Range Of Neurological Conditions Research Articles

THE RELATIONSHIP BETWEEN OXIDATIVE STRESS AND NEUROLOGICAL DISORDERS: MINI REVIEW

Oxidative stress is one of the main causes of neuronal dysfunction and death, mainly due to excessive formation of reactive oxygen species and depletion of antioxidant reserves. Oxidative stress is characterized by an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense mechanisms of the body. This process is involved in the onset and development of many neurological diseases. In this review, we analyzed and summarized the results of studies showing the association of neurological diseases, such as stroke, Parkinson’s disease, and other neurological diseases, with excessive formation of oxidative stress products. This article aims to provide an overview of the relationship between oxidative stress and a range of neurological conditions, shedding light on the underlying mechanisms and potential therapeutic implications.

Intravenous immunoglobulin alteration in response to adverse reactions in neurological conditions: A retrospective cohort study.

Intravenous immunoglobulin (IVIg) is an important treatment in a range of neurological conditions. There is currently limited evidence regarding the frequency and management of IVIg-associated adverse reactions (AR) in neurological disorders. A single-centre 18-month retrospective cohort study was conducted for all patients at a single tertiary hospital receiving IVIg as an inpatient or the medical day unit. Electronic medical record AR and alerts were reviewed for entries relating to IVIg, and prescribing records associated with recent IVIg administration were reviewed for the use of premedications. Case note review was undertaken to identify AR associated with alterations in IVIg treatment (such as reduction in rate, use of premedications or cessation of IVIg). Demographic, patient, and treatment factors were analysed for associations with AR necessitating alteration in IVIg treatment. This study included 98 individuals who received IVIg during the study period. Of these, 12 (12.1%) patients required an alteration in their IVIg treatment. In total, 3 (3.1%) of the 98 included patients required a reduced rate of IVIg, and 10 (10.2%) patients received premedication. The most common premedications were normal saline at the time of the infusion, cetirizine, and hydrocortisone. No demographic factors, indications or comorbidities were found to be associated with an increased likelihood of AR. However, an IVIg daily dose of >35 g and >45 g were associated with an increased likelihood of requiring IVIg treatment alteration due to AR. Alterations to IVIg treatment due to AR are commonly required in neurology patients, and may be associated with higher daily doses of IVIg.

Mitochondria Transfer in Brain Injury and Disease.

Intercellular mitochondria transfer is a novel form of cell signalling in which whole mitochondria are transferred between cells in order to enhance cellular functions or aid in the degradation of dysfunctional mitochondria. Recent studies have observed intercellular mitochondria transfer between glia and neurons in the brain, and mitochondrial transfer has emerged as a key neuroprotective mechanism in a range of neurological conditions. In particular, artificial mitochondria transfer has sparked widespread interest as a potential therapeutic strategy for brain disorders. In this review, we discuss the mechanisms and effects of intercellular mitochondria transfer in the brain. The role of mitochondrial transfer in neurological conditions, including neurodegenerative disease, brain injury, and neurodevelopmental disorders, is discussed as well as therapeutic strategies targeting mitochondria transfer in the brain.

Investigation of CACNA1I Cav3.3 Dysfunction in Hemiplegic Migraine.

Familial hemiplegic migraine (FHM) is a severe neurogenetic disorder for which three causal genes, CACNA1A, SCN1A, and ATP1A2, have been implicated. However, more than 80% of referred diagnostic cases of hemiplegic migraine (HM) are negative for exonic mutations in these known FHM genes, suggesting the involvement of other genes. Using whole-exome sequencing data from 187 mutation-negative HM cases, we identified rare variants in the CACNA1I gene encoding the T-type calcium channel Cav3.3. Burden testing of CACNA1I variants showed a statistically significant increase in allelic burden in the HM case group compared to gnomAD (OR = 2.30, P = 0.00005) and the UK Biobank (OR = 2.32, P = 0.0004) databases. Dysfunction in T-type calcium channels, including Cav3.3, has been implicated in a range of neurological conditions, suggesting a potential role in HM. Using patch-clamp electrophysiology, we compared the biophysical properties of five Cav3.3 variants (p.R111G, p.M128L, p.D302G, p.R307H, and p.Q1158H) to wild-type (WT) channels expressed in HEK293T cells. We observed numerous functional alterations across the channels with Cav3.3-Q1158H showing the greatest differences compared to WT channels, including reduced current density, right-shifted voltage dependence of activation and inactivation, and slower current kinetics. Interestingly, we also found significant differences in the conductance properties exhibited by the Cav3.3-R307H and -Q1158H variants compared to WT channels under conditions of acidosis and alkalosis. In light of these data, we suggest that rare variants in CACNA1I may contribute to HM etiology.

