The maternal brain: Region‐specific patterns of brain aging are traceable decades after childbirth

Pregnancy involves maternal brain adaptations, but little is known about how parity influences women's brain aging trajectories later in life. In this study, we replicated previous findings showing less apparent brain aging in women with a history of childbirths, and identified regional brain aging patterns linked to parity in 19,787 middle‐ and older‐aged women. Using novel applications of brain‐age prediction methods, we found that a higher number of previous childbirths were linked to less apparent brain aging in striatal and limbic regions. The strongest effect was found in the accumbens—a key region in the mesolimbic reward system, which plays an important role in maternal behavior. While only prospective longitudinal studies would be conclusive, our findings indicate that subcortical brain modulations during pregnancy and postpartum may be traceable decades after childbirth

Prediction of brain age and cognitive age: Quantifying brain and cognitive maintenance in aging

The concept of brain maintenance refers to the preservation of brain integrity in older age, while cognitive reserve refers to the capacity to maintain cognition in the presence of neurodegeneration or aging‐related brain changes. While both mechanisms are thought to contribute to individual differences in cognitive function among older adults, there is currently no “gold standard” for measuring these constructs. Using machine‐learning methods, we estimated brain and cognitive age based on deviations from normative aging patterns in the Whitehall II MRI substudy cohort (N = 537, age range = 60.34–82.76), and tested the degree of correspondence between these constructs, as well as their associations with premorbid IQ, education, and lifestyle trajectories. In line with established literature highlighting IQ as a proxy for cognitive reserve, higher premorbid IQ was linked to lower cognitive age independent of brain age. No strong evidence was found for associations between brain or cognitive age and lifestyle trajectories from midlife to late life based on latent class growth analyses. However, post hoc analyses revealed a relationship between cumulative lifestyle measures and brain age independent of cognitive age. In conclusion, we present a novel approach to characterizing brain and cognitive maintenance in aging, which may be useful for future studies seeking to identify factors that contribute to brain preservation and cognitive reserve mechanisms in older age

Detection of Epileptogenic Cortical Malformations with Surface-Based MRI Morphometry

Magnetic resonance imaging has revolutionized the detection of structural abnormalities in patients with epilepsy. However, many focal abnormalities remain undetected in routine visual inspection. Here we use an automated, surface-based method for quantifying morphometric features related to epileptogenic cortical malformations to detect abnormal cortical thickness and blurred gray-white matter boundaries. Using MRI morphometry at 3T with surface-based spherical averaging techniques that precisely align anatomical structures between individual brains, we compared single patients with known lesions to a large normal control group to detect clusters of abnormal cortical thickness, gray-white matter contrast, local gyrification, sulcal depth, jacobian distance and curvature. To assess the effects of threshold and smoothing on detection sensitivity and specificity, we systematically varied these parameters with different thresholds and smoothing levels. To test the effectiveness of the technique to detect lesions of epileptogenic character, we compared the detected structural abnormalities to expert-tracings, intracranial EEG, pathology and surgical outcome in a homogeneous patient sample. With optimal parameters and by combining thickness and GWC, the surface-based detection method identified 92% of cortical lesions (sensitivity) with few false positives (96% specificity), successfully discriminating patients from controls 94% of the time. The detected structural abnormalities were related to the seizure onset zones, abnormal histology and positive outcome in all surgical patients. However, the method failed to adequately describe lesion extent in most cases. Automated surface-based MRI morphometry, if used with optimized parameters, may be a valuable additional clinical tool to improve the detection of subtle or previously occult malformations and therefore could improve identification of patients with intractable focal epilepsy who may benefit from surgery

