Sex and Gender Science: The World Writes on the Body.

Sex and Gender Science seeks to better acknowledge that the body cannot be removed from the world it inhabits. We believe that to best answer any neuroscience question, the biological and the social need to be addressed through both objective means to learn, "how it is like" and subjective means to learn, "what it is like." We call bringing the biological and social together, "Situated Neuroscience" and the mixing of approaches to do so, Very Mixed Methods. Taken together, they constitute an approach to Sex and Gender Science. In this chapter, we describe neural phenomena for which considering sex and gender together produces a fuller knowledge base: sleep, pain, memory, and concussion. For these brain phenomena examples, studying only quantitative measures does not reveal the full impact of these lived experiences on the brain but studying only the qualitative would not reveal how the brain responds. We discuss how Sex and Gender Science allows us to begin to bring together biology and its social context and acknowledge where context can contribute to resolving ignorance to offer more expansive, complementary, and interrelating pictures of an intricate neuro-landscape.

Perfusion MRI using endogenous deoxyhemoglobin as a contrast agent: Preliminary data.

PURPOSE: To demonstrate the feasibility of mapping cerebral perfusion metrics with BOLD MRI during modulation of pulmonary venous oxygen saturation. METHODS: A gas blender with a sequential gas delivery breathing circuit was used to implement rapid isocapnic changes in the partial pressure of oxygen of the arterial blood. Partial pressure of oxygen was initially lowered to a baseline of 40 mmHg. It was then rapidly raised to 95 mmHg for 20 s before rapidly returning to baseline. The induced cerebral changes in deoxyhemoglobin concentration were tracked over time using BOLD MRI in 6 healthy subjects and 1 patient with cerebral steno-occlusive disease. BOLD signal change, contrast-to-noise ratio, and time delay metrics were calculated. Perfusion metrics such as mean transit time, relative cerebral blood volume, and relative cerebral blood flow were calculated using a parametrized method with a mono-exponential residue function. An arterial input function from within the middle cerebral artery was used to scale relative cerebral blood volume and calculate absolute cerebral blood volume and cerebral blood flow. RESULTS: In normal subjects, average gray and white matter were: BOLD change = 6.3 ± 1.2% and 2.5 ± 0.6%, contrast-to-noise ratio = 4.3 ± 1.3 and 2.6 ± 0.7, time delay = 2.3 ± 0.6 s and 3.6 ± 0.7 s, mean transit time = 3.9 ± 0.6 s and 5.5 ± 0.6 s, relative cerebral blood volume = 3.7 ± 0.9 and 1.6 ± 0.4, relative cerebral blood flow = 70.1 ± 8.3 and 20.6 ± 4.0, cerebral blood flow volume = 4.1 ± 0.9 mL/100 g and 1.8 ± 0.5 mL/100 g, and cerebral blood flow = 97.2 ± 18.7 mL/100 g/min and 28.7 ± 5.9 mL/100 g/min. CONCLUSION: This study demonstrates that induced abrupt changes in deoxyhemoglobin can function as a noninvasive vascular contrast agent that may be used for cerebral perfusion imaging.

Normal BOLD Response to a Step CO2 Stimulus After Correction for Partial Volume Averaging.

Cerebrovascular reactivity (CVR) is defined as the change in cerebral blood flow induced by a change in a vasoactive stimulus. CVR using BOLD MRI in combination with changes in end-tidal CO2 is a very useful method for assessing vascular performance. In recent years, this technique has benefited from an advanced gas delivery method where end-tidal CO2 can be targeted, measured very precisely, and validated against arterial blood gas sampling (Ito et al., 2008). This has enabled more precise comparison of an individual patient against a normative atlas of healthy subjects. However, expected control ranges for CVR metrics have not been reported in the literature. In this work, we calculate and report the range of control values for the magnitude (mCVR), the steady state amplitude (ssCVR), and the speed (TAU) of the BOLD response to a standard step stimulus, as well as the time delay (TD) as observed in a cohort of 45 healthy controls. These CVR metrics maps were corrected for partial volume averaging for brain tissue types using a linear regression method to enable more accurate quantitation of CVR metrics. In brief, this method uses adjacent voxel CVR metrics in combination with their tissue composition to write the corresponding set of linear equations for estimating CVR metrics of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). After partial volume correction, mCVR and ssCVR increase as expected in gray matter, respectively, by 25 and 19%, and decrease as expected in white matter by 33 and 13%. In contrast, TAU and TD decrease in gray matter by 33 and 13%. TAU increase in white matter by 24%, but TD surprisingly decreased by 9%. This correction enables more accurate voxel-wise tissue composition providing greater precision when reporting gray and white matter CVR values.

