Single-Task and Dual-Task Gait Performance After Sport-Related Concussion: A Machine Learning Statistical Approach.

BACKGROUND: This study evaluated 2 different dual-task (DT) conditions during tandem gait (TG) to predict sport-related concussion (SRC) diagnosis. HYPOTHESIS: The best (fastest) single-task (ST) gait will differ between groups (controls vs SRC; baseline vs SRC), with auditory pure switching task (APST) response rate being the most important behavioral variable to aid prediction of SRC. STUDY DESIGN: Cohort design. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 409 National Collegiate Athletic Association Division I student-athlete controls and 21 team-physician-diagnosed SRC participated. All data were collected at preseason physicals (baseline) and within 7 days of injury for SRC. Each participant completed 3 conditions of TG in a pseudorandomized order: (1) ST, (2) DT with serial-7s (SS) subtractions, and (3) DT with APST. Outcomes of time-to-complete for TG and behavioral (eg, responses per second) for SS and APST were recorded for each trial. RESULTS: ST Trials 2 (P = 0.03) and 3 (P = 0.01) were significantly different between controls and SRC. ST Trial 3 (P = 0.04) was significantly different between baseline and SRC. Average responses per second for APST were significantly different between- (P < 0.01) and within- (P = 0.01) group. CONCLUSION: The results suggest that ST is significantly slower after SRC. However, DT (both SS and APST) time-to-complete are also important variables when predicting the SRC diagnosis. It is advised that both ST and DT be administered when making clinical decisions regarding postural instability after SRC. CLINICAL RELEVANCE: The best ST TG time to complete gait is an important objective marker of concussion while DT paradigms, specifically SS and APST, are highly variable. DT may be more useful for clinical observable signs of SRC. Both SS and APST have unique usefulness, but APST response rate per second can be relied upon numerically for clinical decisions.

Short communication: Binocular rivalry dynamics during locomotion.

Locomotion has been shown to impact aspects of visual processing in both humans and animal models. In the current study, we assess the impact of locomotion on the dynamics of binocular rivalry. We presented orthogonal gratings, one contrast-modulating at 0.8 Hz (matching average step frequency) and the other at 3.2 Hz, to participants using a virtual reality headset. We compared two conditions: stationary and walking. We continuously monitored participants' foot position using tracking devices to measure the step cycle. During the walking condition, participants viewed the rivaling gratings for 60-second trials while walking on a circular path in a virtual reality environment. During the stationary condition, observers viewed the same stimuli and environment while standing still. The task was to continuously indicate the dominant percept via button press using handheld controllers. We found no significant differences between walking and standing for normalized dominance duration distributions, mean normalized dominance distributions, mean alternation rates, or mean fitted frequencies. Although our findings do not align with prior research highlighting distinctions in normalized dominance distributions between walking and standing, our study contributes unique evidence indicating that alternation rates vary across the step cycle. Specifically, we observed that the number of alternations is at its lowest during toe-off phases and reaches its peak at heel strike. This novel insight enhances our understanding of the dynamic nature of alternation patterns throughout the step cycle.

Continuous peripersonal tracking accuracy is limited by the speed and phase of locomotion.

Recent evidence suggests that perceptual and cognitive functions are codetermined by rhythmic bodily states. Prior investigations have focused on the cardiac and respiratory rhythms, both of which are also known to synchronise with locomotion-arguably our most common and natural of voluntary behaviours. Compared to the cardiorespiratory rhythms, walking is easier to voluntarily control, enabling a test of how natural and voluntary rhythmic action may affect sensory function. Here we show that the speed and phase of human locomotion constrains sensorimotor performance. We used a continuous visuo-motor tracking task in a wireless, body-tracking virtual environment, and found that the accuracy and reaction time of continuous reaching movements were decreased at slower walking speeds, and rhythmically modulated according to the phases of the step-cycle. Decreased accuracy when walking at slow speeds suggests an advantage for interlimb coordination at normal walking speeds, in contrast to previous research on dual-task walking and reach-to-grasp movements. Phasic modulations of reach precision within the step-cycle also suggest that the upper limbs are affected by the ballistic demands of motor-preparation during natural locomotion. Together these results show that the natural phases of human locomotion impose constraints on sensorimotor function and demonstrate the value of examining dynamic and natural behaviour in contrast to the traditional and static methods of psychological science.

