Regional Brain Volumes Research Articles

Childhood Book Availability Helps to Preserve Cognitive Function in Older Adults With Low Education: Results From the NEIGE Study.

It is well known that low educational attainment is associated with cognitive function decline in older age. Childhood book availability may help to preserve cognitive function in older adults with low education. The study objective was to examine the association between childhood book availability and cognitive function among older adults with low educational attainment, and to investigate the mediating effect of the volume of reading-related brain regions (e.g., superior temporal cortex). A cross-sectional study of community-dwelling older Japanese adults aged 65-84 years was conducted (n = 474). Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Childhood book availability was assessed using a retrospective questionnaire. Brain region volume was measured using magnetic resonance imaging. Multivariate regression modeling and structural equation modeling were used for analysis. Both high educational attainment and childhood book availability were independently associated with high MMSE score. Stratification of educational level showed that childhood book availability was positively associated with MMSE score among participants with low educational attainment (coefficient = 1.48, 95% confidence interval [CI]: 0.31 to 2.66), but not among those with moderate or high educational attainment (coefficient = -0.01, 95% CI: -1.44 to 1.42 and -1.21, 95% CI: -3.85 to 1.42, respectively). Among participants with low educational attainment, left superior temporal cortex volume mediated the association between childhood book availability and MMSE score. The availability of books in childhood helps to preserve cognitive function in older adults with low education via left superior temporal cortex volume. Further research is needed to replicate these findings.

Parental status and markers of brain and cellular age: A 3D convolutional network and classification study

Recent research shows prominent effects of pregnancy and the parenthood transition on structural brain characteristics in humans. Here, we present a comprehensive study of how parental status and number of children born/fathered links to markers of brain and cellular ageing in 36,323 UK Biobank participants (age range 44.57–82.06 years; 52% female). To assess global effects of parenting on the brain, we trained a 3D convolutional neural network on T1-weighted magnetic resonance images, and estimated brain age in a held-out test set. To investigate regional specificity, we extracted cortical and subcortical volumes using FreeSurfer, and ran hierarchical clustering to group regional volumes based on covariance. Leukocyte telomere length (LTL) derived from DNA was used as a marker of cellular ageing. We employed linear regression models to assess relationships between number of children, brain age, regional brain volumes, and LTL, and included interaction terms to probe sex differences in associations. Lastly, we used the brain measures and LTL as features in binary classification models, to determine if markers of brain and cellular ageing could predict parental status. The results showed associations between a greater number of children born/fathered and younger brain age in both females and males, with stronger effects observed in females. Volume-based analyses showed maternal effects in striatal and limbic regions, which were not evident in fathers. We found no evidence for associations between number of children and LTL. Classification of parental status showed an Area under the ROC Curve (AUC) of 0.57 for the brain age model, while the models using regional brain volumes and LTL as predictors showed AUCs of 0.52. Our findings align with previous population-based studies of middle- and older-aged parents, revealing subtle but significant associations between parental experience and neuroimaging-based surrogate markers of brain health. The findings further corroborate results from longitudinal cohort studies following parents across pregnancy and postpartum, potentially indicating that the parenthood transition is associated with long-term influences on brain health.

439 Optimal Targets, Connectivity, and Tissue Integrity for Deep Brain Stimulation in Patients With Disorders of Consciousness

INTRODUCTION: Disorders of consciousness (DOC) are characterized by alterations in arousal and/or awareness resulting from brain injuries. Deep brain stimulation (DBS) is an emerging treatment to restore arousal/awareness in DOC. However, little is known about optimal targets and whether outcomes depend on brain connectivity, tissue integrity, or reorganization potential. METHODS: Retrospective analysis of 38 patients with DOC who underwent unilateral DBS targeting thalamic centromedian nucleus (ages = 12-65 years). DOC resulted from anoxic (n = 26) or traumatic (n = 12) injuries. Patients were classified as ‘responders’ or ‘non-responders’ using Coma/Near Coma and Coma Recovery Scales. Volumes of tissue activated (VTAs) assessed DBS locations associated with favorable response. Correlations were also performed with age, regional brain volumes from pre-operative MRI, and structural connectivity calculated from patients’ VTAs using normative diffusion MRI. RESULTS: 8/38 patients were responders and 24/38 non-responders; outcomes are pending in 6/38 patients due to <3 months follow-up. Favorable response was associated with younger age (median age = 19 years in responders, 42 years in non-responders) and greater volumes of whole-brain grey matter and subcortical regions including putamen, pallidum, caudate, and cerebellum. Responders also tended to have deeper and more medial implantations, with VTAs engaging parafascicular nucleus, reticular nucleus, and peri-midbrain red nucleus. In responders, VTA connectivity was higher with superior frontal gyrus, caudate, pallidum, and cerebellum, and lower with sensorimotor and occipital cortex. CONCLUSIONS: Efficacious DBS for DOC is linked to younger age, greater preservation of whole-brain grey-matter, greater volumes of and connectivity with select subcortical areas (pallidum, caudate, cerebellum), stronger connectivity with superior frontal gyrus, and stimulation of locations inferomedial to the centromedian nucleus. Findings may assist with optimizing patient selection, DBS targeting, and post-implantation programming.

