Cortical sites critical to language function act as connectors between language subnetworks.

Historically, eloquent functions have been viewed as localized to focal areas of human cerebral cortex, while more recent studies suggest they are encoded by distributed networks. We examined the network properties of cortical sites defined by stimulation to be critical for speech and language, using electrocorticography from sixteen participants during word-reading. We discovered distinct network signatures for sites where stimulation caused speech arrest and language errors. Both demonstrated lower local and global connectivity, whereas sites causing language errors exhibited higher inter-community connectivity, identifying them as connectors between modules in the language network. We used machine learning to classify these site types with reasonably high accuracy, even across participants, suggesting that a site's pattern of connections within the task-activated language network helps determine its importance to function. These findings help to bridge the gap in our understanding of how focal cortical stimulation interacts with complex brain networks to elicit language deficits.

Virtual stimulation of the interictal EEG network localizes the EZ as a measure of cortical excitability.

Introduction: For patients with drug-resistant epilepsy, successful localization and surgical treatment of the epileptogenic zone (EZ) can bring seizure freedom. However, surgical success rates vary widely because there are currently no clinically validated biomarkers of the EZ. Highly epileptogenic regions often display increased levels of cortical excitability, which can be probed using single-pulse electrical stimulation (SPES), where brief pulses of electrical current are delivered to brain tissue. It has been shown that high-amplitude responses to SPES can localize EZ regions, indicating a decreased threshold of excitability. However, performing extensive SPES in the epilepsy monitoring unit (EMU) is time-consuming. Thus, we built patient-specific in silico dynamical network models from interictal intracranial EEG (iEEG) to test whether virtual stimulation could reveal information about the underlying network to identify highly excitable brain regions similar to physical stimulation of the brain. Methods: We performed virtual stimulation in 69 patients that were evaluated at five centers and assessed for clinical outcome 1 year post surgery. We further investigated differences in observed SPES iEEG responses of 14 patients stratified by surgical outcome. Results: Clinically-labeled EZ cortical regions exhibited higher excitability from virtual stimulation than non-EZ regions with most significant differences in successful patients and little difference in failure patients. These trends were also observed in responses to extensive SPES performed in the EMU. Finally, when excitability was used to predict whether a channel is in the EZ or not, the classifier achieved an accuracy of 91%. Discussion: This study demonstrates how excitability determined via virtual stimulation can capture valuable information about the EZ from interictal intracranial EEG.

Does exercise modality and posture influence cerebrovascular and cardiovascular systems similarly?

Cerebral hemodynamics have been quantified during exercise via transcranial Doppler ultrasound, as it has high-sensitivity to movement artifacts and displays temporal superiority. Currently, limited research exists regarding how different exercise modalities and postural changes impact the cerebrovasculature across the cardiac cycle. Ten participants (4 females and 6 males) ages 20-29 completed three exercise tests (treadmill, supine, and upright cycling) to volitional fatigue. Physiological data collected included middle cerebral artery velocity (MCAv), blood pressure (BP), heart rate, and respiratory parameters. Normalized data were analyzed for variance and effect sizes were calculated to examine differences between physiological measures across the three exercise modalities. Systolic MCAv was greater during treadmill compared to supine and upright cycling (p < 0.001, (large) effect size), and greater during upright versus supine cycling (p < 0.017, (large)). Diastolic MCAv was lower during treadmill versus cycling exercise only at 60% maximal effort (p < 0.005, (moderate)) and no differences were observed between upright and supine cycling. No main effect was found for mean and diastolic BP (p > 0.05, (negligible)). Systolic BP was lower during treadmill versus supine cycling at 40% and 60% intensity (p < 0.05, (moderate-large)) and greater during supine versus upright at only 60% intensity (p < 0.003, (moderate)). The above differences were not explained by partial pressure of end-tidal carbon dioxide levels (main effect: p = 0.432). The current study demonstrates the cerebrovascular and cardiovascular systems respond heterogeneously to different exercise modalities and aspects of the cardiac cycle. As physiological data were largely similar between tests, differences associated with posture and modality are likely contributors.

