Blood Oxygen Level-Dependent Lag Patterns Differ Between Rest and Task Conditions, but Are Largely Typical in Autism

Lisa E. Mash, Annika C. Linke, Yangfeifei Gao, Molly Wilkinson, Michael A. Olson, R. Joanne Jao Keehn, Ralph Axel Müller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background/Introduction: Autism spectrum disorder (ASD) is characterized by atypical functional connectivity (FC) within and between distributed brain networks. However, FC findings have often been inconsistent, possibly due to a focus on static FC rather than brain dynamics. Lagged connectivity analyses aim at evaluating temporal latency, and presumably neural propagation, between regions. This approach may, therefore, reveal a more detailed picture of network organization in ASD than traditional FC methods. Methods: The current study evaluated whole-brain lag patterns in adolescents with ASD (n = 28) and their typically developing peers (n = 22). Functional magnetic resonance imaging data were collected during rest and during a lexico-semantic decision task. Optimal lag was calculated for each pair of regions of interest by using cross-covariance, and mean latency projections were calculated for each region. Results: Latency projections did not regionally differ between groups, with the same regions emerging among the "earliest"and "latest."Although many of the longest absolute latencies were preserved across resting-state and task conditions, lag patterns overall were affected by condition, as many regions shifted toward zero-lag during task performance. Lag structure was also strongly associated with literature-derived estimates of arterial transit time. Discussion: Results suggest that lag patterns are broadly typical in ASD but undergo changes during task performance. Moreover, lag patterns appear to reflect a combination of neural and vascular sources, which should be carefully considered when interpreting lagged FC. Altered brain dynamics have been proposed in autism spectrum disorder (ASD). Lagged functional connectivity analysis uses cross-correlation between functional magnetic resonance imaging (fMRI) time series to determine regional latency. Few studies have examined blood oxygen level-dependent (BOLD) lag in ASD, and findings have been inconsistent. Using multi-echo fMRI data with improved artifact detection and removal, we find differences in lag structure between task and rest states, but not between adolescents with ASD and typically developing peers. Additional analyses exploring links with arterial transit time, however, highlight the impact of vascular organization on BOLD lag patterns and its potential to confound measures of neural dynamics.

Original languageEnglish (US)
Pages (from-to)234-245
Number of pages12
JournalBrain Connectivity
Issue number3
StatePublished - Apr 2022


  • BOLD dynamics
  • autism spectrum disorder
  • functional MRI
  • functional connectivity

ASJC Scopus subject areas

  • General Neuroscience


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