Association between mammillary body atrophy and memory impairment in retired athletes with a history of repetitive mild traumatic brain injury

Cognitive dysfunction, especially memory impairment, is a typical clinical feature of long-term symptoms caused by repetitive mild traumatic brain injury (rmTBI). The current study aims to investigate the relationship between regional brain atrophy and cognitive impairments in retired athletes with a long history of rmTBI. Overall, 27 retired athletes with a history of rmTBI (18 boxers, 3 kickboxers, 2 wrestlers, and 4 others; rmTBI group) and 23 age/sex-matched healthy participants (control group) were enrolled. MPRAGE on 3 T MRI was acquired and segmented. The TBV and TBV–adjusted regional brain volumes were compared between groups, and the relationship between the neuropsychological test scores and the regional brain volumes were evaluated. Total brain volume (TBV) and regional brain volumes of the mammillary bodies (MBs), hippocampi, amygdalae, thalami, caudate nuclei, and corpus callosum (CC) were estimated using the SPM12 and ITK–SNAP tools. In the rmTBI group, the regional brain volume/TBV ratio (rmTBI vs. control group, Mann–Whitney U test, p < 0.05) underwent partial correlation analysis, adjusting for age and sex, to assess its connection with neuropsychological test results. Compared with the control group, the rmTBI group showed significantly lower the MBs volume/TBV ratio (0.13 ± 0.05 vs. 0.19 ± 0.03 × 10−3, p < 0.001). The MBs volume/TBV ratio correlated with visual memory, as assessed, respectively, by the Rey–Osterrieth Complex Figure test delayed recall (ρ = 0.62, p < 0.001). In conclusion, retired athletes with rmTBI have MB atrophy, potentially contributing to memory impairment linked to the Papez circuit disconnection.

Oligodendrocyte progenitor cells' fate after neonatal asphyxia-Puzzling implications for the development of hypoxic-ischemic encephalopathy.

Premature birth or complications during labor can cause temporary disruption of cerebral blood flow, often followed by long-term disturbances in brain development called hypoxic-ischemic (HI) encephalopathy. Diffuse damage to the white matter is the most frequently detected pathology in this condition. We hypothesized that oligodendrocyte progenitor cell (OPC) differentiation disturbed by mild neonatal asphyxia may affect the viability, maturation, and physiological functioning of oligodendrocytes. To address this issue, we studied the effect of temporal HI in the in vivo model in P7 rats with magnetic resonance imaging (MRI), microscopy techniques and biochemical analyses. Moreover, we recreated the injury in vitro performing the procedure of oxygen-glucose deprivation on rat neonatal OPCs to determine its effect on cell viability, proliferation, and differentiation. In the in vivo model, MRI evaluation revealed changes in the volume of different brain regions, as well as changes in the directional diffusivity of water in brain tissue that may suggest pathological changes to myelinated neuronal fibers. Hypomyelination was observed in the cortex, striatum, and CA3 region of the hippocampus. Severe changes to myelin ultrastructure were observed, including delamination of myelin sheets. Interestingly, shortly after the injury, an increase in oligodendrocyte proliferation was observed, followed by an overproduction of myelin proteins 4 weeks after HI. Results verified with the in vitro model indicate, that in the first days after damage, OPCs do not show reduced viability, intensively proliferate, and overexpress myelin proteins and oligodendrocyte-specific transcription factors. In conclusion, despite the increase in oligodendrocyte proliferation and myelin protein expression after HI, the production of functional myelin sheaths in brain tissue is impaired. Presented study provides a detailed description of oligodendrocyte pathophysiology developed in an effect of HI injury, resulting in an altered CNS myelination. The described models may serve as useful tools for searching and testing effective of effective myelination-supporting therapies for HI injuries.

