Cortex Volume Research Articles

Attention speed and anterior cingulate cortex volume in female and male veterans with suicide ideation and attempts

IntroductionAn average of 17.5 Veterans died by suicide each day in 2021, highlighting the importance of research and prevention efforts aimed at suicide risk. Attentional processes have emerged as a possible predictor of suicide behaviors (SB), yet associated neural correlates remain understudied, particularly in the Veteran population.MethodsThe current study examines sustained and selective attention performance as indexed by the Ruff 2 & 7 Selective Attention Test and anterior cingulate cortex (ACC) volume as they relate to SB in Veterans. A subset of Veterans also completed a structural magnetic resonance imaging protocol. Participants were grouped on history of suicidal ideation (SI), suicide attempt (SA), and no SB (HC).ResultsAnalyses from the Ruff 2 & 7 test showed that Veterans with a history of SA performed more slowly on Automatic Detection Speed (ADS) and Controlled Search Speed (CSS) compared to Veterans with SI and no SB. SI and SA group differences on ADS and CSS remained after Bonferroni correction, and CSS differences remained after controlling for depressive and anxious symptoms. There were no between-group differences on Ruff 2 & 7 Accuracy measures. When analyses were divided by sex, males with a history of SA performed more slowly than SI and HC on ADS and more slowly on CSS and Total Speed than males with a history of SI. Results remained significant after controlling for depressive and anxious symptoms. When Bonferroni corrections were applied, males with a history of SA performed more slowly on ADS, CSS, and Total Speed compared to males with a history of SI. Female Veterans with a history of SA performed more slowly than female HC on CSS only; however, these findings were no longer significant after controlling for depressive and anxious symptoms. No significant differences were found between female groups on ADS or Total Speed. Measures of left rostral ACC gray matter (GM) volume for the combined female and male Veteran sample were positively correlated with ADS and CSS scores in HC but not SA. Conversely, right rostral ACC GM volume negatively correlated with ADS and CSS scores in the SA group but not HC. Right rostral ACC white matter volume correlated positively with ADS and CSS in HC.DiscussionThese findings highlight associations between attention speed, ACC volume, and SB even after controlling for acute mood symptoms, in addition to emphasizing the importance of including sex in analyses.

Evaluating conversion from mild cognitive impairment to Alzheimer disease with structural MRI: a machine learning study

Abstract Alzheimer's Disease (AD) is a disabling neurodegenerative disorder for which no effective treatment currently exists. To predict the diagnosis of AD could be crucial for patients’ outcome, but current AD biomarkers are either invasive, time-consuming, or expensive. Thus, developing Magnetic Resonance Imaging (MRI)-based computational methods for AD early diagnosis would be essential to narrow down the phenotypic measures predictive of cognitive decline. Amnestic Mild Cognitive Impairment (aMCI) is associated with higher risk for AD, and here we aimed to identify MRI-based quantitative rules to predict aMCI to possible AD conversion, applying different machine learning algorithms sequentially. At baseline, T1-weighted brain images were collected for 104 aMCI patients and processed to obtain 146 volumetric measures of cerebral grey matter regions (ROIs). One year later, patients were classified as converter (aMCI-c=32) or non-converter, i.e., clinically and neuropsychologically stable (aMCI-s=72) based on cognitive performance. Feature selection was performed by Random Forest (RF) and the identified seven ROIs volumetric data were used to implement Support Vector Machine (SVM) and Decision-Tree (DT) classification algorithms. Both SVM and DT reached an average accuracy of 86% in identifying aMCI-c and aMCI-s. DT found a critical threshold volume of the right entorhinal cortex (EC-r) as the first feature for differentiating aMCI-c/aMCI-s. Almost all aMCI-c had an EC-r volume <1286mm3, while more than half aMCI-s patients had a volume above the identified threshold for this structure. Other key regions for the classification between aMCI-c/aMCI-s were the left lateral occipital (LOC-l), the middle temporal gyrus and the temporal pole cortices. Our study reinforces previous evidence suggesting that the morphometry of the EC-r and LOC-l best predicts aMCI to AD conversion. Further investigations are needed prior to deeming our findings as a broadly applicable predictive framework. However, here, a first indication was derived for volumetric thresholds that, being easy to obtain, may assist in early identification of AD in clinical practice, thus contributing to establishing MRI as a useful non-invasive prognostic instrument for dementia onset.

