Subcortical Volumes Research Articles

Pathway-specific polygenic scores for Alzheimer's disease are associated with changes in brain structure in younger and older adults.

Genome-wide association studies have identified multiple Alzheimer's disease risk loci with small effect sizes. Polygenic risk scores, which aggregate these variants, are associated with grey matter structural changes. However, genome-wide scores do not allow mechanistic interpretations. The present study explored associations between disease pathway-specific scores and grey matter structure in younger and older adults. Data from two separate population cohorts were used as follows: the Avon Longitudinal Study of Parents and Children, mean age 19.8, and UK Biobank, mean age 64.4 (combined n = 18 689). Alzheimer's polygenic risk scores were computed using the largest genome-wide association study of clinically assessed Alzheimer's to date. Relationships between subcortical volumes and cortical thickness, pathway-specific scores and genome-wide scores were examined. Increased pathway-specific scores were associated with reduced cortical thickness in both the younger and older cohorts. For example, the reverse cholesterol transport pathway score showed evidence of association with lower left middle temporal cortex thickness in the younger Avon participants (P = 0.034; beta = -0.013, CI -0.025, -0.001) and in the older UK Biobank participants (P = 0.019; beta = -0.003, CI -0.005, -4.56 × 10-4). Pathway scores were associated with smaller subcortical volumes, such as smaller hippocampal volume, in UK Biobank older adults. There was also evidence of positive association between subcortical volumes in Avon younger adults. For example, the tau protein-binding pathway score was negatively associated with left hippocampal volume in UK Biobank (P = 8.35 × 10-05; beta = -11.392, CI -17.066, -5.718) and positively associated with hippocampal volume in the Avon study (P = 0.040; beta = 51.952, CI 2.445, 101.460). The immune response score had a distinct pattern of association, being only associated with reduced thickness in the right posterior cingulate in older and younger adults (P = 0.011; beta = -0.003, CI -0.005, -0.001 in UK Biobank; P = 0.034; beta = -0.016, CI -0.031, -0.001 in the Avon study). The immune response score was associated with smaller subcortical volumes in the older adults, but not younger adults. The disease pathway scores showed greater evidence of association with imaging phenotypes than the genome-wide score. This suggests that pathway-specific polygenic methods may allow progress towards a mechanistic understanding of structural changes linked to polygenic risk in pre-clinical Alzheimer's disease. Pathway-specific profiling could further define pathophysiology in individuals, moving towards precision medicine in Alzheimer's disease.

Interactive effect of orthostatic hypotension on gray matter atrophy associated with hyposmia and RBD in de novo Parkinson's disease.

Orthostatic hypotension (OH) is a potential modifiable risk factor for cognitive impairment in patients with Parkinson's disease (PD). Although other risk factors for dementia, hyposmia and REM sleep behavior disorder (RBD), are closely associated with autonomic dysfunction in PD, little is known about how these risk factors influence cognitive function and cerebral pathology. We investigated how these three factors contribute to gray matter atrophy by considering the interaction of OH with hyposmia and RBD. We analyzed cortical thickness, subcortical gray matter volume, and cognitive measures from 78 patients with de novo PD who underwent the head-up tilt test for the diagnosis of OH. Whole-brain analyses with Monte Carlo corrections revealed that hyposmia was associated with decreased cortical thickness in a marginal branch of the cingulate sulcus among patients with OH, and cortical thickness in this area correlated with cognitive functioning only in patients with OH. Subcortical gray matter volume analysis indicated that severe RBD was associated with decreased volume in the left hippocampus and bilateral amygdala among patients with OH. Even in early PD, OH exerts effects on gray matter atrophy and cognitive dysfunction by interacting with RBD and hyposmia. OH might exacerbate cerebral pathology induced by hyposmia or RBD.

