medRxiv - Neurology最新文献

{"title":"Effect of chronic sedative-hypnotic use on sleep architecture and brain oscillations in older adults with chronic insomnia.","authors":"Loic Barbaux, Aurore A. Perrault, Nathan E. Cross, Oren M. Weiner, Mehdi Es-sounni, Florence B. Pomares, Lukia Tarelli, Margaret McCarthy, Antonia Maltezos, Dylan Smith, Kirsten Gong, Jordan O Byrne, Victoria Yue, Caroline Desrosiers, Doris Clerc, Francis Andriamampionona, David Lussier, Suzanne Gilbert, Cara Tannenbaum, Jean- Philippe Gouin, Thien Thanh Dang-Vu","doi":"10.1101/2024.09.12.24313583","DOIUrl":"https://doi.org/10.1101/2024.09.12.24313583","url":null,"abstract":"Rationale: High rates of insomnia in older adults lead to widespread benzodiazepine (BZD) and benzodiazepine receptor agonist (BZRA) use, even though chronic use has been shown to disrupt sleep regulation and impact cognition. Little is known about sedative-hypnotic effects on NREM slow oscillations (SO) and spindles, including their coupling, which is crucial for memory, especially in the elderly. Objectives: Our objective was to investigate the effect of chronic sedative-hypnotic use on sleep macro-architecture, EEG relative power, as well as SO and spindle characteristics and coupling. Methods: One hundred and one individuals (66.05 +/- 5.84 years, 73% female) completed a one-night study and were categorized into three groups: good sleepers (GS, n=28), individuals with insomnia (INS, n=26) or individuals with insomnia who chronically use either BZD or BZRA to manage their insomnia difficulties (MED, n=47; dose equivalent in Diazepam: 6.1 +/- 3.8 mg/week). We performed a comprehensive comparison of sleep architecture, EEG relative spectrum, and associated brain oscillatory activities, focusing on NREM brain oscillations crucial for sleep-dependent memory consolidation (i.e., SO and spindles) and their temporal coupling. Results: Chronic use of BZD/BZRA worsened sleep architecture and spectral activity compared to older adults with and without insomnia disorder. The use of BZD/BZRAs also altered the characteristics of sleep-related brain oscillations and their synchrony. An exploratory interaction model suggested that BZD use exacerbated sleep alterations compared to BZRA, and higher BZD/BZRA dosage worsened alteration in sleep micro-architecture and EEG spectrum. Conclusions: Our results suggest that chronic use of sedative-hypnotics is detrimental to sleep when compared to drug-free GS and INS. Such alteration of sleep regulation; at the macro and micro-architectural levels; may contribute to the reported association between sedative-hypnotic use and cognitive impairment in older adults. Keywords: benzodiazepine, sleep, brain oscillation, ageing","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-intensity focused ultrasound stimulation in stroke: An intensity escalation phase I safety and feasibility study","authors":"Ziping Huang, Charalambos C Charalambous, Mengyue Chen, Taewon Kim, Estate Sokhadze, Allen Song, Sin-Ho Jung, Shashank Shekhar, Jody Feld, Xiaoning Jiang, Wuwei Feng","doi":"10.1101/2024.09.12.24313472","DOIUrl":"https://doi.org/10.1101/2024.09.12.24313472","url":null,"abstract":"BACKGROUND: Low-intensity focused ultrasound stimulation (LIFUS) has recently emerged as a promising neuromodulation tool for certain neuropsychiatric diseases. However, its safety and feasibility in stroke patients remains unknown. Intensity is a critical safety parameter for LIFUS. We aimed to determine the maximum safe and tolerable intensity of LIFUS in stroke patients, and to explore its effect on upper- extremity motor learning and corticospinal excitability.\u0000METHODS: Subjects with first-ever stroke participated in this Phase I study. We adopted the classic 3+3 dose-escalation paradigm to sham/0, 1, 2, 4, 6, and 8 W/cm² spatial-peak pulse-average intensity (I_SPPA, estimated in-vivo transcranial value; LOW: sham/0, 1 and 2 W/cm², HIGH: 4, 6 and 8 W/cm²). Stopping rules (dose limiting toxicities) were pre-defined: ≥2^nd-degree scalp burn, clinical seizures, ≥20% topical apparent diffusion coefficient change, or participant discontinuation due to any reason. A 12-minute LIFUS was applied over the ipsilesional motor cortex while participants were concurrently practicing three blocks of motor sequence learning (MSL) task using the affected hand. We collected the occurrences of pre-defined adverse events, post- minus-pre improvements in MSL response time, and post-minus-pre differences in corticospinal excitability quantified by motor evoked potentials.