Adiposity is Associated with Regional Cortical Thinning

BACKGROUND: Although obesity is associated with structural changes in brain grey matter, findings have been inconsistent and the precise nature of these changes is unclear. Inconsistencies may partly be due to the use of different volumetric morphometry methods, and the inclusion of participants with comorbidities that exert independent effects on brain structure. The latter concern is particularly critical when sample sizes are modest. The purpose of the current study was to examine the relationship between cortical grey matter and body mass index (BMI), in healthy participants, excluding confounding comorbidities and using a large sample size. SUBJECTS: A total of 202 self-reported healthy volunteers were studied using surface-based morphometry, which permits the measurement of cortical thickness, surface area and cortical folding, independent of each other. RESULTS: Although increasing BMI was not associated with global cortical changes, a more precise, region-based analysis revealed significant thinning of the cortex in two areas: left lateral occipital cortex (LOC) and right ventromedial prefrontal cortex (vmPFC). An analogous region-based analysis failed to find an association between BMI and regional surface area or folding. Participants' age was also found to be negatively associated with cortical thickness of several brain regions; however, there was no overlap between the age- and BMI-related effects on cortical thinning. CONCLUSIONS: Our data suggest that the key effect of increasing BMI on cortical grey matter is a focal thinning in the left LOC and right vmPFC. Consistent implications of the latter region in reward valuation, and goal control of decision and action suggest a possible shift in these processes with increasing BMI.We thank all the participants and the staff of the Wolfson Brain Imaging Centre. This work was supported by the Bernard Wolfe Health Neuroscience Fund (NM, HZ, ISF, PCF), the Wellcome Trust (RGAG/144 to N.M, RGAG/188 to ISF, RNAG/259 to PCF) and the Medical Research Council (G0701497 to KDE).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ijo.2016.42

Smaller spared subcortical nuclei are associated with worse post-stroke sensorimotor outcomes in 28 cohorts worldwide

Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Deep grey matter structures play a critical role in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behaviour at different timepoints after stroke. We pooled high-resolution T1-weighted MRI brain scans and behavioural data in 828 individuals with unilateral stroke from 28 cohorts worldwide. Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behaviour to non-lesioned subcortical volumes (Bonferroni-corrected, P < 0.004). We tested subacute (≤90 days) and chronic (≥180 days) stroke subgroups separately, with exploratory analyses in early stroke (≤21 days) and across all time. Sub-analyses in chronic stroke were also performed based on class of sensorimotor deficits (impairment, activity limitations) and side of lesioned hemisphere. Worse sensorimotor behaviour was associated with a smaller ipsilesional thalamic volume in both early (n = 179; d = 0.68) and subacute (n = 274, d = 0.46) stroke. In chronic stroke (n = 404), worse sensorimotor behaviour was associated with smaller ipsilesional putamen (d = 0.52) and nucleus accumbens (d = 0.39) volumes, and a larger ipsilesional lateral ventricle (d = -0.42). Worse chronic sensorimotor impairment specifically (measured by the Fugl-Meyer Assessment; n = 256) was associated with smaller ipsilesional putamen (d = 0.72) and larger lateral ventricle (d = -0.41) volumes, while several measures of activity limitations (n = 116) showed no significant relationships. In the full cohort across all time (n = 828), sensorimotor behaviour was associated with the volumes of the ipsilesional nucleus accumbens (d = 0.23), putamen (d = 0.33), thalamus (d = 0.33) and lateral ventricle (d = -0.23). We demonstrate significant relationships between post-stroke sensorimotor behaviour and reduced volumes of deep grey matter structures that were spared by stroke, which differ by time and class of sensorimotor measure. These findings provide additional insight into how different cortico-thalamo-striatal circuits support post-stroke sensorimotor outcomes

Differential Development of Human Brain White Matter Tracts

Neuroscience is increasingly focusing on developmental factors related to human structural and functional connectivity. Unfortunately, to date, diffusion-based imaging approaches have only contributed modestly to these broad objectives, despite the promise of diffusion-based tractography. Here, we report a novel data-driven approach to detect similarities and differences among white matter tracts with respect to their developmental trajectories, using 64-direction diffusion tensor imaging. Specifically, using a cross-sectional sample comprising 144 healthy individuals (7 to 48 years old), we applied k-means cluster analysis to separate white matter voxels based on their age-related trajectories of fractional anisotropy. Optimal solutions included 5-, 9- and 14-clusters. Our results recapitulate well-established tracts (e.g., internal and external capsule, optic radiations, corpus callosum, cingulum bundle, cerebral peduncles) and subdivisions within tracts (e.g., corpus callosum, internal capsule). For all but one tract identified, age-related trajectories were curvilinear (i.e., inverted ‘U-shape’), with age-related increases during childhood and adolescence followed by decreases in middle adulthood. Identification of peaks in the trajectories suggests that age-related losses in fractional anisotropy occur as early as 23 years of age, with mean onset at 30 years of age. Our findings demonstrate that data-driven analytic techniques may be fruitfully applied to extant diffusion tensor imaging datasets in normative and neuropsychiatric samples