Older adults with a history of falling exhibit altered cortical oscillatory mechanisms during continuous postural maintenance.

Background and Aim: The significant risk of falling in older adults 65 years or older presents a substantial problem for these individuals, their caretakers, and the health-care system at large. As the proportion of older adults in the United States is only expected to grow over the next few decades, a better understanding of physiological and cortical changes that make an older adult more susceptible to a fall is crucial. Prior studies have displayed differences in postural dynamics and stability in older adults with a fall history (FH) and those who are non-fallers (NF), suggesting surplus alterations that occur in some older adults (i.e., FH group) in addition to the natural aging process. Methods: The present study measured postural dynamics while the FH, NF, and young adult (YA) groups performed continuous postural maintenance. In addition, electroencephalography activity was recorded while participants performed upright postural stance to examine any group differences in cortical areas involved in postural control. Results: As expected, older participants (FH and NF) exhibited worse postural stability, as evidenced by increased excursion, compared to the YA group. Further, while NF and YA show increased alpha activity in occipital areas during the most demanding postural task (eyes closed), the FH group did not show any differences in occipital alpha power between postural tasks. Conclusions: As alpha activity reflects suppression of bottom-up processing and thus diversion of cognitive resources toward postural centers during more demanding postural maintenance, deficits in this regulatory function in the FH group are a possible impaired cortical mechanism putting these individuals at greater fall risk. Relevance for Patients: Impaired inhibitory function in older adults may impact postural control and increase their risk of falling. Interventions that aim at addressing cortical processing deficits may improve postural stability and facilitate independent living in this population.

Sport-related concussion adopt a more conservative approach to straight path walking and turning during tandem gait.

BACKGROUND: It is currently unknown what specific neuronal deficits influence postural instability following SRC; however, the modulation of postural control relies heavily on the appropriate integration of sensory information from the visual, vestibular, and somatosensory system. It is possible symptom provocation of vestibular or ocular function is related to unsteady gait patterns during tandem gait. AIM: The purpose of this study was to evaluate the differences in temporal and center of pressure (CoP) metrics during discrete events of instrumented tandem gait (iTG) among those with sport-related concussion (SRC) compared to healthy controls. Secondarily, this study attempted to evaluate the relationship between iTG CoP metrics and the Vestibular/Ocular Motor Screening (VOMS) Exam. MATERIALS AND METHODS: 30 collegiate athletes with SRC and 30 healthy controls completed three single task (ST) iTG trials on an instrumented walkway and the VOMS. All individuals with SRC were assessed within 24-48 h post-injury while all controls were measured during pre-participation physicals. CoP metrics in the anteroposterior (AP) and mediolateral (ML) directions and time to completion were evaluated during the first, turn and second pass of iTG between groups. VOMS score was correlated to the CoP metrics across the discrete events. RESULTS: Athletes with SRC took longer to complete tandem gait (P<0.001) along with the first pass, second pass but not the turn when compared to the control group. SRC had slower velocity in the AP direction during both the first (P<0.001) and second pass (P<0.001) with increased postural sway in the ML direction during the first pass (P=0.014). During the turn, athletes with SRC had postural sway in the ML direction (P=0.008). Finally, VOMS score was weakly negatively related to CoP velocity in the AP direction during first (r=-0.39) and second (r=-0.36) pass while being weakly positively related to postural sway during the turn (r=-0.30). CONCLUSIONS: Athletes with SRC adopted a more conservative walking pattern and the presence of vestibular and/or ocular symptoms influence the ability to perform heel-to-toe walking. RELEVANCE FOR PATIENTS: Individuals with SRC will walk slower during heel-to-toe walking and move more in the ML direction with great movement in the ML direction while en pointe turning. This may increase given the total amount of vestibular or vision symptoms following the SRC.

