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Assessing chance in neuro-vascular interactions.

D P Aksenov1, E D Doubovikov2, N A Serdyukova3

  • 1Department of Radiology, Endeavor Health, 2650 Ridge Ave, Evanston, IL, 60201, USA; Department of Anesthesiology, Endeavor Health, 2650 Ridge Ave, Evanston, IL, 60201, USA; University of Chicago, Pritzker School of Medicine, 5841 S Maryland Ave, Chicago, IL, 60637, USA; Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, E310, Evanston, IL, 60208, USA.

Neuroimage
|December 25, 2025
PubMed
Summary

Correlations between brain activity and blood flow signals are often misleading due to autocorrelation. A new statistical framework using surrogates accurately calibrates these tests, revealing selective neurovascular coupling during rest.

Keywords:
Autocorrelation biasNeurovascular couplingResting-state fMRI / functional connectivitySurrogate data (AAFT / Fourier surrogates)Tissue oxygen (PO₂)Vasomotion

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Area of Science:

  • Neuroscience
  • Physiology
  • Biophysics

Background:

  • Interpreting correlations between neuronal activity and hemodynamic signals is challenging due to strong autocorrelation.
  • Standard statistical tests can overestimate neurovascular coupling during rest by underestimating false positives.

Purpose of the Study:

  • To develop and validate a surrogate-based statistical framework for calibrating inference in autocorrelated physiological signals.
  • To accurately assess neurovascular coupling by distinguishing genuine interactions from random associations in resting-state data.

Main Methods:

  • Utilized simultaneous recordings of cortical oxygen tension (PO₂), single-unit firing, and local field potentials (LFP) in awake rabbits.
  • Applied amplitude-adjusted Fourier surrogates to generate null distributions that preserve temporal structure while removing cross-dependence.
  • Integrated lag optimization, multiple comparison controls, and population-level inference scaling.

Main Results:

  • Found significant PO₂ correlations with delta-band LFP and a subset of single neurons, exceeding chance levels under surrogate testing.
  • Correlations with other LFP bands were not significant, and aggregated neuronal activity (multi-unit signals) did not predict PO₂.
  • Identified that small, synchronized neuronal subpopulations, rather than global activity, produced robust associations with PO₂.

Conclusions:

  • Refined understanding of resting-state neurovascular coupling, demonstrating that apparent broad correlations resolve into selective and reproducible effects with calibrated testing.
  • The surrogate-based inference framework effectively prevents misinterpretation of autocorrelated data.
  • The proposed method offers a generalizable approach for time-series analysis in various scientific domains, including electrophysiology and neuroimaging.