Changes in Brain Structure and Function in a Multisport Cohort of Retired Female and Male Athletes, Many Years after Suffering a Concussion: Implications for Neuroplasticity and Neurodegenerative Disease Pathogenesis.

Cumulative effects of traumatic brain injury is of increasing concern, especially with respect to its role in the etiology and pathogenesis of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Compare regional brain volume and connectivity between athletes with a history of concussion and controls. We evaluated whole-brain volumetric effects with Bayesian regression models and functional connectivity with network-based statistics, in 125 retired athletes (a mean of 11 reported concussions) and 36 matched controls. Brain regions significantly lower in volume in the concussed group included the middle frontal gyrus, hippocampus, supramarginal gyrus, temporal pole, and inferior frontal gyrus. Conversely, brain regions significantly larger included the hippocampal and collateral sulcus, middle occipital gyrus, medial orbital gyrus, caudate nucleus, lateral orbital gyrus, and medial postcentral gyrus. Functional connectivity analyses revealed increased edge strength, most marked in motor domains. Numerous edges of this network strengthened in athletes were significantly weakened with concussion. Aligned to meta-analytic neuroimaging data, the observed changes suggest functional enhancement within the motor, sensory, coordination, balance, and visual processing domains in athletes, attenuated by concussive head injury with a negative impact on memory and language. These findings suggest that engagement in sport may benefit the brain across numerous domains, but also highlights the potentially damaging effects of concussive head injury. Future studies with longitudinal cohorts including autopsy examination are needed to determine whether the latter reflects tissue loss from brain shearing, or the onset of a progressive Alzheimer's disease like proteinopathy.

Association Between Serum NT-proBNP and Gray Matter Atrophy Patterns in an Older Japanese Population: The Hisayama Study.

Several population-based studies have reported that higher serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are associated with brain morphological changes. However, no population-based studies have examined the relationship between serum NT-proBNP and various regional brain volumes in detail. We here analyzed the brain MRI data of 1201 community-dwelling Japanese aged ≥65 years. Regional gray matter volumes (GMV) and intracranial volume (ICV) were estimated by applying voxel-based morphometry (VBM) methods. The associations of serum NT-proBNP with regional GMV/ICV were examined by analysis of covariance. The regional gray matter atrophy patterns associated with elevated serum NT-proBNP levels were investigated using VBM without a priori regions of interest. The multivariable-adjusted means of the frontal, temporal, hippocampal, parahippocampal, and entorhinal GMV/ICV decreased significantly with elevated serum NT-proBNP levels (all p for trend and q values of false discovery rate correction < .05). In VBM, elevated serum NT-proBNP levels were correlated with atrophy of the bilateral hippocampi, bilateral amygdalas, bilateral parahippocampal gyri, bilateral entorhinal areas, bilateral fusiform gyri, left middle temporal gyrus, left inferior temporal gyrus, right central operculum, right posterior orbital gyrus, bilateral middle frontal gyri, anterior cingulate gyrus and bilateral medial frontal cortices. In a sensitivity analysis excluding 254 participants with mild cognitive impairment or dementia, serum NT-proBNP levels were correlated with atrophy of the bilateral hippocampi, bilateral amygdalas, bilateral parahippocampal gyri, bilateral fusiform gyri, and left middle frontal gyrus. Our data suggest that elevated serum NT-proBNP levels are associated with gray matter atrophy in brain regions that play an important role in cognitive function.

Psychosis in Alzheimer’s disease is associated with specific changes in brain MRI volume, cognition and neuropathology

Psychosis in Alzheimer’s Disease (AD) is prevalent and indicates poor prognosis. However, the neuropathological, cognitive and brain atrophy patterns underlying these symptoms have not been fully elucidated. In this study, we evaluated 178 patients with AD neuropathological change (ADNC) and ante-mortem volumetric brain magnetic resonance imaging (MRI). Presence of psychosis was determined using the Neuropsychiatric Inventory Questionnaire. Clinical Dementia Rating Sum-of-boxes (CDR-SB) was longitudinally compared between groups with a follow-up of 3000 days using mixed-effects multiple linear regression. Neuropsychological tests closest to the time of MRI and brain regional volumes were cross-sectionally compared. Psychosis was associated with lower age of death, higher longitudinal CDR-SB scores, multi-domain cognitive deficits, higher neuritic plaque severity, Braak stage, Lewy Body pathology (LB) and right temporal lobe regional atrophy. Division according to the presence of LB showed differential patterns of AD-typical pathology, cognitive deficits and regional atrophy. In conclusion, psychosis in ADNC with and without LB has clinical value and associates with subgroup patterns of neuropathology, cognition and regional atrophy.