Exploring predementia: Understanding the characteristics of subjective cognitive decline plus from India.

Subjective cognitive decline (SCD) is the early predementia syndrome. that occurs even before the development of objective cognitive decline. SCD plus refers to an additional set of criteria that increases the likelihood of developing mild cognitive impairment and further progressing to Alzheimer's disease (AD). Studying the progression of SCD-plus participants will help in understanding the importance of diagnosing this condition at an early stage and delaying its onset. The present tries to examine neurocognitive changes in individuals who met the criteria of SCD-plus patients. The study also investigated the imaging correlates of these individuals in both cohorts. This study included 94 participants from Srinivaspura Aging, Neuro Senescence, and COGnition (SANSCOG) and Tata Longitudinal Study of Aging (TLSA) cohorts who satisfy the criteria of SCD plus. Mann-Whitney U test was used to compare the SCD plus participants and healthy controls. Regression analysis was performed to find the association between SCD plus and cognition. The SCD-plus group performed poorer than the healthy group in episodic memory delayed recall (p = 0.049), name face recognition (p = 0.023), and letter fluency (p = 0.004) tasks. The generalized linear model revealed that the SCD-plus group had lower left cerebellar cortex (p = 0.010) and right inferior occipital cortex (p = 0.016) volumes than the healthy control group. The participants in the SCD-plus group performed poorly on memory and language-related tasks, and the volumes of the associated brain regions decreased. This study suggested that the SCD-plus group had characteristics similar to AD group and can help in identifying AD at the earliest.

Neural deterioration and compensation in visual short-term memory among individuals with amnestic mild cognitive impairment.

Visual short-term memory (VSTM) is a critical indicator of Alzheimer's disease (AD), but whether its neural substrates could adapt to early disease progression and contribute to cognitive resilience in amnestic mild cognitive impairment (aMCI) has been unclear. Fifty-five aMCI patients and 68 normal controls (NC) performed a change-detection task and underwent multimodal neuroimaging scanning. Among the atrophic brain regions in aMCI, VSTM performance correlated with the volume of the right prefrontal cortex (PFC) but not the medial temporal lobe (MTL), and this correlation was mainly present in patients with greater MTL atrophy. Furthermore, VSTM was primarily correlated with frontal structural connectivity in aMCI but was correlated with more distributed frontal and MTL connectivity in NC. This study provided evidence on neural adaptation in the precursor stages of AD, highlighting the compensatory role of PFC as MTL deteriorated and suggesting potential targets in early intervention for cognitive preservation. Atrophic left medial temporal lobe (MTL) no longer correlated with visual short-term memory (VSTM) in amnestic mild cognitive impairment (aMCI). Atrophic right middle frontal area continued to correlate with VSTM in aMCI. Frontal brain-behavior correlation was mainly present in the aMCI subgroup with greater medial temporal lobe (MTL) atrophy. Reliance of VSTM on frontal connectivity increased in compensation for MTL dysfunction.

Structure and hormonal output of the adrenal gland after experimental estrogenization of male rats.

Orchidectomy and estrogenization of the male represent a procedure that is applicable in sex reassignment or in prostate cancer therapy. This approach has an influence on the hypothalamic-pituitary-adrenal axis and thus affects cardiovascular function and metabolism. We utilized orchidectomized rats to evaluate the effects of estradiol on the structure and hormonal output of the adrenal gland. Adult Wistar rats were divided into sham-operated (SO; n=7), orchidectomized (Orx; n=7), and estradiol-treated orchidectomized (Orx+E; n=7) groups. Estradiol-dipropionate (0.625 mg/kg b.m.) was administered subcutaneously for three weeks, while the SO and Orx groups received vehicle alone. Set objectives were achieved using histochemistry/immunohistochemistry, stereology, and immunoassays. In Orx+E rats, the hormonal milieu was characterized by decreased testosterone and increased ACTH, compared with the Orx group. Also, orchidectomy and estradiol treatment provoked a significant increase in adrenal cortex volume and volume of ZF per se, with increased cell and nuclei volumes in all three adrenocortical zones (ZG, ZF, and ZR), in comparison with Orx rats. Concentrations of aldosterone in blood, as well as corticosterone in blood and adrenal tissue were increased, while circulating DHEA was decreased (with increased immunoexpression of adrenocortical CYP 17 enzyme), all in Orx+E compared with Orx animals. The wide zonal distribution of VEGF and the pronounced blood supply within the ZF of Orx+E animals acted to support the synthesis and secretion of corticosteroids. These results seem cautionary in the context of young male estrogenization, given the negative impact of high mineralocorticoids and glucocorticoids on cardiovascular function and metabolism.