Cognitive empathy across the lifespan.

To describe the development of cognitive empathy across the lifespan from a very large cohort using a standardized measure of cognitive empathy ability. Participants (n=4545, age bands <5y to >75y, 60% female) were a convenience sample recruited voluntarily from visitors to the Glasgow Science Centre in the UK, who completed the Reading the Mind in the Eyes Test. When compared to preceding age groups, we found significant developmental gains in empathy ability in children aged 6 to 7 years (p=0.048, d=0.45) and again at 10 to 12 years (p=0.042, d=0.23), followed by a slight reduction in ability during adolescence (p=0.087, d=-0.18), and functional maturity in those aged 19 to 25 years (p=0.001, d=0.76). Cognitive empathy abilities remained relatively stable across adulthood but gradually declined in people over 65 years, with notable decline in males over 75 years (p=0.001, d=-0.98). Females performed better than males at all ages. Understanding developmental issues in cognitive empathy could influence approaches to moral and social education for children, and health and social care support for older people. Standardized cognitive empathy tests could also provide novel approaches in the early detection of developmental vulnerabilities in a range of neurological conditions, and within neuropsychiatric and neurodegenerative disorders in which cognitive empathy is known to be impaired. Cognitive empathy is a late-developing ability and changes across the lifespan. Cognitive empathy increases during childhood but with potentially altered abilities during adolescence. Cognitive empathy matures during early adulthood and gradually declines in older age. There is a female advantage in cognitive empathy abilities.

Use of Nutritional Supplements Based on L-Theanine and Vitamin B6 in Children with Tourette Syndrome, with Anxiety Disorders: A Pilot Study.

Background: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by tics and co-occurring disorders. It has been suggested that anxiety occurs in 2–45% patients affected by Tourette syndrome. Despite dietary and nutritional factors have been found to affect a range of neurological conditions, no more studies have investigated the relationship between nutritional supplements and tics. Objective: To evaluate the effectiveness of supplementation of both L-Theanine and Vitamin B6 in reducing tics and co-occurring disorders in a sample of youth with chronic tic disorder (CTD) or Tourette syndrome with anxiety symptoms. Design: A open-label trial. Patients affected by Tourette syndrome were randomized to receive nutritional supplements based on L-Theanine and vitamin B6, or psychoeducation (PE). Participants: 34 children (30 boys and 4 girls) aged between 4 and 17 years affected by Tourette syndrome or chronic tic disorder, associated with anxiety symptoms. Results: Patients in both groups showed a reduction in the severity of tic and anxiety symptoms. Supplementation with L-Theanine and vitamin B6 was significantly more effective than psychoeducation in reducing tics and co-occurring disorders, as measured by neuropsychological findings. Conclusions: Supplementation of both L-Theanine and Vitamin B6 may help in the treatment of tic disorders associated with anxious symptoms. Between-group differences in clinician-rated severity did reach statistical significance only for tics. Despite this finding, further placebo-controlled trials are needed.

The genetic and epigenetic profile of serumS100β in the Lothian Birth Cohort 1936 and its relationship to Alzheimer's disease.

