Timothy D. Law

The power of the mind: the cortex as a critical determinant of muscle strength/weakness

We tested the hypothesis that the nervous system, and the cortex in particular, is a critical determinant of muscle strength/weakness and that a high level of corticospinal inhibition is an important neurophysiological factor regulating force generation. A group of healthy individuals underwent 4 wk of wrist-hand immobilization to induce weakness. Another group also underwent 4 wk of immobilization, but they also performed mental imagery of strong muscle contractions 5 days/wk. Mental imagery has been shown to activate several cortical areas that are involved with actual motor behaviors, including premotor and M1 regions. A control group, who underwent no interventions, also participated in this study. Before, immediately after, and 1 wk following immobilization, we measured wrist flexor strength, voluntary activation (VA), and the cortical silent period (SP; a measure that reflect corticospinal inhibition quantified via transcranial magnetic stimulation). Immobilization decreased strength 45.1 ± 5.0%, impaired VA 23.2 ± 5.8%, and prolonged the SP 13.5 ± 2.6%. Mental imagery training, however, attenuated the loss of strength and VA by ∼50% (23.8 ± 5.6% and 12.9 ± 3.2% reductions, respectively) and eliminated prolongation of the SP (4.8 ± 2.8% reduction). Significant associations were observed between the changes in muscle strength and VA (r = 0.56) and SP (r = -0.39). These findings suggest neurological mechanisms, most likely at the cortical level, contribute significantly to disuse-induced weakness, and that regular activation of the cortical regions via imagery attenuates weakness and VA by maintaining normal levels of inhibition.

Resistance Exercise to Prevent and Manage Sarcopenia and Dynapenia.

For well over 20 centuries, the muscle wasting (sarcopenia) and weakness (dynapenia) that occurs with old age has been a predominant concern for mankind. Exercise has long been suggested as a treatment to combat sarcopenia and dynapenia, as it exerts effects on both the nervous and muscular systems that are critical to positive physiological and functional adaptations (e.g., enhanced muscle strength). For more than two decades, scientists have recognized the profound role that progressive resistance exercise training (RET) can have on increasing muscle strength, muscle size, and functional capacity in older adults. In this review article, we discuss how RET can be used in the management and prevention of sarcopenia and dynapenia. We first provide an overview of the evidence for this notion and highlight certain critical factors—namely, exercise intensity, volume, and progression—that are key to optimizing the resistance exercise prescription. We then highlight how many, if not most, of the commonly prescribed exercise programs for seniors are not the “best practices” and subsequently present easy-to-read guidelines for a well-rounded RET program designed for the management and prevention of sarcopenia and dynapenia, including example training programs for the beginner through programs for the advanced senior resistance exerciser. These guidelines have been written for the academician as well as the student and health-care provider across a variety of disciplines, including those in the long-term care industry, such as wellness instructors or activity directors.

Weaker Seniors Exhibit Motor Cortex Hypoexcitability and Impairments in Voluntary Activation

BACKGROUNDnWeakness predisposes seniors to a fourfold increase in functional limitations. The potential for age-related degradation in nervous system function to contribute to weakness and physical disability has garnered much interest of late. In this study, we tested the hypothesis that weaker seniors have impairments in voluntary (neural) activation and increased indices of GABAergic inhibition of the motor cortex, assessed using transcranial magnetic stimulation.nnnMETHODSnYoung adults (N = 46; 21.2±0.5 years) and seniors (N = 42; 70.7±0.9 years) had their wrist flexion strength quantified along with voluntary activation capacity (by comparing voluntary and electrically evoked forces). Single-pulse transcranial magnetic stimulation was used to measure motor-evoked potential amplitude and silent period duration during isometric contractions at 15% and 30% of maximum strength. Paired-pulse transcranial magnetic stimulation was used to measure intracortical facilitation and short-interval and long-interval intracortical inhibition. The primary analysis compared seniors to young adults. The secondary analysis compared stronger seniors (top two tertiles) to weaker seniors (bottom tertile) based on strength relative to body weight.nnnRESULTSnThe most novel findings were that weaker seniors exhibited: (i) a 20% deficit in voluntary activation; (ii) ~20% smaller motor-evoked potentials during the 30% contraction task; and (iii) nearly twofold higher levels of long-interval intracortical inhibition under resting conditions.nnnCONCLUSIONSnThese findings indicate that weaker seniors exhibit significant impairments in voluntary activation, and that this impairment may be mechanistically associated with increased GABAergic inhibition of the motor cortex.

