Structural Brain Changes Research Articles

A DAT1 gene and APOE ε4 interaction is associated with apathy and structural brain changes in mild cognitive impairment and Alzheimer's disease.

Apathy in patients with Alzheimer's disease (AD) is associated with significant morbidity and is often one of the first neuropsychiatric symptoms to present in mild cognitive impairment (MCI). Apathy is associated with accelerated cognitive decline and atrophy in fronto-striatal regions of the brain. Previous work has shown a link between apathy and the APOE gene in the context of AD, as the APOE ε4 allele is already known to be associated with the onset of AD. However, other genetic associations with apathy are largely unexplored. To examine whether interactions between genetic variants related to neurotransmitter systems and regional brain atrophy are associated with apathy in patients with MCI and AD. In a sample of individuals with AD (n = 266), MCI (n = 518), and cognitively normal controls (n = 378), a partial least squares correspondence analysis modeled interactions between single nucleotide polymorphisms, structural whole-brain imaging variables, and apathy. An interaction was found between apathy, the possession of an APOE ε4 allele combined with minor homozygosity for the DAT1 (dopamine transporter 1) gene, and regional brain atrophy. This interaction was closely linked to the MCI and AD groups. The results point to an association of a dopaminergic genetic marker and apathy in the AD continuum and may inform future design of clinical trials of apathy, as well as new treatment targets.

Investigating sex-related differences in brain structure and function in bipolar I disorder using multimodal MRI

BackgroundPast research has highlighted that bipolar I disorder is associated with significant changes in brain structure and function. Notably, the manifestation and progression of bipolar I disorder have been known to differ between males and females. However, the relationship between sex-related differences and bipolar I disorder diagnosis affecting these changes was not fully understood. This study aimed to investigate the sex-by-diagnosis interactions concerning the structural and functional features of the brain in individuals with bipolar I disorder.MethodsBoth structural and functional MRI data were obtained from 105 individuals with bipolar I disorder (36 males and 69 females) and 210 healthy controls (72 males and 138 females). Voxel-wise analyses of gray matter volume and functional connectivity were conducted using a general linear regression model. This model included age, sex, diagnosis, and a sex-by-diagnosis interaction as predictors to explore potential sex-related differences in the brain features of participants with bipolar I disorder.ResultsThe gray matter volume analysis revealed significant sex-by-diagnosis interactions in six brain regions: the left caudate (p < 0.001), left thalamus (p < 0.001), right caudate (p = 0.003), right thalamus (p < 0.001), left anterior cingulate gyrus (p = 0.022), and left middle/posterior cingulate gyrus (p = 0.015). Using these regions as seeds, we detected a significant sex-by-diagnosis interaction in the functional connectivity alteration between the left thalamus and right angular gyrus (p = 0.019).ConclusionsOur findings revealed a noteworthy sex-by-diagnosis interaction, with male individuals with bipolar I disorder displaying larger gray matter volume and altered functional connectivity in the limbic system compared to female individuals with bipolar I disorder and healthy participants. These results hint at potential sex-related differences in the pathophysiology of the limbic system in bipolar I disorder, which may have significant implications for understanding the underlying mechanisms in bipolar I disorder. Our findings could contribute to developing more personalized treatment approaches for individuals with bipolar I disorder.

Beyond the mosaic model of brain evolution: Rearing environment defines local and global plasticity.

Comparative animal studies have identified a trend toward a more global structural organization as brains become larger, suggesting that brain regions grow in sync as predicted by the concerted model of brain evolution. At the same time, brain plasticity studies have identified a boost in local brain structure triggered by the environment, suggesting that brain regions grow independently, as predicted by the mosaic model. Nevertheless, it is unclear whether the environment can also trigger shifts toward a more global brain structure, that is, whether phenotypic plasticity proceeds in a concerted fashion. Here, we examined the impact of radically different rearing environments on brain organization in a teleost fish, the three-spined stickleback (Gasterosteus aculeatus). We computed novel indices of local and global brain structure across groups reared in the two environments and entered them as predictors of differences in brain and body sizes. Changes in local brain structure predicted differences in both body and brain sizes, whereas changes in global brain structure only predicted differences in brain size. Our findings highlight the emergence of brain plasticity in a population as local and global changes that are both compatible with the concerted model.

