Cognitive Events Research Articles

Cognitive progression independent of relapse in multiple sclerosis

Background: Substantial physical-disability worsening in relapsing-remitting multiple sclerosis (RRMS) occurs outside of clinically recorded relapse. This phenomenon, termed progression independent of relapse activity (PIRA), is yet to be established for cognitive decline. Methods: Retrospective analysis of RRMS patients. Cognitive decline was defined using reliable-change-index cut-offs for each test (Symbol Digit Modalities Test, Brief Visuospatial Memory Test–Revised, California Verbal Learning Test–II). Decline was classified as PIRA if the following conditions were met: no relapse observed between assessments nor within 9 months of cognitive decline. Results: The study sample (n = 336) was 80.7% female with a mean (standard deviation (SD)) age, disease duration, and observation period of 43.1 (9.5), 10.8 (8.4), and 8.1 (3.1) years, respectively. A total of 169 (50.3%) subjects were cognitively impaired at baseline relative to age-, sex-, and education-matched HCs. Within subjects who experienced cognitive decline (n = 167), 89% experienced cognitive PIRA. A total of 141 (68.1%) cognitive decline events were observed independent of EDSS worsening. Cognitive PIRA was more likely to be observed with increased assessments (p < 0.001) and lower assessment density (p < 0.001), accounting for baseline clinical factors. Conclusion: These results establish the concept of cognitive PIRA and further our understanding of progressive cognitive decline in RRMS.

Association Between Statin Use and Dementia, and Related Mechanisms: A Bibliometric Analysis from 2007 to 2023.

Emerging evidence suggests the potential of hydroxymethylglutaryl-coenzyme A (HMG-CoA, statins) as a therapeutic option for dementia. The primary objective of this study is to assess the current state of research on statins use in dementia, with a focus on identifying pivotal questions within the field. A systemic search for publications on statin use in dementia between 2007 and 2023 was conducted, utilizing the Web of Science Core Collection. The scientific output was analyzed from various perspectives through VOSviewer, CiteSpace, and the bibliometrics website (https://bibliometric.com/). 560 articles authored by 2,977 individuals and 999 institutions across 58 countries were included, which were published in 295 periodicals and cited 21,176 references from 16,424 authors. The annual publication output remained steady, while the number of citations increased consistently. The U.S. and Mayo Clinic emerged as the most significant country and institution, respectively. B. McGuinness and D.L. Sparks were the most eminent authors. Journal of Alzheimer's Disease was the most influential journal. Three sets of keywords and the top 10 references were identified, suggesting pivotal questions within the field. While statins show promising potential as a treatment option for dementia, their use remains uncertain due to the reported short-term cognitive impairment events and questionable long-term protective effects against dementia. The pivotal question is to ascertain the association between statins and cognition. The mechanisms underlying the effects of statins on cognition are multifaceted. This study provides insights into the current status within the field of statin use in dementia.

Incorporating Individual-Level Treatment Effects and Outcome Preferences Into Personalized Blood Pressure Target Recommendations.

There are no shared decision-making frameworks for selecting blood pressure (BP) targets for individuals with hypertension. This study addressed whether results from the SPRINT (Systolic Blood Pressure Intervention Trial) could be tailored to individuals using predicted risks and simulated preferences. Among 8202 SPRINT participants, Cox models were developed and internally validated to predict each individual's absolute difference in risk from intensive versus standard BP lowering for cardiovascular events, cognitive impairment, death, and serious adverse events (AEs). Individual treatment effects were combined using simulated preference weights into a net benefit, which represents a weighted sum of risk differences across outcomes. Net benefits were compared among those above versus below the median AE risk. In simulations for which cardiovascular, cognitive, and death events had much greater weight than the AEs of BP lowering, the median net benefit was 3.3 percentage points (interquartile range [IQR], 2.0-5.7), and 100% of participants had a net benefit favoring intensive BP lowering. When simulating benefits and harms to have similar weights, the median net benefit was 0.8 percentage points (IQR, 0.2-2.2), and 87% had a positive net benefit. Compared with participants at lower risk of AEs from BP lowering, those at higher risk had a greater net benefit from intensive BP lowering despite experiencing more AEs (P<0.001 in both simulations). Most SPRINT participants had a predicted net benefit that favored intensive BP lowering, but the degree of net benefit varied considerably. Tailoring BP targets using each patient's risks and preferences may provide more refined BP target recommendations.