Correlations between cognitive reserve, gray matter, and cerebrospinal fluid volume in healthy elders and mild cognitive impairment patients.

To explore the effect of cognitive reserve (CR) on brain volume and cerebrospinal fluid (CSF) in patients with mild cognitive impairment (MCI) and healthy elders (HE). 31 HE and 50 MCI patients were collected in this study to obtain structural MRI, cognitive function, and composite CR scores. Educational attainment, leisure time, and working activity ratings from two groups were used to generate cognitive reserve index questionnaire (CRIq) scores. The different volumes of brain regions and CSF were obtained using uAI research portal in both groups, which were taken as the regions of interest (ROI), the correlation analysis between ROIs and CRIq scores were conducted. The scores of CRIq, CRIq-leisure time, and CRIq-education in HE group were significantly higher than patients in MCI group, and the montreal cognitive assessment (MoCA) and minimum mental state examination (MMSE) scores were positively correlated with the CRIq, CRIq-education in both groups, and were positively correlated with CRIq-leisure time in MCI group. The scores of auditory verbal learning test (AVLT) and verbal fluency test (VFT) were also positively correlated with CRIq, CRIq-leisure time, and CRIq-education in MCI group, but the score of AVLT was only positively correlated with CRIq in HE group. Moreover, in MCI group, the volume of the right middle cingulate cortex and the right parahippocampal gyrus were negatively correlated with the CRIq, and the volume of CSF, peripheral CSF, and third ventricle were positively correlated with the CRIq-leisure time score. The result of mediation analysis suggested that right parahippocampal gryus mediated the main effect of the relationship between CRIq and MoCA score in MCI group. People with higher CR show better levels of cognitive function, and MCI patients with higher CR showed more severe volume atrophy of the right middle cingulate cortex and the right parahippocampal gyrus, but more CSF at a given level of global cognition.

Characterization of brain development with neuroimaging in a female mouse model of chemotherapy treatment of acute lymphoblastic leukemia.

Survivors of pediatric acute lymphoblastic leukemia (ALL) exhibit abnormal neurocognitive outcomes that are possibly due to exposures to neurotoxic chemotherapy agents. This study aimed to determine the feasibility of characterizing long-term neuroanatomical changes with in vivo neuroimaging in a preclinical model of treatment for ALL. Female mice (C57BL/6) were randomly assigned to a saline control group (n=10) or a treatment group (n=10) that received intrathecal methotrexate and oral dexamethasone (IT-MTX + DEX). Mice were subsequently scanned three times on a 7T MRI at ages 3, 6, and 12 months (T1, T2, and T3, respectively), which corresponds with human age-equivalents spanning early to late adulthood. Regional brain volumes were automatically segmented, and volume change between timepoints (i.e., T1 to T2; and T2 to T3) were compared between groups (i.e., saline vs. IT-MTX + DEX). Five mice in the IT-MTX + DEX group, and seven mice in the saline group completed all three scans. Between T1 and T2, volumetric change was significantly different between groups in total gray matter [estimate =2.06, 95% confidence interval (CI): 0.27-3.84], the cerebrum (estimate =1.62, 95% CI: 0.14-3.09), claustrum (estimate =0.06, 95% CI: 0.02-0.09), amygdala (estimate =0.16, 95% CI: 0.03-0.29), and striatum (estimate =0.18, 95% CI: 0.01-0.35), with the IT-MTX + DEX group exhibiting a more robust increase in volume than the saline-treated group. Between T2 and T3, group differences in structural brain development were evident for total white matter (estimate =-0.14, 95% CI: -0.27 to -0.01), and the corpus callosum (estimate =-0.09, 95% CI: -0.19 to 0.00) and amygdala (estimate =-0.05, 95% CI: -0.10 to 0.00). In contrast to the rapid brain growth observed earlier in development (i.e., T1 to T2), the IT-MTX + DEX group exhibited an attenuated increase in volume relative to the saline-treated group between T2 and T3. The results demonstrate feasibility of modeling pediatric ALL treatment in a preclinical model and highlight the potential of using preclinical neuroimaging models to gain insight into brain development throughout survivorship.

Linking sarcopenia, brain structure and cognitive performance: a large-scale UK Biobank study.

