Cortical Thickness In Brain Regions Research Articles

Neuroimaging and epigenetic analysis reveal novel epigenetic loci in major depressive disorder.

Epigenetic modifications, such as DNA methylation, contribute to the pathophysiology of major depressive disorder (MDD). This study aimed to identify novel MDD-associated epigenetic loci using DNA methylation profiles and explore the correlations between epigenetic loci and cortical thickness changes in patients with MDD. A total of 350 patients with MDD and 161 healthy controls (HCs) were included in the epigenome-wide association studies (EWAS). We analyzed methylation, copy number alteration (CNA), and gene network profiles in the MDD group. A total of 234 patients with MDD and 135 HCs were included in neuroimaging methylation analysis. Pearson's partial correlation analysis was used to estimate the correlation between cortical thickness of brain regions and DNA methylation levels of the loci. In total, 2018 differentially methylated probes (DMPs) and 351 differentially methylated regions (DMRs) were identified. DMP-related genes were enriched in two networks involved in the central nervous system. In neuroimaging analysis, patients with MDD showed cortical thinning in the prefrontal regions and cortical thickening in several occipital regions. Cortical thickness of the left ventrolateral prefrontal cortex (VLPFC, i.e. pars triangularis) was negatively correlated with eight DMPs associated with six genes (EML6, ZFP64, CLSTN3, KCNMA1, TAOK2, and NT5E). Through combining DNA methylation and neuroimaging analyses, negative correlations were identified between the cortical thickness of the left VLPFC and DNA methylation levels of eight DMPs. Our findings could improve our understanding of the pathophysiology of MDD.

Susceptibility or resilience to childhood peer abuse can be explained by cortical thickness in brain regions involved in emotional regulation

Experiencing peer abuse in childhood can damage mental health, but some people exhibit resilience against these negative outcomes. However, it remains uncertain which specific changes in brain structures are associated with this type of resilience. We categorized 217 participants into three groups: resilience group, susceptibility group, and healthy control group, based on their experiences of peer abuse and mental health problems. They underwent MRI scans to measure cortical thickness in various brain regions of the prefrontal cortex. We employed covariance analysis to compare cortical thickness among these groups. Individuals who resilient to anxiety exhibited smaller cortical thickness in the bilateral inferior frontal gyrus (IFG), and with larger thickness in the right medial orbitofrontal cortex (mOFC), while those resilient to stress was associated with smaller thickness in both the bilateral IFG and bilateral middle frontal gyrus (MFG). These findings deepen our understanding of the neural mechanisms underlying resilience and offer insight into improving individual resilience.

Amyloid beta-independent sleep markers associated with early regional tau burden and cortical thinning.

Sleep is crucial for memory consolidation and the clearance of toxic proteins associated with Alzheimer's disease (AD). We examined the association between sleep characteristics and imaging biomarkers of early amyloid beta (Aβ) and tau pathology as well as neurodegeneration in brain regions known to be affected in the incipient stages of AD. Thirty-nine cognitively unimpaired (CU) participants of the Harvard Aging Brain Study underwent at-home polysomnography as well as tau positron emission tomography (flortaucipir-PET), amyloid PET (Pittsburgh compound B [PiB]-PET), and magnetic resonance imaging-derived assessment of cortical thickness (CT). Increased N1 sleep was associated with a higher tau PET signal (β=0.009, p=0.001) and lower CT in the temporal composite region of interest (β=-0.017, p=0.007). Decreased slow-wave sleep (SWS) was associated with higher tau burden in the temporal composite (β=-0.008, p=0.005) and lower CT (β=0.008, p=0.002), even after controlling for global PiB-PET. In CU older adults, lower SWS and higher N1 sleep were associated with higher tau burden and lower CT in brain regions associated with early tau deposition and vulnerable to AD-related neurodegeneration through mechanisms dissociable from amyloid deposition. We report the results of an observational study, which leveraged -a well-characterized cohort of healthy aging (Harvard Aging Brain Study) by adding in-home full polysomnograms.By adding at-home polysomnograms to this unique and deeply phenotyped cohort, we examined variations in sleep architecture that are associated with Alzheimer's disease (AD) pathologic changes.Our results confirmed the association of sleep changes with early tau and cortical neurodegenerative changes that were independent of amyloid.The results will be of importance in monitoring sleep-related variations in relation to the natural history of AD pathology and in designing sleep-focused clinical trials.

