BRICseq Bridges Brain-wide Interregional Connectivity to Neural Activity and Gene Expression in Single Animals.

Comprehensive analysis of neuronal networks requires brain-wide measurement of connectivity, activity, and gene expression. Although high-throughput methods are available for mapping brain-wide activity and transcriptomes, comparable methods for mapping region-to-region connectivity remain slow and expensive because they require averaging across hundreds of brains. Here we describe BRICseq (brain-wide individual animal connectome sequencing), which leverages DNA barcoding and sequencing to map connectivity from single individuals in a few weeks and at low cost. Applying BRICseq to the mouse neocortex, we find that region-to-region connectivity provides a simple bridge relating transcriptome to activity: the spatial expression patterns of a few genes predict region-to-region connectivity, and connectivity predicts activity correlations. We also exploited BRICseq to map the mutant BTBR mouse brain, which lacks a corpus callosum, and recapitulated its known connectopathies. BRICseq allows individual laboratories to compare how age, sex, environment, genetics, and species affect neuronal wiring and to integrate these with functional activity and gene expression.

Analysis of Common Exercise Modalities in Improving Athletic Performance in Older Adults: A Narrative Review.

ABSTRACT: Exercise leads to robust cardiovascular, musculoskeletal, and psychological benefits that improve quality of life and longevity for older adults, but accompanying improvements in athletic parameters are less well explored. The aim of this review is to summarize some of the most common exercise modalities, namely, Pilates, martial arts (tai chi, Japanese-style karate, hard martial arts), locomotion (brisk walking/jogging and running), Masters sports, resistance training, and high-intensity interval training, in improving athletic performance for older adults. Regular participation in these activities can have robust yet unique impacts on physical performance that prolong exercise participation. In particular, this review will explore benefits in cardiorespiratory fitness, power, strength, flexibility, and balance, thereby hopefully improving endurance, exercise adherence, and overall fall risk. A narrative literature review was performed to explore benefits, pitfalls, and recommendations for some of the most popular exercise modalities for older adults.

Vertical Hydrologic Exchange Flows Control Methane Emissions from Riverbed Sediments.

CH4 emissions from inland waters are highly uncertain in the current global CH4 budget, especially for streams, rivers, and other lotic systems. Previous studies have attributed the strong spatiotemporal heterogeneity of riverine CH4 to environmental factors such as sediment type, water level, temperature, or particulate organic carbon abundance through correlation analysis. However, a mechanistic understanding of the basis for such heterogeneity is lacking. Here, we combine sediment CH4 data from the Hanford reach of the Columbia River with a biogeochemical-transport model to show that vertical hydrologic exchange flows (VHEFs), driven by the difference between river stage and groundwater level, determine CH4 flux at the sediment-water interface. CH4 fluxes show a nonlinear relationship with the magnitude of VHEFs, where high VHEFs introduce O2 into riverbed sediments, which inhibit CH4 production and induce CH4 oxidation, and low VHEFs cause transient reduction in CH4 flux (relative to production) due to reduced advective CH4 transport. In addition, VHEFs lead to the hysteresis of temperature rise and CH4 emissions because high river discharge caused by snowmelt in spring leads to strong downwelling flow that offsets increasing CH4 production with temperature rise. Our findings reveal how the interplay between in-stream hydrologic flux besides fluvial-wetland connectivity and microbial metabolic pathways that compete with methanogenic pathways can produce complex patterns in CH4 production and emission in riverbed alluvial sediments.

Rethinking Aerobic Respiration in the Hyporheic Zone under Variation in Carbon and Nitrogen Stoichiometry.

Hyporheic zones (HZs)─zones of groundwater-surface water mixing─are hotspots for dissolved organic matter (DOM) and nutrient cycling that can disproportionately impact aquatic ecosystem functions. However, the mechanisms affecting DOM metabolism through space and time in HZs remain poorly understood. To resolve this gap, we investigate a recently proposed theory describing trade-offs between carbon (C) and nitrogen (N) limitations as a key regulator of HZ metabolism. We propose that throughout the extent of the HZ, a single process like aerobic respiration (AR) can be limited by both DOM thermodynamics and N content due to highly variable C/N ratios over short distances (centimeter scale). To investigate this theory, we used a large flume, continuous optode measurements of dissolved oxygen (DO), and spatially and temporally resolved molecular analysis of DOM. Carbon and N limitations were inferred from changes in the elemental stoichiometric ratio. We show sequential, depth-stratified relationships of DO with DOM thermodynamics and organic N that change across centimeter scales. In the shallow HZ with low C/N, DO was associated with the thermodynamics of DOM, while deeper in the HZ with higher C/N, DO was associated with inferred biochemical reactions involving organic N. Collectively, our results suggest that there are multiple competing processes that limit AR in the HZ. Resolving this spatiotemporal variation could improve predictions from mechanistic models, either via more highly resolved grid cells or by representing AR colimitation by DOM thermodynamics and organic N.

