Clinical Outcomes and Systemic Complications Related to the Severity and Etiology of Status Epilepticus Using a Common Data Model.

BACKGROUND: Status epilepticus (SE) is a critical neurological emergency in patients with neurological and nonneurological diseases. Mortality rises with SE severity. However, whether brain injury or systemic organ dysfunction causes death after SE remains unclear. We studied clinical outcomes and systemic dysfunctions associated with SE using standardized data from the common data model. This model includes clinical evaluations and treatments that provide real-world evidence for standard practice. METHODS: This retrospective cohort study used the common data model database of a single tertiary academic medical center. Patients diagnosed with SE (corresponding to G41 of the International Classification of Diseases 10 and administration of antiseizure medication) between January 1, 2001, and January 1, 2018, were enrolled. Demographics, classifications of SE severity, and outcomes were collected as operational definitions by using a common data model format. Systemic complications were defined based on the Sequential Organ Failure Assessment criteria. RESULTS: The electronic medical records of 1,825,196 patients were transformed into a common data model, and 410 patients were enrolled. The proportion of patients classified as having nonrefractory SE was 65.4% (268/410), followed by refractory (28.5%, 117/410) and super-refractory SE (6.1%, 25/410). Patients with more severe SE had longer intensive care unit and hospital stays. Renal dysfunction and thrombocytopenia were higher in the in-hospital death group (P = 0.002 and 0.003, respectively). In multivariable analysis, the Acute Physiology and Chronic Health Evaluation II score and platelet count were significantly different in the in-hospital death group (odds ratio, 1.169, P = 0.004; and 0.989, P = 0.043). CONCLUSIONS: Systemic complications after SE, especially low platelet counts, were linked to worse outcomes and increased mortality in a common data model. The common data model offers expandability and comprehensive analysis, making it a potentially valuable tool for SE research.

Embracing diversity and inclusivity in an academic setting: Insights from the Organization for Human Brain Mapping.

Scientific research aims to bring forward innovative ideas and constantly challenges existing knowledge structures and stereotypes. However, women, ethnic and cultural minorities, as well as individuals with disabilities, are systematically discriminated against or even excluded from promotions, publications, and general visibility. A more diverse workforce is more productive, and thus discrimination has a negative impact on science and the wider society, as well as on the education, careers, and well-being of individuals who are discriminated against. Moreover, the lack of diversity at scientific gatherings can lead to micro-aggressions or harassment, making such meetings unpleasant, or even unsafe environments for early career and underrepresented scientists. At the Organization for Human Brain Mapping (OHBM), we recognized the need for promoting underrepresented scientists and creating diverse role models in the field of neuroimaging. To foster this, the OHBM has created a Diversity and Inclusivity Committee (DIC). In this article, we review the composition and activities of the DIC that have promoted diversity within OHBM, in order to inspire other organizations to implement similar initiatives. Activities of the committee over the past four years have included (a) creating a code of conduct, (b) providing diversity and inclusivity education for OHBM members, (c) organizing interviews and symposia on diversity issues, and (d) organizing family-friendly activities and providing childcare grants during the OHBM annual meetings. We strongly believe that these activities have brought positive change within the wider OHBM community, improving inclusivity and fostering diversity while promoting rigorous, ground-breaking science. These positive changes could not have been so rapidly implemented without the enthusiastic support from the leadership, including OHBM Council and Program Committee, and the OHBM Special Interest Groups (SIGs), namely the Open Science, Student and Postdoc, and Brain-Art SIGs. Nevertheless, there remains ample room for improvement, in all areas, and even more so in the area of targeted attempts to increase inclusivity for women, individuals with disabilities, members of the LGBTQ+ community, racial/ethnic minorities, and individuals of lower socioeconomic status or from low and middle-income countries. Here, we present an overview of the DIC's composition, its activities, future directions and challenges. Our goal is to share our experiences with a wider audience to provide information to other organizations and institutions wishing to implement similar comprehensive diversity initiatives. We propose that scientific organizations can push the boundaries of scientific progress only by moving beyond existing power structures and by integrating principles of equity and inclusivity in their core values.

Mortality Risk within 14 Days after Coronavirus Disease 2019 Diagnosis in Dementia Patients: A Nationwide Analysis.

