Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/620443

Contributions of white matter connectivity and BOLD modulation to cognitive aging: A lifespan structure-function association study

Webb, C. E.·Rodrigue, K. M.·Hoagey, D. A.·Foster, C. M.·Kennedy, K. M.
View original source ↗Export metadata ↓

Abstract

The ability to flexibly modulate brain activation to increasing cognitive challenge decreases with aging. This age-related decrease in dynamic range of function of regional gray matter may be, in part, due to age-related degradation of regional white matter tracts. Here, a lifespan sample of 171 healthy adults (aged 20-94) underwent MRI scanning including diffusion-weighted imaging (for tractography) and functional imaging (a digit n-back task). We utilized structural equation modeling to test the hypothesis that age-related decrements in white matter microstructure are associated with altered BOLD modulation, and both in turn, are associated with scanner-task accuracy and executive function performance. Specified structural equation model evidenced good fit, demonstrating that increased age negatively affects n-back task accuracy and executive function performance in part due to both degraded white matter tract microstructure and reduced task-difficulty related BOLD modulation. We further demonstrated that poorer white matter microstructure integrity was associated with weakened BOLD modulation, particularly in regions showing positive modulation effects, as opposed to negative modulation effects. This structure-function association study provides further evidence that structural connectivity influences functional activation, and the two mechanisms in tandem are predictive of cognitive performance, both during the task, and for cognition measured outside the scanner environment.

Source connections

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Webb, C. E., Rodrigue, K. M., Hoagey, D. A., Foster, C. M., Kennedy, K. M.. 2019-04-26. Contributions of white matter connectivity and BOLD modulation to cognitive aging: A lifespan structure-function association study. https://doi.org/10.1101/620443

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Rab10 and Arhgef7 interact to promote axon extension by linking vesicle supply and exocytosis

The formation of functional neural circuits begins with the extension of a single axon by immature neurons. Axon elongation requires an expansion of the plasma membrane that depends on the polarization of vesicle trafficking and exocytosis. It is not completely understood how the increased transport of vesicles into the growing axon is linked to their subsequent insertion into the plasma membrane. An analysis of early stages of neuronal differentiation indicates that an asymmetry in neurite length precedes axon specification and the accumulation of PPVs in the nascent axon. We show that increasing the transport of vesicles in unpolarized neurons is sufficient to promote the extension of additional axons. This effect indicates that an increased supply of vesicles stimulates their subsequent insertion into the membrane to allow neurite growth. The link between vesicle transport and exocytosis is mediated by the interaction of Rab10 with Arhgef7. Rab10 stimulates Arhgef7 activity on PPVs as a GEF for Cdc42b to promote axon extension through exocyst-dependent exocytosis, suggesting that their interaction links the increased supply of PPVs to their exocytosis.

neuroscience↗
bioRxiv2026

Subcellular Spatial Profiling Unveils Links Between Neuritic Plaques with Selective Tau Vulnerability in Alzheimer's Disease

Alzheimer's disease (AD) features widespread extracellular amyloid-{beta} plaques but selective intraneuronal tau accumulation in cortical layers II/III and V, while layer IV remains relatively resistant. Here, we combined subcellular spatial transcriptomics with co-registered A{beta} and pTau immunohistochemistry to determine why neurons exposed to comparable plaque-associated pathology differ in somatic pTau accumulation. Plaque-associated neuritic stress occurred similarly across layers, but layer IV neurons showed attenuated pTau accumulation and reduced somatic expression of a shared neurite-soma stress program involving DCTN1, CALM3, NORAD, and PIN1. Trajectory analysis within layers identified tau-vulnerable and resistant neuronal states implicating calcium signaling, retrograde transport, and lysosomal function. Notably, astrocytic APOE-neuronal LRP1 co-expression increased significantly along the pTau-vulnerable trajectory, and APOE {epsilon}4 was associated with stronger coupling of local plaque pathology to pTau-associated molecular programs. These findings reveal neuronal programs and neuron-glia interactions underlying selective tau vulnerability and resistance in AD, highlighting potential tau-targeting therapeutics.

neuroscience↗
bioRxiv2026

Widespread oscillatory suppression in autism persists in the absence of psychotropic medication.

Purpose: Investigate the neural oscillatory activity associated with autism spectrum disorder (ASD) using electroencephalographic (EEG) recordings in children and adolescents. Compare the corresponding oscillatory power between ASD patients taking psychotropic medication with a drug-naive group. Methods: ASD diagnosis was done using DSM-IV and CARS (Childhood Autism Rating Scale). EEG recordings employed 22 scalp electrodes (10/20 system). ASD vs. neurotypical groups were matched for sex and age (5 females; average age: ~10 years old). We analyzed the resting state (eyes open) EEG power spectrum during ~2-minute recordings. The multitaper FFT method was used to estimate spectral power for the delta, theta, alpha, beta and gamma frequency bands. We pooled together data from several electrodes to compute comprehensive power spectra and assess the oscillatory behavior of macro brain regions. Results: We observed widespread (~4Hz - 20Hz) oscillatory suppression comprising the theta, alpha and beta frequency bands. The most widespread and robust ASD-associated power suppression was in the high theta and alpha bands. Delta and gamma bands showed no significant power change for any of the brain regions studied. Results from a subgroup of patients (N = 9) who never used psychotropics confirmed these findings, indicating that they are not an artifact of medication. Conclusion: Suppression in theta, alpha and beta oscillations may offer insights into the neurophysiological underpinnings of autism and could be used as an accessible and comprehensive tool in ASD diagnosis, regardless of the patients being or not on medication.

neuroscience↗