The long term effects of sports concussion on retired Australian football players: a study using Transranial Magnetic Stimulation

This study investigated corticomotor excitability and inhibition, cognitive functioning, and fine motor dexterity in retired elite and amateur Australian football (AF) players who had sustained concussions during their playing careers. Forty male AF players who played at the elite level (n=20; mean age 49.7±5.7 years) or amateur level (n=20; mean age 48.4±6.9 years), and had sustained on average 3.2 concussions 21.9 years previously, were compared with 20 healthy age-matched male controls (mean age 47.56±6.85 years). All participants completed assessments of fine dexterity, visuomotor reaction time, spatial working memory (SWM), and associative learning (AL). Transcranial magnetic stimulation (TMS) was used to measure corticospinal excitability: stimulus-response (SR) curves and motor evoked potential (MEP) 125% of active motor threshold (aMT); and intracortical inhibition: cortical silent period (cSP), short-interval intracortical inhibition (SICI), and long-interval intracortical inhibition (LICI). Healthy participants performed better in dexterity (p=0.003), reaction (p=0.003), and movement time (p=0.037) than did both AF groups. Differences between AF groups were found in AL (p=0.027) and SWM (p=0.024). TMS measures revealed that both AF groups showed reduced cSP duration at 125% aMT (p>0.001) and differences in SR curves (p>0.001) than did healthy controls. Similarly, SICI (p=0.012) and LICI (p=0.009) were reduced in both AF groups compared with controls. Regression analyses revealed a significant contribution to differences in motor outcomes with the three measures of intracortical inhibition. The measures of inhibition differed, however, in terms of which performance measure they had a significant and unique predictive relationship with, reflecting the variety of participant concussion injuries. This study is the first to demonstrate differences in motor control and intracortical inhibition in AF players who had sustained concussions during their playing career two decades previously

Spatial distribution of cerebral white matter lesions predicts progression to mild cognitive impairment and dementia

CONTEXT White matter lesions (WML) increase the risk of dementia. The relevance of WML location is less clear. We sought to determine whether a particular WML profile, based on the density and location of lesions, could be associated with an increased risk of mild cognitive impairment (MCI) or dementia over the following 7 years. METHODS In 426 healthy subjects from a cohort of community-dwelling people aged 65 years and over (ESPRIT Project), standardized cognitive and neurological evaluations were repeated after 2, 4 and 7 years. Patterns of WML were computed with a supervised data mining approach (decision trees) using the regional WML volumes (frontal, parietal, temporal, and occipital regions) and the total WML volume estimated at baseline. Cox proportional hazard models were then constructed to study the association between WML patterns and risk of MCI/dementia. RESULTS Total WML volume and percentage of WML in the temporal region proved to be the best predictors of progression to MCI and dementia. Specifically, severe total WML load with a high proportion of lesions in the temporal region was significantly associated with the risk of developing MCI or dementia. CONCLUSIONS Above a certain threshold of damage, a pattern of WML clustering in the temporal region identifies individuals at increased risk of MCI or dementia. As this WML pattern is observed before the onset of clinical symptoms, it may facilitate the detection of patients at risk of MCI/dementia.The ESPRIT Project is financed by the regional government of Languedoc-Roussillon (http://www.laregion.fr), the Agence Nationale de la Recherche (ANR: http://www.agence-nationale-recherche.fr) and an unconditional grant from Novartis (http://www.novartis.fr). This study is also supported by France Alzheimer (http://www.francealzheimer.org/)

Galaxy-scale Star Formation on the Red Sequence: the Continued Growth of S0s and the Quiescence of Ellipticals

This paper examines star formation (SF) in relatively massive, primarily early-type galaxies (ETGs) at z~0.1. A sample is drawn from bulge-dominated GALEX/SDSS galaxies on the optical red sequence with strong UV excess and yet quiescent SDSS spectra. High-resolution far-UV imaging of 27 such ETGs using HST ACS/SBC reveals structured UV morphology in 93% of the sample, consistent with low-level ongoing SF (~0.5 Ms/yr). In 3/4 of the sample the SF is extended on galaxy scales (25-75 kpc), while the rest contains smaller (5-15 kpc) SF patches in the vicinity of an ETG - presumably gas-rich satellites being disrupted. Optical imaging reveals that all ETGs with galaxy-scale SF in our sample have old stellar disks (mostly S0 type). None is classified as a true elliptical. In our sample, galaxy-scale SF takes the form of UV rings of varying sizes and morphologies. For the majority of such objects we conclude that the gas needed to fuel current SF has been accreted from the IGM, probably in a prolonged, quasi-static manner, leading in some cases to additional disk buildup. The remaining ETGs with galaxy-scale SF have UV and optical morphologies consistent with minor merger-driven SF or with the final stages of SF in fading spirals. Our analysis excludes that all recent SF on the red sequence resulted from gas-rich mergers. We find further evidence that galaxy-scale SF is almost exclusively an S0 phenomenon (~20% S0s have SF) by examining the overall optically red SDSS ETGs. Conclusion is that significant number of field S0s maintain or resume low-level SF because the preventive feedback is not in place or is intermittent. True ellipticals, on the other hand, stay entirely quiescent even in the field.Comment: Accepted for publication in ApJ. Contains color figures, but compatible with non-color printer

