Integrity Of Uncinate Fasciculus Research Articles

A - 19 Exploring White Matter Correlates of Fluid Cognitive Functioning in those 85+

Abstract Objective In individuals aged 85+, maintenance of white matter integrity (WMI) is crucial for maintaining communication between brain regions. White matter hyperintensities (WMH), common in aging, are linked with reduced cognitive function. While fluid cognitive functions typically decline with aging, some oldest older adults maintain performance akin to much younger individuals. Methods We examined the relationship between WMI, WMH, and fluid cognitive functioning in individuals aged 85+. WMI and WMH were assessed using two types of MRI imaging and fluid and crystallized cognitive performance were measured using the NIH Toolbox. Cognitive metrics were compared to WMI and WMH. Results Age significantly predicted fluid cognition (β = 0.49, p < 0.05, R^2 = 0.25, p < 0.01). Incorporating white matter measures improved prediction. Notably, cingulate gyrus FA and uncinate fasciculus FA significantly contributed to explained variance (ΔR^2 = 0.12, p < 0.01; ΔR^2 = 0.17, p < 0.01). Splenium corpus callosum MD and fornix column body ad were also significant predictors (ΔR^2 = 0.23, p < 0.01; ΔR^2 = 0.18, p < 0.01).n. Conclusion This study shows the significant impact of age and regional WMI on fluid cognitive function. Age did predict fluid cognition, and consideration of the white matter integrity of the cingulate gyrus and uncinate fasciculus integrity enhanced this association. Further, the integrity of the splenium of the corpus callosum and fornix also played crucial roles. These findings highlight the importance of preservation of white matter health for cognitive well-being in older adults 85 + .

Impact of white matter networks on risk for memory decline following resection versus ablation in temporal lobe epilepsy

BackgroundWith expanding neurosurgical options in epilepsy, it is important to characterise each options’ risk for postoperative cognitive decline. Here, we characterise how patients’ preoperative white matter (WM) networks relates to...

Decreased uncinate fasciculus integrity in functional seizures following traumatic brain injury.

The uncinate fasciculus (UF) has been implicated previously in contributing to the pathophysiology of functional (nonepileptic) seizures (FS). FS are frequently preceded by adverse life events (ALEs) and present with comorbid psychiatric symptoms, yet neurobiological correlates of these factors remain unclear. To address this gap, using advanced diffusion magnetic resonance imaging (dMRI), UF tracts in a large cohort of patients with FS and pre-existing traumatic brain injury (TBI + FS) were compared to those in patients with TBI without FS (TBI-only). We hypothesized that dMRI measures in UF structural connectivity would reveal UF differences when controlling for TBI status. Partial correlation tests assessed the potential relationships with psychiatric symptom severity measures. Participants with TBI-only (N = 46) and TBI + FS (N = 55) completed a series of symptom questionnaires and MRI scanning. Deterministic tractography via diffusion spectrum imaging (DSI) was implemented in DSI studio (https://dsi-studio.labsolver.org) with q-space diffeomorphic reconstruction (QSDR), streamline production, and manual segmentation to assess bilateral UF integrity. Fractional anisotropy (FA), radial diffusivity (RD), streamline counts, and their respective asymmetry indices (AIs) served as estimates of white matter integrity. Compared to TBI-only, TBI + FS participants demonstrated decreased left hemisphere FA and RD asymmetry index (AI) for UF tracts (both p < .05, false discovery rate [FDR] corrected). Additionally, TBI + FS reported higher symptom severity in depression, anxiety, and PTSD measures (all p < .01). Correlation tests comparing UF white matter integrity differences to psychiatric symptom severity failed to reach criteria for significance (all p > .05, FDR corrected). In a large, well-characterized sample, participants with FS had decreased white matter health after controlling for the history of TBI. Planned follow-up analysis found no evidence to suggest that UF connectivity measures are a feature of group differences in mood or anxiety comorbidities for FS. These findings suggest that frontolimbic structural connectivity may play a role in FS symptomology, after accounting for prior ALEs and comorbid psychopathology severity.