Background: Circulating S100 calcium-binding protein (S100β) is a marker of brain inflammation that has been associated with a range of neurological conditions. To provide insight into the molecular regulation of S100β and its potential causal associations with Alzheimer's disease, we carried out genome- and epigenome-wide association studies (GWAS/EWAS) of serum S100β levels in older adults and performed Mendelian randomisation with Alzheimer's disease. Methods: GWAS (N=769, mean age 72.5 years, sd = 0.7) and EWAS (N=722, mean age 72.5 years, sd = 0.7) of S100β levels were performed in participants from the Lothian Birth Cohort 1936. Conditional and joint analysis (COJO) was used to identify independent loci. Expression quantitative trait locus (eQTL) analyses were performed for lead loci that had genome-wide significant associations with S100β. Bidirectional, two-sample Mendelian randomisation was used to test for causal associations between S100β and Alzheimer's disease. Colocalisation between S100β and Alzheimer's disease GWAS loci was also examined. Results: We identified 154 SNPs from chromosome 21 that associated (P<5x10 -8) with S100β protein levels. The lead variant was located in the S100β gene (rs8128872, P=5.0x10 -17). We found evidence that two independent causal variants existed for both transcription of S100β and S100β protein levels in our eQTL analyses . No CpG sites were associated with S100β levels at the epigenome-wide significant level (P<3.6x10 -8); the lead probe was cg06833709 (P=5.8x10 -6), which mapped to the LGI1 gene. There was no evidence of a causal association between S100β levels and Alzheimer's disease or vice versa and no evidence for colocalisation between S100β and Alzheimer's disease loci. Conclusions: These data provide insight into the molecular regulators of S100β levels. This context may aid in understanding the role of S100β in brain inflammation and neurological disease.

The genetic and epigenetic profile of serum S100β in the Lothian Birth Cohort 1936 and its relationship to Alzheimer’s disease

Background: Circulating S100 calcium-binding protein (S100β) is a marker of brain inflammation that has been associated with a range of neurological conditions. To provide insight into the molecular regulation of S100β and its potential causal associations with Alzheimer’s disease, we carried out genome- and epigenome-wide association studies (GWAS/EWAS) of serum S100β levels in older adults and performed Mendelian randomisation with Alzheimer’s disease. Methods: GWAS (N=769, mean age 72.5 years, sd = 0.7) and EWAS (N=722, mean age 72.5 years, sd = 0.7) of S100β levels were performed in participants from the Lothian Birth Cohort 1936. Conditional and joint analysis (COJO) was used to identify independent loci. Expression quantitative trait locus (eQTL) analyses were performed for lead loci that had genome-wide significant associations with S100β. Bidirectional, two-sample Mendelian randomisation was used to test for causal associations between S100β and Alzheimer’s disease. Colocalisation between S100β and Alzheimer’s disease GWAS loci was also examined. Results: We identified 154 SNPs from chromosome 21 that associated (P<5x10 -8) with S100β protein levels. The lead variant was located in the S100β gene (rs8128872, P=5.0x10 -17). We found evidence that two independent causal variants existed for both transcription of S100β and S100β protein levels in our eQTL analyses . No CpG sites were associated with S100β levels at the epigenome-wide significant level (P<3.6x10 -8); the lead probe was cg06833709 (P=5.8x10 -6), which mapped to the LGI1 gene. There was no evidence of a causal association between S100β levels and Alzheimer’s disease or vice versa and no evidence for colocalisation between S100β and Alzheimer’s disease loci. Conclusions: These data provide insight into the molecular regulators of S100β levels. This context may aid in understanding the role of S100β in brain inflammation and neurological disease.

The genetic and epigenetic profile of serumS100β in the Lothian Birth Cohort 1936 and its relationship to Alzheimer's disease.

