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Recent research suggests that infection with Onchocerca volvulus induces neurocognitive decline. This study sought to compare the cognitive outcomes of elderly persons based on onchocerciasis infection status and report the overall prevalence of dementia in the rural Ntui Health District in Cameroon. A community-based approach was used to recruit 103 participants aged ≥60 years. Dementia screening was done using the Community Screening Interview for Dementia (CSID) tool with a cut-off value of ≤29.5. O. volvulus infection was determined via microscopic examination of skin snips and serological testing of Ov16 antibodies using rapid diagnostic tests. Overall, the prevalence of dementia was 10.7%. Among the tested individuals, 17.9% (15/84) and 62.1% (41/66) were positive for O. volvulus and Ov16 antibodies, respectively. A multivariable linear regression model of CSID scores found a significant positive association with education level (8.654; 95% CI: 2.0870 to 15.222). However, having a positive skin snip for O. volvulus (-3.399; 95% CI: -6.805 to 0.007) and inhaling tobacco (-5.441; 95% CI: -9.137 to -1.744) tended to lower the CSID scores. Ongoing onchocerciasis transmission in the Ntui Health District may constitute a risk factor for dementia. Strengthening onchocerciasis elimination and adopting healthier lifestyles would contribute to dementia prevention among the elderly residing in endemic communities.
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This cohort study of applicants to US MD-PhD programs examines the association of application outcomes with family income.
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Hospitalización , Humanos , Factores SocioeconómicosRESUMEN
A bidirectional communication exists between the brain and the gut, in which the gut microbiota influences cognitive function and vice-versa. Gut dysbiosis has been linked to several diseases, including Alzheimer's disease and related dementias (ADRD). However, the relationship between gut dysbiosis and markers of cerebral small vessel disease (cSVD), a major contributor to ADRD, is unknown. In this cross-sectional study, we examined the connection between the gut microbiome, cognitive, and neuroimaging markers of cSVD in the Framingham Heart Study (FHS). Markers of cSVD included white matter hyperintensities (WMH), peak width of skeletonized mean diffusivity (PSMD), and executive function (EF), estimated as the difference between the trail-making tests B and A. We included 972 FHS participants with MRI scans, neurocognitive measures, and stool samples and quantified the gut microbiota composition using 16S rRNA sequencing. We used multivariable association and differential abundance analyses adjusting for age, sex, BMI, and education level to estimate the association between gut microbiota and WMH, PSMD, and EF measures. Our results suggest an increased abundance of Pseudobutyrivibrio and Ruminococcus genera was associated with lower WMH and PSMD (p values < 0.001), as well as better executive function (p values < 0.01). In addition, in both differential and multivariable analyses, we found that the gram-negative bacterium Barnesiella intestinihominis was strongly associated with markers indicating a higher cSVD burden. Finally, functional analyses using PICRUSt implicated various KEGG pathways, including microbial quorum sensing, AMP/GMP-activated protein kinase, phenylpyruvate, and ß-hydroxybutyrate production previously associated with cognitive performance and dementia. Our study provides important insights into the association between the gut microbiome and cSVD, but further studies are needed to replicate the findings.
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Enfermedades de los Pequeños Vasos Cerebrales , Disbiosis , Humanos , Estudios Transversales , ARN Ribosómico 16S , Bacterias , Proteínas Quinasas Activadas por AMPRESUMEN
This cohort study analyzes the attrition rates of students from MD-PhD training programs by race and ethnicity.