Abstract 14065: Functional and Structural Alterations in Stress-Related Neural Networks Implicated in Atherosclerosis

Introduction: While a link between chronic stress and cardiovascular disease (CVD) is well established, the neurocircuit alterations underlying this association remain unclear. We leveraged advanced multimodal imaging to gain insights into neurocircuit alterations that associate with atherosclerosis. Methods: Individuals with posttraumatic stress disorder (PTSD), trauma-exposed controls without PTSD (TC), and healthy controls (HC) were prospectively enrolled. Participants underwent whole-body 18 F-fluorodeoxyglucose positron emission tomography/magnetic resonance (FDG-PET/MR) imaging. Stress-related neural network activity (SNNA) was assessed on PET as amygdala metabolic activity relative to regulatory (ventromedial prefrontal cortex [vmPFC]) activity. The structural integrity of the uncinate fasciculus, the major white matter tract connecting the amygdala to vmPFC, was assessed using diffusion tensor imaging (DTI). Atherosclerotic burden was assessed on MR as vessel normalized wall index and standard deviation (SD) of vessel wall thickness. Results: Of 91 participants (24 PTSD, 42 TC, 24 HC), 57% were female, and the median age was 37 years. Compared to controls, individuals with PTSD had higher SNNA (Fig 1A) and lower uncinate fasciculus integrity (Fig 1B). SNNA and uncinate fasciculus integrity were negatively correlated (r = - 0.30, p=0.008). Those with PTSD had higher ascending aorta normalized wall indices (p=0.018, adjusted for Framingham risk score). Notably, the SD of carotid wall thickness correlated positively with SNNA and negatively with uncinate fasciculus integrity (Fig 1C &amp; D). Conclusion: These findings suggest that increases in the amygdala relative to vmPFC metabolic activity or disruptions of their structural interconnections may potentiate atherosclerosis. Interventions targeting this stress-related neural network may reduce adverse brain-heart interactions and related cardiovascular disease burden.

Right uncinate fasciculus supports socioemotional sensitivity in health and neurodegenerative disease

The uncinate fasciculus (UF) connects fronto-insular and temporal gray matter regions involved in visceral emotional reactivity and semantic appraisal, but the precise role of this tract in socioemotional functioning is not well-understood. Using the Revised-Self Monitoring (RSMS) informant questionnaire, we examined whether fractional anisotropy (FA) in the right UF corresponded to socioemotional sensitivity during face-to-face interactions in 145 individuals (40 healthy older adults [NC], and 105 patients with frontotemporal lobar degeneration [FTLD] syndromes in whom this tract is selectively vulnerable, including 31 behavioral variant frontotemporal dementia [bvFTD], 39 semantic variant primary progressive aphasia [svPPA], and 35 nonfluent variant primary progressive aphasia [nfvPPA]). Voxelwise and region-of-interest-based DWI analyses revealed that FA in the right but not left UF significantly predicted RSMS score in the full sample, and in NC and svPPA subgroups alone. Right UF integrity did not predict RSMS score in the bvFTD group, but gray matter volume in the right orbitofrontal cortex adjacent to the UF was a significant predictor. Our results suggest that better socioemotional sensitivity is specifically supported by right UF white matter, highlighting a key neuro-affective relationship found in both healthy aging and neurologically affected individuals. The finding that poorer socioemotional sensitivity corresponded to right UF damage in svPPA but was more robustly influenced by gray matter atrophy adjacent to the UF in bvFTD may have important implications for endpoint selection in clinical trial design for patients with FTLD.

White matter tract integrity, but not amyloid burden, is related to cognition in cognitively normal older adults

AbstractBackgroundThe increased focus on preclinical Alzheimer’s disease (AD) necessitates an understanding of how general biomarkers of neuronal injury and AD‐specific biomarkers differentially contribute to the cognitive performance in cognitively normal individuals. It has been suggested that alterations in limbic white matter (WM) tracts may precede both gray matter atrophy and clinical impairment (Teipel et al., 2016). However, few studies have evaluated whether limbic tract alterations are associated with cognitive performance in individuals with normal cognition. To address this gap, this cross‐sectional, multi‐modal imaging study examined whether measures of WM tract integrity, using diffusion tensor imaging (DTI) (including fornix, hippocampal cingulum, and uncinate fasciculus), were related to cognitive performance, independent of cortical amyloid burden in cognitively normal individuals.MethodAnalyses included 130 cognitively normal participants from the BIOCARD Study (Table 1) who completed cognitive assessments, diffusion‐weighted MR and 11C‐PiB PET imaging during their annual visit. Cognitive performance was captured by cognitive composite scores reflecting verbal episodic memory, executive function, and visuospatial processing. WM tract integrity was measured by fractional anisotropy (FA) and radial diffusivity (RD) in the 3 above‐mentioned ROIs. PiB PET amyloid positivity was derived from cortical distribution volume ratios (cDVR) using cerebellar gray matter as the reference.Linear regressions (covarying age, sex, and education) were used to test 4 a priori cognition‐WM associations. The following relationships were examined: episodic memory and fornix and hippocampal cingulum integrity; executive function and uncinate fasciculus integrity; visuospatial processing and hippocampal cingulum integrity.ResultIn the linear regression models (Table 2), lower hippocampal cingulum FA and greater hippocampal cingulum RD were each associated with better episodic memory performance. Additionally, lower uncinate fasciculus RD (but not FA) was associated with better executive function performance. In contrast, amyloid positivity (i.e., cDVR &gt; 1.06) was unrelated to any of the cognitive composite scores (all ps &gt; .35).ConclusionMeasures of WM tract integrity account for variability in cognitive performance among cognitively normal individuals, and this association is independent of amyloid burden. Additional analyses are needed to determine whether these microstructural measures reflect general, age‐related markers of neuronal injury vs. alterations related to preclinical AD.