The lung-brain axis: genetic evidence for causal effects of asthma, allergic rhinitis, and chronic rhinosinusitis on brain structure.

Previous studies have indicated Asthma, allergic rhinitis (AR) and chronic rhinosinusitis (CRS) may influence brain structure. However, it remains unclear whether these three airway conditions cause brain structural changes and which specific brain regions are affected. We conducted a Mendelian randomization (MR) to explore the causal effect of AR, CRS, and asthma on brain structure. Reverse MR was conducted to investigate potential impact of changes in brain structure on AR, CRS, and asthma. Additionally, to enhance our understanding of the lung-brain axis, we examined bidirectional relationships between Alzheimer's disease, Parkinson's disease, insomnia, major depression, neuroticism, attention deficit hyperactivity disorder and these three respiratory disorders Findings: The genetically predicted CRS could reduce the surface area in the banks of the superior temporal sulcus, paracentral, and superior frontal. Asthma had an association with a decrease in the surface area of the entorhinal, fusiform, and temporal pole, as well as a reduction in the volume of amygdala. Asthma could also increase the thickness of pericalcarine. Reverse MR showed that changes in the surface area of pars opercularis and thickness of entorhinal cortex had a potential effect on CRS. Besides, bidirectional MR between 3 airway disorders and 6 neuropsychiatric disorders indicated neuroticism could raised risk for asthma, and major depression could increased the risk of CRS and asthma Conclusion: Our MR analysis revealed a potential causal relationship among CRS, asthma, and atrophy in specific functional areas of the human brain, supporting the existence of a lung-brain axis.

Brain Function and Structure Changes in the Prognosis Prediction of Prolonged Disorders of Consciousness.

To observe the functional differences in the key brain areas in patients with different levels of consciousness after severe brain injury, and provide reference for confirming the objective diagnosis indicators for prolonged disorders of consciousness (pDoCs). This prospective study enrolled patients with pDoCs hospitalized in the department of rehabilitation medicine of our Hospital. Levels of consciousness and clinical outcomes were assessed according to diagnostic criteria and behavioral scales. Resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) of 30 patients with different levels of consciousness was performed. The patients were grouped as conscious or unconscious according to whether they regained consciousness during the 12-month follow-up. Thirty patients were enrolled, including eight with unresponsive wakefulness syndrome/vegetative state, eight with minimally conscious state, six with emergence from the minimally conscious state, and eight with a locked-in syndrome. There were 19 and 11 patients in the conscious and unconscious groups. Compared with the unconscious group, the left basal nucleus was activated in the conscious group, and there were significant differences in white matter fiber bundles. Correlations were observed between the regional homogeneity (ReHo) value of the cerebellum and the Glasgow coma scale score (r = 0.387, P = 0.038) and between the ReHo value of the left temporal and the coma recovery scale-revised score (r = 0.394, P = 0.035). The left insula and cerebellum might be important for regaining consciousness. The brain function activity and structural remodeling of the key brain regions and the activation level of the cerebellum are correlated with clinical behaviors and have potential application value for the prognosis prediction of pDoCs patients.

Cancer-Related Cognitive Impairment and the Potential of Dietary Interventions for the Prevention and Mitigation of Neurodegeneration.

Approximately 35% of long-term cancer survivors experience ongoing cancer-related cognitive impairment (CRCI). Yet, few efficacious interventions exist to prevent or ameliorate CRCI. The underlying biological processes driving CRCI are complex and are reported to include changes in brain structure and function, increased oxidative stress and inflammation, and alterations in gut microbiome composition. Some of the mechanisms promoting CRCI have the potential to be modified through behavioral changes, such as dietary changes. Compelling evidence from randomized controlled trials and observational research supports the positive impacts of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet on cognition outside of the context of cancer, but studies investigating the MIND diet as an intervention for people who experience CRCI are lacking. This review examines the current state of the science for cognitive outcomes of dietary interventions in aging populations and discusses future opportunities to adapt these interventions to cancer populations.