Implications of frailty before and after intensive care unit admission.

PURPOSE OF REVIEW: In the decade since the first publications related to frailty in those with critical illness, the study of frailty has rapidly increased. The purpose of this review is to update the reader on recent advances across several important areas of frailty research: how best to identify frailty in those with critical illness, studies describing the relationship between frailty and delirium, and how frailty affects outcomes for those with coronavirus disease 2019 (COVID-19), which, despite rates and severity of acute infection declining, still tremendously impacts patients long after the acute infection, resulting in symptoms of long COVID-19. RECENT FINDINGS: A number of frailty assessment tools exist, to date, the Clinical Frailty Scale based on the deficit accumulation approach to defining frailty, is the most commonly used in ICU studies. Several novel frailty instruments for the ICU are being developed. Because tools assessing frailty by the phenotypic and deficit accumulation approaches identify different populations, careful choice of a frailty assessment tool is warranted.Frailty and delirium are hypothesized to represent different clinical expressions of a similar underlying vulnerability, thus identifying frailty may be a useful means by which to identify patients at high risk of becoming delirious. Recent studies show that frailty at ICU admission is a predictor of the development of delirium.Finally, frailty and its outcomes were studied in patients with COVID-19. As with other causes of critical illness, frailty was highly prevalent in those admitted to the ICU and is associated with greater mortality. Frailty was also associated with increased decisions to limit life support treatments, but these decisions were not different among those admitted with COVID-19 or for other reasons. SUMMARY: Frailty in those with critical illness is an emerging field of study. Future work to define the optimal means by which to identify this syndrome and how best to manage critically ill patients with frailty are needed.

Gender Differences Regarding Palliative Care Consultation Among Persons Hospitalized With Heart Failure.

CONTEXT: Palliative care is increasingly recognized as an important aspect of heart failure (HF) management, but data on gender differences regarding palliative care needs are scarce. OBJECTIVE: We retrospectively studied patients hospitalized with a primary diagnosis of HF who received an initial palliative care consultation in the Mount Sinai Health System to examine gender differences. METHODS: From electronic health records, we extracted patient information, diagnostic codes, and the palliative care consult assessment which included the Karnofsky performance status (KPS) and the Edmonton symptom assessment scale (ESAS). The population was stratified according to self-identified gender. Unadjusted and adjusted generalized linear models were fitted to study the association of gender with KPS and ESAS scores. RESULTS: Among 667 patients with HF who received a palliative care consultation, 327 (49.0%) were women. Women with HF were older than men and less likely to be married. As compared to men, women had worse functional status, were less likely to have capacity to designate a surrogate medical decision-maker, had a higher symptom burden and were more likely to experience severe symptoms at the time of initial palliative care consultation. Differences in functional status and symptom burden were particularly pronounced in young women and women identifying as Black or Hispanic. The association of gender with functional status and symptom burden remained statistically significant after adjusting for possible confounders. CONCLUSION: As compared to men, women with HF were more severely impaired at the time of palliative care consult, and dedicated efforts to better address their needs are warranted.

Real-time monitoring of voltage-responsive biomolecular binding onto electro-switchable surfaces.

Voltage-responsive biosensors capable of monitoring real-time adsorption behavior of biological analytes onto electroactive surfaces offer attractive strategies for disease detection, separations, and other adsorption-dependent analytical techniques. Adsorption of biological analytes onto electrically switchable surfaces can be modelled using neutravidin and biotin. Here, we report self-assembled monolayers formed from voltage-switchable biotinylated molecules on gold surfaces with tunable sensitivity to neutravidin in response to applied voltages. By using electrochemical quartz crystal microbalance (EQCM), we demonstrated real-time switchable behavior of these bio-surfaces and investigate the range of sensitivity by varying the potential of the same surfaces from -400 mV to open circuit potential (+155 mV) to +300 mV. We compared the tunability of the mixed surfaces to bare Au surfaces, voltage inert surfaces, and switchable biotinylated surfaces. Our results indicate that quartz crystal microbalance allows real-time changes in analyte binding behavior, which enabled observing the evolution of neutravidin sensitivity as the applied voltage was shifted. EQCM could in principle be used in kinetic studies or to optimize voltage-switchable surfaces in adsorption-based diagnostics.

