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Chemotherapy can result in toxic side effects in the brain. Intake of marine-based omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), alter brain fatty acids, potentially improving brain function. However, it is unclear if alpha-linolenic acid (ALA), the plant-based n-3, affects brain PUFAs during chemotherapy. The objective of this study was to examine the effects of dietary ALA, EPA and DHA, with high or low sucrose, on brain PUFAs in a mouse model of chemotherapy. Secondarily, the use of liver PUFAs as surrogate measures of brain PUFAs was examined. Lipid peroxidation (4-HNE) and neurotrophic markers (BDNF) were assessed. Female C57Bl/6 mice (n = 90) were randomized to 1 of 5 diets (high EPA + DHA/high or low sucrose, high ALA/high or low sucrose, or control with no EPA + DHA/low ALA/low sucrose) and injected with doxorubicin-based chemotherapy or saline. Brain EPA and DHA were greater (p < 0.0001) with high EPA + DHA diets, regardless of sucrose; there were no significant differences in brain PUFAs between high ALA diets and control. Chemotherapy-treated mice had higher brain and liver DHA (p < 0.05) and lower brain and liver linoleic acid (p < 0.0001). Brain n-3 and n-6 PUFAs were strongly correlated with liver n-3 (r = 0.8214, p < 0.0001) and n-6 PUFAs (r = 0.7568, p < 0.0001). BDNF was correlated with brain total PUFAs (r = 0.36; p < 0.05). In conclusion, dietary ALA in proportions approximately two times greater than consumed by humans did not appreciably increase brain n-3 PUFAs compared to low ALA intake. Liver PUFAs may be a useful surrogate marker of brain PUFAs in this mouse model.

A 26-year-old man, suffering from complex congenital cyanotic heart disease (CCHD) with Eisenmenger complex, presented with seizures. Non-contrast CT (NCCT) scan of brain showed chronic infract with encephalomalacic changes in the left high parietal region with vividly hyperdense intracranial

A 39-year-old previously healthy man presented with insidiously progressive paresthesia in his lower extremities and worsening of gait and balance. MRI demonstrated T2-hyperintense signal abnormalities involving the thalami, midbrain, dentate nuclei, and adjacent deep cerebellar white matter, which are characteristic of cerebrotendinous xanthomatosis (CTX) (figure). Magnetic resonance spectroscopy revealed typical lipid peaks at 0.9 and 1.3 ppm,1 and serology analysis indicated sterol 27-hydroxylase deficiency,2 confirming the diagnosis. CTX is a rare lipid storage disease with unique clinical and imaging findings, and effective treatment with positive outcomes if initiated early, raising the importance of awareness and early recognition of this disease.2

Introduction Widespread white matter abnormalities and alterations in glutamate levels have been reported in patients with schizophrenia. We hypothesized that alterations in white matter integrity and glutamate levels in individuals at clinical high risk (CHR) for psychosis are associated with the subsequent development of psychosis. Methods Participants included 33 antipsychotic naive CHR (Female 7/Male 26, Age 19.55 (4.14) years) and 38 healthy controls (Female 10/Male 28, Age 20.92 (3.37) years). Whole brain diffusion tensor imaging for fractional anisotropy (FA) and right frontal white matter proton magnetic resonance spectroscopy for glutamate levels were acquired. CHR participants were clinically followed for 2 years to determine conversion to psychosis. Results CHR participants that transitioned to psychosis (N = 7, 21%) were characterized by significantly lower FA values in the posterior thalamic radiation compared to those who did not transition and healthy controls. In the CHR group that transitioned to psychosis only, positive exploratory correlations between glutamate levels and FA values of the posterior thalamic radiation and the retrolenticular part of the internal capsule and a negative correlation between glutamate levels and the cingulum FA values were found. Conclusion The results of the present study highlight that alterations in white matter structure and glutamate are related with the conversion to psychosis.

Background and purpose A wide range of neuroradiological findings has been reported in patients with coronavirus disease 2019 (COVID-19), ranging from subcortical white matter changes to infarcts, haemorrhages and focal contrast media enhancement. These have been descriptively but inconsistently reported and correlations with clinical findings and biomarkers have been difficult to extract from the literature. The purpose of this study was to quantify the extents of neuroradiological findings in a cohort of patients with COVID-19 and neurological symptoms, and to investigate correlations with clinical findings, duration of intensive care and biomarkers in blood. Material and methods Patients with positive SARS-CoV-2 and at least one new-onset neurological symptom were included from April until July 2020. Nineteen patients were examined regarding clinical symptoms, biomarkers in blood and MRI of the brain. In order to quantify the MRI findings, a semi-quantitative neuroradiological severity scale was constructed a priori, and applied to the MR images by two specialists in neuroradiology. Results and conclusions The score from the severity scale correlated significantly with blood biomarkers of CNS injury (glial fibrillary acidic protein, total-tau, ubiquitin carboxyl-terminal hydrolase L1) and inflammation (C-reactive protein), Glasgow Coma Scale score, and the number of days spent in intensive care. The underlying radiological assessments had inter-rater agreements of 90.5%/86% (for assessments with 2/3 alternatives). Total intraclass correlation was 0.80. Previously reported neuroradiological findings in COVID-19 have been diverse and heterogenous. In this study, the extent of findings in MRI examination of the brain, quantified using a structured report, shows correlation with relevant biomarkers.

Docosahexaenoic acid (DHA) shows anti-inflammatory/proresolution effects in the brain. Higher red blood cell (RBC) DHA in humans is associated with improved cognitive performance and a lower risk for suicide. Here, we hypothesized that binding to the 18 kDa translocator protein (TSPO), a proxy for microglia levels, will be higher in individuals with low DHA relative to high DHA levels. We also postulated that higher TSPO would predict poor cognitive performance and impaired stress resilience.RBC DHA screening was performed in 320 healthy males. [sup11/supC]PBR28 positron emission tomography was used to measure binding to TSPO in 38 and 32 males in the lowest and highest RBC DHA quartiles. Volumes of distribution expressed relative to total plasma ligand concentration (VsubT/sub) was derived using an arterial input function-based kinetic analysis in 14 brain regions.[sup11/supC]PBR28 VsubT/subwas significantly lower (by 12% and 20% in C/T and C/C rs6971 genotypes) in males with low RBC DHA than in males with high RBC DHA. Regional VsubT/subwas correlated positively and negatively with RBC DHA and serum triglycerides, respectively. No relationships between VsubT/suband cognitive performance or stress resilience measures were present.Contrary to our hypothesis, we found lower TSPO binding in low-DHA than in high-DHA subjects. It is unclear as to whether low TSPO binding reflects differences in microglia levels and/or triglyceride metabolism in this study. Future studies with specific targets are necessary to confirm the effect of DHA on microglia. These results underscore the need to consider lipid parameters as a factor when interpreting TSPO positron emission tomography clinical findings.

Late-life depression (LLD) is characterized by accelerated biological aging. Accelerated brain aging, estimated from structural magnetic resonance imaging (sMRI) data by a machine learning algorithm, is associated with LLD diagnosis, poorer cognitive performance, and disability. We hypothesized that accelerated brain aging moderates the antidepressant response.Following MRI, participants entered an 8-week randomized, controlled trial of escitalopram. Nonremitting participants then entered an open-label 8-week trial of bupropion.Ninety-five individuals with LLD.A machine learning algorithm estimated each participant's brain age from sMRI data. This was used to calculate the brain-age gap (BAG), or how estimated age differed from chronological age. Secondary sMRI measures of aging pathology included white matter hyperintensity (WMH) volumes and hippocampal volumes. Mixed models examined the relationship between sMRI measures and change in depression severity. Initial analyses tested for a moderating effect of MRI measures on change in depression severity with escitalopram. Subsequent analyses tested for the effect of MRI measures on change in depression severity over time across trials.In the blinded initial phase, BAG was not significantly associated with a differential response to escitalopram over time. BAG was also not associated with a change in depression severity over time across both arms in the blinded phase or in the subsequent open-label bupropion phase. We similarly did not observe effects of WMH volume or hippocampal volume on change in depression severity over time.sMRI markers of accelerated brain aging were not associated with treatment response in this sequential antidepressant trial.

Introduction: Comorbid mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) are common in military service members. The aim of this study is to investigate brain metabolic i...