Brain surface area and function alterations are correlated with cognition in patients with end-stage renal disease.

Cognitive decline may occur in patients with end-stage renal disease (ESRD), and is particularly severe in patients with ESRD undergoing hemodialysis; however, the mechanism of this relationship between cognitive decline and ESRD is unclear. Cortical-based structural and functional analysis can be used to understand these cortical changes and their relationship with cognitive decline in non-dialysis and maintenance dialysis ESRD patients. This study aimed to examine whether there was any correlation between alterations in cortical and resting-state function changes and cognitive decline in patients diagnosed with ESRD. The study included a total of 126 participants who underwent laboratory assessments, neuropsychological tests, and brain magnetic resonance imaging (MRI). Of the 126 patients, 40 were ESRD without hemodialysis (ESRD-ND) patients, 40 were ESRD with hemodialysis (ESRD-HD) patients, and 46 were healthy controls (HCs). In terms of the cortical changes, the thickness and volume of the left medial temporal cortex were smaller in the ESRD-ND group than in the HC group. The thickness and volume of the double medial temporal cortex were reduced in the ESRD-HD group compared to the ESRD-ND group. The cortical volume in the anterior cingulate and medial prefrontal cortex (AntCing_MedPFC) was reduced in ESRD-HD group compared to both the ESRD-ND and HC groups. In terms of the functional changes, the regional homogeneity (ReHo) of the double medial temporal cortex was higher in the ESRD-HD group than in the ESRD-ND group, and higher in the ESRD-ND group than in the HC group. The ReHo of the AntCing_MedPFC was higher in both the ESRD-HD and ESRD-ND groups than in the HC group. The correlation analysis after covariation-correction showed that the cortical thickness (r=0.360, P=0.026) and cortical volume (r=0.440, P=0.006) of the medial temporal lobe in the ESRD-HD group were positively correlated with the Montreal Cognitive Assessment (MoCA) score. The cortical thickness (r=0.571, P<0.001) and cortical volume (r=0.529, P=0.001) of the posterior cingulated gyrus were positively correlated with the MoCA score in the ESRD-ND group. Our findings suggest that ESRD patients undergo more cognitively related cortical structural and functional changes than HCs. Dialysis can aggravate or cause changes in new brain regions. Changes in the cortex and volume of the posterior cingulate gyrus in ESRD patients is an important cause of cognitive decline. Damage to the medial temporal lobe by dialysis exacerbates this trend.

Spatiotemporal neurodegeneration of the substantia nigra and its connecting cortex and subcortex in Parkinson's disease.

Neurodegeneration is uneven in Parkinson's disease (PD). This study aimed to investigate spatiotemporal neurodegeneration in functional subregions of the substantia nigra (SN) and their connected cortex and subcortex in people with PD. A total of 120 patients with early-stage PD, 45 patients with advanced PD, and 120 healthy controls (HCs) were enrolled. The SN, cortex, and subcortex were divided into sensorimotor, associative, and limbic regions, respectively. Iron deposition in the SN was assessed by quantitative susceptibility mapping (QSM). Cortex and subcortex volumes were calculated based on T1-weighted imaging. Region of interest (ROI) analysis and voxel-based analysis (VBA) were performed to explore spatiotemporal neurodegeneration in patients with PD. p values were corrected for false discovery rate. In the ROI analysis, the QSM values for the limbic (p = 0.018) and sensorimotor SN subregions (p = 0.018) were higher in PD patients than in HCs, but were not higher in the associative SN subregion (p = 0.295). In VBA, all SN functional subregions had clusters with higher QSM values in PD patients than in HCs (p < 0.001). The limbic SN subregion was the only one in which iron deposition increased from early-stage to advanced PD (p = 0.023). The QSM values of VBA_limbic, sensorimotor, and associative SN had subregion-specific correlations with disease severity (p = 0.001 for the limbic and sensorimotor subregions, p = 0.003 for the associative subregion), motor symptoms (p = 0.057 for the limbic and sensorimotor subregion), and depression scores (p = 0.036 for the limbic subregion). Iron deposition in SN functional subregions and atrophy of cortical and subcortical structures connected with the SN showed spatiotemporal selectivity. These findings reveal the potential pathogenesis of clinical heterogeneity in PD.

