Increased Resting-State BOLD Turnover (TBOLD) is Associated With Decreased Cognitive Performance During Aging.

Increasing evidence documents turnover of the resting-state blood-oxygen-level dependent signal (TBOLD) as a key measure of local cortical brain status. Here we evaluated contemporaneous and lagged associations between TBOLD and cognitive function in 711 participants in the Human Connectome Project on Aging (HCP-A; 316 males and 395 females, age range 36-90 years). We found that TBOLD was negatively associated with Montreal Cognitive Assessment (MoCA) Total scores and with performance on 2 subscales, Delayed Recall and Visuospatial/Executive Function, controlling for sex, age, and handedness.

Association between neurovascular coupling and neural signals in the resting state as revealed by a combined fMRI and magnetoencephalography study in humans.

The blood oxygenation level-dependent (BOLD) activation reflects hemodynamic events mediated by neurovascular coupling. During task performance, the BOLD hemodynamic response in a relevant area is mainly driven by the high levels of synaptic activity (reflected in local field potentials, LFPs) but, in contrast, during a task-free, resting state, the contribution to BOLD of such neural events is small, as expected by the comparatively (to the task state) low level of neural events. Concomitant recording of BOLD and LFP at rest in animal experiments has estimated the neural contribution to BOLD to ∼10%.

Negative association between neurovascular coupling and cortical gray matter volume during the lifespan.

Recent studies have established the moment-to-moment turnover of the blood-oxygen-level-dependent signal (TBOLD) at resting state as a key measure of local cortical brain function. Here, we sought to extend that line of research by evaluating TBOLD in 70 cortical areas with respect to corresponding brain volume, age, and sex across the lifespan in 1,344 healthy participants including 633 from the Human Connectome Project (HCP)-Development cohort (294 males and 339 females, age range 8-21 yr) and 711 healthy participants from HCP-Aging cohort (316 males and 395 females, 36-90 yr old). In both groups, we found that ) TBOLD increased with age, ) volume decreased with age, and ) TBOLD and volume were highly significantly negatively correlated, independent of age.

Changes of gray matter volumes of subcortical regions across the lifespan: a Human Connectome Project study.

We assessed changes in gray matter volume (GMV) of nine subcortical regions (accumbens, amygdala, brainstem, caudate, cerebellar cortex, pallidum, putamen, thalamus, and ventral diencephalon) across the lifespan in a large sample of participants in the Human Connectome Project ( = 2,458, 5-90 yr old, 1,113 males and 1,345 females). 3T MRI data were acquired using a harmonized protocol and were processed in an identical way for all brains. GMVs of individual regions were adjusted for estimated total intracranial volume and regressed against age.

Differential reduction of gray matter volume with age in 35 cortical areas in men (more) and women (less).

It is known that brain volume decreases with age. Here, we assessed the rate of this decrease in gray matter volume of 35 cortical regions in a large sample of healthy participants ( = 712, age range 36-90 yr) of the Human Connectome Project-Aging. We evaluated the difference in this rate between men ( = 316) and women ( = 396) and found that the volumes of cortical areas decreased by an average of 5.

The brain landscape of the two-hit model of posttraumatic stress disorder.

The neurophysiological mechanisms underlying the development of posttraumatic stress disorder (PTSD) are poorly understood. Here we test a proposal that PTSD symptoms reflect fixed, highly correlated neural networks resulting from massive engagement of sensory inputs and the sequential involvement of those projections to limbic areas. Three-tesla functional magnetic resonance imaging (fMRI) data were acquired at rest in 15 veterans diagnosed with PTSD and 21 healthy control veterans from which zero-lag cross correlations between 50 brain areas ( = 1,225 pairs) were computed and analyzed.

Heritability of brain neurovascular coupling.

The moment-to-moment variation of neurovascular coupling in the brain was determined by computing the moment-to-moment turnover of the blood-oxygen-level-dependent signal (TBOLD) at resting state. Here we show that ) TBOLD is heritable, ) its heritability estimates are highly correlated between left and right hemispheres, and ) the degree of its heritability is determined, in part, by the anatomical proximity of the brain areas involved. We also show that the regional distribution of TBOLD in the cortex is significantly associated with that of the vesicular acetylcholine transporter.