Lethality of Cardiovascular Events Highlights the Variable Impact of Complication Type Between Thoracoscopic and Open Pulmonary Lobectomies

BACKGROUNDnThis study examines the impact of postoperative complications by type on perioperative mortality in lobectomies performed by thoracoscopic (video-assisted thoracoscopic surgery [VATS]) and open thoracotomy (OPEN) approaches for primary lung cancer.nnnMETHODSnA retrospective analysis of the Healthcare and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) database from 2007 to 2010 was performed. Patients with primary lung malignancies undergoing pulmonary lobectomy were selected using International Classification of Diseases, 9th edition, Clinical Modification (ICD-9-CM) codes. Perioperative complications within a 30-day period from the operation were identified and recorded using ICD-9-CM codes. Multivariate statistical analysis was performed using Poisson and logistic regression modeling.nnnRESULTSnThere were 24,253 patients included in the analysis, with 5,223 in the VATS cohort and 19,030 in the OPEN cohort. An increased number of complications were associated with increased mortality in both the VATS and OPEN cohorts. The probability of mortality was higher in the OPEN cohort, with 0 or 1 complication, but this difference was lost as the number of complications increased. When categorized by complication type, pulmonary, cardiovascular, wound-related, systemic, and gastrointestinal complications were commonly associated with mortality in both groups. When comparing the number of complications by type between the VATS and OPEN cohorts, cardiovascular (odds ratio [OR], 2.19; p = 0.001) and wound-related (OR, 1.77; p = 0.041) complications were more strongly associated with mortality in the VATS cohort.nnnCONCLUSIONSnWhen cardiovascular complications occur after VATS lobectomy, their impact appears to be more significant than those occurring after OPEN lobectomies. This observation deserves further study because of a likely multifactorial explanation.

Surgical Results and Outcomes After Reimplantation for the Management of Anomalous Aortic Origin of the Right Coronary Artery.

BACKGROUNDnAnomalous aortic origin of the right coronary artery (AAORCA) has been reported to cause myocardial ischemia, leading to angina, dyspnea, and decreased exercise tolerance. Reimplantation is a repair technique devised to exclude the abnormal intramural portion of the anomalous artery and avoid the known late attrition of saphenous vein grafts. Our study aims to evaluate the medium-term clinical outcomes with this technique.nnnMETHODSnA retrospective review was made of patients who underwent repair of AAORCA by reimplantation between 2002 and 2014 in two institutions in Western Australia. Follow-up computed tomography coronary angiography was used to assess the status of the reimplanted right coronary artery (RCA). Data on survival, freedom from symptoms, cardiac events, and cardiac interventions were also analyzed.nnnRESULTSnOf the 16 patients (aged 17 to 70 years old), 14xa0(88%) were symptomatic before surgery, with angina (50%) and exertional dyspnea (56%) being the most common symptoms. Surgical reimplantation was successful in 15 patients (94%) without operative mortality. One patient required saphenous vein bypass grafting of the RCA intraoperatively after presumed failed repair and difficulty weaning from cardiopulmonary bypass. All patients who had successful reimplantation of AAORCA were symptom-free after surgery, and none had subsequent cardiac events attributable to the RCA or required further interventions. Ten patients (67%) had computed tomography coronary angiography after surgery; none had stenosis, kinking, or compression of the RCA by thexa0pulmonary artery. Two further patients (including thexa0patient who underwent saphenous vein grafting forxa0presumed failed reimplantation) underwent conventionalxa0angiography, which demonstrated patent reimplantations.nnnCONCLUSIONSnTo the best of our knowledge, this is the largest reported series of anomalous RCA managed by surgical reimplantation. Our results suggest that this technique is safe and has excellent medium to long-term results regarding symptom-free survival.