INTRODUCTION: The study evaluated the increased mortality risk within 14 days of coronavirus disease 2019 (COVID-19) diagnosis in dementia patients. METHODS: This retrospective study was conducted from February to April 2020 using the COVID-19 patients' database from the Korea Disease Control and Prevention Agency. The risk factors for early death within 14 days were determined using generalized logistic regression performed in a stepwise manner. Dementia patients diagnosed with COVID-19 were used for the study. The propensity score-matched cohort was included as controls. The differences in mortality within 14 days after COVID-19 diagnosis between the dementia patients and controls were evaluated. RESULTS: We enrolled 5,349 COVID-19 patients from the database; 224 had dementia as comorbidity. The mortality rate within 14 days after COVID-19 diagnosis in dementia patients and the controls was 23.7% versus 1.7%, respectively, before propensity score matching (PSM) (p < 0.001), and 23.7% versus 9.2% after PSM (p < 0.001). The hazard ratio (HR) for mortality within 14 days in COVID-19 patients with dementia was significant even after PSM (HR 5.104, 95% confidence interval 2.889-5.673, p < 0.001). The survival curve of dementia patients was steeply inclined within 14 days after COVID-19 diagnosis, resulting in 70.7% of all deaths in dementia patients. CONCLUSIONS: COVID-19 patients with dementia had a higher risk of early death within 14 days. Thus, prompt intervention is necessary for dementia patients after COVID-19 diagnosis.

Cerebral white matter abnormalities in patients with charcot-marie-tooth disease.

Here, we report the structural evidence of cerebral white matter abnormalities in Charcot-Marie-Tooth (CMT) patients and the relationship between these abnormalities and clinical disability. Brain diffusion tensor imaging (DTI) was performed in CMT patients with demyelinating (CMT1A/CMT1E), axonal (CMT2A/CMT2E), or intermediate (CMTX1/DI-CMT) peripheral neuropathy. Although all patients had normal brain magnetic resonance imaging, all genetic subgroups except CMT1A had abnormal DTI findings indicative of significant cerebral white matter abnormalities: decreased fractional anisotropy and axial diffusivity, and increased radial diffusivity. DTI abnormalities were correlated with clinical disability, suggesting that there is comorbidity of central nervous system damage with peripheral neuropathy in CMT patients. ANN NEUROL 2017;81:147-151.

Interactive effects of seizure frequency and lateralization on intratemporal effective connectivity in temporal lobe epilepsy.

OBJECTIVE: Patients with temporal lobe epilepsy (TLE) show brain connectivity changes in association with cognitive impairment. Seizure frequency and lateralization are 2 important clinical factors that characterize epileptic seizures. In this study, we sought to examine an interactive effect of the 2 seizure factors on intratemporal effective connectivity based on resting-state functional magnetic resonance imaging (rsfMRI) in patients with TLE. METHODS: For rsfMRI data acquired from 48 TLE patients and 45 healthy controls, we applied stochastic dynamical causal modeling to infer effective connectivity between 3 medial temporal lobe (MTL) regions, including the hippocampus (Hipp), parahippocampal gyrus (PHG), and amygdala (Amyg), ipsilateral to the seizure focus. We searched for the effect of the 2 seizure factors, seizure frequency (good vs poor seizure control) and lateralization (left vs right TLE), on connection strengths and their relationship with the level of verbal memory and language impairment. RESULTS: Impairment of verbal memory and language function was mainly affected by seizure lateralization, consistent with preferential involvement of the left MTL in verbal mnemonic processing. For the fully connected model, which was selected as the effective connectivity structure that best explained the observed rsfMRI time series, alterations in connection strengths were primarily influenced by seizure frequency; there was an increase in the strength of the Hipp to PHG connection in TLE patients with poor seizure control, whereas the strength of the Amyg to PHG connection increased in those with good seizure control. Furthermore, the association between connection strength alterations and cognitive impairment was interactively affected by both seizure frequency and lateralization. SIGNIFICANCE: These findings suggest an interactive effect as well as an individual effect of seizure frequency and lateralization on neuroimaging features and cognitive function. This potential interaction needs to be evaluated in the consideration of multiple seizure factors.

Comparison of levetiracetam and oxcarbazepine monotherapy among Korean patients with newly diagnosed focal epilepsy: A long-term, randomized, open-label trial.