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We investigated whether pharmacological increase of "M-type" (KCNQ, Kv7) K + channel currents by the M-channel opener, retigabine (RTG), acutely after repetitive traumatic brain injuries (rTBIs), prevents or reduces their long-term detrimental effects. rTBIs were studied using a blast shock air wave mouse model. Animals were monitored by video and electroencephalogram (EEG) records for nine months after the last injury to assess the occurrence of post-traumatic seizures (PTS), post-traumatic epilepsy (PTE), sleep-wake cycle architecture alterations, and the power of the EEG signals. We evaluated the development of long-term changes in the brain associated with various neurodegenerative diseases in mice by examining transactive response DNA-binding protein 43 (TDP-43) expression and nerve fiber damage ~ 2 years after the rTBIs. We observed acute RTG treatment to reduce the duration of PTS and impair the development of PTE. Acute RTG treatment also prevented post-injury hypersomnia, nerve fiber damage, and cortical TDP-43 accumulation and translocation from the nucleus to the cytoplasm. Mice that developed PTE displayed impaired rapid eye movement (REM) sleep, and there were significant correlations between seizure duration and time spent in the different stages of the sleep-wake cycle. We observed acute RTG treatment to impair injury-induced reduction of age-related increase in gamma frequency power of the EGG, which has been suggested to be necessary for a healthy aged brain. The data show that RTG, administered acutely post-TBI, is a promising, novel therapeutic option to blunt/prevent several long-term effects of rTBIs. Furthermore, our results show a direct relationship between sleep architecture and PTE.
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Lesiones Traumáticas del Encéfalo , Epilepsia Postraumática , Ratones , Animales , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Convulsiones/tratamiento farmacológico , Convulsiones/etiología , Carbamatos/farmacología , Carbamatos/uso terapéuticoRESUMEN
Importance: Diversity in the biomedical research workforce is essential for addressing complex health problems. Female investigators and investigators from underrepresented ethnic and racial groups generate novel, impactful, and innovative research, yet they are significantly underrepresented among National Institutes of Health (NIH) investigators. Objective: To examine the gender, ethnic, and racial distribution of super NIH investigators who received 3 or more concurrent NIH grants. Design, Setting, and Participants: This cross-sectional study included a national cohort of NIH-funded principal investigators (PIs) from the NIH Information for Management, Planning, Analysis, and Coordination (IMPAC II) database from 1991 to 2020. Exposures: Self-identified gender, race and ethnicity, annual number of NIH grant receipt, career stage, and highest degree. Main Outcomes and Measures: Distribution of investigators receiving 3 or more research project grants, referred to as super principal investigators (SPIs), by gender, race, and ethnicity. Results: Among 33â¯896 investigators in fiscal year 2020, 7478 (22.01%) identified as Asian, 623 (1.8%) as Black, 1624 (4.8%) as Hispanic, and 22â¯107 (65.2%) as White; 21â¯936 (61.7%) identified as men; and 8695 (35.3%) were early-stage investigators. Between 1991 and 2020, the proportion of SPIs increased 3-fold from 704 (3.7%) to 3942 (11.3%). However, SPI status was unequal across gender, ethnic, and racial groups. Women and Black PIs were significantly underrepresented among SPIs, even after adjusting for career stage and degree, and were 34% and 40% less likely than their male and White colleagues, respectively, to be an SPI. Black women PIs were the least likely to be represented among SPIs and were 71% less likely to attain SPI status than White men PIs (adjusted odds ratio, 0.29; 95% CI, 0.21-0.41). Conclusions and Relevance: In this cross-sectional study of a national cohort of NIH-funded investigators, the gender, ethnic, and racial gaps in receipt of multiple research project grants among NIH investigators was clearly apparent and warrants further investigation and interventions.
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Investigación Biomédica , Diversidad, Equidad e Inclusión , National Institutes of Health (U.S.) , Femenino , Humanos , Masculino , Asiático , Población Negra , Estudios Transversales , Estados UnidosRESUMEN
This cross-sectional study examines trends in number of awards and funding of general and diversity F31 predoctoral fellowships from 2001 to 2020.