A prospective 5-year longitudinal study detects neurocognitive and imaging correlates of seizure remission in self-limiting Rolandic epilepsy

ObjectiveSelf-limiting Rolandic epilepsy (RE) is the most common epilepsy in school-age children. Seizures are generally infrequent, but cognitive, language, and motor coordination problems can significantly impact the child’s life. To better understand brain structure and function changes in RE, we longitudinally assessed neurocognition, cortical thickness, and subcortical volumes. MethodsAt baseline, we recruited 30 participants diagnosed with RE and 24-healthy controls and followed up for 4.94 ± 0.8 years when the participants with RE were in seizure remission. Measures included were as follows: T1-weighted magnetic resonance brain imaging (MRI) with FreeSurfer analysis and detailed neuropsychological assessments. MRI and neuropsychological data were compared between baseline and follow-up in seizure remission. ResultsLongitudinal MRI revealed excess cortical thinning in the left-orbitofrontal (p = 0.0001) and pre-central gyrus (p = 0.044).There is a significant association (p = 0.003) between a reduction in cortical thickness in the left-orbitofrontal cluster and improved processing of filtered words.Longitudinal neuropsychology revealed significant improvements in the symptoms of developmental coordination disorder (DCD, p = 0.005) in seizure remission. ConclusionsThere is evidence for altered development of neocortical regions between active seizure state and seizure remission in RE within two clusters maximal in the left-orbitofrontal and pre-central gyrus. There is significant evidence for improvement in motor coordination between active seizures and seizure remission and suggestive evidence for a decline in fluid intelligence and gains in auditory processing.

Gray Matter Changes Following Mild COVID-19: An MR Morphometric Study in Healthy Young People.

Although COVID-19 is primarily an acute respiratory infection, 5%-40% of patients develop late and prolonged symptoms with frequent neurological complaints, known as long COVID syndrome. The presentation of the disease suggests that COVID infection may cause functional and/or morphological central nervous system alterations, but studies published in the literature report contradictory findings. To investigate the chronic effects of COVID-19 on cerebral grey matter in a group of young patients without comorbidities, with mild course of COVID infection and no medical complaints at the time of examination. Prospective. Thirty-eight young (age = 26.6 ± 5.0 years; male/female = 14/24), adult participants who recovered from mild COVID infection without a history of clinical long COVID and 37 healthy control subjects (age = 25.9 ± 2.8 years; male/female = 14/23). Three Tesla, 3D T1-weighted magnetization-prepared rapid gradient-echo, 2D T2-weighted turbo spin-echo. MRI-based morphometry and volumetry along with neuropsychological testing and self-assessed questionnaire. Fisher's exact test, Mann-Whitney U-test, and multiple linear regression analyses were used to assess differences between COVID and healthy control groups. P < 0.05 was used as cutoff for significance. In the COVID group, significantly lower bilateral mean cortical thickness (left/right-hemisphere: 2.51 ± 0.06 mm vs. 2.56 ± 0.07 mm, η2 p = 0.102/2.50 ± 0.06 mm vs. 2.54 ± 0.07 mm, η2 p = 0.101), lower subcortical gray matter (57881 ± 3998 mm3 vs. 60470 ± 5211 mm3, η2 p = 0.100) and lower right olfactory bulb volume (52.28 ± 13.55 mm3 vs. 60.98 ± 15.8 mm3, η2 p = 0.078) were found. In patients with moderate to severe anosmia, cortical thickness was significantly lower bilaterally, as compared to patients without olfactory function loss (left/right-hemisphere: 2.50 ± 0.06 mm vs. 2.56 ± 0.05 mm, η2 = 0.173/2.49 ± 0.06 mm vs. 2.55 ± 0.05 mm, η2 = 0.189). Using further exploratory analysis, significantly reduced cortical thickness was detected locally in the right lateral orbitofrontal cortex in the COVID group (2.53 ± 0.10 mm vs. 2.60 ± 0.09 mm, η2 p = 0.112). Even without any subjective or objective neurological complaints at the time of the MR scan, subjects in the COVID group showed gray matter alterations in cortical thickness and subcortical gray matter volume. 2 TECHNICAL EFFICACY: Stage 3.