Physical Activity and Neurodegenerative Diseases: Potential Role in Prevention and Therapy

Physical activity and exercise are low-cost interventions in primary and secondary prevention of several noncommunicable disease (e.g. cardiovascular diseases, chronic kidney disease, neurodegenerative and neurovascular disease). In the context of demographic change, the relative and absolute numbers of patients with neurological, especially neurodegenerative disease, will increase. Based on missing causal therapies and high costs, non-pharmacological (e.g. physical activity) approaches for healthy aging are gaining attention. Epidemiological, observational, and randomized controlled studies have shown that physical activity can enhance brain plasticity and improve cognitive vitality over lifespan. However, the underlying neurobiological mechanisms are still largely unknown. Physical activity can influence different risk factors for neurovascular and neurodegenerative diseases (e.g. arterial hypertension, obesity). Moreover, physical activity can induce cellular and molecular changes (level 1) followed by structural and functionals brain changes (level 2) and/or behavioural adaptations (level 3). In this clinical review we summarize the role of physical activity in the prevention and therapy of neurological disease.

Cognitive impact and brain structural changes in long COVID patients: a cross-sectional MRI study two years post infection in a cohort from Argentina

ObjectiveLong COVID is a condition characterised by persistent symptoms after a SARS-CoV-2 infection, with neurological manifestations being particularly frequent. Existing research suggests that long COVID patients not only report cognitive symptoms but also exhibit measurable cognitive impairment. Neuroimaging studies have identified structural alterations in brain regions linked to cognitive functions. However, most of these studies have focused on patients within months of their initial infection. This study aims to explore the longer-term cognitive effects and brain structural changes in long COVID patients, approximately two years post-infection, in a cohort from San Martín, Buenos Aires, Argentina.MethodsWe conducted a cross-sectional study involving 137 participants: 109 with long COVID symptoms and 28 healthy controls. The participants underwent an initial clinical assessment, completed a structured questionnaire and standardised scales, underwent a cognitive assessment, and had a brain MRI scan. Structural MRI images were processed via FreeSurfer and FSL to obtain volumetric measures for subcortical and cortical regions, along with regional cortical thickness. Differences between groups for these variables were analysed using ANCOVA, with permutation tests applied to correct for multiple comparisons.ResultsLong COVID patients reported persistent cognitive symptoms such as memory problems and brain fog, with higher levels of fatigue and reduced quality of life compared to controls. Despite subjective cognitive complaints, cognitive tests did not reveal significant differences between groups, except for the TMT-A (p = 0.05). MRI analysis revealed decreased volume in the cerebellum (p = 0.03), lingual gyrus (p = 0.04), and inferior parietal regions (p = 0.03), and reduced cortical thickness in several areas, including the left and right postcentral gyri (p = 0.02, p = 0.03) and precuneus (p = 0.01, p = 0.02).ConclusionsThis study highlights the enduring impact of long COVID on quality of life and physical activity, with specific brain structural changes identified two years post-infection. Although cognitive tests did not show clear impairment, the observed brain atrophy and significant reduction in quality of life emphasize the need for comprehensive interventions and further longitudinal studies to understand the long-term effects of long COVID on cognition and brain health.

The relation between cerebral morphological abnormalities in major depressive disorder and antidepressant treatment

Abstract. The cerebral morphological abnormalities caused by Major Depressive Disorder (MDD) are markedly different from those of many other cerebral parts in non-patients. This brain disorder may be coordinated by antidepressant treatment. This paper investigates the links between antidepressant medication and morphological features in MDD using a literature review method. The paper finds that there is a positive response and feedback on these neurobiological alterations. The relationship between morphological features and treatment may make it easier to objectively observe the effects of antidepressants on MDD patients. The review emphasizes the importance of understanding the cerebral morphological changes associated with MDD, as well as how antidepressant therapy can potentially modulate these alterations. By exploring the relationship between pharmacological interventions and structural brain changes, the paper provides insights into the neurobiological mechanisms underlying the therapeutic effects of antidepressants. This knowledge can enhance the advancement of more focused and efficient therapy approaches for patients with Major Depressive Disorder.