\u0000RESULTS: I_SPPA was escalated to 8 W/cm² with eighteen stroke participants without meeting stopping rules. Compared to the LOW, the HIGH performed significantly better on the MSL (24.7±13.3% vs. 13.2±10.9%, p=0.01). Similarly, the HIGH also showed signs of increased corticospinal excitability (32.0±34.3% vs. 12.9±48.0%) but did not reach significance, p=0.53.\u0000CONCLUSIONS: Our Phase I safety study suggests that a single session of 12-minute LIFUS up to 8 W/cm² I_SPPA is safe and feasible in stroke patients. Higher LIFUS intensities can induce greater MSL retention. The next logical step is to conduct a Phase II study to further test the efficacy of LIFUS and monitor its safety profiles in stroke patients.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"88 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WearGait-PD: An Open-Access Wearables Dataset for Gait in Parkinson's Disease and Age-Matched Controls","authors":"Anthony J Anderson, David Eguren, Michael A Gonzalez, Naima Khan, Sophia Watkinson, Michael Caiola, Siegfried S Hirczy, Cyrus P Zabetian, Kelly Mills, Emile Moukheiber, Laureano Moro-Velazquez, Najim Dehak, Chelsie Motley, Brittney C Muir, Ankur A Butala, Kimberly L Kontson","doi":"10.1101/2024.09.11.24313476","DOIUrl":"https://doi.org/10.1101/2024.09.11.24313476","url":null,"abstract":"Wearable movement sensors are powerful tools for objectively characterizing and quantifying movement. They enhance the precise characterization of gait, balance, and motor symptoms in Parkinson's disease and related disorders, facilitating in-clinic and remote assessments, disease management, and therapeutic intervention development. Access to high-quality data from these sensors can accelerate discoveries in this clinical population. The WearGait-PD open-access dataset contains raw inertial measurement unit (IMU) and sensorized insole data from individuals with PD and age-matched controls, synchronized to a gait walkway reference system. IMU data include 3-degree of freedom (DOF) acceleration, rotational velocity, magnetic field strength, and orientation for each of 13 sensors on the participant's body. Sensor insole data include absolute pressure from 16 sensors in each insole and 3-DOF acceleration and rotational velocity. Walkway data include 2D position and relative pressure for each active sensor during every footfall. Frame-by-frame annotation of participant actions during gait and balance tasks was incorporated using synchronized video cameras. All data were associated with demographic information and clinical evaluations (e.g., medications, DBS-status, MDS-UPDRS scores).","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SAHVER: Subarachnoid Hemorrhage Volumetric Expediting Resolution","authors":"saif salman, Yujia Wei, melina wirtz, bradley erickson, rohan sharma, Nicholas Brandmeir, Behnam Rezai Jahromi, david miller, nadia albaramony, rabih tawk, William David Freeman","doi":"10.1101/2024.09.09.24312803","DOIUrl":"https://doi.org/10.1101/2024.09.09.24312803","url":null,"abstract":"Introduction: Subarachnoid Hemorrhage Volumetric Artificial Intelligence (SAHVAI) is a novel model that segments and quantifies Subarachnoid Hemorrhage Volume (SAHV) on non-contrast CT (NCCT) scans and generates a 3D brain volumetric map called SAHVAI-3D. It is enhanced into SAHVAI-4D when measured over time. Precise measurement of SAHV is critical to future discoveryies. For example, IRRAflow is a FDA-approved ventricular irrigation and drainage system that can expedite removal of SAH blood products.\u0000Objective: Utilize SAHVAI model to compare and quantify the course of SAHV resolution over time and generate SAHVAI-3D brain maps to help visualize significant SAHV resolution patterns and predict vasospasm. Methods: We applied SAHVAI to SAH cases with mFS(3-4) using the NCCT scans among three groups. Group A included 1 SAH patient treated with the IRRAflow system. Group B included one SAH patient presented GCS 15 two days after ictus with no requirement for EVD. Group C included 10 patients who underwent regular EVD placement per standard of care. Results: Group A showed expedited resolution of SAHV (1.87mL/day) with an mRS of 0 on discharge and minimal vasospasm (Figures 1, 2). Group B showed 16mL increase in SAHV suspected for aneurysmal rebleeding days (5-9), and the patient later died (mRS of 6) (Figure 3). Group C showed reduction of SAHV of ~ 0.5ml /day (Figure 4). Further, the resultant 3D brain maps revealed that areas with the highest density of blood concentration were correlated with the severity and location of the vasospasm in all groups (Table 1). Conclusion: SAHVAI, SAHVAI-3D and SAHVAI-4D are novel methods that reliably quantifies SAHV blood volume and changes over time including SAH blood resolution or rebleeding events. SAHVER is a model that shows how interventions such as IRRAflow can expedite SAHV resolution compared to passive EVD and non-CSF drainage groups.