Brainstem and subcortical regions volume loss in patients with degenerative cervical myelopathy and its association with spinal cord compression severity

BackgroundIn recent years, structural and functional reorganization of the brain and changes in brainstem structural connectivity have been shown in patients with degenerative cervical myelopathy (DCM). We hypothesized that volume loss in the basal ganglia, thalami, and brainstem structures exists and is associated with spinal cord compression severity in patients with DCM. MethodsForty-seven patients with DCM and 25 patients with cervical radiculopathy were evaluated using cervical spinal cord and brain magnetic resonance imaging (MRI). Brainstem structures, basal ganglia, and thalami volumes were evaluated with FreeSurfer and compared between groups with correction for individual intracranial volume, as well as patient age and sex. Additionally, spinal cord MRI data were analysed with the Spinal Cord Toolbox, and cross-sectional area (CSA) and fractional anisotropy (FA) values were calculated. Correlations between MR-morphometry data and spinal cord structural changes, as well as disease duration, were also evaluated in patients with DCM. ResultsA statistically significant reduction in the volume of the whole brainstem was revealed in the DCM group compared to the radiculopathy group (p < 0.01, FDR-corrected). Additionally, reductions in medulla oblongata, pons and midbrain volumes were found in patients with DCM (p < 0.01, p < 0.01 and p < 0.05, respectively, FDR-corrected). Additionally, a trend in the loss of volume of the left putamen was found (p = 0.087, FDR-corrected). Furthermore, medulla oblongata volume was correlated with spinal cord compression severity (R = 0.54, adjusted p < 0.001) and white matter damage (R = 0.46, adjusted p < 0.05) in patients with DCM. Negative correlations between the duration of the disease and the severity of spinal cord compression (R = −0.42, adjusted p < 0.05) and white matter damage (R = −0.49, adjusted p < 0.05) were also revealed, as well as a trend toward a negative association between the duration of the disease and the volume of the medulla oblongata (R = −0.35; adjusted p < 0.1). ConclusionsWe revealed a reduction in the volume of brainstem structures in patients with DCM compared to patients with radiculopathy. Moreover, we found that these changes are associated with cord compression severity.

A Shared Multivariate Brain-Behavior Relationship in a Transdiagnostic Sample of Adolescents

BackgroundInternalizing and externalizing psychopathology typically present in early childhood and can have negative implications on general functioning and quality of life. Prior work has linked increased psychopathology symptoms with altered brain structure. Multivariate analysis such as partial least squares correlation can help identify patterns of covariation between brain regions and psychopathology symptoms. This study examined the relationship between gray matter volume (GMV) and psychopathology symptoms in adolescents with various psychiatric diagnoses. MethodsStructural magnetic resonance imaging data were collected from 490 participants with various internalizing and externalizing diagnoses (197 female/293 male; age = 14.68 ± 2.35 years; IQ = 104.05 ± 13.11). Cortical and subcortical volumes were parcellated using the Desikan-Killiany atlas. Partial least squares correlation was used to identify multivariate linear relationships between GMV and the Strength and Difficulties Questionnaire difficulties domains (emotional, peer, conduct, and hyperactivity issues). Resampling approaches were used to determine significance (permutation test), stability (bootstrap resampling), and reproducibility (split-half resampling) of identified relationships. ResultsWe found a significant, stable, and largely reproducible dimension that linked lower Strength and Difficulties Questionnaire scores (less impairment) across all difficulties domains with greater widespread GMV (singular value = 1.17, accounts for 87.1% of the covariance; p < .001). This dimension emphasized the relationship between lower conduct problems and greater GMV in frontotemporal regions. ConclusionsOur results indicate that the most significant and stable brain-behavior relationship in a transdiagnostic sample is a domain-general relationship, linking lower psychopathology symptom scores to greater global GMV. This finding suggests that a shared brain-behavior relationship may be present across adolescents with and without clinically significant psychopathology symptoms.

