Identifying and characterizing systematic temporally-lagged BOLD artifacts

&NA; Residual noise in the BOLD signal remains problematic for fMRI – particularly for techniques such as functional connectivity, where findings can be spuriously influenced by noise sources that can covary with individual differences. Many such potential noise sources – for instance, motion and respiration – can have a temporally lagged effect on the BOLD signal. Thus, here we present a tool for assessing residual lagged structure in the BOLD signal that is associated with nuisance signals, using a construction similar to a peri‐event time histogram. Using this method, we find that framewise displacements – both large and very small – were followed by structured, prolonged, and global changes in the BOLD signal that depend on the magnitude of the preceding displacement and extend for tens of seconds. This residual lagged BOLD structure was consistent across datasets, and independently predicted considerable variance in the global cortical signal (as much as 30–40% in some subjects). Mean functional connectivity estimates varied similarly as a function of displacements occurring many seconds in the past, even after strict censoring. Similar patterns of residual lagged BOLD structure were apparent following respiratory fluctuations (which covaried with framewise displacements), implicating respiration as one likely mechanism underlying the displacement‐linked structure observed. Global signal regression largely attenuates this artifactual structure. These findings suggest the need for caution in interpreting results of individual difference studies where noise sources might covary with the individual differences of interest, and highlight the need for further development of preprocessing techniques for mitigating such structure in a more nuanced and targeted manner. HighlightsIntroduces an approach for revealing residual lagged structure in the BOLD signal.Reveals robust, predictable artifact; linked with variation in mean FC.Artifact follows large & small displacements and is linked with respiration.Global signal regression eliminates artifact, helping to avoid spurious conclusions.A MATLAB script for general data exploration & quality assessment is provided.

[1]  Timothy O. Laumann,et al.  Data Quality Influences Observed Links Between Functional Connectivity and Behavior , 2017, Cerebral cortex.

[2]  Hang Joon Jo,et al.  The perils of global signal regression for group comparisons: a case study of Autism Spectrum Disorders , 2013, Front. Hum. Neurosci..

[3]  Mark Jenkinson,et al.  The minimal preprocessing pipelines for the Human Connectome Project , 2013, NeuroImage.

[4]  Daniel P. Kennedy,et al.  Idiosyncratic Brain Activation Patterns Are Associated with Poor Social Comprehension in Autism , 2015, The Journal of Neuroscience.

[5]  Timothy O. Laumann,et al.  Methods to detect, characterize, and remove motion artifact in resting state fMRI , 2014, NeuroImage.

[6]  Christos Davatzikos,et al.  Benchmarking of participant-level confound regression strategies for the control of motion artifact in studies of functional connectivity , 2017, NeuroImage.

[7]  R. Adolphs,et al.  Building a Science of Individual Differences from fMRI , 2016, Trends in Cognitive Sciences.

[8]  Michael B. Miller,et al.  One dataset, many conclusions: BOLD variability’s complicated relationships with age and motion artifacts , 2014, Brain Imaging and Behavior.

[9]  Richard G. Wise,et al.  Physiological noise modelling for spinal functional magnetic resonance imaging studies , 2008, NeuroImage.

[10]  K. Ohki,et al.  Transient neuronal coactivations embedded in globally propagating waves underlie resting-state functional connectivity , 2016, Proceedings of the National Academy of Sciences.

[11]  Jesper Andersson,et al.  A multi-modal parcellation of human cerebral cortex , 2016, Nature.

[12]  Thomas T. Liu,et al.  The global signal in fMRI: Nuisance or Information? , 2017, NeuroImage.

[13]  Abraham Z. Snyder,et al.  Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion , 2012, NeuroImage.

[14]  Steen Moeller,et al.  The Human Connectome Project: A data acquisition perspective , 2012, NeuroImage.

[15]  K. Pelphrey,et al.  Perspective: Brain scans need a rethink , 2012, Nature.

[16]  Karl J. Friston,et al.  Movement‐Related effects in fMRI time‐series , 1996, Magnetic resonance in medicine.

[17]  Peter A. Bandettini,et al.  Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fMRI , 2006, NeuroImage.

[18]  X Hu,et al.  Retrospective estimation and correction of physiological fluctuation in functional MRI , 1995, Magnetic resonance in medicine.

[19]  Thomas T. Liu,et al.  Noise contributions to the fMRI signal: An overview , 2016, NeuroImage.

[20]  Catie Chang,et al.  Influence of heart rate on the BOLD signal: The cardiac response function , 2009, NeuroImage.

[21]  Ludovica Griffanti,et al.  Automatic denoising of functional MRI data: Combining independent component analysis and hierarchical fusion of classifiers , 2014, NeuroImage.

[22]  Timothy O. Laumann,et al.  On Global fMRI Signals and Simulations , 2017, Trends in Cognitive Sciences.

[23]  Jonathan D. Power A simple but useful way to assess fMRI scan qualities , 2017, NeuroImage.