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Trials for Wolfram Syndrome Neurodegeneration: Novel Design, Endpoints, and Analysis Models","authors":"Guoqiao Wang, Zhaolong Adrian Li, Ling Chen, Heather Lugar, Tamara Hershey","doi":"10.1101/2024.09.10.24313426","DOIUrl":"https://doi.org/10.1101/2024.09.10.24313426","url":null,"abstract":"Objective\u0000Wolfram syndrome, an ultra-rare condition, currently lacks effective treatment options. The rarity of this disease presents significant challenges in conducting clinical trials, particularly in achieving sufficient statistical power (e.g., 80%). The objective of this study is to propose a novel clinical trial design based on real-world data to reduce the sample size required for conducting clinical trials for Wolfram syndrome. Methods\u0000We propose a novel clinical trial design with three key features aimed at reducing sample size and improve efficiency: (i) Pooling historical/external controls from a longitudinal observational study conducted by the Washington University Wolfram Research Clinic. (ii) Utilizing run-in data to estimate model parameters. (iii) Simultaneously tracking treatment effects in two endpoints using a multivariate proportional linear mixed effects model. Results\u0000Comprehensive simulations were conducted based on real-world data obtained through the Wolfram syndrome longitudinal observational study. Our simulations demonstrate that this proposed design can substantially reduce sample size requirements. Specifically, with a bivariate endpoint and the inclusion of run-in data, a sample size of approximately 30 per group can achieve over 80% power, assuming the placebo progression rate remains consistent during both the run-in and randomized periods. In cases where the placebo progression rate varies, the sample size increases to approximately 50 per group. Conclusions\u0000For rare diseases like Wolfram syndrome, leveraging existing resources such as historical/external controls and run-in data, along with evaluating comprehensive treatment effects using bivariate/multivariate endpoints, can significantly expedite the development of new drugs.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"198 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A prebiotic diet intervention can restore faecal short chain fatty acids in Parkinson's Disease yet fails to restore the gut microbiome homeostasis","authors":"Janis Rebecca Bedarf, Stefano Romano, Silke Sophie Heinzmann, Anthony Duncan, Maria H Traka, Duncan Ng, Daniella Segovia-Lizano, Marie-Christine Simon, Arjan Narbad, Ullrich Wuellner, Falk Hildebrand","doi":"10.1101/2024.09.09.24313184","DOIUrl":"https://doi.org/10.1101/2024.09.09.24313184","url":null,"abstract":"ABSTRACT\u0000Despite extensive research, current treatment of Parkinson's Disease (PD) remains symptomatic and disease modifying approaches are urgently required. A promising approach is to target the gut-brain-axis by modifying the intestinal microbiota and the herein produced metabolites.\u0000We decided to test this approach by modifying key metabolites of bacterial intestinal fermentation: short chain fatty acids (SCFA), known to be decreased in PD patients. A prospective, controlled pilot study was conducted in 11 couples, with one PD patient and healthy spouse as control (CO) each. Participants followed a 4-week diet rich in dietary fibre in addition to the intake of a prebiotic sirup (Lactulose). Metagenomes and metabolites of the gut microbiota, urinary metabolites and clinical characteristics were assessed. The short-term dietary intervention significantly augmented gastrointestinal SCFA production, likely associated with increased Bifidobacteria spp. PD associated gastrointestinal symptoms improved with increasing SCFA levels. The pre-existing bacterial dysbiosis associated with PD, such as depletion of genera Blautia, Dorea, and Erysipelatoclostridium in PD, persisted within the study period. Some pathobionts, i.e. Klebsiella, were reduced after the intervention. Bacterial metabolite composition (both faecal and urine metabolomes) shifted towards the composition of the healthy control in PD after the intervention. Among these brain-relevant gut metabolic functions improved in PD patients, such as S-Adenosyl methionine (SAM), 3,4-Dihydroxyphenylacetic acid (DOPAC), Glutathione (GSH), Tryptophan and inositol related changes, involved in neuroprotective and antioxidant pathways. Despite the small cohort size and short-term study period a minor dietary intervention was sufficient to improve gastrointestinal symptoms in PD and altered metabolic parameters in a presumed neuroprotective manner, warranting further investigation in larger cohorts.