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Atypical antipsychotic drugs (AAPDs) are widely used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of AAPD treatment before the brain is fully developed. Indeed, we and others have previously reported that treatment of adolescent rats with olanzapine (OLA; a widely prescribed AAPD) on postnatal days 28–49, under dosing conditions that approximate those employed therapeutically in humans, causes long-term behavioral and neurobiological perturbations. We have begun to study the mechanisms of these effects. Dopamine (DA) and serotonin (5HT) regulate many neurodevelopmental processes. Currently approved AAPDs exert their therapeutic effects principally through their DAergic activities, although in schizophrenia (SZ) and some other diseases for which AAPDs are prescribed, DAergic dysfunction is accompanied by abnormalities of glutamatergic (GLUergic) and γ-aminobutyric acidergic (GABAergic) transmission. Here, we use proton magnetic resonance spectroscopy ( 1 H MRS) to investigate the effects of adolescent OLA administration on GABA and GLU levels. We found that the treatment caused long-term reductions in the levels of both GLU and GABA in the nucleus accumbens (NAc) of adult rats treated with OLA during adolescence. The NAc is a key node in the brain's “reward” system, whose function is also disrupted in schizophrenia. Further research into potential, OLA-induced changes in the levels of GLU and GABA in the NAc and other brain areas, and the dynamics and mechanisms of those changes, are an essential step for devising new adjunct therapies for existing AAPDs and for designing new drugs that increase therapeutic effects and reduce long-term abnormalities when administered to pediatric patients. [ABSTRACT FROM AUTHOR]

Elevated plasma neurofilament light chain (NfL) is associated with dementia though underlying mechanisms remain unknown. We examined cross-sectional relationships of time-dependent plasma NfL with selected brain structural magnetic resonance imaging (sMRI) prognostic markers of dementia. The sample was drawn from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, selecting participants with complete v 1 (2004–2009) and v 2 (2009–2013) plasma NfL exposure and ancillary sMRI data at v scan (2011–2015, n = 179, mean v 1 to v scan time: 5.4 years). Multivariable-adjusted linear regression models were conducted, overall, by sex, and race, correcting for multiple testing with q-values. NfL (v1) was associated with larger WMLV (both Log e transformed), after 5–6 years' follow-up, overall (β = +2.131 ± 0.660, b = +0.29, p = 0.001, and q = 0.0029) and among females. NfLv 2 was linked to a 125 mm3 lower left hippocampal volume (p = 0.004 and q = 0.015) in reduced models, mainly among males, as was observed for annualized longitudinal change in NfL (δNfL bayes). Among African American adults, NfL v1 was inversely related to total, gray and white matter volumes. Plasma NfL may reflect future brain pathologies in middle-aged adults. [ABSTRACT FROM AUTHOR]

Data from diffusion magnetic resonance imaging (dMRI) can be used to reconstruct fiber tracts, for example, in muscle and white matter. Estimation of fiber orientations (FOs) is a crucial step in the reconstruction process and these estimates can be corrupted by noise. In this paper, a new method called Fiber Orientation Reconstruction using Neighborhood Information (FORNI) is described and shown to reduce the effects of noise and improve FO estimation performance by incorporating spatial consistency. FORNI uses a fixed tensor basis to model the diffusion weighted signals, which has the advantage of providing an explicit relationship between the basis vectors and the FOs. FO spatial coherence is encouraged using weighted ℓ 1 -norm regularization terms, which contain the interaction of directional information between neighbor voxels. Data fidelity is encouraged using a squared error between the observed and reconstructed diffusion weighted signals. After appropriate weighting of these competing objectives, the resulting objective function is minimized using a block coordinate descent algorithm, and a straightforward parallelization strategy is used to speed up processing. Experiments were performed on a digital crossing phantom, ex vivo tongue dMRI data, and in vivo brain dMRI data for both qualitative and quantitative evaluation. The results demonstrate that FORNI improves the quality of FO estimation over other state of the art algorithms. [ABSTRACT FROM AUTHOR]

