliable in patients with stroke to assesses motor functioning. PR (defined as 70% of difference between initial score and maximum possible recovery) was calculated from the initial measurements. HRQOL was measured using Neuro-QOL domains: upper extremity, depression, and cognition domains. PR was evaluated with HRQOL domains using binomial logistic regression. Results: Final analysis included 84 patients (mean age 67.8±16.4 years; 44% male; 51.2% White). For both Fugl-Meyer Upper Extremity and Motricity Index, the PR threshold was met for 48.8% of patients. Failure to meet Motricity Index PR was only associated with increased odds of HRQOL depression impairment (adjusted odds ratio, 11.8 [95% CI, 1.23–112.7]). Failure to meet Fugl-Meyer Upper Extremity PR threshold was not associated with HRQOL impairment after adjustment. Conclusions: Our findings suggest that reaching the PR threshold provides poor discrimination of HRQOL. Despite not meeting expected PR thresholds, patients can still maintain un-impaired HRQOL, suggesting other factors play a role in preserved HRQOL.

Where Dopaminergic and Cholinergic Systems Interact: A Gateway for Tuning Neurodegenerative Disorders

Historically, many investigations into neurodegenerative diseases have focused on alterations in specific neuronal populations such as, for example, the loss of midbrain dopaminergic neurons in Parkinson’s disease (PD) and loss of cholinergic transmission in Alzheimer’s disease (AD). However, it has become increasingly clear that mammalian brain activities, from executive and motor functioning to memory and emotional responses, are strictly regulated by the integrity of multiple interdependent neuronal circuits. Among subcortical structures, the dopaminergic nigrostriatal and mesolimbic pathways as well as cholinergic innervation from basal forebrain and brainstem, play pivotal roles in orchestrating cognitive and non-cognitive symptoms in PD and AD. Understanding the functional interactions of these circuits and the consequent neurological changes that occur during degeneration provides new opportunities to understand the fundamental inter-workings of the human brain as well as develop new potential treatments for patients with dysfunctional neuronal circuits. Here, excerpted from a session of the European Behavioral Pharmacology Society meeting (Braga, Portugal, August 2019), we provide an update on our recent work in behavioral and cellular neuroscience that primarily focuses on interactions between cholinergic and dopaminergic systems in PD models, as well as stress in AD. These brief discussions include descriptions of (1) striatal cholinergic interneurons (CINs) and PD, (2) dopaminergic and cholinergic modulation of impulse control, and (3) the use of an implantable cell-based system for drug delivery directly the into brain and (4) the mechanisms through which day life stress, a risk factor for AD, damage protein and RNA homeostasis leading to AD neuronal malfunction.

O-076 Neurodevelopmental morbidity in children born after ART: a Nordic register study from the Committee of Nordic ART and Safety (CoNARTaS) group

Study question Does the risk of neurodevelopmental disorders differ between singletons born after various assisted reproductive techniques (ART) and spontaneous conception (SC) until young adulthood? Summary answer ART children had a slightly increased rate of learning and motor functioning disorders, autism spectrum disorders (ASD), and ADHD and conduct disorders. What is known already Studies on the impact of ART on offspring have reported both increased risk and comparable incidences of neurodevelopmental disorders between ART and SC offspring. The most studied neurodevelopmental disorders with ART are autism spectrum disorders (ASD.) There is, however, no consensus on the risk of ASD for ART children. The risk for other neurodevelopmental disorders, like attention-deficit hyperactivity disorders (ADHD) or tic disorder among ART children, is also a debated issue, as studies are scarce. Study design, size, duration A Nordic register-based cohort study including all singleton live births (N = 5 076 444) after ART (n = 116 909) or SC (n = 4 959 535) between 1995 and 2014 in Denmark and Finland, 1995 and 2015 in Sweden; and 2005 and 2015 in Norway. Children with intellectual disability (ICD-10: F70-F79) are excluded. The children are followed up to young adulthood (the year 2014 in Denmark and Finland, and 2015 in Norway and Sweden). Participants/materials, setting, methods Offspring outcomes were defined as following ICD-10 diagnoses: learning and motor functioning disorders (F80-83), ASD (F84), ADHD and conduct disorders (F90-F92), and tic disorders/Tourette (F95). We calculated crude and adjusted hazard ratios (HR) for neurodevelopmental diagnoses using Cox regression. Adjustments were made for the country, maternal age at the delivery, parity, smoking, and maternal psychiatric morbidity. Main results and the role of chance The cumulative incidences of neurodevelopmental disorders in the cohort were 1.74% for F90-F92, 1.40% for F80-83, 0.66% for F84, and 0.22% for F95. In crude Cox-regression ART children had an increased likelihood during the follow-up of being diagnosed with F84 (HR 1.12 [95% CI 1.04-1.21]) and F95 (HR 1.21 [95% CI 1.06-1.38]), but not with F80-83 (HR 1.01 [95% CI 0.96-1.07]) or F90-92 (HR 0.82 [95% CI 0.77-0.86]). After adjustments the likelihood was increased for F80-83 (HR 1.20 [95% CI 1.13-1.27]), F84 (HR 1.12 [95% CI 1.03-1.24]), and F90-92 (HR 1.09 [95% CI 1.04-1.19]), but nor for F95 (HR 1.13 [95% CI 0.99-1.30]). After adjustments, intracytoplasmic sperm injection children compared with in vitro fertilization children had similar likelihood during follow-up for F80-83 (1.06 [95% CI 0.89–1.25]), for F84 (HR 0.92 [95% CI 0.76–1.11]), for F90-92 (HR 0.96 [95% CI 0.83–1.12]), and for F95 (HR 1.16 [95% CI 0.83–1.63]). After adjustments, frozen embryo transfer children compared with fresh embryo transfer children had similar likelihood during follow-up for F80-83 (HR 1.11 [95% CI 0.90–1.37]), F84 (HR 0.98 [95% CI 0.76–1.27]), F90-92 (HR 0.96 [95% CI 0.78–1.19]), and F95 (HR 0.83 [95% CI 0.51–1.35]). Limitations, reasons for caution There may be residual confounding by unknown or unmeasured confounders. We lack information on possible confounders like the reason and length of infertility, maternal substance use other than self-reported smoking status, paternal age, and parental somatic morbidity. Additional limitations are differences in registration practice and data availability between study countries. Wider implications of the findings This is the largest singleton cohort and the first multinational study on the risk for neurodevelopmental disorders among ART children. While the rate of some neurodevelopmental disorders was increased among ART children, the absolute risk was moderate. The type of ART did not associate with the incidence of neurodevelopmental disorders. Trial registration number ISRCTN11780826

Tracking motor activity in Virtual Reality to reveal cognitive functioning: A preliminary study

A challenge for cognitive research is the better understanding of how motor activity influences and is influenced by other cognitive domains. We developed a preliminary study to investigate whether tracking motor functioning in virtual reality provides useful insight on cognitive functioning. We chose the flankers task as an assessment measure and built a VR environment into which seven participants completed more than 1250 trials. In addition to classical results of the flankers task showing that incongruent stimuli induce slower responses than others., we also identified how individuals are able to correct their initially incorrect motor response. This indicator may shed new light into the functioning of cognitive control in the future. We discuss the potential offered by virtual reality technology for cognitive assessment through embodied considerations of cognition.