Network excitability of stimulation-induced spectral responses helps localize the seizure onset zone.

OBJECTIVE: While evoked potentials elicited by single pulse electrical stimulation (SPES) may assist seizure onset zone (SOZ) localization during intracranial EEG (iEEG) monitoring, induced high frequency activity has also shown promising utility. We aimed to predict SOZ sites using induced cortico-cortical spectral responses (CCSRs) as an index of excitability within epileptogenic networks. METHODS: SPES was conducted in 27 epilepsy patients undergoing iEEG monitoring and CCSRs were quantified by significant early (10-200 ms) increases in power from 10 to 250 Hz. Using response power as CCSR network connection strengths, graph centrality measures (metrics quantifying each site's influence within the network) were used to predict whether sites were within the SOZ. RESULTS: Across patients with successful surgical outcomes, greater CCSR centrality predicted SOZ sites and SOZ sites targeted for surgical treatment with median AUCs of 0.85 and 0.91, respectively. We found that the alignment between predicted and targeted SOZ sites predicted surgical outcome with an AUC of 0.79. CONCLUSIONS: These findings indicate that network analysis of CCSRs can be used to identify increased excitability of SOZ sites and discriminate important surgical targets within the SOZ. SIGNIFICANCE: CCSRs may supplement traditional passive iEEG monitoring in seizure localization, potentially reducing the need for recording numerous seizures.

Longevity of a Brain-Computer Interface for Amyotrophic Lateral Sclerosis.

The durability of communication with the use of brain-computer interfaces in persons with progressive neurodegenerative disease has not been extensively examined. We report on 7 years of independent at-home use of an implanted brain-computer interface for communication by a person with advanced amyotrophic lateral sclerosis (ALS), the inception of which was reported in 2016. The frequency of at-home use increased over time to compensate for gradual loss of control of an eye-gaze-tracking device, followed by a progressive decrease in use starting 6 years after implantation. At-home use ended when control of the brain-computer interface became unreliable. No signs of technical malfunction were found. Instead, the amplitude of neural signals declined, and computed tomographic imaging revealed progressive atrophy, which suggested that ALS-related neurodegeneration ultimately rendered the brain-computer interface ineffective after years of successful use, although alternative explanations are plausible. (Funded by the National Institute on Deafness and Other Communication Disorders and others; ClinicalTrials.gov number, NCT02224469.).

Healthcare Use and Expenditures in Rural Survivors of Hospitalization for Sepsis.