Associations between Age and Cortical Thickness in Brain Regions Supporting Speech Motor Control

AbstractBackgroundPrior research has demonstrated consistent associations between age and cortical thickness, as well as longitudinal reductions in cortical thickness in older adults (e.g., Salat et al., 2004; Storsve et al., 2014). To date, the aging of regions supporting speech production has not been directly investigated. Such information is, however, needed to differentiate age‐related cortical atrophy in speech regions from that occurring due to underlying neurodegenerative diseases. We examined cross‐sectional associations between age and cortical thickness of brain regions supporting speech motor control. These areas include subregions of the premotor cortex, primary motor area, supplementary motor area, pars opercularis, posterior inferior frontal sulcus, and insula as defined by the Directions Into Velocities of Articulators (DIVA) model ‐ a model for neural representation and mechanisms of speech motor control (Tourville & Guenther, 2011).MethodThe data were obtained from the Alzheimer’s Disease Neuroimaging Initiative GO/2 (ADNI). Participants included 163 (77 M, 86 F) cognitively intact adults aged 56‐89 years (Mean = 73.45, SD = 6.23). All participants were right‐handed and had at least 12 years of education (Mean = 16.53, SD = 2.55). Whole‐brain T1‐weighted MRI images were acquired by a 3‐Tesla Siemens scanner. FreeSurfer software was used for cortical surface reconstruction and to extract the cortical thickness of speech regions as identified by the SpeechLabel Parcellation System (Cai et al., 2014) developed based on the DIVA model.ResultSignificant associations between age and cortical thickness was observed in subregions of left premotor cortex, primary motor area, supplementary motor area, and presupplementary motor area with more limited effects in the right hemisphere. Cortical thickness of pars opercularis, posterior inferior frontal sulcus, and insula did not show significant changes over the aging process. Cross‐sectional interactions were found with regions in the left hemisphere being thicker at younger ages and having a larger negative age slope compared to their corresponding regions in the right hemisphere.ConclusionThe findings of the study suggest that certain speech‐related regions show atrophy with aging, however, these changes are not uniform. In addition, laterality in cortical thickness of speech regions at younger ages was observed to diminish over the normal aging process.

Remote cortical atrophy and language outcomes after chronic left subcortical stroke with aphasia.

ObjectiveSubcortical stroke can cause a variety of language deficits. However, the neural mechanisms underlying subcortical aphasia after stroke remain incompletely elucidated. We aimed to determine the effects of distant cortical structures on aphasia outcomes and examine the correlation of cortical thickness measures with connecting tracts integrity after chronic left subcortical stroke.MethodsThirty-two patients and 30 healthy control subjects underwent MRI scanning and language assessment with the Western Aphasia Battery-Revised (WAB-R) subtests. Among patients, the cortical thickness in brain regions that related to language performance were assessed by the FreeSurfer software. Fiber tracts connecting the identified cortical regions to stroke lesions were reconstructed to determine its correlations with the cortical thickness measures across individual patient.ResultsCortical thickness in different parts of the left fronto-temporo-parietal (FTP) regions were positively related to auditory-verbal comprehension, spontaneous speech and naming/word finding abilities when controlling for key demographic variables and lesion size. Cortical thickness decline in the identified cortical regions was positively correlated with integrity loss of fiber tracts connected to stroke lesions. Additionally, no significant difference in cortical thickness was found across the left hemisphere between the subgroup of patients with hypoperfusion (HP) and those without HP at stroke onset.ConclusionsThese findings suggest that remote cortical atrophy independently predicts language outcomes in patients with chronic left subcortical stroke and aphasia and that cortical thinning in these regions might relate to integrity loss of fiber tracts connected to stroke lesions.

Neuroanatomical Correlates of Semantic Features of Narrative Speech in Semantic and Logopenic Variants of Primary Progressive Aphasia.