Critical analysis of the evaluation of postoperative dysphagia following an anterior cervical discectomy and fusion.

BACKGROUND AND PURPOSE: Postoperative dysphagia is a known complication of anterior cervical discectomy and fusion (ACDF) with reported incidences ranging from 1 to 79%. No standardized guidelines exist for spine surgeons to evaluate postoperative dysphagia after ACDF. A systematic method may be beneficial in distinguishing transient postoperative dysphagia secondary to intubation from those with postoperative complications. This study evaluates the causes, recognition, and clinical evaluation of postoperative dysphagia following ACDF. METHODS: International classification of disease (ICD) and current procedural terminology (CPT) codes were used to identify ACDF patients and compared to anterior lumbar discectomy and fusion (ALDF), serving as a control group, between the years 2015-2019 and those diagnosed with dysphagia within 1 year. Demographics, operative details, and clinical evaluation were reviewed. Exclusion criteria included history of head and neck procedures, cancer, stroke, radiation, and trauma. RESULTS: One hundred thirty-one ACDF and 93 ALDF patients met inclusion criteria. Twenty-seven (20.6%) ACDF patients were diagnosed with dysphagia within 1 year. Less than half of the dysphagia patients had the word "dysphagia" documented in their 1-month spine surgeon follow up visit. Only 66% of dysphagia patients had specialist evaluation and one third of those patients were referred by their surgeon. Only six patients received diagnostic barium swallow evaluations. CONCLUSION: Postoperative dysphagia risk increases in ACDF compared to ALDF, likely due to underlying anatomy. Postoperative dysphagia symptoms are not effectively documented by spine surgeons and as a result underevaluated by dysphagia specialists. Patients may benefit from more extensive pre- and post-operative screening, evaluation, and referral regarding dysphagia symptoms following ACDF.

The Impact of Supplements on Sports Performance for the Trained Athlete: A Critical Analysis.

ABSTRACT: Elite athletes often use nutritional supplements to improve performance and gain competitive advantage. The prevalence of nutrient supplementation ranges from 40% to 100% among trained athletes, yet few athletes have a trusted source of information for their supplement decisions and expected results. This critical analysis review evaluates systematic reviews, meta-analyses, randomized control trials, and crossover trials investigating commonly used supplements in sport: caffeine, creatine, beta-alanine (ß-alanine), branched chain amino acids (BCAAs), and dietary nitrates. By reviewing these supplements' mechanisms, evidence relating directly to improving sports performance, and ideal dosing strategies, we provide a reference for athletes and medical staff to personalize supplementation strategies. Caffeine and creatine impact power and high-intensity athletes, ß-alanine, and BCAA mitigate fatigue, and dietary nitrates improve endurance. With each athlete having different demands, goals to maximize their performance, athletes and medical staff should collaborate to personalize supplementation strategies based on scientific backing to set expectations and potentiate results.

Inferring single-trial neural population dynamics using sequential auto-encoders.

Neuroscience is experiencing a revolution in which simultaneous recording of thousands of neurons is revealing population dynamics that are not apparent from single-neuron responses. This structure is typically extracted from data averaged across many trials, but deeper understanding requires studying phenomena detected in single trials, which is challenging due to incomplete sampling of the neural population, trial-to-trial variability, and fluctuations in action potential timing. We introduce latent factor analysis via dynamical systems, a deep learning method to infer latent dynamics from single-trial neural spiking data. When applied to a variety of macaque and human motor cortical datasets, latent factor analysis via dynamical systems accurately predicts observed behavioral variables, extracts precise firing rate estimates of neural dynamics on single trials, infers perturbations to those dynamics that correlate with behavioral choices, and combines data from non-overlapping recording sessions spanning months to improve inference of underlying dynamics.

Phrenic Nerve Reconstruction for Effective Surgical Treatment of Diaphragmatic Paralysis.