This open-label, multicenter, randomized phase IV trial (NCT01498822) of noninferiority design compared the long-term effectiveness, safety, and tolerability of levetiracetam (LEV) monotherapy with those of oxcarbazepine (OXC) monotherapy in adults with newly diagnosed focal epilepsy. Korean patients (16-80 years), with ≥2 unprovoked focal seizures in the year preceding the trial, who had not taken any antiepileptic drugs (AEDs) in the last 6 months, were randomized to receive LEV or OXC (1:1). Effectiveness, safety, and tolerability were assessed over a 50-week period. Treatment failure rates (per protocol set) were 15/118 (12.7%) in the LEV-treated group and 30/128 (23.4%) in the OXC-treated group, an absolute difference of -10.7% (95% confidence interval [CI] -20.2, -1.2). Because the upper 95% CI limit was less than the pre-specified noninferiority margin of 15%, LEV was considered noninferior to OXC. Twenty-four-week and 48-week seizure freedom rates were 53.8% and 34.7% for LEV vs. 58.5% and 40.9% for OXC. Both LEV and OXC were well tolerated, with 8.7% and 8.6% of patients reporting serious treatment-emergent adverse events, respectively. By comparing LEV with OXC, another newer AED, LEV can be considered a useful option as initial monotherapy for patients with newly diagnosed focal epilepsy.

Seizure Control and Memory Impairment Are Related to Disrupted Brain Functional Integration in Temporal Lobe Epilepsy.

Brain functional integration can be disrupted in patients with temporal lobe epilepsy (TLE), but the clinical relevance of this disruption is not completely understood. The authors hypothesized that disrupted functional integration over brain regions remote from, as well as adjacent to, the seizure focus could be related to clinical severity in terms of seizure control and memory impairment. Using resting-state functional MRI data acquired from 48 TLE patients and 45 healthy controls, the authors mapped functional brain networks and assessed changes in a network parameter of brain functional integration, efficiency, to examine the distribution of disrupted functional integration within and between brain regions. The authors assessed whether the extent of altered efficiency was influenced by seizure control status and whether the degree of altered efficiency was associated with the severity of memory impairment. Alterations in the efficiency were observed primarily near the subcortical region ipsilateral to the seizure focus in TLE patients. The extent of regional involvement was greater in patients with poor seizure control: it reached the frontal, temporal, occipital, and insular cortices in TLE patients with poor seizure control, whereas it was limited to the limbic and parietal cortices in TLE patients with good seizure control. Furthermore, TLE patients with poor seizure control experienced more severe memory impairment, and this was associated with lower efficiency in the brain regions with altered efficiency. These findings indicate that the distribution of disrupted brain functional integration is clinically relevant, as it is associated with seizure control status and comorbid memory impairment.

Is obstructive sleep apnea associated with the presence of intracranial cerebral atherosclerosis?

PURPOSE: Intracranial cerebral atherosclerosis (ICAS) is one of critical atherosclerosis which closely related with stroke. Obstructive sleep apnea (OSA) is associated with systemic atherosclerosis, but it is unclear whether OSA is related with the presence of ICAS. We aimed to investigate the association between the presence of ICAS and severity of OSA in patients with suspected OSA. METHODS: This retrospective, cross-sectional study included 283 patients who suspected OSA (presence of one or more OSA-related symptom and high-risk category in Berlin questionnaire) and underwent polysomnography and brain magnetic resonance angiography (MRA). The ICAS was defined as ≥50% decrease of luminal diameter in MRA. The severity of OSA was defined by apnea-hypopnea index (AHI). RESULTS: The mean age was 60.7 ± 13.5 years, and 55.8% (158/283) were male in all included patients. The 53 (18.7%) patients had ICAS and 117 (41.3%) patients had moderate to severe OSA (AHI ≥ 15). Higher AHI was noted in patients with ICAS compared to those without ICAS (31.7 ± 25.8 versus 15.2 ± 17.4, p = 0.001). In multivariable logistic analyses, after adjusting for age, sex, and variables with p < 0.1 in univariable analyses (hypertension, diabetes mellitus, atrial fibrillation, previous stroke history, body mass index, lipid-lowing agents, arousal index, and minimum oxygen saturation), moderate to severe OSA were independently related with the presence of ICAS (odds ratio 4.17, 95% confidence interval 1.40-12.40, p = 0.010). CONCLUSIONS: Our findings suggest that moderate to severe OSA is associated with the presence of ICAS in patients with suspected OSA.

