We present a brain development index (BDI) that concisely summarizes complex imaging patterns of structural brain maturation along a single dimension using a machine learning methodology. The brain was found to follow a remarkably consistent developmental trajectory in a sample of 621 subjects of ages 8-22 participating in the Philadelphia Neurodevelopmental Cohort, reflected by a cross-validated correlation coefficient between chronologic age and the BDI of r = 0.89. Critically, deviations from this trajectory related to cognitive performance. Specifically, subjects whose BDI was higher than their chronological age displayed significantly superior cognitive processing speed compared with subjects whose BDI was lower than their actual age. These results indicate that the multiparametric imaging patterns summarized by the BDI can accurately delineate trajectories of brain development and identify individuals with cognitive precocity or delay.

ObjectiveTo identify early changes in brain structure and function that are associated with cardiovascular risk factors (CVRF).DesignCross-sectional brain Magnetic Resonance I (MRI) study.SettingCommunity based cohort in three U.S. sites.ParticipantsA Caucasian and African-American sub-sample (n= 680; mean age 50.3 yrs) attending the 25 year follow-up exam of the Coronary Artery Risk Development in Young Adults Study.Primary and Secondary Outcomes3T brain MR images processed for quantitative estimates of: total brain (TBV) and abnormal white matter (AWM) volume; white matter fractional anisotropy (WM-FA); and gray matter cerebral blood flow (GM-CBF). Total intracranial volume is TBV plus cerebral spinal fluid (TICV). A Global Cognitive Function (GCF) score was derived from tests of speed, memory and executive function.ResultsAdjusting for TICV and demographic factors, current smoking was significantly associated with lower GM-CBF and TBV, and more AWM (all <0.05); SA with lower GM-CBF, WM-FA and TBV (p=0.01); increasing BMI with decreasing GM-CBF (p<0003); hypertension with lower GM-CBF, WM-FA, and TBV and higher AWM (all <0.05); and diabetes with lower TBV (p=0.007). The GCS was lower as TBV decreased, AWM increased, and WM-FA (all p<0.01).ConclusionIn middle age adults, CVRF are associated with brain health, reflected in MRI measures of structure and perfusion, and cognitive functioning. These findings suggest markers of mid-life cardiovascular and brain health should be considered as indication for early intervention and future risk of late-life cerebrovascular disease and dementia.

Objective Human voluntary movement is associated with two changes in electroencephalography (EEG) that can be observed as early as 1.5 s prior to movement: slow DC potentials and frequency power shifts in the alpha and beta bands. Our goal was to determine whether and when we can reliably predict human natural movement BEFORE it occurs from EEG signals ONLINE IN REAL-TIME. Methods We developed a computational algorithm to support online prediction. Seven healthy volunteers participated in this study and performed wrist extensions at their own pace. Results The average online prediction time was 0.62 ± 0.25 s before actual movement monitored by EMG signals. There were also predictions that occurred without subsequent actual movements, where subjects often reported that they were thinking about making a movement. Conclusion Human voluntary movement can be predicted before movement occurs. Significance The successful prediction of human movement intention will provide further insight into how the brain prepares for movement, as well as the potential for direct cortical control of a device which may be faster than normal physical control.

US National Institutes of Health and National Multiple Sclerosis Society.

OBJECTIVEUnderstanding the effect of diabetes as well as of alternative treatment strategies on cerebral structure is critical for the development of targeted interventions against accelerated neurodegeneration in type 2 diabetes. We investigated whether diabetes characteristics were associated with spatially specific patterns of brain changes and whether those patterns were affected by intensive versus standard glycemic treatment.RESEARCH DESIGN AND METHODSUsing baseline MRIs of 488 participants with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) study, we applied a new voxel-based analysis methodology to identify spatially specific patterns of gray matter and white matter volume loss related to diabetes duration and HbA1c. The longitudinal analysis used 40-month follow-up data to evaluate differences in progression of volume loss between intensive and standard glycemic treatment arms.RESULTSParticipants with longer diabetes duration had significantly lower gray matter volumes, primarily in certain regions in the frontal and temporal lobes. The longitudinal analysis of treatment effects revealed a heterogeneous pattern of decelerated loss of gray matter volume associated with intensive glycemic treatment. Intensive treatment decelerated volume loss, particularly in regions adjacent to those cross-sectionally associated with diabetes duration. No significant relationship between low versus high baseline HbA1c levels and brain changes was found. Finally, regions in which cognitive change was associated with longitudinal volume loss had only small overlap with regions related to diabetes duration and to treatment effects.CONCLUSIONSApplying advanced quantitative image pattern analysis methods on longitudinal MRI data of a large sample of patients with type 2 diabetes, we demonstrate that there are spatially specific patterns of brain changes that vary by diabetes characteristics and that the progression of gray matter volume loss is slowed by intensive glycemic treatment, particularly in regions adjacent to areas affected by diabetes.

