Emotional State Affects the Initiation of Forward Gait

The aim of the current study was to determine the extent to which pleasant and unpleasant emotional states impact the initiation of forward gait. Participants initiated gait and walked for several steps following the presentation of low arousing pleasant, high arousing pleasant, low arousing unpleasant, high arousing unpleasant, and neutral pictures. Reaction time, displacement, and velocity of the center of pressure (COP) trajectory, and length and velocity of the first and second steps were calculated. Exposure to the highly arousing unpleasant pictures reduced reaction times compared to all other affective conditions. Compared to the low arousing unpleasant pictures, exposure to the high and low arousing pleasant pictures increased the displacement of the COP movement during the anticipatory postural adjustment phase of gait initiation. Additionally, exposure to the low arousing pleasant pictures increased the velocity of the COP movement during the anticipatory postural adjustment phase, compared to the high and low arousing unpleasant pictures. Exposure to the high and low arousing pleasant pictures increased the velocity of the first step relative to the low arousing unpleasant pictures. These findings demonstrate that highly arousing unpleasant emotional states accelerate the initial motor response, but pleasant emotional states generally facilitate the initiation of forward gait due to the approach-oriented directional salience of the movement. These findings extend the scope of the motivational direction hypothesis by demonstrating the effects of emotional reactivity on the initiation of gait

Decreased static and dynamic postural control in children with autism spectrum disorders

The purpose of this study was to investigate postural control in children with Autism Spectrum Disorders (ASD) during static and dynamic postural challenges. We evaluated postural sway during quiet standing and the center of pressure (COP) shift mechanism during gait initiation for thirteen children with ASD and twelve age matched typically developing (TD) children. Children with ASD produced 438% greater normalized mediolateral sway (p<0.05) and 104% greater normalized anteroposterior sway (p<0.05) than TD children. Consequently, normalized sway area was also significantly greater (p<0.05) in the group with ASD. Similarly, the maximum separation between the COP and center of mass (COM) during quiet stance was 100% greater in the anteroposterior direction (p<0.05) and 146% greater in the resultant direction (p<0.05) for children with ASD. No significant difference was observed in the mediolateral direction, in spite of the 123 % greater separation detected in children with ASD. During gait initiation, no group differences were detected in the posterior COP shift mechanism, suggesting the mechanism for generating forward momentum is intact. However, significantly smaller lateral COP shifts (p<0.05) were observed in children with ASD, suggesting instability or an alternative strategy for generating momentum in the mediolateral direction. These results help clarify some discrepancies in the literature, suggesting an impaired or immature control of posture, even under the most basic conditions when no afferent or sensory information have been removed or modified. Additionally, these findings provide new insight into dynamic balance in children with ASD

Changes in Midline Tremor and Gait Following Deep Brain Stimulation for Essential Tremor

Background: Essential tremor (ET) is a common movement disorder characterized by kinetic and postural tremor in the upper extremities and frequently in the midline. Persons with ET often also exhibit gait ataxia. Previous studies have observed associations between midline tremor severity and gait ataxia in persons with ET, suggesting a common pathophysiology distinct from that of upper extremity tremor. However, a causal link between midline tremor and gait impairment has not been established. Methods: We investigated tremor and gait in 24 persons with ET before and after implantation of unilateral deep brain stimulation into the ventralis intermedius nucleus of the thalamus. Results: Stimulation significantly improved tremor in the targeted upper extremity and midline. However, gait was unaffected at the cohort level. Furthermore, improvement in midline tremor was not significantly associated with gait improvement. Discussion: These findings revealed that midline tremor and gait impairment may be dissociable in persons with ET

Shannon and Renyi Entropies to Classify Effects of Mild Traumatic Brain Injury on Postural Sway

Background: Mild Traumatic Brain Injury (mTBI) has been identified as a major public and military health concern both in the United States and worldwide. Characterizing the effects of mTBI on postural sway could be an important tool for assessing recovery from the injury. Methodology/Principal Findings: We assess postural sway by motion of the center of pressure (COP). Methods for data reduction include calculation of area of COP and fractal analysis of COP motion time courses. We found that fractal scaling appears applicable to sway power above about 0.5 Hz, thus fractal characterization is only quantifying the secondary effects (a small fraction of total power) in the sway time series, and is not effective in quantifying long-term effects of mTBI on postural sway. We also found that the area of COP sensitively depends on the length of data series over which the COP is obtained. These weaknesses motivated us to use instead Shannon and Renyi entropies to assess postural instability following mTBI. These entropy measures have a number of appealing properties, including capacity for determination of the optimal length of the time series for analysis and a new interpretation of the area of COP. Conclusions: Entropy analysis can readily detect postural instability in athletes at least 10 days post-concussion so that it appears promising as a sensitive measure of effects of mTBI on postural sway

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Development of a Subject- Specific Foot-Ground Contact Model for Walking

Computational walking simulations could facilitate the development of improved treatments for clinical conditions affecting walking ability. Since an effective treatment is likely to change a patient&apos;s foot-ground contact pattern and timing, such simulations should ideally utilize deformable foot-ground contact models tailored to the patient&apos;s foot anatomy and footwear. However, no study has reported a deformable modeling approach that can reproduce all six ground reaction quantities (expressed as three reaction force components, two center of pressure (CoP) coordinates, and a free reaction moment) for an individual subject during walking. This study proposes such an approach for use in predictive optimizations of walking. To minimize complexity, we modeled each foot as two rigid segments-a hindfoot (HF) segment and a forefoot (FF) segment-connected by a pin joint representing the toes flexion-extension axis. Ground reaction forces (GRFs) and moments acting on each segment were generated by a grid of linear springs with nonlinear damping and Coulomb friction spread across the bottom of each segment. The stiffness and damping of each spring and common friction parameter values for all springs were calibrated for both feet simultaneously via a novel three-stage optimization process that used motion capture and ground reaction data collected from a single walking trial. The sequential three-stage process involved matching (1) the vertical force component, (2) all three force components, and finally (3) all six ground reaction quantities. The calibrated model was tested using four additional walking trials excluded from calibration. With only small changes in input kinematics, the calibrated model reproduced all six ground reaction quantities closely (root mean square (RMS) errors less than 13 N for all three forces, 25 mm for anterior-posterior (AP) CoP, 8 mm for medial-lateral (ML) CoP, and 2 NÁm for the free moment) for both feet in all walking trials. The largest errors in AP CoP occurred at the beginning and end of stance phase when the vertical ground reaction force (vGRF) was small. Subject-specific deformable foot-ground contact models created using this approach should enable changes in foot-ground contact pattern to be predicted accurately by gait optimization studies, which may lead to improvements in personalized rehabilitation medicine