Logan Schneider

Prediction of human voluntary movement before it occurs.

OBJECTIVE Human voluntary movement is associated with two changes in electroencephalography (EEG) that can be observed as early as 1.5 s prior to movement: slow DC potentials and frequency power shifts in the alpha and beta bands. Our goal was to determine whether and when we can reliably predict human natural movement BEFORE it occurs from EEG signals ONLINE IN REAL-TIME. METHODS We developed a computational algorithm to support online prediction. Seven healthy volunteers participated in this study and performed wrist extensions at their own pace. RESULTS The average online prediction time was 0.62±0.25 s before actual movement monitored by EMG signals. There were also predictions that occurred without subsequent actual movements, where subjects often reported that they were thinking about making a movement. CONCLUSION Human voluntary movement can be predicted before movement occurs. SIGNIFICANCE The successful prediction of human movement intention will provide further insight into how the brain prepares for movement, as well as the potential for direct cortical control of a device which may be faster than normal physical control.

Intermittent theta-burst transcranial magnetic stimulation for treatment of Parkinson disease

Objective: To investigate the safety and efficacy of intermittent theta-burst stimulation (iTBS) in the treatment of motor symptoms in Parkinson disease (PD). Background: Progression of PD is characterized by the emergence of motor deficits, which eventually respond less to dopaminergic therapy and pose a therapeutic challenge. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. iTBS is a novel type of rTMS that may be more efficacious than conventional rTMS. Methods: In this randomized, double-blind, sham-controlled study, we investigated safety and efficacy of iTBS of the motor and dorsolateral prefrontal cortices in 8 sessions over 2 weeks (evidence Class I). Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, Unified Parkinsons Disease Rating Scale (UPDRS), and additional clinical, neuropsychological, and neurophysiologic measures. Results: We investigated 26 patients with mild to moderate PD: 13 received iTBS and 13 sham stimulation. We found beneficial effects of iTBS on mood, but no improvement of gait, bradykinesia, UPDRS, and other measures. EEG/EMG monitoring recorded no pathologic increase of cortical excitability or epileptic activity. Few reported discomfort or pain and one experienced tinnitus during real stimulation. Conclusion: iTBS of the motor and prefrontal cortices appears safe and improves mood, but failed to improve motor performance and functional status in PD. Classification of evidence: This study provides Class I evidence that iTBS was not effective for gait, upper extremity bradykinesia, or other motor symptoms in PD.

Genetic Basis of Chronotype in Humans: Insights From Three Landmark GWAS

Study Objectives: Chronotype, or diurnal preference, refers to behavioral manifestations of the endogenous circadian system that governs preferred timing of sleep and wake. As variations in circadian timing and system perturbations are linked to disease development, the fundamental biology of chronotype has received attention for its role in the regulation and dysregulation of sleep and related illnesses. Family studies indicate that chronotype is a heritable trait, thus directing attention toward its genetic basis. Although discoveries from molecular studies of candidate genes have shed light onto its genetic architecture, the contribution of genetic variation to chronotype has remained unclear with few related variants identified. In the advent of large‐scale genome‐wide association studies (GWAS), scientists now have the ability to discover novel common genetic variants associated with complex phenotypes. Three recent large‐scale GWASs of chronotype were conducted on subjects of European ancestry from the 23andMe cohort and the UK Biobank. This review discusses the findings of these landmark GWASs in the context of prior research. Methods: We systematically reviewed and compared methodological and analytical approaches and results across the three GWASs of chronotype. Results: A good deal of consistency was observed across studies with 9 genes identified in 2 of the 3 GWASs. Several genes previously unknown to influence chronotype were identified. Conclusions: GWAS is an important tool in identifying common variants associated with the complex chronotype phenotype, the findings of which can supplement and guide molecular science. Future directions in model systems and discovery of rare variants are discussed.