Neurological Complications Resulting from Non-Oral Occupational Methanol Poisoning.

Methanol poisoning results in neurological complications including visual disturbances, bilateral putaminal hemorrhagic necrosis, parkinsonism, cerebral edema, coma, or seizures. Almost all reported cases of methanol poisoning are caused by oral ingestion of methanol. However, recently there was an outbreak of methanol poisoning via non-oral exposure that resulted in severe neurological complications to a few workers at industrial sites in Korea. We present 3 patients who had severe neurological complications resulting from non-oral occupational methanol poisoning. Even though initial metabolic acidosis and mental changes were improved with hemodialysis, all of the 3 patients presented optic atrophy and ataxia or parkinsonism as neurological complications resulting from methanol poisoning. In order to manage it adequately, as well as to prevent it, physicians should recognize that methanol poisoning by non-oral exposure can cause neurologic complications.

Computational modeling of epileptiform activities in medial temporal lobe epilepsy combined with in vitro experiments.

In this paper, we propose a comprehensive computational model that is able to reproduce three epileptiform activities. The model targets a hippocampal formation that is known to be an important lesion in medial temporal lobe epilepsy. It consists of four sub-networks consisting of excitatory and inhibitory neurons and well-known signal pathways, with consideration of propagation delay. The three epileptiform activities involve fast and slow interictal discharge and ictal discharge, and those activities can be induced in vitro by application of 4-Aminopyridine in entorhinal cortex combined hippocampal slices. We model the three epileptiform activities upon previously reported biological mechanisms and verify the simulation results by comparing them with in vitro experimental data obtained using a microelectrode array. We use the results of Granger causality analysis of recorded data to set input gains of signal pathways in the model, so that the compatibility between the computational and experimental models can be improved. The proposed model can be expanded to evaluate the suppression effect of epileptiform activities due to new treatment methods.

Clinical predictors of seizure recurrence after the first post-ischemic stroke seizure.

BACKGROUND: The number of patients suffering post-stroke seizure after ischemic stroke (PSSi) is quite considerable, especially because ischemic stroke is more prevalent than hemorrhage in the general population. This study aimed to determine the predicting factors for seizure recurrence in ischemic stroke survivors and develop a clinical scoring system for the prediction of risks for seizure recurrence after the first PSSi. METHODS: We reviewed 3792 ischemic stroke patients who had admitted to Ewha Womans University hospital between 2001 and 2012. A total of 124 (3.3 %) patients who experienced PSSi were recruited (mean follow-up for 44.4 months). Medical records concerning the etiology, functional disability, seizure onset latency from stroke, type of seizure, electroencephalography (EEG), and neuroimaging findings were statistically analyzed to derive a seizure recurrence risk scoring system. RESULTS: Seizures recurred in 35.4 % (17/48) of early PSSi patients (≤1 week since stroke onset) and 48.7 % (37/76) of late PSSi (>1 week) patients. Atrial fibrillation, large sized, and cortical stroke lesion were more common in late onset PSSi compared to those in early onset PSSi (p < 0.05). Seizure recurrence tended to be more prevalent in early PSSi patients with male gender, atrial fibrillation or cortical stroke lesion, severe functional disability, and partial seizures. Seizure recurrence in late PSSi group was more common in patients of young age (≤65 years old), male gender, large lesion size, and partial seizure type. The validity of seizure recurrence risk score in the early PSSi group was better when evaluating based on gender, atrial fibrillation, cortical lesion, functional disability, and partial seizure type, with sensitivity of 70.6 % and specificity of 71.0 %. CONCLUSIONS: Our study characterized the high risk group for seizure recurrence in patients with the first PSSi. PSSi patients with high risk score of seizure recurrence had a greater chance of developing epilepsy later. Therefore, they should be considered for further treatment such as antiepileptic drug medication in clinical practice.

The effect of recurrent seizures on cognitive, behavioral, and quality-of-life outcomes after 12 months of monotherapy in adults with newly diagnosed or previously untreated partial epilepsy.

