Assessing uncertainty in dynamic functional connectivity

ABSTRACT Functional connectivity (FC) – the study of the statistical association between time series from anatomically distinct regions (Friston, 1994, 2011) – has become one of the primary areas of research in the field surrounding resting state functional magnetic resonance imaging (rs‐fMRI). Although for many years researchers have implicitly assumed that FC was stationary across time in rs‐fMRI, it has recently become increasingly clear that this is not the case and the ability to assess dynamic changes in FC is critical for better understanding of the inner workings of the human brain (Hutchison et al., 2013; Chang and Glover, 2010). Currently, the most common strategy for estimating these dynamic changes is to use the sliding‐window technique. However, its greatest shortcoming is the inherent variation present in the estimate, even for null data, which is easily confused with true time‐varying changes in connectivity (Lindquist et al., 2014). This can have serious consequences as even spurious fluctuations caused by noise can easily be confused with an important signal. For these reasons, assessment of uncertainty in the sliding‐window correlation estimates is of critical importance. Here we propose a new approach that combines the multivariate linear process bootstrap (MLPB) method and a sliding‐window technique to assess the uncertainty in a dynamic FC estimate by providing its confidence bands. Both numerical results and an application to rs‐fMRI study are presented, showing the efficacy of the proposed method. HighlightsUncertainty estimation of fMRI‐based dynamic functional connectivity is proposed.Multivariate Linear Process Bootstrap is adapted to correlated bivariate time series.Empirical simulation results show appropriate statistical coverage properties.Two new statistical summaries of dynamic functional connectivity are proposed.Method applied to the resting state fMRI data shows efficacy of our method

[1]  Carsten Jentsch,et al.  Covariance matrix estimation and linear process bootstrap for multivariate time series of possibly increasing dimension , 2015, 1506.00816.

[2]  David T. Jones,et al.  Non-Stationarity in the “Resting Brain’s” Modular Architecture , 2012, PloS one.

[3]  Martin A. Lindquist,et al.  Detecting functional connectivity change points for single-subject fMRI data , 2013, Front. Comput. Neurosci..

[4]  Catie Chang,et al.  Time–frequency dynamics of resting-state brain connectivity measured with fMRI , 2010, NeuroImage.

[5]  Efstathios Paparoditis,et al.  Bootstrap methods for dependent data: A review , 2011 .

[6]  Karl J. Friston Functional and Effective Connectivity: A Review , 2011, Brain Connect..

[7]  Eswar Damaraju,et al.  Tracking whole-brain connectivity dynamics in the resting state. , 2014, Cerebral cortex.

[8]  Daniel A. Handwerker,et al.  Periodic changes in fMRI connectivity , 2012, NeuroImage.

[9]  David A. Leopold,et al.  Dynamic functional connectivity: Promise, issues, and interpretations , 2013, NeuroImage.

[10]  Karl J. Friston Functional and effective connectivity in neuroimaging: A synthesis , 1994 .

[11]  Dimitri Van De Ville,et al.  On spurious and real fluctuations of dynamic functional connectivity during rest , 2015, NeuroImage.

[12]  Min Chen,et al.  Multi-parametric neuroimaging reproducibility: A 3-T resource study , 2011, NeuroImage.

[13]  Gustavo Deco,et al.  Can sliding-window correlations reveal dynamic functional connectivity in resting-state fMRI? , 2016, NeuroImage.

[14]  Martin A. Lindquist,et al.  Dynamic connectivity detection: an algorithm for determining functional connectivity change points in fMRI data , 2015, Front. Neurosci..

[15]  O. Tervonen,et al.  Resting state fMRI reveals a default mode dissociation between retrosplenial and medial prefrontal subnetworks in ASD despite motion scrubbing , 2013, Front. Hum. Neurosci..

[16]  D. Politis,et al.  Banded and tapered estimates for autocovariance matrices and the linear process bootstrap , 2010 .

[17]  Martin A. Lindquist,et al.  Evaluating dynamic bivariate correlations in resting-state fMRI: A comparison study and a new approach , 2014, NeuroImage.

[18]  N. Filippini,et al.  Distinct patterns of brain activity in young carriers of the APOE e4 allele , 2009, NeuroImage.

[19]  Martin A. Lindquist,et al.  Dynamic connectivity regression: Determining state-related changes in brain connectivity , 2012, NeuroImage.