Menopause, anti-Müllerian hormone and cognition in a cohort of women with persistent symptoms following TBI: a case for future research.

Objectives: Primary: To explore anti-Müllerian Hormone (AMH) levels in community dwelling women following TBI. Secondary: To explore the relation of AMH to menstrual cycle, cognition, distress and symptoms of menopause.Setting: Large adult TBI outpatient clinic in Toronto Canada.Research design: Prospective study of 10 women with persistent symptoms who were one or more years post TBI.Methods: Consenting participants provided a serum sample for AMH levels, and completed the Menopause Rating Scale (MRS), Symptom Checklist-90 r (SCL-90 r), Repeatable Battery for the Assessment of Neurological Status (RBANS) and a health questionnaire.Main outcomes and results: This study found lower than expected levels of AMH in 50% of participants relative to age matched norms and 50% of participants experienced new onset of menstrual changes. Also notable were findings of lower-than-expected cognitive scores in women over 35 and reports of menopause-related symptoms across all ages groups.Conclusions: As our understanding of the role of AMH grows, examining changes in this novel biomarker in the long-term post-TBI is warranted. Future research should be sufficiently powered to expand on and validate the study's findings.

Assessing the effectiveness of workplace accommodations in facilitating return to work after traumatic brain injury: a systematic review protocol.

INTRODUCTION: Returning to work and sustaining employment can be a significant challenge for traumatic brain injury (TBI) survivors. Within the literature, there is recurring support for the role of workplace accommodations in effective and early return-to-work (RTW). To date, however, there has been a lack of systematic reviews exploring the specific role of workplace accommodations within the context of RTW after TBI. The primary objective of this protocol is to outline the methodological approach that will be undertaken to systematically review the literature and to assess the effectiveness of workplace accommodations in facilitating RTW. METHODS AND ANALYSIS: A total of nine databases will be searched systematically using the concepts 'Brain injury,' 'RTW' and 'Job Accommodations.' Study selection will be performed independently by three reviewers, based on predetermined eligibility criteria through two rounds of screening using, first, the title and abstract, followed by a full-text search. Extracted information will include the study's purpose, design, and setting; the data source and type; the severity of TBI and the diagnostic criterion used; a comprehensive description of the intervention provided; the RTW outcome variables and the statistical methods used, etc. The data will be tabulated and narratively synthesised. Systematic review registration: This protocol has been registered with International Prospective Register of Systematic Reviews. ETHICS AND DISSEMINATION: As this review intends to use pre-existing published studies hence research ethics board approvals will not be required. Nevertheless, this review will follow the ethical and governance standards in the data management and presentation of results. The findings from this review will potentially be published in a peer-reviewed scientific journal (electronically and in print). The results of this review will be presented at both national/international conferences and shared with stakeholders influencing RTW practices. PROSPERO REGISTRATION NUMBER: CRD42016043517.

A Promising Subject-Level Classification Model for Acute Concussion Based on Cerebrovascular Reactivity Metrics.