The impact of chronic kidney disease on cognitive function.

The risk of cognitive impairment is higher in people with CKD than in the general population. The complex relationship between CKD and cognitive dysfunction has not been extensively characterized. Here, we review epidemiological associations, specific patterns of CKD-related cognitive impairment, the underlying mechanisms, and recently published data on relevant biomarkers. Despite some discrepancies, recent published studies have confirmed that CKD is associated with cognitive function (e.g. incident cognitive events). Although patients with CKD often exhibit impairments in executive functions and attention, it is noteworthy that other cognitive functions (e.g. memory) can be preserved. The key mechanisms described recently include vascular damage, genetic factors, the accumulation of uremic toxins, disruption of the blood-brain barrier, glymphatic system dysfunction, and changes in the gut-brain axis. Kidney function is increasingly seen as a game changer in the interpretation of biomarkers of cognitive impairment and, especially, hallmarks of Alzheimer disease. The data reviewed here highlight the need for interdisciplinary collaboration between nephrologists and neurologists in the care of patients with CKD at risk of cognitive impairment. In order to further improving diagnosis and therapy, future research must elucidate the mechanisms underlying the CKD-cognitive impairment association and confirm the value of biomarkers.

Long-term neurocognitive effects of chimeric antigen receptor T-cell therapy: Integrating assessments into nursing practice.

Chimeric antigen receptor t-cell (CAR-T) therapy is a newly evolving therapy with well-known acute neurotoxic effects. While the long-term neurotoxic effects of this therapy are under-researched, they exist in subsets of the post-treatment population. Nurses can focus on assessments before and after CAR-T therapy to determine the degree to which these neurotoxic effects progress. These assessments include subjective and objective tools, as well as an understanding of risk factors associated with a higher degree of adverse cognitive events. By utilizing current research, hematological nurses can advocate for this unmet need to be monitored and intervened upon to improve patient outcomes.

Harnessing the frontal aslant tract’s structure to assess its involvement in cognitive functions: new insights from 7-T diffusion imaging

The first therapeutical goal followed by neurooncological surgeons dealing with prefrontal gliomas is attempting supramarginal tumor resection preserving relevant neurological function. Therefore, advanced knowledge of the frontal aslant tract (FAT) functional neuroanatomy in high-order cognitive domains beyond language and speech processing would help refine neurosurgeries, predicting possible relevant cognitive adverse events and maximizing the surgical efficacy. To this aim we performed the recently developed correlational tractography analyses to evaluate the possible relationship between FAT’s microstructural properties and cognitive functions in 27 healthy subjects having ultra-high-field (7-Tesla) diffusion MRI. We independently assessed FAT segments innervating the dorsolateral prefrontal cortices (dlPFC-FAT) and the supplementary motor area (SMA-FAT). FAT microstructural robustness, measured by the tract’s quantitative anisotropy (QA), was associated with a better performance in episodic memory, visuospatial orientation, cognitive processing speed and fluid intelligence but not sustained selective attention tests. Overall, the percentual tract volume showing an association between QA-index and improved cognitive scores (pQACV) was higher in the SMA-FAT compared to the dlPFC-FAT segment. This effect was right-lateralized for verbal episodic memory and fluid intelligence and bilateralized for visuospatial orientation and cognitive processing speed. Our results provide novel evidence for a functional specialization of the FAT beyond the known in language and speech processing, particularly its involvement in several higher-order cognitive domains. In light of these findings, further research should be encouraged to focus on neurocognitive deficits and their impact on patient outcomes after FAT damage, especially in the context of glioma surgery.

