A complete pedigree-based graph workflow for rare candidate variant analysis.

Methods that use a linear genome reference for genome sequencing data analysis are reference-biased. In the field of clinical genetics for rare diseases, a resulting reduction in genotyping accuracy in some regions has likely prevented the resolution of some cases. Pangenome graphs embed population variation into a reference structure. Although pangenome graphs have helped to reduce reference mapping bias, further performance improvements are possible. We introduce VG-Pedigree, a pedigree-aware workflow based on the pangenome-mapping tool of Giraffe and the variant calling tool DeepTrio using a specially trained model for Giraffe-based alignments. We demonstrate mapping and variant calling improvements in both single-nucleotide variants (SNVs) and insertion and deletion (indel) variants over those produced by alignments created using BWA-MEM to a linear-reference and Giraffe mapping to a pangenome graph containing data from the 1000 Genomes Project. We have also adapted and upgraded deleterious-variant (DV) detecting methods and programs into a streamlined workflow. We used these workflows in combination to detect small lists of candidate DVs among 15 family quartets and quintets of the Undiagnosed Diseases Program (UDP). All candidate DVs that were previously diagnosed using the Mendelian models covered by the previously published methods were recapitulated by these workflows. The results of these experiments indicate that a slightly greater absolute count of DVs are detected in the proband population than in their matched unaffected siblings.

Multicenter Study of Long-Term Outcomes and Quality of Life in PHACE Syndrome after Age 10.

OBJECTIVE: To characterize long-term outcomes of PHACE syndrome. STUDY DESIGN: Multicenter study with cross-sectional interviews and chart review of individuals with definite PHACE syndrome ≥10 years of age. Data from charts were collected across multiple PHACE-related topics. Data not available in charts were collected from patients directly. Likert scales were used to assess the impact of specific findings. Patient-Reported Outcomes Measurement Information System (PROMIS) scales were used to assess quality of life domains. RESULTS: A total of 104/153 (68%) individuals contacted participated in the study at a median of 14 years of age (range 10-77 years). There were infantile hemangioma (IH) residua in 94.1%. Approximately one-half had received laser treatment for residual IH, and the majority (89.5%) of participants were satisfied or very satisfied with the appearance. Neurocognitive manifestations were common including headaches/migraines (72.1%), participant-reported learning differences (45.1%), and need for individualized education plans (39.4%). Cerebrovascular arteriopathy was present in 91.3%, with progression identified in 20/68 (29.4%) of those with available follow-up imaging reports. Among these, 6/68 (8.8%) developed moyamoya vasculopathy or progressive stenoocclusion, leading to isolated circulation at or above the level of the circle of Willis. Despite the prevalence of cerebrovascular arteriopathy, the proportion of those with ischemic stroke was low (2/104; 1.9%). PROMIS global health scores were lower than population norms by at least 1 SD. CONCLUSIONS: PHACE syndrome is associated with long-term, mild to severe morbidities including IH residua, headaches, learning differences, and progressive arteriopathy. Primary and specialty follow-up care is critical for PHACE patients into adulthood.

Hidradenitis suppurativa disease control associated with type of hormonal contraceptive use.

Hidradenitis suppurativa (HS) is a painful chronic skin condition of apocrine gland regions. This retrospective cohort study aimed to assess the impact of hormonal contraception type on HS disease control in adult women. In total, 160 patients were included, with the majority identifying as Black or African American (73.1%). Multivariate logistic regression showed that oestrogen-progesterone users were 3.14 times more likely to experience stable or improved HS than progesterone-only users (adjusted odds ratio 3.14, 95% CI 1.18-8.35; P = 0.02). Further investigation is needed to elucidate the antiandrogenic mechanisms affecting HS symptom response to hormonal contraceptives.

Regimen for accelerated propranolol initial dosing (RAPID).