Repetitive head impacts affect mediolateral postural sway entropy in the absence of vision following a competitive athletic season: preliminary findings.

BACKGROUND: Repetitive head impacts (RHIs) have received more notice over the past decade. More sensitive measures, such as postural control, have been used to evaluate if there are biomechanical changes after RHI exposure. Similar to the clinical findings, most of the studies have failed to find any significant changes across an athletic season. However, these studies included those with a concussion history and only assessed postural control in the eyes open (EO) condition, rather than in both the EO and eyes closed (EC) conditions. AIM: The purpose of this study was to investigate postural control changes during quiet stance following a season of RHI in Division I football athletes who did not have a prior diagnosed signet ring cell compared to a group of non-RHI athletes with no history of a diagnosed sport-related concussion. MATERIALS AND METHODS: Eighteen male Division I athletes were recruited and met the inclusion criteria: Nine football athletes (RHI group) and nine baseball athletes (CON group). All athletes performed three 30 s trials while standing with feet together on a force platform during EC and EO conditions. Center of pressure data was analyzed with sample entropy (SampEn) in the anteroposterior (AP) and mediolateral (ML) directions. SampEn data were analyzed with a three-level linear mixed effects model or the multilevel model, with the three levels being condition, time, and group. RESULTS: The analysis reported no significant effect for SampEn AP, but reported a significant three-way interaction (Group by Task by Time) for SampEn ML. Specifically, SampEn ML was significantly higher for EC than EO for both groups. CONCLUSIONS: There are postural control changes from pre- to post-season, with the main contributor being EC postural control. Thus, there could be a change in the sensory reweighting dynamics due to RHI and the effect of sport. RELEVANCE FOR PATIENTS: RHI may be better assessed in the clinical setting with EC, rather than with EO. Furthermore, clinicians should include tasks that deprive sensory inputs to examine the effects of RHI.

Baseline Postural Control and Lower Extremity Injury Incidence Among Those With a History of Concussion.

CONTEXT: Lower extremity musculoskeletal (LEMSK) injury may be more prevalent among those with a history of sport-related concussion (SRC). OBJECTIVE: To investigate the relationship between baseline postural control metrics and the LEMSK injury incidence in National Collegiate Athletic Association Division I student-athletes with a history of SRC. SETTING: National Collegiate Athletic Association Division I athletes. DESIGN: Cohort study. PATIENTS OR OTHER PARTICIPANTS: Of 84 total athletes (62 males), 42 had been previously diagnosed with an SRC, and 42 were matched controls based on age, sex, height, weight, and sport. MAIN OUTCOME MEASURE(S): During the preseason baseline evaluation, all participants performed 3 trials of eyes-open and eyes-closed upright quiet stance on a force platform. Medical charts were assessed for all the LEMSK injuries that occurred from preseason baseline to 1 year later. Center-of-pressure data in the anteroposterior and mediolateral directions were filtered before we calculated root mean square and mean excursion velocity; the complexity index was calculated from the unfiltered data. Factorial analysis-of-variance models were used to examine differences between groups and across conditions for root mean square; mean excursion velocity, complexity index, and tests of association to examine between-groups LEMSK differences; and logistic regression models to predict LEMSK. RESULTS: Concussion history and injury incidence were related in the SRC group (P = .043). The complexity index of the SRC group was lower with eyes closed (14.08 ± 0.63 versus 15.93 ± 0.52) and eyes open (10.25 ± 0.52 vs 11.80 ± 0.57) in the mediolateral direction than for the control participants (P < .05). Eyes-open root mean square in the mediolateral direction was greater for the SRC group (5.00 ± 0.28 mm) than the control group (4.10 ± 0.22 mm). Logistic regression models significantly predicted LEMSK only in control participants. CONCLUSIONS: These findings may suggest that LEMSK after SRC cannot be predicted from postural-control metrics at baseline.

