Accurate segmentation of thalamic nuclei, crucial for understanding their role in healthy cognition and in pathologies, is challenging to achieve on standard T1-weighted (T1w) magnetic resonance imaging (MRI) due to poor image contrast. White-matter-nulled (WMn) MRI sequences improve intrathalamic contrast but are not part of clinical protocols or extant databases. Here, we introduce Histogram-based polynomial synthesis (HIPS), a fast preprocessing step that synthesizes WMn-like image contrast from standard T1w MRI using a polynomial approximation. HIPS was incorporated into our Thalamus Optimized Multi-Atlas Segmentation (THOMAS) pipeline, developed and optimized for WMn MRI. HIPS-THOMAS was compared to a convolutional neural network (CNN)-based segmentation method and THOMAS modified for T1w images (T1w-THOMAS). The robustness and accuracy of the three methods were tested across different image contrasts, scanner manufacturers, and field strength. HIPS-synthesized images improved intra-thalamic contrast and thalamic boundaries, and their segmentations yielded significantly better mean Dice, lower percentage of volume error, and lower standard deviations compared to both the CNN method and T1w-THOMAS. Finally, using THOMAS, HIPS-synthesized images were as effective as WMn images for identifying thalamic nuclei atrophy in alcohol use disorders subjects relative to healthy controls, with a higher area under the ROC curve compared to T1w-THOMAS (0.79 vs 0.73).
To determine the dynamics of white matter vulnerability to excessive alcohol consumption, diffusion tensor imaging (DTI) was used in an animal model of alcohol exposure. Quantitative, in vivo fiber tracking results are presented from rats with DTI conducted at 3 time points: baseline; after 4 days of intragastric alcohol to blood alcohol levels of ~250mg/dL; and after one week of recovery. Binge alcohol followed by a week of sobriety resulted in rapidly reversible decreases in fractional anisotropy (FA), a measure of the coherence of fiber tracts, in callosal genu and fimbria-fornix but not splenium; and increases in mean diffusivity (MD), an index of freely diffusing water in tissue, selective to the fimbria-fornix. These effects were confirmed with tract-based spatial statistics (TBSS). The directionality of changes in DTI metrics reproduce those observed in human alcoholism. That a single exposure to binge alcohol can cause substantial transient changes detectable in DTI metrics demonstrates the potential for rapid neuroplasticity.
Abstract Background. Poor sleep can undermine the health of people in general and may be especially disruptive to those with chronic conditions including HIV infection. Methods. Here, clinically well-described people living with HIV infection [PLWH] (74 men, 35 women) and healthy control (38 men, 35 women) participants were administered the Pittsburgh Sleep Quality Index (PSQI), which is a validated measure of subjective sleep with a global score ≥ 5 able to distinguish good from poor sleepers. In addition, participants completed neuropsychological tests assessing executive functioning, working memory, and learning and memory. Results. PLWH (6.8±3.7) had higher global PSQI scores than those of healthy controls (4.1±2.8): 39.7% of uninfected controls and 68.8% of PLWH had a PSQI ≥ 5 indicative of poor sleep. There were no relations between the global PSQI score and any evaluated variables among healthy-control individuals or with demographic or HIV-related variables in PLWH. Instead, a higher global PSQI score among PLWH was associated with worse “Quality of Life” measures including scores on the Global Assessment of Functioning (GAF, p = .0007), the Medical Outcomes Study survey (21-item short form, SF-21, p < .0001), and Activities of Daily Living-Instrumental (ADL-I, p = .0041); and more depressive symptoms as determined by the Beck Depression Index (BDI, p < .0001). Further, in PLWH, a higher global PSQI score was associated with poor performance on a working memory task, the digit backward span (p = .0036). In PLWH, the 5 variables together explained 32.3% of the global PSQI score variance; only 3 variables – the SF-21, BDI, and digit backward scores – explained 30.6% of the variance. Conclusions. To the extent that poor subjective sleep contributes to impaired working memory in HIV, we speculate that this impairment may be ameliorated by improved sleep health.