BACKGROUND: Infantile hemangiomas are common vascular tumors in children. Propranolol has proven effective in treating infantile hemangiomas and while generally safe, has potential risk for more serious side effects of hypoglycemia, hypotension, bradycardia, bronchospasm, and cardiovascular or respiratory compromise. Current prescribing guidelines recommend initiating propranolol doses at 1 mg/kg/day, with up-titration to 2 mg/kg/day. This study aims to compare the incidence of adverse events in infants and children treated with propranolol initiated at 1 mg/kg/day versus being initiated directly at 2 mg/kg/day. METHODS: A retrospective cohort study was conducted using medical records of patients receiving propranolol therapy for infantile hemangiomas between October 2018-March 2021 at the Children's Hospital of Philadelphia. Patients were categorized by initial propranolol dosage: 1 or 2 mg/kg/day. The primary outcome measures included parent-reported adverse events, hypotension (defined by the Pediatric Advanced Life Support criteria), and bradycardia (defined as <1st percentile for age) following propranolol initiation. RESULTS: Out of the 244 patients identified, 123 were initiated at the 1 mg/kg/day dose, and 121 at the 2 mg/kg/day dose. There was no significant difference in the incidence of adverse events between the two groups (p = .057). Additionally, among patients initiated at 2 mg/kg/day, there were no significant differences in the incidence of age-related or weight-related adverse events for those younger than 2 months or those in the 1st or 2nd quartile for weight (p = .53). CONCLUSION: Infants and children initiated at 2 mg/kg/day did not demonstrate an increased incidence of adverse events associated with propranolol compared to those initiated at 1 mg/kg/day. These findings provide clinical evidence for the practice of accelerated propranolol initiation dosing.

Pediatric dermatologists versus AI bots: Evaluating the medical knowledge and diagnostic capabilities of ChatGPT.

This study evaluates the clinical accuracy of OpenAI's ChatGPT in pediatric dermatology by comparing its responses on multiple-choice and case-based questions to those of pediatric dermatologists. ChatGPT's versions 3.5 and 4.0 were tested against questions from the American Board of Dermatology and the "Photoquiz" section of Pediatric Dermatology. Results show that human pediatric dermatology clinicians generally outperformed both ChatGPT iterations, though ChatGPT-4.0 demonstrated comparable performance in some areas. The study highlights the potential of AI tools in aiding clinicians with medical knowledge and decision-making, while also emphasizing the need for continual advancements and clinician oversight in using such technologies.

REGIONAL POPULATION MOBILITY AND OUTPATIENT RETINA VISITS IN THE UNITED STATES DURING THE COVID-19 PANDEMIC.

PURPOSE: To characterize how community mobility patterns across the United States correlate with local changes in retina visits during the pandemic. METHODS: Outpatient retina clinic visits were linked to population mobility by combining multiple public data sets, including the Google Community Mobility Reports and data from the Centers for Disease Control and Infection. Percentage change from baseline in daily-average number of retina visits by county and mobility were measured by county. RESULTS: A total of 2,159,689 patient visits were examined across 332 counties. Daily-average retina visits decreased by 7.0%, 19.0%, 5.0%, and 4.0% from Quarter 1 to 4 of 2020. This decrease was negatively correlated with increased incident of COVID-19 deaths for Quarters 1 to 3 (r = -0.13, r = -0.16, and r = -0.15, respectively, P < 0.001) and increased incident cases for Quarters 1 and 2 (r = -0.18, r = -0.13, respectively, P < 0.001). Daily-average retina visits relative to baseline were significantly lower for metropolitan counties in Quarters 1 and 2, compared with urban and rural (P < 0.001). The decline in retina visits had greatest association with decline in workplace visits in Quarters 1 to 3 (r = 0.27, r = 0.09, r = 0.12, respectively, P < 0.001 for all). CONCLUSION: This study provides insight into how regional mobility patterns may help to explain and predict patient behaviors and retina outpatient visit responses during the COVID-19 pandemic.

Resting-state magnetoencephalography source magnitude imaging with deep-learning neural network for classification of symptomatic combat-related mild traumatic brain injury.

Combat-related mild traumatic brain injury (cmTBI) is a leading cause of sustained physical, cognitive, emotional, and behavioral disabilities in Veterans and active-duty military personnel. Accurate diagnosis of cmTBI is challenging since the symptom spectrum is broad and conventional neuroimaging techniques are insensitive to the underlying neuropathology. The present study developed a novel deep-learning neural network method, 3D-MEGNET, and applied it to resting-state magnetoencephalography (rs-MEG) source-magnitude imaging data from 59 symptomatic cmTBI individuals and 42 combat-deployed healthy controls (HCs). Analytic models of individual frequency bands and all bands together were tested. The All-frequency model, which combined delta-theta (1-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), and gamma (30-80 Hz) frequency bands, outperformed models based on individual bands. The optimized 3D-MEGNET method distinguished cmTBI individuals from HCs with excellent sensitivity (99.9 ± 0.38%) and specificity (98.9 ± 1.54%). Receiver-operator-characteristic curve analysis showed that diagnostic accuracy was 0.99. The gamma and delta-theta band models outperformed alpha and beta band models. Among cmTBI individuals, but not controls, hyper delta-theta and gamma-band activity correlated with lower performance on neuropsychological tests, whereas hypo alpha and beta-band activity also correlated with lower neuropsychological test performance. This study provides an integrated framework for condensing large source-imaging variable sets into optimal combinations of regions and frequencies with high diagnostic accuracy and cognitive relevance in cmTBI. The all-frequency model offered more discriminative power than each frequency-band model alone. This approach offers an effective path for optimal characterization of behaviorally relevant neuroimaging features in neurological and psychiatric disorders.