The domino effect of teacher cognitive presence triggering events and resolution on student’s grit

The aim of this current study is to assess the essential role of teacher cognitive presence within the context of the community of inquiry framework in relation to enhancing students’ academic perseverance, more specifically this type of presence influences the most students’ academic perseverance. In order to test this hypothesis, an online questionnaire was created, including the community of inquiry scale and the grit scale. A total of 529 valid and consented answers were collected. We have further analyzed the structure of the variables network with network analysis and then we have employed several sequential mediation analyses testing the impact of cognitive presence triggering events and resolution on the relationship between all the other presences and students’ academic perseverance. A circular structure has emerged in network analysis and eight significant full complementary sequential mediation analysis. Results confirm the domino effect of teacher cognitive presence triggering events and resolution on student’s grit under the community of inquiry framework.

Mimetic schemas in multimodal contact-establishing communication

Contact-establishing is deservedly characterized as the major function of communication. Until recently, it has been mostly subjected to linguistic analysis aimed at identifying its discursive markers. Meanwhile, contact-establishing frequently appears in gesturing. The current work develops a cognitive view to gesture and speech alignment, and addresses multimodal contact-establishing communication as mediated by mimetic schemas or bodily schemas shared by communicants who engage in face-to-face and body-to-body interaction. Based on a multimodal experiment where participants engage into task-oriented expository dialogue, we identified two most common contact-establishing recurrent gestures, palm-up-open-hand (PUOH) and palm-down-open-hand (PDOH) gestures contingent on two mimetic schemas, SHOW and RESTRAIN. In the study, we explore the distribution of these two schemas in their sub-schemas in gesture and speech. Following the participants’ contact-establishing PUOH and PDOH gestures (manifesting SHOW and RESTRAIN sub-schemas) and verbal cues (cognitive, pragmatic, and functional semantic dimensions), we determined the multimodal alignment patterns mediated by SHOWand RESTRAIN mimetic schemas in contactestablishing communication. Additionally, the clusters of PUOH and PDOH contactestablishing gestures were determined via their linguistic correspondences since they account for common thinking-for-speaking growth points and the language profiles of PUOH and PDOH contact-establishing gestures. The results allowed to scale the mimetic sub-schemas as manifesting event and referent features such as situatedness, embodiment, performativity, referent definiteness, referent foregrounding, reification, dynamicity, addressing, agentivity, referentiality. Overall, we established that in cognitive dimension non-situated events prevail in PUOH gestures while situated events prevail in PDOH gestures. In pragmatic dimension there is the difference in constativity in PUOH gestures and in performativity in PDOH gestures. In functional semantic dimension PDOH gestures commonly occur with acts, while PUOH gestures are more frequented with attributes. Additionally, we identified that within-cluster distance in PDOH gestures is more obvious than in PUOH gestures, which signifies that the typological differences (mediated indirectly by linguistic characteristics) in PDOH gestures are more distinct. The data obtained provide new evidence in multimodal contact-establishing communication.

The effects of omega-3, DHA, EPA, Souvenaid® in Alzheimer's disease: A systematic review and meta-analysis.

Alzheimer's disease (AD) is the most common cause of dementia worldwide. Omega-3 fatty acids (n-3-PUFA) are essential to normal neural development and function. Souvenaid®, a medical supplement that contains n-3-PUFA's: eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA), has emerged as an alternative, slowing cognitive decline in AD patients. In this study, we investigated the effect of dietary supplementation with n-3-PUFA, EPA, DHA, and Souvenaid® in AD patients. This systematic review and meta-analysis aim to establish the relationship between n-3-PUFA, EPA, DHA, and Souvenaid® with cognitive effects, ventricular volume and adverse events in AD patients. A systematic search of randomized control trials (RCT), cohorts, and case-control studies was done in PubMed, Scopus, Web of Science, Cochrane, and Embase for AD adult patients with dietary supplementation with n-3-PUFA, EPA, DHA, or Souvenaid® between 2003 and 2024. We identified 14 studies with 2766 subjects aligned with our criteria. Most publications described positive cognitive outcomes from supplements (58%). The most common adverse events reported were gastrointestinal symptoms. CDR scale showed reduced progression of cognitive decline (SMD = -0.4127, 95% CI: [-0.5926; -0.2327]), without subgroup differences between different dietary supplement interventions. ADCS-ADL, MMSE, ADAS-cog, adverse events, and ventricular volume did not demonstrate significant differences. However, Souvenaid® showed a significant negative effect (SMD = -0.3593, 95% CI: -0.5834 to -0.1352) in ventricular volumes. The CDR scale showed reduced progression of cognitive decline among patients with n-3-PUFA supplemental interventions, with no differences between different n-3-PUFA supplements.