The dynamic shaping of local cortical circuitry by sex and age, and its relation to pattern comparison processing speed.

Previous resting-state functional magnetic resonance imaging (fMRI) studies have shown that the strength of local neural interactions decreases with distance. Here, we extend that line of research to evaluate effects of sex and age on local cortical circuitry in six cortical areas (superior frontal, precentral, postcentral, superior parietal, inferior parietal, and lateral occipital) using data acquired from 1,054 healthy young adults who participated in the Human Connectome Project. We confirmed previous findings that the strength of zero-lag correlations between prewhitened, resting-state, blood level oxygenation-dependent (BOLD) fMRI time series decreased with distance locally and documented that the rate of decrease with distance (spatial steepness) ) was progressively lower from anterior to posterior areas, ) was greater in women, especially in anterior areas, ) increased with age, particularly for women, ) was significantly correlated with percent inhibition, and ) was positively and highly significantly correlated with pattern comparison processing speed (PCPS).

BOLD turnover in task-free state: variation among brain areas and effects of age and human leukocyte antigen (HLA) DRB1*13.

Blood oxygen level dependent (BOLD) signal in functional magnetic resonance imaging (fMRI) is frequently used as a proxy for underlying neural activity. Although this is a plausible assumption for experiments where a task is performed, it may not hold to the same degree for conditions of fMRI recording in a task-free, "resting" state where neural synaptic events are weak and, hence, neurovascular coupling and endothelial vascular factors become more prominent (Hillman Annu Rev Neurosci 37:161-181, 2014, 10.1146/annurev-neuro-071013-014111).

Functional cortical associations and their intraclass correlations and heritability as revealed by the fMRI Human Connectome Project.

We report on the functional connectivity (FC), its intraclass correlation (ICC), and heritability among 70 areas of the human cerebral cortex. FC was estimated as the Pearson correlation between averaged prewhitened Blood Oxygenation Level-Dependent time series of cortical areas in 988 young adult participants in the Human Connectome Project. Pairs of areas were assigned to three groups, namely homotopic (same area in the two hemispheres), ipsilateral (both areas in the same hemisphere), and heterotopic (nonhomotopic areas in different hemispheres).

Effects of sex and age on presumed inhibitory interactions in 6 areas of the human cerebral cortex as revealed by the fMRI Human Connectome Project.

Cortical inhibition is theorized to reflect an underlying property of human brain function, sharpening tuning and shaping connectivity. Although age and sex effects on large-scale resting-state brain connectivity have been well documented, effects on local cortical inhibition have received relatively limited attention. Here, we evaluated age and sex effects on presumed local inhibitory interactions in 6 lateral cortical areas using resting-state functional magnetic resonance imaging (fMRI) data acquired from 1054 young adults who participated in the Human Connectome Project.

Human Connectome Project: heritability of brain volumes in young healthy adults.

Here we report on the heritability and Intraclass Correlation Coefficients (ICCs) of brain volumes in 1,103 young healthy adults with mean age 29.2 years. Among them are: 153 monozygotic (MZ) twin pairs and 86 dizygotic (DZ) twin pairs, 133 non-twin siblings of MZ twins, 76 non-twin siblings of DZ twins, 335 siblings, and 81 unrelated individuals.

Behavioral-genetic associations in the Human Connectome Project.

The Human Connectome Project (HCP) provides a rich dataset of quantitative and domain-specific behavioral measures from twins and extensive family structures. This makes the dataset a unique and a valuable resource to investigate heritability and determine individual differences. Using a set of measures of behavioral domains (motor, emotion, personality, sensory, and cognition), we estimated the intraclass correlations (ICCs) and heritability of 56 behavioral measures for 4 genetically identified groups of participants: monozygotic (MZ) twins, dizygotic (DZ) twins, non-twin siblings (SB), and unrelated individuals (NR).

A Two-Hit Model of The Biological Origin of Posttraumatic Stress Disorder (PTSD).

Posttraumatic stress disorder (PTSD) is a debilitating disorder that can develop following exposure to a traumatic event. Although the cause of PTSD is known, the brain mechanisms of its development remain unknown, especially why it arises in some people but not in others. Most of the research on PTSD has dealt with psychological and brain mechanisms underlying its symptomatology, including intrusive memories, fear and avoidance (see ref.