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Investigación Biomédica , Becas , Estados Unidos , Humanos , National Institutes of Health (U.S.)RESUMEN
Importance: Diverse research teams are critical to solving complex health problems and producing high-quality medical research. Objective: To examine the associations of student sex and racial and ethnic identity with publication rates during medical school. Design, Setting, and Participants: This cohort study assessed individual-level data of US MD graduates from medical school who matriculated in academic years 2014 to 2015 and 2015 to 2016. Data were obtained from the Association of American Medical Colleges and analyzed from October 2021 to January 2022. Main Outcomes and Measures: Outcomes of interest included students' self-reported participation in unique research experiences, number of publications, and computed publications per research experience. Poisson regressions were constructed to determine the association of sex and racial and ethnic identity with research outcomes using adjusted rate ratios (aRRs). Results: Among 31â¯474 graduates, 15â¯159 (48.2%) identified as women and 4344 (13.8%) identified as underrepresented in medicine by race and ethnicity (URIM; including American Indian, Alaska Native, Black, Hawaiian Native, Hispanic/Latinx, and Pacific Islander individuals). Students who attended National Institutes of Health (NIH) top 40 research-ranked schools reported higher number of research experiences and publication counts, resulting in a higher publication rate compared with students from non-top 40 schools (median [IQR] 1.60 [1.00-3.00] vs 1.25 [0.50-2.33]; P < .001). Women reported a higher number of research experiences than men but a significantly lower number of publications (top 40 schools: aRR, 0.89; 95% CI, 0.87-0.90; non-top 40 schools: aRR, 0.93; 95% CI, 0.92-0.95). This resulted in a significantly lower publication rate among women (top 40 schools: aRR, 0.85; 95% CI, 0.83-0.86; non-top 40 schools: aRR, 0.91; 95% CI, 0.90-0.92). Compared with White students, Asian students had higher publication rates at both NIH top 40 schools (aRR, 1.10; 95% CI, 1.08-1.12) and non-top 40 schools (aRR, 1.07; 95% CI, 1.05-1.08), while lower publication rates were reported among Black students (top 40 schools: aRR, 0.83; 95% CI, 0.80-0.86; non-top 40 schools: aRR, 0.88; 95% CI, 0.85-0.95) and Hispanic students attending non-top 40 schools (aRR, 0.93; 95% CI, 0.90-0.95). Conclusions and Relevance: These findings illustrate that inequities in the physician-scientist workforce began early in training and highlight key areas for intervention, such as funding support and mentorship training during undergraduate medical education, that may promote the future success of a diverse physician-scientist workforce.
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Educación de Pregrado en Medicina , Facultades de Medicina , Masculino , Estados Unidos , Femenino , Humanos , Etnicidad , Estudios de Cohortes , National Institutes of Health (U.S.)RESUMEN
PURPOSE: To examine demographic characteristics of matriculants to U.S. MD-PhD programs by sex and race/ethnicity from academic years (AYs) 2009-2018 and explore the relationships between trends in the percentage of female and underrepresented minority (URM) matriculants to programs with and without Medical Scientist Training Program (MSTP) funding. METHOD: Linear regression and time trend analysis of the absolute percentage of matriculants into all U.S. MD-PhD programs was performed for self-reported sex and race/ethnicity, using Association of American Medical Colleges data for AYs 2009-2018, including an interaction for MSTP funding status (yes/no) and year. Linear regression of the percentage of programs matriculating no female or no URM students between AYs 2009 and 2018 was performed, focusing on programs in the top 3 quartiles by size (i.e., those matriculating 4 or more students per year). RESULTS: Between AYs 2009 and 2018, the percentage of matriculants to all MD-PhD programs who were female (38.0%-46.0%, 1.05%/year, P = .002) or URM (9.8%-16.7%, 0.77%/year, P < .001) increased. The annual percentage gains of URM matriculants were greater at MSTP-funded programs compared with non-MSTP-funded programs (0.50%/year, P = .046). Moreover, among MD-PhD programs in the top 3 quartiles by size, the percentage of programs with no female matriculants decreased by 0.40% per year ( P = .02) from 4.6% in 2009 to 1.6% in 2018, and the percentage of programs with no URM matriculants decreased by 3.41% per year ( P < .001) from 49% in 2009 to 22% in 2018. CONCLUSIONS: A consistent and sustained increase in the percentage of female and URM matriculants to MD-PhD programs from AYs 2009-2018 was observed, but the annual increases in the percentages across groups were small, and the demographics of the MD-PhD workforce still do not reflect the diversity of the U.S. general population.