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reactivation of Human Herpesvirus 6 and Epstein-Barr Virus in relapsing remitting multiple sclerosis: association with disabilities, disease progression, and inflammatory processes.","authors":"Abbas F. Almulla, Aristo Vojdani, Yingqian Zhang, Elroy Vojdani, Michael F. Maes","doi":"10.1101/2024.09.10.24313388","DOIUrl":"https://doi.org/10.1101/2024.09.10.24313388","url":null,"abstract":"Background: Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the\u0000central nervous system (CNS). Reactivation of Human herpesvirus 6 (HHV-6) and\u0000Epstein-Barr virus (EBV) is observed in MS.\u0000Objectives: This study investigates immunoglobulins (Ig)G, IgM, and IgA directed\u0000against EBV nuclear antigen EBNA-366-406, HHV-6 and EBV deoxyuridine-\u0000triphosphatase (dUTPase), and different immune profiles in 58 patients with relapsing\u0000remitting MS (RRMS) compared to 60 healthy controls.\u0000Methods: We employed enzyme-linked immunosorbent assays (ELISA) to measure the\u0000immunoglobulins to viral antigens. Multiplex immunoassays were used to measure\u0000cytokines, chemokines and growth factor levels that were used to compute immune\u0000profiles, including M1 macrophage, T helper (Th)-1, Th-17, and overall immune\u0000activation. We assessed disabilities using the Expanded Disability Status Scale (EDSS)\u0000and disease progression using the Multiple Sclerosis Severity Score (MSSS).\u0000Results: IgG/IgA/IgM directed to the three viral antigens were significantly higher in\u0000RRMS than in controls. RRMS was significantly discriminated from controls by using\u0000IgG and IgM against HHV-6 dUTPase, yielding an accuracy of 91.5% (sensitivity=87.3%\u0000and specificity=95.2%). Neural network analysis showed that using IgG to EBV-\u0000dUTPase, IgM to EBV-dUTPase, and immune profiles yielded an area under the ROC\u0000curve of 1 and a predictive accuracy of 97.1%. There were strong associations between\u0000IgG/IgM responses to HHV-6 and EBV-dUTPases and the EDSS/MSSS scores and\u0000aberrations in M1, Th-17, profiles, and overall immune activation.\u0000Conclusions: HHV-6 and EBV reactivation play a key role in RRMS and these effects\u0000are mediated by activation of cytokine profiles.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"68 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Associations Between Imaging-derived Phenotypes and Risk of Alzheimer's Disease and Other Neurodegenerative Disorders:A Mendelian Randomization Study","authors":"Zhichun Chen, Jun Liu, Yong You","doi":"10.1101/2024.09.10.24313402","DOIUrl":"https://doi.org/10.1101/2024.09.10.24313402","url":null,"abstract":"Background Accumulating observational studies have suggested associations between imaging-derived phenotypes (IDPs) and common neurodegenerative disorders, especially Alzheimer's disease (AD). The goal of this study is to evaluate the causal associations between structural and functional IDPs and 4 neurodegenerative disorders, including AD, Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS). Methods Bidirectional two-sample Mendelian randomization (MR) studies were conducted using summary statistics obtained from genome-wide association studies of 3909 IDPs from UK biobank and 4 neurodegenerative disorders.\u0000Results Forward MR analysis showed that volume of cerebral white matter in the left hemisphere was associated with increased risk of ALS (odds ratio [OR] = 1.15, 95% confidence interval [CI] = 1.09-1.22, P = 3.52 x 10-6). In reverse MR analysis, we revealed genetically determined risk of AD and MS were associated with multiple IDPs (all P < 1.28 x 10-5[0.05/3909], 9 IDPs in AD and 4 IDPs in MS). For example, genetically determined risk of AD was causally associated with reduced volume of gray matter in right ventral striatum (OR = 0.95, 95% CI = 0.93-0.97, P = 4.68 x 10-7) and lower rfMRI amplitudes in several nodes (ICA25 node 9, ICA25 node 8, and ICA100 node 11). Additionally, genetically determined risk of MS was causally associated with reduced volume in left putamen (OR = 0.97, 95% CI = 0.97-0.98, P = 4.47 x 10-7) and increased orientation dispersion index in right hippocampus (OR = 1.03, 95% CI = 1.01-1.04, P = 2.02 x 10-6). Conclusions Our study suggested plausible causal associations between risk of NDDs and brain IDPs. These findings might hold promise for identifying new disease mechanisms and developing novel preventative therapies for NDDs at the brain imaging levels.