PURPOSE: The purpose of this study was to determine whether seizure recurrence has a negative impact on cognition, psychological function, and health-related quality of life (HRQoL) over a 12-month period of monotherapy in adults with newly diagnosed or previously untreated partial epilepsy. METHODS: Seizure freedom (SF) was defined as no seizure recurrence during the 40-week maintenance period of medication. Neuropsychological tests, the Symptom Checklist-90 (SCL-90), and the Quality of Life in Epilepsy-31 (QOLIE-31) were administered at baseline and after 48 weeks of carbamazepine or lamotrigine monotherapy. Seventy-three patients successfully continued treatment until the 48-week follow-up time point. Fifty patients (68.5%) had SF, and the remaining 23 were not seizure-free (NSF). A seizure outcome group-by-time interaction was analyzed using a linear mixed model. RESULTS: A group-by-time interaction was identified for the total QOLIE-31 score (p<0.05) and score on two QOLIE-31 subscales (social function: p<0.001 and seizure worry: p<0.001), with a significant improvement over time only present in the SF group (all p<0.001). There was no significant group-by-time interaction for most cognitive function tests, with the exception of the serial clustering score (p<0.01) and number of recognition hits on the California Verbal Learning Test (p<0.05). Serial clustering did not differ between the SF and NSF groups at baseline, but was significantly more used in the NSF group than in the SF group at 48 weeks (p<0.01). There was no significant group-by-time interaction for any dimension of the SCL-90. CONCLUSION: Recurrent seizures had a significant effect on HRQoL, a subtle effect on cognitive performance, and no effect on psychological symptoms over one year in newly diagnosed or previously untreated adults with partial epilepsy.

Retention Rates and Successful Treatment with Antiseizure Medications in Newly-Diagnosed Epilepsy Patients.

PURPOSE: Treatment for epilepsy primarily involves antiseizure medications (ASMs), which can be characterized using the clinical data warehouse (CDW) database. In this study, we compared retention rates and time to successful treatment for various ASMs to reflect both efficacy and adverse effects in patients with newly diagnosed epilepsy. MATERIALS AND METHODS: We identified newly diagnosed epilepsy patients with ASM treatment for more than 12 months using CDW of a tertiary referral hospital. Clinical characteristics were compared between groups with successful and unsuccessful treatment. Cox regression analysis was performed to evaluate independent variables of age, sex, comorbidities, and attributes of ASM regimens. RESULTS: Of 2515 eligible participants, 46.2% were successfully treated with the first ASM regimen, and 74.7% with all ASM regimens with the median time-to-treatment success of 14 months. Participants with second-generation ASM as the first ASM were more likely to be successfully treated with the first regimen compared to those with first-generation ASM (51.6% vs. 42.3%, p<0.001) and more successfully treated [hazard ratio (HR)=1.26; 95% confidence interval (CI): 1.15-1.39]. Overall, valproic acid was the most common ASM across a wide range of ages under 65 years, while levetiracetam in patients aged over 65 years or lamotrigine in female adult patients. Clinical factors associated with less favorable treatment outcomes included renal disease (HR=0.78; 95% CI: 0.66-0.92), liver disease (HR=0.65; 95% CI: 0.52-0.81), depression (HR=0.70; 95% CI: 0.57-0.84), and mechanical ventilation (HR=0.58; 95% CI: 0.50-0.67). CONCLUSION: Second-generation ASMs have the advantage of more successful treatment with fewer ASM regimen changes compared with first-generation drugs. Various comorbid conditions as well as age and sex should be considered when selecting ASMs.

Seizure localization using three-dimensional surface projections of intracranial EEG power.

Intracranial EEG (icEEG) provides a critical road map for epilepsy surgery but it has become increasingly difficult to interpret as technology has allowed the number of icEEG channels to grow. Borrowing methods from neuroimaging, we aimed to simplify data analysis and increase consistency between reviewers by using 3D surface projections of intracranial EEG poweR (3D-SPIER). We analyzed 139 seizures from 48 intractable epilepsy patients (28 temporal and 20 extratemporal) who had icEEG recordings, epilepsy surgery, and at least one year of post-surgical follow-up. We coregistered and plotted icEEG ß frequency band signal power over time onto MRI-based surface renderings for each patient, to create color 3D-SPIER movies. Two independent reviewers interpreted the icEEG data using visual analysis vs. 3D-SPIER, blinded to any clinical information. Overall agreement rates between 3D-SPIER and icEEG visual analysis or surgery were about 90% for side of seizure onset, 80% for lobe, and just under 80% for sublobar localization. These agreement rates were improved when flexible thresholds or frequency ranges were allowed for 3D-SPIER, especially for sublobar localization. Interestingly, agreement was better for patients with good surgical outcome than for patients with poor outcome. Localization using 3D-SPIER was measurably faster and considered qualitatively easier to interpret than visual analysis. These findings suggest that 3D-SPIER could be an improved diagnostic method for presurgical seizure localization in patients with intractable epilepsy and may also be useful for mapping normal brain function.