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Etnicidad , Médicos , Humanos , Grupos Minoritarios , Estados Unidos , Recursos HumanosRESUMEN
BACKGROUND: Acceptance into U.S. MD-PhD dual-degree programs is highly competitive, and the lengthy training program requires transitioning between multiple phases (pre-clinical-, PhD-research-, and clinical-training phases), which can be stressful. Challenges faced during MD-PhD training could exacerbate self-doubt and anxiety. Impostor phenomenon is the experience of feeling like a fraud, with some high-achieving, competent individuals attributing their successes to luck or other factors rather than their own ability and hard work. To our knowledge, impostor phenomenon among MD-PhD trainees has not been described. This study examined impostor phenomenon experiences during MD-PhD training and reasons trainees attributed to these feelings. METHODS: Individuals in science and medicine fields participated in an online survey that included the 20-item Clance Impostor Phenomenon Scale (CIPS); higher scores (range 20-100) indicate more frequent impostor phenomenon. Some respondents who reported experiencing impostor phenomenon also voluntarily completed a semi-structured interview, sharing experiences during training that contributed to feelings of impostor phenomenon. Interview transcripts were coded and analysed using the constant comparative method and analytic induction to identify themes. RESULTS: Of 959 survey respondents (students and professionals in science and medicine), 13 MD-PhD students and residents completed the survey, nine of whom (five male, four female; four white, five other race-ethnicity) also completed an interview. These participants experienced moderate-to-intense scores on the CIPS (range: 46-96). Four themes emerged from the interview narratives that described participants' experiences of IP: professional identity formation, fear of evaluation, minority status, and, program-transition experiences. All reported struggling to develop a physician-scientist identity and lacking a sense of belonging in medicine or research. CONCLUSIONS: Impostor experiences that MD-PhD participants attributed to bias and micro-aggressions in social interactions with peers, faculty, and patients challenged their professional identity formation as physician-scientists. It is important to further examine how MD-PhD-program structures, cultures, and social interactions can lead to feelings of alienation and experiences of impostor phenomenon, particularly for students from diverse and underrepresented populations in medicine.
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Medicina , Médicos , Trastornos de Ansiedad , Femenino , Humanos , Masculino , Autoimagen , Estudiantes , Encuestas y CuestionariosRESUMEN
Traumatic brain injury (TBI) remains one of the greatest public health concerns with increasing morbidity and mortality rates worldwide. Our group reported that stimulation of astrocyte mitochondrial metabolism by P2Y1 receptor agonists significantly reduced cerebral edema and reactive gliosis in a TBI model. Subsequent data on the pharmacokinetics (PK) and rapid metabolism of these compounds suggested that neuroprotection was likely mediated by a metabolite, AST-004, which binding data indicated was an adenosine A3 receptor (A3R) agonist. The neuroprotective efficacy of AST-004 was tested in a control closed cortical injury (CCCI) model of TBI in mice. Twenty-four (24) hours post-injury, mice subjected to CCCI and treated with AST-004 (0.22 mg/kg, injected 30 min post-trauma) exhibited significantly less secondary brain injury. These effects were quantified with less cell death (PSVue794 fluorescence) and loss of blood brain barrier breakdown (Evans blue extravasation assay), compared to vehicle-treated TBI mice. TBI-treated mice also exhibited significantly reduced neuroinflammatory markers, glial-fibrillary acidic protein (GFAP, astrogliosis) and ionized Ca2+-binding adaptor molecule 1 (Iba1, microgliosis), both at the mRNA (qRT-PCR) and protein (Western blot and immunofluorescence) levels, respectively. Four (4) weeks post-injury, both male and female TBI mice presented a significant reduction in freezing behavior during contextual fear conditioning (after foot shock). AST-004 treatment prevented this TBI-induced impairment in male mice, but did not significantly affect impairment in female mice. Impairment of spatial memory, assessed 24 and 48 h after the initial fear conditioning, was also reduced in AST-004-treated TBI-male mice. Female TBI mice did not exhibit memory impairment 24 and 48 h after contextual fear conditioning and similarly, AST-004-treated female TBI mice were comparable to sham mice. Finally, AST-004 treatments were found to increase in vivo ATP production in astrocytes (GFAP-targeted luciferase activity), consistent with the proposed mechanism of action. These data reveal AST-004 as a novel A3R agonist that increases astrocyte energy production and enhances their neuroprotective efficacy after brain injury.