The semantic variant of a primary progressive aphasia (svPPA) is characterized by progressive disruption of semantic knowledge. This study aimed to compare the semantic features of words produced during a narrative speech in svPPA and the logopenic variant of PPA (lvPPA) and to explore their neuroanatomical correlates. Six patients with svPPA and sixteen with lvPPA underwent narrative speech tasks. For all the content words, a semantic depth index (SDI) was determined based on the taxonomic structure of a large lexical database. Study participants underwent an MRI examination. Cortical thickness measures were extracted according to the Desikan atlas. Correlations were computed between SDI and the thickness of cortical regions. Mean SDI was lower for svPPA than for lvPPA. Correlation analyses showed a positive association between the SDI and the cortical thickness of the bilateral temporal pole, parahippocampal and entorhinal cortices, and left middle and superior temporal cortices. Disruption of semantic knowledge observed in svPPA leads to the production of generic terms in narrative speech, and the SDI may be useful for quantifying the level of semantic impairment. The measure was associated with the cortical thickness of brain regions associated with semantic memory.

Association Between Cerebral Cortical Microinfarcts and Perilesional Cortical Atrophy on 3T MRI.

Cerebral cortical microinfarcts (CMIs) are a novel MRI marker of cerebrovascular disease (CeVD) that predicts accelerated cognitive decline. Presence of CMIs is known to be associated with global cortical atrophy, although the mechanism linking the two is unclear. Our primary objective was to examine the relation between CMIs and cortical atrophy and to establish possible perilesional atrophy surrounding CMIs. Our secondary objective was to examine the role of cortical atrophy in CMI-associated cognitive impairment. Patients were recruited from 2 Singapore memory clinics between December 2010 and September 2013 and included if they received the diagnosis no objective cognitive impairment, cognitive impairment (with or without a history of stroke), or Alzheimer or vascular dementia. Cortical thickness, chronic CMIs, and MRI markers of CeVD were assessed on 3T MRI. Patients underwent cognitive testing. Cortical thickness was compared globally between patients with and without CMIs, regionally within individual patients with CMIs comparing brain regions with CMIs to the corresponding contralateral region without CMIs, and locally within individuals patients in a 50-mm radius of CMIs. Global cortical thickness was analyzed as mediator in the relation between CMI and cognitive performance. Of the 238 patients (mean age 72.5 years, SD 9.1 years) enrolled, 75 had ≥1 CMIs. Patient with CMIs had a 2.1% lower global cortical thickness (B = -0.049 mm, 95% confidence interval [CI] 0.091 to -0.007, p = 0.022) compared to patients without CMIs, after correction for age, sex, education, and intracranial volume. In patients with CMIs, cortical thickness in brain regions with CMIs was 2.2% lower than in contralateral regions without CMIs (B = -0.048 mm [95% CI -0.071 to -0.026], p < 0.001). In a 20-mm radius area surrounding the CMI core, cortical thickness was lower than in the area 20 to 50 mm from the CMI core (mean difference -0.06 mm [-0.10 to -0.02], p = 0.002). Global cortical thickness was a significant mediator in the relationship between CMI presence and cognitive performance as measure with the Mini-Mental State Examination (B = -0.12 [-0.22 to -0.01], p = 0.025). We found cortical atrophy surrounding CMIs, suggesting a perilesional effect in a cortical area many times larger than the CMI core. Our findings support the notion that CMIs affect brain structure beyond the actual lesion site.

Imaging the aging brain: study design and baseline findings of the SENIOR cohort

BackgroundCurrent demographic trends point towards an aging society entailing increasing occurrence and burden of neurodegenerative diseases. In this context, understanding physiological aging and its turning point into neurodegeneration is essential for the development of possible biomarkers and future therapeutics of brain disease.MethodsThe SENIOR study represents a longitudinal, observational study including cognitively healthy elderlies aged between 50 and 70 years old at the time of inclusion, being followed annually over 10 years. Our multimodal protocol includes structural, diffusion, functional, and sodium magnetic resonance imaging (MRI) at 3 T and 7 T, positron emission tomography (PET), blood samples, genetics, audiometry, and neuropsychological and neurological examinations as well as assessment of neuronal risk factors.ResultsOne hundred forty-two participants (50% females) were enrolled in the SENIOR cohort with a mean age of 60 (SD 6.3) years at baseline. Baseline results with multiple regression analyses reveal that cerebral white matter lesions can be predicted by cardiovascular and cognitive risk factors and age. Cardiovascular risk factors were strongly associated with juxtacortical and periventricular lesions. Intra-subject across-test variability as a measure of neuropsychological test performance and possible cognitive marker predicts white matter volume and is significantly associated with risk profile. Division of the cohort into subjects with a higher and lower risk profile shows significant differences in intra-subject across-test variability and volumes as well as cortical thickness of brain regions of the temporal lobe. There is no difference between the lower- and higher-risk groups in amyloid load using PET data from a subset of 81 subjects.ConclusionsWe here describe the study protocol and baseline findings of the SENIOR observational study which aim is the establishment of integrated, multiparametric maps of normal aging and the identification of early biomarkers for neurodegeneration. We show that intra-subject across-test variability as a marker of neuropsychological test performance as well as age, gender, and combined risk factors influence neuronal decline as represented by decrease in brain volume, cortical thickness, and increase in white matter lesions. Baseline findings will be used as underlying basis for the further implications of aging and neuronal degeneration as well as examination of brain aging under different aspects of brain pathology versus physiological aging.