OBJECTIVES: Sepsis survivors have greater healthcare use than those surviving hospitalizations for other reasons, yet factors associated with greater healthcare use in this population remain ill-defined. Rural Americans are older, have more chronic illnesses, and face unique barriers to healthcare access, which could affect postsepsis healthcare use. Therefore, we compared healthcare use and expenditures among rural and urban sepsis survivors. We hypothesized that rural survivors would have greater healthcare use and expenditures. DESIGN, SETTING, AND PATIENTS: To test this hypothesis, we used data from 106,189 adult survivors of a sepsis hospitalization included in the IBM MarketScan Commercial Claims and Encounters database and Medicare Supplemental database between 2013 and 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified hospitalizations for severe sepsis and septic shock using the International Classification of Diseases, 9th Edition (ICD-9) or 1CD-10 codes. We used Metropolitan Statistical Area classifications to categorize rurality. We measured emergency department (ED) visits, inpatient hospitalizations, skilled nursing facility admissions, primary care visits, physical therapy visits, occupational therapy visits, and home healthcare visits for the year following sepsis hospitalizations. We calculated the total expenditures for each of these categories. We compared outcomes between rural and urban patients using multivariable regression and adjusted for covariates. After adjusting for age, sex, comorbidities, admission type, insurance type, U.S. Census Bureau region, employment status, and sepsis severity, those living in rural areas had 17% greater odds of having an ED visit (odds ratio [OR] 1.17; 95% CI, 1.13-1.22; p < 0.001), 9% lower odds of having a primary care visit (OR 0.91; 95% CI, 0.87-0.94; p < 0.001), and 12% lower odds of receiving home healthcare (OR 0.88; 95% CI, 0.84-0.93; p < 0.001). Despite higher levels of ED use and equivalent levels of hospital readmissions, expenditures in these areas were 14% (OR 0.86; 95% CI, 0.80-0.91; p < 0.001) and 9% (OR 0.91; 95% CI, 0.87-0.96; p < 0.001) lower among rural survivors, respectively, suggesting these services may be used for lower-acuity conditions. CONCLUSIONS: In this large cohort study, we report important differences in healthcare use and expenditures between rural and urban sepsis survivors. Future research and policy work is needed to understand how best to optimize sepsis survivorship across the urban-rural continuum.

Feasibility of superimposed supine cycling and lower body negative pressure as an effective means of prolonging exercise tolerance in individuals experiencing persisting post-concussive symptoms: Preliminary results.

To examine the feasibility, utility and safety of superimposed lower body negative pressure (LBNP) and tilt during supine cycling in individuals suffering from persisting post-concussive symptoms (PPCS). Eleven individuals aged 17-31 (6 females/5 males) participated in two randomized separate visits, 1 week apart. A ramp-incremental test was performed during both visits until volitional failure. Visits included no pressure (control) or LBNP at -40 Torr (experimental) with head-up tilt at 15 degrees (females) or 30 degrees (males). Transcranial Doppler ultrasound was utilized to quantify middle cerebral artery velocity (MCAv), while symptom reports were filled out before and 0, 10, and 60 min post-exertion. Ratings of exertion and overall condition followed similar trends for participants across both tests. The relative increase in MCAv was blunted during the experimental condition (8%) compared to control (24%), while a greater heart rate (17 beats/min) was achieved during the LBNP condition (P = 0.047). Symptom severity at the 0 and 10 min post-exertion time points displayed negligible-to-small effect sizes between conditions (Wilcoxon's r < 0.11). Symptom reporting was lower at the 60 min post-exertion time point with these displaying a moderate effect size (Wilcoxon's r = 0.31). The combination of LBNP and tilt during supine cycling did not change the participants' subjective interpretation of the exertional test but attenuated the hyperpnia-induced vasodilatory MCAv response, while also enabling participants to achieve a higher heart rate during exercise and reduced symptoms 1 h later. As this protocol is safe and feasible, further research is warranted in this area for developing PPCS treatment options. HIGHLIGHTS: What is the central question of this study? What are the feasibility, safety and utility of combining head-up tilt with lower body negative pressure during supine cycling for blunting the increase in cerebral blood velocity seen during moderate-intensity exercise in individuals experiencing persisting post-concussion symptoms? What is the main finding and its importance? Although no differences were found in symptoms between conditions within the first 10 min following exertion, symptom severity scores showed a clinically meaningful reduction 60 min following the experimental condition compared to the non-experimental control condition.

The Neurophysiological Effects of Craniosacral Treatment on Heart Rate Variability: A Systematic Review of Literature and Meta-Analysis.