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Lesiones Traumáticas del Encéfalo , Fármacos Neuroprotectores , Adenosina/metabolismo , Adenosina/farmacología , Animales , Astrocitos/metabolismo , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/metabolismo , Modelos Animales de Enfermedad , Femenino , Gliosis/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Neuroprotección , Fármacos Neuroprotectores/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéuticoRESUMEN
BACKGROUND: This report highlights a rapidly progressive case of Creutzfeldt-Jakob Disease (CJD) whose time from symptom onset to death spanned less than two months. We also explore the most recently available in-patient demographics data for discharges with CJD in the United States. METHODS: We reviewed a CJD case and systematically analyzed a retrospective cohort of CJD discharges using the Healthcare Cost and Utilization Project (HCUP) to evaluate the existing national data on the status of CJD demographics and dispositions in the United States in 2016. RESULTS: An estimated total of 710 hospital discharges with a diagnosis of CJD were seen across the United States in 2016. According to HCUP, the average age of patients was 66.15⯱â¯11.54 years with 48.6 % female. Average time to intubation from admission to hospital was 4.71⯱â¯7.32 days with a rate of intubation of 6.34 %. The mean hospital cost was $19,901.25 ± $18,743.48. The rate of in-hospital mortality was 8.45 %. No significant geographical differences were noted (pâ¯=â¯0.49). No significant differences were seen among incidence in specific ethnic groups (pâ¯=â¯0.33) or income quartiles (pâ¯=â¯0.90). CONCLUSIONS: Our data shows that the incidence of CJD in 2016 appears to be equally distributed among individuals in the United States by demographic categories. Additionally, our case-study from 2019 illustrates an important example for diagnosing a rapidly-progressing case of CJD.
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Encéfalo/diagnóstico por imagen , Síndrome de Creutzfeldt-Jakob/epidemiología , Adolescente , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/diagnóstico por imagen , Progresión de la Enfermedad , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos/epidemiología , Adulto JovenRESUMEN
INTRODUCTION: Epilepsy affects about 1% of the world's population (over 50 million). Of these, one-third have refractory or medication-resistant epilepsy. This group of people drives the development and testing of new interventions for epilepsy. To better address the needs of people with epilepsy, the characteristics of clinical trials, as well as the gaps in the population of interest, need to be evaluated. METHODS: We searched the www.ClinicalTrials.gov database using the keywords "seizure" or "epilepsy" between 9/1/2008-9/1/2018 and filtering for Interventional Clinical trials. The data were categorized by three equal time intervals (tertiles), and evaluated by type of intervention (behavioral, diet, device, drug, other), primary purpose (treatment, diagnosis, prevention, or basic science), gender, age, phase (Phase1 to Phase 4 trials), length and status of the study, enrollment/recruitment/randomization, location, blinding status, assignment group (single/parallel/crossover/factorial/sequential), and funding. We focused on drugs and devices and used a binary logistic regression model to analyze the role of time, length of study, funding, location, randomization, and age. RESULTS: We found 359 epilepsy clinical trials; of these, 245 (68.2%) clinical trials involved drugs, and 55 (15.3%) were device trials. Over the three tertiles, the percentage of device trials increased while medication trials decreased. Device:drug trial odds ratios increased six times by the third tertile. Also, the results showed that clinical trials for drugs and devices occurred more in adults than children. Industry funding decreased 20% over time. The US contribution to clinical research was stable, but device trials were more likely to occur outside of the US. CONCLUSION: Drugs constitute the substantial fields of interventional trials in epilepsy but decreased in proportion over the last decade, while the presence of the device trials steadily increased. Device trials focused on treatment and diagnosis of seizures and have been more invested in non-US countries.