Impact of urban environmental exposures on cognitive performance and brain structure of healthy individuals at risk for Alzheimer’s dementia

BackgroundAir quality might contribute to incidence of dementia-related disorders, including Alzheimer’s dementia (AD). The aim of our study is to evaluate the effect of urban environmental exposures (including exposure to air pollution, noise and green space) on cognitive performance and brain structure of cognitively unimpaired individuals at risk for AD. Participants and methodsThe ALFA (ALzheimer and FAmilies) study is a prospective cohort of middle-age, cognitively unimpaired subjects, many of them offspring of AD patients. Cognitive performance was measured by the administration of episodic memory and executive function tests (N = 958). Structural brain imaging was performed in a subsample of participants to obtain morphological information of brain areas, specially focused on cortical thickness, known to be affected by AD (N = 228). Land Use Regression models were used to estimate residential exposure to air pollutants. The daily average noise level at the street nearest to each participant's residential address was obtained from noise maps. For each participant residential green exposure indicators, such as surrounding greenness or amount of green, were generated. General linear models were conducted to assess the association between environmental exposures, cognitive performance and brain structure in a cross-sectional analysis. ResultsNo significant associations were observed between urban environmental exposures and the cognitive composite (p > 0.1). Higher exposure to air pollutants, but not noise, was associated with lower cortical thickness in brain regions known to be affected by AD, especially NO2 (β = −16.4; p = 0.05) and PM10 (β = −5.34; p = 0.05). On the other hand, increasing greenness indicators was associated with greater thickness in these same areas (β = 0.08; p = 0.03). ConclusionIn cognitively unimpaired adults with increased risk for AD, increased exposure to air pollution was suggested to be associated with greater global atrophy and reduced volume and thickness in specific brain areas known to be affected in AD, thus suggesting a potential link between environmental exposures and cerebral vulnerability to AD. Although more research in the field is needed, air pollution reduction is crucial for decreasing the burden of age-related disorders.

Neuroanatomical predictors of L-DOPA response in older adults with psychomotor slowing and depression: A pilot study

Declining function in dopamine circuits is implicated in normal aging and late-life depression (LLD). Dopamine augmentation recently has shown therapeutic promise, but predictors of response are unknown. Depressed elders with slowed gait underwent baseline magnetic resonance imaging (MRI) and [11C]raclopride positron emission tomography (PET). Subjects then received open treatment with carbidopa/levodopa (L-DOPA) for three weeks. Linear regressions examined relationships between baseline MRI measures, [11C]raclopride binding, and behavioral outcomes. Among N=16 participants aged 72.5±6.8 years, higher left superior temporal gyrus volume was associated with higher processing speed at baseline, while cortical thinning in a processing speed network was associated with greater improvement following L-DOPA. Greater volume and cortical thickness in brain regions associated with mobility were associated with higher baseline gait speed. Higher baseline white matter hyperintensity volume predicted less post-L-DOPA improvement on dual task gait speed and IDS-SR scores. Higher [11C]raclopride binding in the associative striatum was associated with cortical thickness in some, but not all, processing speed brain regions, while higher binding in sensorimotor striatum was significantly associated with left caudate volume. Limiting the conclusions drawn from this pilot study are the small sample size and open administration of L-DOPA. Greater baseline brain volumes and cortical thickness in regions supporting cognition and gait were associated with higher behavioral performance, while lower structural integrity was associated with increased responsivity to L-DOPA. If substantiated in larger studies, these findings could facilitate the targeting of dopaminergic treatments to those LLD patients most likely to respond.