Sarcopenia refers to age-related loss of muscle mass and function and is related to impaired somatic and brain health, including cognitive decline and Alzheimer's disease. However, the relationships between sarcopenia, brain structure and cognition are poorly understood. Here, we investigate the associations between sarcopenic traits, brain structure and cognitive performance. We included 33 709 UK Biobank participants (54.2% female; age range 44-82 years) with structural and diffusion magnetic resonance imaging, thigh muscle fat infiltration (n = 30 561) from whole-body magnetic resonance imaging (muscle quality indicator) and general cognitive performance as indicated by the first principal component of a principal component analysis across multiple cognitive tests (n = 22 530). Of these, 1703 participants qualified for probable sarcopenia based on low handgrip strength, and we assigned the remaining 32 006 participants to the non-sarcopenia group. We used multiple linear regression to test how sarcopenic traits (probable sarcopenia versus non-sarcopenia and percentage of thigh muscle fat infiltration) relate to cognitive performance and brain structure (cortical thickness and area, white matter fractional anisotropy and deep and lower brain volumes). Next, we used structural equation modelling to test whether brain structure mediated the association between sarcopenic and cognitive traits. We adjusted all statistical analyses for confounders. We show that sarcopenic traits (probable sarcopenia versus non-sarcopenia and muscle fat infiltration) are significantly associated with lower cognitive performance and various brain magnetic resonance imaging measures. In probable sarcopenia, for the included brain regions, we observed widespread significant lower white matter fractional anisotropy (77.1% of tracts), predominantly lower regional brain volumes (61.3% of volumes) and thinner cortical thickness (37.9% of parcellations), with |r| effect sizes in (0.02, 0.06) and P-values in (0.0002, 4.2e-29). In contrast, we observed significant associations between higher muscle fat infiltration and widespread thinner cortical thickness (76.5% of parcellations), lower white matter fractional anisotropy (62.5% of tracts) and predominantly lower brain volumes (35.5% of volumes), with |r| effect sizes in (0.02, 0.07) and P-values in (0.0002, 1.9e-31). The regions showing the most significant effect sizes across the cortex, white matter and volumes were of the sensorimotor system. Structural equation modelling analysis revealed that sensorimotor brain regions mediate the link between sarcopenic and cognitive traits [probable sarcopenia: P-values in (0.0001, 1.0e-11); muscle fat infiltration: P-values in (7.7e-05, 1.7e-12)]. Our findings show significant associations between sarcopenic traits, brain structure and cognitive performance in a middle-aged and older adult population. Mediation analyses suggest that regional brain structure mediates the association between sarcopenic and cognitive traits, with potential implications for dementia development and prevention.

Comparison of approaches to control for intracranial volume in research on the association of brain volumes with cognitive outcomes.

Most neuroimaging studies linking regional brain volumes with cognition correct for total intracranial volume (ICV), but methods used for this correction differ across studies. It is unknown whether different ICV correction methods yield consistent results. Using a brain-wide association approach in the MRI substudy of UK Biobank (N = 41,964; mean age = 64.5 years), we used regression models to estimate the associations of 58 regional brain volumetric measures with eight cognitive outcomes, comparing no correction and four ICV correction approaches. Approaches evaluated included: no correction; dividing regional volumes by ICV (proportional approach); including ICV as a covariate in the regression (adjustment approach); and regressing the regional volumes against ICV in different normative samples and using calculated residuals to determine associations (residual approach). We used Spearman-rank correlations and two consistency measures to quantify the extent to which associations were inconsistent across ICV correction approaches for each possible brain region and cognitive outcome pair across 2320 regression models. When the association between brain volume and cognitive performance was close to null, all approaches produced similar estimates close to the null. When associations between a regional volume and cognitive test were not null, the adjustment and residual approaches typically produced similar estimates, but these estimates were inconsistent with results from the crude and proportional approaches. For example, when using the crude approach, an increase of 0.114 (95% confidence interval [CI]: 0.103-0.125) in fluid intelligence was associated with each unit increase in hippocampal volume. However, when using the adjustment approach, the increase was 0.055 (95% CI: 0.043-0.068), while the proportional approach showed a decrease of -0.025 (95% CI: -0.035 to -0.014). Different commonly used methods to correct for ICV yielded inconsistent results. The proportional method diverges notably from other methods and results were sometimes biologically implausible. A simple regression adjustment for ICV produced biologically plausible associations.

Placental Pathology Contributes to Impaired Volumetric Brain Development in Neonates With Congenital Heart Disease.