Neuroanatomical Variability and Substance Use Initiation in Late Childhood and Early Adolescence

The extent to which neuroanatomical variability associated with early substance involvement, which is associated with subsequent risk for substance use disorder development, reflects preexisting risk and/or consequences of substance exposure remains poorly understood. To examine neuroanatomical features associated with early substance use initiation and to what extent associations may reflect preexisting vulnerability. Cohort study using data from baseline through 3-year follow-up assessments of the ongoing longitudinal Adolescent Brain Cognitive Development Study. Children aged 9 to 11 years at baseline were recruited from 22 sites across the US between June 1, 2016, and October 15, 2018. Data were analyzed from February to September 2024. Substance use initiation through 3-year follow-up (ie, age <15 years). Self-reported alcohol, nicotine, cannabis, and other substance use initiation and baseline magnetic resonance imaging (MRI)-derived estimates of brain structure (ie, global and regional cortical volume, thickness, surface area, sulcal depth, and subcortical volume). Covariates included family (eg, familial relationships), pregnancy (eg, prenatal exposure to substances), child (eg, sex and pubertal status), and MRI (eg, scanner model) variables. Among 9804 children (mean [SD] baseline age, 9.9 [0.6] years; 5160 boys [52.6%]; 213 Asian [2.2%], 1474 Black [15.0%], 514 Hispanic/Latino [5.2%], 29 American Indian [0.3%], 10 Pacific Islander [0.1%], 7463 White [76.1%], and 75 other [0.7%]) with nonmissing baseline neuroimaging and covariate data, 3460 (35.3%) reported substance use initiation before age 15. Initiation of any substance or alcohol use was associated with thinner cortex in prefrontal regions (eg, rostral middle frontal gyrus, β = -0.03; 95% CI, -0.02 to -0.05; P = 6.99 × 10-6) but thicker cortex in all other lobes, larger globus pallidus and hippocampal volumes, as well as greater global indices of brain structure (eg, larger whole brain volume, β = 0.05; 95% CI, 0.03 to 0.06; P = 2.80 × 10-8) following Bonferroni or false discovery rate multiple testing correction. Cannabis use initiation was associated with lower right caudate volume (β = -0.03; 95% CI, -0.01 to -0.05; P = .002). Post hoc examinations restricting to postbaseline initiation suggested that the majority of associations, including thinner prefrontal cortex and greater whole brain volume, preceded initiation. In this cohort study of children, preexisting neuroanatomical variability was associated with substance use initiation. In addition to putative neurotoxic effects of substance exposure, brain structure variability may reflect predispositional risk for initiating substance use earlier in life with potential cascading implications for development of later problems.

Cortical lesions impact cognitive decline in multiple sclerosis via volume loss of nonlesional cortex.

To assess the interrelationship between cortical lesions and cortical thinning and volume loss in people with multiple sclerosis within cortical networks, and how this relates to future cognition. In this longitudinal study, 230 people with multiple sclerosis and 60 healthy controls underwent 3 Tesla MRI at baseline and neuropsychological assessment at baseline and 5-year follow-up. Cortical regions (N = 212) were divided into seven functional networks. Regions were defined as either lesional or normal-appearing cortex based on presence of a cortical lesion on artificial intelligence-generated double inversion-recovery scans. Cortical volume and thickness were determined within lesional or normal-appearing cortex. Prevalence of at least one cortical lesion was highest in the limbic (73%) followed by the default mode network (70.9%). Multiple sclerosis-related cortical thinning was more pronounced in lesional (mean Z-score = 0.70 ± 0.84) compared to normal-appearing cortex (-0.45 ± 0.60; P < 0.001) in all, except sensorimotor, networks. Cognitive dysfunction, particularly of verbal memory, visuospatial memory, and inhibition, at follow-up was best predicted by baseline network volume of normal-appearing cortex of the default mode network [B (95% CI) = 0.31 (0.18; 0.43), P < 0.001]. Mediation analysis showed that the effect of cortical lesions on future cognition was mediated by volume loss of the normal-appearing instead of lesional cortex, independent of white matter lesion volume. Multiple sclerosis-related cortical thinning was worse in lesional compared to normal-appearing cortex, while volume loss of normal-appearing cortex was most predictive of subsequent cognitive decline, particularly in the default mode network. Mediation analyses indicate that cortical lesions impact cognitive decline plausibly by inducing atrophy, rather than through a direct effect.

