The effects of hemodynamic lag on functional connectivity and behavior after stroke

Stroke disrupts the brain's vascular supply, not only within but also outside areas of infarction. We investigated temporal delays (lag) in resting state functional magnetic resonance imaging signals in 130 stroke patients scanned two weeks, three months and 12 months post stroke onset. Thirty controls were scanned twice at an interval of three months. Hemodynamic lag was determined using cross-correlation with the global gray matter signal. Behavioral performance in multiple domains was assessed in all patients. Regional cerebral blood flow and carotid patency were assessed in subsets of the cohort using arterial spin labeling and carotid Doppler ultrasonography. Significant hemodynamic lag was observed in 30% of stroke patients sub-acutely. Approximately 10% of patients showed lag at one-year post-stroke. Hemodynamic lag corresponded to gross aberrancy in functional connectivity measures, performance deficits in multiple domains and local and global perfusion deficits. Correcting for lag partially normalized abnormalities in measured functional connectivity. Yet post-stroke FC-behavior relationships in the motor and attention systems persisted even after hemodynamic delays were corrected. Resting state fMRI can reliably identify areas of hemodynamic delay following stroke. Our data reveal that hemodynamic delay is common sub-acutely, alters functional connectivity, and may be of clinical importance

The Effect of Vascularization and Tissue Type on Cryosurgical Procedures

Cryosurgery is a minimally-invasive surgical procedure that is used in the treatment of multiple types of cancer. Although cryosurgical treatments, which involve the application of extreme cold to diseased or cancerous tissue, are often used in the treatment of near-surface skin cancer, they have also been used to treat several other types of internal cancers, including those in the prostate, liver, and kidney. Although fundamentally similar, many of these tissues differ significantly in properties such as density, vascularization, and thermal conductivity. A major issue in cryosurgery is adapting the procedure to different tissue types. In this study, the effect of tissue perfusivity on the outcomes of cryosurgery was modeled using the COMSOL software. For the purposes of comparison, the properties of lung tissue, which is highly perfused and not as conductive, and liver tissue, which is mildly perfused and more conductive, were used. The procedure was modeled as a 10 mm diameter cryoprobe set at a temperature of -196?C in a cylindrical region of tissue 8 cm in height and 8 cm in diameter. The time required for a 26mm diameter spherical tumor to reach -45?C was determined in four scenarios, lung tissue and liver tissue both with and without blood perfusion. Although metabolic heat generation was also included, sensitivity analysis showed it to be a minor factor in the cooling process. Results showed blood perfusivity to have a significant effect on freezing time in lung tissue and a relatively minor one in liver tissue: although the addition of perfusion caused freezing time in the liver to increase from 200 to 250 seconds, the addition of perfusion in the lung tissue caused the freezing front to never reach the tumor edge. Sensitivity analyses also revealed the freezing process to be highly sensitive to conductivity as well. It was therefore concluded that although blood perfusion is one of the most important heat transfer processes in cryosurgery, tissue conductivity is just as, if not more important. We recommend that cryosurgery continue to be used as a treatment for liver tumors, but further studies are needed to determine its efficacy in highly perfused, porous tissue such as the lung

Stronger prediction of motor recovery and outcome post-stroke by cortico-spinal tract integrity than functional connectivity

<div><p>Objectives</p><p>To examine longitudinal changes in structural and functional connectivity post-stroke in patients with motor impairment, and define their importance for recovery and outcome at 12 months.</p><p>Methods</p><p>First-time stroke patients (N = 31) were studied at 1–2 weeks, 3 months, and 12 months post-injury with a validated motor battery and resting-state fMRI to measure inter-hemispheric functional connectivity (FC). Fractional anisotropy (FA) of the cortico-spinal tract (CST) was derived from diffusion tensor imaging as a measure of white matter organization. ANOVAs were used to test for changes in FC, FA, and motor performance scores over time, and regression analysis related motor outcome to clinical and neuroimaging variables.</p><p>Results</p><p>FA of the ipsilesional CST improved significantly from 3 to 12 months and was strongly correlated with motor performance. FA improved even in the absence of direct damage to the CST. Inter-hemispheric FC also improved over time, but did not correlate with motor performance at 12 months. Clinical variables (early motor score, education level, and age) predicted 80.4% of the variation of motor outcome, and FA increased the predictability to 84.6%. FC did not contribute to the prediction of motor outcome.</p><p>Conclusions</p><p>Stroke causes changes to the CST microstructure that can account for behavioral variability even in the absence of demonstrable lesion. Ipsilesional CST undergoes remodeling post-stroke, even past the three-month window when most of the motor recovery happens. FA of the CST, but not inter-hemispheric FC, can improve to the prediction of motor outcome based on early motor scores.</p></div

A Review of Contemporary Assessment Tools for Use with Transgender and Gender Nonconforming Adults