Sleep, event appraisal, and affect: An ecological momentary assessment study

BackgroundAppraisal theory posits that emotions result from cognitive appraisals of events and situations. Experimental work suggests that sleep influences cognitive processes and event appraisal, which the present study examines in real life. Poor sleep influences brain regions involved in the appraisal-to-emotion process, and tired participants showed more conservative appraisal and reported less positive and more negative affect. In the present study, we tested whether sleep duration and/or quality predicted more pleasant event appraisal and whether sleep moderated the association between event appraisal and affect. MethodsParticipants (N = 892) from the general Dutch population reported thrice daily on event appraisal and various emotions for 30 days and once daily on sleep duration and quality. We constructed multilevel models to account for the nested structure of our data (observations within participants). ResultsMultilevel regression analyses showed that on days when participants reported having slept longer and better than their average, their event appraisal was more positive. Subjective sleep duration and quality did not influence the relationship between event appraisal and affect. Hence, poor sleep predicted changes in cognitive functioning, as people appraised situations as more unpleasant. LimitationsWe measured subjective sleep duration and quality with two single items and focused on only pleasantness dimension of event appraisal. ConclusionsResults match perspectives on emotions as multicomponent systems involving appraisal processes. Understanding the elements of event appraisal may help unravel the detrimental effects of poor sleep on mental health and well-being.

The presence of digital criticism in contemporary Arab monetary discourse; between the logic of proof and the question of value

The imposition of this virtual space makes sense in bringing creative pathways and spheres of criticism closer to the rest of both literature and critics, expanding opportunities to meet and learn about the new literary version and enabling those working in this field to demonstrate literary citizenship and poetry in these digital discourses; This new space was the world's pre-eminent cognitive and scientific event at the beginning of this century, given the ease of resource and taking in all applied processes or practices through hyperlinks and interactive pages that do not know the place and time, but the lesson in producing connectedness and making a digital vulture in these communicative spaces. This study monitors the presence of digital criticism in contemporary Arab monetary discourse by monitoring the reasons for engagement and addressing these digital literary models, in cash, reading and interpretation, and presenting them to readers' audiences through interactive media (electronic magazines, social media platforms), as well as following up on the methodological steps used to criticize digital Arab literary works. The most important cognitive returns and communication dimensions are described. This study concludes that this new critical experience is beginning to resonate in the Arab scientific and cultural arena by expanding the circles of communication and communication between Arab literature and critics, and by contributing to the formation of a worthy literary and critical movement.

Head Injury Treatment With Healthy and Advanced Dietary Supplements: A Pilot Randomized Controlled Trial of the Tolerability, Safety, and Efficacy of Branched Chain Amino Acids in the Treatment of Concussion in Adolescents and Young Adults.

