The missing link between action and cognition

The study of the neural correlates of motor behaviour at the systems level has received increasing consideration in recent years. One emerging observation from this research is that neural regions typically associated with cognitive operations may also be recruited during the performance of motor tasks. This apparent convergence between action and cognition - domains that have most often been studied in isolation - becomes especially apparent when examining new complex motor skills such as those involving sequencing or coordination, and when taking into account external (environment-related) factors such as feedback availability and internal (performer-related) factors such as pathology. Neurally, overlap between action and cognition is prominent in frontal lobe areas linked to response selection and monitoring. Complex motor tasks are particularly suited to reveal the crucial link between action and cognition and the generic brain areas at the interface between these domains.     

REPIMPACT - a prospective longitudinal multisite study on the effects of repetitive head impacts in youth soccer

Brain Imaging and Behavior - Repetitive head impacts (RHI) are common in youth athletes participating in contact sports. RHI differ from concussions; they are considered hits to the head that...     

A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis

Androgens control spermatogenesis, but germ cells themselves do not express a functional androgen receptor (AR). Androgen regulation is thought to be mediated by Sertoli and peritubular myoid cells, but their relative roles and the mechanisms involved remain largely unknown. Using Cre/loxP technology, we have generated mice with a ubiquitous knockout of the AR as well as mice with a selective AR knockout in Sertoli cells (SC) only. Mice with a floxed exon 2 of the AR gene were crossed with mice expressing Cre recombinase ubiquitously or selectively in SC (under control of the anti-Müllerian hormone gene promoter). AR knockout males displayed a complete androgen insensitivity phenotype. Testes were located abdominally, and germ cell development was severely disrupted. In contrast, SC AR knockout males showed normal testis descent and development of the male urogenital tract. Expression of the homeobox gene Pem, which is androgen-regulated in SC, was severely decreased. Testis weight was reduced to 28% of that in WT littermates. Stereological analysis indicated that the number of SC was unchanged, whereas numbers of spermatocytes, round spermatids, and elongated spermatids were reduced to 64%, 3%, and 0% respectively of WT. These changes were associated with increased germ cell apoptosis and grossly reduced expression of genes specific for late spermatocyte or spermatid development. It is concluded that cell-autonomous action of the AR in SC is an absolute requirement for androgen maintenance of complete spermatogenesis, and that spermatocyte/spermatid development/survival critically depends on androgens.     

Underconnectivity of the superior temporal sulcus predicts emotion recognition deficits in autism

Neurodevelopmental disconnections have been assumed to cause behavioral alterations in autism spectrum disorders (ASDs). Here, we combined measurements of intrinsic functional connectivity (iFC) from resting-state functional magnetic resonance imaging (fMRI) with task-based fMRI to explore whether altered activity and/or iFC of the right posterior superior temporal sulcus (pSTS) mediates deficits in emotion recognition in ASD. Fifteen adults with ASD and 15 matched-controls underwent resting-state and task-based fMRI, during which participants discriminated emotional states from point light displays (PLDs). Intrinsic FC of the right pSTS was further examined using 584 (278 ASD/306 controls) resting-state data of the Autism Brain Imaging Data Exchange (ABIDE). Participants with ASD were less accurate than controls in recognizing emotional states from PLDs. Analyses revealed pronounced ASD-related reductions both in task-based activity and resting-state iFC of the right pSTS with fronto-parietal areas typically encompassing the action observation network (AON). Notably, pSTS-hypo-activity was related to pSTS-hypo-connectivity, and both measures were predictive of emotion recognition performance with each measure explaining a unique part of the variance. Analyses with the large independent ABIDE dataset replicated reductions in pSTS-iFC to fronto-parietal regions. These findings provide novel evidence that pSTS hypo-activity and hypo-connectivity with the fronto-parietal AON are linked to the social deficits characteristic of ASD.     

Task switching in traumatic brain injury relates to cortico‐subcortical integrity

Suppressing and flexibly adapting actions are a critical part of our daily behavioral repertoire. Traumatic brain injury (TBI) patients show clear impairments in this type of action control; however, the underlying mechanisms are poorly understood. Here, we tested whether white matter integrity of cortico‐subcortical pathways could account for impairments in task switching, an important component of executive functioning. Twenty young adults with TBI and eighteen controls performed a switching task requiring attention to global versus local stimulus features. Diffusion weighted images were acquired and whole brain tract‐based spatial statistics (TBSS) were used to explore where white matter damage was associated with switching impairment. A crossing fiber model and probabilistic tractography further identified the specific fiber populations. Relative to controls, patients with a history of TBI had a higher switch cost and were less accurate. The TBI group showed a widespread decline in fractional anisotropy (FA) throughout the TBSS skeleton. FA in the superior corona radiata showed a negative relationship with switch cost. More specifically, this involved cortico‐subcortical loops with the (pre‐)supplementary motor area and superior frontal gyrus. These findings provide evidence for damage to frontal‐subcortical projections in TBI, which is associated with task switching impairments. Hum Brain Mapp 35:2459–2469, 2014. © 2013 Wiley Periodicals, Inc.     

Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide Using Non–First-Degree Related Donors

Outcomes of nonmyeloablative (NMA) haploidentical (haplo) blood or marrow transplant (BMT) with post-transplantation cyclophosphamide (PTCy) using non–first-degree relatives are unknown. We evaluated 33 consecutive adult patients (median age, 56 years) with hematologic malignancies who underwent NMA haplo T cell–replete BMT with PTCy at Johns Hopkins using second- or third-degree related donors. Donors consisted of 10 nieces (30%), 9 nephews (27%), 7 first cousins (21%), 5 grandchildren (15%), and 2 uncles (6%). Thirty-one patients (94%) reached full donor chimerism by day 60. The estimated cumulative incidence (CuI) of grades II to IV acute graft-versus-host disease (aGVHD) at day 180 was 24% (90% confidence interval [CI], 9% to 38%). Only 1 patient experienced grades III to IV aGVHD. At 1 year the CuI of chronic GVHD was 10% (90% CI, 0% to 21%). The CuI of nonrelapse mortality at 1 year was 5% (90% CI, 0% to 14%). At 1 year the probability of relapse was 31% (90% CI, 12% to 49%), progression-free survival 64% (90% CI, 48% to 86%), and overall survival 95% (90% CI, 87% to 100%). The 1-year probability of GVHD-free, relapse-free survival was 57% (90% CI, 41% to 79%). NMA haplo BMT with PTCy from non–first-degree relatives is an acceptably safe and effective alternative donor platform, with results similar to those seen with first-degree relatives.     

Disclosure and health-seeking behaviour following intimate partner violence before and during pregnancy in Flanders, Belgium: a survey surveillance study

OBJECTIVES: The objectives were to estimate the prevalence of physical and sexual intimate partner violence (IPV) among a regional sample of the general obstetric population as the lifetime prevalence, as the 1-year period prevalence before pregnancy, and as the prevalence during the index pregnancy; to assess the rates of disclosure and help-seeking behaviour with IPV; and to determine the acceptability of screening for IPV. STUDY DESIGN: A multi-centred survey surveillance study was carried out among pregnant women attending five large hospitals in the province of East Flanders, Belgium as a regional probability sample of the general obstetric population. Data were collected through an anonymous, written questionnaire that included the Abuse Assessment Screen and additional questions on the circumstances of the most recent episode of physical or sexual violence, on disclosure and help-seeking behaviour, on reporting assault to the police, and on the acceptability of routine screening for IPV. RESULTS: The sampling frame consisted of 1362 women who received the questionnaire at the antenatal service during a 2-month study period, of which 537 (mean age 29.4 years, S.D. 4.09) returned the envelope (response rate 39.4%). The lifetime prevalence of IPV was estimated to be 10.1% (95% CI 7.7-13.0%) and the period prevalence of IPV during pregnancy and/or in the year preceding pregnancy 3.4% (95% CI 2.1-5.4%). There was a significant difference in the reported lifetime prevalence of IPV between women attending with a partner and those who came to the prenatal visit unattended by their partner in particular (6.8% versus 13.9%, p=0.010). Overall, only 19.2% (23 out of 120) and as few as 6.6% (4 out of 61) of the victims of physical and sexual abuse respectively sought medical care by consulting a general practitioner, gynaecologist, or an emergency department. Routine screening for IPV by a general practitioner or gynaecologist was found to be largely acceptable. CONCLUSIONS: In our highly medicalised society, women experiencing partner violence rarely disclose abuse to the widely available health care services, unless they are directly asked about it, which appears an acceptable practice. Hence, there is a definite need to improve women's awareness regarding abuse and their help-seeking behaviour at a public health level.     

A standardized framework for the validation and verification of clinical molecular genetic tests

The validation and verification of laboratory methods and procedures before their use in clinical testing is essential for providing a safe and useful service to clinicians and patients. This paper outlines the principles of validation and verification in the context of clinical human molecular genetic testing. We describe implementation processes, types of tests and their key validation components, and suggest some relevant statistical approaches that can be used by individual laboratories to ensure that tests are conducted to defined standards.