Dysregulated neurofluid coupling as a new noninvasive biomarker for primary progressive aphasia

Accumulation of pathological tau is one of the primary causes of Primary Progressive Aphasia (PPA). The glymphatic system is crucial for removing metabolite waste from the brain whereas impairments in glymphatic clearance in PPA are poorly understood. Thus, this study aims to investigate the role of dysregulated macroscopic cerebrospinal fluid (CSF) movement in PPA. Fifty-six PPA individuals and ninety-four healthy controls were included in our analysis after excluding those with excessive head motions during the scan. The coupling strength between blood-oxygen-level-dependent (BOLD) signals in the gray matter and CSF flow was calculated using Pearson correlation and compared between the groups. Its associations with clinical characteristics including scores from Clinical Dementia Rating (CDR), Mini-Mental State Exam, Geriatric Depression Scale and with morphological measures in the hippocampus and entorhinal cortex were examined. PPA subjects exhibited weaker global BOLD-CSF coupling compared to HCs, indicating impairments in glymphatic function in the patients (p = 0.01). In the PPA but not HC group, global BOLD-CSF coupling correlated with the CDR scores (p = 0.04) and hippocampal volume (p = 0.009). The observed decoupling between global brain activity and CSF flow and its association with symptomatology and brain structural changes in PPA converges with previous reports on the same measure in other neurodegenerative diseases. These findings support the potential role of global BOLD-CSF coupling as a noninvasive marker for glymphatic dysregulation in PPA.

Deep Learning-Based Pediatric Brain Region Segmentation and Volumetric Analysis for General Growth Pattern in Healthy Children.

To establish a quantitative reference for brain structural changes in children with neurological disorders, we employed deep learning technique to brain region segmentation and volumetric analysis within a cohort of healthy children. In this study, we recruited 312 participants aged 1.5 to 14.5years (210 boys and 102 girls), dividing them into five age groups. High-resolution structural T1-weighted images were obtained, and an established toolkit utilizing deep learning algorithms was employed for brain region segmentation. For each age group, the volumes of gray matter and white matter, along with the thickness and surface area of the cortex, were calculated and compared between boys and girls. The results indicated that the volumes of gray matter and white matter in both bilateral cerebral hemispheres, as well as the total brain volume, increased with age. Furthermore, the volumes of the left and right hippocampus, amygdala, and thalamus also demonstrated an increase as age progressed. Conversely, cortical thickness and surface area decreased with age. Our findings provide a quantitative reference for understanding brain structural changes in children with neurological disorders.

A diffusion tensor imaging-based multidimensional study of brain structural changes after long-term high-altitude exposure and their relationships with cognitive function.

Brain structure changes after long-term adaptation to the high-altitude environment; however, related studies are few, results are in consistent, and long-term effects on cognitive function and pathophysiological mechanisms are unclear. Therefore, diffusion tensor imaging (DTI) was used to investigate the damage to white matter fiber tracts and correlations between brain structural abnormalities and cognitive function. Forty healthy Han people living on the high-altitude and 40 healthy Han people living on the plains were enrolled in this study and underwent magnetic resonance imaging, emotional state assessment, and cognitive function tests. The sex, age, education level, and social status of the two groups were not different. The tract-based spatial statistics (TBSS) method was used to analyze the DTI parameters of the white matter fiber tracts of the two groups. Moreover, the partial correlation method (age and sex as covariates) was used to analyze the correlations between the intergroup differences in the DTI parameters and a series of clinical indicators of emotional state and cognitive function. Two-sample t tests, Mann-Whitney U test, generalized linear model, or chi-square tests were used for statistical analysis. Compared with those individuals in the plain group, the scores on the PSQI, SDS, SAS, PHQ-9, and GAD-7 of individuals in the high-altitude group were higher, while the scores on the DST-Backwards, MoCA, and MMSE in the high-altitude group were lower. The fractional anisotropy (FA) value of the body of the corpus callosum in the high-altitude group was lower than that in the plain group. The FA value of the body of the corpus callosum in the plain group was negatively correlated with the Logical Memory, while no significant correlation was found in the high-altitude group. This study revealed that long-term exposure to a high-altitude environment could lead to a series of changes in sleep, emotion, and cognitive function and irreversible damage to the white matter microstructure of the body of the corpus callosum, which is the related brain region responsible for logical memory. The absence of logical memory impairment in the healthy Han Chinese population living on the high-altitude in this study may be due to the existence of adaptive compensation after long-term high-altitude exposure.

Early-Life Stress Influences the Transcriptional Activation of Alpha-2A Adrenergic Receptor and Associated Protein Kinase A Signaling Molecules in the Frontal Cortex of Rats.