Chrysanthemum morifolium and Its Bioactive Substance Enhanced the Sleep Quality in Rodent Models via Cl- Channel Activation.

Dried Chrysanthemum morifolium (Chry) flowers have been used in Korea as a traditional insomnia treatment. In this study, the sleep-promoting activity and improving sleep quality of Chry extract (ext) and its active substance linarin were analyzed by pentobarbital-induced sleep experiment in mice and electroencephalography (EEG), electromyogram (EMG) analysis in rats. In a dose-dependent manner, Chry ext and linarin promoted longer sleep duration in the pentobarbital-induced sleep test compared to pentobarbital-only groups at both hypnotic and subhypnotic doses. Chry ext administration also significantly improved sleep quality, as seen in the relative power of low-frequency (delta) waves when compared with the control group. Linarin increased Cl- uptake in the SH-SY5Y human cell line and chloride influx was reduced by bicuculline. After administration of Chry ext, the hippocampus, frontal cortex, and hypothalamus from rodents were collected and blotted for glutamic acid decarboxylase (GAD)65/67 and gamma-aminobutyric acid (GABA)A receptors subunit expression levels. The expression of α1-subunits, ß2-subunits, and GAD65/67 of the GABAA receptor was modulated in the rodent brain. In conclusion, Chry ext augments pentobarbital-induced sleep duration and enhances sleep quality in EEG waves. These effects might be due to the activation of the Cl- channel.

Age-integrated artificial intelligence framework for sleep stage classification and obstructive sleep apnea screening.

Introduction: Sleep is an essential function to sustain a healthy life, and sleep dysfunction can cause various physical and mental issues. In particular, obstructive sleep apnea (OSA) is one of the most common sleep disorders and, if not treated in a timely manner, OSA can lead to critical problems such as hypertension or heart disease. Methods: The first crucial step in evaluating individuals' quality of sleep and diagnosing sleep disorders is to classify sleep stages using polysomnographic (PSG) data including electroencephalography (EEG). To date, such sleep stage scoring has been mainly performed manually via visual inspection by experts, which is not only a time-consuming and laborious process but also may yield subjective results. Therefore, we have developed a computational framework that enables automatic sleep stage classification utilizing the power spectral density (PSD) features of sleep EEG based on three different learning algorithms: support vector machine, k-nearest neighbors, and multilayer perceptron (MLP). In particular, we propose an integrated artificial intelligence (AI) framework to further inform the risk of OSA based on the characteristics in automatically scored sleep stages. Given the previous finding that the characteristics of sleep EEG differ by age group, we employed a strategy of training age-specific models (younger and older groups) and a general model and comparing their performance. Results: The performance of the younger age-specific group model was similar to that of the general model (and even higher than the general model at certain stages), but the performance of the older age-specific group model was rather low, suggesting that bias in individual variables, such as age bias, should be considered during model training. Our integrated model yielded an accuracy of 73% in sleep stage classification and 73% in OSA screening when MLP algorithm was applied, which indicates that patients with OSA could be screened with the corresponding accuracy level only with sleep EEG without respiration-related measures. Discussion: The current outcomes demonstrate the feasibility of AI-based computational studies that when combined with advances in wearable devices and relevant technologies could contribute to personalized medicine by not only assessing an individuals' sleep status conveniently at home but also by alerting them to the risk of sleep disorders and enabling early intervention.

Machine Learning-assisted Quantitative Mapping of Intracortical Axonal Plasticity Following a Focal Cortical Stroke in Rodents.