Independent and combined effects of methamphetamine use disorders and APOEε4 allele on cognitive performance and brain morphometry.

Prior studies showed that methamphetamine (METH) users had greater than normal age-related brain atrophy; whether having the apolipoprotein E (APOE)-ε4 allele may be a contributory factor has not been evaluated. We aimed to determine the independent and combined effects of chronic heavy METH use and having at least one copy of the APOE-ε4 allele (APOE-ε4+) on brain morphometry and cognition, especially in relation to aging. We compared brain morphometry and cognitive performance in 77 individuals with chronic heavy METH use (26 APOE-ε4+, 51 APOE-ε4-) and 226 Non-METH users (66 APOE-ε4+, 160 APOE-ε4-), using a 2 × 2 design (two-way analysis of co-variance). Vertex-wise cortical volumes, thickness and seven subcortical volumes, were automatically measured using FreeSurfer. Linear regression between regional brain measures, and cognitive scores that showed group differences were evaluated. Group differences in age-related decline in brain and cognitive measures were also explored. Regardless of APOE-ε4 genotype, METH users had lower Motor Z-scores (P = 0.005), thinner right lateral-orbitofrontal cortices (P < 0.001), smaller left pars-triangularis gyrus volumes (P = 0.004), but larger pallida, hippocampi and amygdalae (P = 0.004-0.006) than nonusers. Across groups, APOE-ε4+ METH users had the smallest volumes of superior frontal cortical gyri bilaterally, and of the smallest volume in left rostral-middle frontal gyri (all P-values <0.001). Smaller right superior-frontal gyrus predicted poorer motor function only in APOE-ε4+ participants (interaction-P < 0.001). Cortical volumes and thickness declined with age similarly across all participants; however, APOE-ε4-carriers showed thinner right inferior parietal cortices than noncarriers at younger age (interaction-P < 0.001). Chronic heavy use and having at least one copy of the APOE-ε4 allele may have synergistic effects on brain atrophy, particularly in frontal cortices, which may contribute to their poorer cognitive function. However, the enlarged subcortical volumes in METH users replicated prior studies, and are likely due to METH-mediated neuroinflammation.

Brain Volumes and Cognition in Patients with Sickle Cell Anaemia: A Systematic Review and Meta-Analysis.

Cognitive decline is a major problem in paediatric and adult patients with sickle cell anaemia (SCA) and affects the quality of life. Multiple studies investigating the association between quantitative and qualitative neuroimaging findings and cognition have had mixed results. Hence, the aetiology of cognitive decline in this population is not clearly understood. Several studies have established cerebral atrophy in SCA children as well as adults, but the relationship between cognition and brain volumes remains unclear. The purpose of this systematic review was therefore to evaluate the literature on regional brain volumes and their association with cognitive outcomes. We also meta-analysed studies which compared regional brain volumes between patients and controls. Studies report that patients with SCA tend to have lower grey matter volumes, including total subcortical volumes in childhood as compared to controls, which stabilise in young adulthood and may be subjected to decline with age in older adulthood. White matter volumes remain stable in children but are subjected to reduced volumes in young adulthood. Age and haemoglobin are better predictors of cognitive outcomes as compared to regional brain volumes.

Structural brain differences in essential tremor and Parkinson’s disease deep brain stimulation patients