Plasma neurofilament light chain (NfL)'s link to dementia may be mediated through white matter integrity (WMI). In this study, we examined plasma NfL's relationships with diffusion tensor magnetic resonance imaging markers: global and cortical white matter fractional anisotropy (FA) and trace (TR). Plasma NfL measurements at 2 times (v 1 : 2004–2009 and v 2 : 2009–2013) and ancillary dMRI (v scan : 2011–2015) were considered (n = 163, mean time v 1 to v scan = 5.4 years and v 2 to v scan : 1.1 years). Multivariable-adjusted regression models, correcting for multiple-testing revealed that, overall, higher NfL v1 was associated with greater global TR (β ± SE: +0.0000560 ± 0.0000186, b = 0.27, p = 0.003, q = 0.012), left frontal WM TR (β ± SE: + 0.0000706 ± 0.0000201, b ± 0.30, p = 0.001, q = 0.0093) and right frontal WM TR (β ± SE: + 0.0000767 ± 0.000021, b ± 0.31, p < 0.001, q = 0.0093). These associations were mainly among males and White adults. Among African American adults only, NfL v2 was associated with greater left temporal lobe TR. "Tracking high" in NfL was associated with reduced left frontal FA (Model 2, body mass index-adjusted: β ± SE:-0.01084 ± 0.00408, p = 0.009). Plasma NfL is a promising biomarker predicting future brain white matter integrity (WMI) in middle-aged adults. [ABSTRACT FROM AUTHOR]

• Greater RDW v1 was associated with poorer WMI, among males only, particularly in terms of lower mean global fractional anisotropy (FA). • No such associations were found for anemia and δRDW (overall or sex-specific), or for RDW exposures among females and the non-anemic group. Anemia (blood hemoglobin [Hb] <13 g/dL among males; <12 g/dL among females) and elevated red cell distribution width (RDW) are potential risk factors for reduced brain white matter integrity (WMI), reflected by lower fractional anisotropy or increased mean diffusivity. Cross-sectional data with exposure-outcome lag time was used, whereby hematological exposures (RDW and Hb) and covariates were compiled from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study with available visit 1 (v 1 ; 2004–2009) and/or v 2 (2009–2013) data; while diffusion tensor magnetic resonance imaging (dMRI) outcome data were collected at HANDLS SCAN visit (v scan : 2011–2015, n = 214, mean follow-up from v 1 ±SD: 5.6 ± 1.8 year). Multivariable-adjusted linear regression analyses were conducted, overall, stratifying by sex, and further restricting to the nonanemic for RDW exposures in part of the analyses. Among males, RDW (v1) was linked with lower global mean fractional anisotropy (standardized effect size b = −0.30, p = 0.003, q < 0.05; basic model), an association only slightly attenuated with further covariate adjustment. Anemia was not a risk factor for poor WMI, independently of RDW. Ultimately, pending further longitudinal evidence, initial RDW appears to be associated with poorer WMI among males. [ABSTRACT FROM AUTHOR]

Pronounced spin phase artifacts appear in diffusion-weighted imaging (DWI) with only minor subject motion. While DWI data corruption is often identified as signal drop out in diffusion-weighted (DW) magnitude images, DW phase images may have higher sensitivity for detecting subtle subject motion. This article describes a novel method to return a metric of subject motion, computed using an image texture analysis of the DW phase image. This Phase Image Texture Analysis for Motion Detection in dMRI (PITA-MDD) method is computationally fast and reliably detects subject motion from diffusion-weighted images. A threshold of the motion metric was identified to remove motion-corrupted slices, and the effect of removing corrupted slices was assessed on the reconstructed FA maps and fiber tracts. Using a motion-metric threshold to remove the motion-corrupted slices results in superior fiber tracts and fractional anisotropy maps. When further compared to a state-of-the-art magnitude-based motion correction method, PITA-MDD was able to detect comparable corrupted slices in a more computationally efficient manner. In this study, we evaluated the use of DW phase images to detect motion corruption. The proposed method can be a robust and fast alternative for automatic motion detection in the brain with multiple applications to inform prospective motion correction or as real-time feedback for data quality control during scanning, as well as after data is already acquired. [ABSTRACT FROM AUTHOR]

This study was designed to test the hypothesis that prenatal exposure of guinea pigs to the organophosphorus (OP) pesticide chlorpyrifos (CPF) disrupts the structural and functional integrity of the brain. Pregnant guinea pigs were injected with chlorpyrifos (25 mg/kg, s.c.) or vehicle (peanut oil) once per day for 10 consecutive days, starting approximately on the 50th day of gestation. Cognitive behavior of female offspring was examined starting at 40–45 post-natal days (PND) using the Morris water maze (MWM), and brain structural integrity was analyzed at PND 70 using magnetic resonance imaging (MRI) methods, including T 2 -weighted anatomical scans and diffusion kurtosis imaging (DKI). The offspring of exposed mothers had significantly decreased body weight and brain volume, particularly in the frontal regions of the brain including the striatum. Furthermore, the offspring demonstrated significant spatial learning deficits in MWM recall compared to the vehicle group. Diffusion measures revealed reduced white matter integrity within the striatum and amygdala that correlated with spatial learning performance. These findings reveal the lasting effect of prenatal exposure to CPF as well as the danger of mother to child transmission of CPF in the environment. [ABSTRACT FROM AUTHOR]