Interaction effect of alcohol consumption and Alzheimer disease polygenic risk score on the brain cortical thickness of cognitively normal subjects.

Alcohol consumption and genetic risk for Alzheimer disease (AD) are among many factors known to be associated with brain structure in cognitively healthy adults. It is unclear, however, whether the effect of alcohol consumption on brain structure varies depending on a person's level of genetic risk for AD. We hypothesized that there is an interaction effect of alcohol consumption and a 33-SNP AD polygenic risk score (PRS) on the cortical thickness of brain regions known to be affected early in the course of AD. Studying 6,213 cognitively healthy subjects from the UK Biobank, we found a significant interaction effect of the 33-SNP AD PRS and alcohol consumption on this AD Cortical Thickness Signature. Stratified, among those who consume 12-24g/day of alcohol, the 33-SNP AD PRS had a significant, positive association with AD Cortical Thickness Signature, with high-risk subjects having the greatest AD Cortical Thickness Signature. There were no significant associations of the 33-SNP AD PRS with AD Cortical Thickness Signature among the nondrinker or <1, 1-6, 6-12, 24-48, or >48g/day groups. It is unclear whether this interaction is due to a detrimental or beneficial effect of moderate alcohol consumption in those with the highest genetic risk for AD.

Sexual Dimorphism Within Brain Regions Controlling Speech Production.

Neural processing of speech production has been traditionally attributed to the left hemisphere. However, it remains unclear if there are structural bases for speech functional lateralization and if these may be partially explained by sexual dimorphism of cortical morphology. We used a combination of high-resolution MRI and speech-production functional MRI to examine cortical thickness of brain regions involved in speech control in healthy males and females. We identified greater cortical thickness of the left Heschl’s gyrus in females compared to males. Additionally, rightward asymmetry of the supramarginal gyrus and leftward asymmetry of the precentral gyrus were found within both male and female groups. Sexual dimorphism of the Heschl’s gyrus may underlie known differences in auditory processing for speech production between males and females, whereas findings of asymmetries within cortical areas involved in speech motor execution and planning may contribute to the hemispheric localization of functional activity and connectivity of these regions within the speech production network. Our findings highlight the importance of consideration of sex as a biological variable in studies on neural correlates of speech control.

ASSOCIATIONS BETWEEN CYTOKINES AND CORTICAL THICKNESS IN PATIENTS WITH LATE-LIFE DEPRESSION

Introduction Late-life depression (LLD), defined as depression that occurs after the age of 60 years, is associated with a poor quality of life, cognitive impairment, and increased morbidity and mortality. Immune factors are now recognized as involved in the pathophysiology of depression. We aimed to evaluate the relationship between plasma cytokine levels and cortical thickness in patients with LLD. Methods Blood samples and structural magnetic resonance imaging scans (Siemens 3T Prisma) were acquired in 29 older adults (≥60 years old) with major depression (62% female; mean age, 70.7 (7.3) years; mean MADRS 15.9 (3.2)). Associations between plasma cytokine levels (log-transformed) and cortical thickness were evaluated in a multivariate analysis using partial least squares. Cytokines with detectable levels in at least 27 of the 29 subjects (exotaxin, IFN-a2, GRO, MDC, IL-12(p70), sCD40L, IL-8, IP-10, MCP-1, MIP-1b, TNF-a, and VEGF) were included in the analysis. Results The first latent variable was significant (accounting for 32% of the cross-block covariance, p=.036) and reflected negative correlations between exotaxin, IL-8, IP-10, MIP-1b, and TNF-a levels and cortical thickness in numerous brain regions, including cingulate, insular, temporal, orbitofrontal, and prefrontal cortices (Figure 1). Conclusions Patients with LLD who have high plasma levels of exotoxin, IL-8, IP-10, MIP-1b, and TNF-a have less cortical thickness in brain regions previously implicated in depression than patients with LLD who have lower levels of these chemokines and pro-inflammatory cytokines. The affected brain regions have functions in self-referential processes, emotional regulation, social cognition, and attentional switching. Thus, the observed reductions in cortical thickness may contribute to the emotional, cognitive, and behavioral disturbances in LLD. Recently, chemokines have been implicated in many neurobiological processes and are considered to play a role in linking peripheral and central inflammation. The present results further support the importance of chemokines and proinflammatory cytokines in depressive pathophysiology. This research was funded by Sponsored by NIMH R01 MH097892, NCCIH AT009198, MH086481; Alzheimer's Research & Prevention Foundation, Allergan, PCORI; Advisory Board: Alzheimer's Research & Prevention Foundation; Royalties for books from Oxford University Press and Hopkins University Press.