What we think before a voluntary movement

A central feature of voluntary movement is the sense of volition, but when this sense arises in the course of movement formulation and execution is not clear. Many studies have explored how the brain might be actively preparing movement before the sense of volition; however, because the timing of the sense of volition has depended on subjective and retrospective judgments, these findings are still regarded with a degree of scepticism. EEG events such as beta event-related desynchronization and movement-related cortical potentials are associated with the brains programming of movement. Using an optimized EEG signal derived from multiple variables, we were able to make real-time predictions of movements in advance of their occurrence with a low false-positive rate. We asked participants what they were thinking at the time of prediction: Sometimes they were thinking about movement, and other times they were not. Our results indicate that the brain can be preparing to make voluntary movements while participants are thinking about something else.

Education Research: Neurology resident education Trending skills, confidence, and professional preparation

Objective: To survey US-trained graduating neurology residents who are American Academy of Neurology members, in an effort to trend perceived quality and completeness of graduate neurology education. Methods: An electronic survey was sent to all American Academy of Neurology members graduating from US neurology residency programs in the Spring of 2014. Results: Of 805 eligible respondents, 24% completed the survey. Ninety-three percent of adult neurology residents and 56% of child neurology residents reported plans to pursue fellowship training after residency. Respondents reported a desire for additional training in neurocritical care, neuro-oncology, neuromuscular diseases, botulinum toxin injection, and nerve blocks. There remains a clear deficit in business training of neurology residents, although there was notable improvement in knowledge of coding and office management compared to previous surveys. Discussion: Although there are still areas of perceived weakness in neurology training, graduating neurology residents feel generally well prepared for their chosen careers. However, most still pursue fellowship training for reasons that are little understood. In addition to certain subspecialties and procedures, practice management remains deficient in neurology training and is a point of future insecurity for most residents. Future curriculum changes should consider resident-reported gaps in knowledge, with careful consideration of improving business training.

International Issues: Obtaining an adult neurology residency position in the United States An overview

Around the world, there are marked differences in neurology training, including training duration and degree of specialization. In the United States, adult neurology residency is composed of 1 year of internal medicine training (preliminary year) and 3 years of neurology-specific training. Child neurology, which is not the focus of this article, is 2 years of pediatrics and 3 years of neurology training. The route to adult neurology residency training in the United States is standardized and is similar to most other US specialties. Whereas US medical graduates often receive stepwise guidance from their medical school regarding application for residency training, international graduates often enter this complex process with little or no such assistance. Despite this discrepancy, about 10%–15% of residency positions in the United States are filled by international medical graduates.1,2 In adult neurology specifically, 35% of matched positions were filled by international graduates in 2013, 75% of whom were not US citizens.1 In an effort to provide a preliminary understanding of the application process and related terminology (table 1) and thereby encourage international residency applicants, we describe the steps necessary to apply for neurology residency in the United States.

Automatic, electrocardiographic-based detection of autonomic arousals and their association with cortical arousals, leg movements, and respiratory events in sleep

Study Objectives The current definition of sleep arousals neglects to address the diversity of arousals and their systemic cohesion. Autonomic arousals (AA) are autonomic activations often associated with cortical arousals (CA), but they may also occur in relation to a respiratory event, a leg movement event or spontaneously, without any other physiological associations. AA should be acknowledged as essential events to understand and explore the systemic implications of arousals. Methods We developed an automatic AA detection algorithm based on intelligent feature selection and advanced machine learning using the electrocardiogram. The model was trained and tested with respect to CA systematically scored in 258 (181 training size/77 test size) polysomnographic recordings from the Wisconsin Sleep Cohort. Results A precision value of 0.72 and a sensitivity of 0.63 were achieved when evaluated with respect to CA. Further analysis indicated that 81% of the non-CA-associated AAs were associated with leg movement (38%) or respiratory (43%) events. Conclusions The presented algorithm shows good performance when considering that more than 80% of the false positives (FP) found by the detection algorithm appeared in relation to either leg movement or respiratory events. This indicates that most FP constitute autonomic activations that are indistinguishable from those with cortical cohesion. The proposed algorithm provides an automatic system trained in a clinical environment, which can be utilized to analyze the systemic and clinical impacts of arousals.