Craniosacral treatment (CST) is an osteopathic technique grounded in the assumption that there is an intrinsic, fine movement of the cerebrospinal fluid. This rhythmic movement can be utilized for diagnostic and therapeutic purposes by palpation and manipulation of the skull, spine, and associated connective tissues. Therapeutic benefit is likely due to action on the autonomic nervous system (ANS), specifically through the vagus nerve. Current literature on the neurophysiological effects of CST is limited, which has contributed to controversy regarding its effectiveness. Heart rate variability (HRV) as a measure of cardiovascular stress and autonomic system activity is thus proposed as a tool to evaluate the neurophysiologic effects of CST. HRV can be analyzed in two different bands, high-frequency (HF) and low-frequency (LF) power associated with a parasympathetic and sympathetic response. In this meta-analysis, we provide a brief introduction to CST, analyze three primary studies, and summarize the therapeutic benefits and pitfalls of this alternative treatment on the ANS. A significant negative HF standardized mean difference after CST was observed; standardized mean difference = -0.46; 95% CI (-0.79,-0.14). No significant effect on LF power was observed. We conclude that CST does provide a moderate short-term increase in parasympathetic activity. These findings suggest that CST may be used to treat patients with an overactive sympathetic state. Further studies should be conducted for comparison against a control group to eliminate the possibility of a placebo effect and to elucidate long-term effects.

Multiplex genome editing eliminates the Warburg Effect without impacting growth rate in mammalian cells.

The Warburg effect is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production, as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production via knockout have failed in mammalian bioprocessing since lactate dehydrogenase has proven essential. However, here we eliminated the Warburg effect in Chinese hamster ovary (CHO) and HEK293 cells by simultaneously knocking out lactate dehydrogenase and regulators involved in a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA. In contrast to long-standing assumptions about the role of aerobic glycolysis, Warburg-null cells maintain wildtype growth rate while producing negligible lactate. Further characterization of Warburg-null CHO cells showed a compensatory increase in oxygen consumption, a near total reliance on oxidative metabolism, and higher cell densities in fed-batch cell culture. These cells remained amenable for production of diverse biotherapeutic proteins, reaching industrially relevant titers and maintaining product glycosylation. Thus, the ability to eliminate the Warburg effect is an important development for biotherapeutic production and provides a tool for investigating a near-universal metabolic phenomenon.

Increasing pitch count is associated with increasing elbow flexion angle at ball release in youth baseball pitchers.

BACKGROUND: Baseball is one of the most popular sports among youth athletes in the United States, and among these players, pitchers are at a particularly high risk of sustaining an injury. Overuse of the arm from repetitive pitching is a common mechanism for injury. Despite the attention that overuse injury has received, little is known regarding the mechanism that leads to elbow injury. This study aims to determine the effect of increasing pitch count on elbow flexion at ball release in a youth pitching cohort. The authors hypothesize that elbow flexion would increase as pitch count increases. METHODS: Study subjects included volunteers from youth baseball players from local teams and public advertisements. Retroreflective markers attached to bony landmarks were placed on the players according to International Shoulder Group recommendations. Pitchers threw an indoor simulated game. Three-dimensional marker trajectories were collected using a 12-camera optical motion capture system, and ball velocity was captured using a radar gun. Voluntary maximal isometric strength of the internal and external rotators was evaluated before and after pitching. Paired 2-tailed t tests were performed to determine if a significant change occurred between the fresh and fatigued sets. RESULTS: Twelve adolescent male pitchers were recruited. Eleven of 12 pitchers completed the prescribed 6 sets of 15 pitches, culminating in a 90-pitch simulated game. The ball speed in the second set was found to be the highest in all pitchers and was considered the "peak set" (P = .021), whereas ball speed was the slowest in the sixth set of pitches and was therefore considered the "fatigue set" (P = .001). There was a moderate but statistically significant inverse correlation between elbow flexion at ball release and maximum internal rotation velocity (P = .005). Elbow flexion at ball release was also significantly positively correlated with shoulder abduction at ball release (P = .004). Elbow flexion at ball release was not significantly correlated with ball velocity (P = .108). CONCLUSIONS: In a simulated game laboratory setting, increasing pitch count was associated with increasing elbow flexion angle at ball release in youth baseball pitchers. These findings demonstrate that pitching with fatigue may cause biomechanical changes that have been associated with increased rates of elbow injury in the adult throwing population. Further investigation on the association between elbow flexion angle and elbow injury in the youth baseball population is needed.