Motor predictors of cortical brain development and full-IQ in children born extremely preterm with and without discrete white matter abnormalities.

To describe the cortical brain development and full-IQ performance in middle school age children after extremely preterm (EPT) birth considering discrete white matter abnormalities (WMA). In addition, to assess possible early motor predictors of cortical brain development and full-IQ in children born EPT with and without discrete WMA diagnosed at 10 years. T1-weighted MRI images from fifty-one children born before 27 weeks' gestation and 40 full-term born controls (Mage=10.09 years; SDage=0.77) were scored for discrete WMA and analyzed with Freesurfer (v7.2.0). The assessments included motor assessments (i.e., fine- and gross motor function) of Bayley Scales of Infant and Toddler Development - Third Edition (BSID-III) at a mean age of 2½ years. Full-IQ was also assessed with Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V) at 12 years. No differences were displayed in motor function or full-IQ score between children born EPT with and without discrete WMA at 10 years. Moreover, no global differences were found in cortex volume. However, bilateral mean cortical thicknesses (CTh) were exhibited to be thicker in children born EPT with discrete WMA. Children born EPT with discrete WMA exhibited regional increases mainly in the frontal and temporal lobes apart from left caudal anterior cingulate gyrus (mean difference = -0.11 (-0.22, -0.01), p = 0.026). Full-IQ was predicted by impairments in fine motor skills in children born EPT with discrete WMA, explaining 42.9% of the variance. Bilateral mean and regional CTh were found to be greater in children born EPT with discrete WMA at 10 years compared to those without. Fine motor function at 2½ years was a strong predictor of full-IQ dependent in children with discrete WMA.

Distinct impact modes of polygenic disposition to dyslexia in the adult brain.

Dyslexia is a common and partially heritable condition that affects reading ability. In a study of up to 35,231 adults, we explored the structural brain correlates of genetic disposition to dyslexia. Individual dyslexia-disposing genetic variants showed distinct patterns of association with brain structure. Independent component analysis revealed various brain networks that each had their own genomic profiles related to dyslexia susceptibility. Circuits involved in motor coordination, vision, and language were implicated. Polygenic scores for eight traits genetically correlated with dyslexia, including cognitive, behavioral, and reading-related psychometric measures, showed partial similarities to dyslexia in terms of brain-wide associations. Notably, microstructure of the internal capsule was consistently implicated across all of these genetic dispositions, while lower volume of the motor cortex was more specifically associated with dyslexia genetic disposition alone. These findings reveal genetic and neurobiological features that may contribute to dyslexia and its associations with other traits at the population level.

Phonemic word fluency is related to temporal and striatal gray matter volume in healthy older adults

ABSTRACT Word fluency (WF) tasks that tap verbal and executive function show deteriorating performance by advancing age. To address the scarcely studied age-related brain correlates of WF, we employed whole-brain voxel-based morphometry to examine gray matter (GM) correlates of semantic and phonemic WF in 46 healthy older adults. Lower phonemic WF score was related to smaller anterior medial temporal GM volume as well as smaller GM volume in the putamen bilaterally. A disproportionally weak score on phonemic WF in relation to semantic WF was associated with smaller GM volume in the left inferior frontal cortex, the right anterior medial temporal lobe, and the right striatum. There were no significant associations for semantic WF. The fact that our temporal and subcortical findings were bilateral and right-lateralized, may reflect age-related compensation by these brain areas.

