Biology subjects

Neylan, T. C.

Publications and source records attributed to Neylan, T. C..

6 recordsLinked to original sources

bioRxiv2026

Sleep and emotional memory: translating neural response at encoding to memory accuracy in men and women with and without PTSD

BackgroundGrowing evidence suggests that sleep plays an important role in PTSD outcomes, potentially due to its influence on emotional memory consolidation, though these mechanisms remain unknown. This study sought to test the hypotheses that sleep neurophysiology, PTSD status, and sex moderates the degree to which the late positive potential (LPP) mediates memory accuracy for affective visual stimuli. MethodsN = 39 participants (18 female) viewed 75 negative and 75 neutral IAPS images while EEG was recorded. After viewing the images, participants took a two-hour long nap which was followed by a memory assessment. Memory accuracy was measured using d = Z(hit rate) - Z(false alarm rate), where hit rate refers to the proportion of images seen during the memory assessment that are correctly identified as being previously seen, false alarm rate refers to the proportion of images seen during the memory assessment that are incorrectly identified as being previously seen, and Z() is the inverse cumulative distribution function of the standard normal distribution function. ResultsThe early (300 - 1000 ms) and late (1000 - 1500 ms) LPP mediated enhanced discrimination accuracy for emotional compared to neural stimuli (d) (ps < 0.001). The association between the late LPP and d was moderated by sleep such that the association was stronger when participants spent proportionately more time in N3 and REM (p = 0.02). The differences in reactivity between emotional and neutral images for both the early and late LPP were attenuated in PTSD+ individuals vs. controls (ps < 0.001). Despite mediation results showing greater d for emotional compared to neutral stimuli, women showed overall worse memory accuracy for negative compared to neutral stimuli (p < 0.001) whereas men showed no difference (p = 0.64). ConclusionsN3 and REM sleep play a critical role for memory of stimuli that produce large and sustained neural responses. PTSD is marked by a diminished ability to distinguish between negative and neutral information. More research is critical to understand sex effects on emotional memory.

neuroscience↗

bioRxiv2024

The wake and sleep-modulating neurons of the lateral hypothalamic area demonstrate a differential pattern of degeneration in Alzheimers disease

BackgroundSleep-wake dysfunction is an early and common event in Alzheimers disease (AD). The lateral hypothalamic area (LHA) regulates the sleep and wake cycle through wake-promoting orexinergic neurons (OrxN) and sleep-promoting melanin-concentrating hormone or MCHergic neurons (MCHN). These neurons share close anatomical proximity with functional reciprocity. This study investigated LHA OrxN and MCHN loss patterns in AD individuals. Understanding the degeneration pattern of these neurons will be instrumental in designing potential therapeutics to slow down the disease progression and remediate the sleep-wake dysfunction in AD. MethodsPostmortem human brain tissue from donors with AD (across progressive stages) and controls were examined using unbiased stereology. Formalin-fixed, celloidin-embedded hypothalamic sections were stained with Orx-A/MCH, p-tau (CP13), and counterstained with gallocyanin. Orx or MCH-positive neurons with or without CP13 inclusions and gallocyanin-stained neurons were considered for stereology counting. Additionally, we extracted RNA from the LHA using conventional techniques. We used customized Neuropathology and Glia nCounter(R) (Nanostring) panels to study gene expression. Wald statistical test was used to compare the groups, and the genes were considered differentially expressed when the p-value was <.05. ResultsWe observed a progressive decline in OrxN alongside a relative preservation of MCHN. OrxN decreased by 58% (p=.03) by Braak stages (BB) 1-2 and further declined to 81% (p=.03) by BB 5-6. Conversely, MCHN demonstrated a non-statistical significant decline (27%, p=.1088) by BB 6. We observed a progressive increase in differentially expressed genes (DEGs), starting with glial profile changes in BB2. While OrxN loss was observed, Orx-related genes showed upregulation in BB 3-4 compared to BB 0-1. GO and KEGG terms related to neuroinflammatory pathways were mainly enriched. ConclusionsTo date, OrxN loss in the LHA represents the first neuronal population to die preceding the loss of LC neurons. Conversely, MCHN shows resilience to AD p-tau accumulation across Braak stages. The initial loss of OrxN correlates with specific neuroinflammation, glial profile changes, and overexpression of HCRT, possibly due to hyperexcitation following compensation mechanisms. Interventions preventing OrxN loss and inhibiting p-tau accumulation in the LHA could prevent neuronal loss in AD and, perhaps, the progression of the disease.

neuroscience↗

bioRxiv2024

The lipidome of posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) can develop after trauma exposure. Some studies report that women develop PTSD at twice the rate of men, despite greater trauma exposure in men. Lipids and their metabolites (lipidome) regulate a myriad of key biological processes and pathways such as membrane integrity, oxidative stress, and neuroinflammation in the brain by maintaining neuronal connectivity and homeostasis. In this study, we analyzed the lipidome of 40 individuals with PTSD and 40 trauma-exposed non-PTSD individuals. Plasma samples were analyzed for lipidomics using Quadrupole Time-of-Flight (QToF) mass spectrometry. Additionally, [~] 90 measures were collected, on sleep, mental and physical health indices. Sleep quality worsened as PTSD severity increased in both sexes. The lipidomics analysis identified a total of 348 quantifiable known lipid metabolites and 1951 lipid metabolites that are yet unknown; known metabolites were part of 13 classes of lipids. After adjusting for sleep quality, in women with PTSD, only one lipid subclass, phosphatidylethanolamine (PE) was altered, whereas, in men with PTSD, 9 out of 13 subclasses were altered compared to non-PTSD women and men, respectively. Severe PTSD was associated with 22% and 5% of altered lipid metabolites in men and women, respectively. Of the changed metabolites, only 0.5% measures (2 PEs and cholesterol) were common between women and men with PTSD. Several sphingomyelins, PEs, ceramides, and triglycerides were increased in men with severe PTSD. The triglycerides and ceramide metabolites that were most highly increased were correlated with cholesterol metabolites and systolic blood pressure in men but not always in women with PTSD. Alterations in triglycerides and ceramides are linked with cardiac health and metabolic function in humans. Thus, disturbed sleep and higher weight may have contributed to changes in the lipidome found in PTSD.