The Brain Matures with Stronger Functional Connectivity and Decreased Randomness of Its Network

We investigated the development of the brain's functional connectivity throughout the life span (ages 5 through 71 years) by measuring EEG activity in a large population-based sample. Connectivity was established with Synchronization Likelihood. Relative randomness of the connectivity patterns was established with Watts and Strogatz' (1998) graph parameters C (local clustering) and L (global path length) for alpha (∼10 Hz), beta (∼20 Hz), and theta (∼4 Hz) oscillation networks. From childhood to adolescence large increases in connectivity in alpha, theta and beta frequency bands were found that continued at a slower pace into adulthood (peaking at ∼50 yrs). Connectivity changes were accompanied by increases in L and C reflecting decreases in network randomness or increased order (peak levels reached at ∼18 yrs). Older age (55+) was associated with weakened connectivity. Semi-automatically segmented T1 weighted MRI images of 104 young adults revealed that connectivity was significantly correlated to cerebral white matter volume (alpha oscillations: r = 33, p<01; theta: r = 22, p<05), while path length was related to both white matter (alpha: max. r = 38, p<001) and gray matter (alpha: max. r = 36, p<001; theta: max. r = 36, p<001) volumes. In conclusion, EEG connectivity and graph theoretical network analysis may be used to trace structural and functional development of the brain

Frontally mediated inhibitory processing and white matter microstructure: age and alcoholism effects

RationaleThe NOGO P3 event-related potential is a sensitive marker of alcoholism, relates to EEG oscillation in the δ and θ frequency ranges, and reflects activation of an inhibitory processing network. Degradation of white matter tracts related to age or alcoholism should negatively affect the oscillatory activity within the network.ObjectiveThis study aims to evaluate the effect of alcoholism and age on δ and θ oscillations and the relationship between these oscillations and measures of white matter microstructural integrity.MethodsData from ten long-term alcoholics to 25 nonalcoholic controls were used to derive P3 from Fz, Cz, and Pz using a visual GO/NOGO protocol. Total power and across trial phase synchrony measures were calculated for δ and θ frequencies. DTI, 1.5 T, data formed the basis of quantitative fiber tracking in the left and right cingulate bundles and the genu and splenium of the corpus callosum. Fractional anisotropy and diffusivity (λL and λT) measures were calculated from each tract.ResultsNOGO P3 amplitude and δ power at Cz were smaller in alcoholics than controls. Lower δ total power was related to higher λT in the left and right cingulate bundles. GO P3 amplitude was lower and GO P3 latency was longer with advancing age, but none of the time-frequency analysis measures displayed significant age or diagnosis effects.ConclusionsThe relation of δ total power at CZ with λT in the cingulate bundles provides correlational evidence for a functional role of fronto-parietal white matter tracts in inhibitory processing

Lithium and GSK3-β promoter gene variants influence white matter microstructure in bipolar disorder

Lithium is the mainstay for the treatment of bipolar disorder (BD) and inhibits glycogen synthase kinase 3-β (GSK3-β). The less active GSK3-β promoter gene variants have been associated with less detrimental clinical features of BD. GSK3-β gene variants and lithium can influence brain gray matter structure in psychiatric conditions. Diffusion tensor imaging (DTI) measures of white matter (WM) integrity showed widespred disruption of WM structure in BD. In a sample of 70 patients affected by a major depressive episode in course of BD, we investigated the effect of ongoing long-term lithium treatment and GSK3-β promoter rs334558 polymorphism on WM microstructure, using DTI and tract-based spatial statistics with threshold-free cluster enhancement. We report that the less active GSK3-β rs334558*C gene-promoter variants, and the long-term administration of the GSK3-β inhibitor lithium, were associated with increases of DTI measures of axial diffusivity (AD) in several WM fiber tracts, including corpus callosum, forceps major, anterior and posterior cingulum bundle (bilaterally including its hippocampal part), left superior and inferior longitudinal fasciculus, left inferior fronto-occipital fasciculus, left posterior thalamic radiation, bilateral superior and posterior corona radiata, and bilateral corticospinal tract. AD reflects the integrity of axons and myelin sheaths. We suggest that GSK3-β inhibition and lithium could counteract the detrimental influences of BD on WM structure, with specific benefits resulting from effects on specific WM tracts contributing to the functional integrity of the brain and involving interhemispheric, limbic, and large frontal, parietal, and fronto-occipital connections