BackgroundEssential tremor (ET) and Parkinson’s disease (PD) are the most common tremor disorders and are common indications for deep brain stimulation (DBS). In some patients, PD and ET symptoms overlap and diagnosis can be challenging based on clinical criteria alone. The objective of this study was to identify structural brain differences between PD and ET DBS patients to help differentiate these disorders and improve our understanding of the different brain regions involved in these pathologic processes. MethodsWe included ET and PD patients scheduled to undergo DBS surgery in this observational study. Patients underwent 3T brain MRI while under general anesthesia as part of their procedure. Cortical thicknesses and subcortical volumes were quantified from T1-weighted images using automated multi-atlas segmentation. We used logistic regression analysis to identify brain regions associated with diagnosis of ET or PD. Results149 ET and 265 PD patients were included. Smaller volumes in the pallidum and thalamus and reduced thickness in the anterior orbital gyrus, lateral orbital gyrus, and medial precentral gyrus were associated with greater odds of ET diagnosis. Conversely, reduced volumes in the caudate, amygdala, putamen, and basal forebrain, and reduced thickness in the orbital part of the inferior frontal gyrus, supramarginal gyrus, and posterior cingulate were associated with greater odds of PD diagnosis. ConclusionsThese findings identify structural brain differences between PD and ET patients. These results expand our understanding of the different brain regions involved in these disorders and suggest that structural MRI may help to differentiate patients with these two disorders.

Subcortical volumetric alterations in four major psychiatric disorders: a mega-analysis study of 5604 subjects and a volumetric data-driven approach for classification.

Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2-3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection.

Sex Difference in Cigarette-Smoking Status and Its Association with Brain Volumes Using Large-Scale Community-Representative Data.

Cigarette smoking is believed to accelerate age-related neurodegeneration. Despite significant sex differences in both smoking behaviors and brain structures, the active literature is equivocal in parsing out a sex difference in smoking-associated brain structural changes. The current study examined subcortical and lateral ventricle gray matter (GM) volume differences among smokers, active, past, and never-smokers, stratified by sex. The current study data included 1959 Dallas Heart Study (DHS) participants with valid brain imaging data. Stratified by gender, multiple-group comparisons of three cigarette-smoking groups were conducted to test whether there is any cigarette-smoking group differences in GM volumes of the selected regions of interest (ROIs). The largest subcortical GM volumetric loss and enlargement of the lateral ventricle were observed among past smokers for both females and males. However, these observed group differences in GM volumetric changes were statistically significant only among males after adjusting for age and intracranial volumes. The study findings suggest a sex difference in lifetime-smoking-associated GM volumetric changes, even after controlling for aging and intracranial volumes.

Mapping Brain Structure Variability in Chronic Pain: The Role of Widespreadness and Pain Type and Its Mediating Relationship With Suicide Attempt

BackgroundChronic pain affects nearly 20% of the U.S. population. It is a leading cause of disability globally and is associated with a heightened risk for suicide. The role of the central nervous system in the perception and maintenance of chronic pain has recently been accepted, but specific brain circuitries involved have yet to be mapped across pain types in a large-scale study. MethodsWe used data from the UK Biobank (N = 21,968) to investigate brain structural alterations in individuals reporting chronic pain compared with pain-free control participants and their mediating effect on history of suicide attempt. ResultsChronic pain and, more notably, chronic multisite pain was associated with, on average, lower surface area throughout the cortex after adjusting for demographic, clinical, and neuropsychiatric confounds. Only participants with abdominal pain showed lower subcortical volumes, including the amygdala and brainstem, and lower cerebellum volumes. Participants with chronic headaches showed a widespread thicker cortex compared with control participants. Mediation analyses revealed that precuneus thickness mediated the relationship of chronic multisite pain and history of suicide attempt. Mediating effects were also identified specific to localized pain, with the strongest effect being amygdala volume in individuals with chronic abdominal pain. ConclusionsResults support a widespread effect of chronic pain on brain structure and distinct brain structures underlying chronic musculoskeletal pain, visceral pain, and headaches. Mediation effects of regions in the extended ventromedial prefrontal cortex subsystem suggest that exacerbated negative internal states, negative self-referencing, and impairments in future planning may underlie suicidal behaviors in individuals with chronic pain.

Differentiating between common PSP phenotypes using structural MRI: a machine learning study.