Editorial: “From brain to body: the impact of nervous system declines on muscle performance in aging”

Around 30% of women and 15% of men in the United States over 60 years self-report that they are unable to lift or carry 10 pounds, and ~50% of women and 40% of men report difficulty in stooping, crouching, or kneeling (Louie and Ward, 2010). Further, more than 40% of seniors have limitations in performing one or more daily tasks (e.g., walking two to three blocks, transferring from sitting to standing) that are essential for maintaining physical independence (Louie and Ward, 2010). While many factors contribute to reductions in physical function, one contributor is skeletal muscle impairments (e.g., muscle weakness) (Manini et al., 2007). While the nervous system is widely recognized for its role in coordination, its role in determining the performance characteristics of aged skeletal muscle has largely been understudied. n nHistorically, it was believed that the reductions in muscle performance were primarily resultant of age-associated adaptations in skeletal muscle (e.g., muscle atrophy). However, the vast range of motions and forces that humans can achieve arises from the activity of more than 600 skeletal muscles, which are under the control of the nervous system. As such, the nervous system is in all likelihood a critical contributor to all aspects of aged-related changes in muscle performance, and as a consequence, motor behavior (Rosso et al., 2013). Indeed a growing body of research indicates that a good predictor of impending cognitive decline in older adults is a slowed and stooped gait, which has been assigned the term “motoric cognitive risk syndrome” (Verghese et al., 2013, 2014a,b). In this Frontiers in Aging Neuroscience research topic, we solicited articles on a broad range of issues surrounding: (1) the age-related changes in nervous system anatomical, physiological, and biochemical changes in the central and/or peripheral nervous systems; (2) the functional role of these nervous system changes in contributing to altered skeletal muscle performance and/or mobility; and (3) the physical and pharmacologic interventions that act via the nervous system to enhance muscle performance and/or mobility. We invited individuals, both via invitation and an open call for manuscripts, engaged in aging, neuroscience, and/or applied physiology research focused within the scope of this research topic, to contribute an original research article, review article, clinical case study, hypothesis and theory article, method article, opinion article, or technology report. n nIn this issue we present 12 articles within this scope. Specifically, in this issue we present 2 review articles, 1 theory article, and 9 original research articles. Below we highlight some of the most notable findings from this research topic issue: n n nA general theme at the level of brain activation that arises is the dedifferentiation and compensatory activation. Coppi et al. (2014) and McGregor et al. (2013) both found increased interhemispheric interactions and decreased interhemispheric inhibition in older adults. Similarly, Heetkamp et al. (2014) found older adults to exhibit more diffuse, bilateral brain activation patterns during unilateral motor tasks. In the theory and hypothesis paper by Sleimen-Malkoun et al. (2014), the concept of differentiation in aging is co-constructed with the loss of complexity framework, presenting an argument that these patterns of decline are inherent at the level of brain, muscle, and behavior. In a similar vein, Berchicci et al. (2014) showed that exercise reduces the amount of brain activation needed to perform cognitive tasks in older adults, and Yao et al. (2014) reports that older adults require greater activation in higher-order cortical fields for controlling eccentric muscle contractions. n n nAnother general theme that arises in the Vanden Noven et al. (2014) and Hasson and Sternad (2014) original articles is that increasing task complexity in older people results in increased motor variability. Of particular interest was the finding from Vanden Noven et al. (2014) indicating that motor performance was dramatically impaired when a high demand cognitive task was performed concomitant with the motor function task. Findings of this nature have implications for injury risk reduction approaches as well as ergonomic applications. n n nTwo original articles by scientists from the University of Florida examined the neural contributors to mobility in older people. The first of these, from Cruz-Almeida et al. (2014) indicates that sensory tactile perception at the first metatarsal head was associated with both usual and maximal walking speed, while the second article by Clark et al. (2014) observed that the changes in activity of the prefrontal cortex during performance of complex walking tasks were linked to the quality of gait in older adults. Additionally, one of the review articles from Iosa et al. (2014) discusses mobility issues associated with aging, specifically the decline in upright gait stability. They point out that the loss of skeletal muscle with aging, even in healthy older adults, contributes to the inability to maintain an upright posture during walking along with decreased sensory and cognitive declines. A confluence of these declines, they argue, contributes to increased instability and risk of falls. n n nThe last of the articles, a review by Gonzalez-Freire et al. (2014), points out that aging and its associated loss of muscle mass and strength, are related to neuromuscular junction dysfunction. As a result, they postulate that interventions such as exercise and calorie restriction can positively affect the neuromuscular junction. n n n nOverall, the articles within this Research Topic point to an intimate relationship between brain and nervous system function and its impact of muscle activation, and consequently, motor behavior. Physical fitness and exercise seem to be a central component in maintaining both brain and nervous system health, as well as motor function, against the effects of aging.