Invariant and heritable local cortical organization as revealed by fMRI.

Neural interactions in local cortical networks critically depend on the distance between interacting elements: the shorter the distance, the stronger the interactions. Here we quantified these interactions in six cortical areas of 854 individuals, including monozygotic and dizygotic twins, nontwin siblings, and nonrelated individuals. We found that the strength of zero-lag correlation between prewhitened, resting-state, blood level oxygenation-dependent functional magnetic resonance imaging time series decreased with distance as a power law.

Protective Effect of Human Leukocyte Antigen (HLA) Allele DRB1*13:02 on Age-Related Brain Gray Matter Volume Reduction in Healthy Women.

Background: Reduction of brain volume (brain atrophy) during healthy brain aging is well documented and dependent on genetic, lifestyle and environmental factors. Here we investigated the possible dependence of brain gray matter volume reduction in the absence of the Human Leukocyte Antigen (HLA) allele DRB1*13:02 which prevents brain atrophy in Gulf War Illness (James et al., 2017).

Human Leukocyte Antigen (HLA) and Gulf War Illness (GWI): HLA-DRB1*13:02 Spares Subcortical Atrophy in Gulf War Veterans.

Background: Gulf War Illness (GWI) is a multisystem disorder that has affected a substantial number of veterans who served in the 1990-91 Gulf War. The brain is prominently affected, as manifested by the presence of neurological, cognitive and mood symptoms. We reported previously on the protective role of six Human Leukocyte Antigen (HLA) alleles in GWI (Georgopoulos et al.

Subcortical brain atrophy in Gulf War Illness.

Gulf War Illness (GWI) is a multisystem disorder that has affected a substantial number of veterans who served in the 1990-1991 Gulf War. The brain is prominently affected, as manifested by the presence of neurological, cognitive and mood symptoms. Although brain dysfunction in GWI has been well documented (EBioMedicine 12:127-32, 2016), abnormalities in brain structure have been debated.

Neural mechanisms underlying the exploration of small city maps using magnetoencephalography.

The neural mechanisms underlying spatial cognition in the context of exploring realistic city maps are unknown. We conducted a novel brain imaging study to address the question of whether and how features of special importance for map exploration are encoded in the brain to make a spatial decision. Subjects explored by eyes small city maps exemplifying five different street network types in order to locate a hypothetical City Hall, while neural activity was recorded continuously by 248 magnetoencephalography (MEG) sensors at high temporal resolution.

Diagnosis of posttraumatic stress disorder (PTSD) based on correlations of prewhitened fMRI data: outcomes and areas involved.

Successful diagnosis of PTSD has been achieved using neural correlations from prewhitened magnetoencephalographic (MEG) time series (Georgopoulos et al. in J Neural Eng 7:16011, 2010. doi:10.

Cognitive mechanisms underlying instructed choice exploration of small city maps.

We investigated the cognitive mechanisms underlying the exploration and decision-making in realistic and novel environments. Twelve human subjects were shown small circular U.S.

Exploring small city maps.

The exploration of city maps has exploded recently due to the wide availability, increasing use of, and reliance on small positioning and navigational devices for personal use. In this study, subjects explored small, 3-mile diameter circular maps exemplifying five different types of street networks common in the United States, in order to locate a hypothetical city hall. Chosen locations indicated that subjects are able to identify more accessible sites.

A compact and realistic cerebral cortical layout derived from prewhitened resting-state fMRI time series: Cherniak's adjacency rule, size law, and metamodule grouping upheld.

We used hierarchical tree clustering to derive a functional organizational chart of 52 human cortical areas (26 per hemisphere) from zero-lag correlations calculated between single-voxel, prewhitened, resting-state BOLD fMRI time series in 18 subjects. No special "resting-state networks" were identified. There were four major features in the resulting tree (dendrogram).

A voxel-by-voxel parametric fMRI study of motor mental rotation: hemispheric specialization and gender differences in neural processing efficiency.

Differences between men and women in brain size, cognitive performance and lateralization of brain activation have been perennial and controversial issues. Here we show that in a motor mental rotation task where women and men performed equally well, the slope of the functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) signal per degree of mental rotation was overall 2.4x higher in men than in women.