Introduction: The human brain shows modest traits of sexual dimorphism, with the female brain, on average, 10% smaller than the male brain. These differences do not imply a lowered cognitive performance, but suggest a more optimal brain organization in women. Here we evaluate the patterns of functional connectivity (FC) in women and men from the Connectomics of Brain Aging and Dementia sample. Methods: We used phase locking values to calculate FC from the magnetoencephalography time series in a sample of 138 old adults (87 females and 51 males). We compared the FC patterns between sexes, with the intention of detecting regions with different levels of connectivity. Results: We found a frontal cluster, involving anterior cingulate and the medial frontal lobe, where women showed higher FC values than men. Involved connections included the following: (1) medial parietal areas, such as posterior cingulate cortices and precunei; (2) right insula; and (3) medium cingulate and paracingulate cortices. Moreover, these differences persisted when considering only cognitively intact individuals, but not when considering only cognitively impaired individuals. Discussion: Increased anteroposterior FC has been identified as a biomarker for increased risk of developing cognitive impairment or dementia. In our study, cognitively intact women showed higher levels of FC than their male counterparts. This result suggests that neurodegenerative processes could be taking place in these women, but the changes are undetected by current diagnosis tools. FC, as measured here, might be valuable for early identification of this neurodegeneration.

Systemic lupus erythematosus presenting with neuropsychiatric symptoms (NPSLE) along with posterior reversible encephalopathy syndrome (PRES) is rare. A young woman of 29 years presented with various neuropsychiatric symptoms along with low-grade fever, occasional headache, skin rash, arthralgias and gradually became non-ambulatory over last 6 months. After admission, she had an episode of generalised tonic-clonic seizure, followed by drowsiness. She was normotensive. Investigations revealed no evidence of any underlying infection, normal renal functions and electrolytes; but other parameters were supportive to a diagnosis of NPSLE. MRI brain showed vasogenic oedema characterised by symmetrical hyperintensities over posterior brain regions in T2 and fluid attenuated inversion recovery images with no restricted diffusion in diffusion weighted image suggestive of PRES. A diagnosis of NPSLE presenting with PRES, particularly in the absence of hypertension and abnormal renal functions was made, which is a rare presentation. She responded well to immunomodulatory therapy with methylprednisolone and monthly cyclophosphamide.

Integrating animals into therapy is applied increasingly in patients in a minimally conscious state (MCS). This pilot study investigates the effect of animal presence on frontal brain activity in MCS patients compared to healthy subjects. O; 2; HB, HHb and tHb of two MCS patients and two healthy adults was measured in frontal cortex using functional near-infrared spectroscopy during three sessions with a live animal and three sessions with a mechanical toy animal present. Each session had five phases: (1) baseline, (2) watching animal, (3) passive contact, (4) active contact, (5) neutral. Data were descriptively analysed. All participants showed the largest hemodynamic response during direct contact with the live or toy animal compared to "baseline" and "watching." During active contact, three of the four participants showed a stronger response when stroking the live compared to the toy animal. All participants showed an inverted signal with higher HHb than O; 2; Hb concentrations while stroking the live or toy animal. Animal contact leads to a neurovascular reaction in both MCS patients and healthy subjects, indicating elevated neural activity in the frontal cortex. We conclude that while a toy animal can elicit attention processes, active contact to a living animal is combined with emotional processes.

Background: Both major depressive disorder (MDD) and schizophrenia (SCH) are characterized by neurodevelopmental abnormalities; however, transdiagnostic and diagnosis-specific patterns of such abno...

Background: Idiopathic generalized epilepsy (IGE) is a collection of generalized nonlesional epileptic network disorders. Around 20-40% of patients with IGE are refractory to antiseizure medication, and mechanisms underlying refractoriness are poorly understood. Here, we characterize structural brain network alterations and determine whether network alterations differ between patients with refractory and nonrefractory IGE. Methods: Thirty-three patients with IGE (10 nonrefractory and 23 refractory) and 39 age- and sex-matched healthy controls were studied. Network nodes were segmented from T1-weighted images, while connections between these nodes (edges) were reconstructed from diffusion magnetic resonance imaging (MRI). Diffusion networks of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and streamline count (Count) were studied. Differences between all patients, refractory, nonrefractory, and control groups were computed using network-based statistics. Nodal volume differences between groups were computed using Cohen's d effect size calculation. Results: Patients had significantly decreased bihemispheric FA and Count networks and increased MD and RD networks compared with controls. Alterations in network architecture, with respect to controls, differed depending on treatment outcome, including predominant FA network alterations in refractory IGE and increased nodal volume in nonrefractory IGE. Diffusion MRI networks were not influenced by nodal volume. Discussion: Although a nonlesional disorder, patients with IGE have bihemispheric structural network alterations that may differ between patients with refractory and nonrefractory IGE. Given that distinct nodal volume and FA network alterations were observed between treatment outcome groups, a multifaceted network analysis may be useful for identifying imaging biomarkers of refractory IGE.

Multiple sclerosis (MS) is a heterogenous condition with differences between patients regarding disease presentation, imaging features, disease activity, prognosis and treatment responses. Following the discovery of new biomarkers, the concept of MS has evolved, with syndromes previously considered to be its variants now recognised as separate entities, including aquaporin-4 (AQP4)-antibody (Ab) neuromyelits optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-Ab disease (MOGAD). In line with their distinct pathology, the newly emerging conditions have imaging characteristics which are dissimilar to typical MS. Progress in reclassifying such demyelinating CNS conditions has highlighted the challenge in meaningful categorisation of atypical presentations at the borders of MS, such as antibody-negative neuromyelitis optica-like syndromes, tumefactive demyelinating lesions, or Balo's concentric sclerosis. In this review, we discuss the increasing role of imaging in distinguishing MS from non-MS CNS inflammatory/demyelinating conditions and defining undetermined borderline cases. This progress relies both on better characterisation of imaging features of these conditions on conventional imaging in terms of their appearance and location, as well as on the implementation of novel image acquisition and/or post-processing techniques allowing for more in-depth lesion assessment, including the presence of a central vein sign or paramagnetic rim.

Funding Information: Source(s) of financial support: The study was supported by State funding for University‐level health research (TYH 2013311, Y122417012, and Y102218018), the Signe and Ane Gyllenberg Foundation, the Emil Aaltonen Foundation, and the Finnish Medical Foundation. Funding Information: Eija Kalso has received personal fees for participation in advisory board meetings of Pfizer and Orion Pharma, unrelated to this work. Dr. Juhani Ojala reports grants from Suomen Lääketieteen säätiö, outside the submitted work. Dr. Jukka Vanhanen reports grants from The Emil Aaltonen Foundation, grants from State funding for university‐level health research, during the conduct of the study. Part of Dr. Mari A. Kaunisto's salary is covered by a large Finnish biobank study FinnGen, funded by 12 international pharmaceutical companies (Abbvie, AstraZeneca, Biogen, Celgene, Genentech, a member of the Roche Group, GSK, Janssen, Maze Therapeutics, Merck/MSD, Novartis, Pfizer, and Sanofi) and Business Finland. Pantelis Lioumis has been consulting Nexstim Ltd. for issues not related to this study, such as motor and speech functional mapping until 2016. Dr. Jukka Putaala reports personal fees from Boehringer‐Ingelheim, personal fees and other from Bayer, grants and personal fees from BMS‐Pfizer, grants and personal fees from Abbott/St. Jude Medical, other from Vital Signum, other from Nokia Technologies, other from Bittium, other from BcB Medical, personal fees from Portola, personal fees from Terve Media, grants from Business Finland, grants from Amgen, personal fees from Herantis Pharma, other from Medixine, outside the submitted work; and he has participated in the European Stroke Organisation's guideline working groups on 1) poststroke hyperglycemia and 2) secondary prevention in patients with AF. He also has participated in the Finnish Duodecim Society's guideline working group on Ischemic stroke and TIA. The remaining authors have no potential conflicts to disclose. Conflict of Interest: Publisher Copyright: ©2021 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals LLC on behalf of International Neuromodulation Society. Objectives: Central poststroke pain (CPSP), a neuropathic pain condition, is difficult to treat. Repetitive transcranial magnetic stimulation (rTMS) targeted to the primary motor cortex (M1) can alleviate the condition, but not all patients respond. We aimed to assess a promising alternative rTMS target, the secondary somatosensory cortex (S2), for CPSP treatment. Materials and Methods: This prospective, randomized, double-blind, Sham-controlled three-arm crossover trial assessed navigated rTMS (nrTMS) targeted to M1 and S2 (10 sessions, 5050 pulses per session at 10 Hz). Participants were evaluated for pain, depression, anxiety, health-related quality of life, upper limb function, and three plasticity-related gene polymorphisms including Dopamine D2 Receptor (DRD2). We monitored pain intensity and interference before and during stimulations, and at one month. A conditioned pain modulation test was performed using the cold pressor test. This assessed the efficacy of the descending inhibitory system, which maytransmit TMS effects in pain control. Results: We prescreened 73 patients, screened 29, and included 21, of whom 17 completed the trial. NrTMS targeted to S2 resulted in long-term (from baseline to one-month follow-up) pain intensity reduction of ≥30% in 18% (3/17) of participants. All stimulations showed a short-term effect on pain (17–20% pain relief), with no difference between M1, S2, or Sham stimulations, indicating a strong placebo effect. Only nrTMS targeted to S2 resulted in a significant long-term pain intensity reduction (15% pain relief). The cold pressor test reduced CPSP pain intensity significantly (p = 0.001), indicating functioning descending inhibitory controls. The homozygous DRD2 T/T genotype is associated with the M1 stimulation response. Conclusions: S2 is a promising nrTMS target in the treatment of CPSP. The DRD2 T/T genotype might be a biomarker for M1 nrTMS response, but this needs confirmation from a larger study.