ABSTRACT: Diaphragmatic paralysis due to phrenic nerve injury may cause orthopnea, exertional dyspnea, and sleep-disordered breathing. Phrenic nerve reconstruction may relieve symptoms and improve respiratory function. A retrospective review of 400 consecutive patients undergoing phrenic nerve reconstruction for diaphragmatic paralysis at 2 tertiary treatment centers was performed between 2007 and 2019. Symptomatic patients were identified, and the diagnosis was confirmed on radiographic evaluations. Assessment parameters included pulmonary spirometry (forced expiratory volume in 1 second and FVC), maximal inspiratory pressure, compound muscle action potentials, diaphragm thickness, chest fluoroscopy, and Short Form 36 Health Survey Questionnaire (SF-36) survey. There were 81 females and 319 males with an average age of 54 years (range, 19-79 years). The mean duration from diagnosis to surgery was 29 months (range, 1-320 months). The most common etiologies were acute or chronic injury (29%), interscalene nerve block (17%), and cardiothoracic surgery (15%). The mean improvements in forced expiratory volume in 1 second and FVC at 1 year were 10% (P < 0.01) and 8% (P < 0.05), respectively. At 2-year follow-up, the corresponding values were 22% (P < 0.05) and 18% (P < 0.05), respectively. Improvement on chest fluoroscopy was demonstrated in 63% and 71% of patients at 1 and 2-year follow-up, respectively. There was a 20% (P < 0.01) improvement in maximal inspiratory pressure, and compound muscle action potentials increased by 82% (P < 0.001). Diaphragm thickness demonstrated a 27% (P < 0.01) increase, and SF-36 revealed a 59% (P < 0.001) improvement in physical functioning. Symptomatic diaphragmatic paralysis should be considered for surgical treatment. Phrenic nerve reconstruction can achieve symptomatic relief and improve respiratory function. Increasing spirometry and improvements on Sniff from 1 to 2 years support incremental recovery with longer follow-up.

Application of the ORBEYE three-dimensional exoscope for microsurgical procedures.

BACKGROUND: Advances in digital imaging, screen technology, and optics have led to the development of extracorporeal telescopes, also known as exoscopes, as alternatives to surgical loupes (SLs) and traditional operating microscopes (OMs) for surgical magnification. Theoretical advantages of the exoscope over conventional devices include improved surgeon ergonomics; superior three-dimensional, high-definition optics; and greater ease-of-use. The ORBEYE exoscope, in particular, has demonstrated early efficacy in the surgical arena. The purpose of this study was to compare the ORBEYE with conventional microscopy. METHODS: In this case-control pilot study, we compared the ORBEYE (n = 22) with conventional microscopy (n = 27) across 49 consecutive microsurgical cases during a 6-week period. Both visualization methods consisted of breast, and head and neck cases, while the ORBEYE was also used for extremity and lymphedema microsurgical cases. The ORBEYE was utilized during flap dissection and microvascular anastomosis. Baseline demographics, operative time, ischemia time, and intra- and postoperative microvascular complications were examined and compared. Attending surgeons completed an ergonomics and performance survey postoperatively comparing the ORBEYE with their previous use of SL/OM using a 5-point Likert scale. RESULTS: There was no difference in operative time (507 ± 132 min vs. 522 ± 139, p = .714), ischemia time (77.9 ± 31.4 min vs. 77.5 ± 36.0, p = .972), or microsurgical complications (0% vs. 4%, p = 1) between the ORBEYE and conventional microscopy groups. In a survey administered immediately postoperatively, surgeons reported favorable ergonomics, excellent image quality, and ease of equipment manipulation using the exoscope. CONCLUSIONS: The ORBEYE is an effective microsurgical tool and may be considered as an alternative to conventional optical magnification technology.

Orthognathic Surgical Treatment in a Patient With Hyperimmunoglobulin E Syndrome.

Autosomal-dominant hyperimmunoglobulin E syndrome (HIES), or Job syndrome, is a rare, multisystem, primary immunodeficiency disorder. Additionally, patients may also suffer from connective tissue, dental, and bone malformations. While current management of HIES is directed at prophylactic antibiotics to prevent infections, there is limited work describing surgical considerations for these patients, particularly with respect to hardware placement. Here we report a case of a patient with HIES who underwent orthognathic surgery for maxillary advancement and mandibular setback to address his severe class III malocclusion. The patient's postoperative course was complicated by significant infection, requiring multiple operations and ultimately, hardware removal after bone healing. Although this patient ultimately had a good outcome, the role of orthognathic surgery with implant placement in patients with HIES should be approached with caution and careful consideration.

The Relationship Between Hiatal Hernia and Cricopharyngeus Muscle Dysfunction.

