The relationship between brain activation and mitochondrial complex I protein levels during cognitive function in healthy humans: an BCPP-EF PET and functional MRI study of task switching

Shatalina, E.; Whitehurst, T.; Chika Onwordi, E.; Whittington, A.; Mansur, A.; Arumuham, A.; Reis Marques, T.; Gunn, R. N.; Natesan, S.; Nour, M. M.; Rabiner, E. A.; Wall, M. B.; Howes, O. D.

doi:10.1101/2024.09.25.614887

bioRxiv · 10.1101/2024.09.25.614887

The relationship between brain activation and mitochondrial complex I protein levels during cognitive function in healthy humans: an BCPP-EF PET and functional MRI study of task switching

Shatalina, E.·Whitehurst, T.·Chika Onwordi, E.·Whittington, A.·Mansur, A.·Arumuham, A.·Reis Marques, T.·Gunn, R. N.·Natesan, S.·Nour, M. M.·Rabiner, E. A.·Wall, M. B.·Howes, O. D.

View original source ↗Export metadata ↓

Abstract

Mitochondrial complex I is the largest enzyme complex in the respiratory chain and can be non-invasively measured using [18F]BCPP-EF positron emission tomography (PET). Neurological conditions associated with mitochondria complex I pathology are also associated with altered blood oxygen level dependent (BOLD) response and impairments in cognition. To evaluate the link between mitochondrial complex I, cognition and associated neural activity, 23 cognitively healthy adults underwent a [18F]BCPP-EF PET scan and a functional magnetic resonance imaging (fMRI) scan during which they performed a task switching exercise. We found significant positive associations between [18F]BCPP-EF volume of distribution (VT), which measures mitochondrial complex I levels and the task switching fMRI response (Partial Least Squares (PLS) Canonical Analysis (CA), first component r=0.51, p=0.03). Exploratory Pearsons correlations showed significant positive associations between mitochondrial complex I levels and the fMRI response in regions including the dorsolateral prefrontal cortex (r=0.61, p=0.0019), insula (r=0.46, p=0.0264) parietal-precuneus (r=0.51, p=0.0139) and anterior cingulate cortex (r=0.45, p=0.0293). Mitochondrial complex I levels across task-relevant regions were also predictive of task switching accuracy (PLS-Regression (PLS-R), R2=0.48, RMSE=0.154, p=0.011) and of switch cost (PLS-R, R^2=0.38, RMSE=0.07, p=0.048). Our findings suggest that higher mitochondrial complex I levels may underlie an individuals ability to exhibit a stronger BOLD response during task switching and are predictive of better task switching performance. This provides the first evidence linking the BOLD response with mitochondrial complex I and suggests a possible biological mechanism for aberrant BOLD response in conditions associated with mitochondrial complex I dysfunction, that should be tested in future studies.

Explore related subjects

neuroscience Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Shatalina, E., Whitehurst, T., Chika Onwordi, E., Whittington, A., Mansur, A., Arumuham, A., Reis Marques, T., Gunn, R. N., Natesan, S., Nour, M. M., Rabiner, E. A., Wall, M. B., Howes, O. D.. 2024-09-27. The relationship between brain activation and mitochondrial complex I protein levels during cognitive function in healthy humans: an BCPP-EF PET and functional MRI study of task switching. https://doi.org/10.1101/2024.09.25.614887

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↗