Anticipatory Postural Adjustments and Spatial Organization of Motor Cortex: Evidence of Adaptive Compensations in Healthy Older Adults

During anticipated postural perturbations induced by limb movement, the central nervous system generates anticipatory postural adjustments (APAs) in the trunk and hip musculature to minimize disturbances to equilibrium. Age-related changes in functional organization of the nervous system may contribute to changes in APAs in healthy older adults. Here we examined if altered APAs of trunk/hip musculature in older adults are accompanied by changes in the representation of these muscles in motor cortex. Twelve healthy older adults, 5 with a history of falls and 7 nonfallers, were compared with 13 young adults. APAs were assessed during a mediolateral arm raise task in standing. Temporal organization of postural adjustments was quantified as latency of APAs in the contralateral external oblique, lumbar paraspinals, and gluteus medius relative to activation of the deltoid. Spatial organization was quantified as extent of synergistic coactivation between muscles. Volume and location of the muscle representations in motor cortex were mapped using transcranial magnetic stimulation. We found that older adults demonstrated significantly delayed APAs in the gluteus medius muscle. Spatial organization of the three muscles in motor cortex differed between groups, with the older adults demonstrating more lateral external oblique representation than the other two muscles. Separate comparisons of the faller and nonfaller subgroups with young adults indicated that nonfallers had the greatest delay in gluteus medius APAs and a reduced distance between the representational areas of the lumbar paraspinals and gluteus medius. This study indicates that altered spatial organization of motor cortex accompanies altered temporal organization of APA synergies in older adults

The Role of Gut Health in Parkinson’s disease: The Impact on Motor Symptoms and Fitness Levels