Although the precise etiology of cricopharyngeus muscle (CPM) dysfunction (CPMD) is uncertain, many have hypothesized that a hypertrophied CPM may develop as a protective compensation against gastroesophageal reflux disease (GERD). The purpose of this investigation was to evaluate the association between CPMD and the presence of hiatal hernia (HH) in an attempt to elucidate the potential etiology of CPMD. The charts of individuals who underwent video fluoroscopic esophagrams between 01/01/14 and 10/30/16 were reviewed from an electronic database. A group of 50 subjects with reported HH were identified and age- and gender-matched to an individual without HH. The prevalence of CPMD was compared between groups. The mean (± SD) age of the HH cohort was 64 (± 13.4) years and 64 (± 12.8) years for the group without HH (p > 0.05). Thirty-eight percent was male. The frequency of CPMD in the HH group was 78% versus 58% in the non-HH group (p < 0.05). Individuals with a HH were 2.57 times more likely to have evidence of CPMD (95% CI 1.07- 6.15). Although these data suggest an association between GERD and CPMD, further research is required before a causal relationship can be presumed.

Posterior Parietal Cortex Guides Visual Decisions in Rats.

Neurons in putative decision-making structures can reflect both sensory and decision signals, making their causal role in decisions unclear. Here, we tested whether rat posterior parietal cortex (PPC) is causal for processing visual sensory signals or instead for accumulating evidence for decision alternatives. We disrupted PPC activity optogenetically during decision making and compared effects on decisions guided by auditory versus visual evidence. Deficits were largely restricted to visual decisions. To further test for visual dominance in PPC, we evaluated electrophysiological responses after individual sensory events and observed much larger response modulation after visual stimuli than auditory stimuli. Finally, we measured trial-to-trial spike count variability during stimulus presentation and decision formation. Variability decreased sharply, suggesting that the network is stabilized by inputs, unlike what would be expected if sensory signals were locally accumulated. Our findings suggest that PPC plays a causal role in processing visual signals that are accumulated elsewhere.SIGNIFICANCE STATEMENT Defining the neural circuits that support decision making bridges a gap between our understanding of simple sensorimotor reflexes and our understanding of truly complex behavior. However, identifying brain areas that play a causal role in decision making has proved challenging. We tested the causal role of a candidate component of decision circuits, the rat posterior parietal cortex (PPC). Our interpretation of the data benefited from our use of animals trained to make decisions guided by either visual or auditory evidence. Our results suggest that PPC plays a causal role specifically in visual decision making and may support sensory aspects of the decision, such as interpreting the visual signals so that evidence for a decision can be accumulated elsewhere.

Neural population dynamics during reaching.

Most theories of motor cortex have assumed that neural activity represents movement parameters. This view derives from what is known about primary visual cortex, where neural activity represents patterns of light. Yet it is unclear how well the analogy between motor and visual cortex holds. Single-neuron responses in motor cortex are complex, and there is marked disagreement regarding which movement parameters are represented. A better analogy might be with other motor systems, where a common principle is rhythmic neural activity. Here we find that motor cortex responses during reaching contain a brief but strong oscillatory component, something quite unexpected for a non-periodic behaviour. Oscillation amplitude and phase followed naturally from the preparatory state, suggesting a mechanistic role for preparatory neural activity. These results demonstrate an unexpected yet surprisingly simple structure in the population response. This underlying structure explains many of the confusing features of individual neural responses.

Perspectives on classical controversies about the motor cortex.

Primary motor cortex has been studied for more than a century, yet a consensus on its functional contribution to movement control is still out of reach. In particular, there remains controversy as to the level of control produced by motor cortex ("low-level" movement dynamics vs. "high-level" movement kinematics) and the role of sensory feedback. In this review, we present different perspectives on the two following questions: What does activity in motor cortex reflect? and How do planned motor commands interact with incoming sensory feedback during movement? The four authors each present their independent views on how they think the primary motor cortex (M1) controls movement. At the end, we present a dialogue in which the authors synthesize their views and suggest possibilities for moving the field forward. While there is not yet a consensus on the role of M1 or sensory feedback in the control of upper limb movements, such dialogues are essential to take us closer to one.

Tensor Analysis Reveals Distinct Population Structure that Parallels the Different Computational Roles of Areas M1 and V1.