OBJECTIVE To synthesize and critically appraise literature exploring patient perceptions regarding the therapeutic use of noninvasive brain stimulation. MATERIAL AND METHODS A systematic search of CINHAL, PUBMED, Web of Science, and Medline was performed. Reference lists of relevant articles were also screened. Studies exploring participant perceptions regarding the therapeutic use of noninvasive brain stimulation were eligible for inclusion. Perceptions were divided into three domains: knowledge, experience, and attitudes. Noninvasive brain stimulation was defined as any neuromodulation technique that alters brain activity but does not require invasive methods such as surgery. No restrictions were placed upon study design or participant population. Two reviewers performed data extraction and risk of bias assessment. Data relating to methodological characteristics, participant demographics, type of noninvasive brain stimulation, and nature of perceptions (knowledge, experience, or attitudes) were extracted. RESULTS Four studies comprising data from 163 participants met the inclusion criteria. All studies investigated perceptions of repetitive transcranial magnetic stimulation (rTMS) in psychiatric populations. Most participants perceived rTMS to be safe and beneficial, demonstrated low-levels of fear, and were willing to recommend the intervention to others. No studies were found investigating patient perception of transcranial direct current stimulation (tDCS). CONCLUSION The findings from this review suggest that rTMS is well accepted as a therapeutic treatment among psychiatric populations, providing support for its clinical utility. Future work is needed to determine if similar findings exist for other conditions (e.g., chronic pain) and for other therapeutic forms of brain stimulation (e.g., tDCS).

Background: To improve the treatment outcomes of patients with schizophrenia, research efforts have focused on identifying brain-based markers of treatment response. Personal characteristics regard...

It is under debate how preferential perfusion of the brain (brain-sparing) in fetal growth restriction (FGR) relates to long-term neurodevelopmental outcome. Epigenetic modification of neurotrophic genes by altered fetal oxygenation may be involved. To explore this theory, we performed a follow-up study of 21 FGR children, in whom we prospectively measured the prenatal cerebroplacental ratio (CPR) with Doppler sonography. At 4 years of age, we tested their neurodevelopmental outcome using the Wechsler Preschool and Primary Scale of Intelligence, the Child Behavior Checklist, and the Behavior Rating Inventory of Executive Function. In addition, we collected their buccal DNA to determine the methylation status at predefined genetic regions within the genes hypoxia-inducible factor-1 alpha (HIF1A), vascular endothelial growth factor A (VEGFA), erythropoietin (EPO), EPO-receptor (EPOR), brain-derived neurotrophic factor (BDNF), and neurotrophic tyrosine kinase, receptor, type 2 (NTRK2) by pyrosequencing. We found that FGR children with fetal brain-sparing (CPR n = 8) demonstrated a trend (0.05 < p < 0.1) toward hypermethylation of HIF1A and VEGFA at their hypoxia-response element (HRE) compared with FGR children without fetal brain-sparing. Moreover, in cases with fetal brain-sparing, we observed statistically significant hypermethylation at a binding site for cyclic adenosine monophophate response element binding protein (CREB) of BDNF promoter exon 4 and hypomethylation at an HRE located within the NTRK2 promoter (both p VEGFA was associated with a poorer Performance Intelligence Quotient, while hypermethylation of BDNF was associated with better inhibitory self-control (both p

Purpose and background Post-traumatic olfactory dysfunction (PTOD), mostly caused by head injury, is thought to be associated with changes in the structure and function of the brain olfactory processing areas. Training and repeated exposure to odorants lead to enhanced olfactory capability. This study investigated the effects of a 16-weeks olfactory training (OT) on olfactory function and brain structure. Methods Twenty-five patients with PTOD were randomly divided in three groups: (1) 9 control patients who did not receive any training, (2) 9 patients underwent classical OT by 4 fixed odors, and (3) 7 patients underwent modified OT coming across 4 sets of 4 different odors sequentially. Before and after the training period, all patients performed olfactory function tests and structural magnetic resonance imaging (MRI). Sniffin’ Sticks test was used to assess olfactory function. MRI data were analyzed using voxel-based morphometry and surface-based morphometry. Results Both trained groups showed a considerable recovery of olfactory function, especially in odor identification. MRI data analysis revealed that the classical OT leads to increases in cortical thickness/density of several brain regions, including the right superior and middle frontal gyrus, and bilateral cerebellums. In addition, the modified OT yielded a lower extent of cortical measures in the right orbital frontal cortex and right insular. Following modified OT, a positive correlation was observed between the odor identification and the right orbital frontal cortex. Conclusion Both olfactory training methods can improve olfactory function and that the improvement is associated with changes in the structure of olfactory processing areas of the brain.

A 52-year-old woman with cystic fibrosis presented to the emergency department with expressive aphasia and right-sided hemiparesis. CT scan of the brain revealed a left middle cerebral artery territory infarct. A diagnosis of cerebral paradoxical embolisation associated with patent foramen ovale and a history of deep venous thrombosis was made. The patient underwent endovascular thrombectomy and percutaneous closure of patent foramen ovale. Current literature, including five published case reports, pertaining to the subject is discussed. The unique aspects of the case are highlighted, including the particular risk of cerebral paradoxical embolisation in patients with cystic fibrosis. The result of this case report, in context to previously reported literature, suggests that clinicians should be aware of paradoxical embolisation in patients with cystic fibrosis via an intracardiac shunt, particularly with implanted vascular access devices and a history of deep venous thrombosis.

BACKGROUND: Patients with breast cancer frequently report cognitive impairment both during and after completion of therapy. Evidence suggests that cancer-related cognitive impairments are related to widespread neural network dysfunction. The default mode network (DMN) is a large conserved network that plays a critical role in integrating the functions of various neural systems. Disruption of the network may play a key role in the development of cognitive impairment. METHODS: We compared neuroimaging and neurocognitive data from 43 newly diagnosed primary breast cancer patients (mean age = 48, standard deviation [SD] = 8.9 years) and 50 frequency-matched healthy female controls (mean age = 50, SD = 10 years) before treatment and 1 year after treatment completion. Functional and effective connectivity measures of the DMN were obtained using graph theory and Bayesian network analysis methods, respectively. RESULTS: Compared with healthy females, the breast cancer group displayed higher global efficiency and path length post-treatment (p

During the past decade, the pediatric suicide rate has nearly tripled. Yet, little is known about suicide behavior (SB) in children. Identification of risk factors associated with SB during childhood may be critical to preventing future attempts. The purpose of this study was to examine the relationship between neurocognitive performance and suicide ideation (SI) in children.The present study utilized baseline data from 11,875 participants in the Adolescent Brain Cognitive Development (ABCD) study, a longitudinal study that follows 9- and 10-year-old children through late adolescence to examine factors that influence developmental trajectories. Suicidality was assessed by the Kiddie Schedule for Affective Disorder and Schizophrenia (KSADS) suicide module completed by the parent. Neurocognitive ability was assessed using the NIH Toolbox Cognition measures administered to the youth.Children with a history of SI reported by their parent or concordant parent and youth report of SI demonstrated lower performance on the NIH Toolbox Picture Sequence Memory Test compared to children without SI. The difference in performance on the memory task remained significant when including demographic characteristics, family history of suicide, and internalizing symptoms in the model as covariates.To our knowledge, this is the first study to identify decreased episodic memory in children with SI. These findings are similar to results from adult and adolescent studies which have reported decreased memory performance among suicide attempters. Deficits in episodic memory may impact a child's ability to problem-solve and generate potential future outcomes, which may increase the risk for SB. Early identification of memory deficits in children may inform suicide prevention and intervention efforts.Highlights6% of parents and children reported a history of active suicide ideation in children.Children with a history of suicide ideation had lower episodic memory performance.Early identification of memory deficits may inform suicide intervention efforts.