Marked Increases in Resting-State MEG Gamma-Band Activity in Combat-Related Mild Traumatic Brain Injury.

Combat-related mild traumatic brain injury (mTBI) is a leading cause of sustained impairments in military service members and veterans. Recent animal studies show that GABA-ergic parvalbumin-positive interneurons are susceptible to brain injury, with damage causing abnormal increases in spontaneous gamma-band (30-80 Hz) activity. We investigated spontaneous gamma activity in individuals with mTBI using high-resolution resting-state magnetoencephalography source imaging. Participants included 25 symptomatic individuals with chronic combat-related blast mTBI and 35 healthy controls with similar combat experiences. Compared with controls, gamma activity was markedly elevated in mTBI participants throughout frontal, parietal, temporal, and occipital cortices, whereas gamma activity was reduced in ventromedial prefrontal cortex. Across groups, greater gamma activity correlated with poorer performances on tests of executive functioning and visuospatial processing. Many neurocognitive associations, however, were partly driven by the higher incidence of mTBI participants with both higher gamma activity and poorer cognition, suggesting that expansive upregulation of gamma has negative repercussions for cognition particularly in mTBI. This is the first human study to demonstrate abnormal resting-state gamma activity in mTBI. These novel findings suggest the possibility that abnormal gamma activities may be a proxy for GABA-ergic interneuron dysfunction and a promising neuroimaging marker of insidious mild head injuries.

MEG Working Memory N-Back Task Reveals Functional Deficits in Combat-Related Mild Traumatic Brain Injury.

Combat-related mild traumatic brain injury (mTBI) is a leading cause of sustained cognitive impairment in military service members and Veterans. However, the mechanism of persistent cognitive deficits including working memory (WM) dysfunction is not fully understood in mTBI. Few studies of WM deficits in mTBI have taken advantage of the temporal and frequency resolution afforded by electromagnetic measurements. Using magnetoencephalography (MEG) and an N-back WM task, we investigated functional abnormalities in combat-related mTBI. Study participants included 25 symptomatic active-duty service members or Veterans with combat-related mTBI and 20 healthy controls with similar combat experiences. MEG source-magnitude images were obtained for alpha (8-12 Hz), beta (15-30 Hz), gamma (30-90 Hz), and low-frequency (1-7 Hz) bands. Compared with healthy combat controls, mTBI participants showed increased MEG signals across frequency bands in frontal pole (FP), ventromedial prefrontal cortex, orbitofrontal cortex (OFC), and anterior dorsolateral prefrontal cortex (dlPFC), but decreased MEG signals in anterior cingulate cortex. Hyperactivations in FP, OFC, and anterior dlPFC were associated with slower reaction times. MEG activations in lateral FP also negatively correlated with performance on tests of letter sequencing, verbal fluency, and digit symbol coding. The profound hyperactivations from FP suggest that FP is particularly vulnerable to combat-related mTBI.

Brain Amygdala Volume Increases in Veterans and Active-Duty Military Personnel With Combat-Related Posttraumatic Stress Disorder and Mild Traumatic Brain Injury.

OBJECTIVE: To identify amygdalar volumetric differences associated with posttraumatic stress disorder (PTSD) in individuals with comorbid mild traumatic brain injury (mTBI) compared with those with mTBI-only and to examine the effects of intracranial volume (ICV) on amygdala volumetric measures. SETTING: Marine Corps Base and VA Healthcare System. PARTICIPANTS: A cohort of veterans and active-duty military personnel with combat-related mTBI (N = 89). DESIGN: Twenty-nine participants were identified with comorbid PTSD and mTBI. The remaining 60 formed the mTBI-only control group. Structural images of brains were obtained with a 1.5-T MRI scanner using a T1-weighted 3D-IR-FSPGR pulse sequence. Automatic segmentation was performed in Freesurfer. MAIN MEASURES: Amygdala volumes with/without normalizations to ICV. RESULTS: The comorbid mTBI/PTSD group had significantly larger amygdala volumes, when normalized to ICV, compared with the mTBI-only group. The right and left amygdala volumes after normalization to ICV were 0.122% ± 0.012% and 0.118% ± 0.011%, respectively, in the comorbid group compared with 0.115% ± 0.012% and 0.112% ± 0.009%, respectively, in the mTBI-only group (corrected P < .05). CONCLUSIONS: The ICV normalization analysis performed here may resolve previous literature discrepancies. This is an intriguing structural finding, given the role of the amygdala in the challenging neuroemotive symptoms witnessed in casualties of combat-related mTBI and PTSD.