Stroke destroys neurons and their connections leading to focal neurological deficits. Although limited, many patients exhibit a certain degree of spontaneous functional recovery. Structural remodeling of the intracortical axonal connections is implicated in the reorganization of cortical motor representation maps, which is considered to be an underlying mechanism of the improvement in motor function. Therefore, an accurate assessment of intracortical axonal plasticity would be necessary to develop strategies to facilitate functional recovery following a stroke. The present study developed a machine learning-assisted image analysis tool based on multi-voxel pattern analysis in fMRI imaging. Intracortical axons originating from the rostral forelimb area (RFA) were anterogradely traced using biotinylated dextran amine (BDA) following a photothrombotic stroke in the mouse motor cortex. BDA-traced axons were visualized in tangentially sectioned cortical tissues, digitally marked, and converted to pixelated axon density maps. Application of the machine learning algorithm enabled sensitive comparison of the quantitative differences and the precise spatial mapping of the post-stroke axonal reorganization even in the regions with dense axonal projections. Using this method, we observed a substantial extent of the axonal sprouting from the RFA to the premotor cortex and the peri-infarct region caudal to the RFA. Therefore, the machine learningassisted quantitative axonal mapping developed in this study can be utilized to discover intracortical axonal plasticity that may mediate functional restoration following stroke.

Earlier chronotype in midlife as a predictor of accelerated brain aging: a population-based longitudinal cohort study.

STUDY OBJECTIVES: Evidence suggests that sleep-wake cycle disruption could be an early manifestation of neurodegeneration and might even be a risk factor for developing diseases in healthy adults. We investigated the impact of circadian phase change on structural and functional brain deterioration in a late-adulthood population. METHODS: We analyzed the data of 1874 participants (mean age 58.6 ± 6.3 years, 50.3% female) from the Korean Genome and Epidemiology Study, who were identified as cognitively unimpaired. The mid-sleep time on free days corrected for sleep debt on workdays (MSFsc) at baseline was adopted as an indicator of the chronotype and used to categorize the participants into three groups. The relationships between the chronotype and longitudinal changes in the gray matter volume (GMV) and cognitive function were investigated (mean interval: 4.2 ± 0.5 years). RESULTS: The mean MSFsc of the participants was 2:45 am. The earlier MSFsc was linearly associated with smaller right entorhinal GMV (ß [SE] = 0.02 [0.01]; p = .001) and lower visual memory function test scores at baseline. Longitudinally, the earlier MSFsc at baseline was only significantly associated with more rapid atrophy in the temporal lobe (ß [SE] = 0.18 [0.07]; p = .018) and not with other brain lobes or subregions. Moreover, the earlier MSFsc was associated with more deteriorated verbal learning and visual memory function test scores. CONCLUSIONS: An earlier chronotype in midlife, measured using a questionnaire, can be a valuable indicator for individuals who should be closely monitored for the development of neurodegenerative disorders.

Impaired consciousness in epilepsy investigated by a prospective responsiveness in epilepsy scale (RES).

PURPOSE: Impaired consciousness in epileptic seizures has a major negative impact on patient quality of life. Prior work on epileptic unconsciousness has mainly used retrospective and nonstandardized methods. Our goal was to validate and to obtain initial data using a standardized prospective testing battery. METHODS: The responsiveness in epilepsy scale (RES) was used on 52 patients during continuous video-electroencephalography (EEG) monitoring. RES begins with higher-level questions and commands, and switches adaptively to more basic sensorimotor responses depending on patient performance. RES continues after seizures and includes postictal memory testing. Scoring was conducted based on video review. KEY FINDINGS: Testing on standardized seizure simulations yielded good intrarater and interrater reliability. We captured 59 seizures from 18 patients (35% of participants) during 1,420 h of RES monitoring. RES impairment was greatest during and after tonic-clonic seizures, less in partial seizures, and minimal in auras and subclinical seizures. In partial seizures, ictal RES impairment was significantly greater if EEG changes were present. Maximum RES impairment (lowest ictal score) was also significantly correlated with long postictal recovery time, and poor postictal memory. SIGNIFICANCE: We found that prospective testing of responsiveness during seizures is feasible and reliable. RES impairment was related to EEG changes during seizures, as well as to postictal memory deficits and recovery time. With a larger patient sample it is hoped that this approach can identify brain networks underlying specific components of impaired consciousness in seizures. This may allow the development of improved treatments targeted at preventing dysfunction in these networks.