Metamorphosis of the central nervous system in &lt;i&gt;Habrobracon hebetor&lt;/i&gt; (Hymenoptera, Braconidae)

The structure of the central nervous system (CNS) of Habrobracon hebetor Say 1836 during the development from prepupa to imago was studied using histological methods and three-dimensional computer modeling. The metamorphosis of the CNS in H. hebetor largely coincides with the previously described changes in related groups of Hymenoptera. During development, the thoracic and abdominal ganglia of the nerve cord converge, the concentration of which reaches a maximum by the imago. The most noticeable changes in the CNS occur at the pupa I stage, when a sharp increase in the volumes of the cell cortex and neuropil in the CNS ganglia, an increase in the relative volume of the ganglia and an increase in the size of nerve cells are observed. The increase in the cell cortex of the ganglia is followed by its decrease by the imago stage, while the volume of the neuropil is significantly increased by the time the adult individual appears. An increase in the volumes of the key neuropil centers occurs throughout development from prepupa to imago. After a rapid increase in the size of nerve cells at the beginning of pupal development, it is decreased, with the average size of nerve cells in the imago being the same as in the prepupa. The number of nerve cells during pupal development is first increased, vs decreased at the imaginal stage, but not as much as in miniature Hymenoptera.

Multi-Night Electroencephalography Reveals Positive Association Between Sleep Efficiency and Hippocampal Subfield and Entorhinal Cortex Volumes in Healthy Aging.

Age-related atrophy of the human hippocampus and the enthorinal cortex starts accelerating at around age 60. Due to the contributions of these regions to many cognitive functions seamlessly used in everyday life, this can heavily impact the lives of elderly people. The hippocampus is not a unitary structure, and mechanisms of its age-related decline appear to differentially affect its subfields. Human and animal studies have suggested that altered sleep is associated with hippocampal atrophy. Yet, we know little about subfield specific effects of altered sleep in healthy aging and their effect on cognition. Here, in a sample of 118 older middle-aged and older adults (Mage = 63.25 y, range: 50-80 y), we examined the association between highly reliable hippocampal subfield and entorhinal cortex volumetry (n = 112), sleep measures derived from multi-night recordings of portable electroencephalography (n = 61) and episodic memory (n = 117). Objective sleep efficiency-but not self-report measures of sleep-was associated with entorhinal cortex volume when controlling for age. Age-related differences in subfield volumes were associated with objective sleep efficiency, but not with self-report measures of sleep. Moreover, participants characterized by a common multivariate pattern of subfield volumes that contributed to positive sleep-subfield volume associations, showed lower rates of forgetting. Our results showcase the benefit of objective sleep measures in identifying potential contributors of age-related differences in brain-behavior couplings.

Prenatal Tobacco Exposure, Brain Subcortical Volumes, and Gray-White Matter Contrast

Maternal tobacco use during pregnancy (MTDP) remains a major public health challenge. However, the complete spectrum of effects of MTDP is not fully understood. To examine the longitudinal associations of MTDP and children's brain morphometric subcortical volume and gray-white matter contrast (GWC) development. Cohort study of children aged 9 to 10 years at wave 1 (October 2016 to October 2018) and at a 2-year follow-up (wave 2; August 2018 to January 2021; aged 11-12 years) across 21 US sites in the Adolescent Brain Cognitive Development (ABCD) Study. Data were analyzed from October 2023 to October 2024. MTDP. Morphometric brain measures of subcortical volume and GWC. Among the 11 448 children (51.5% male; 13.1% Black; 24.0% Hispanic; and 52.9% White) at wave 1, 1607 (16.6%; 95% CI, 13.0%-20.2%) were identified with MTDP exposure. At wave 1, children with MTDP exposure (vs no exposure) exhibited lower GWC in widespread brain regions primarily located in the frontal (eg, superior frontal; regression coefficient [B] = -0.0019; SE, 0.0006; P = .004), parietal (eg, supramarginal; B = -0.0021; SE, 0.0007; P = .002) and temporal lobes (eg, middle temporal; B = -0.0024; SE, 0.0007; P < .001). These differences in GWC continued to be significant at wave 2. In regard to subcortical volume, children with MTDP exposure demonstrated smaller volume of the lateral ventricle (B = -257.5; SE, 78.6; P = .001) and caudate (B = -37.7; SE, 14.0; P = .01) in the left hemisphere at wave 1, and lower volume of the caudate in both left (B = -48.7; SE, 15.9; P = .002) and right hemisphere (B = -45.5; SE, 16.1; P = .01) at wave 2. This cohort study found that MTDP exposure was associated with lower GWC across the whole cortex and smaller caudate nuclei volume compared with no exposure, signifying the importance of preventing MTDP and necessitating further research on this topic.

Progressive structural alterations associated with negative symptoms in schizophrenia: A causal structural covariance network analysis.