Background: Circulating S100 calcium-binding protein (S100β) is a marker of brain inflammation that has been associated with a range of neurological conditions. To provide insight into the molecular regulation of S100β and its potential causal associations with Alzheimer's disease, we carried out genome- and epigenome-wide association studies (GWAS/EWAS) of serum S100β levels in older adults and performed Mendelian randomisation with Alzheimer's disease. Methods: GWAS (N=769, mean age 72.5 years, sd = 0.7) and EWAS (N=722, mean age 72.5 years, sd = 0.7) of S100β levels were performed in participants from the Lothian Birth Cohort 1936. Conditional and joint analysis (COJO) was used to identify independent loci. Expression quantitative trait locus (eQTL) analyses were performed for lead loci that had genome-wide significant associations with S100β. Bidirectional, two-sample Mendelian randomisation was used to test for causal associations between S100β and Alzheimer's disease. Colocalisation between S100β and Alzheimer's disease GWAS loci was also examined. Results: We identified 154 SNPs from chromosome 21 that associated (P<5x10 -8) with S100β protein levels. The lead variant was located in the S100β gene (rs8128872, P=5.0x10 -17). We found evidence that two independent causal variants existed for both transcription of S100β and S100β protein levels in our eQTL analyses . No CpG sites were associated with S100β levels at the epigenome-wide significant level (P<3.6x10 -8); the lead probe was cg06833709 (P=5.8x10 -6), which mapped to the LGI1 gene. There was no evidence of a causal association between S100β levels and Alzheimer's disease or vice versa and no evidence for colocalisation between S100β and Alzheimer's disease loci. Conclusions: These data provide insight into the molecular regulators of S100β levels. This context may aid in understanding the role of S100β in brain inflammation and neurological disease.

NLRP3 Inflammasome-Dependent Increases in High Mobility Group Box 1 Involved in the Cognitive Dysfunction Caused by Tau-Overexpression.

Tau hyperphosphorylation is a characteristic alteration present in a range of neurological conditions, such as traumatic brain injury (TBI) and neurodegenerative diseases. Treatments targeting high-mobility group box protein 1 (HMGB1) induce neuroprotective effects in these neuropathologic conditions. However, little is known about the interactions between hyperphosphorylated tau and HMGB1 in neuroinflammation. We established a model of TBI with controlled cortical impacts (CCIs) and a tau hyperphosphorylation model by injecting the virus encoding human P301S tau in mice, and immunofluorescence, western blotting analysis, and behavioral tests were performed to clarify the interaction between phosphorylated tau (p-tau) and HMGB1 levels. We demonstrated that p-tau and HMGB1 were elevated in the spatial memory-related brain regions in mice with TBI and tau-overexpression. Animals with tau-overexpression also had significantly increased nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation, which manifested as increases in apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), activating caspase-1 and interleukin 1 beta (IL-1β) levels. In addition, NLRP3–/– mice and the HMGB1 inhibitor, glycyrrhizin, were used to explore therapeutic strategies for diseases with p-tau overexpression. Compared with wild-type (WT) mice with tau-overexpression, downregulation of p-tau and HMGB1 was observed in NLRP3–/– mice, indicating that HMGB1 alterations were NLRP3-dependent. Moreover, treatment with glycyrrhizin at a late stage markedly reduced p-tau levels and improved performance in the Y- and T-mazes and the ability of tau-overexpressing mice to build nests, which revealed improvements in spatial memory and advanced hippocampal function. The findings identified that p-tau has a triggering role in the modulation of neuroinflammation and spatial memory in an NLRP3-dependent manner, and suggest that treatment with HMGB1 inhibitors may be a better therapeutic strategy for tauopathies.

Sorting nexin-27 regulates AMPA receptor trafficking through the synaptic adhesion protein LRFN2.

The endosome-associated cargo adaptor sorting nexin-27 (SNX27) is linked to various neuropathologies through sorting of integral proteins to the synaptic surface, most notably AMPA receptors. To provide a broader view of SNX27-associated pathologies, we performed proteomics in rat primary neurons to identify SNX27-dependent cargoes, and identified proteins linked to excitotoxicity, epilepsy, intellectual disabilities, and working memory deficits. Focusing on the synaptic adhesion molecule LRFN2, we established that SNX27 binds to LRFN2 and regulates its endosomal sorting. Furthermore, LRFN2 associates with AMPA receptors and knockdown of LRFN2 results in decreased surface AMPA receptor expression, reduced synaptic activity, and attenuated hippocampal long-term potentiation. Overall, our study provides an additional mechanism by which SNX27 can control AMPA receptor-mediated synaptic transmission and plasticity indirectly through the sorting of LRFN2 and offers molecular insight into the perturbed function of SNX27 and LRFN2 in a range of neurological conditions.

