Lag-adjusted functional network connectivity reveals sensorimotor and higher cognitive network alterations in
Malvika Sridhar1, Sir-Lord Wiafe1, Zening Fu1
1Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Atlanta, GA.
Research Square
|July 3, 2026
Summary
Major Depressive Disorder (MDD) shows altered brain network timing. Lag-adjusted functional connectivity reveals disrupted coordination between sensory, emotional, and cognitive brain networks in MDD patients.
Area of Science:
- Neuroscience
- Psychiatry
- Computational Neuroscience
Background:
- Major Depressive Disorder (MDD) is associated with widespread brain network dysfunction.
- Traditional functional connectivity methods may overlook crucial temporal dynamics in neural interactions.
- Lag-adjusted functional connectivity offers a more sensitive approach to characterize brain network alterations by considering time lags and intrinsic neural timescales (INTs).
Purpose of the Study:
- To investigate alterations in brain network coordination in MDD using lag-adjusted functional connectivity.
- To identify specific network differences between individuals with MDD and healthy controls.
- To explore the temporal ordering and intrinsic neural timescales (INTs) of brain networks in MDD.
Main Methods:
- Applied the NeuroMark framework to resting-state fMRI data from 235 MDD patients and 284 healthy controls.
- Identified 105 intrinsic connectivity networks (ICNs) and upsampled their time series to 100 ms resolution.
- Computed lag-adjusted functional connectivity via maximal cross-correlation within a ±2s window at 0.1s intervals and analyzed group differences using regression.
Main Results:
- Significant differences in lag-adjusted functional connectivity were found between MDD and control groups (p < 0.05).
- MDD exhibited hyperconnectivity in salience-sensorimotor and sensorimotor-temporoinsular networks.
- MDD showed hypoconnectivity in salience-higher cognitive temporal/frontal and temporoparietal-visual networks, with evidence of compressed inter-network timing.
Conclusions:
- Lag-adjusted functional connectivity is a valuable tool for detecting impaired neural coordination in MDD beyond simple connectivity strength.
- Altered coordination among sensory, emotional, and cognitive processes is a key feature of brain network disruption in MDD.
- The findings suggest a non-random bias in temporal ordering and compressed inter-network timing in MDD.
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