Grey and white matter correlates of behavioural disinhibition assessed under semi-ecological conditions in behavioural variant frontotemporal dementia.

Behavioural variant frontotemporal dementia (bvFTD) is partly characterised by inhibition disorders. Neural correlates of disinhibition being poorly known, we aim to identify grey and white matter impairments associated to behavioural disinhibition. We assess behavioural disinhibition in a semi-ecological setting, noting occurrences of 16 behaviours - derived from clinical criteria of bvFTD - related to compulsivity, impulsivity or social disinhibition, in a population of 20 bvFTD and 20 healthy controls (HC). Subjects also undergo an MRI. In this study, voxel-based morphometry and diffusion tensor tractography (DTI) are used to investigate grey and white matter changes in bvFTD patients compared to HC. Grey matter atrophy and DTI metrics - fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) - are then correlated to behavioural disinhibition scores. Grey matter analysis was conducted on 15 bvFTD and 18 HC. Results mainly show an alteration of frontal and anterior temporal regions as well as subcortical regions (e.g., thalamus) in bvFTD patients compared to HC. Social disinhibition is correlated with a huge atrophy of the frontotemporal regions and of the cingulate cortex, while compulsivity and impulsivity are associated to smaller areas of the orbitofrontal and temporal regions. Based on these results, white matter analysis was conducted on 10 bvFTD patients and 11 HC. Results show a significant decrease of FA and increase of RD in the cingulum, the forceps minor (FM) and the uncinate fasciculus (UF) in bvFTD patients. In addition, patients show a significant increase of MD in the FM and the UF, as well as a significant increase of AD in the FM and right UF. Among bvFTD patients, compulsivity is associated to a weaker integrity of the cingulum while social disinhibition is correlated to alterations of the left UF. On the contrary, impulsivity is correlated with greater integrity of the bilateral uncinate. The cingulum is already known to be impaired in obsessive-compulsive disorder and UF impairments are related to behavioural and social disinhibition. Furthermore, positive correlation between impulsive behaviours and UF integrity are already reported, which is consistent with our findings based on a semi-ecological assessment of behavioural disinhibition.

Hyperarousal symptoms and decreased right hemispheric frontolimbic white matter integrity predict poorer sleep quality in combat-exposed veterans

ABSTRACT Objective Disrupted sleep is common following combat deployment. Contributors to risk include posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI); however, the mechanisms linking PTSD, mTBI, and sleep are unclear. Both PTSD and mTBI affect frontolimbic white matter tracts, such as the uncinate fasciculus. The current study examined the relationship between PTSD symptom presentation, lateralized uncinate fasciculus integrity, and sleep quality. Method Participants include 42 combat veterans with and without PTSD and mTBI. Freesurfer and Tracula were used to establish specific white matter ROI integrity via 3-T MRI. The Pittsburgh Sleep Quality Index and PTSD Checklist were used to assess sleep quality and PTSD symptoms. Results Decreased fractional anisotropy in the right uncinate fasciculus (β = −1.11, SE = 0.47, p < .05) and increased hyperarousal symptom severity (β = 3.50, SE = 0.86, p < .001) were associated with poorer sleep quality. Conclusion Both right uncinate integrity and hyperarousal symptom severity are associated withsleep quality in combat veterans. The right uncinate is a key regulator of limbic behavior and sympathetic nervous system reactivity, a core component of hyperarousal. Damage to this pathway may be one mechanism by which mTBI and/or PTSD could create vulnerability for sleep problems following combat deployment.