Cortical firing rates frequently display elaborate and heterogeneous temporal structure. One often wishes to compute quantitative summaries of such structure-a basic example is the frequency spectrum-and compare with model-based predictions. The advent of large-scale population recordings affords the opportunity to do so in new ways, with the hope of distinguishing between potential explanations for why responses vary with time. We introduce a method that assesses a basic but previously unexplored form of population-level structure: when data contain responses across multiple neurons, conditions, and times, they are naturally expressed as a third-order tensor. We examined tensor structure for multiple datasets from primary visual cortex (V1) and primary motor cortex (M1). All V1 datasets were 'simplest' (there were relatively few degrees of freedom) along the neuron mode, while all M1 datasets were simplest along the condition mode. These differences could not be inferred from surface-level response features. Formal considerations suggest why tensor structure might differ across modes. For idealized linear models, structure is simplest across the neuron mode when responses reflect external variables, and simplest across the condition mode when responses reflect population dynamics. This same pattern was present for existing models that seek to explain motor cortex responses. Critically, only dynamical models displayed tensor structure that agreed with the empirical M1 data. These results illustrate that tensor structure is a basic feature of the data. For M1 the tensor structure was compatible with only a subset of existing models.

Shared Medical Appointments for Adolescent Breast Reduction.

Adolescents with macromastia face serious physical, emotional, and social burdens because of their large breast size. Studies have shown that reduction mammoplasty results in improvement in physical symptoms and quality of life for these patients. Shared medical appointments (SMAs), defined as individual patient-physician encounters that occur in a group setting, have been successfully applied to clinics for adult patients seeking breast reduction for this condition. We decided to apply the SMA model to our clinic for preoperative evaluation of adolescent patients with macromastia. The purpose of this article is to describe how our clinic implemented SMAs, evaluate changes in clinic efficiency, measure patient quality of life before surgery, and assess patient and provider satisfaction with the SMA model.From February to June 2016, our department instituted SMAs for preoperative evaluation of female adolescent patients with macromastia. We measured days from referral to appointment for 25 patients who attended SMAs and compared this with a retrospective cohort of 21 patients who attended traditional visits from 2013 to 2015.Clinic efficiency was measured in new patients per hour. During SMAs, we also administered the BREAST-Q, Pediatric Quality of Life Inventory, and patient and provider satisfaction surveys. Mean days between referral and office visit was reduced from 75.3 with traditional visits to 40.3 with shared appointments, although this finding was not statistically significant (P = 0.69). New patients per hour increased from 1.33 with traditional visits to 3 with SMAs, without reducing time spent on education or with the surgeon. The mean preoperative BREAST-Q scores were less than 40 for the 4 tested domains, and the mean (SD) total Pediatric Quality of Life Inventory score was 56.7 (14.8). Patients and the provider reported high satisfaction with SMAs, and the provider wishes to continue using SMAs in the clinic.In conclusion, SMAs resulted in high patient and provider satisfaction and increased clinic efficiency, without sacrificing time spent on education or with the surgeon. Low quality-of-life scores demonstrate a need for these patients to be evaluated and treated for their condition. Measuring patient-reported outcomes with validated surveys and improving clinic efficiency without sacrificing patient care have the potential to increase value at our institution.

Long-Term Follow-Up after Phrenic Nerve Reconstruction for Diaphragmatic Paralysis: A Review of 180 Patients.

Background Phrenic nerve reconstruction has been evaluated as a method of restoring functional activity and may be an effective alternative to diaphragm plication. Longer follow-up and a larger cohort for analysis are necessary to confirm the efficacy of this procedure for diaphragmatic paralysis. Methods A total of 180 patients treated with phrenic nerve reconstruction for chronic diaphragmatic paralysis were followed for a median 2.7 years. Assessment parameters included: 36-Item Short Form Health Survey (SF-36) physical functioning survey, spirometry, chest fluoroscopy, electrodiagnostic evaluation, a five-item questionnaire to assess specific functional issues, and overall patient-reported outcome. Results Overall, 134 males and 46 females with an average age of 56 years (range: 10-79 years) were treated. Mean baseline percent predicted values for forced expiratory volume in 1 second, forced vital capacity, vital capacity, and total lung capacity, were 61, 63, 67, and 75%, respectively. The corresponding percent improvements in percent predicted values were: 11, 6, 9, and 13% (p ≤ 0.01; ≤ 0.01; ≤ 0.05; ≤ 0.01). Mean preoperative SF-36 physical functioning survey scores were 39%, and an improvement to 65% was demonstrated following surgery (p ≤ 0.0001). Nerve conduction latency, improved by an average 23% (p ≤ 0.005), and there was a corresponding 125% increase in diaphragm motor amplitude (p ≤ 0.0001). A total of 89% of patients reported an overall improvement in breathing function. Conclusion Long-term assessment of phrenic nerve reconstruction for diaphragmatic paralysis indicates functional correction and symptomatic relief.