BackgroundAltered peripheral immune/inflammatory system and brain volumetric changes have been implicated in the pathophysiology of bipolar disorder (BD). This study aimed to evaluate how peripheral levels of cytokines are related to volumetric brain changes in euthymic patients with BD.MethodsEuthymic patients with BD (n = 21) and healthy controls (n = 22) were enrolled in this exploratory study. Blood samples were collected on the same day of clinical assessment and neuroimaging. Cytokines were measured through cytometric bead array method. Neuroimaging data were acquired using a sagittal three-dimensional magnetic resonance imaging T1-weighted fast field echo sequence and was processed using FreeSurfer.ResultsCompared to controls, BD patients had significantly lower volumes in the cingulate, medial-orbitofrontal (MOF) and parahippocampal regions. We found a negative correlation between right MOF volume and interferon-gamma levels (β = −0.431, P = .049) and a positive correlation between interleukin-10 levels and left posterior cingulate volume (β = 0.457, P = .048).ConclusionOur results support the involvement of inflammatory pathways in structural brain changes in BD.

Over the past few years, neuroimaging studies have been performed in young adults with perinatally acquired HIV (PHIV) to study the impact of HIV infection on the central nervous system (CNS), but no recent review have been published. This review aims to identify brain areas where PHIV eems to have greater impact taking into account demographic, behavioral, and clinical characteristics in PHIV infected patients. For this purpose, PubMed and Medline searches were carried out which included studies from 2010 to April 2020. We performed a systematic review and included 26 articles using structural (brain morphometry and diffusion tensor imaging) and functional magnetic resonance imaging methods involving 1182 PHIV-infected participants. Ample evidence has been provided of HIV effects on underlying brain structure. However, information recorded in the studies is commonly incomplete and results sometimes contradictory. In addition to future improvements and dissemination of tools for the developing brain MRI processing and analysis, the inclusion of data related to HIV infection itself (including clinical and immunovirological characteristics as well as detailed information about antiretroviral treatment such as age at ART initiation) may be of vital importance to the better understanding of the impact of the disease on CNS.

Background and Purpose: Delirium, an acute reduction in cognitive functioning, hinders stroke recovery and contributes to cognitive decline. Right-hemisphere stroke is linked with higher delirium incidence, likely, due to the prevalence of spatial neglect (SN), a right-brain disorder of spatial processing. This study tested if symptoms of delirium and SN after right-hemisphere stroke are associated with abnormal function of the right-dominant neural networks specialized for maintaining attention, orientation, and arousal. Methods: Twenty-nine participants with right-hemisphere ischemic stroke undergoing acute rehabilitation completed delirium and SN assessments and functional neuroimaging scans. Whole-brain functional connectivity of 4 right-hemisphere seed regions in the cortical-subcortical arousal and attention networks was assessed for its relationship to validated SN and delirium severity measures. Results: Of 29 patients, 6 (21%) met the diagnostic criteria for delirium and 16 (55%) for SN. Decreased connectivity of the right basal forebrain to brain stem and basal ganglia predicted more severe SN. Increased connectivity of the arousal and attention network regions with the parietal, frontal, and temporal structures in the unaffected hemisphere was also found in more severe delirium and SN. Conclusions: Delirium and SN are associated with decreased arousal network activity and an imbalance of cortico-subcortical hemispheric connectivity. Better understanding of neural correlates of poststroke delirium and SN will lead to improved neuroscience-based treatment development for these disorders. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03349411.

Introduction Silent cerebral infarcts (SCI) are common in patients with sickle cell disease (SCD) and thought to be caused by a mismatch between oxygen delivery and consumption. The mechanism underlying insufficient oxygen utilization is related to severity of anemia, and paradoxically, to the elevated cerebral blood flow (CBF) observed in SCD patients. CBF is elevated as a compensatory mechanism to maintain oxygen delivery, but high CBF levels can result in rapid transit of blood through the brain capillaries, limiting offloading of oxygen to the tissue; a process called arteriovenous shunting. One way to assess functional arteriovenous shunting is to use noncontrast perfusion MRI techniques in which we can assess the signal intensity of an endogenous blood tracer when it reaches the sagittal sinus. This venous signal (VS) reflects the amount of labeled blood that has not exchanged with the brain parenchyma. Under normal physiological conditions, the VS intensity will increase approximately proportionally with CBF as we expect only some of the water to exchange with tissue as it flows by. However, it is unknown whether functional shunting scales with CBF only, or whether other hemodynamic processes play a role in patients with SCD. We hypothesize that, under pathophysiological conditions such as in SCD patients, more labeled blood may pass unexchanged through the capillaries, which results in higher VS. In the present study, we investigated functional shunting by quantifying VS and assessed its association with hemodynamic, demographic and laboratory parameters in both pediatric and adult SCD patients, and controls. In addition, VS-CBF relationship was studied by further increasing CBF after a vasodilatory challenge. Methods We included 28 children (mean age 12.7 ± 2.3, 9 F) and 38 adults (mean age 32.1 ± 11.2, 14 F) with SCD (HbSS and HbS), and 10 healthy race-matched adult controls (mean age 36.4 ± 15.9, 4 F). For the CBF and VS measurements, pseudo-continuous arterial spin labelling (pCASL) data were acquired using 3T MRI. We segmented the ASL blood pool in the sagittal sinus to determine a common region of interest for each group. We used these images as masks to calculate average VS. Notably, for the comparison between children and adults the ratio between VS to gray matter CBF was used (VGR) instead of the VS, to take into account higher CBF in children. To get more insight into the oxygen utilization, oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2) were calculated. In adult participants acetazolamide (ACZ) was used as a vasodilatory challenge. The hematologic laboratory parameters hemoglobin (Hb) and LDH were used as markers of anemia and hemolysis, respectively. Results VS as a marker of cerebral shunting was higher in both adult and pediatric patients with SCD as compared to controls (p Conclusion Our results show that the VS in the sagittal sinus on ASL images can be used to assess functional arteriovenous shunting in the brain. Given its negative association with CMRO 2 in combination with the negative association with hemoglobin and positive correlation with LDH, this functional shunting seems to reflect pathophysiologic shunting related to higher disease severity. Future studies will focus on the relation between functional shunting and the prevalence of SCI, investigating its link to aberrant capillary oxygen exchange in SCD. Figure 1 Figure 1. Disclosures Vaclavu: Philips Healthcare: Research Funding. Biemond: GBT: Honoraria, Research Funding, Speakers Bureau; Novo Nordisk: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria; Sanquin: Research Funding.

BACKGROUND: The analysis of brain activity in different conditions is an important research area in neuroscience. OBJECTIVE: This paper analyzed the correlation between the brain and skin activities in rest and stimulations by information-based analysis of electroencephalogram (EEG) and galvanic skin resistance (GSR) signals. METHODS: We recorded EEG and GSR signals of eleven subjects during rest and auditory stimulations using three pieces of music that were differentiated based on their complexity. Then, we calculated the Shannon entropy of these signals to quantify their information contents. RESULTS: The results showed that music with greater complexity has a more significant effect on altering the information contents of EEG and GSR signals. We also found a strong correlation (r= 0.9682) among the variations of the information contents of EEG and GSR signals. Therefore, the activities of the skin and brain are correlated in different conditions. CONCLUSION: This analysis technique can be utilized to evaluate the correlation among the activities of various organs versus brain activity in different conditions.

BACKGROUND AND AIMS: Conditions such as irritable bowel syndrome (IBS), functional dyspepsia, and functional constipation are among the prevalent gastrointestinal (GI) disorders classified as disorders of gut-brain interaction (DGBI), which can adversely affect the lives of sufferers. This study aimed to assess the degree and consequences of overlapping DGBI in a large population-based global scale. METHODS: Internet survey data from 54,127 adults (49.1% women) in 26 countries were analyzed by 4 GI anatomic regions (esophageal, gastroduodenal, bowel, and anorectal). The number of DGBI-affected GI regions was assessed, including associations with sex, age, disease severity, quality of life, psychosocial variables, and health care utilization. RESULTS: A total of 40.3% of surveyed individuals met Rome IV criteria for a DGBI. The percentages with 1-4 DGBI-affected GI regions were 68.3%, 22.3%, 7.1%, and 2.3%, respectively. The IBS symptom severity score increased significantly from 1 (207.6) to 4 (291.6) regions, as did non-GI symptom reporting (somatization), anxiety and depression, concerns and embarrassment about bowel function, doctor visits, medications, and abdominal surgeries (all P < .0001). Quality of life decreased with increasing number of DGBI regions (P < .0001). In a logistic mixed model, non-GI symptoms (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.08-1.10), being very vs not concerned (OR, 2.55; 95% CI, 2.27-2.90), being very vs not embarrassed about bowel function (OR, 1.20; 95% CI, 1.08-1.33), and mean number of doctor visits (OR, 1.23; 95% CI, 1.115-1.32) were most strongly associated with number of DGBI regions. CONCLUSIONS: DGBI in multiple anatomic GI regions is associated with increased psychological comorbidity, health care utilization, and IBS severity. Physician awareness of overlap could improve quality of care, prevent unnecessary interventions, and yield more positive health outcomes. ispartof: CLINICAL GASTROENTEROLOGY AND HEPATOLOGY vol:20 issue:5 pages:E945-E956 ispartof: location:United States status: published