Regional estimates of cortical thickness in brain areas involved in control of surgically restored limb movement in patients with tetraplegia

Context/Objective: Spinal cord injury (SCI) causes atrophy of brain regions linked to motor function. We aimed to estimate cortical thickness in brain regions that control surgically restored limb movement in individuals with tetraplegia. Design: Cross-sectional study. Setting: Sahlgrenska University hospital, Gothenburg, Sweden. Participants: Six individuals with tetraplegia who had undergone surgical restoration of grip function by surgical transfer of one elbow flexor (brachioradialis), to the paralyzed thumb flexor (flexor pollicis longus). All subjects were males, with a SCI at the C6 or C7 level, and a mean age of 40 years (range = 31–48). The average number of years elapsed since the SCI was 13 (range = 6–26). Outcome measures: We used structural magnetic resonance imaging (MRI) to estimate the thickness of selected motor cortices and compared these measurements to those of six matched control subjects. The pinch grip control area was defined in a previous functional MRI study. Results: Compared to controls, the cortical thickness in the functionally defined pinch grip control area was not significantly reduced (P = 0.591), and thickness showed a non-significant but positive correlation with years since surgery in the individuals with tetraplegia. In contrast, the anatomically defined primary motor cortex as a whole exhibited substantial atrophy (P = 0.013), with a weak negative correlation with years since surgery. Conclusion: Individuals with tetraplegia do not seem to have reduced cortical thickness in brain regions involved in control of surgically restored limb movement. However, the studied sample is very small and further studies with larger samples are required to establish these findings.

Olfactory dysfunction in Alzheimer's disease– and Lewy body–related cognitive impairment

IntroductionOlfactory dysfunction is common in Alzheimer's disease– and Lewy body–related disorders, but its neural correlates have not been clearly elucidated. MethodsWe retrospectively recruited 237 patients with Alzheimer's disease–related cognitive impairment (ADCI) and 217 with Lewy body–related cognitive impairment (LBCI). They were identically evaluated using the Cross-Cultural Smell Identification Test, neuropsychological tests, and brain magnetic resonance imaging. ResultsLBCI had more severe olfactory dysfunction than ADCI. Patients with more severe cognitive dysfunction had worse olfactory function in both groups. In ADCI, lower Cross-Cultural Smell Identification Test scores correlated with a lower cortical thickness in brain regions typically affected in Alzheimer's disease, most prominently in the right parahippocampal cortex, whereas in LBCI, the scores correlated with white matter abnormalities in regions vulnerable to Lewy body, including subcortical regions of the orbitofrontal and frontoparietal cortices. DiscussionOur results suggest that cortical atrophy in ADCI and white matter abnormalities in LBCI play important roles in olfactory dysfunction.

Concussion History Predicts Reduced Cortical Thickness in Special Operations Forces Personnel

Special Operations Forces (SOF) personnel are at high risk for repetitive blast and head impact exposure. Non-invasive neuroimaging techniques, such as magnetic resonance imaging (MRI), have identified concussion-related structural differences even when observable behavioral and cognitive deficits are absent. The relationship between injury history, neuroimaging, and standard clinical tests has not previously been defined in the SOF population. PURPOSE: To compare cortical morphology, symptom scores, and neurocognition in SOF personnel with and without concussion history. METHODS: SOF personnel completed an assessment battery including 3T high-resolution MRI and the Immediate Postconcussion Assessment and Cognitive Test (ImPACT). We examined symptom reporting and the ImPACT composite scores for verbal and visual memory, visual-motor processing speed, reaction time, and impulse control. The SOF personnel were categorized by self-reported concussion history (no history vs. 1+ concussions). We used FreeSurfer (v6) to reconstruct and segment the cerebral cortex. Cortical thickness was regressed on concussion history controlling for estimated total intracranial volume. The symptom reporting and ImPACT composite scores were regressed on concussion history. RESULTS: We imaged 166 SOF personnel (160 males; 65 self-reported concussion history) using MRI. Of these, 155 completed the ImPACT during a healthy baseline testing session. Two brain regions had reduced cortical thickness associated with concussion history, controlling for the total intracranial volume: left pericalcarine (t164=2.00, p=0.04); and left parahippocampal (t164=2.81, p=0.006). One region had larger cortical thickness in those with a concussion history: right transverse temporal (t164=2.35, p=0.02). Concussion history did not predict symptom or ImPACT composite score differences (p>0.05). CONCLUSIONS: Concussion history predicted cortical thickness in brain regions associated with vision and memory, which are cognitive functions affected following concussive injury. The ImPACT composites were not sensitive to concussion history. Supported by the United States Army Special Operations Command (USASOC)