Smooth Pursuit and Saccades after Sport-Related Concussion.

Smooth pursuit eye movements (SPEMs) and saccadic eye movements are both commonly impaired following sport-related concussion (SRC). Typical oculomotor assessments measure individual eye movements in a series of restrictive tests designed to isolate features such as response times. These measures lack ecological validity for athletes because athletes are adept at simple tasks designed for the general population. Yet, because eye movement metrics are sensitive and well-characterized neuroanatomically, it would be valuable to test whether athletes exhibit abnormal eye movements with more challenging tasks. To address this gap in knowledge, we collected eye-tracking data during a sport-like task to gain insight on gaze behavior during active self-motion. SPEMs and saccadic eye movements were recorded during a sport-like visual task within 24-48 h following SRC. Thirty-six Division I student-athletes were divided into SRC and control (CON) groups. All participants completed two blocks of the Wii Fit© soccer heading game (WF) while wearing a monocular infrared eye tracker. Eye movement classification systems quantified saccadic amplitude (SA), velocity (SV), and count (SC); as well as SPEM velocity (SPV) and amplitude (SPA). Separate Mann-Whitney U tests evaluated SPA and SC and found no significant effects (SPA, p = 0.11; SC, p = 0.10). A multi-variate analysis of variance (MANOVA) for remaining variables revealed SPV was significantly greater in CON (p < 0.05), but the SRC group had greater SA and SV (p < 0.05). These findings suggest that during a sport-like task, to maintain foveation SRC subjects used larger amplitude, faster saccades, but exhibited slower SPEMs. Measuring oculomotor function during ecologically valid, sport-like tasks may serve as a concussion biomarker and provide insights into eye movement control after SRC.

The effect of acute pain on executive function.

BACKGROUND AND AIM: Executive functions are high-level cognitive processes that allow a person to success-fully engage in an independent and self-fulfilling life. Previous literature indicates that chronic pain can affect executive function, but there are limited studies that investigate the effect of acute pain on executive function. The purpose of this study was to determine if acute pain affects executive function in recreationally active indi-viduals who sustained a musculoskeletal injury. METHODS: Twenty-four recreationally active participants who presented with acute pain following a muscu-loskeletal injury underwent a neuropsychological battery within 72 hours of injury. Follow up testing occurred within two weeks from the initial testing session when participants were pain free. Pain intensity was measured using the Visual Analog Scale (VAS). The neuropsychological battery consisted of the following tests: Digit Span (DS), Rey Auditory Verbal Learning Test (RAVLT), and Trail Making Test B (TMT-B). The DS was bro-ken into two separate scores, the RAVLT four scores, and TMT-B one score. Seven paired samples t-tests were conducted using an adjusted alpha level of 0.007. RESULTS: Participants had significantly improved scores when pain free in DS forwards (p < 0.007) and TMT-B (p < 0.007). No significant difference was observed for the DS backward (p = 0.023), RAVLT A1 (p = 0.563), RAVLT sum A1 to A5 (p = 0.953), RAVLT A6 (p = 1.0), RAVLT recognition list A (p = 0.009). These results suggest that immediate recall and complex attention may be diminished in individ-uals who experience acute pain due to a musculoskeletal injury. CONCLUSIONS: Results from this study suggest acute pain from musculoskeletal injuries may disrupt executive function. RELEVANCE FOR PATIENTS: Patients should be aware that there may be cognitive changes after a musculoskeletal injury. Knowing which cognitive domains may be impaired during acute pain could impact clinical practice and further benefit patients suffering from pain and its associated symptoms.

Clinical Assessments of Balance in Adults with Concussion: An Update.