Association between Uncinate Fasciculus Integrity and Agoraphobia Symptoms in Female Patients with Panic Disorder.

ObjectiveAlthough neural correlates of sub-clinical agoraphobia (AG) symptoms have been previously suggested, only a few studies evaluating structural changes of the brain have been conducted in agoraphobic patients with panic disorder (PD). We investigated and compared white matter (WM) micro-structural alterations between PD patients with AG (PD ＋ AG) and those without AG (PD − AG).MethodsOur study included 56 female PD patients, of which 25 were diagnosed with AG and 31 were diagnosed without AG. Diffusion tensor imaging was performed to investigate micro-structural changes in the WM tracts related to fronto-temporo-occipital areas (uncinate fasciculus, cingulum bundle, inferior longitudinal/fronto-occipital fasciculus, fornix column and body, and fornix/stria terminalis). All participants were subjected to the Anxiety Sensitivity Inventory-Revised (ASI-R), Beck Depression Inventory-II (BDI-II), and Albany Panic and Phobia questionnaires.ResultsThe fractional anisotropy values of the right uncinate fasciculus in PD ＋ AG were significantly lower than that of PD − AG and showed significant correlations with BDI-II and ASI-R total scores. Mean diffusivity and radial diffusivity values of the right uncinate fasciculus were significantly higher in PD ＋ AG as compared to PD − AG.ConclusionOur findings suggest that the uncinate fasciculus may be associated with AG symptoms in PD, possibly through demyelination. Our findings may contribute to the neurobiological evidence regarding the association between AG and WM structural changes in PD.

Integrity of the uncinate fasciculus is associated with the onset of bipolar disorder: a 6-year followed-up study

Patients with Bipolar Disorder (BD) are associated with aberrant uncinate fasciculus (UF) that connects amygdala-ventral prefrontal cortex (vPFC) system, but the casual relationship is still uncertain. The research aimed to investigate the integrity of UF among offspring of patients with BD and investigate its potential causal association with subsequent declaration of BD. The fractional anisotropy (FA) and mean diffusivity (MD) of UF were compared in asymptomatic offspring (AO, n = 46) and symptomatic offspring (SO, n = 45) with a parent with BD, and age-matched healthy controls (HCs, n = 35). Logistic regressions were performed to assess the predictive effect of UF integrity on the onset of BD. The three groups did not differ at baseline in terms of FA and MD of the UF. Nine out of 45 SO developed BD over a follow-up period of 6 years, and the right UF FA predicted the onset of BD (p = 0.038, OR = 0.212, 95% CI = 0.049–0.917). The ROC curve revealed that the right UF FA predicted BD onset (area-under-curve = 0.859) with sensitivity of 88.9% and specificity of 77.3%. The complementary whole-brain tract-based spatial statistics (TBSS) showed that widespread increases of FA were found in the SO group compared with HCs, but were not associated with the onset of BD. Our data provide evidence supporting the causal relationship between the white matter structural integrity of the amygdala-vPFC system and the onset of BD in genetically at-risk offspring of BD patients.

Age-related differences in structural and functional prefrontal networks during a logical reasoning task.

In logical reasoning, difficulties in inhibition of currently-held beliefs may lead to unwarranted conclusions, known as belief bias. Aging is associated with difficulties in inhibitory control, which may lead to deficits in inhibition of currently-held beliefs. No study to date, however, has investigated the underlying neural substrates of age-related differences in logical reasoning and the impact of belief load. The aim of the present study was to delineate age differences in brain activity during a syllogistic logical reasoning task while the believability load of logical inferences was manipulated. Twenty-nine, healthy, younger and thirty, healthy, older adults (males and females) completed a functional magnetic resonance imaging experiment in which they were asked to determine the logical validity of conclusions. Unlike younger adults, older adults engaged a large-scale network including anterior cingulate cortex and inferior frontal gyrus during conclusion stage. Our functional connectivity results suggest that while older adults engaged the anterior cingulate network to overcome their intuitive responses for believable inferences, the inferior frontal gyrus network contributed to higher control over responses during both believable and unbelievable conditions. Our functional results were further supported by structure-function-behavior analyses indicating the importance of cingulum bundle and uncinate fasciculus integrity in rejection of believable statements. These novel findings lend evidence for age-related differences in belief bias, with potentially important implications for decision making where currently-held beliefs and given assumptions are in conflict.