Neonates with congenital heart disease are at risk for impaired brain development in utero, predisposing children to postnatal brain injury and adverse long-term neurodevelopmental outcomes. Given the vital role of the placenta in fetal growth, we assessed the incidence of placental pathology in fetal congenital heart disease and explored its association with total and regional brain volumes, gyrification, and brain injury after birth. Placentas from 96 term singleton pregnancies with severe fetal congenital heart disease were prospectively analyzed for macroscopic and microscopic pathology. We applied a placental pathology severity score to relate placental abnormalities to neurological outcome. Postnatal, presurgical magnetic resonance imaging was used to analyze brain volumes, gyrification, and brain injuries. Placental analyses revealed the following abnormalities: maternal vascular malperfusion lesions in 46%, nucleated red blood cells in 37%, chronic inflammatory lesions in 35%, delayed maturation in 30%, and placental weight below the 10th percentile in 28%. Severity of placental pathology was negatively correlated with cortical gray matter, deep gray matter, brainstem, cerebellar, and total brain volumes (r=-0.25 to -0.31, all P<0.05). When correcting for postmenstrual age at magnetic resonance imaging in linear regression, this association remained significant for cortical gray matter, cerebellar, and total brain volume (adjusted R2=0.25-0.47, all P<0.05). Placental pathology occurs frequently in neonates with severe congenital heart disease and may contribute to impaired brain development, indicated by the association between placental pathology severity and reductions in postnatal cortical, cerebellar, and total brain volumes.

Bridging the gap: improving correspondence between low-field and high-field magnetic resonance images in young people.

Portable low-field-strength magnetic resonance imaging (MRI) systems represent a promising alternative to traditional high-field-strength systems with the potential to make MR technology available at scale in low-resource settings. However, lower image quality and resolution may limit the research and clinical potential of these devices. We tested two super-resolution methods to enhance image quality in a low-field MR system and compared their correspondence with images acquired from a high-field system in a sample of young people. T1- and T2-weighted structural MR images were obtained from a low-field (64mT) Hyperfine and high-field (3T) Siemens system in N = 70 individuals (mean age = 20.39 years, range 9-26 years). We tested two super-resolution approaches to improve image correspondence between images acquired at high- and low-field: (1) processing via a convolutional neural network ('SynthSR'), and (2) multi-orientation image averaging. We extracted brain region volumes, cortical thickness, and cortical surface area estimates. We used Pearson correlations to test the correspondence between these measures, and Steiger Z tests to compare the difference in correspondence between standard imaging and super-resolution approaches. Single pairs of T1- and T2-weighted images acquired at low field showed high correspondence to high-field-strength images for estimates of total intracranial volume, surface area cortical volume, subcortical volume, and total brain volume (r range = 0.60-0.88). Correspondence was lower for cerebral white matter volume (r = 0.32, p = 0.007, q = 0.009) and non-significant for mean cortical thickness (r = -0.05, p = 0.664, q = 0.664). Processing images with SynthSR yielded significant improvements in correspondence for total brain volume, white matter volume, total surface area, subcortical volume, cortical volume, and total intracranial volume (r range = 0.85-0.97), with the exception of global mean cortical thickness (r = 0.14). An alternative multi-orientation image averaging approach improved correspondence for cerebral white matter and total brain volume. Processing with SynthSR also significantly improved correspondence across widespread regions for estimates of cortical volume, surface area and subcortical volume, as well as within isolated prefrontal and temporal regions for estimates of cortical thickness. Applying super-resolution approaches to low-field imaging improves regional brain volume and surface area accuracy in young people. Finer-scale brain measurements, such as cortical thickness, remain challenging with the limited resolution of low-field systems.

Clinical and neuroimaging predictors of benzodiazepine response in catatonia: A machine learning approach

Catatonia is a well characterized psychomotor syndrome combining motor, behavioural and neurovegetative signs. Benzodiazepines are the first-choice treatment, effective in 70 % of cases. Currently, the factors associated with benzodiazepine resistance remain unknown. We aimed to develop machine learning models using clinical and neuroimaging data to predict benzodiazepine response in catatonic patients. This study examined a cohort of catatonic patients who underwent standardized clinical evaluation, 3 T brain MRI, and benzodiazepine trial. Based on clinical response, patients were classified as benzodiazepine responders or non-responders. Cortical thickness and regional brain volumes were measured. Two machine learning models (linear model and gradient boosting tree model) were developed to identify predictors of treatment response using clinical, demographic, and neuroimaging data. The cohort included 65 catatonic patients, comprising 30 benzodiazepine responders and 35 non-responders. Using clinical data alone, the linear model achieved 63% precision, 51% recall, a specificity of 61%, and 58% AUC, while the gradient boosting tree (GBT) model attained 46% precision, 60% recall, a specificity of 62% and 64% AUC. Incorporating neuroimaging data improved model performance, with the linear model achieving 66% precision, 57% recall, a specificity of 67%, and 70% AUC, and the GBT model attaining 50% precision, 50% recall, a specificity of 62% and 70% AUC. The integration of imaging data with demographic and clinical information significantly enhanced the predictive performance of the models. The duration of the catatonic syndrome, along with the presence of mitgehen (passive obedience) and immobility/stupor, and the volume of the right medial orbito-frontal cortex emerged as important factors in predicting non-response to benzodiazepines.