Early life is a highly sensitive period associated with profound changes in brain structure and function. Adverse experiences of early-life stress (ELS) are prominent risk factors for the precipitation of major depressive disorder (MDD). In recent years, dysfunction of the central noradrenergic (NA) system and subsequent deficits in norepinephrine (NE) signaling have gained increasing attention in the pathophysiology of MDD. However, the role of the α-2A adrenergic receptor and its downstream second messenger signaling system has not been investigated in connection to early-life stress-induced depression, limiting valuable insights into neurobiological mechanisms underlying this disorder. In this study, we used maternal separation (MS) as a rodent model of ELS to investigate whether ELS-induced depressive behavior is related to the α-2A adrenergic receptor and its associated second messenger signaling cascade. To do so, we studied expression levels of the α-2A adrenergic receptor (Adra2a), G alpha proteins (stimulatory subunit-Gαs [Gnas] and inhibitory subunit-Gαi [Gnai1 and Gnai2]), and downstream protein kinase A (PKA) catalytic [Prkarcα and Prkarcβ] and regulatory subunits [Prkar1α, Prkar1β, Prkar2α, and Prkar2β]) in the frontal cortex (FC) of MS rats. We found reduced sucrose preference in MS animals, along with reduced transcript levels of Adra2a, Gnai2, Prkar1β, and Prkarcβ. These findings suggest that ELS exposure may contribute to depression symptomatology via alterations in the expression of key genes involved in the NA system, highlighting potential mechanisms underlying ELS-induced depressive behavior.

Role of Cardiovascular Risk in Associations of Brain-Derived Neurotrophic Factor with Longitudinal Brain and Cognitive Trajectories in Older Adults

ABSTRACT Background Higher levels of brain-derived neurotrophic factor (BDNF) have been associated with better neurocognitive outcomes. BDNF is present in cardiovascular tissue, and some evidence suggests it may benefit cardiovascular function. The current study assessed whether there is a mediating and/or moderating role of cardiovascular health in the relationship between BDNF and brain and cognitive outcomes. Method We examined longitudinal data from 397 older adults (aged 54–89;164 females, 233 males) enrolled in the Alzheimer’s Disease Neuroimaging Initiative with available plasma BDNF, medical, neuroimaging, and cognitive assessments. We used path analysis and linear regression to estimate the mediating and moderating roles of two measures of cardiovascular health, the Framingham Risk Score (FRS) and pulse pressure, in the relationships between BDNF and longitudinal changes in brain structure (white matter hyperintensity volume, hippocampal volume, and primary visual cortex volume) and cognitive function (executive function, episodic memory, and language). Results There was no significant association of plasma BDNF with FRS or pulse pressure (ps > 0.31), precluding mediation. There were no robust associations between BDNF and longitudinal change in any brain structural or cognitive measures (ps > .12). Higher FRS was significantly associated with greater increases in WMH volume (ps < .01). FRS and pulse pressure were not associated with any other brain structural or cognitive outcomes (ps > .07). Conclusion These results suggest that cardiovascular health may not play an important role in the influence of BDNF on neurocognitive health in older adults.

Valuing the importance of sex differences in prodromal Alzheimer's disease based on structural magnetic resonance imaging.

Alzheimer's disease (AD) can be optimally managed from a healthcare point of view if detected at a prodromal stage. Amnestic mild cognitive impairment (MCI) is known as prodromal AD, has attracted extensive attention and research. To identify the differences in cognitive function and structural magnetic resonance imaging (MRI) features between men and women with MCI on the basis of A/T/N classification system ("A" means amyloid-β biomarker, "T" means tau biomarker, and "N" means neurodegeneration biomarker as determined by clinical imaging (e.g., positron emission tomography, magnetic resonance imaging (MRI)) or by the measurement of total tau protein (T-tau) in the cerebrospinal fluid (CSF)) and to further explore the correlation between them. 406 MCI subjects were selected from the Alzheimer's Disease Neuroimaging Initiative database and divided into male and female MCI groups. Differences in demographic characteristics, biomarkers, cognitive assessment performance, and regions of interest (ROIs) of structural MRI were compared between the two groups. The correlations between brain structural changes quantified by MRI and cognitive abilities were investigated through linear regression models. Compared with male MCI subjects, females had significantly higher T-tau concentration in CSF. There were significant differences in ROIs between the sex groups. In the male MCI group, the average cortical thicknesses of the right posterior cingulate, right anterior cingulate and right supramarginal gyrus were more closely correlated with cognitive function. In the female MCI group, the volume of the right rostral anterior cingulate, and the surface area and average cortical thickness of the right isthmus of the cingulate gyrus were more closely correlated with cognitive function. Based on A/T/N classification system, the structural MRI data analysis was closely correlated with the difference of cognitive function from patients with prodromal AD in a sex-dependent manner.