Longitudinal Diffusion Tensor Imaging Study of Adolescents and Young Adults With Bipolar Disorder

Longitudinal neuroimaging during adolescence/young adulthood, when bipolar disorder (BD) commonly emerges, can help elucidate the neurodevelopmental pathophysiology of BD. Adults with BD have shown reduced structural integrity in the uncinate fasciculus (UF), a white matter (WM) tract providing major connections between the amygdala and ventral prefrontal cortex (vPFC), important in emotion regulation. In this longitudinal diffusion tensor imaging (DTI) study of adolescents/young adults, we hypothesized differences in age- and time-related changes in UF integrity in BD compared to healthy controls (HC). Two DTI scans were obtained in 27 adolescents/young adults with BD and 37 HC adolescents/young adults, on average approximately 2.5 years apart. Interactions between diagnosis with age and with time for UF fractional anisotropy (FA) were assessed. Exploratory analyses were performed including euthymic-only participants with BD, and for potential influences of demographic and clinical factors. Whole-brain analyses were performed to explore for interactions in other regions. There were significant interactions between diagnosis with age and with time for UF FA (p< .05). Healthy control adolescents/young adults showed significant UF FA increases with age and over time (p< .05), whereas no significant changes with age or over time were observed in the adolescents/young adults with BD. Significant interactions with age and time were also observed in analyses including euthymic-only participants with BD (p< .05). These findings provide neuroimaging evidence supporting differences in UF WM structural development during adolescence/young adulthood, suggesting that differences in the development of an amygdala-vPFC system subserving emotion regulation may be a trait feature of BD neurodevelopment.

White matter correlates of psychopathic traits in a female community sample.

Psychopathy comprises interpersonal, affective, lifestyle and antisocial facets that vary dimensionally in the population and are associated with criminal offending and adverse psychosocial outcomes. Evidence associating these facets with white matter microstructure of the uncinate fasciculus and the cingulum tracts is inconsistent and derives principally from studies of male offenders. In a sample of 99 young women presenting a range of scores on the Psychopathy Checklist: Screening Version, we used Diffusion Tensor Imaging, tractography and Tract-Based Spatial Statistics to investigate microstructure across the brain and of the uncinate fasciculus and cingulum. Right uncinate fasciculus microstructure was negatively associated with the interpersonal facet, while cingulum integrity was not associated with any facet of psychopathy. Whole-brain analyses revealed that both affective and lifestyle facets were negatively correlated with white matter microstructure adjacent to the fusiform gyrus, and the interpersonal facet correlated negatively with the integrity of the fornix. Findings survived adjustment for the other facet scores, and age, verbal and performance IQ. A similar negative association between the interpersonal facet and uncinate fasciculus integrity was previously observed in male offenders. Thus, previous evidence showing that psychopathic traits are associated with functional and structural abnormalities within limbic networks may also apply to females.

Effects of sensitivity to life stress on uncinate fasciculus segments in early adolescence.

Previous research suggests that exposure to early life stress (ELS) affects the structural integrity of the uncinate fasciculus (UF), a frontolimbic white matter tract that undergoes protracted development throughout adolescence. Adolescence is an important transitional period characterized by the emergence of internalizing psychopathology such as anxiety, particularly in individuals with high levels of stress sensitivity. We examined the relations among sensitivity to ELS, structural integrity of the UF, and anxiety symptoms in 104 early adolescents. We conducted structured interviews to assess exposure to ELS and obtained subjective and objective ratings of stress severity, from which we derived an index of ELS sensitivity. We also acquired diffusion MRI and conducted deterministic tractography to visualize UF trajectories and to compute measures of structural integrity from three distinct segments of the UF: frontal, insular, temporal. We found that higher sensitivity to ELS predicted both reduced fractional anisotropy in right frontal UF and higher levels of anxiety symptoms. These findings suggest that fibers in frontal UF, which are still developing throughout adolescence, are most vulnerable to the effects of heightened sensitivity to ELS, and that reduced structural integrity of frontal UF may underlie the relation between early stress and subsequent internalizing psychopathology.

Emotion detection deficits and changes in personality traits linked to loss of white matter integrity in primary progressive aphasia.