Editors' note: Telemedicine in neurology: Telemedicine Work Group of the American Academy of Neurology update

In “Telemedicine in neurology: Telemedicine Work Group of the American Academy of Neurology update,” Hatcher-Martin et al. review the literature on telemedicine for concussion, dementia, epilepsy, headache, movement, multiple sclerosis, neuromuscular, and inpatient neurology consults. The authors conclude that telemedicine expedites care, increases access, reduces cost, and improves diagnostic accuracy and health outcomes, but that further studies are needed to understand the role for telemedicine in neurology. Devanathan notes that telemedicine has successfully been used in India to provide guidance for clinicians and patients in distant parts of the country about a range of neurologic conditions. Similarly, Mao et al. describe the positive impact of teleneuroimmunology in China. However, both Devanathan and Mao et al. caution that establishment of guidelines about telemedicine is imperative to optimize care and prevent litigation. Since the publication of this article, the COVID-19 pandemic has precipitated the rapid incorporation of telemedicine into every specialty of neurology in countries around the world, and we have gained better insight to the advantages and disadvantages of virtual visits. We anticipate that widespread adoption of teleneurology will spur further investigation and innovation provided that it continues to be supported by insurance companies. In “Telemedicine in neurology: Telemedicine Work Group of the American Academy of Neurology update,” Hatcher-Martin et al. review the literature on telemedicine for concussion, dementia, epilepsy, headache, movement, multiple sclerosis, neuromuscular, and inpatient neurology consults. The authors conclude that telemedicine expedites care, increases access, reduces cost, and improves diagnostic accuracy and health outcomes, but that further studies are needed to understand the role for telemedicine in neurology. Devanathan notes that telemedicine has successfully been used in India to provide guidance for clinicians and patients in distant parts of the country about a range of neurologic conditions. Similarly, Mao et al. describe the positive impact of teleneuroimmunology in China. However, both Devanathan and Mao et al. caution that establishment of guidelines about telemedicine is imperative to optimize care and prevent litigation. Since the publication of this article, the COVID-19 pandemic has precipitated the rapid incorporation of telemedicine into every specialty of neurology in countries around the world, and we have gained better insight to the advantages and disadvantages of virtual visits. We anticipate that widespread adoption of teleneurology will spur further investigation and innovation provided that it continues to be supported by insurance companies.

An in-plane, mirror-symmetric visualization tool for deep brain stimulation electrodes.

Deep brain stimulation (DBS) is used to treat a range of neurologic conditions. Determining the anatomic location of the DBS lead and inferring the microelectrode recording track from co-registered pre-operative and post-operative scans is important for stereotactic surgery and neurophysiology research. Reslicing images with the DBS lead in-plane while maintaining mirror symmetry is not possible with current clinical navigation software. Therefore, we developed an open source software tool in Matlab for visualizing DBS lead placement and anatomic segmentation with computed tomography and magnetic resonance images. The code and graphical user interface are available at: github.com/camplaboratory/DBS_reslice.

Sex differences in movement disorders.

In a range of neurological conditions, including movement disorders, sex-related differences are emerging not only in brain anatomy and function, but also in pathogenesis, clinical features and response to treatment. In Parkinson disease (PD), for example, oestrogens can influence the severity of motor symptoms, whereas elevation of androgens can exacerbate tic disorders. Nevertheless, the real impact of sex differences in movement disorders remains under-recognized. In this article, we provide an up-to-date review of sex-related differences in PD and the most common hyperkinetic movement disorders, namely, essential tremor, dystonia, Huntington disease and other chorea syndromes, and Tourette syndrome and other chronic tic disorders. We highlight the most relevant clinical aspects of movement disorders that differ between men and women. Increased recognition of these differences and their impact on patient care could aid the development of tailored approaches to the management of movement disorders and enable the optimization of preclinical research and clinical studies.