Bilateral volume reduction in posterior hippocampus in psychosis of epilepsy

Objective Psychosis of epilepsy (POE) occurs more frequently in temporal lobe epilepsy, raising the question as to whether abnormalities of the hippocampus are aetiologically important. Despite decades of investigation, it is unclear whether hippocampal volume is reduced in POE, perhaps due to small sample sizes and methodological limitations of past research. Methods In this study, we examined the volume of the total hippocampus, and the hippocampal head, body and tail, in a large cohort of patients with POE and patients with epilepsy without psychosis (EC). One hundred adults participated: 50 with POE and 50 EC. Total and subregional hippocampal volumes were manually traced and compared between (1) POE and EC; (2) POE with temporal lobe epilepsy, extratemporal lobe epilepsy and generalised epilepsy; and (3) patients with POE with postictal psychosis (PIP) and interictal psychosis (IP). Results Compared with EC the POE group had smaller total left hippocampus volume (13.5% decrease, p<0.001), and smaller left hippocampal body (13.3% decrease, p=0.002), and left (41.5% decrease, p<0.001) and right (36.4% decrease, p<0.001) hippocampal tail volumes. Hippocampal head volumes did not differ between groups. Conclusion Posterior hippocampal volumes are bilaterally reduced in POE. Volume loss was observed on a posteroanterior gradient, with severe decreases in the tail and moderate volume decreases in the body, with no difference in the hippocampal head. Posterior hippocampal atrophy is evident to a similar degree in PIP and IP. Our findings converge with those reported for the paradigmatic psychotic disorder, schizophrenia, and suggest that posterior hippocampal atrophy may serve as a biomarker of the risk for psychosis, including in patients with epilepsy.JA is supported by an Australian Postgraduate Award

Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations

Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p &lt; 5 × 10−9, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies. Delineation of the genetic architecture of hematological traits in a multi-ethnic dataset allows identification of rare variants with strong effects specific to non-European populations and improved fine mapping of GWAS variants using the trans-ethnic approach

Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps

We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci,135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency 2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).Peer reviewe

Neuroplasticity in normal and brain injured patients: Potential relevance of ear wiggling locus of control and cortical projections

Recovery after brain insult is variable. Research has shown that activation of higher-order cognitive processes create larger gains in recovery than repetitive tasks, most likely due to neuroplasticity. That is, neuroplasticity is promoted by task complexity. Ear wiggling is a rare skill among humans yet may activate and promote advanced recovery after a brain injury. Increased cognitive complexity of learning a new task could allow insights into plasticity in learning new motor tasks and the role of cognitive complexity in learning that task. This paper focuses on a hypothesis relating to white matter pathways dormant in most people (such as those related to ear wiggling). If these pathways can be triggered by electrical/magnetic stimulation and/or higher-order thought into becoming consciously controllable, then it is possible that activation of a dormant, complex skill may assist in re-growth or repair of brain-damaged pathways. The broader potential impact of the proposed hypothesis is that ear wiggling could be used for improving the recovery of TBI or stroke subjects via neuroplasticity processes

Diffusion tensor imaging reveals no white matter impairments among adults with autism spectrum disorder

Abnormalities within white matter (WM) have been identified in autism spectrum disorder (ASD). Although there is some support for greater neurobiological deficits among females with ASD, there is little research investigating sex differences in WM in ASD. We used diffusion tensor imaging (DTI) to investigate WM aberration in 25 adults with high-functioning ASD and 24 age-, sex- and IQ-matched controls. Tract-based spatial statistics (TBSS) was used to explore differences in WM in major tract bundles. The effects of biological sex were also investigated. TBSS revealed no differences in fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), or axial diffusivity (AD) between groups. There were no effects of biological sex. We consider whether methodological differences between past studies have contributed to the highly heterogeneous findings in the literature. Finally, we suggest that, among a high-functioning sample of adults with ASD, differences in WM microstructure may not be related to clinical impairment

Acute motor, neurocognitive and neurophysiological change following concussion injury in Australian amateur football. A prospective multimodal investigation

Objectives: This multimodal study investigated the motor, neurocognitive and neurophysiological responses following a sports related concussion injury in the acute-phase (up to 10 days) in sub-elite Australian football players. Design: Between-group, repeated measures. Methods: Over the course of one season (six months), 43 male players from one football club (25.1 ± 4.5 years) were assessed for fine motor dexterity, visuomotor reaction time, implicit learning and attention. Motor cortex excitability and inhibition were assessed using transcranial magnetic stimulation. Results: Of the 43 players, eight suffered concussion injuries, and were compared to 15 non-concussed players (active control) who returned for follow up testing. Post-concussion assessments using the aforementioned tests were carried out at 48 and 96 h, and 10 days. Compared to the non-concussed players, those who suffered concussion showed slowed fine dexterity (P = 0.02), response (P = 0.02) and movement times (P = 0.01) 48 h post-concussion. Similarly, attentional performance was reduced in the concussed group at all time points (48 h: P < 0.01; 96 h: P < 0.01; and 10 days: P = 0.02) post-concussion. TMS revealed significantly increased corticospinal inhibition at 48 (P = 0.04) and 96 h post concussion (P = 0.02) with significant correlations between increased corticospinal inhibition and response (r = 0.48; P < 0.01), movement time (r = 0.42; P = 0.02), and attention performance (r = 0.44; P = 0.01). Conclusions: This study has demonstrated that acutely concussed Australian football players show abnormalities in motor, cognitive and neurophysiological measures with variable rates of recovery. These findings suggest that measuring the recovery of concussed athletes should incorporate a range of testing modalities rather than relying on one area of measurement in determining return to pla