Differentiating Progressive supranuclear palsy-Richardson's syndrome (PSP-RS) from PSP-Parkinsonism (PSP-P) may be extremely challenging. In this study, we aimed to distinguish these two PSP phenotypes using MRI structural data. Sixty-two PSP-RS, 40 PSP-P patients and 33 control subjects were enrolled. All patients underwent brain 3T-MRI; cortical thickness and cortical/subcortical volumes were extracted using Freesurfer on T1-weighted images. We calculated the automated MR Parkinsonism Index (MRPI) and its second version including also the third ventricle width (MRPI 2.0) and tested their classification performance. We also employed a Machine learning (ML) classification approach using two decision tree-based algorithms (eXtreme Gradient Boosting [XGBoost] and Random Forest) with different combinations of structural MRI data in differentiating between PSP phenotypes. MRPI and MRPI 2.0 had AUC of0.88 and 0.81, respectively, in differentiating PSP-RS from PSP-P. ML models demonstrated that the combination of MRPI and volumetric/thickness data was more powerful than each feature alone. The two ML algorithms showed comparable results, and the best ML model in differentiating between PSP phenotypes used XGBoost with a combination of MRPI, cortical thickness and subcortical volumes (AUC 0.93 ± 0.04). Similar performance (AUC 0.93 ± 0.06) was also obtained in a sub-cohort of 59 early PSP patients. The combined use of MRPI and volumetric/thickness data was more accurate than each MRI feature alone in differentiating between PSP-RS and PSP-P. Our study supports the use of structural MRI to improve the early differential diagnosis between common PSP phenotypes, which may be relevant for prognostic implications and patient inclusion in clinical trials.

Brain MRI segmentation of Zika-Exposed normocephalic infants shows smaller amygdala volumes.

Infants with congenital Zika syndrome (CZS) are known to exhibit characteristic brain abnormalities. However, the brain anatomy of Zika virus (ZIKV)-exposed infants, born to ZIKV-positive pregnant mothers, who have normal-appearing head characteristics at birth, has not been evaluated in detail. The aim of this prospective study is, therefore, to compare the cortical and subcortical brain structural volume measures of ZIKV-exposed normocephalic infants to age-matched healthy controls. We acquired T2-MRI of the whole brain of 18 ZIKV-exposed infants and 8 normal controls on a 3T MRI scanner. The MR images were auto-segmented into eight tissue types and anatomical regions including the white matter, cortical grey matter, deep nuclear grey matter, corticospinal fluid, amygdala, hippocampus, cerebellum, and brainstem. We determined the volumes of these regions and calculated the total intracranial volume (TICV) and head circumference (HC). We compared these measurements between the two groups, controlling for infant age at scan, by first comparing results for all subjects in each group and secondly performing a subgroup analysis for subjects below 8 weeks of postnatal age at scan. ZIKV-exposed infants demonstrated a significant decrease in amygdala volume compared to the control group in both the group and subgroup comparisons (p<0.05, corrected for multiple comparisons using FDR). No significant volume differences were observed in TICV, HC, or any specific brain tissue structures or regions. Study limitations include small sample size, which was due to abrupt cessation of extramural funding as the ZIKV epidemic waned. ZIKV-exposed infants exhibited smaller volumes in the amygdala, a brain region primarily involved in emotional and behavioral processing. This brain MRI finding may lead to poorer behavioral outcomes and warrants long-term monitoring of pediatric cases of infants with gestational exposure to Zika virus as well as other neurotropic viruses.

Independent effects of posttraumatic stress disorder diagnosis and metabolic syndrome status on prefrontal cortical thickness and subcortical gray matter volumes.