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rest-Activity Rhythm Phenotypes in Adults with Epilepsy and Intellectual Disability","authors":"Nandani Adhyapak, Mark A Abboud, Grace E Cardenas, Vaishnav Krishnan","doi":"10.1101/2024.09.09.24313145","DOIUrl":"https://doi.org/10.1101/2024.09.09.24313145","url":null,"abstract":"Objective: Sleep and rest-activity rhythms (RARs) are perturbed in many forms of neuropsychiatric illness. In this study, we applied wrist actigraphy to describe the extent of RAR perturbations in adults with epilepsy and intellectual disability (E+ID). We examined whether RAR phenotypes obtained cross-sectionally correlate with epilepsy severity, deficits in adaptive function and/or comorbid psychopathology. Methods: Primary caregivers of E+ID adults provided informed consent during routine ambulatory clinic visits and were asked to complete standardized surveys of overall epilepsy severity (GASE, Global Assessment of Severity of Epilepsy), adaptive function (ABAS-3, Adaptive Behavior Assessment System-3) and psychopathology (ABCL, Adult Behavior Checklist). Caregivers were also asked to ensure that subjects wore an Actiwatch-2 device continuously on their nondominant wrist for at least ten days. From recorded actograms, we calculated RAR amplitude, acrophase, robustness, intradaily variability (IV), interdaily stability (IS) and estimates of sleep quantity and timing. We compared these RAR metrics against those from (i) a previously published cohort of adults with epilepsy without ID (EID), and (ii) a cohort of age- and sex-matched intellectually able subjects measured within the Study of Latinos (SOL) Ancillary actigraphy study (SOL). Within E+ID subjects, we applied k-means analysis to divide subjects into three actigraphically distinct clusters. Results: 46 E+ID subjects (median age 26 [20-68], 47% female) provided a median recording duration of 11 days [range 6-27]. Surveys reflected low to extremely low levels of adaptive function (ABAS3 General Adaptive Composite score: median 50 [49-75]), and low/subclinical levels of psychopathology (ABCL total score: median 54.5 [25-67]). Compared with E-ID (n=57) and SOL (n=156) cohorts, E+ID subjects displayed significantly lower RAR amplitude, robustness and IS, with significantly higher IV and total daily sleep. K-means clustering of E+ID subjects recognized an intermediate cluster B, with RAR values indistinguishable to E-ID. Cluster A subjects displayed pronounced hypoactivity and hypersomnia with high rates of rhythm fragmentation, while cluster C subjects featured hyper-robust and high amplitude RARs. All three clusters were similar in age, body mass index, antiseizure medication (ASM) polytherapy, ABAS3 and ABCL scores. We qualitatively describe RAR examples from all three clusters. Interpretation: We show that adults with epilepsy and intellectual disability display a wide spectrum of RAR phenotypes that do not neatly correlate with measures of adaptive function or epilepsy severity. Prospective studies are necessary to determine whether continuous actigraphic monitoring can sensitively capture changes in chronobiological health that may arise with disease progression, iatrogenesis (e.g., ASM toxicity) or acute health deteriorations (e.g., seizure exacerbation, pneumonia). Similar long-term d","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantifying physical degradation alongside recording and stimulation performance of 980 intracortical microelectrodes chronically implanted in three humans for 956-2246 days","authors":"D. A. Bjånes, S. Kellis, R. Nickl, B. Baker, T. Aflalo, L. Bashford, S. Chivukula, M. S. Fifer, L. E. Osborn, B. Christie, B. A. Wester, P. A. Celnik, D. Kramer, K. Pejsa, N. E. Crone, W. S. Anderson, N. Pouratian, B. Lee, C. Y. Liu, F. Tenore, L. Rieth, R. A. Andersen","doi":"10.1101/2024.09.09.24313281","DOIUrl":"https://doi.org/10.1101/2024.09.09.24313281","url":null,"abstract":"<strong>Motivation</strong> The clinical success of brain-machine interfaces depends on overcoming both biological and material challenges to ensure a long-term stable connection for neural recording and stimulation. Therefore, there is a need to quantify any damage that microelectrodes sustain when they are chronically implanted in the human cortex.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}