Objective: We hypothesized that greater cardiorespiratory fitness is associated with lower odds of having unfavorable brain MRI findings. Methods:We studied 565 healthy, middle-aged, black and white men and women in the CARDIA (Coronary Artery Risk Development in Young Adults) Study. The fitness measure was symptomlimited maximal treadmill test duration (Max dur ); brain MRI was measured 5 years later. Brain MRI measures were analyzed as means and as proportions below the 15th percentile (above the 85th percentile for white matter abnormal tissue volume).Results: Per 1-minute-higher Max dur , the odds ratio for having less whole brain volume was 0.85 (p 5 0.04) and for having low white matter integrity was 0.80 (p 5 0.02), adjusted for age, race, sex, clinic, body mass index, smoking, alcohol, diet, physical activity, education, blood pressure, diabetes, total cholesterol, and lung function (plus intracranial volume for white matter integrity). No significant associations were observed between Max dur and abnormal tissue volume or blood flow in white matter. Findings were similar for associations with continuous brain MRI measures.Conclusions: Greater physical fitness was associated with more brain volume and greater white matter integrity measured 5 years later in middle-aged adults. Cardiorespiratory fitness (CRF), measured by treadmill duration, correlates with reduced cardiovascular diseases and overall mortality rates.

Not much is known about brain structural change in younger populations and minorities. The cross-sectional relationship between depressive symptomatology and racial discrimination with structural measures of brain tissue volume was investigated using magnetic resonance images of 710 participants in the Coronary Artery Risk Development in Young Adults CARDIA Study in 2010. Those reporting depressive symptoms and racial discrimination had lower total brain matter volume compared with those who reported neither (−8.8 mL, 95% confidence interval (CI): −16.4, −1.2), those who reported depressive symptoms only (−10.9 mL, 95% CI: −20.4, −1.4), and those who reported racial discrimination only (−8.6 mL, 95% CI: −16.5, −0.8). Results were similar for total normal white matter. There were 103% higher odds (odds ratio = 2.03, 95% CI: 1.32, 3.14) of being in the highest quartile of white matter hyperintensities in those with depressive symptoms only compared to those without. Although tests for interaction by race were not statistically significant, sensitivity analyses stratified by race revealed inverse associations with total brain matter and total white matter volumes only among black participants with combined depressive symptomatology and experience of racial discrimination, and positive associations only among white participants with depressive symptoms with presence of white matter hyperintensities, suggesting future studies may focus on race.

BACKGROUND AND PURPOSE: White matter lesions are 1 age-related manifestation of cerebrovascular disease, but subthreshold abnormalities have been identified in nonlesional WM. We hypothesized that structural and physiologic MR imaging findings of early cerebrovascular disease can be measured in middle-aged subjects in tissue adjacent to WM lesions, termed "penumbra."MATERIALS AND METHODS: WM lesions were defined using automated segmentation in 463 subjects, 43-56 years of age, from the Coronary Artery Risk Development in Young Adults (CARDIA) longitudinal observational cohort study. We described 0-to 2-mm and 2-to 4-mm-thick spatially defined penumbral WM tissue ROIs as rings surrounding WM lesions. The remaining WM was defined as distant normal-appearing WM. Mean signal intensities were measured for FLAIR, T1-, and T2-weighted images, and from fractional anisotropy, mean diffusivity, CBF, and vascular reactivity maps. Group comparisons were made using Kruskal-Wallis and pair-wise t tests. RESULTS:Lesion volumes averaged 0.738 Ϯ 0.842 cm 3 (range, 0.005-7.27 cm 3 ). Mean signal intensity for FLAIR, T2, and mean diffusivity was increased, while T1, fractional anisotropy, and CBF were decreased in white matter lesions versus distant normal-appearing WM, with penumbral tissues showing graded intermediate values (corrected P Ͻ .001 for all group/parameter comparisons). Vascular reactivity was significantly elevated in white matter lesions and penumbral tissue compared with distant normal-appearing white matter (corrected P Յ .001). CONCLUSIONS:Even in relatively healthy 43-to 56-year-old subjects with small white matter lesion burden, structural and functional MR imaging in penumbral tissue reveals significant signal abnormalities versus white matter lesions and other normal WM. Findings suggest that the onset of WM injury starts by middle age and involves substantially more tissue than evident from focal white matter lesions visualized on structural imaging. ABBREVIATIONS: BMI ϭ body mass index; BOLD ϭ blood oxygen level-dependent; dNAWM ϭ distant normal-appearing white matter; FA ϭ fractional anisotropy; MD ϭ mean diffusivity; NAWM ϭ normal-appearing white matter; RF score ϭ risk factor score; VR ϭ vascular reactivity; WML ϭ white matter lesion C erebral white matter lesions (WMLs), or leukoaraiosis, are common age-related MR imaging findings but may be pres-ent in younger individuals. 1 WMLs are associated with cognitive decline, 2-4 future infarction, depression, 5 and poor clinical prognosis. 6 WMLs commonly affect terminal vascular territories and their burden progresses 7 by expansion of existing lesions and development of new lesions.Pathologically, WMLs demonstrate capillary loss, arterial tortuosity, gliosis, 8 demyelination, and ischemia. 9 Imaging has shown physiologic abnormalities in WMLs, including decreased cerebral blood flow 10,11 and vascular reactivity (VR), 12 and in-