Postural instability is a cardinal indicator of concussion. Assessments of the postural control system range from clinical to laboratory tests that assess the balance of the individual. In a previous article regarding clinical assessment of balance in adults with concussion, we reviewed the importance of balance as a component in concussion evaluations. The purpose of this review article is to update the information previously published in 2014. Since 2014, research has provided evidence for the incorporation of dynamic methods for evaluating balance postconcussion with particular emphasis on sensory system integration and dual tasking. Therefore, this review will examine the current state of knowledge on how concussion injuries affect postural control, advancements in evaluating balance postconcussion, such as novel eye-tracking techniques, and current recommendations for best practices for balance assessment.

Inhibition of Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia.

While acute myeloid leukemia (AML) comprises many disparate genetic subtypes, one shared hallmark is the arrest of leukemic myeloblasts at an immature and self-renewing stage of development. Therapies that overcome differentiation arrest represent a powerful treatment strategy. We leveraged the observation that the majority of AML, despite their genetically heterogeneity, share in the expression of HoxA9, a gene normally downregulated during myeloid differentiation. Using a conditional HoxA9 model system, we performed a high-throughput phenotypic screen and defined compounds that overcame differentiation blockade. Target identification led to the unanticipated discovery that inhibition of the enzyme dihydroorotate dehydrogenase (DHODH) enables myeloid differentiation in human and mouse AML models. In vivo, DHODH inhibitors reduced leukemic cell burden, decreased levels of leukemia-initiating cells, and improved survival. These data demonstrate the role of DHODH as a metabolic regulator of differentiation and point to its inhibition as a strategy for overcoming differentiation blockade in AML.

Convergent evolution of phenotypic integration and its alignment with morphological diversification in Caribbean Anolis ecomorphs.

The adaptive landscape and the G-matrix are keys concepts for understanding how quantitative characters evolve during adaptive radiation. In particular, whether the adaptive landscape can drive convergence of phenotypic integration (i.e., the pattern of phenotypic variation and covariation summarized in the P-matrix) is not well studied. We estimated and compared P for 19 morphological traits in eight species of Caribbean Anolis lizards, finding that similarity in P among species was not correlated with phylogenetic distance. However, greater similarity in P among ecologically similar Anolis species (i.e., the trunk-ground ecomorph) suggests the role of convergent natural selection. Despite this convergence and relatively deep phylogenetic divergence, a large portion of eigenstructure of P is retained among our eight focal species. We also analyzed P as an approximation of G to test for correspondence with the pattern of phenotypic divergence in 21 Caribbean Anolis species. These patterns of covariation were coincident, suggesting that either genetic constraint has influenced the pattern of among-species divergence or, alternatively, that the adaptive landscape has influenced both G and the pattern of phenotypic divergence among species. We provide evidence for convergent evolution of phenotypic integration for one class of Anolis ecomorph, revealing yet another important dimension of evolutionary convergence in this group.

Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation.

Anemia of inflammation develops in settings of chronic inflammatory, infectious, or neoplastic disease. In this highly prevalent form of anemia, inflammatory cytokines, including IL-6, stimulate hepatic expression of hepcidin, which negatively regulates iron bioavailability by inactivating ferroportin. Hepcidin is transcriptionally regulated by IL-6 and bone morphogenetic protein (BMP) signaling. We hypothesized that inhibiting BMP signaling can reduce hepcidin expression and ameliorate hypoferremia and anemia associated with inflammation. In human hepatoma cells, IL-6-induced hepcidin expression, an effect that was inhibited by treatment with a BMP type I receptor inhibitor, LDN-193189, or BMP ligand antagonists noggin and ALK3-Fc. In zebrafish, the induction of hepcidin expression by transgenic expression of IL-6 was also reduced by LDN-193189. In mice, treatment with IL-6 or turpentine increased hepcidin expression and reduced serum iron, effects that were inhibited by LDN-193189 or ALK3-Fc. Chronic turpentine treatment led to microcytic anemia, which was prevented by concurrent administration of LDN-193189 or attenuated when LDN-193189 was administered after anemia was established. Our studies support the concept that BMP and IL-6 act together to regulate iron homeostasis and suggest that inhibition of BMP signaling may be an effective strategy for the treatment of anemia of inflammation.