Walk on the wild side: estimating the global magnitude of visits to protected areas.

How often do people visit the world's protected areas (PAs)? Despite PAs covering one-eighth of the land and being a major focus of nature-based recreation and tourism, we don't know. To address this, we compiled a globally-representative database of visits to PAs and built region-specific models predicting visit rates from PA size, local population size, remoteness, natural attractiveness, and national income. Applying these models to all but the very smallest of the world's terrestrial PAs suggests that together they receive roughly 8 billion (8 x 109) visits/y-of which more than 80% are in Europe and North America. Linking our region-specific visit estimates to valuation studies indicates that these visits generate approximately US $600 billion/y in direct in-country expenditure and US $250 billion/y in consumer surplus. These figures dwarf current, typically inadequate spending on conserving PAs. Thus, even without considering the many other ecosystem services that PAs provide to people, our findings underscore calls for greatly increased investment in their conservation.

A pilot treatment study for mild traumatic brain injury: Neuroimaging changes detected by MEG after low-intensity pulse-based transcranial electrical stimulation.

BACKGROUND: Mild traumatic brain injury (mTBI) is a leading cause of sustained impairments in military service members, Veterans, and civilians. However, few treatments are available for mTBI, partially because the mechanism of persistent mTBI deficits is not fully understood. METHODS: We used magnetoencephalography (MEG) to investigate neuronal changes in individuals with mTBI following a passive neurofeedback-based treatment programme called IASIS. This programme involved applying low-intensity pulses using transcranial electrical stimulation (LIP-tES) with electroencephalography monitoring. Study participants included six individuals with mTBI and persistent post-concussive symptoms (PCS). MEG exams were performed at baseline and follow-up to evaluate the effect of IASIS on brain functioning. RESULTS: At the baseline MEG exam, all participants had abnormal slow-waves. In the follow-up MEG exam, the participants showed significantly reduced abnormal slow-waves with an average reduction of 53.6 ± 24.6% in slow-wave total score. The participants also showed significant reduction of PCS scores after IASIS treatment, with an average reduction of 52.76 ± 26.4% in PCS total score. CONCLUSIONS: The present study demonstrates, for the first time, the neuroimaging-based documentation of the effect of LIP-tES treatment on brain functioning in mTBI. The mechanisms of LIP-tES treatment are discussed, with an emphasis on LIP-tES's potentiation of the mTBI healing process.

Investigating elementary school children's daily physical activity and sedentary behaviours during weekdays.

The purpose of the study was to quantify the contributions of physical education, exergaming (active video games that also are a type of exercise), recess, lunch break and after-school time segments to children's daily physical activity and sedentary behaviours. Participants were 138 second and third graders (71 girls) who attended 20-min recess and 75-min lunch time daily, 25-min regular physical education or exergaming-based classes being alternated daily. The after-school period was defined as 3:20-10:00pm. Physical activity was assessed via accelerometry and the dependent variables were children's time spent in moderate-to-vigorous physical activity (MVPA), light physical activity and sedentary behaviour. Children's percentages of time spent in MVPA (P < .001; except for the difference between exergaming and lunch break: P = .63), light physical activity (P < .001) and sedentary behaviour (P < .001) differed significantly across the time segments (i.e., physical education/exergaming, recess, lunch break and after-school). Additionally, children accumulated significantly more MVPA (t = 10.22, P < .001) but less light physical activity (t = -3.17, P = .002) and sedentary behaviour (t = -3.91, P < .001) in physical education than in exergaming. Overall, physical education was more effective in generating MVPA than other segments over the school day. The after-school segment holds potential as an avenue for promoting children's MVPA, as this long period could be better utilised to organise structured physical activity.

Intramuscular olanzapine versus intramuscular haloperidol plus lorazepam for the treatment of acute schizophrenia with agitation: An open-label, randomized controlled trial.