Multi-omic characterization of antibody-producing CHO cell lines elucidates metabolic reprogramming and nutrient uptake bottlenecks.

Characterizing the phenotypic diversity and metabolic capabilities of industrially relevant manufacturing cell lines is critical to bioprocess optimization and cell line development. Metabolic capabilities of production hosts limit nutrient and resource channeling into desired cellular processes and can have a profound impact on productivity. These limitations cannot be directly inferred from measured data such as spent media concentrations or transcriptomics. Here, we present an integrated multi-omic analysis pipeline combining exo-metabolomics, transcriptomics, and genome-scale metabolic network analysis and apply it to three antibody-producing Chinese Hamster Ovary cell lines to identify reprogramming features associated with high-producing clones and metabolic bottlenecks limiting product formation in an industrial bioprocess. Analysis of individual datatypes revealed a decreased nitrogenous byproduct secretion in high-producing clones and the topological changes in peripheral metabolic pathway expression associated with phase shifts. An integrated omics analysis in the context of the genome-scale metabolic model elucidated the differences in central metabolism and identified amino acid utilization bottlenecks limiting cell growth and antibody production that were not evident from exo-metabolomics or transcriptomics alone. Thus, we demonstrate the utility of a multi-omics characterization in providing an in-depth understanding of cellular metabolism, which is critical to efforts in cell engineering and bioprocess optimization.

Robot-related injuries in the workplace: An analysis of OSHA Severe Injury Reports.

Industrial robots are increasingly commonplace, but research on prototypical accidents and injuries has been sparse, hindering evidence-based safety strategies. Using Severe Injury Reports (SIRs) from the U.S. Occupational Safety and Health Administration (OSHA), we identified 77 robot-related accidents from 2015-2022. Of these, 54 involved stationary robots, resulting in 66 injuries, mainly finger amputations and fractures to the head and torso. Mobile robots caused 23 accidents, leading to 27 injuries, mainly fractures to the legs and feet. A two-stage deductive-inductive thematic analysis was performed using text data from the final narratives in the reports to discover patterns in tasks, precipitating mechanisms, and contributing factors. Findings highlight the need for guards and collision avoidance systems that detect individual extremities. Post-contact strategies should focus on mitigating finger amputations. More structured and detailed narratives in the SIRs are needed.

3D genomic analysis reveals novel enhancer-hijacking caused by complex structural alterations that drive oncogene overexpression.

Cancer genomes are composed of many complex structural alterations on chromosomes and extrachromosomal DNA (ecDNA), making it difficult to identify non-coding enhancer regions that are hijacked to activate oncogene expression. Here, we describe a 3D genomics-based analysis called HAPI (Highly Active Promoter Interactions) to characterize enhancer hijacking. HAPI analysis of HiChIP data from 34 cancer cell lines identified enhancer hijacking events that activate both known and potentially novel oncogenes such as MYC, CCND1, ETV1, CRKL, and ID4. Furthermore, we found enhancer hijacking among multiple oncogenes from different chromosomes, often including MYC, on the same complex amplicons such as ecDNA. We characterized a MYC-ERBB2 chimeric ecDNA, in which ERBB2 heavily hijacks MYC's enhancers. Notably, CRISPRi of the MYC promoter led to increased interaction of ERBB2 with MYC enhancers and elevated ERBB2 expression. Our HAPI analysis tool provides a robust strategy to detect enhancer hijacking and reveals novel insights into oncogene activation.

NREM sleep brain networks modulate cognitive recovery from sleep deprivation.