There is increasing recognition of the need for culturally sensitive services for individuals who identify as transgender and gender nonconforming (TGNC), and only recently have empirical studies appeared in the literature that inform best practices for TGNC people. Competent, culturally appropriate clinical services and research depend upon methodologically sound assessment of key constructs, but it is unclear whether appropriate self-report or clinician-rated assessment tools for adults exist. This article reviewed existing published measures to identify areas of strength as well as existing gaps in the available research. The search strategy for this systematic review identified any published article describing a self-report or clinician-rated scale for assessing transgender-related concerns. Each measure was reviewed for information on its scope, reliability, validity, strengths, limitations, and source. The majority of these questionnaires was developed with the TGNC communities and targeted important factors that affect quality of life for TGNC people. Limitations included limited evidence for validity, reliability, and sensitivity to change. Overall, the field is moving in the direction of TGNC-affirming assessment, and promising measures have been created to monitor important aspects of quality of life for TGNC people. Future research should continue to validate these measures for use in assessing clinical outcomes and the monitoring of treatment progress

Harm avoidance is associated with progression of parkinsonism in community-dwelling older adults: a prospective cohort study

BACKGROUND: We tested the hypothesis that harm avoidance, a trait associated with behavioral inhibition, is associated with the rate of change in parkinsonism in older adults. METHODS: At baseline harm avoidance was assessed with a standard self-report instrument in 969 older people without dementia participating in the Rush Memory and Aging Project, a longitudinal community-based cohort study. Parkinsonism was assessed annually with a modified version of the motor section of the Unified Parkinson’s Disease Rating Scale (mUPDRS). RESULTS: Average follow-up was 5 years. A linear mixed-effects model controlling for age, sex and education showed that for an average participant (female, 80 years old at baseline, with 14 years of education and a harm avoidance score of 10), the overall severity of parkinsonism increased by about 0.05 unit/ year (Estimate, 0.054, S.E., 0.007, p <0.001) and that the level of harm avoidance was associated with the progression of parkinsonism (Estimate, 0.004, S.E., 0.001, p <0.001). Thus, for an average participant, every 6 point (~1 SD) increase in harm avoidance score at baseline, the rate of progression of parkinsonism increased about 50% compared to an individual with an average harm avoidance score. This amount of change in parkinsonism over the course of the study was associated with about a 5% increased risk of death. The association between harm avoidance and progression of parkinsonism persisted when controlling for cognitive function, depressive symptoms, loneliness, neuroticism, late-life cognitive, social and physical activities and chronic health conditions. CONCLUSION: A higher level of the harm avoidance trait is associated with a more rapid progression of parkinsonism in older adults

Abnormal white matter blood-oxygen-level-dependent signals in chronic mild traumatic brain injury

Concussion, or mild traumatic brain injury (mTBI), can cause persistent behavioral symptoms and cognitive impairment, but it is unclear if this condition is associated with detectable structural or functional brain changes. At two sites, chronic mTBI human subjects with persistent post-concussive symptoms (three months to five years after injury) and age- and education-matched healthy human control subjects underwent extensive neuropsychological and visual tracking eye movement tests. At one site, patients and controls also performed the visual tracking tasks while blood-oxygen-level-dependent (BOLD) signals were measured with functional magnetic resonance imaging. Although neither neuropsychological nor visual tracking measures distinguished patients from controls at the level of individual subjects, abnormal BOLD signals were reliably detected in patients. The most consistent changes were localized in white matter regions: anterior internal capsule and superior longitudinal fasciculus. In contrast, BOLD signals were normal in cortical regions, such as the frontal eye field and intraparietal sulcus, that mediate oculomotor and attention functions necessary for visual tracking. The abnormal BOLD signals accurately differentiated chronic mTBI patients from healthy controls at the single-subject level, although they did not correlate with symptoms or neuropsychological performance. We conclude that subjects with persistent post-concussive symptoms can be identified years after their TBI using fMRI and an eye movement task despite showing normal structural MRI and DTI

Susceptibility to neurofibrillary tangles: role of the PTPRD locus and limited pleiotropy with other neuropathologies

Tauopathies, including Alzheimer’s disease (AD) and other neurodegenerative conditions, are defined by a pathological hallmark: neurofibrillary tangles (NFT). NFT accumulation is thought to be closely linked to cognitive decline in AD. Here, we perform a genome-wide association study for NFT pathologic burden and report the association of the PTPRD locus (rs560380, p=3.8×10−8) in 909 prospective autopsies. The association is replicated in an independent dataset of 369 autopsies. The association of PTPRD with NFT is not dependent on the accumulation of amyloid pathology. In contrast, we find that the ZCWPW1 AD susceptibility variant influences NFT accumulation and that this effect is mediated by an accumulation of amyloid β plaques. We also performed complementary analyses to identify common pathways that influence multiple neuropathologies which co-exist with NFT and found suggestive evidence that certain loci may influence multiple different neuropathological traits, including tau, amyloid β plaques, vascular injury and Lewy bodies. Overall, these analyses offer an evaluation of genetic susceptibility to NFT, a common endpoint for multiple different pathologic processes