The effects of testosterone and insulin-like growth factor 1 on motor system form and function.

In this perspective article, we review the effects of selected anabolic hormones on the motoric system and speculate on the role these hormones may have on influencing muscle and physical function via their impact on the nervous system. Both muscle strength and anabolic hormone levels decline around middle age into old age over a similar time period, and several animal and human studies indicate that exogenously increasing anabolic hormones (e.g., testosterone and insulin-like growth factor-1 (IGF-1)) in aged subjects is positively associated with improved muscle strength. While most studies in humans have focused on the effects of anabolic hormones on muscle growth, few have considered the impact these hormones have on the motoric system. However, data from animals demonstrate that administering either testosterone or IGF-1 to cells of the central and peripheral motor system can increase cell excitability, attenuate atrophic changes, and improve regenerative capacity of motor neurons. While these studies do not directly indicate that changes in anabolic hormones contribute to reduced human performance in the elderly (e.g., muscle weakness and physical limitations), they do suggest that additional research is warranted along these lines.

Effects of spine loading in a patient with post-decompression lumbar disc herniation: observations using an open weight-bearing MRI

PurposeOur objective was to use an open weight-bearing MRI to identify the effects of different loading conditions on the inter-vertebral anatomy of the lumbar spine in a post-discectomy recurrent lumbar disc herniation patient.MethodsA 43-year-old male with a left-sided L5-S1 post-decompression re-herniation underwent MR imaging in three spine-loading conditions: (1) supine, (2) weight-bearing on standing (WB), and (3) WB with 10xa0% of body mass axial loading (WBxa0+xa0AL) (5xa0% through each shoulder). A segmentation-based proprietary software was used to calculate and compare linear dimensions, angles and cross sections across the lumbar spine.ResultsThe L5 vertebrae showed a 4.6xa0mm posterior shift at L5-S1 in the supine position that changed to an anterior translation >2.0xa0mm on WB. The spinal canal sagittal thickness at L5-S1 reduced from supine to WB and WBxa0+xa0AL (13.4, 10.6, 9.5xa0mm) with corresponding increases of 2.4 and 3.5xa0mm in the L5-S1 disc protrusion with WB and WBxa0+xa0AL, respectively. Change from supine to WB and WBxa0+xa0AL altered the L5-S1 disc heights (10.2, 8.6, 7.0xa0mm), left L5-S1 foramen heights (12.9, 11.8, 10.9xa0mm), L5-S1 segmental angles (10.3°, 2.8°, 4.3°), sacral angles (38.5°, 38.3°, 40.3°), L1–L3–L5 angles (161.4°, 157.1°, 155.1°), and the dural sac cross sectional areas (149, 130, 131xa0mm2). Notably, the adjacent L4–L5 segment demonstrated a retro-listhesis >2.3xa0mm on WB.ConclusionWe observed that with weight-bearing, measurements indicative of spinal canal narrowing could be detected. These findings suggest that further research is warranted to determine the potential utility of weight-bearing MRI in clinical decision-making.