Decrease in cognitive performance after sleep deprivation followed by recovery after sleep suggests its key role, and especially non-rapid eye movement (NREM) sleep, in the maintenance of cognition. It remains unknown whether brain network reorganization in NREM sleep stages N2 and N3 can uniquely be mapped onto individual differences in cognitive performance after a recovery nap following sleep deprivation. Using resting state functional magnetic resonance imaging (fMRI), we quantified the integration and segregation of brain networks during NREM sleep stages N2 and N3 while participants took a 1-hour nap following 24-hour sleep deprivation, compared to well-rested wakefulness. Here, we advance a new analytic framework called the hierarchical segregation index (HSI) to quantify network segregation across spatial scales, from whole-brain to the voxel level, by identifying spatio-temporally overlapping large-scale networks and the corresponding voxel-to-region hierarchy. Our results show that network segregation increased in the default mode, dorsal attention and somatomotor networks during NREM sleep compared to wakefulness. Segregation within the visual, limbic, and executive control networks exhibited N2 versus N3 sleep-specific voxel-level patterns. More segregation during N3 was associated with worse recovery of working memory, executive attention, and psychomotor vigilance after the nap. The level of spatial resolution of network segregation varied among brain regions and was associated with the recovery of performance in distinct cognitive tasks. We demonstrated the sensitivity and reliability of voxel-level HSI to provide key insights into within-region variation, suggesting a mechanistic understanding of how NREM sleep replenishes cognition after sleep deprivation.

Genomic sequences of Mycobacterium smegmatis A cluster phages LBerry, Pembroke, and Zolita.

LBerry, Pembroke, and Zolita are newly isolated bacteriophages that infect Mycobacterium smegmatis mc²155. Based on gene content similarity, LBerry and Pembroke are assigned to cluster A3, and Zolita is assigned to cluster A5. LBerry and Pembroke are 99% identical to Anaysia and Caviar, and Zolita is 99% identical to SydNat.

Prospective multicenter study of continuous tonic-clonic seizure monitoring on Apple Watch in epilepsy monitoring units and ambulatory environments.

OBJECTIVE: Evaluate the performance of a custom application developed for tonic-clonic seizure (TCS) monitoring on a consumer-wearable (Apple Watch) device. METHODS: Participants with a history of convulsive epileptic seizures were recruited for either Epilepsy Monitoring Unit (EMU) or ambulatory (AMB) monitoring; participants without epilepsy (normal controls [NC]) were also enrolled in the AMB group. Both EMU and AMB participants wore an Apple Watch with a research app that continuously recorded accelerometer and photoplethysmography (PPG) signals, and ran a fixed-and-frozen tonic-clonic seizure detection algorithm during the testing period. This algorithm had been previously developed and validated using a separate training dataset. All EMU convulsive events were validated by video-electroencephalography (video-EEG); AMB events were validated by caregiver reporting and follow-ups. Device performance was characterized and compared to prior monitoring devices through sensitivity, false alarm rate (FAR; false-alarms per 24 h), precision, and detection delay (latency). RESULTS: The EMU group had 85 participants (4,279 h, 19 TCS from 15 participants) enrolled across four EMUs; the AMB group had 21 participants (13 outpatient, 8 NC, 6,735 h, 10 TCS from 3 participants). All but one AMB participant completed the study. Device performance in the EMU group included a sensitivity of 100 % [95 % confidence interval (CI) 79-100 %]; an FAR of 0.05 [0.02, 0.08] per 24 h; a precision of 68 % [48 %, 83 %]; and a latency of 32.07 s [standard deviation (std) 10.22 s]. The AMB group had a sensitivity of 100 % [66-100 %]; an FAR of 0.13 [0.08, 0.24] per 24 h; a precision of 22 % [11 %, 37 %]; and a latency of 37.38 s [13.24 s]. Notably, a single AMB participant was responsible for 8 of 31 false alarms. The AMB FAR excluding this participant was 0.10 [0.07, 0.14] per 24 h. DISCUSSION: This study demonstrates the practicability of TCS monitoring on a popular consumer wearable (Apple Watch) in daily use for people with epilepsy. The monitoring app had a high sensitivity and a substantially lower FAR than previously reported in both EMU and AMB environments.