Non-cognitive features including personality changes are increasingly recognized in the three PPA variants (semantic-svPPA, non fluent-nfvPPA, and logopenic-lvPPA). However, differences in emotion processing among the PPA variants and its association with white matter tracts are unknown. We compared emotion detection across the three PPA variants and healthy controls (HC), and related them to white matter tract integrity and cortical degeneration. Personality traits in the PPA group were also examined in relation to white matter tracts. Thirty-three patients with svPPA, nfvPPA, lvPPA, and 32 HC underwent neuropsychological assessment, emotion evaluation task (EET), and MRI scan. Patients' study partners were interviewed on the Clinical Dementia Rating Scale (CDR) and completed an interpersonal traits assessment, the Interpersonal Adjective Scale (IAS). Diffusion tensor imaging of uncinate fasciculus (UF), superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), and voxel-based morphometry to derive gray matter volumes for orbitofrontal cortex (OFC), anterior temporal lobe (ATL) regions were performed. In addition, gray matter volumes of white matter tract-associated regions were also calculated: inferior frontal gyrus (IFG), posterior temporal lobe (PTL), inferior parietal lobe (IPL) and occipital lobe (OL). ANCOVA was used to compare EET performance. Partial correlation and multivariate linear regression were conducted to examine association between EET and neuroanatomical regions affected in PPA. All three variants of PPA performed significantly worse than HC on EET, and the svPPA group was least accurate at recognizing emotions. Performance on EET was related to the right UF, SLF, and ILF integrity. Regression analysis revealed EET performance primarily relates to the right UF integrity. The IAS subdomain, cold-hearted, was also associated with right UF integrity. Disease-specific emotion recognition and personality changes occur in the three PPA variants and are likely associated with disease-specific neuroanatomical changes. Loss of white matter integrity contributes as significantly as focal atrophy in behavioral changes in PPA.

Persistent amygdala novelty response is associated with less anterior cingulum integrity in trauma-exposed women.

ObjectivesWe investigated the potential role of cingulum and uncinate fasciculus integrity in trauma-related neural hypervigilance, indexed by less discrimination between amygdala activation to novel and familiar affective images.Participants22 women (mean age 21.7 ± 3.9 years) with a history of trauma, and 20 no-trauma controls (mean age 21.9 ± 4.8 years).MeasuresTrauma exposure and trauma-related symptoms were assessed during structured clinical interview. White matter integrity in the anterior cingulum, parahippocampal cingulum, and uncinate fasciculus was measured using diffusion weighted imaging. Amygdala response to novel and familiar affective scenes was measured with functional magnetic resonance imaging.ResultsTrauma-exposed women showed less discrimination between novel and familiar negative images in the amygdala compared to no-trauma controls. In trauma-exposed women, less amygdala discrimination between novel and familiar affective images was associated with less structural integrity in the anterior cingulum, but was not associated with structural integrity of the parahippocampal cingulum or the uncinate fasciculus.ConclusionsThe anterior cingulum might play an important role in impaired novelty discrimination for affective information in the amygdala. This impairment is potentially driven by inefficient habituation and could contribute to persistent behavioral hypervigilance following trauma exposure.

White matter microstructure of the uncinate fasciculus is associated with subthreshold posttraumatic stress disorder symptoms and fear potentiated startle during early extinction in recently deployed Service Members

Early intervention following combat deployment has the potential to prevent posttraumatic stress disorder (PTSD), but there is a need for greater understanding of the factors that contribute to PTSD symptom progression. This study investigated: (1) fear-potentiated startle during a fear extinction, (2) white matter microstructure, and (3) PTSD symptom severity, in 48 recently deployed service members (SMs) who did not have sufficient PTSD symptoms to meet criteria for a clinical diagnosis. Electromyography startle during a conditional discrimination paradigm, diffusion tensor imaging, and the Clinician Administered PTSD Scale were assessed in a cohort of SMs within 2 months after their return from Iraq or Afghanistan. Significant correlations were found between left uncinate fasciculus (UF) white matter tract integrity and total PTSD symptoms, r=−0.343, p=0.018; the left UF and hyperarousal symptoms, r=−0.29, p=0.047; right UF integrity and total PTSD symptoms r=−0.3371, p=0.01; right UF integrity and hyperarousal symptoms r=−0.332, p=0.023; left UF and startle during early extinction, r=.31, p=0.033. Our results indicate that compromise of UF tract frontal-limbic connections are associated with greater PTSD symptom severity and lower startle response during extinction. In a subthreshold population, such a relationship between brain structure, physiological reactivity, and behavioral expression may reveal vulnerabilities that could have significant implications for PTSD symptom development.