Higher cerebral blood flow on four-dimensional flow magnetic resonance imaging in young women.

We investigated the reduction in regional brain volume and cerebral blood flow (CBF) with aging and explored potential sex differences in healthy brains. Three-dimensional (3D) T1-weighted magnetic resonance imaging (MRI), time-of-flight magnetic resonance angiography, and four-dimensional (4D) flow MRI were performed on 129 healthy volunteers aged 22-92 years. The brains of healthy volunteers were segmented into 21 subregions using 3D T1-weighted MRI and CBFs in 16 major intracranial arteries were measured using 4D flow MRI. The cortical gray matter volume decreased linearly with aging, whereas the cerebral white matter volume increased until the 40s and then decreased, and the subcortical gray matter volume changed little with aging. The cortical gray matter volume was significantly associated with the total CBF of the major intracranial arteries distal to the circle of Willis; however, the cerebral white matter and subcortical gray matter volumes were not. Generally, women have higher total CBF than men, particularly in their 40s and younger, despite the smaller intracranial volume and smaller diameters of intracranial arteries than men. This may contribute to the higher incidence of subarachnoid hemorrhage due to cerebral aneurysms and migraine in women.

Investigating the synergistic effects of hormone replacement therapy, apolipoprotein E and age on brain health in the UK Biobank.

Global prevalence of Alzheimer's Disease has a strong sex bias, with women representing approximately two-thirds of the patients. Yet, the role of sex-specific risk factors during midlife, including hormone replacement therapy (HRT) and their interaction with other major risk factors for Alzheimer's Disease, such as apolipoprotein E (APOE)-e4 genotype and age, on brain health remains unclear. We investigated the relationship between HRT (i.e., use, age of initiation and duration of use) and brain health (i.e., cognition and regional brain volumes). We then consider the multiplicative effects of HRT and APOE status (i.e., e2/e2, e2/e3, e3/e3, e3/e4 and e4/e4) via a two-way interaction and subsequently age of participants via a three-way interaction. Women from the UK Biobank with no self-reported neurological conditions were included (N = 207,595 women, mean age = 56.25 years, standard deviation = 8.01 years). Generalised linear regression models were computed to quantify the cross-sectional association between HRT and brain health, while controlling for APOE status, age, time since attending centre for completing brain health measure, surgical menopause status, smoking history, body mass index, education, physical activity, alcohol use, ethnicity, socioeconomic status, vascular/heart problems and diabetes diagnosed by doctor. Analyses of structural brain regions further controlled for scanner site. All brain volumes were normalised for head size. Two-way interactions between HRT and APOE status were modelled, in addition to three-way interactions including age. Results showed that women with the e4/e4 genotype who have used HRT had 1.82% lower hippocampal, 2.4% lower parahippocampal and 1.24% lower thalamus volumes than those with the e3/e3 genotype who had never used HRT. However, this interaction was not detected for measures of cognition.No clinically meaningful three-way interaction between APOE, HRT and age was detected when interpreted relative to the scales of the cognitive measures used and normative models of ageing for brain volumes in this sample. Differences in hippocampal volume between women with the e4/e4 genotype who have used HRT and those with the e3/e3 genotype who had never used HRT are equivalent to approximately 1-2 years of hippocampal atrophy observed in typical health ageing trajectories in midlife (i.e., 0.98%-1.41% per year). Effect sizes were consistent within APOE e4/e4 group post hoc sensitivity analyses, suggesting observed effects were not solely driven by APOE status and may, in part, be attributed to HRT use. Although, the design of this study means we cannot exclude the possibility that women who have used HRT may have a predisposition for poorer brain health.