BACKGROUND/PURPOSE: To compare the efficacy and safety profile between intramuscular (IM) olanzapine and IM haloperidol plus IM lorazepam in acute schizophrenic patients with moderate to severe agitation. METHODS: This was a prospective, randomized, open-label study. Acutely agitated patients with schizophrenia or schizoaffective disorder (n = 67) were randomized to receive 10 mg IM olanzapine (n = 37) or 5 mg IM haloperidol plus 2 mg IM lorazepam (n = 30). Agitation was measured with Positive and Negative Syndrome Scale Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES) during the first 2 hours and at 24 hours after the first injection. Safety was assessed using the Simpson-Angus Scale and Barnes Akathisia Rating Scale and by recording adverse events at 24 hours following the first injection. The Clinical Global Impression-Severity scale was also rated. RESULTS: The PANSS-EC scores decreased significantly at 2 hours after the first injection in both groups (olanzapine: -10.2, p < 0.001; haloperidol + lorazepam: -9.9, p < 0.001). Haloperidol plus lorazepam was not inferior to olanzapine in reducing agitation at 2 hours. There were no significant differences in PANSS-EC or ACES scores between the two groups within 2 hours following the first injection. The frequencies of adverse events and changes in Clinical Global Impression-Severity, Simpson-Angus Scale, and Barnes Akathisia Rating Scale scores from baseline to 24 hours showed no significant differences between the groups. CONCLUSION: The findings suggest that IM haloperidol (5 mg) plus lorazepam (2 mg) is not inferior to IM olanzapine (10 mg) in the treatment of acute schizophrenic patients with moderate to severe agitation (ClinialTrials.gov identifier number NCT00797277).

MEG source imaging method using fast L1 minimum-norm and its applications to signals with brain noise and human resting-state source amplitude images.

The present study developed a fast MEG source imaging technique based on Fast Vector-based Spatio-Temporal Analysis using a L1-minimum-norm (Fast-VESTAL) and then used the method to obtain the source amplitude images of resting-state magnetoencephalography (MEG) signals for different frequency bands. The Fast-VESTAL technique consists of two steps. First, L1-minimum-norm MEG source images were obtained for the dominant spatial modes of sensor-waveform covariance matrix. Next, accurate source time-courses with millisecond temporal resolution were obtained using an inverse operator constructed from the spatial source images of Step 1. Using simulations, Fast-VESTAL's performance was assessed for its 1) ability to localize multiple correlated sources; 2) ability to faithfully recover source time-courses; 3) robustness to different SNR conditions including SNR with negative dB levels; 4) capability to handle correlated brain noise; and 5) statistical maps of MEG source images. An objective pre-whitening method was also developed and integrated with Fast-VESTAL to remove correlated brain noise. Fast-VESTAL's performance was then examined in the analysis of human median-nerve MEG responses. The results demonstrated that this method easily distinguished sources in the entire somatosensory network. Next, Fast-VESTAL was applied to obtain the first whole-head MEG source-amplitude images from resting-state signals in 41 healthy control subjects, for all standard frequency bands. Comparisons between resting-state MEG sources images and known neurophysiology were provided. Additionally, in simulations and cases with MEG human responses, the results obtained from using conventional beamformer technique were compared with those from Fast-VESTAL, which highlighted the beamformer's problems of signal leaking and distorted source time-courses.

Stress and depression among male police officers in Taiwan: Severity, determinants, and coping strategies.

BACKGROUND: Police work, known for its high stress, exhibits elevated depression rates. OBJECTIVE: This study explores stress and depression in male officers, examining personality traits, coping strategies, family, and social support. Aligned with the diathesis-stress hypothesis and job demands-resources model, it aims to illuminate these factors in policing. METHODS: Two hundred and sixty-four male police officers from Yunlin, Taiwan were enrolled in this study. Structured measurements of stress level, depression symptoms, personality traits, family functioning, and social support were made. We used multiple regression analysis to assess predictors of stress level and depression and identified coping strategies used by the police officers. RESULTS: Of the 264 male police officers, 36.4% had clinically significant depression. Occupational stress was mostly related to organizational factors. Multivariate regression analyses showed that age, personality traits, officer's rank, and period of education obtained could predict police officers' occupational stress. Personality traits, social support, occupational stress, and period of education obtained could predict depression. The most frequently used coping strategies were drinking and smoking. CONCLUSIONS: The results of our study support the diathesis-stress hypothesis and the job demands-resources model. Enhancing male police officers' mental well-being requires addressing key factors like social support and occupational stress. Strategic measures, such as mental health education, destigmatization, counseling, and community-building, are vital. Policymakers should collaborate with mental health professionals for tailored interventions, fostering a healthier work environment.