Background: Spatio-temporal evolution of cord atrophy in multiple sclerosis (MS) has not been investigated yet. Objective: To evaluate voxel-wise distribution and 1-year changes of cervical cord atrophy in a multicentre MS cohort. Methods: Baseline and 1-year 3D T1-weighted cervical cord scans and clinical evaluations of 54 healthy controls (HC) and 113 MS patients (14 clinically isolated syndromes (CIS), 77 relapsing-remitting (RR), 22 progressive (P)) were used to investigate voxel-wise cord volume loss in patients versus HC, 1-year volume changes and clinical correlations (SPM12). Results: MS patients exhibited baseline cord atrophy versus HC at anterior and posterior/lateral C1/C2 and C4–C6 ( p < 0.05, corrected). While CIS patients showed baseline volume increase at C4 versus HC ( p < 0.001, uncorrected), RRMS exhibited posterior/lateral C1/C2 atrophy versus CIS, and PMS showed widespread cord atrophy versus RRMS ( p < 0.05, corrected). At 1 year, 13 patients had clinically worsened. Cord atrophy progressed in MS, driven by RRMS, at posterior/lateral C2 and C3–C6 ( p < 0.05, corrected). CIS patients showed no volume changes, while PMS showed circumscribed atrophy progression. Baseline cord atrophy at posterior/lateral C1/C2 and C3–C6 correlated with concomitant and 1-year disability ( r = −0.40/–0.62, p < 0.05, corrected). Conclusions: Voxel-wise analysis characterized spinal cord neurodegeneration over 1 year across MS phenotypes and helped to explain baseline and 1-year disability.

Purpose Timely identification and treatment of intracranial hematomas in patients with brain injury is essential for successful treatment. This study evaluates Infra-scanner as a handy medical screening tool for diagnosing, on-site, cerebral hematomas in patients with head injury. Materials and methods Patients referred to the emergency department of university hospitals with mild to moderate brain trauma, up to 12 h from injury were included. NIR sensors of infra-scan device were placed on the right and left frontal, temporal, peritoneal and occipital parts of the head and light absorption was recorded. Positive or negative cerebral hemorrhage cases were compared with contrast-enhanced CT scan results as the gold standard. Diagnostic parameters of the device and cases related to bleeding were analyzed and reported. Results A total of 300 patients were studied. Sensitivity of the infrasound scanner in the Iranian study population was 94.8 (95% CI: 88% -100) and its specificity was 86.9 (95% CI: 79% -99% 99). Negative predictive value (NPV) was 90.3% and positive predictive value (PPV) was 92.9%. Sensitivity in men (95.7%) (95%CI, 90% -1) was more than women (95% CI, 81% -99%)90%. At the ages of less than 36 years, sensitivity (95.3%) and specificity (87.1%) were more than sensitivity (94.4%) and specificity (86.5%) over 36 years old. If the test had been performed in less than / equal to two hours from trauma, the sensitivity (94.9%) and the specificity (92%) were greater than the sensitivity (94.6%) and the specificity (75%) during when the scan had been performed in more than two hours from trauma. In general, in extra-axial bleeding including EDH, SAH, SDH, the sensitivity was 95.1% and the specificity was 84.5%, while in intra-axial bleeding, including ICH and IVH, the sensitivity was lower (93.9%) and the specificity was 91.7. The sensitivity of the device in detecting bleeding in the occipital lobe (95.8%) was higher than other brain lobes. Conclusion This study shows that Infra-scanner is useful in initial examination and screening of patients with head injury and can be used as an adjunct to a CT scan or when not available and may allow earlier treatment which reduce the secondary damage to the hematoma.

Objective Few reports have described the real-world outcomes of rituximab, methotrexate (MTX), procarbazine, and vincristine (R-MPV) plus response-adapted whole-brain radiotherapy (WBRT) for elderly patients with primary central nervous system lymphoma (PCNSL). We evaluated the outcome of this regimen. Methods We evaluated >60-year-old patients with newly diagnosed PCNSL who received R-MPV plus WBRT from January 2010 to December 2019 at Toyohashi Municipal Hospital. The patients' characteristics, regimen enforcement, response rate, survival, and toxicity were analyzed. Patients Ten patients were consecutively enrolled. Their median age was 69 years old, and 60% had a performance status of 3 or 4 before induction therapy. Results Seven patients achieved a complete response after induction, and all 10 patients achieved a complete response after consolidation. Seven received reduced-dose WBRT at 23.4 Gy, and 2 received WBRT at 45 Gy. The median follow-up was 44.4 months; the 3-year progression-free survival and overall survival rates were 60% and 80%, respectively; and the cumulative incidence of relapse was 40%. The incidence of symptomatic delayed neurotoxicity was 70%. Of the 7 patients who received reduced-dose WBRT, 4 (57%) developed delayed neurotoxicity, including 1 severely affected patient. Only one patient survived without relapse and delayed neurotoxicity. The ratio of patients who developed relapse or delayed neurotoxicity that impaired daily life was 33% and 100% in the MTX high- and low-intensity groups, respectively. Conclusion This regimen in elderly patients is unsatisfactory because of delayed neurotoxicity. We should consider maintaining an adequate MTX intensity, postponing or minimizing WBRT, and choosing high-dose consolidation therapy for select patients.

Background: Language dysfunction is rarely seen in patients with unruptured brain arteriovenous malformation (AVM) albeit the AVM nidus involving language areas, which provides a unique disease model to study language reorganization. The objective of this study was to investigate the impairment and reorganization patterns and characteristics of language-related white matter in AVMs located at different brain areas. Methods: Thirty-three patients with AVMs involving language areas were prospectively enrolled. Patients were categorized into 3 groups according to the lesion locations: the frontal (14 patients), temporal (15 patients), and parietal groups (4 patients). Thirty age- and sex-matched healthy controls were enrolled as comparison. All participants underwent diffusion tensor imaging scans, and automated fiber quantification method was applied to quantitatively study the difference of segmented language-related white matter connectivity between 3 AVM groups and control group. Results: Language functions were normal in all subjects according to Western Aphasia Battery test. In the frontal group, fractional anisotropy (FA) value decreased in the left arcuate fascicle and increased in left superior longitudinal fasciculus and uncinate fascicle; in the temporal group, FA values decreased in left inferior fronto-occipital fascicle and inferior longitudinal fascicle and increased in right anterior thalamic radiation and uncinate fascicle; in the parietal group, FA values decreased in left arcuate fascicle and inferior longitudinal fascicle and increased in bilateral anterior thalamic radiations and uncinate fascicles and right inferior fronto-occipital fascicle. In fascicles with decreased FA values, the increase of radial diffusivity was common, and fascicles with increased FA values usually presented along with increased axial diffusivity values. Conclusions: Remodeling of language-related white matter occurs when traditional language areas are involved by AVM nidus, and its reorganization patterns vary with locations of AVM nidus. Fascicle impairment is mainly caused by the myelin deficits, and its plasticity may be dominated by the axon remodeling procedure.

Novel treatment modalities, such as non-invasive brain stimulation (NIBS), typically focus on patient groups that have failed multiple treatment interventions. Despite its promise, the clinical translation of NIBS in schizophrenia has been limited. One important obstacle to implementation is the inconsistent reporting of treatment resistance in the clinical trial literature contributing to heterogeneity in reported effects. In response, we develop a numerical approach to synthesize quality of assessment of Treatment-Resistant Schizophrenia (TRS) and apply this to studies investigating therapeutic response to NIBS in patients with schizophrenia. Literature search conducted through PubMed database identified 119 studies investigating Transcranial Magnetic Stimulation and Transcranial Electrical Stimulation in treating resistant schizophrenia symptoms. A quality score out of 11 was assigned to each study based on adherence to the international consensus guidelines for TRS developed by the Treatment Response and Resistance in Psychosis (TRRIP) group. Results revealed an overall paucity of studies with thorough assessment and/or reporting of TRS phenomenon, as evidenced by a mean quality score of 3.38/11 (SD: 1.01) for trials and 5.16/11 (SD: 1.57) for case reports, though this improved minimally since the publication of consensus criteria. Most studies considered treatment-resistance as a single dimensional construct by reporting resistance of a single symptom, and failed to establish treatment adherence, resistance time course and functional impairment. We conclude that the current NIBS literature in schizophrenia do not reflect its true effects on treatment-resistance. There is an urgent need to improve assessment and reporting standards of clinical trials that target TRS.