[24]  Timothy O. Laumann,et al.  Evaluation of Denoising Strategies to Address Motion-Correlated Artifacts in Resting-State Functional Magnetic Resonance Imaging Data from the Human Connectome Project , 2016, Brain Connect..

[25]  César Caballero-Gaudes,et al.  Methods for cleaning the BOLD fMRI signal , 2016, NeuroImage.

[26]  Irene Tracey,et al.  Resting fluctuations in arterial carbon dioxide induce significant low frequency variations in BOLD signal , 2004, NeuroImage.

[27]  Arno Klein,et al.  A reproducible evaluation of ANTs similarity metric performance in brain image registration , 2011, NeuroImage.

[28]  Catie Chang,et al.  Relationship between respiration, end-tidal CO2, and BOLD signals in resting-state fMRI , 2009, NeuroImage.

[29]  Danielle S Bassett,et al.  Motion artifact in studies of functional connectivity: Characteristics and mitigation strategies , 2019, Human brain mapping.

[30]  G H Glover,et al.  Image‐based method for retrospective correction of physiological motion effects in fMRI: RETROICOR , 2000, Magnetic resonance in medicine.

[31]  Mark A. Elliott,et al.  Impact of in-scanner head motion on multiple measures of functional connectivity: Relevance for studies of neurodevelopment in youth , 2012, NeuroImage.

[32]  Rasmus M. Birn,et al.  The role of physiological noise in resting-state functional connectivity , 2012, NeuroImage.

[33]  Kevin Murphy,et al.  The impact of global signal regression on resting state correlations: Are anti-correlated networks introduced? , 2009, NeuroImage.

[34]  Simon B. Eickhoff,et al.  An improved framework for confound regression and filtering for control of motion artifact in the preprocessing of resting-state functional connectivity data , 2013, NeuroImage.

[35]  Andrea Sbarbati,et al.  Reproducibility of BOLD signal change induced by breath holding , 2009, NeuroImage.

[36]  Evan M. Gordon,et al.  On the Stability of BOLD fMRI Correlations , 2016, Cerebral cortex.

[37]  Timothy O. Laumann,et al.  Sources and implications of whole-brain fMRI signals in humans , 2017, NeuroImage.

[38]  M. Raichle,et al.  Lag structure in resting-state fMRI. , 2014, Journal of neurophysiology.

[39]  Mary E. Meyerand,et al.  The Influence of Physiological Noise Correction on Test-Retest Reliability of Resting-State Functional Connectivity , 2014, Brain Connect..

[40]  Uri Hasson,et al.  Shared and idiosyncratic cortical activation patterns in autism revealed under continuous real‐life viewing conditions , 2009, Autism research : official journal of the International Society for Autism Research.

[41]  W. Roth,et al.  Physiologic instability in panic disorder and generalized anxiety disorder , 2001, Biological Psychiatry.

[42]  M. Raichle,et al.  Human cortical–hippocampal dialogue in wake and slow-wave sleep , 2016, Proceedings of the National Academy of Sciences.

[43]  J. Hajnal,et al.  Artifacts due to stimulus correlated motion in functional imaging of the brain , 1994, Magnetic resonance in medicine.

[44]  Mark W. Woolrich,et al.  Resting-state fMRI in the Human Connectome Project , 2013, NeuroImage.

[45]  Daniel P. Kennedy,et al.  Enhancing studies of the connectome in autism using the autism brain imaging data exchange II , 2017, Scientific Data.

[46]  Daniel P. Kennedy,et al.  Largely typical patterns of resting-state functional connectivity in high-functioning adults with autism. , 2014, Cerebral cortex.

[47]  Mert R. Sabuncu,et al.  The influence of head motion on intrinsic functional connectivity MRI , 2012, NeuroImage.

[48]  L. Uddin Mixed Signals: On Separating Brain Signal from Noise , 2017, Trends in Cognitive Sciences.

[49]  Hazem H. Refai,et al.  Subject specific BOLD fMRI respiratory and cardiac response functions obtained from global signal , 2013, NeuroImage.

[50]  Kevin Murphy,et al.  Towards a consensus regarding global signal regression for resting state functional connectivity MRI , 2017, NeuroImage.

[51]  Jonathan D. Power,et al.  Recent progress and outstanding issues in motion correction in resting state fMRI , 2015, NeuroImage.

[52]  M. Raichle,et al.  Lag threads organize the brain’s intrinsic activity , 2015, Proceedings of the National Academy of Sciences.

[53]  Hang Joon Jo,et al.  Trouble at Rest: How Correlation Patterns and Group Differences Become Distorted After Global Signal Regression , 2012, Brain Connect..

[54]  Peter A. Bandettini,et al.  The respiration response function: The temporal dynamics of fMRI signal fluctuations related to changes in respiration , 2008, NeuroImage.

[55]  R. Malach,et al.  Intersubject Synchronization of Cortical Activity During Natural Vision , 2004, Science.

[56]  R. Cameron Craddock,et al.  A comprehensive assessment of regional variation in the impact of head micromovements on functional connectomics , 2013, NeuroImage.