Verbal Memory Performance and Reduced Cortical Thickness of Brain Regions Along the Uncinate Fasciculus in Young Adult Cannabis Users.

Introduction: Memory impairment is one of the most commonly reported effects of cannabis use, especially among those who initiate use earlier, perhaps due to the effects of delta-9- tetrahydrocannabinol on cannabinoid (CB1) receptors in the brain. Studies have increasingly investigated whether cannabis use is associated with impairments in verbal memory, and with alterations in brain structures underlying verbal memory. The uncinate fasciculus (UF), a long-range white matter tract, connects regions with densely localized CB1 receptors that are important in verbal memory. This study investigated the impact of cannabis use on UF structures and its association with memory performance in young adult cannabis users (CU) and non-using controls (CON).Materials and Methods: Nineteen CU and 22 CON completed a verbal memory task and a neuroimaging protocol, in which diffusion tensor imaging and structural scans were collected. We compared memory performance, diffusion and tractography measures of the UF, and cortical thickness of regions connected by the UF, between CU and CON. In regions showing a significant group effect, we also examined associations between verbal memory performance, cortical thickness, and age of onset of cannabis use.Results: Compared to non-users, CU had worse memory performance, decreased fiber bundle length in the UF, and decreased cortical thickness of brain regions along the UF such as the entorhinal cortex and fusiform gyrus. Verbal memory performance was significantly associated with age of onset of cannabis use, indicating that those who initiated cannabis use at an earlier age performed worse. Cortical thickness of the entorhinal cortex was significantly correlated with age of first use and memory performance.Conclusion: This study provides evidence that cannabis use, especially when initiated at a young age, may be associated with worse verbal memory and altered neural development along the UF. Reductions in cortical thickness in regions implicated in memory processes may underlie weaknesses in verbal memory performance.

REGIONAL AV1451 UPTAKE AND CORTICAL THICKNESS IN RELATION TO MEMORY, LANGUAGE AND EXECUTIVE FUNCTIONING IN AMYLOID-POSITIVE SUBJECTS

Tau pathology is thought to spread in a characteristic manner, leading to cell loss and inducing cognitive decline. However, it is unclear to what degree Tau-PET, a marker of neurofibrillary tau pathology (NFT) tracks cognitive symptoms relative to structural MRI, which more directly reflects neuronal injury. In a group of amyloid positive (Ab+) controls, patients with Mild Cognitive Impairment (MCI) and dementia, we investigate the association of memory, language and executive functioning with Tau-PET and MRI-based cortical thickness in brain regions putatively associated with these domains. We included Ab+ individuals, as determined by Florbetapir PET, (10 controls, 14 MCI and 5 dementia patients) from ADNI who had AV1451 Tau-PET, structural MRI and cognitive data within 6 months of each other. Cortical thickness and normalized SUVR from the Tau-PET scans were measured in regions of interest obtained using multi-atlas segmentation. Composite z-scores of delayed recall, recognition, language and executive functioning were calculated, adjusting for age, gender and education using the linear regression equation from 122 Ab- controls from ADNIGO/2. Significant associations of AV1451 uptake in medial temporal lobe (MTL) structures with memory were found (Table 1), but AV1451 uptake did not correlate significantly with language and executive functioning in regions generally considered to support these functions. Cortical thickness measures were significantly associated with all cognitive domains. Stepwise regression analyses showed that mainly structural measures were significant predictors of memory and executive functioning, but AV1451 uptake was also included in the models for memory (Table 2). None of the predictors significantly predicted language in regression models. These preliminary findings show a stronger association of cognitive functioning with structural brain measures than with AV1451 uptake. Perhaps atrophy provides a tighter link with cognitive decline than tau pathology, possibly because NFTs precede the neurodegeneration which produces cognitive impairment and/or because tau pathology does not capture other contributors to loss of neuronal integrity. The more complementary relationship of AV1451 uptake and structural MRI 5 may reflect that in early AD tangle pathology is the primary driver of neuronal integrity in this region, as opposed to language and executive networks.