Spinal cord injury (SCI) can result in significant neurological impairment and functional and cognitive deficits. It is well established that SCI results in focal neurodegeneration that gradually spreads to other cord areas. On the other hand, traumatic brain injury (TBI) is strongly associated with tau protein pathology and neurodegeneration that can spread in areas throughout the brain. Tau is a microtubule-associated protein abundant in neurons and whose abnormalities result in neuronal cell death. While SCI and TBI have been extensively studied, there is limited research on the relationship between SCI and brain tau pathology. As a result, in this study, we examined tau pathology in spinal cord and brain samples obtained from severe SCI mouse models at various time points. The effects of severe SCI on locomotor function, spatial memory, anxiety/risk-taking behavior were investigated. Immunostaining and immunoblotting confirmed a progressive increase in tau pathology in the spinal cord and brain areas. Moreover, we used electron microscopy to examine brain samples and observed disrupted mitochondria and microtubule structure following SCI. SCI resulted in motor dysfunction, memory impairment, and abnormal risk-taking behavior. Notably, eliminating pathogenic cis P-tau via systemic administration of appropriate monoclonal antibodies restored SCI's pathological and functional consequences. Thus, our findings suggest that SCI causes severe tauopathy that spreads to brain areas, indicating brain dysfunction. Additionally, tau immunotherapy with an anti-cis P-tau antibody could suppress pathogenic outcomes in SCI mouse models, with significant clinical implications for SCI patients. SCI induces profound pathogenic cis p-tau, which diffuses into the brain through CSF, resulting in brain neurodegeneration and cognitive decline.

Susac's syndrome is a rare microangiopathy affecting small vessels of the retina, inner ear and brain. It is characterised by a triad of symptoms: encephalopathy, visual defects, and sensorineural hearing loss. The disease is probably caused by an autoimmune process. Diagnosis is based on the typical symptoms, brain MRI, and, most importantly, fluorescein angiography. It is important to distinguish between Susac's syndrome and multiple sclerosis or migraine with aura, because misdiagnosis leads to the wrong treatment. To date, no detailed guidelines for the treatment of Susac's syndrome have been developed. Immunosuppression seems to be effective. It must be remembered that early and aggressive treatment is crucial, and that delays in diagnosis, and as a result in treatment implementation, worsen the prognosis.

Background: Magnetic resonance imaging (MRI) of brain volume measures are widely used outcomes in secondary progressive multiple sclerosis (SPMS), but it is unclear whether they are associated with physical and cognitive disability. Objective: To investigate the association between MRI outcomes and physical and cognitive disability worsening in people with SPMS. Methods: We used data from ASCEND, a large randomized controlled trial ( n = 889). We investigated the association of change in whole brain and gray matter volume, contrast enhancing lesions, and T2 lesions with significant worsening on the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), Nine-Hole Peg Test (NHPT), and Symbol Digit Modalities Test (SDMT) with logistic regression models. Results: We found no association between MRI measures and EDSS or SDMT worsening. T25FW worsening at 48 and 96 weeks, and NHPT worsening at 96 weeks were associated with cumulative new or newly enlarging T2 lesions at 96 weeks. NHPT worsening at 48 and 96 weeks was associated with normalized brain volume loss at 48 weeks, but not with other MRI outcomes. Conclusion: The association of standard MRI outcomes and disability was noticeably weak and inconsistent over 2 years of follow-up. These MRI outcomes may not be useful surrogates of disability measures in SPMS.

Sleep pressure, the driving force of the homeostatic sleep regulation, is accumulated during wakefulness and dissipated during sleep. Sleep deprivation (SD) has been used as a method to acutely increase animal’s sleep pressure for investigating the molecular changes under high sleep pressure. However, SD induces changes not only reflecting increased sleep pressure but also inevitable stresses and prolonged wake state itself. The Sik3Sleepy mutant mice (Sleepy) exhibit constitutively high sleep pressure despite sleeping longer, and have been useful as a model of increased sleep pressure. Here we conducted a cross-comparison of brain metabolomic profiles between SD versus ad lib slept mice, as well as Sleepy mutant versus littermate wild-type mice. Targeted metabolome analyses of whole brains quantified 203 metabolites in total, of which 43 metabolites showed significant changes in SD, whereas three did in Sleepy mutant mice. The large difference in the number of differential metabolites highlighted limitations of SD as methodology. The cross-comparison revealed that a decrease in betaine and an increase in imidazole dipeptides are associated with high sleep pressure in both models. These metabolites may be novel markers of sleep pressure at the whole-brain level. Furthermore, we found that intracerebroventricular injection of imidazole dipeptides increased subsequent NREM sleep time, suggesting the possibility that imidazole dipeptides may participate in the regulation of sleep in mice.

INTRODUCTION: An important but under-investigated confound of functional magnetic resonance imaging (fMRI) is body posture. Although it is well established that body position changes cerebral blood flow, the amount of cerebrospinal fluid in the brain, intracranial pressure, and even the firing rate of certain cell types, there is currently no study that directly examines its effect on fMRI measurements. Moreover, fMRI is typically done in a supine position, which often does not correspond to how these processes are performed in everyday settings. METHODS: In this study, 20 healthy adults underwent resting-state fMRI under three body positions: supine, right lateral decubitus (RLD), and left lateral decubitus (LLD). We first investigated whether there were differences in overall organization of whole-brain connectivity between conditions using graph theory. Second, we examined whether functional connectivity of two most studied default mode network (DMN) seeds to the rest of the brain was altered as a function of body position. RESULTS: Nonparametric statistical analyses revealed that global network measures differed among conditions, with the supine and LLD showing identical results which differed when compared to the RLD. There was decreased connectivity for DMN seeds in the RLD condition compared to the supine and LLD, but there were no significant differences between the latter two conditions. DISCUSSION: Potential mechanisms underlying these alterations include gravity, changes in physiology, and body anatomy. Our results suggest that, compared to supine and LLD, the RLD position leads to changes in whole-brain and DMN connectivity. Finally, depending on the research question, combining imaging modalities that allow for more naturalistic settings provides a better understanding of certain phenomena. IMPACT STATEMENT: Functional connectivity is sensitive to several confounds, including motion, heart rate, and respiration. Body posture is also an important but under-investigated confound. In this study, healthy adults were scanned in three different positions to investigate whether posture results in changes in connectivity. We found that connectivity was identical if participants were facing up or lying on their left, but it was altered when they were lying on their right. Results suggest that posture can lead to connectivity changes and, in some cases, the combined use of functional magnetic resonance imaging with other techniques might provide a better understanding of the phenomenon of interest.

Background: Subclinical vascular brain lesions are highly prevalent in elderly patients with stroke. Little is known about predisposing factors and their impact on long-term outcome of patients with stroke at a young age. Methods: We quantified magnetic resonance-defined subclinical vascular brain lesions, including lacunes and white matter hyperintensities, perivascular spaces and cerebral microbleeds, and assessed total small-vessel disease (SVD) score in patients with first-ever acute ischemic stroke aged 18 to 45 years, and followed them up, as part of the multicentre Italian Project on Stroke in Young Adults. The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. We assessed the predictive accuracy of magnetic resonance features and whether the addition of these markers improves outcome prediction over a validated clinical tool, such as the Italian Project on Stroke in Young Adults score. Results: Among 591 patients (males, 53.8%; mean age, 37.5±6.4 years), 117 (19.8%) had subclinical vascular brain lesions. Family history of stroke was associated with lacunes (odds ratio, 2.24 [95% CI, 1.30–3.84]) and total SVD score (odds ratio, 2.06 [95% CI, 1.20–3.53] for score≥1), hypertension with white matter hyperintensities (odds ratio, 2.29 [95% CI, 1.22–4.32]). After a median follow-up of 36.0 months (25th–75th percentile, 38.0), lacunes and total SVD score were associated with primary end point (hazard ratio, 2.13 [95% CI, 1.17–3.90] for lacunes; hazard ratio, 2.17 [95% CI, 1.20–3.90] for total SVD score ≥1), and the secondary end point brain ischemia (hazard ratio, 2.55 [95% CI, 1.36–4.75] for lacunes; hazard ratio, 2.61 [95% CI, 1.42–4.80] for total SVD score ≥1). The predictive performances of the models, including magnetic resonance features were comparable to those of the random model. Adding individual magnetic resonance features to the Italian Project on Stroke in Young Adults score did not improve model prediction. Conclusions: Subclinical vascular brain lesions affect ≈2 in 10 young adults with ischemic stroke. Although lacunes and total SVD score are associated with thrombotic recurrence, they do not improve accuracy of outcome prediction over validated clinical predictors.

Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations.In this study, we obtained resting-state functional magnetic resonance imaging (R-fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18-60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel-mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns.As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q 0.002, z = -7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age-related change in males instead of females. Besides, the reduction in MTG was found to be a male-special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First-episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs.We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres.