While Parkinson’s disease (PD) has traditionally been considered a central nervous system disease, recent groundbreaking research argues that PD symptomology is influenced by gut microbiota alterations (dysbiosis).1 People with PD suffer from dysbiosis,2-6 and gut symptoms characteristic of dysbiosis, like constipation.7,8 Given this evidence, strategies that improve gut health in PD are warranted. One possible strategy is exercise. In non-PD populations, fitness status is linked to gut health,9-13 and exercise which increases fitness status improves the gut.14-19 It is now known that exercise improves motor symptoms in PD,20-23 but the gut may be a moderator of these improvements. However, no study has taken the crucial first step to link fitness with motor and gut symptoms in PD. In addition, there is a need to determine whether norms for fitness status 24 indicate PD symptom severity to provide clinicians with a benchmark by which they can improve the fitness of people with PD. PURPOSE: We aimed to 1) associate fitness, motor symptoms, and constipation and 2) determine the influence of aerobic fitness norms on motor symptoms and constipation in 19 people with PD. METHODS: Constipation was measured via the ROME-IV survey (summing nine symptom questions). Fitness was defined as estimated oxygen consumption (VO2) via a 6-minute walk test (6MW). Normative classifications were used to determine whether participants met (HI) or did not meet aerobic fitness status (LO).25 Motor symptoms were assessed via the Unified Parkinson’s Disease Rating Scale III (UPDRS-III). A linear regression was used to associate VO2 peak, UPDRS-III, and constipation. A MANOVA was used to compare symptoms between HI and LO groups. RESULTS: VO2 peak was inversely associated with constipation (t= 2.67, p=.018, effect size = -.48, 95% CI= -.86 to -.10) and UPDRS-III scores (t= -2.35, p= .033, effect size= -.48, 95% CI= -.92 to -.04). The HI group had lower constipation (p=.018) and UPDRS-III scores (p=.03) than the LO group. DISCUSSION: Not only is there a link between aerobic fitness, motor function, and constipation in people with PD, but there seems to be aerobic fitness benchmarks (i.e., HI vs. LO) that clinicians can use to improve the fitness status of their patients. In doing so, this can not only lead to improvements in motor function, but also improved gut health in people with PD. REFERENCES 1. McCann H, Cartwright H, Halliday GM. Neuropathology of alpha-synuclein propagation and braak hypothesis. Mov Disord. 2016;31(2):152-160. 2. Aho VTE, Pereira PAB, Voutilainen S, et al. Gut microbiota in Parkinson\u27s disease: Temporal stability and relations to disease progression. EBioMedicine. 2019;44:691-707. 3. Scheperjans F, Aho V, Pereira PA, et al. Gut microbiota are related to Parkinson\u27s disease and clinical phenotype. Mov Disord. 2015;30(3):350-358. 4. Heintz-Buschart A, Pandey U, Wicke T, et al. The nasal and gut microbiome in Parkinson\u27s disease and idiopathic rapid eye movement sleep behavior disorder. Mov Disord. 2018;33(1):88-98. 5. Cilia R, Piatti M, Cereda E, et al. Does Gut Microbiota Influence the Course of Parkinson\u27s Disease? A 3-Year Prospective Exploratory Study in de novo Patients. J Parkinsons Dis. 2021;11(1):159-170. 6. Ren T, Gao Y, Qiu Y, et al. Gut Microbiota Altered in Mild Cognitive Impairment Compared With Normal Cognition in Sporadic Parkinson\u27s Disease. Front Neurol. 2020;11:137. 7. Fasano A, Visanji NP, Liu LW, Lang AE, Pfeiffer RF. Gastrointestinal dysfunction in Parkinson\u27s disease. Lancet Neurol. 2015;14(6):625-639. 8. Adams-Carr KL, Bestwick JP, Shribman S, Lees A, Schrag A, Noyce AJ. Constipation preceding Parkinson\u27s disease: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2016;87(7):710-716. 9. Clarke SF, Murphy EF, O\u27Sullivan O, et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. 2014;63(12):1913-1920. 10. Durk RP, Castillo E, Marquez-Magana L, et al. Gut Microbiota Composition Is Related to Cardiorespiratory Fitness in Healthy Young Adults. Int J Sport Nutr Exerc Metab. 2019;29(3):249-253. 11. Yang Y, Shi Y, Wiklund P, et al. The Association between Cardiorespiratory Fitness and Gut Microbiota Composition in Premenopausal Women. Nutrients. 2017;9(8). 12. Estaki M, Pither J, Baumeister P, et al. Cardiorespiratory fitness as a predictor of intestinal microbial diversity and distinct metagenomic functions. Microbiome. 2016;4(1):42. 13. Barton W, Penney NC, Cronin O, et al. The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level. Gut. 2018;67(4):625-633. 14. Cronin O, Barton W, Skuse P, et al. A Prospective Metagenomic and Metabolomic Analysis of the Impact of Exercise and/or Whey Protein Supplementation on the Gut Microbiome of Sedentary Adults. mSystems. 2018;3(3). 15. Resende AS, Leite GSF, Lancha Junior AH. Changes in the Gut Bacteria Composition of Healthy Men with the Same Nutritional Profile Undergoing 10-Week Aerobic Exercise Training: A Randomized Controlled Trial. Nutrients. 2021;13(8). 16. Louis S, Tappu RM, Damms-Machado A, Huson DH, Bischoff SC. Characterization of the Gut Microbial Community of Obese Patients Following a Weight-Loss Intervention Using Whole Metagenome Shotgun Sequencing. PLoS One. 2016;11(2):e0149564. 17. Kang SS, Jeraldo PR, Kurti A, et al. Diet and exercise orthogonally alter the gut microbiome and reveal independent associations with anxiety and cognition. Mol Neurodegener. 2014;9:36. 18. Campbell SC, Wisniewski PJ, Noji M, et al. The Effect of Diet and Exercise on Intestinal Integrity and Microbial Diversity in Mice. PLoS One. 2016;11(3):e0150502. 19. Allen JM, Mailing LJ, Cohrs J, et al. Exercise training-induced modification of the gut microbiota persists after microbiota colonization and attenuates the response to chemically-induced colitis in gnotobiotic mice. Gut Microbes. 2018;9(2):115-130. 20. Uhrbrand A, Stenager E, Pedersen MS, Dalgas U. Parkinson\u27s disease and intensive exercise therapy--a systematic review and meta-analysis of randomized controlled trials. J Neurol Sci. 2015;353(1-2):9-19. 21. Li Y, Song H, Shen L, Wang Y. The efficacy and safety of moderate aerobic exercise for patients with Parkinson\u27s disease: a systematic review and meta-analysis of randomized controlled trials. Ann Palliat Med. 2021;10(3):2638-2649. 22. Fisher BE, Wu AD, Salem GJ, et al. The effect of exercise training in improving motor performance and corticomotor excitability in people with early Parkinson\u27s disease. Arch Phys Med Rehabil. 2008;89(7):1221-1229. 23. Tabak R, Aquije G, Fisher BE. Aerobic exercise to improve executive function in Parkinson disease: a case series. J Neurol Phys Ther. 2013;37(2):58-64. 24. Rikli RE, Jones CJ. Senior fitness test manual. Champaign, IL: Human Kinetics; 2001. 25. Enright PL, Sherrill DL. Reference equations for the six-minute walk in healthy adults. Am J Respir Crit Care Med. 1998;158(5 Pt 1):1384-1387