Cognitive decline in Cushing's syndrome: A systematic review.

The neurocognitive and psychiatric effects of Cushing's syndrome (CS) are well recognized and negatively impact quality of life. The aim of this systematic review is to compare neurocognitive disease, psychiatric symptoms, and structural brain changes in patients with Cushing's disease (CD)/CS and those with non-functioning pituitary adenoma (NFPA), both before and after surgical treatment, and in comparison to healthy controls. Possible predictors of persistent neurocognitive symptoms and reduced quality of life in patients with CS are highlighted. We reviewed the English literature published in Medline/Pubmed until 2021 to identify eligible studies. This systematic review was registered on Prospero and reported following the PRISMA statement guidelines. The initial literature search yielded 1772 articles, of which 1096 articles remained after removing duplicates. After excluding case reports, animal studies, narrative reviews, comparative reviews, and articles not in English, 86 papers underwent full-text review. Studies eligible for inclusion met the following criteria: (1) described patients with CD/CS, (2) reports of psychiatric symptoms, (3) written in English or with available English translation, and (4) published in a peer-reviewed journal. The full-text review process identified 40 eligible studies. The 40 studies included a total of 2603 participants with CD or CS, with 45.2% of the total participants having CD. The majority of studies were case-control studies and used validated questionnaires such as the Beck's Depression Index, Trail Making Test, Hospital Anxiety and Depression Scale, and Cushing Quality of Life for screening. Compared to NFPA controls, patients with CD who had greater baseline serum cortisol levels had worse cognitive function, even after surgical remission. This suggests a possible association between greater baseline cortisol levels in patients with CS and persistent cognitive impairment. A longer duration of uncontrolled CS was associated with worse cognitive function; however, there was no association found between the length of remission and memory. Overall brain volume was increased in patients in remission from CD compared to active disease. However, temporal and frontal lobe volumes did not recover to normal volumes. Patients with CS experience neurocognitive dysfunction, psychiatric disorders, and diminished quality of life, and symptoms may persist after curative surgery. We found several factors consistently associated with persistent cognitive and neuropsychiatric symptoms in patients with CS including higher pre-operatively baseline cortisol production, longer duration of disease, frontal and temporal lobe atrophy, and the presence of cognitive and neuropsychiatric symptoms at baseline. Larger prospective studies are required to validate these findings.

Causal relationship between cortical structural changes and onset of anxiety disorder: evidence from Mendelian randomization.

Previous studies have reported a correlation between anxiety disorders and changes in brain structure, yet the specific alterations in brain region volumes remain unclear. This study aimed to infer the causal relationship between anxiety disorders and changes in brain structure volume through Mendelian Randomization analysis. We selected 63 cortical structure volumes from the GWAS database as exposure data and anxiety disorder data from the FinnGen and UK Biobank databases as outcomes. We found a significant correlation between atrophy in the Left precentral volume area (Odds Ratio [OR] = 0.935, 95% Confidence intervals [CI]: 0.891-0.981, P value, P = 0.007) and an increased risk of anxiety disorders. Additionally, changes identified in specific brain regions, such as atrophy in the Right rostral anterior cingulate area (OR = 0.993, 95% CI: 0.987-0.999, P = 0.025) and increased volume in the Left superior parietal area (OR = 1.001, 95% CI: 1.000-1.001, P = 0.028), may correlate with an increased risk of anxiety disorders. Furthermore, both phenotypes demonstrated directional consistency in their respective and overall meta-analyzed OR values pre- and post-merger, enhancing the reliability of the results. This study elucidates the causal relationship between anxiety disorders and specific brain structures, providing new insights for further research into psychiatric disorders.

Distinct brain and neurocognitive transformations after bariatric surgery: a pilot study.