Concussion is a common injury in the adolescent and young adult populations. Although branched chain amino acid (BCAA) supplementation has shown improvements in neurocognitive and sleep function in pre-clinical animal models of mild-to-moderate traumatic brain injury (TBI), to date, no studies have been performed evaluating the efficacy of BCAAs in concussed adolescents and young adults. The goal of this pilot trial was to determine the efficacy, tolerability, and safety of varied doses of oral BCAA supplementation in a group of concussed adolescents and young adults. The study was conducted as a pilot, double-blind, randomized controlled trial of participants ages 11-34 presenting with concussion to outpatient clinics (sports medicine and primary care), urgent care, and emergency departments of a tertiary care pediatric children's hospital and an urban tertiary care adult hospital, between June 24, 2014 and December 5, 2020. Participants were randomized to one of five study arms (placebo and 15 g, 30 g, 45 g, and 54 g BCAA treatment daily) and followed for 21 days after enrollment. Outcome measures included daily computerized neurocognitive tests (processing speed, the a priori primary outcome; and attention, visual learning, and working memory), symptom score, physical and cognitive activity, sleep/wake alterations, treatment compliance, and adverse events. In total, 42 participants were randomized, 38 of whom provided analyzable data. We found no difference in our primary outcome of processing speed between the arms; however, there was a significant reduction in total symptom score (decrease of 4.4 points on a 0-54 scale for every 500 g of study drug consumed, p value for trend = 0.0036, [uncorrected]) and return to physical activity (increase of 0.503 points on a 0-5 scale for every 500 g of study drug consumed, p value for trend = 0.005 [uncorrected]). There were no serious adverse events. Eight of 38 participants reported a mild (not interfering with daily activity) or moderate (limitation of daily activity) adverse event; there were no differences in adverse events by arm, with only two reported mild adverse events (both gastrointestinal) in the highest (45 g and 54 g) BCAA arms. Although limited by slow enrollment, small sample size, and missing data, this study provides the first demonstration of efficacy, as well as safety and tolerability, of BCAAs in concussed adolescents and young adults; specifically, a dose-response effect in reducing concussion symptoms and a return to baseline physical activity in those treated with higher total doses of BCAAs. These findings provide important preliminary data to inform a larger trial of BCAA therapy to expedite concussion recovery.

Machine Learning Classification of Event-Related Brain Potentials during a Visual Go/NoGo Task.

Machine learning (ML) methods are increasingly being applied to analyze biological signals. For example, ML methods have been successfully applied to the human electroencephalogram (EEG) to classify neural signals as pathological or non-pathological and to predict working memory performance in healthy and psychiatric patients. ML approaches can quickly process large volumes of data to reveal patterns that may be missed by humans. This study investigated the accuracy of ML methods at classifying the brain's electrical activity to cognitive events, i.e., event-related brain potentials (ERPs). ERPs are extracted from the ongoing EEG and represent electrical potentials in response to specific events. ERPs were evoked during a visual Go/NoGo task. The Go/NoGo task requires a button press on Go trials and response withholding on NoGo trials. NoGo trials elicit neural activity associated with inhibitory control processes. We compared the accuracy of six ML algorithms at classifying the ERPs associated with each trial type. The raw electrical signals were fed to all ML algorithms to build predictive models. The same raw data were then truncated in length and fitted to multiple dynamic state space models of order nx using a continuous-time subspace-based system identification algorithm. The 4nx numerator and denominator parameters of the transfer function of the state space model were then used as substitutes for the data. Dimensionality reduction simplifies classification, reduces noise, and may ultimately improve the predictive power of ML models. Our findings revealed that all ML methods correctly classified the electrical signal associated with each trial type with a high degree of accuracy, and accuracy remained high after parameterization was applied. We discuss the models and the usefulness of the parameterization.

Interleaved Propofol-Ketamine Maintains DBS Physiology and Hemodynamic Stability: A Double-Blind Randomized Controlled Trial.

The gold standard anesthesia for deep brain stimulation (DBS) surgery is the "awake" approach, using local anesthesia alone. Although it offers high-quality microelectrode recordings and therapeutic-window assessment, it potentially causes patients extreme stress and might result in suboptimal surgical outcomes. General anesthesia or deep sedation is an alternative, but may reduce physiological testing reliability and lead localization accuracy. The aim is to investigate a novel anesthesia regimen of ketamine-induced conscious sedation for the physiological testing phase of DBS surgery. Parkinson's patients undergoing subthalamic DBS surgery were randomly divided into experimental and control groups. During physiological testing, the groups received 0.25 mg/kg/h ketamine infusion and normal saline, respectively. Both groups had moderate propofol sedation before and after physiological testing. The primary outcome was recording quality. Secondary outcomes included hemodynamic stability, lead accuracy, motor and cognitive outcome, patient satisfaction, and adverse events. Thirty patients, 15 from each group, were included. Intraoperatively, the electrophysiological signature and lead localization were similar under ketamine and saline. Tremor amplitude was slightly lower under ketamine. Postoperatively, patients in the ketamine group reported significantly higher satisfaction with anesthesia. The improvement in Unified Parkinson's disease rating scale part-III was similar between the groups. No negative effects of ketamine on hemodynamic stability or cognition were reported perioperatively. Ketamine-induced conscious sedation provided high quality microelectrode recordings comparable with awake conditions. Additionally, it seems to allow superior patient satisfaction and hemodynamic stability, while maintaining similar post-operative outcomes. Therefore, it holds promise as a novel alternative anesthetic regimen for DBS. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Identification of key neuronal mechanisms triggered by dimethyl fumarate in SH-SY5Y human neuroblastoma cells through a metabolomic approach