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Anticonvulsivantes/uso terapéutico , Epilepsia Refractaria/tratamiento farmacológico , Epilepsia/tratamiento farmacológico , Convulsiones/tratamiento farmacológico , Quimioterapia Combinada/métodos , Femenino , Humanos , Masculino , Calidad de VidaRESUMEN
Nearly three million people in the USA suffer traumatic brain injury (TBI) yearly; however, there are no pre- or post-TBI treatment options available. KCNQ2-5 voltage-gated K+ channels underlie the neuronal "M current", which plays a dominant role in the regulation of neuronal excitability. Our strategy towards prevention of TBI-induced brain damage is predicated on the suggested hyper-excitability of neurons induced by TBIs, and the decrease in neuronal excitation upon pharmacological augmentation of M/KCNQ K+ currents. Seizures are very common after a TBI, making further seizures and development of epilepsy disease more likely. Our hypothesis is that TBI-induced hyperexcitability and ischemia/hypoxia lead to metabolic stress, cell death and a maladaptive inflammatory response that causes further downstream morbidity. Using the mouse controlled closed-cortical impact blunt TBI model, we found that systemic administration of the prototype M-channel "opener", retigabine (RTG), 30 min after TBI, reduces the post-TBI cascade of events, including spontaneous seizures, enhanced susceptibility to chemo-convulsants, metabolic stress, inflammatory responses, blood-brain barrier breakdown, and cell death. This work suggests that acutely reducing neuronal excitability and energy demand via M-current enhancement may be a novel model of therapeutic intervention against post-TBI brain damage and dysfunction.
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Anticonvulsivantes/farmacología , Lesiones Traumáticas del Encéfalo/metabolismo , Carbamatos/farmacología , Canales de Potasio KCNQ/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fenilendiaminas/farmacología , Animales , Ratones , Ratones Endogámicos C57BLRESUMEN
Repetitive blast traumatic brain injury (TBI) affects numerous soldiers on the battlefield. Mild TBI has been shown to have long-lasting effects with repeated injury. We have investigated effects on neuronal excitability after repetitive, mild TBI in a mouse model of blast-induced brain injury. We exposed mice to mild blast trauma of an average peak overpressure of 14.6 psi, repeated across three consecutive days. While a single exposure did not reveal trauma as indicated by the glial fibrillary acidic protein indicator, three repetitive blasts did show significant increases. As well, mice had an increased indicator of inflammation (Iba-1) and increased tau, tau phosphorylation, and altered cytokine levels in the spleen. Video-electroencephalographic monitoring 48 h after the final blast exposure demonstrated seizures in 50% (12/24) of the mice, most of which were non-convulsive seizures. Long-term monitoring revealed that spontaneous seizures developed in at least 46% (6/13) of the mice. Patch clamp recording of dentate gyrus hippocampus neurons 48 h post-blast TBI demonstrated a shortened latency to the first spike and hyperpolarization of action potential threshold. We also found that evoked excitatory postsynaptic current amplitudes were significantly increased. These findings indicate that mild, repetitive blast exposures cause increases in neuronal excitability and seizures and eventual epilepsy development in some animals. The non-convulsive nature of the seizures suggests that subclinical seizures may occur in individuals experiencing even mild blast events, if repeated.