Aberrant brain structures in schizophrenia have been widely explored. However, the causal effects of negative symptoms on brain structural alterations are still unclear. This study aims to explore the synchronous and progressive alterations in gray matter volume (GMV) associated with negative symptoms. 81 Deficit schizophrenia (DS) patients, 101 non-deficit schizophrenia (NDS) patients, and 177 healthy controls (HCs) were enrolled in this study. T1-weighted images were collected, and the severity of clinical symptoms in patients was evaluated. Then voxel-based morphometry and source-based morphometry were using for gray matter segmentation and structural covariance network construction. Finally, DS patients were ranked based on the severity of negative symptoms, and a causal structural covariance network (CaSCN) was constructed using Granger causality analysis. Twenty-four independent components were identified. Among them, 20 components showed smaller GMV in patient with schizophrenia compared to HCs. Furthermore, DS exhibited decreased GMV in right inferior frontal gyrus triangular part, bilateral para-hippocampal gyrus, and bilateral anterior cerebellum compared to NDS. Both patient groups showed increased structural covariance across various brain regions compared to HCs. Additionally, DS exhibited decreased structural covariance in left middle frontal gyrus, bilateral inferior frontal gyrus and right superior frontal gyrus compared to NDS. In CaSCN, as negative symptoms worsened, the volume of bilateral caudate decreased along with the atrophy of bilateral para-hippocampal gyrus, the volume of bilateral thalamus increased along with the decline in multiple brain regions, and the decreased volume of bilateral posterior cingulate cortex resulted in increased volume of bilateral lingual gyrus and other brain regions. The present study demonstrated the specific brain structural covariance patterns in DS, providing new evidence for the causal effects of negative symptoms on progressive structural abnormalities in schizophrenia.

Repeated exposure to high-dose nicotine induces prefrontal gray matter atrophy in adolescent male rats

Incidences of seizure after e-cigarette use in adolescents and young adults have been reported, raising the concern about the risk of nicotine overconsumption. Few previous studies have investigated the effects of nicotine at high doses on brain and behavior in adolescent animals. In this study, the effects of a 15-day repeated nicotine treatment at a daily dose of 2 mg/kg body weight were investigated in adolescent and adult male rats. Nicotine treatment abolished body weight gain in the adults, but did not affect the body weight significantly in the adolescents. Only the nicotine-treated adolescents showed significant changes in brain anatomy 1 day post-treatment, which manifested as a significant reduction of whole-brain gray matter (GM) volume, a further reduction of regional GM volume in the medial prefrontal cortex (mPFC) and altered GM volume covariations between the mPFC and a number of brain regions. The mPFC of nicotine-treated adolescent rats did not exhibit evident signs of neuronal degeneration and reactive astrocytosis, but showed a significantly decreased expression of presynaptic marker synaptophysin (SYN), along with a significantly increased oxidative stress and a significantly elevated expressions of microglial marker ionized calcium binding adaptor molecule 1 (IBA1). Together, these results suggested that repeated nicotine overdosing may shift regional redox, modulate microglia-mediated pruning, and give rise to structural/connectivity deficits in the mPFC of adolescent male rats.

Neural substrates of alerting dysfunction in females with Multiple Sclerosis

MS is a disease characterised by demyelination of the central nervous system resulting in decreased quality of life, increased anxiety, depression, fatigue, and cognitive dysfunction. Attention is frequently impaired in MS. A previous study demonstrated impairment specifically in the attentional alerting domain. However, this study did not establish whether the impairment was in intrinsic or extrinsic alertness, and did not examine the neural substrates associated with the impairment. To examine the alerting deficit in MS and establish the associated neural substrates, 40 female patients with MS and 40 age and gender match controls completed an alertness-motor paradigm designed to test both intrinsic and extrinsic alertness during functional magnetic resonance imaging. We found the MS group had a significant deficit in extrinsic alertness, which was associated with a lack of dorsal prefrontal cortex (DPFC) activation. In addition, reduced gray matter volume in the dorsal prefrontal cortex, thalamus, and basal ganglia were observed. Both fMRI and VBM correlations were observed between fatigue severity scale (FSS) scores and the DPFC. The combined results of our functional and structural MRI data analysis demonstrate that attention deficits in females with MS are a result of the complex relationship between brain tissue loss having a significant impact on functional brain regions subserving executive control of cognitive functions. Understanding the underlying mechanisms of cognitive performance and how they relate to fatigue are crucial to developing novel treatments for the symptoms of MS.