Dimethyl fumarate (DMF) is an old drug used for psoriasis treatment that has recently been repurposed to treat relapse–remitting multiple sclerosis, mostly due to its neuro- and immunomodulatory actions. However, mining of a pharmacovigilance database recently ranked DMF as the second pharmaceutical most associated with cognitive adverse events. To our best knowledge, the signaling mechanisms underlying its therapeutic and neurotoxic outcomes remain mostly undisclosed. This work thus represents the first-hand assessment of DMF-induced metabolic changes in undifferentiated SH-SY5Y human neuroblastoma cells, through an untargeted metabolomic approach using gas chromatography–mass spectrometry (GC–MS). The endometabolome was analyzed following 24 h and 96 h of exposure to two pharmacologically relevant DMF concentrations (0.1 and 10 μM). None of these conditions significantly reduced metabolic activity (MTT reduction assay). Our data showed that 24 h-exposure to DMF at both concentrations tested mainly affected metabolic pathways involved in mitochondrial activity (e.g., citric acid cycle, de novo triacylglycerol biosynthesis), and the synthesis of catecholamines and serotonin by changing the levels of their respective precursors, namely phenylalanine (0.68-fold decrease for 10 μM DMF vs vehicle), and tryptophan (1.36-fold increase for 0.1 μM DMF vs vehicle). Interestingly, taurine, whose levels can be modulated via Nrf2 signaling (DMF’s primary target), emerged as a key mediator of DMF’s neuronal action, displaying a 3.86-fold increase and 0.27-fold decrease for 10 μM DMF at 24 h and 96 h, respectively. A 96 h-exposure to DMF seemed to mainly trigger pathways associated with glucose production (e.g., gluconeogenesis, glucose-alanine cycle, malate-aspartate shuttle), possibly related to the metabolism of DMF into monomethyl fumarate and its further conversion into glucose via activation of the citric acid cycle. Overall, our data contribute to improving the understanding of the events associated with neuronal exposure to DMF.

Guidelines for Seizure Prophylaxis in Adults Hospitalized with Moderate-Severe Traumatic Brain Injury: A Clinical Practice Guideline for Health Care Professionals from the Neurocritical Care Society.

There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASMs) in patients with moderate-severe traumatic brain injury (TBI). We conducted a systematic review and meta-analysis of articles assessing ASM prophylaxis in adults with moderate-severe TBI (acute radiographic findings and requiring hospitalization). The population, intervention, comparator, and outcome (PICO) questions were as follows: (1) Should ASM versus no ASM be used in patients with moderate-severe TBI and no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? (3) If an ASM is used, should a long versus short (> 7 vs. ≤ 7days) duration of prophylaxis be used? The main outcomes were early seizure, late seizure, adverse events, mortality, and functional outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to generate recommendations. The initial literature search yielded 1998 articles, of which 33 formed the basis of the recommendations: PICO 1: We did not detect any significant positive or negative effect of ASM compared to no ASM on the outcomes of early seizure, late seizure, adverse events, or mortality. PICO 2: We did not detect any significant positive or negative effect of PHT/fPHT compared to LEV for early seizures or mortality, though point estimates suggest fewer late seizures and fewer adverse events with LEV. PICO 3: There were no significant differences in early or late seizures with longer versus shorter ASM use, though cognitive outcomes and adverse events appear worse with protracted use. Based on GRADE criteria, we suggest that ASM or no ASM may be used in patients hospitalized with moderate-severe TBI (weak recommendation, low quality of evidence). If used, we suggest LEV over PHT/fPHT (weak recommendation, very low quality of evidence) for a short duration (≤ 7days, weak recommendation, low quality of evidence).