Point-to-point repetitive control of functional electrical stimulation for drop-foot

Drop-Foot is a common problem resulting from a range of neurological conditions, and prevents normal leg swing during gait, leading to abnormal, inefficient motion with an increased risk of falling. It damages the quality of life of over 122,000 people in the US and 11,400 people in the UK every year.Functional electrical stimulation (FES) addresses drop-foot by artificially contracting the tibialis anterior, and has had considerable success both clinically and commercially. However current commercial controllers are open loop and have long set-up times. The few controllers in the research domain are predominantly open-loop, lack accuracy, and struggle with muscle delays, non-linearities and the onset of fatigue. More advanced controllers require extensive sensor data and/or are highly dependent on an identified model. Recent developments have shown model based controllers combined with learning can facilitate higher accuracy, however previous attempts employed batch-wise learning, and led to disjointed control signals.This paper applies repetitive control (RC) to drop-foot for the first time, facilitating a continuous, smooth process of learning with no resetting. To maximise performance, a comprehensive extension to the traditional RC framework is undertaken to enable only isolated time points to be tracked, improving robustness and reducing memory and communication requirements. Experimental data confirms that RC can achieve normal gait when applied to FES-assisted gait with no voluntary effort. The new ‘point-to-point’ RC framework outperformed traditional RC, while using only 5 data points per gait cycle and minimal control effort.

Resting-state fMRI data of awake dogs (Canis familiaris) via group-level independent component analysis reveal multiple, spatially distributed resting-state networks

Resting-state networks are spatially distributed, functionally connected brain regions. Studying these networks gives us information about the large-scale functional organization of the brain and alternations in these networks are considered to play a role in a wide range of neurological conditions and aging. To describe resting-state networks in dogs, we measured 22 awake, unrestrained individuals of both sexes and carried out group-level spatial independent component analysis to explore whole-brain connectivity patterns. In this exploratory study, using resting-state functional magnetic resonance imaging (rs-fMRI), we found several such networks: a network involving prefrontal, anterior cingulate, posterior cingulate and hippocampal regions; sensorimotor (SMN), auditory (AUD), frontal (FRO), cerebellar (CER) and striatal networks. The network containing posterior cingulate regions, similarly to Primates, but unlike previous studies in dogs, showed antero-posterior connectedness with involvement of hippocampal and lateral temporal regions. The results give insight into the resting-state networks of awake animals from a taxon beyond rodents through a non-invasive method.

The formyl peptide receptor agonist FPRa14 induces differentiation of Neuro2a mouse neuroblastoma cells into multiple distinct morphologies which can be specifically inhibited with FPR antagonists and FPR knockdown using siRNA.

The N-formyl peptide receptors (FPRs) have been identified within neuronal tissues and may serve as yet undetermined functions within the nervous system. The FPRs have been implicated in the progression and invasiveness of neuroblastoma and other cancers. In this study the effects of the synthetic FPR agonist FPRa14, FPR antagonists and FPR knockdown using siRNA on mouse neuroblastoma neuro2a (N2a) cell differentiation plus toxicity were examined. The FPRa14 (1–10μM) was found to induce a significant dose-dependent differentiation response in mouse neuroblastoma N2a cells. Interestingly, three distinct differentiated morphologies were observed, with two non-archetypal forms observed at the higher FPRa14 concentrations. These three forms were also observed in the human neuroblastoma cell-lines IMR-32 and SH-SY5Y when exposed to 100μM FPRa14. In N2a cells combined knockdown of FPR1 and FPR2 using siRNA inhibited the differentiation response to FPRa14, suggesting involvement of both receptor subtypes. Pre-incubating N2a cultures with the FPR1 antagonists Boc-MLF and cyclosporin H significantly reduced FPRa14-induced differentiation to near baseline levels. Meanwhile, the FPR2 antagonist WRW4 had no significant effect on FPRa14-induced N2a differentiation. These results suggest that the N2a differentiation response observed has an FPR1-dependent component. Toxicity of FPRa14 was only observed at higher concentrations. All three antagonists used blocked FPRa14-induced toxicity, whilst only siRNA knockdown of FPR2 reduced toxicity. This suggests that the toxicity and differentiation involve different mechanisms. The demonstration of neuronal differentiation mediated via FPRs in this study represents a significant finding and suggests a role for FPRs in the CNS. This finding could potentially lead to novel therapies for a range of neurological conditions including neuroblastoma, Alzheimer’s disease, Parkinson’s disease and neuropathic pain. Furthermore, this could represent a potential avenue for neuronal regeneration therapies.