Obese patients have worse outcomes after surgery and are at increased risk for perioperative neurocognitive disorders (PND). Our aim was to detail the cognitive trajectories of patients undergoing bariatric surgery (BS) and map distinct structural brain changes using magnetic resonance imaging (MRI) to better understand the association between the vulnerable brain, surgery, and the arc of PND. Prospective pilot study with longitudinal comprehensive cognitive assessments and MRI were performed on obese patients scheduled for BS. We analyzed baseline cognitive function and high-resolution T1-/T2-weighted brain images on 19 obese patients [age, 54 (9) years, BMI, 40 (36, 42) kg m-2] and compared with 50 healthy control subjects [age, 52 (6) years; BMI, 25 (24, 27) kg m-2]. Patients were evaluated within five days of BS (baseline), immediately after (within 48h), and follow up at six months. At baseline, obese patients had significant brain tissue changes seen in MRI and decreased cognitive scores compared to controls (MoCA 26 vs 28, P = 0.017). Surgery induced further gray matter volume and brain tissue changes along with reduced cognitive scores within the immediate postoperative period (MoCA 26 vs 24, P < 0.001). At six months, we observed reversal of brain alterations for most patients and a concomitant rebound of cognitive scores to patient's baseline status. Bariatric surgery resulted in worsening of preexisting brain structural integrity and lower cognitive function for obese patients compared to baseline. These distinct brain lesions are consistent with specific domains of cognition. Most of these changes reverted to patient's baseline condition within six months after surgery.

Volumetric Integrated Classification Index: An Integrated Voxel-Based Morphometry and Machine Learning Interpretable Biomarker for Post-Traumatic Stress Disorder.

PTSD is a complex mental health condition triggered by individuals' traumatic experiences, with long-term and broad impacts on sufferers' psychological health and quality of life. Despite decades of research providing partial understanding of the pathobiological aspects of PTSD, precise neurobiological markers and imaging indicators remain challenging to pinpoint. This study employed VBM analysis and machine learning algorithms to investigate structural brain changes in PTSD patients. Data were sourced ADNI-DoD database for PTSD cases and from the ADNI database for healthy controls. Various machine learning models, including SVM, RF, and LR, were utilized for classification. Additionally, the VICI was proposed to enhance model interpretability, incorporating SHAP analysis. The association between PTSD risk genes and VICI values was also explored through gene expression data analysis. Among the tested machine learning algorithms, RF emerged as the top performer, achieving high accuracy in classifying PTSD patients. Structural brain abnormalities in PTSD patients were predominantly observed in prefrontal areas compared to healthy controls. The proposed VICI demonstrated classification efficacy comparable to the optimized RF model, indicating its potential as a simplified diagnostic tool. Analysis of gene expression data revealed significant associations between PTSD risk genes and VICI values, implicating synaptic integrity and neural development regulation. This study reveals neuroimaging and genetic characteristics of PTSD, highlighting the potential of VBM analysis and machine learning models in diagnosis and prognosis. The VICI offers a promising approach to enhance model interpretability and guide clinical decision-making. These findings contribute to a better understanding of the pathophysiological mechanisms of PTSD and provide new avenues for future diagnosis and treatment.

Association of depression with longitudinal changes in brain structure across the lifespan: A mendelian randomization study.

Understanding the impact of depression on brain aging benefits the prognosis of this disease and of the risk that other age-related brain disorders will develop in the same population. The aim of the present study was to explore the genetic effect of depression on longitudinal changes in brain structure throughout the lifespan using a Mendelian randomization approach. Summary data from a genome-wide association study of 195,321 to 377,277 participants in the FinnGen consortium were used to predict depression, anxiety disorders, mood disorders, and antidepressant use genetically. Data from 15,640 participants in the ENIGMA consortium were included to predict changes in 15 brain structures throughout the lifespan. The causal relationship between these depressive traits and the brain structure parameters was assessed by two-sample Mendelian randomization (including inverse-variance weighted). Sensitivity analyses were conducted for quality control. Depression slowed the decrease of cortical gray matter volume significantly throughout the lifespan (p = 0.001). Depression, anxiety, and mood disorders nominally decreased the rates of change of volume in the cerebellum gray matter, lateral ventricles, and cortical gray matter throughout the lifespan (p = 0.048, p = 0.021, p = 0.038, respectively). Antidepressants did not affect these rates of change significantly (p > 0.05). Sensitivity analyses confirmed the reliability of this study. Depression and its main symptoms have a slight effect on longitudinal changes in a few brain structures throughout the lifespan at the genetic level. These findings do not support the notion that depression affects macro-aging in the brain crucially.