Posttraumatic stress disorder (PTSD) and metabolic syndrome (MetS) are associated with overlapping brain structural differences. These often involve brain structures involved in the regulation of appetite, food intake, satiety, and reward processing. We examined the individual and interactive effects of PTSD diagnosis and MetS on cortical thickness and subcortical gray matter volumes in patients with PTSD (n = 104) compared to trauma-exposed controls (n = 97). Multivariate models were constructed for FreeSurfer-generated prefrontal cortical thickness and subcortical gray matter regions-of-interest (ROIs) to explore the effects of PTSD diagnosis and MetS as predictors, adjusting for relevant socio-demographic and clinical covariates. Individual prefrontal cortical and subcortical limbic ROIs were also selected based on apriori evidence of their involvement in both PTSD and MetS. The mean age of the sample (n = 201; 78% female) was 41.6 (SD, 13.1) years. PTSD and MetS status showed independent associations with prefrontal cortical thickness and subcortical gray matter volumes across multiple ROIs, adjusting for age, sex, scanner sequence, alcohol, and tobacco use. PTSD and MetS are independently associated with brain structural differences, including thinner prefrontal cortical thickness and smaller subcortical gray matter volumes, across multipleROIs implicated in the hedonic and homeostatic regulation of food intake.

Associations of Glucose Metabolism Status with Brain Macrostructure and Microstructure: Findings from the UK Biobank.

Evidence linking glucose metabolism status with brain macro- and microstructure is limited and inconsistent. We aim to investigate the associations of glucose metabolism status with brain macrostructure and microstructure, including brain volumes, subcortical gray matter volumes, and white matter microstructural metrics. This study enrolled 29 251 participants from the UK Biobank. Glucose metabolism status was classified into normal glucose metabolism (NGM), prediabetes, type 2 diabetes (T2D) with HbA1c <7%, and T2D with HbA1c ≥7%. Brain macrostructural metrics included volumes of total and subcortical gray matter, white matter, white matter hyperintensity (WMH), cerebrospinal fluid, and brain stem. Brain microstructural metrics included fractional anisotropy (FA) and mean diffusivity in white matter tracts. Multivariable linear regression models were used to estimate β values and 95% CI. After multivariable adjustment including demographic and lifestyle factors, medical history, and total intracranial volume, those with prediabetes had smaller total and subcortical gray matter volumes than participants with NGM, while atrophy of total and subcortical gray matter was more pronounced in those with T2D (all P trend < .05). Moreover, participants with T2D had larger volumes of white matter and WMH (both P trend < .05). For brain microstructure, participants with prediabetes had lower FA values in commissural fibers (β -0.04; 95% CI -0.08, -0.003). Global and tract-specific microstructural abnormalities of white matter were observed in participants with T2D, especially for T2D with HbA1c ≥ 7% (all P trend < .05), except for FA values in projection fibers. These findings suggest that interventions for hyperglycemia at an earlier stage may help protect brain health.

Chromosomal inversion polymorphisms shape human brain morphology

The impact of chromosomal inversions on human brain morphology remains underexplored. We studied 35 common inversions classified from genotypes of 33,018 adults with European ancestry. The inversions at 2p22.3, 16p11.2, and 17q21.31 reach genome-wide significance, followed by 8p23.1 and 6p21.33, in their association with cortical and subcortical morphology. The 17q21.31, 8p23.1, and 16p11.2 regions comprise the LRRC37, OR7E, and NPIP duplicated gene families. We find the 17q21.31 MAPT inversion region, known for harboring neurological risk, to be the most salient locus among common variants for shaping and patterning the cortex. Overall, we observe the inverted orientations decreasing brain size, with the exception that the 2p22.3 inversion is associated with increased subcortical volume and the 8p23.1 inversion is associated with increased motor cortex. These significant inversions are in the genomic hotspots of neuropsychiatric loci. Our findings are generalizable to 3,472 children and demonstrate inversions as essential genetic variation to understand human brain phenotypes.

Assessments of variability in cortical and subcortical measurements and within-network connectivity of the brain using test-retest data.