Potential competing interests: The author(s) declared that no potential competing interests exist.This manuscript presents data from 10 Alzheimer's disease (AD), 8 Dementia with Lewy Bodies (DLB), and 11 healthy-control postmortem brain tissue samples with analyses focused on Amyloid beta (Ab), Tau, and P-Synuclein immunohistochemistry and the relationship between these markers and microglial morphology in the human hippocampus.The authors have developed an automated analyses procedure called the "Microglia and Immune Cells Morphologies Analyser and Classifier (MIC-MAC)" pipeline.In addition to confocal microscopy analyses to determine volumes of Ab, Tau, and P-Synuclein in CA1-CA4 hippocampal tissue, MIC-MAC was used to classify thousands of microglia per sample.Tau was found to be highest in CA1 (lowest in CA4); Ab lowest in CA1 (highest in CA4); P-Synuclein showed negligible staining (highest in CA1, lowest in CA4); this staining pattern/distribution was similar in AD and DLB with the only notable difference being a higher degree/severity in AD relative to DLB.Microglia in the diseased (i.e., AD and DLB) relative to healthy control hippocampal tissue were more compact and less ramified.It is suggested that the "severity, distribution, and overlap of co-occurrence of Ab, Tau, and P-Synuclein impact microglia phenotypic heterogeneity" but the data as presented are challenging to follow.In general, the manuscript requires editing for clarification.Methods need to be better detailed.The MIC-MAC pipeline should be better presented -with evidence for its validity and reliability -in the Introduction.Both the methods and results need to be re-written so that readers can better grasp and potentially replicate the current findings.In the discussion, comments regarding whether the observed microglial morphological changes are beneficial or detrimental should be provided.
Human studies are necessary to identify and classify the brain systems predisposing individuals to develop alcohol use disorders and those modified by alcohol, while animal models of alcoholism are essential for a mechanistic understanding of how chronic voluntary alcohol consumption becomes compulsive, how brain systems become damaged, and how damage resolves. Our current knowledge of the neuroscience of alcohol dependence has evolved from the interchange of information gathered from both human alcoholics and animal models of alcoholism. Together, studies in humans and animal models have provided support for the involvement of specific brain structures over the course of alcohol addiction, including the prefrontal cortex, basal ganglia, cerebellum, amygdala, hippocampus,
The application of data-driven deep learning to identify sex differences in developing brain structures of pre-adolescents has heretofore not been accomplished. Here, the approach identifies sex differences by analyzing the minimally processed MRIs of the first 8144 participants (age 9 and 10 years) recruited by the Adolescent Brain Cognitive Development (ABCD) study. The identified pattern accounted for confounding factors (i.e., head size, age, puberty development, socioeconomic status) and comprised cerebellar (corpus medullare, lobules III, IV/V, and VI) and subcortical (pallidum, amygdala, hippocampus, parahippocampus, insula, putamen) structures. While these have been individually linked to expressing sex differences, a novel discovery was that their grouping accurately predicted the sex in individual pre-adolescents. Another novelty was relating differences specific to the cerebellum to pubertal development. Finally, we found that reducing the pattern to a single score not only accurately predicted sex but also correlated with cognitive behavior linked to working memory. The predictive power of this score and the constellation of identified brain structures provide evidence for sex differences in pre-adolescent neurodevelopment and may augment understanding of sex-specific vulnerability or resilience to psychiatric disorders and presage sex-linked learning disabilities.
Abstract This article provides an overview of recent advances in understanding the effects of alcohol use disorders (AUD) on the brain from the perspective of magnetic resonance imaging (MRI) research in preclinical models and clinical studies. As a noninvasive investigational tool permitting assessment of morphological, metabolic, and hemodynamic changes over time, MRI offers insight into the dynamic course of alcoholism beginning with initial exposure through periods of binge drinking and escalation, sobriety, and relapse and has been useful in differential diagnosis of neurological diseases associated with AUD. Structural MRI has revealed acute and chronic effects of alcohol on both white and gray matter volumes. MR Spectroscopy, able to quantify brain metabolites in vivo, has shed light on biochemical alterations associated with alcoholism. Diffusion tensor imaging permits microstructural characterization of white matter fiber tracts. Functional MRI has allowed for elucidation of hemodynamic responses at rest and during task engagement. Positron emission tomography, a non‐MRI imaging tool, has led to a deeper understanding of alcohol‐induced receptor and neurotransmitter changes during various stages of drinking and abstinence. Together, such in vivo imaging tools have expanded our understanding of the dynamic course of alcoholism including evidence for regional specificity of the effects of AUD, hints at mechanisms underlying the shift from casual to compulsive use of alcohol, and profound recovery with sustained abstinence.
Pharmacologically-treated people living with HIV infection have near-normal life spans with more than 50 % living into at-risk age for dementia and a disproportionate number relative to uninfected people engaging in unhealthy drinking. Accelerated aging in HIV occurs in some brain structures including the multinucleated thalamus. Unknown is whether aging with HIV affects thalamic nuclei and associated functions differentially and whether the common comorbidity of alcohol use disorder (AUD) + HIV accelerates aging.