Mild traumatic brain injury is associated with reduced cortical thickness in those at risk for Alzheimer's disease.

Moderate-to-severe traumatic brain injury is one of the strongest environmental risk factors for the development of neurodegenerative diseases such as late-onset Alzheimer's disease, although it is unclear whether mild traumatic brain injury, or concussion, also confers risk. This study examined mild traumatic brain injury and genetic risk as predictors of reduced cortical thickness in brain regions previously associated with early Alzheimer's disease, and their relationship with episodic memory. Participants were 160 Iraq and Afghanistan War veterans between the ages of 19 and 58, many of whom carried mild traumatic brain injury and post-traumatic stress disorder diagnoses. Whole-genome polygenic risk scores for the development of Alzheimer's disease were calculated using summary statistics from the largest Alzheimer's disease genome-wide association study to date. Results showed that mild traumatic brain injury moderated the relationship between genetic risk for Alzheimer's disease and cortical thickness, such that individuals with mild traumatic brain injury and high genetic risk showed reduced cortical thickness in Alzheimer's disease-vulnerable regions. Among males with mild traumatic brain injury, high genetic risk for Alzheimer's disease was associated with cortical thinning as a function of time since injury. A moderated mediation analysis showed that mild traumatic brain injury and high genetic risk indirectly influenced episodic memory performance through cortical thickness, suggesting that cortical thinning in Alzheimer's disease-vulnerable brain regions is a mechanism for reduced memory performance. Finally, analyses that examined the apolipoprotein E4 allele, post-traumatic stress disorder, and genetic risk for schizophrenia and depression confirmed the specificity of the Alzheimer's disease polygenic risk finding. These results provide evidence that mild traumatic brain injury is associated with greater neurodegeneration and reduced memory performance in individuals at genetic risk for Alzheimer's disease, with the caveat that the order of causal effects cannot be inferred from cross-sectional studies. These results underscore the importance of documenting head injuries even within the mild range as they may interact with genetic risk to produce negative long-term health consequences such as neurodegenerative disease.

Childhood abuse and reduced cortical thickness in brain regions involved in emotional processing.

Alterations in gray matter development represent a potential pathway through which childhood abuse is associated with psychopathology. Several prior studies find reduced volume and thickness of prefrontal (PFC) and temporal cortex regions in abused compared with nonabused adolescents, although most prior research is based on adults and volume-based measures. This study tests the hypothesis that child abuse, independent of parental education, predicts reduced cortical thickness in prefrontal and temporal cortices as well as reduced gray mater volume (GMV) in subcortical regions during adolescence. Structural MRI scans were obtained from 21 adolescents exposed to physical and/or sexual abuse and 37 nonabused adolescents (ages 13-20). Abuse was operationalized using dichotomous and continuous measures. We examined associations between abuse and brain structure in several a priori-defined regions, controlling for parental education, age, sex, race, and total brain volume for subcortical GMV. Significance was evaluated at p<.05 with a false discovery rate correction. Child abuse exposure and severity were associated with reduced thickness in ventromedial prefrontal cortex (PFC), right lateral orbitofrontal cortex, right inferior frontal gyrus, bilateral parahippocampal gyrus (PHG), left temporal pole, and bilateral inferior, right middle, and right superior temporal gyri. Neither abuse measure predicted cortical surface area or subcortical GMV. Bilateral PHG thickness was inversely related to externalizing symptoms. Child abuse, an experience characterized by a high degree of threat, is associated with reduced cortical thickness in ventromedial and ventrolateral PFC and medial and lateral temporal cortex in adolescence. Reduced PHG thickness may be a mediator linking abuse with externalizing psychopathology, although prospective research is needed to evaluate this possibility.