Mechanical loading and orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA): a comprehensive review.

The importance of mechanical loading and its relationship to orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA) is beginning to receive attention. This review explores the current efficacy of orthobiologic interventions, notably platelet-rich plasma (PRP), bone marrow aspirate (BMA), and mesenchymal stem/stromal cells (MSCs), in combating PTOA drawing from a comprehensive review of both preclinical animal models and human clinical studies. This review suggests why mechanical joint loading, such as running, might improve outcomes in PTOA management in conjunction with orthiobiologic administration. Accumulating evidence underscores the influence of mechanical loading on chondrocyte behavior and its pivotal role in PTOA pathogenesis. Dynamic loading has been identified as a key factor for optimal articular cartilage (AC) health and function, offering the potential to slow down or even reverse PTOA progression. We hypothesize that integrating the activation of mechanotransduction pathways with orthobiologic treatment strategies may hold a key to mitigating or even preventing PTOA development. Specific loading patterns incorporating exercise and physical activity for optimal joint health remain to be defined, particularly in the clinical setting following joint trauma.

Clinical effectiveness of nirmatrelvir plus ritonavir for patients with COVID-19 and preexisting psychiatric disorders.

OBJECTIVES: This study assessed the clinical effectiveness of the combination of nirmatrelvir and ritonavir (NMV-r) in treating nonhospitalized patients with COVID-19 who have preexisting psychiatric disorders. METHODS: Patients diagnosed with COVID-19 and psychiatric disorders between 1 March 2020, and 1 December 2022, were included using the TriNetX network. The primary outcome was the composite outcome of all-cause emergency department (ED) visits, hospitalization, or death within 30 days. RESULTS: Propensity score matching yielded two cohorts of 20,633 patients each. The composite outcome of all-cause ED visits, hospitalization, or death within 30 days was 3.57% (737 patients) in the NMV-r cohort and 5.69% (1176) in the control cohort, resulting in a reduced risk in the NMV-r cohort (HR: 0.657; 95% confidence interval (CI): 0.599-0.720). The NMV-r cohort exhibited a lower risk of all-cause hospitalization (HR: 0.385; 95% CI: 0.328-0.451) and all-cause death (HR: 0.110; 95% CI: 0.053-0.228) compared with the control group. CONCLUSION: NMV-r could mitigate the risk of adverse outcomes in nonhospitalized patients with COVID-19 and preexisting psychiatric disorders. However, only a limited number of patients in this population received adequate treatment, thus emphasizing the importance of promoting its appropriate use.

EMG-projected MEG high-resolution source imaging of human motor execution: Brain-muscle coupling above movement frequencies.

Magnetoencephalography (MEG) is a non-invasive functional imaging technique for pre-surgical mapping. However, movement-related MEG functional mapping of primary motor cortex (M1) has been challenging in presurgical patients with brain lesions and sensorimotor dysfunction due to the large numbers of trials needed to obtain adequate signal to noise. Moreover, it is not fully understood how effective the brain communication is with the muscles at frequencies above the movement frequency and its harmonics. We developed a novel Electromyography (EMG)-projected MEG source imaging technique for localizing early-stage (-100 to 0 ms) M1 activity during ~l min recordings of left and right self-paced finger movements (~1 Hz). High-resolution MEG source images were obtained by projecting M1 activity towards the skin EMG signal without trial averaging. We studied delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), gamma (30-90 Hz), and upper-gamma (60-90 Hz) bands in 13 healthy participants (26 datasets) and three presurgical patients with sensorimotor dysfunction. In healthy participants, EMG-projected MEG accurately localized M1 with high accuracy in delta (100.0%), theta (100.0%), and beta (76.9%) bands, but not alpha (34.6%) or gamma/upper-gamma (0.0%) bands. Except for delta, all other frequency bands were above the movement frequency and its harmonics. In three presurgical patients, M1 activity in the affected hemisphere was also accurately localized, despite highly irregular EMG movement patterns in one patient. Altogether, our EMG-projected MEG imaging approach is highly accurate and feasible for M1 mapping in presurgical patients. The results also provide insight into movement-related brain-muscle coupling above the movement frequency and its harmonics.