Aerobic Fitness Levels Relate to Cognitive Function in People with Parkinson’s Disease as Assessed by the 6 Minute Walk Test

While individuals with Parkinson’s disease (PD) present with impaired motor control, 26% demonstrate cognitive impairment independent of dementia1. In fact, cognitive dysfunction often predates motor impairments and can diminish quality of life2 as well as life expectancy3. Fortunately, aerobic exercise has been shown to improve cognition in older adults4 as well as PD patients5-7. However, only a limited number of studies have determined a clear relationship between aerobic fitness levels and cognition in people with PD. Determining whether cognitive status and aerobic fitness levels are associated in people with PD would provide greater evidence for intervention focused on aerobic fitness that has a goal of improving cognition. Using the 6-minute walk test (6MWT), we were able to categorize participants based on their aerobic fitness levels9. This categorization allowed us to test the relationship between cognitive status and aerobic fitness. PURPOSE:The purpose of this study is to identify differences in cognition in people with PD who meet aerobic fitness norms compared to those who do not meet aerobic fitness norms. METHODS:19 people with PD (Hoehn & Yahr stages I-III) were recruited. Aerobic fitness was assessed via estimated oxygen consumption using the 6MWT (VO2 peak) This test has shown test-retest reliability in people with PD8. 6MWT classifications were used to determine if participants met (PD-HI) or did not meet fitness norms (PD-LO). Cognitive function was assessed via the Montreal Cognitive Assessment (MoCA) and scored out of 30 points. To compare the two groups, a Welch’s Two Sample T-Test was performed using the R Statistical Program, and p-values were set to \u3c0.05. RESULTS: The PD-HI group (n=9) had a mean MoCA score of 26.0(+/-1.5). The PD-LO group (n=10) had a mean MoCA score of 22.4(+/-3.2). The PD-HI group had significantly higher MoCA scores compared with the PD-LO group (p=0.004). CONCLUSION: This study is one of the first to observe a relationship between increased MoCA scores and high aerobic fitness status in populations with PD

Identification of potential neuromotor mechanisms of manual therapy in patients with musculoskeletal disablement: rationale and description of a clinical trial

<p>Abstract</p> <p>Background</p> <p>Many health care practitioners use a variety of hands-on treatments to improve symptoms and disablement in patients with musculoskeletal pathology.</p> <p>Research to date indirectly suggests a potentially broad effect of manual therapy on the neuromotor processing of functional behavior within the supraspinal central nervous system (CNS) in a manner that may be independent of modification at the level of local spinal circuits. However, the effect of treatment speed, as well as the specific mechanism and locus of CNS changes, remain unclear.</p> <p>Methods/Design</p> <p>We developed a placebo-controlled, randomized study to test the hypothesis that manual therapy procedures directed to the talocrural joint in individuals with post-acute ankle sprain induce a change in corticospinal excitability that is relevant to improve the performance of lower extremity functional behavior.</p> <p>Discussion</p> <p>This study is designed to identify potential neuromotor changes associated with manual therapy procedures directed to the appendicular skeleton, compare the relative effect of treatment speed on potential neuromotor effects of manual therapy procedures, and determine the behavioral relevance of potential neuromotor effects of manual therapy procedures.</p> <p>Trial Registration</p> <p><url>http://www.clinicaltrials.gov</url> identifier NCT00847769.</p

Alteration in corticospinal excitability, talocrural joint range of motion, and lower extremity function following manipulation in non-disabled individuals