systems biology↗

bioRxiv2022

Sleep spindles favor emotion regulation over memory consolidation of stressors in PTSD

Posttraumatic stress disorder (PTSD) is a trauma-induced debilitating condition, with symptoms that revolve around a declarative memory of a severe stressor. How does the brain process declarative and emotional information of stressors in PTSD? We evaluated the role of NREM sleep spindles in this process after exposure to laboratory stress, in a cohort of human subjects with different levels of PTSD symptoms. Subjects performed two laboratory visits: 1) a stress visit which involved exposure to negatively-valent images in the morning and 2) a control visit. In both visits subjects had a sleep/nap opportunity in the afternoon monitored via electroencephalography (EEG). In the stress visit, self-reported anxiety confirmed elevated stress immediately after stressor exposure (pre-sleep) that decayed to control levels post-sleep. An image recall session took place in the late afternoon. Overall, NREM2 spindle rates were elevated in the stress visit as compared to the control visit. This increase in NREM2 spindle rates, especially over occipital cortex, was significantly greater in subjects with high vs. low PTSD symptoms. However in high-PTSD subjects, NREM2 spindle rates correlated with poorer recall accuracy of stressor images as compared to lower symptomatic individuals while surprisingly correlating with a greater reduction in anxiety levels across sleep. Thus although NREM2 spindles are known to play a role in declarative memory processes, our findings highlight an important role of NREM sleep in favoring sleep-dependent anxiety regulation over memory consolidation after exposure to stressors in PTSD and shed new light on the function of NREM2 spindles in PTSD.

neuroscience↗

bioRxiv2021

Region-specific maladaptive gray matter myelination is associated with differential susceptibility to stress-induced behavior in male rodents and humans

Individual reactions to traumatic stress vary dramatically, yet the biological basis of this variation remains poorly understood. Recent studies demonstrate the surprising plasticity of oligodendrocytes and myelin with stress and experience, providing a potential mechanism by which trauma induces aberrant structural and functional changes in the adult brain. In this study, we utilized a translational approach to test the hypothesis that gray matter myelin contributes to traumatic-stress-induced behavioral variation in both rats and humans. We exposed adult, male rats to a single, severe stressor and used a multimodal approach to characterize avoidance, startle, and fear-learning behavior, as well as oligodendrocyte and myelin content in multiple brain areas. We found that oligodendrocyte cell density and myelin content were correlated with behavioral outcomes in a region-specific manner. Specifically, stress-induced avoidance positively correlated with hippocampal dentate gyrus oligodendrocytes and myelin. Viral overexpression of the oligodendrogenic factor Olig1 in the dentate gyrus was sufficient to induce an anxiety-like behavioral phenotype. In contrast, contextual fear learning positively correlated with myelin in the amygdala and spatial processing regions of the hippocampus. In a group of trauma-exposed US veterans, T1-/T2-weighted magnetic resonance imaging estimates of hippocampal and amygdala myelin associated with symptom profiles in a region-specific manner that mirrored the findings in rats. These results demonstrate a species- independent relationship between region-specific, gray matter oligodendrocytes and myelin and differential behavioral phenotypes following traumatic stress exposure. This study suggests a novel mechanism for brain plasticity that underlies individual variance in sensitivity to traumatic stress.

neuroscience↗

bioRxiv2017

PTSD Blood Transcriptome Mega-Analysis: Shared Inflammatory Pathways Across Genders And Modes Of Traumas

Transcriptome-wide screens of peripheral blood during the onset and development of posttraumatic stress disorder (PTSD) indicate widespread immune dysregulation. However, little is known as to whether biological sex and the type of traumatic event influence shared or distinct biological pathways in PTSD. We performed a combined analysis of five independent PTSD blood transcriptome studies covering seven types of trauma in 229 PTSD and 311 comparison individuals to synthesize the extant data. Analyses by trauma type revealed a clear pattern of PTSD gene expression signatures distinguishing interpersonal (IP)-related traumas from combat-related traumas. Co-expression network analyses integrated all data and identified distinct gene expression perturbations across sex and modes of trauma in PTSD, including one wound-healing module down-regulated in men exposed to combat traumas, one IL12-mediated signaling module up-regulated in men exposed to IP-related traumas, and two modules associated with lipid metabolism and MAPK-activity up-regulated in women exposed to IP-related traumas. Remarkably, a high degree of sharing of transcriptional dysregulation across sex and modes of trauma in PTSD was also observed converging on common signaling cascades, including cytokine, innate immune and type I interferon pathways. Collectively, these findings provide a broad view of immune dysregulation in PTSD and demonstrate inflammatory pathways of molecular convergence and specificity, which may inform mechanisms and diagnostic biomarkers for the disorder.

neuroscience↗