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Traumatismos por Explosión/fisiopatología , Lesiones Traumáticas del Encéfalo/fisiopatología , Neuronas/patología , Convulsiones/fisiopatología , Animales , Traumatismos por Explosión/complicaciones , Lesiones Traumáticas del Encéfalo/complicaciones , Modelos Animales de Enfermedad , Epilepsia Postraumática/etiología , Masculino , Ratones , Ratones Endogámicos C57BL , Convulsiones/etiologíaRESUMEN
PURPOSE: Advances in surface electromyography (sEMG) monitoring allow for long-term data collection in a natural environment, giving objective information that may identify risk of sudden unexpected death in epilepsy and guide clinical decision-making. Generalized tonic-clonic seizure semiology, namely motor tonic and clonic phase duration, may be an important factor in determining the level of seizure control and risk of sudden unexpected death in epilepsy. This study demonstrates a quantitative analysis of sEMG collected with a dedicated wearable device. METHODS: During routine monitoring, 23 generalized tonic-clonic seizures from 19 subjects were simultaneously recorded with video-EEG and sEMG. A continuous wavelet-transform was used to determine the frequency components of sEMG recorded during generalized tonic-clonic seizures. An automated process, incorporating a variant of cross-validation, was created to identify ideal frequencies and magnitude ranges for tonic and clonic phases and determine phase durations. Phase durations determined using sEMG analysis were compared with phase durations determined by independent epileptologists' review of video-EEG. RESULTS: Cross-validation revealed that the optimal frequency bands for tonic and clonic phases are 150 to 270 Hz and 12 to 70 Hz, respectively. The average difference in phase duration calculated using the two methods for tonic and clonic phases and total seizure duration were -0.42 ± 4.94, -5.12 ± 9.68, and -5.11 ± 11.33 seconds, respectively (results presented are TsEMG - TvEEG, µ ± σ). CONCLUSIONS: The automated processing of sEMG presented here accurately identified durations of tonic, clonic, and total motor durations of generalized tonic-clonic seizures similar to durations identified by epileptologists' review of video-EEG.
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Electromiografía/métodos , Convulsiones/fisiopatología , Procesamiento de Señales Asistido por Computador , Adulto , Algoritmos , Femenino , Humanos , MasculinoRESUMEN
Spontaneous ongoing neuronal activity is a prominent feature of the mammalian brain. Temporal and spatial patterns of such ongoing activity have been exploited to examine large-scale brain network organization and function. However, the neurophysiological basis of this spontaneous brain activity as detected by resting-state functional Magnetic Resonance Imaging (fMRI) remains poorly understood. To this end, multi-site local field potentials (LFP) and blood oxygenation level-dependent (BOLD) fMRI were simultaneously recorded in the rat striatum along with local pharmacological manipulation of striatal activity. Results demonstrate that delta (δ) band LFP power negatively, while beta (ß) and gamma (γ) band LFPs positively correlated with BOLD fluctuation. Furthermore, there was strong cross-frequency phase-amplitude coupling (PAC), with the phase of δ LFPs significantly modulating the amplitude of the high frequency signal. Enhancing dopaminergic neuronal activity significantly reduced ventral striatal functional connectivity, δ LFP-BOLD correlation, and the PAC effect. These data suggest that different frequency bands of the LFP contribute distinctively to BOLD spontaneous fluctuation and that PAC is the organizing mechanism through which low frequency LFPs orchestrate neural activity that underlies resting state functional connectivity.