Correlation of Disease Severity, Proinflammatory Cytokines, and Reduced Brain Gray Matter Volumes in Patients with Atopic Dermatitis.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease. However, few studies have investigated brain changes associated with chronic inflammation. We hypothesized that chronic inflammation might be related to brain structural alterations in patients with AD. Objectives: To investigate the association between disease severity (Eczema Area and Severity Index [EASI]), proinflammatory cytokines, and differences in brain gray matter (GM) volume in patients with AD. Methods: Nineteen patients with AD and 19 age- and sex-matched healthy subjects were enrolled. All participants underwent clinical assessment and brain magnetic resonance imaging. Voxel-based morphometry was performed to analyze GM volume differences. Results: Patients with AD exhibited significantly decreased GM volume in many brain regions, such as bilateral precentral gyrus, right frontal pole, and right middle temporal gyrus (P < 0.001), compared with healthy subjects. Notably, in patients with AD, the GM volume in right middle temporal gyrus was negatively associated with both EASI score and proinflammatory cytokines (sIL-2R [soluble interleukin 2 receptor] and TNF-α receptor-1), whereas the GM volume in left precentral gyrus was negatively associated with both EASI score and proinflammatory cytokines (sIL-2R and CRP). Conclusion: Patients with AD demonstrated significant brain GM volume reduction in many brain regions, which is related to disease severity and proinflammatory cytokines.

Depression, anxiety and brain volume after hearing loss and tinnitus: cohort study in the UK Biobank.

Hearing loss and tinnitus have been proposed as potential indicators of impaired mental health and brain morphological changes. To assess the associations of hearing loss and tinnitus with the risk of depression and anxiety and with brain volume. We conducted a community-based cohort study including 129 610 participants aged 40-69 years at recruitment to the UK Biobank with a follow-up period during 2006-2021 to estimate the risk of depression and anxiety after detection of hearing loss and reported tinnitus. We also assessed the associations of hearing loss and tinnitus with brain volume in a subsample with available brain magnetic resonance imaging data (N = 5222). We observed an increased risk of depression among individuals with hearing loss (hazard ratio [HR] 1.14, 95% CI 1.03-1.26), tinnitus (HR 1.30, 95% CI 1.21-1.41) or both (HR 1.32, 95% CI 1.15-1.52), compared with individuals with neither hearing loss nor tinnitus. Similar results were noted for anxiety (HR 1.18, 95% CI 1.07-1.30 for hearing loss; HR 1.32, 95% CI 1.22-1.43 for tinnitus; and HR 1.48, 95% CI 1.30-1.68 for both). Hearing loss was associated with decreased overall brain volume as well as decreased volume of different brain regions. The latter associations disappeared after adjustment for whole intracranial volume. Tinnitus was associated with greater left accumbens and right occipital pole volume after adjustment for the whole intracranial volume. Individuals with tinnitus are at increased risk of depression and anxiety. Hearing loss, on the other hand, is associated with both mood disorders and altered brain morphology.

Automated magnetic resonance imaging quantification of cerebral parenchymal and ventricular volume following subarachnoid hemorrhage: associations with cognition

This study aims to investigate cerebral parenchymal and ventricular volume changes after subarachnoid hemorrhage (SAH) and their potential association with cognitive impairment. 17 patients with aneurysmal SAH (aSAH) and 21 patients with angiographically negative SAH (anSAH) without visually apparent parenchymal loss on conventional magnetic resonance imaging (MRI) were included, along with 76 healthy controls. Volumetric analyses were performed using an automated clinical segmentation and quantification tool. Measurements were compared to on-board normative reference database (n = 1923) adjusted for age, sex, and intracranial volume. Cognition was assessed with tests for psychomotor speed, attentional control, (working) memory, executive functioning, and social cognition. All measurements took place 5 months after SAH. Lower cerebral parenchymal volumes were most pronounced in the frontal lobe (aSAH: n = 6 [35%], anSAH n = 7 [33%]), while higher volumes were most substantial in the lateral ventricle (aSAH: n = 5 [29%], anSAH n = 9 [43%]). No significant differences in regional brain volumes were observed between both SAH groups. Patients with lower frontal lobe volume exhibited significantly lower scores in psychomotor speed (U = 81, p = 0.02) and attentional control (t = 2.86, p = 0.004). Additionally, higher lateral ventricle volume was associated with poorer memory (t = 3.06, p = 0.002). Regional brain volume changes in patients with SAH without visible parenchymal abnormalities on MRI can still be quantified using a fully automatic clinical-grade tool, exposing changes which may contribute to cognitive impairment. Therefore, it is important to provide neuropsychological assessment for both SAH groups, also including those with clinically mild symptoms.