Alterations in Volume and Intrinsic Resting-State Functional Connectivity Detected at Brain MRI in Individuals with Opioid Use Disorder.

Background Structural and functional MRI studies have revealed brain alterations associated with opioid use disorder (OUD). However, previous research has been limited by small sample sizes, few female participants, and single-modality analyses. Purpose To identify structural and functional brain alterations in individuals with OUD using whole-brain data-driven methods to analyze T1-weighted MRI and resting-state functional MRI (rsfMRI). Materials and Methods This secondary analysis of the Collaboration Linking Opioid Use Disorder and Sleep study compared participants with OUD (data collection February 2021 to February 2023) receiving methadone treatment with healthy control participants (data collection February 2018 to May 2023). T1-weighted MRI and rsfMRI were analyzed using tensor-based morphometry and intrinsic connectivity distribution, respectively. Primary outcome measures included regional brain volumes and functional connectivity. Voxel-wise linear regression was used to assess group differences, with family-wise error correction. Pearson partial correlations were used to examine structure-function relationships. Results Compared with healthy control participants (n = 105; median age, 27 years [IQR, 23-37 years]; 58 female), participants with OUD (n = 103; median age, 37 years [IQR, 31.5-46 years]; 62 male) showed smaller volumes (corrected P < .05) in the thalamus (β = -17.42 [95% CI: -26.56, -8.27]) and right medial temporal lobe (β = -8.02 [95% CI: -12.25, -3.78]). Larger volumes (corrected P < .05) were seen in the brainstem (pons and medulla, β = 15.21 [95% CI: 7.03, 23.40]; midbrain, β = 13.04 [95% CI: 6.61, 19.47]) and cerebellum (right, β = 14.96 [95% CI: 7.25, 22.67]; left, β = 14.88 [95% CI: 7.32, 22.43]). An interaction between sex and group was found for medial prefrontal cortex volume (β = -19.38, corrected P < .05), with female participants having smaller volumes than male participants in the OUD group. Increased functional connectivity (corrected P < .05) was noted in the thalamus (β = 0.50 [95% CI: 0.25, 0.75]), right medial temporal lobe (β = 0.43 [95% CI: 0.21, 0.66]), right cerebellum (β = 0.46 [95% CI: 0.21, 0.71]), and brainstem (β = 0.48 [95% CI: 0.22, 0.74]) in the OUD group. Structure and function were positively correlated in the cerebellum (Pearson r = 0.32 [95% CI: 0.17, 0.44], P < .001) and brainstem (Pearson r = 0.23 [95% CI: 0.09, 0.37], P = .002). Conclusion Individuals with OUD showed overlapping structural and functional brain alterations in opioid receptor-dense regions compared with healthy control participants. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Filippi and Messina in this issue.

APOE4 and age affect the brain entorhinal cortex structure and blood arachidonic acid and docosahexaenoic acid levels after mild TBI.

A reduction in the thickness and volume of the brain entorhinal cortex (EC), together with changes in blood arachidonic acid (AA) and docosahexaenoic acid (DHA), are associated with Alzheimer's disease (AD) among apolipoprotein E ε4 carriers. Magnetic Resonance Imaging (n = 631) and plasma lipidomics (n = 181) were performed using the LIMBIC/CENC cohort to examine the influence of ε4 on AA- and DHA-lipids and EC thickness and volume in relation to mild traumatic brain injury (mTBI). Results showed that left EC thickness was higher among ε4 carriers with mTBI. Repeated mTBI (r-mTBI) was associated with reduced right EC thickness after controlling for ε4, age and sex. Age, plus mTBI chronicity were linked to increased EC White Matter Volume (WMV). After controlling for age and sex, the advancing age of ε4 carriers with blast mTBI was associated with reduced right EC Grey Matter Volume (GMV) and thickness. Among ε4 carriers, plasma tau and Aβ40 were associated with mTBI and blast mTBI, respectively. Chronic mTBI, ε4 and AA to DHA ratios in phosphatidylcholine, ethanolamides, and phosphatidylethanolamine were associated with decreased left EC GMV and WMV. Further research is needed to explore these as biomarkers for detecting AD pathology following mTBI.