Premedical Students' Attitudes Toward Primary Care Medicine.

BACKGROUNDnExpanded insurance coverage will likely increase the demand for primary care physicians in the United States. Despite this demand, the number of medical students planning to specialize in primary care is decreasing.nnnOBJECTIVEnTo explore premedical students attitudes toward the primary care specialty.nnnMETHODSnStudents enrolled in premedicine at a large Midwestern university were invited to complete the Primary Care Attitudes Survey (Cronbach α=.76). This 25-item survey measures attitudes about primary care on a 5-point Likert scale, ranging from 1, strongly disagree to 5, strongly agree. Basic sociodemographic characteristics were assessed using descriptive statistics, and frequencies of individual survey responses were calculated using SPSS statistical software version 21.0.nnnRESULTSnA total of 100 premedical students (mean [SD] age, 19.8 [1.5] years; 59 female, 82 white non-Hispanic, and 33 freshman) completed the survey. Of 100 students, 33 planned to pursue primary care; 66 thought that primary care physicians would always have a job; 25 thought that primary care may become obsolete as medicine becomes more specialized; 48 thought that physician assistants and nurse practitioners would take over many primary care duties in the future; 91 thought that primary care physicians make important contributions to medicine; and 84 agreed that primary care focuses on the whole patient.nnnCONCLUSIONSnPremedical students held positive views about the importance of primary care; however, many expressed uncertainty about the stability of primary care careers in the future. Further, a substantial number of students believed common misconceptions about the scope and practice of primary care, such as primary care doctors are gatekeepers and mostly diagnose colds and ear infections.

Poster 100: Cross-Transfer Effects of Blood Flow Restricted Exercise in Patients with Recurrent Low Back Pain

Disclosures: Jennifer Bush: Research Grants Mission Connect grant Objective: To identify correlates of acute opioid use after human traumatic spinal cord injury (SCI) with quality of life outcomes at 1 year. Design: Retrospective chart review. T-tests and Rank-Sum test were used to detect differences between those that responded to the 1year survey (R) and non-responders (NR). Spearman correlation was performed on all variables in the R group. Significant correlates were used in the linear regression models. Setting: Level I trauma center and rehabilitation hospital. Participants: 180 consecutive admissions to the SCI Model Systems (SCIMS) database from 2008-2011. 90 had complete initial medication records, of which 51 answered the subjective pain question on the SCIMS 1 year post-injury survey. Interventions: Not applicable. Main Outcome Measures: Correlates to opioids administered within 4, 12, 24 hours, to 7 days post-injury, and correlates to pain scores at 1 year. Results: The R group (n1⁄451) was administered greater amounts of opioids from24hours to 1week (P<.05) compared toNR (n1⁄439). Therewere 8 variables correlated to opioid subtotals, of which the 24 hour subtotal was most frequently correlated. There were six correlates to pain at 1 year, of which four were opioid subtotals, the earliest being 24 hours (rs 1⁄40.409, P 1⁄4 .005). Linear regression was significant for increases in pain score by 0.007 (P 1⁄4 .01) and mobility score decreases by 0.04 (P 1⁄4 .043) for every 1 mg of morphine equivalents (ME) within 24 hours. For example, a decrease of 143 mgME in 24 hours could result in a decreased pain scoreby 1 point and increasedmobility score by5.72 points at 1 year. Conclusions: There is a positive correlation between acute SCI opioid dosage and chronic pain, and an inverse relationship with mobility at 1 year, supporting the animal evidence of Hook et al. Future prospective studies should be performed to examine the relationship of acute pain medications and long-term outcomes. Level of Evidence: Level IV