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Ritmo Delta/fisiología , Imagen por Resonancia Magnética/métodos , Red Nerviosa/diagnóstico por imagen , Consumo de Oxígeno/fisiología , Descanso/fisiología , Estriado Ventral/diagnóstico por imagen , Animales , Masculino , Red Nerviosa/metabolismo , Ratas , Ratas Sprague-Dawley , Estriado Ventral/metabolismoRESUMEN
OBJECTIVE: There is a high cost associated with recording quality video and electroencephalography (EEG) data in National Association of Epilepsy Center (NAEC) level IV epilepsy monitoring units (EMU). This study considers potential quality measures in EMUs for generalized tonic-clonic (GTC) seizures: types of safety signals, response time, and visibility of patient's limbs for semiology. These quality measures have been summarized across 12 EMUs to estimate response times to GTC seizures and the quality of video data that is captured during admissions. METHODS: Video electroencephalographies (vEEGs) from two prospective regulatory studies for the Brain Sentinel device were reviewed. A total of 232 subjects with a history of GTC seizures underwent routine clinical EMU stays. Fifty-four of the study subjects had 96 GTC seizures. The vEEG of events were reviewed for safety signal used, response time, and visibility of patient's limbs. RESULTS: The average response time from members of the hospital team was 22â¯s from electrographic generalization (minimum -37â¯s, maximum 111â¯s, two no response). For caregivers, average response was 11â¯s (minimum -15â¯s, maximum 33â¯s, 45 not present/no response). In 73% of events, the patient visibility was limited at seizure onset. In 55% of events with limited limb visibility, the visibility was improved (by removing sheets or improving camera angle) >30â¯s after start of the event. The primary safety signals were as follows: an alert from outside the patient room (54%), button press (23%), hospital team present at seizure start (14%), caregiver vocal alert (6%), and no response (2%). SIGNIFICANCE: The average response time of caregivers was twice as fast as the hospital team, underscoring the importance of having a person in the room during onset of a GTC seizure. Diagnostic yield could be improved with more timely removal of patient coverings. It was observed that when patients experienced a GTC seizure, 40% were fully or partially obscured for more than 30â¯s during the event, compromising the ability of epileptologists to evaluate semiology during seizure onset. Automated seizure alarms may help staff get to patients more quickly and improve diagnostic characterization.
Asunto(s)
Cuidadores/estadística & datos numéricos , Electroencefalografía/normas , Epilepsia Tónico-Clónica/diagnóstico , Unidades Hospitalarias/estadística & datos numéricos , Monitoreo Fisiológico/estadística & datos numéricos , Seguridad del Paciente/normas , Convulsiones/diagnóstico , Adolescente , Adulto , Anciano , Niño , Preescolar , Electroencefalografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/normas , Estudios Prospectivos , Factores de Tiempo , Grabación en Video , Adulto JovenRESUMEN
BACKGROUND: fMRI blood oxygenation level-dependent (BOLD) signal has been widely used as a surrogate for neural activity. However, interpreting differences in BOLD fMRI based on underlying neuronal activity remains a challenge. Concurrent rsMRI data collection and electrophysiological recording in combination with microiontophoretically injected modulatory chemicals allows for improved understanding of the relationship between resting state BOLD and neuronal activity. NEW METHODS: Simultaneous fMRI, multi-channel intracortical electrophysiology and focal pharmacological manipulation data to be acquired longitudinally in rats for up to 2 months. Our artifact replacing technique is optimized for combined LFP and rsMRI data collection. RESULTS: Intracortical implantation of a multichannel microelectrode array resulted in minimal distortion and signal loss in fMRI images inside a 9.4T MRI scanner. rsMRI-induced electrophysiology artifacts were replaced using an in-house developed algorithm. Microinjection of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) enhanced dopaminergic neuronal activity in the ventral tegmental area (VTA) and altered LFP signal and fMRI functional connectivity in the striatum. COMPARISONS WITH EXISTING METHOD(S): Nanomanufacturing advances permit the production of MRI-compatible microelectrode arrays (with 16 or more channels), extending research beyond conventional methods limited to fewer channels. Our method permits longitudinal data collection of LFP and rsMRI and our algorithm effectively detects and replaces fMRI-induced electrophysiological noise, permitting rsMRI data collection concomitant with LFP recordings. CONCLUSIONS: Our model consists of longitudinal concurrent fMRI and multichannel intracortical electrophysiological recording during microinjection of pharmacological agents to modulate neural activity in the rat brain. We used commercial micro-electrodes and recording system and can be readily generalized to other labs.