Background: Clinical outcomes of manual therapy procedures, including manipulation, have been studied. However, mechanisms underlying observed improvements remain unclear. Objective: To determine the effect of ankle joint manipulation on corticospinal excitability, ankle dorsiflexion range of motion (DF ROM), and lower extremity functional behavior in nondisabled individuals. Method: Six nondisabled individuals (age range: 31-50 years) received the main outcomes measurements of this study, before and after long axis distraction manipulation of the talocrural joint. Main outcomes measures were motor evoked potential (MEP) amplitude of gastrocnemius (GN) and tibialis anterior (TA) using transcranial magnetic stimulation, ankle DF ROM with the knee flexed and extended using standard goniometric techniques, and unilateral anterior squat reach (ASR) distance. All subjects received the main outcomes measures. Results: Significant increase in GN MEP amplitude (P \u3c .05), but not TA MEP amplitude, were documented following intervention. Significant improvements also were noted in ankle DF ROM with knee extended and flexed (P \u3c .001) and ASR distance (P \u3c .05) Significant correlations were found between standardized change in GN MEP amplitude and ankle dorsiflexion with knee flexed (ρ = .582, ρ 2 = .339, P \u3c .01), and standardized changes in GN MEP amplitude and ASR distance (ρ = .601, ρ 2 = .361, P \u3c .01). Conclusions: Increased corticospinal excitability appears to mediate improvements in ankle DF ROM and lower extremity function following long axis distraction manipulation 1 Assistant Professor, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, to the talocrural joint in nondisabled individuals. These results establish comparative values with which to compare the corticospinal responses to manual therapy intervention in individuals with pathology. INTRODUCTION Ankle sprains are the most common injury to the ankle joint, affecting up to 2 million people and approximately 53 per 10,000 individuals per year. 1,2 Ankle sprains are common in younger and active individuals. 3-8 Certain sports and work activities may result in an even higher incidence and risk for injury. 9-15 Ankle sprains are a clinically important problem because they result in a substantial number of missed work days 8 and participation in sports activity, 3,5 as well as lead to potential early arthritic changes in the talocrural joint. 16 The prognosis for functional recovery following ankle sprain typically includes a rapid clinical improvement within the first two weeks after injury. 17 However, a series of recent studies indicate a subgroup of individuals appears predisposed to continued pain, functional deficits, and prolonged risk for additional reinjury between 6 weeks and 3 years post injury. 17-25 The prolonged disability associated with ankle sprains represents the possibility of increased direct and indirect health care costs associated with ankle sprains, and may be reduced through identification of optimal approaches to clinical management. One reason for continued pain and elevated risk for reinjury may be limited ankle joint mobility, which may occur as either a cause or consequence of ankle sprain. Limited ankle dorsiflexion has been documented as a major short-term sequel to ankle sprain. 26,27 In addition, several studies have identified limited talocrural joint dorsiflexion range of motion (DF ROM) as an important predisposing factor to ankle sprains. 28-30 Limited ankle DF ROM will position the talocrural joint in plantar flexion during weight bearing activities. This position is notable because the most common mechanism of injury for ankle sprains involves plantar flex-ion and inversion of the ankle and foot. The injury mechanism places excessive load on the anterior talofibular ligament (ATFL). With failure of ATFL, secondary restraint to inversion occurs by way of the calcaneo-fibular and posterior talofibular ligaments, placing them at similar risk for injury. Thus, limited ankle DF ROM may result in injury and consequent structural and functional compromise of the ankle lateral collateral ligaments. Physical therapists use mobilization and manipulation to improve ankle DF ROM following ankle sprains. Despite the intuitive appeal of applying these procedures to promote parallel improvements in talocrural DF ROM and functioning in individuals following ankle sprains, this notion has been the focus of relatively few prospective studies. 31 Pellow and Brantingham 32 were among the first to report reduced pain and improved function in individuals with ankle sprains receiving an ankle mortise distraction technique. Whitman and colleagues 33 reported rapid functional improvement after talocrural manipulation in a competitive volleyball player with a mild unilateral

Within-day test-retest reliability of transcranial magnetic stimulation measurements of corticomotor excitability for gastrocnemius and tibialis anterior muscles

Background: Manual therapy interventions targeting the talocrural joint can improve gait and balance functions in individuals following ankle sprains. Less is known about the underlying mechanisms of functional improvements after manual therapy. One hypothesis involves change in corticomotor excitability (CE) following manual therapy procedures. Transcranial magnetic stimulation (TMS) is a brain imaging method that could provide important information regarding potential changes in CE associated with manual therapy techniques applied to the talocrural joint. However, within-day reliability of TMS to measure CE must first be established in order to measure CE changes associated with manual therapy procedures. Objective: To determine the within-day test-retest reliability of TMS CE measures for gastrocnemius (GAS) and tibialis anterior (TA) for use in test-retest designs assessing corticomotor excitability in manual therapy and exercise studies. Method: TMS measures, including motor evoked potential (MEP) amplitude and cortical silent period (CSP), were completed twice on the same day under resting and active conditions in n = 6 nondisabled participants. The absolute reliability (coefficient of variation), relative reliability (intraclass correlation coefficient), standard error of measures, and minimal detectable change outside the 95% confidence interval were calculated for both GAS and TA muscles in each experimental condition. Results: There were no statistically significant differences between the first and second TMS measurements. TMS measurements for GAS and TA demonstrated good absolute and relative test-retest reliability under the active condition, but not the resting condition. Discussion: TMS under the active condition can be reliably used to assess CE even in postural muscles with a small cortical representation area, such as GAS