Disrupted white matter integrity is associated with cognitive deficits in patients with amnestic mild cognitive impairment: An atlas-based study.

Objective:This study investigated white matter integrity in patients with amnestic mild cognitive impairment by diffusion tensor imaging.Methods:A total of 83 patients with amnestic mild cognitive impairment and 85 elderly healthy controls underwent neuropsychological testing and a diffusion tensor imaging scan. Whole-brain white matter data were parcellated into 50 regions based on the anatomical ICBM-DTI-81 atlas, and regional diffusion metrics consisting of fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity were calculated for each region. Diffusion tensor imaging indices were compared between groups, and it was determined that between-group differences were significantly correlated with neurocognitive performance.Results:Relative to the healthy controls group, the amnestic mild cognitive impairment group exhibited poorer cognitive performance in all neuropsychological tests except the complex figure test (p = 0.083) and showed decreased mean fractional anisotropy in the fornix, increased mean diffusivity in the fornix and bilateral uncinate fasciculus, elevated axial diffusivity in the fornix and genu of corpus callosum, and elevated radial diffusivity in the fornix and bilateral uncinate fasciculus (p < 0.05). Behaviorally, integrity of the bilateral uncinate fasciculus was correlated positively with episodic memory function, while left uncinate fasciculus integrity was positively associated with language function in the amnestic mild cognitive impairment group (p < 0.05).Conclusion:White matter abnormalities in neural pathways associated with memory were correlated with neurocognitive deficiencies in amnestic mild cognitive impairment. Given that amnestic mild cognitive impairment is putatively a prodromal syndrome for Alzheimer’s disease, this study furthers our understanding of the white matter changes associated with Alzheimer’s disease pathogenesis in the predementia stage.

Lower structural integrity of the uncinate fasciculus is associated with a history of child maltreatment and future psychological vulnerability to stress.

The experience of child maltreatment is a significant risk factor for the development of later internalizing disorders such as depression and anxiety. This risk is particularly heightened after exposure to additional, more contemporaneous stress. While behavioral evidence exists for such "stress sensitization," little is known about the mechanisms mediating such relationships, particularly within the brain. Here we report that the experience of child maltreatment independent of recent life stress, gender, and age is associated with reduced structural integrity of the uncinate fasciculus, a major white matter pathway between the amygdala and ventromedial prefrontal cortex, in young adults. We further demonstrate that individuals with lower uncinate fasciculus integrity at baseline who subsequently experience stressful life events report higher levels of internalizing symptomatology at follow-up. Our findings suggest a novel neurobiological mechanism linking child maltreatment with later internalizing symptoms, specifically altered structural connectivity within the brain's threat-detection and emotion-regulation circuitry.

Callous-unemotional traits drive reduced white-matter integrity in youths with conduct problems.

Callous-unemotional (CU) traits represent a significant risk factor for severe and persistent conduct problems in children and adolescents. Extensive neuroimaging research links CU traits to structural and functional abnormalities in the amygdala and ventromedial prefrontal cortex. In addition, adults with psychopathy (a disorder for which CU traits are a developmental precursor) exhibit reduced integrity in uncinate fasciculus, a white-matter (WM) tract that connects prefrontal and temporal regions. However, research in adolescents has not yet yielded similarly consistent findings. We simultaneously modeled CU traits and externalizing behaviors as continuous traits, while controlling for age and IQ, in order to identify the unique relationship of each variable with WM microstructural integrity, assessed using diffusion tensor imaging. We used tract-based spatial statistics to evaluate fractional anisotropy, an index of WM integrity, in uncinate fasciculus and stria terminalis in 47 youths aged 10-17 years, of whom 26 exhibited conduct problems and varying levels of CU traits. Whereas both CU traits and externalizing behaviors were negatively correlated with WM integrity in bilateral uncinate fasciculus and stria terminalis/fornix, simultaneously modeling both variables revealed that these effects were driven by CU traits; the severity of externalizing behavior was not related to WM integrity after controlling for CU traits. These results indicate that WM abnormalities similar to those observed in adult populations with psychopathy may emerge in late childhood or early adolescence, and may be critical to understanding the social and affective deficits observed in this population.