Osl-dynamics, a toolbox for modeling fast dynamic brain activity.

Neural activity contains rich spatiotemporal structure that corresponds to cognition. This includes oscillatory bursting and dynamic activity that span across networks of brain regions, all of which can occur on timescales of tens of milliseconds. While these processes can be accessed through brain recordings and imaging, modeling them presents methodological challenges due to their fast and transient nature. Furthermore, the exact timing and duration of interesting cognitive events are often a priori unknown. Here, we present the OHBA Software Library Dynamics Toolbox (osl-dynamics), a Python-based package that can identify and describe recurrent dynamics in functional neuroimaging data on timescales as fast as tens of milliseconds. At its core are machine learning generative models that are able to adapt to the data and learn the timing, as well as the spatial and spectral characteristics, of brain activity with few assumptions. osl-dynamics incorporates state-of-the-art approaches that can be, and have been, used to elucidate brain dynamics in a wide range of data types, including magneto/electroencephalography, functional magnetic resonance imaging, invasive local field potential recordings, and electrocorticography. It also provides novel summary measures of brain dynamics that can be used to inform our understanding of cognition, behavior, and disease. We hope osl-dynamics will further our understanding of brain function, through its ability to enhance the modeling of fast dynamic processes.

Cognitive and psychiatric adverse events during adjunctive cenobamate treatment in phase 2 and phase 3 clinical studies

ObjectiveCognitive and psychiatric adverse events in patients with epilepsy are important determinants of therapeutic outcomes and patient quality of life. We assessed the relationship between adjunctive cenobamate treatment and selected cognitive and psychiatric treatment-emergent adverse events (TEAEs) in adults with uncontrolled focal epilepsy. MethodsThis was a retrospective analysis of pooled populations of patients with focal epilepsy from two phase 2, randomized, double-blind clinical trials; two open-label extensions (OLEs) of those trials; and a long-term, open-label, phase 3 safety study. Occurrence of cognitive and psychiatric TEAEs in patients treated with adjunctive cenobamate or placebo during double-blind treatment were evaluated. Exposure-adjusted incidence rates of the cognitive and psychiatric TEAEs, defined as the number of TEAEs per patient-year of treatment, during up to 7 years of long-term adjunctive cenobamate treatment, were determined in the pooled OLE and phase 3 patient populations. ResultsThe pooled randomized trials resulted in a population of 442 patients treated with cenobamate (100 mg/day: n = 108; 200 mg/day: n = 223; 400 mg/day: n = 111) and 216 placebo-treated patients. The combined open-label studies resulted in pooled populations of cenobamate-treated patients ranging from n = 1690 during Year 1 to n = 103 during Year 7. Among cenobamate-treated (all doses) and placebo-treated patients during double-blind treatment, cognitive TEAEs were reported by ≤ 1.9 % (range, 0 %-1.9 %) and ≤ 0.5 % (range, 0 %-0.5 %), respectively, and psychiatric TEAEs by ≤ 3.6 % (range, 0 %-3.6 %) and ≤ 3.2 % (range, 0 %-3.2 %), respectively. During up to 7 years of open-label adjunctive cenobamate treatment, exposure-adjusted incidence rates of cognitive and psychiatric TEAEs were < 0.018 and < 0.038 events per patient-year, respectively. Discontinuation of adjunctive cenobamate due to cognitive or psychiatric TEAEs assessed in this study during double-blind or open-label treatment occurred in ≤ 0.3 % and ≤ 1.7 % of patients, respectively. ConclusionsCognitive and psychiatric TEAEs were reported by similar numbers of cenobamate- and placebo-treated patients during double-blind adjunctive cenobamate treatment (< 4 % of patients), and exposure-adjusted incidence rates of these TEAEs remained low during open-label cenobamate treatment for up to 7 years. Treatment discontinuations due to these TEAEs were rare. The results of this post-hoc analysis indicate that adjunctive cenobamate treatment exhibits a low incidence of cognitive or psychiatric TEAEs in patients with uncontrolled focal seizures.