Concussion imaging research has primarily focused on neuronal disruption with lesser emphasis directed toward vascular dysfunction. However, blood flow metrics may be more sensitive than measures of neuronal integrity. Vascular dysfunction can be assessed by measuring cerebrovascular reactivity (CVR)-the change in cerebral blood flow per unit change in vasodilatory stimulus. CVR metrics, including speed and magnitude of flow responses to a standardized well-controlled vasoactive stimulus, are potentially useful for assessing individual subjects following concussion given that blood flow dysregulation is known to occur with traumatic brain injury. We assessed changes in CVR metrics to a standardized vasodilatory stimulus during the acute phase of concussion. Using a case control design, 20 concussed participants and 20 healthy controls (HCs) underwent CVR assessment measuring blood oxygen-level dependent (BOLD) magnetic resonance imaging using precise changes in end-tidal partial pressure of CO2 (PETCO2). Metrics were calculated for the whole brain, gray matter (GM), and white matter (WM) using sex-stratification. A leave-one-out receiver operating characteristic (ROC) analysis classified concussed from HCs based on CVR metrics. CVR magnitude was greater and speed of response faster in concussed participants relative to HCs, with WM showing higher classification accuracy compared with GM. ROC analysis for WM-CVR metrics revealed an area under the curve of 0.94 in males and 0.90 in females for speed and magnitude of response respectively. These greater than normal responses to a vasodilatory stimulus warrant further investigation to compare the predictive ability of CVR metrics against structural injury metrics for diagnosis and prognosis in acute concussion.

Sex-specific differences in resting-state functional connectivity of large-scale networks in postconcussion syndrome.

Concussions are associated with a range of cognitive, neuropsychological and behavioral sequelae that, at times, persist beyond typical recovery times and are referred to as postconcussion syndrome (PCS). There is growing support that concussion can disrupt network-based connectivity post-injury. To date, a significant knowledge gap remains regarding the sex-specific impact of concussion on resting state functional connectivity (rs-FC). The aims of this study were to (1) investigate the injury-based rs-FC differences across three large-scale neural networks and (2) explore the sex-specific impact of injury on network-based connectivity. MRI data was collected from a sample of 80 concussed participants who fulfilled the criteria for postconcussion syndrome and 31 control participants who did not have any history of concussion. Connectivity maps between network nodes and brain regions were used to assess connectivity using the Functional Connectivity (CONN) toolbox. Network based statistics showed that concussed participants were significantly different from healthy controls across both salience and fronto-parietal network nodes. More specifically, distinct subnetwork components were identified in the concussed sample, with hyperconnected frontal nodes and hypoconnected posterior nodes across both the salience and fronto-parietal networks, when compared to the healthy controls. Node-to-region analyses showed sex-specific differences across association cortices, however, driven by distinct networks. Sex-specific network-based alterations in rs-FC post concussion need to be examined to better understand the underlying mechanisms and associations to clinical outcomes.

Assault predicts time away from work after claims for work-related mild traumatic brain injury.

INTRODUCTION: Workplace violence carries a substantial economic loss burden. Up to 10% of all traumatic brain injury (TBI) admissions result from physical assault. There remains a paucity of research on assault as a mechanism of injury, taking into account sex, and its association with work re-entry. OBJECTIVES: The aim of this study was to characterise, by sex, the sample of workers who had sustained a work-related mild TBI (wr-mTBI) and to assess the independent influence of assault, as a mechanism of injury, on time away from work. METHODS: A population-based retrospective cohort of workers' compensation claimants in Australia (n=3129) who had sustained a wr-mTBI was used for this study. A multivariable logistic regression analysis assessed whether workers who had sustained wr-mTBI as a result of assault (wr-mTBI-assault) were more likely to claim time off work compared with workers who had sustained a wr-mTBI due to other mechanisms. RESULTS: Among claimants who sustained a wr-mTBI, 9% were as a result of assault. The distribution of demographic and vocational variables differed between the wr-mTBI-assault, and not due to assault, both in the full sample, and separately for men and women. After controlling for potential confounding factors, workers who sustained wr-mTBI-assault, compared with other mechanisms, were more likely to take days off work (OR 2.14, 95% CI 1.53 to 2.99) within a 3-month timeframe. CONCLUSION: The results have policy-related implications. Sex-specific and workplace-specific prevention strategies need to be considered and provisions to support return-to-work and well-being within this vulnerable cohort should be examined.