Impact of Zika Virus on adult human brain structure and functional organization.

ObjectiveTo determine the impact of Zika virus (ZIKV) infection on brain structure and functional organization of severely affected adult patients with neurological complications that extend beyond Guillain–Barré Syndrome (GBS)‐like manifestations and include symptoms of the central nervous system (CNS).MethodsIn this first case–control neuroimaging study, we obtained structural and functional magnetic resonance images in nine rare adult patients in the subacute phase, and healthy age‐ and sex‐matched controls. ZIKV patients showed atypical descending and rapidly progressing peripheral nervous system (PNS) manifestations, and importantly, additional CNS presentations such as perceptual deficits. Voxel‐based morphometry was utilized to evaluate gray matter volume, and resting state functional connectivity and Network Based Statistics were applied to assess the functional organization of the brain.ResultsGray matter volume was decreased bilaterally in motor areas (supplementary motor cortex, specifically Frontal Eye Fields) and beyond (left inferior frontal sulcus). Additionally, gray matter volume increased in right middle frontal gyrus. Functional connectivity increased in a widespread network within and across temporal lobes.InterpretationWe provide preliminary evidence for a link between ZIKV neurological complications and changes in adult human brain structure and functional organization, comprising both motor‐related regions potentially secondary to prolonged PNS weakness, and nonsomatomotor regions indicative of PNS‐independent alternations. The latter included the temporal lobes, particularly vulnerable in a range of neurological conditions. While future studies into the ZIKV‐related neuroinflammatory mechanisms in adults are urgently needed, this study indicates that ZIKV infection can lead to an impact on the brain.

Cl-out is a novel cooperative optogenetic tool for extruding chloride from neurons

Chloride regulation affects brain function in many ways, for instance, by dictating the GABAergic reversal potential, and thereby influencing neuronal excitability and spike timing. Consistent with this, there is increasing evidence implicating chloride in a range of neurological conditions. Investigations about these conditions, though, are made difficult by the limited range of tools available to manipulate chloride levels. In particular, there has been no way to actively remove chloride from neurons; we now describe an optogenetic strategy, ‘Cl-out', to do exactly this. Cl-out achieves its effect by the cooperative action of two different component opsins: the proton pump, Archaerhodopsin and a chloride channel opsin. The removal of chloride happens when both are activated together, using Archaerhodopsin as an optical voltage clamp to provide the driving force for chloride removal through the concurrently opened, chloride channels. We further show that this novel optogenetic strategy can reverse an in vitro epileptogenic phenotype.

The relationship between sleep and working memory in children with neurological conditions

ABSTRACTThe objective of this study is to investigate whether sleep problems might account for the increased working memory deficits observed in school-aged children with neurological conditions. A novel, transdiagnostic approach to the investigation was chosen, and sleep is treated as a process that can potentially account for working memory difficulties across a range of neurological conditions. Prevalence estimates of sleep problems are also examined. Archival data of 237 children aged 6 to 11 years were collected from a Western Australian statewide neuropsychological service for the period 26 July 2011 to 14 January 2014. Measures of parent-reported sleep quality, snoring, and daytime sleepiness were obtained, in addition to objective measures of verbal and spatial working memory, storage capacity, and processing speed. The results of the data analysis reveal that over one third of participants reported having clinically-significant levels of sleep problems and that poor sleep quality is significantly associated with verbal working memory difficulties. This association remains after partialling out the variance contributed to performance by storage capacity and processing speed, suggesting that sleep is impacting upon an executive component of working memory. No other significant associations are observed. The results suggest that poor sleep quality is associated with an executive component of verbal (rather than spatial) working memory in children with neurological conditions. This has implications for the biological mechanisms thought to underlie the relationship between sleep and cognition in children. The results also demonstrate the clinical utility of a transdiagnostic approach when investigating sleep and cognition in children with neurological conditions.