The evaluation and diagnosis of structural changes in brain caused by disease or treatment over time has become one of the important applications of medical imaging methods, in particular MRI, and it is growing. It is critical to evaluate the reliability of the changes in measurements observed in an individual patient for any clinical decision-making. In this paper, we calculated the repeatability coefficient (RC) as a measure of uncertainty for MRI measurements of subcortical volumes and cortical thickness, and within-network connectivity using test-retest data of 20 healthy subjects. We also evaluated changes in 13 patients who received 20 sessions of transcranial magnetic stimulation as a treatment. The most reliable measure seems to be in the thickness of the left occipital with RC% of 3.5 and the least reliable measure is the brain connectivity within visual network using Yeo's atlas with RC% of 29.4. The most sensitive measure to the percentage of true changes in treated patients is the connectivity within subcortical network of AAL with 76.9%.Clinical Relevance- The results of this study can be useful for evaluating changes in the gray matter structures or functional connectivity of the brain due to a neurological disease such as Alzheimer's or Parkinson's. Also, the obtained results can be used to evaluate the changes caused by any intervention or treatment that may have any positive or negative effect on the brain.

Specificity of associations between parental psychopathology and offspring brain structure

Multiple forms of parental psychopathology have been associated with differences in subcortical brain volume. However, few studies have considered the role of comorbidity. Here, we examine if alterations in child subcortical brain structure are specific to parental depression, anxiety, mania, or alcohol/substance use parental psychopathology, common across these disorders, or altered by a history of multiple disorders. We examined 6581 children aged 9 to 10 years old from the ABCD study with no history of mental disorders. We found several significant interactions such that the effects of a parental history of depression, anxiety, and substance use problems on amygdala and striatal volumes were moderated by comorbid parental history of another disorder. Interactions tended to suggest smaller volumes in the presence of a comorbid disorder. However, effect sizes were small, and no associations remained significant after correcting for multiple comparisons. Results suggest that associations between familial risk for psychopathology and offspring brain structure in 9–10-year-olds are modest, and relationships that do exist tend to implicate the amygdala and striatal regions and are moderated by a comorbid parental psychopathology history. Several methodological factors, including controlling for intracranial volume and other forms of parental psychopathology and excluding child psychopathology, likely contribute to inconsistencies in the literature.

Prenatal tobacco exposure on brain morphometry partially mediated poor cognitive performance in preadolescent children.

To evaluate whether prenatal tobacco exposure (PTE) is related to poorer cognitive performance, abnormal brain morphometry, and whether poor cognitive performance is mediated by PTE-related structural brain differences. The Adolescent Brain Cognitive Development study dataset was used to compare structural MRI data and neurocognitive (NIH Toolbox®) scores in 9-to-10-year-old children with (n=620) and without PTE (n=10,989). We also evaluated whether PTE effects on brain morphometry mediated PTE effects on neurocognitive scores. Group effects were evaluated using Linear Mixed Models, covaried for socio-demographics and prenatal exposures to alcohol and/or marijuana, and corrected for multiple comparisons using the false-discovery rate (FDR). Compared to unexposed children, those with PTE had poorer performance (all p-values <0.05) on executive function, working memory, episodic memory, reading decoding, crystallized intelligence, fluid intelligence and overall cognition. Exposed children also had thinner parahippocampal gyri, smaller surface areas in the posterior-cingulate and pericalcarine cortices; the lingual and inferior parietal gyri, and smaller thalamic volumes (all p-values <0.001). Furthermore, among children with PTE, girls had smaller surface areas in the superior-frontal (interaction-FDR-p=0.01), precuneus (interaction-FDR-p=0.03) and postcentral gyri (interaction-FDR-p=0.02), while boys had smaller putamen volumes (interaction-FDR-p=0.02). Smaller surface areas across regions of the frontal and parietal lobes, and lower thalamic volumes, partially mediated the associations between PTE and poorer neurocognitive scores (p-values <0.001). Our findings suggest PTE may lead to poorer cognitive performance and abnormal brain morphometry, with sex-specific effects in some brain regions, in pre-adolescent children. The poor cognition in children with PTE may result from the smaller areas and subcortical brain volumes.