Fecal bacterial diversity of human-habituated wild chimpanzees (Pan troglodytes schweinfurthii) at Mahale Mountains National Park, Western Tanzania.

Although the intestinal flora of chimpanzees has not been studied, insight into this dynamic environment can be obtained through studies on their feces. We analyzed fecal samples from human-habituated, wild chimpanzees at Mahale Mountains National Park, Tanzania, and compared microbial community profiles to determine if members of the same social group were similar. Between July and December 2007, we collected fresh fecal samples from 12 individuals: four juveniles, four adolescents, and four adults, including three parent-offspring pairs. Each sample was analyzed using Terminal-Restriction Fragment Length Polymorphism of amplified 16S rRNA genes. Twelve different profiles were generated, having between 1 and 15 Terminal-Restriction Fragments (T-RFs). Overall, a total of 23 different T-RFs were produced. Putative assignments of T-RFs corresponded to the phyla Firmicutes (Clostridia, Bacilli, and Lactobacilli), Bacteroidetes, Tenericutes (Mollicutes Class), Actinobacteria, and Proteobacteria, as well as to uncultured or unidentified organisms. Firmicutes and Bacteroidetes phyla and Mollicutes Class were the most commonly assigned in 11, 8, and 8 of the samples, respectively, with this being the first report of Mollicutes in wild chimpanzees. Principal Components Analysis (PCA) revealed clustering of nine samples, and 80.5% of the diversity was accounted for by three samples. Morisita indices of community similarity ranged between 0.00 and 0.89, with dissimiliarity (<0.5) between most samples when compared two at a time. Our findings suggest that, although phylotypes are common among individuals, profiles among members of the same social group are host-specific. We conclude that factors other than social group, such as kinship and age, may influence fecal bacterial profiles of wild chimpanzees, and recommend that additional studies be conducted.

Descriptive epidemiology of fatal respiratory outbreaks and detection of a human-related metapneumovirus in wild chimpanzees (Pan troglodytes) at Mahale Mountains National Park, Western Tanzania.

Over the past several years, acute and fatal respiratory illnesses have occurred in the habituated group of wild chimpanzees at the Mahale Mountains National Park, Tanzania. Common respiratory viruses, such as measles and influenza, have been considered possible causative agents; however, neither of these viruses had been detected. During the fatal respiratory illnesses in 2003, 2005 and 2006, regular observations on affected individuals were recorded. Cause-specific morbidity rates were 98.3, 52.4 and 33.8%, respectively. Mortality rates were 6.9, 3.2 and 4.6%; all deaths were observed in infants 2 months-2 years 9 months of age. Nine other chimpanzees have not been seen since the 2006 outbreak and are presumed dead; hence, morbidity and mortality rates for 2006 may be as high as 47.7 and 18.5%, respectively. During the 2005 and 2006 outbreaks, 12 fecal samples were collected from affected and nonaffected chimpanzees and analyzed for causative agents. Analysis of fecal samples from 2005 suggests the presence of paramyxovirus, and in 2006 a human-related metapneumovirus was detected and identified in an affected chimpanzee whose infant died during the outbreak. Our findings provide preliminary evidence that the causative agent associated with these illnesses is viral and contagious, possibly of human origin; and that, possibly more than one agent may be circulating in the population. We recommend that baseline health data be acquired and food wadge and fecal samples be obtained and bio-banked as early as possible when attempting to habituate new groups of chimpanzees or other great apes. For already habituated populations, disease prevention strategies, ongoing health monitoring programs and reports of diagnostic findings should be an integral part of managing these populations. In addition, descriptive epidemiology should be a major component of disease outbreak investigations.