Background: The current ongoing COVID-19 pandemic has compelled us to scrutinize major outbreaks in the past two decades, Severe Acute Respiratory Syndrome (SARS), in 2002, and Middle East Respiratory Syndrome (MERS), in 2012. We aimed to assess the associated neurological manifestations with SARS CoV-2 infection. Methods: In this systematic review, a search was carried out by key-electronic databases, controlled vocabulary, and indexing of trials to evaluate the available pertinent studies which included both medical subject headings (MeSH) and advanced electronic databases comprising PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL). Peer-reviewed studies published in English and Spanish were considered, which reported data on the neurological associations of individuals with suspected or laboratory-confirmed SARS-CoV-2 infection. Outcomes were nervous signs or symptoms, symptom severity, and diagnoses. Findings: Our search identified 45 relevant studies, with 21 case reports, 3 case series, 9 observational studies, 1 retrospective study, 9 retrospective reviews, and 2 prospective reviews. This systematic review revealed that most commonly reported neuronal presentations involved headache, nausea, vomiting and muscular symptoms like fibromyalgia. Anosmia and ageusia, defects in clarity or sharpness of vision (error in visual acuity), and pain may occur in parallel. Notable afflictions in the form of anxiety, anger, confusion, post-traumatic stress symptoms, and post-intensive care syndrome were observed in individuals who were kept in quarantine and those with long-stay admissions in healthcare settings. SARS CoV-2 infection may result in cognitive impairment. Patients with more severe infection exhibited uncommon manifestations, such as acute cerebrovascular diseases (intracerebral haemorrhage, stroke), rhabdomyolysis, encephalopathy, and Guillain-Barré syndrome. Interpretation: SARS-CoV-2 patients experience neuronal presentations varying with the progression of the infection. Healthcare professionals should be acquainted with the divergent neurological symptoms to curb misdiagnosis and limit long-term sequelae. Health-care planners and policymakers must prepare for this eventuality, while the ongoing studies increase our knowledge base on acute and chronic neurological associations of this pathogen.

AIMS This study aimed at clarifying the incidence of recurrent stroke and its etiology in patients with embolic stroke of undetermined source (ESUS) and other stroke subtypes in both the acute and chronic periods. METHODS A total of 645 patients who were admitted with acute ischemic stroke (IS) between March 2015 and August 2019 were enrolled. Among them, 511 patients with ESUS, cardioembolism (CE), large artery atherosclerosis (LAA), or small vessel disease (SVD) were analyzed in this study. After discharge, 391 patients who visited the outpatient clinic were followed up until August 2020. The outcome was stroke recurrence. RESULTS In the acute admission, recurrence rates were 7.6%, 8.1%, 18.8%, and 2.2% in patients with ESUS, CE, LAA, and SVD, respectively, and there were significant differences between the groups. The subtype of recurrence was almost identical to that of the index stroke. In the outpatient clinic, the annual recurrence rates were 4.4%, 4.3%, 6.0%, and 2.9% in ESUS, CE, LAA, and SVD, respectively, and no difference was observed. Subtypes of recurrence in outpatients with ESUS included ESUS, intracerebral hemorrhage (ICH), and SVD. Patients with ESUS and SVD had a higher risk of ICH during follow-up. CONCLUSIONS Although the risk of recurrence was comparable between patients with ESUS and CE and intermediate between patients with LAA and SVD, in the acute admission unit, the risk in outpatients was similar among all subtypes. ESUS was the most recurrent stroke subtype in outpatients with ESUS. The risk of hemorrhagic stroke was significant in patients with SVD and ESUS.

BACKGROUND: Isolated rapid eye movement sleep behavior disorder (iRBD) is prodromal for α-synucleinopathies.OBJECTIVE: The aim of this study was to determine whether pathological cardiac [123 I]meta-iodobenzylguanidine scintigraphy ([123 I]MIBG) is associated with progression of [18 F]fluorodeoxyglucose-positron emission tomography-based Parkinson's disease (PD)-related brain pattern (PDRP) expression in iRBD.METHODS: Seventeen subjects with iRBD underwent [18 F]fluorodeoxyglucose-positron emission tomography brain imaging twice ~3.6 years apart. In addition, [123 I]MIBG and [123 I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computed tomography ([123 I]FP-CIT-SPECT) at baseline were performed. Olfactory, cognitive, and motor functions were tested annually.RESULTS: Twelve of 17 subjects had pathological [123 I]MIBG. At baseline, 6 of 12 of these expressed the PDRP (suprathreshold PDRP z score). At follow-up, 12 of 17 subjects had suprathreshold PDRP z scores, associated with pathological [123 I]MIBG in 92% and with pathological [123 I]FP-CIT-SPECT in 75%. Subjects with pathological [123 I]MIBG had higher PDRP z score change per year (P = 0.027). Three subjects phenoconverted to PD; all had pathological [123 I]MIBG and [123 I]FP-CIT-SPECT, suprathreshold baseline PDRP z scores, and hyposmia.CONCLUSIONS: Pathological [123 I]MIBG was associated with progressive and suprathreshold PDRP z scores at follow-up. Abnormal [123 I]MIBG likely identifies iRBD as prodromal PD earlier than pathological [123 I]FP-CIT-SPECT. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

OBJECTIVE The literature shows discrepancies in stereotactic brain biopsy complication rates, severities, and outcomes. Little is known about the timeline of postbiopsy complications. This study aimed to analyze 1) complications following brain biopsies, using a graded severity scale, and 2) a timeline of complication occurrence. The secondary objectives were to determine factors associated with an increased risk of complications and to assess complication-related management and extra costs. METHODS The authors retrospectively examined 1500 consecutive stereotactic brain biopsies performed in adult patients at their tertiary medical center between April 2009 and April 2019. RESULTS Three hundred eighty-one biopsies (25.4%) were followed by a complication, including 88.2% of asymptomatic hemorrhages. Symptomatic complications involved 3.0% of the biopsies, and 0.8% of the biopsies were fatal. The severity grading scale had a 97.6% interobserver reproducibility. Twenty-three (51.1%) of the 45 symptomatic complications occurred within the 1st hour following the biopsy, while 75.6% occurred within the first 6 hours. Age ≥ 65 years, second biopsy procedures, gadolinium-enhanced lesions, glioblastomas, and lymphomas were predictors of biopsy-related complications. Brainstem biopsy-targeted lesions and cerebral toxoplasmosis were predictive of mortality. Asymptomatic hemorrhage was associated with delayed (> 6 hours) symptomatic complications. Symptomatic complications led to extended hospitalization in 86.7% of patients. The average extra cost for management of a patient with postbiopsy symptomatic complication was $35,702. CONCLUSIONS Symptomatic complications from brain biopsies are infrequent but associated with substantial adverse effects and cost implications for the healthcare system. The use of a severity grading scale, as the authors propose in this article, helps to classify complications according to the therapeutic consequences and the patient’s outcome. Because this study indicates that most complications occur within the first few hours following the biopsy, postbiopsy monitoring can be tailored accordingly. The authors therefore recommend systematic monitoring for 2 hours in the recovery unit and a CT scan 2 hours after the end of the biopsy procedure. In addition, they propose a modern algorithm for optimal postoperative management of patients undergoing stereotactic biopsy.

The coronavirus, also known as SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus-19), with its rapid rate of transmission, has progressed with a great impact on respiratory function and mortality worldwide. The nasal cavity is the promising gateway of SARS-CoV-2 to reach the brain via systemic circulatory distribution. Recent reports have revealed that the loss of involuntary process of breathing control into the brainstem that results in death is a signal of neurological involvement. Early neurological symptoms, like loss of smell, convulsions, and ataxia, are the clues of the involvement of the central nervous system that makes the entry of SARS-CoV-2 further fatal and life-threatening, requiring artificial respiration and emergency admission in hospitals. Studies performed on patients infected with SARS-CoV-2 has revealed three-stage involvement of the Central Nervous System (CNS) in the progression of SARS-CoV-2 infection: Direct involvement of CNS with headache, ataxia, dizziness, altered or impaired consciousness, acute stroke or seizures as major symptoms, peripheral involvement with impaired taste, smell, vision, and altered nociception, and skeletal muscle impairment that includes skeletal muscle disorders leading to acute paralysis in a particular area of the body. In the previous era, most studied and researched viruses were beta coronavirus and mouse hepatitis virus, which were studied for acute and chronic encephalitis and Multiple Sclerosis (MS). Although the early symptoms of SARS-CoV are respiratory pathogenesis, the differential diagnosis should always be considered for neurological perspective to stop the mortalities.