R.A.Fisher, design theory, and the Indian connection

Design Theory, a branch of mathematics, was born out of the experimental statistics research of the population geneticist R. A. Fisher and of Indian mathematical statisticians in the 1930s. The field combines elements of combinatorics, finite projective geometries, Latin squares, and a variety of further mathematical structures, brought together in surprising ways. This essay will present these structures and ideas as well as how the field came together, in itself an interesting story.Comment: 11 pages, 3 figure

Multi-Site Identification and Generalization of Clusters of Walking Behaviors in Individuals With Chronic Stroke and Neurotypical Controls

Background Walking patterns in stroke survivors are highly heterogeneous, which poses a challenge in systematizing treatment prescriptions for walking rehabilitation interventions. Objectives We used bilateral spatiotemporal and force data during walking to create a multi-site research sample to: (1) identify clusters of walking behaviors in people post-stroke and neurotypical controls and (2) determine the generalizability of these walking clusters across different research sites. We hypothesized that participants post-stroke will have different walking impairments resulting in different clusters of walking behaviors, which are also different from control participants. Methods We gathered data from 81 post-stroke participants across 4 research sites and collected data from 31 control participants. Using sparse K-means clustering, we identified walking clusters based on 17 spatiotemporal and force variables. We analyzed the biomechanical features within each cluster to characterize cluster-specific walking behaviors. We also assessed the generalizability of the clusters using a leave-one-out approach. Results We identified 4 stroke clusters: a fast and asymmetric cluster, a moderate speed and asymmetric cluster, a slow cluster with frontal plane force asymmetries, and a slow and symmetric cluster. We also identified a moderate speed and symmetric gait cluster composed of controls and participants post-stroke. The moderate speed and asymmetric stroke cluster did not generalize across sites. Conclusions Although post-stroke walking patterns are heterogenous, these patterns can be systematically classified into distinct clusters based on spatiotemporal and force data. Future interventions could target the key features that characterize each cluster to increase the efficacy of interventions to improve mobility in people post-stroke

Topographic variation in soil erosion and accumulation determined with meteoric ¹⁰Be:Soil erosion and accumulation determined with meteoric 10Be

Understanding natural soil redistribution processes is essential for measuring the anthropogenic impact on landscapes. Although meteoric beryllium-10 (10Be) has been used to determine erosion processes within the Pleistocene and Holocene, fewer studies have used the isotope to investigate the transport and accumulation of the resulting sediment. Here we use meteoric 10Be in hilltop and valley site soil profiles to determine sediment erosion and deposition processes in the Christina River Basin (Pennsylvania, USA). The data indicate natural erosion rates of 14 to 21 mm 10−3yr and soil ages of 26 000 to 57 000 years in hilltop sites. Furthermore, valley sites indicate an alteration in sediment supply due to climate change (from the Pleistocene to the Holocene) within the last 60 000 years and sediment deposition of at least 0.5-2 m during the Wisconsinan glaciation. The change in soil erosion rate was most likely induced by changes in geomorphic processes; probably solifluction and slope wash during the cold period, when ice advanced into the mid latitudes of North America. This study shows the value of using meteoric10Be to determine sediment accumulation within the Quaternary and quantifies major soil redistribution occurred under natural conditions in this region

A Functional Signature Ontology (FUSION) screen detects an AMPK inhibitor with selective toxicity toward human colon tumor cells

AMPK is a serine threonine kinase composed of a heterotrimer of a catalytic, kinase-containing α and regulatory β and γ subunits. Here we show that individual AMPK subunit expression and requirement for survival varies across colon cancer cell lines. While AMPKα1 expression is relatively consistent across colon cancer cell lines, AMPKα1 depletion does not induce cell death. Conversely, AMPKα2 is expressed at variable levels in colon cancer cells. In high expressing SW480 and moderate expressing HCT116 colon cancer cells, siRNA-mediated depletion induces cell death. These data suggest that AMPK kinase inhibition may be a useful component of future therapeutic strategies. We used Functional Signature Ontology (FUSION) to screen a natural product library to identify compounds that were inhibitors of AMPK to test its potential for detecting small molecules with preferential toxicity toward human colon tumor cells. FUSION identified 5′-hydroxy-staurosporine, which competitively inhibits AMPK. Human colon cancer cell lines are notably more sensitive to 5′-hydroxy-staurosporine than are non-transformed human colon epithelial cells. This study serves as proof-of-concept for unbiased FUSION-based detection of small molecule inhibitors of therapeutic targets and highlights its potential to identify novel compounds for cancer therapy development