Integrating the Divided Nasal Cannula Into Routine Polysomnography to Assess Nasal Cycle: Feasibility and Effect on Outcomes

STUDY OBJECTIVES Patients suspected to have sleep-disordered breathing underwent an overnight polysomnography using a divided nasal cannula to gain additional information about the nasal cycle during sleep. METHODS This was a prospective, observational cohort study replacing the undivided nasal cannula with a divided nasal cannula during routine polysomnography (n = 28). RESULTS Integration of the divided nasal cannula pressure transducer system into routine polysomnography was easy and affordable. Most patients (89%) demonstrated nasal cycle changes during the test. Nasal cycle changes tended to occur during body position changes (62%) and transitions from non-rapid eye movement sleep to rapid eye movement sleep (41%). The mean nasal cycle duration was 2.5 ± 2.1 hours. Other sleep study metrics did not reveal statistically significant findings in relation to the nasal cycle. CONCLUSIONS Replacing an undivided nasal cannula with a divided nasal cannula is easy to implement, adding another physiologic measure to polysomnography. Although the divided nasal cannula did not significantly affect traditional polysomnographic metrics such as the apnea-hypopnea index or periodic limb movement index based on this small pilot study, we were able to replicate past nasal cycle findings that may be of interest to sleep clinicians and researchers. Given the ease with which the divided nasal cannula can be integrated, we encourage other sleep researchers to investigate the utility of using a divided nasal cannula during polysomnography.

Periodic limb movements in sleep: Prevalence and associated sleepiness in the Wisconsin Sleep Cohort

OBJECTIVES Periodic limb movements in sleep (PLMS) are thought to be prevalent in elderly populations, but their impact on quality of life remains unclear. We examined the prevalence of PLMS, impact of age on prevalence, and association between PLMS and sleepiness. METHODS We identified limb movements in 2335 Wisconsin Sleep Cohort polysomnograms collected over 12 years. Prevalence of periodic limb movement index (PLMI) ≥15 was calculated at baseline (n = 1084). McNemars test assessed changes in prevalence over time. Association of sleepiness and PLMS evaluated using linear mixed modeling and generalized estimating equations. Models adjusted for confounders. RESULTS Prevalence of PLMI ≥15 at baseline was 25.3%. Longitudinal prevalence increased significantly with age (p = 2.97 × 10-14). Sleepiness did not differ significantly between PLMI groups unless stratified by restless legs syndrome (RLS) symptoms. The RLS+/PLM+ group was sleepier than the RLS+/PLM- group. Multiple Sleep Latency Test trended towards increased alertness in the RLS-/PLM+ group compared to RLS-/PLM-. CONCLUSIONS A significant number of adults have PLMS and prevalence increased with age. No noteworthy association between PLMI category and sleepiness unless stratified by RLS symptoms. SIGNIFICANCE Our results indicate that RLS and PLMS may have distinct clinical consequences and interactions that can help guide treatment approach.

Genetics of vaccination-related narcolepsy

Narcolepsy type 1 is a severe hypersomnia affecting 1/3000 individuals. It is caused by a loss of neurons producing hypocretin/orexin in the hypothalamus. In 2009/2010, an immunization campaign directed towards the new pandemic H1N1 Influenza-A strain was launched and increased risk of narcolepsy reported in Northern European countries following vaccination with Pandemrix®, an adjuvanted H1N1 vaccine resulting in ~250 vaccination-related cases in Finland alone. Using whole genome sequencing data of 2000 controls, exome sequencing data of 5000 controls and HumanCoreExome chip genotypes of 81 cases with vaccination-related narcolepsy and 2796 controls, we, built a multilocus genetic risk score with established narcolepsy risk variants. We also analyzed, whether novel risk variants would explain vaccine-related narcolepsy. We found that previously discovered risk variants had strong predictive power (accuracy of 73% and P<2.2*10−16; and ROC curve AUC 0.88) in vaccine-related narcolepsy cases with only 4.9% of cases being assigned to the low risk category. Our findings indicate genetic predisposition to vaccine-triggered narcolepsy, with the possibility of identifying 95% of people at risk.