Extraneous Load, Patient Census, and Patient Acuity Correlate With Cognitive Load During ICU Rounds

BackgroundCognitive Load Theory asserts that learning and performance degrade when cognitive load exceeds working memory capacity. This is particularly relevant in the learning environment of intensive care unit (ICU) rounds, when multidisciplinary providers integrate complex decision-making and teaching in a noisy, high-stress environment prone to cognitive distractions. Research QuestionWhat features of ICU rounds correlate with high provider cognitive load? Study Design and MethodsThis was an observational, multisite study of multidisciplinary providers during ICU rounds. Investigators recorded rounding characteristics and hourly extraneous cognitive load events during rounds (defined as distractions, episodes of split-attention or repetition, and deviations from standard communication format). Following rounds, investigators measured each provider’s cognitive load using the Provider Task Load (PTL), an instrument derived from the NASA Task Load Index survey that assesses perceived workload associated with complex tasks. Relationships between rounding characteristics, extraneous load, and PTL score were evaluated using mixed-effects modeling. Results76 providers were observed during 32 rounds from December 2020 – May 2021. The mean (±standard deviation) rounding census was 12.5±2.9 patients. The mean rounding time was 2h17m±49m. The mean extraneous load was 20.5±4.5 events per hour, or one event every 2m51sec. This included 8.6±3.4 distractions, 8.2±4.2 communication deviations, 1.9±1.4 repetitions, and 1.8±1.3 episodes of split-attention per hour. Controlling for covariates, the hourly extraneous load events, number of new patients, and number of higher acuity patients were each associated with increased PTL score (slope: 2.40 and 95% CI: 0.76 – 4.04, slope: 5.23 and 95% CI: 2.02 – 8.43, slope: 3.35 and 95% CI: 1.34 – 5.35, respectively). InterpretationIncreased extraneous load, new patients, and patient acuity were associated with higher cognitive load during ICU rounds. These results can help direct how the ICU rounding structure may be modified to reduce workload and optimize provider learning and performance.

Data-Driven Hypothesis Generation in Clinical Research: What We Learned from a Human Subject Study?

Hypothesis generation is an early and critical step in any hypothesis-driven clinical research project. Because it is not yet a well-understood cognitive process, the need to improve the process goes unrecognized. Without an impactful hypothesis, the significance of any research project can be questionable, regardless of the rigor or diligence applied in other steps of the study, e.g., study design, data collection, and result analysis. In this perspective article, the authors provide a literature review on the following topics first: scientific thinking, reasoning, medical reasoning, literature-based discovery, and a field study to explore scientific thinking and discovery. Over the years, scientific thinking has shown excellent progress in cognitive science and its applied areas: education, medicine, and biomedical research. However, a review of the literature reveals the lack of original studies on hypothesis generation in clinical research. The authors then summarize their first human participant study exploring data-driven hypothesis generation by clinical researchers in a simulated setting. The results indicate that a secondary data analytical tool, VIADS-a visual interactive analytic tool for filtering, summarizing, and visualizing large health data sets coded with hierarchical terminologies, can shorten the time participants need, on average, to generate a hypothesis and also requires fewer cognitive events to generate each hypothesis. As a counterpoint, this exploration also indicates that the quality ratings of the hypotheses thus generated carry significantly lower ratings for feasibility when applying VIADS. Despite its small scale, the study confirmed the feasibility of conducting a human participant study directly to explore the hypothesis generation process in clinical research. This study provides supporting evidence to conduct a larger-scale study with a specifically designed tool to facilitate the hypothesis-generation process among inexperienced clinical researchers. A larger study could provide generalizable evidence, which in turn can potentially improve clinical research productivity and overall clinical research enterprise.