Rationale and Objective To investigate age-related brain morphological changes of boys with high functioning autism (HFA). Materials and Methods Forty-six medication-naive boys with HFA and 48 age-matched typically developing boys (4–12 years old) were included in this study. Structural brain images were processed with FreeSurfer to calculate the brain morphometric features including regional volume, surface area, average cortical thickness, and Gaussian curvature. General linear model was used to identify significant effects of diagnosis and age-by-diagnosis interaction. Correlations between age and the brain morphometric variables of significant clusters were explored. Results Primarily, most of the regions with statistically significant intergroup differences were located in the temporal lobe gyri. Importantly, the volume of bilateral superior temporal gyrus (STG) and the average cortical thickness of the right STG demonstrated significantly age-related intergroup differences. Further age-stratified analysis also revealed morphological alterations of STG among subgroups of preschool and school-aged children with or without HFA. Conclusion The findings demonstrated abnormal age-related volume and cortical thickness atrophy of the STG in HFA children, which reflect brain development trajectories of ASD may initiate to diverge from early overgrowth in childhood period. The anatomical localization of specific brain regions would help us better understand the neurobiology alterations of HFA patients and indicate the effect of age should be carefully delineated and examined in future studies about HFA.

Perceptual adaptation is often studied within a single sense. However, our experience of the world is naturally multisensory. Here, we investigated cross-sensory (visual-vestibular) adaptation of self-motion perception. It was previously found that relatively long visual self-motion stimuli (≳ 15s) are required to adapt subsequent vestibular perception, and that shorter duration stimuli do not elicit cross-sensory (visual↔vestibular) adaptation. However, it is not known whether several discrete short-duration stimuli may lead to cross-sensory adaptation (even when their sum, if presented together, would be too short to elicit cross-sensory adaptation). This would suggest that the brain monitors and adapts to supra-modal statistics of events in the environment. Here we investigated whether cross-sensory (visual↔vestibular) adaptation occurs after experiencing several short (1s) self-motion stimuli. Forty-five participants discriminated the headings of a series of self-motion stimuli. To expose adaptation effects, the trials were grouped in 140 batches, each comprising three ‘prior’ trials, with headings biased to the right or left, followed by a single unbiased ‘test’ trial. Right, and left-biased batches were interleaved pseudo-randomly. We found significant adaptation in both cross-sensory conditions (visual prior and vestibular test trials, and vice versa), as well as both unisensory conditions (when prior and test trials were of the same modality – either visual or vestibular). Fitting the data with a logistic regression model revealed that adaptation was elicited by the prior stimuli (not prior choices). These results suggest that the brain monitors supra-modal statistics of events in the environment, even for short-duration stimuli, leading to functional (supra-modal) adaptation of perception.

Purpose Radiation-induced cognitive deficits have a severe negative impact on pediatric brain tumor patients. The severity of cognitive symptoms is related to the age of the child when radiation was applied, with the most severe effects seen in the youngest. Previous studies using whole-brain irradiation (WBRT) in mice confirmed these findings. To understand ipsilateral and contralateral changes in the hippocampus after partial-brain irradiation (PBRT) of the left hemisphere we assessed the neuroplasticity and changes in the microvasculature of the irradiated and non-irradiated hippocampus in juvenile mice. Methods and materials The left hemispheres of 5-week old mice were irradiated with 2, 8, 20 Gray (Gy) and a fractionated dose of 8 Gy in 2 fractions (8 Gy/2f) using a Computed Tomography (CT)-image guided Small Animal Radiation Research Platform (SARRP). Long-Term Potentiation (LTP) has been monitored ex vivo in the hippocampal Cornu Ammonis 1 (CA1) region and was assessed 3 days, 5 and 10 weeks after PBRT in both hemispheres and compared to a sham group. Irradiation effects on the hippocampus microvasculature were quantified by Efficient tissue clearing and Multi-Organ Volumetric Imaging (EMOVI). Results LTP in irradiated hippocampal slices of juvenile mice declines 3 days after radiation, lasts up to 10 weeks in the irradiated part of the hippocampus and correlates with a significantly reduced microvasculature length. Specifically, LTP inhibition is sustained in the irradiated (20 Gy, 8 Gy/2f, 8 Gy, 2 Gy) hippocampus, whereas the contralateral hippocampus remains unaffected after PBRT. LTP inhibition in the irradiated hemisphere after PBRT might be associated with an impaired microvascular network. Conclusion PBRT induces a long-lasting impairment in neuroplasticity and microvessel network of the irradiated hippocampus, whereas the contralateral hippocampus remains unaffected. These findings provide insight into the design of PBRT strategies to better protect the young developing brain from cognitive decline.

Cutaneous infection by Balamuthia mandrillaris is a rare condition that is sometimes complicated by life-threatening CNS involvement. It often evades timely diagnosis due to its rarity and non-specific clinical manifestations. Patients can be either immunocompetent or immunocompromised. It is probably transmitted via inhalation or inoculation through broken skin, and then spreads to the brain and other organs through haematogenous spread. It is important for clinicians to be aware of this disease because rapid diagnosis and subsequent therapy has, in some cases, been associated with survival. In this Grand Round, we report the case of a 7-year-old boy who presented with large, chronic plaques on his face. Several biopsies showed non-specific granulomatous inflammation. The patient deteriorated rapidly and died within 1 month of displaying abnormal symptoms in the CNS. Immunohistochemical staining of skin tissue identified B mandrillaris as the infectious agent. The diagnosis was confirmed with PCR, which detected B mandrillaris DNA in formalin-fixed skin tissue sections. B mandrillaris infection should be considered in the differential diagnosis of patients with chronic granulomatous lesions. We also reviewed the epidemiology, B mandrillaris in nature and in the laboratory, clinical manifestations, histopathology, diagnosis, and treatment of infection.

Orexin and its receptors are involved in the mechanisms of pathological craving for alcohol and psychoactive drugs. The orexin system is also involved in the mechanisms of non-chemical forms of addiction: binge eating and gambling. The aim of this work was to study the level of orexin receptor mRNA in the hypothalamus, hippocampus, and prefrontal cortex of rats prone to impulsivity in behavior in a model for studying the elements of gambling addiction (a variant of the Iowa Gambling Task test). Brain structures were isolated on the 22nd day of the experiment. The expression of the OX1R gene was higher in the hypothalamus by 122% and in the hippocampus by 149% in rats that preferred to receive a high reward, but with a low probability as compared with a group of animals that preferred a low level of reinforcement, but with a 100% probability. In the prefrontal cortex, on the contrary, no significant changes were observed in the level of OX1R mRNA. The level of OX2R mRNA insignificantly changed in the hypothalamus, hippocampus, and prefrontal cortex of rats prone to impulsivity in behavior. The data indicate involvement of OX1R in the hypothalamus and hippocampus in mechanisms mediating impulsive behavior and the choice of the significance of positive reinforcement in terms of its varying strength and probability.Oreksin i ego retseptory vovlecheny v mekhanizmy patologicheskogo vlecheniia k alkogoliu i psikhoaktivnym veshchestvam. Sistema oreksina takzhe uchastvuet v mekhanizmakh nekhimicheskikh form zavisimosti — pishchevoĭ i igrovoĭ. Tsel'iu nastoiashchego issledovaniia bylo izuchenie urovnia mRNK retseptorov oreksina v gipotalamuse, gippokampe i prefrontal'noĭ kore mozga krys, sklonnykh k povyshennoĭ impul'sivnosti v povedenii, v modeli dlia izucheniia élementov igrovoĭ zavisimosti. Dlia étogo ispol'zovali variant metoda Iowa Gambling Task v trekhluchevom labirinte. Struktury mozga vydeliali na 22 den' éksperimenta. Ékspressiia gena oreksinovogo retseptora pervogo tipa (OX1R) byla vyshe v gipotalamuse na 122% i gippokampe — na 149% u krys, predpochitavshikh poluchat' vysokoe voznagrazhdenie, no s nizkoĭ doleĭ veroiatnosti po sravneniiu s gruppoĭ zhivotnykh, predpochitavshikh nizkiĭ uroven' podkrepleniia, no so 100% stepen'iu veroiatnosti. V prefrontal'noĭ kore, naprotiv, ne nabliudalos' dostovernykh izmeneniĭ v urovne mRNK OX1R. Pri issledovanii urovnia mRNK oreksinovogo retseptora vtorogo tipa (OX2R) dostovernykh izmeneniĭ u krys, sklonnykh k povyshennoĭ impul'sivnosti v povedenii, v gipotalamuse, gippokampe i prefrontal'noĭ kore otmecheno ne bylo. Dannye ukazyvaiut na vovlechennost' OX1R v gipotalamuse i gippokampe v mekhanizmy, oposreduiushchie impul'sivnoe povedenie i vybor zhivotnymi znachimosti polozhitel'nogo podkrepleniia v usloviiakh ego razlichnoĭ sily i veroiatnosti.