title: Non-stationarity in the "resting brain's" modular architecture.
abstract: Task-free functional magnetic resonance imaging (TF-fMRI) has great potential for advancing the understanding and treatment of neurologic illness. However, as with all measures of neural activity, variability is a hallmark of intrinsic connectivity networks (ICNs) identified by TF-fMRI. This variability has hampered efforts to define a robust metric of connectivity suitable as a biomarker for neurologic illness. We hypothesized that some of this variability rather than representing noise in the measurement process, is related to a fundamental feature of connectivity within ICNs, which is their non-stationary nature. To test this hypothesis, we used a large (n = 892) population-based sample of older subjects to construct a well characterized atlas of 68 functional regions, which were categorized based on independent component analysis network of origin, anatomical locations, and a functional meta-analysis. These regions were then used to construct dynamic graphical representations of brain connectivity within a sliding time window for each subject. This allowed us to demonstrate the non-stationary nature of the brain's modular organization and assign each region to a "meta-modular" group. Using this grouping, we then compared dwell time in strong sub-network configurations of the default mode network (DMN) between 28 subjects with Alzheimer's dementia and 56 cognitively normal elderly subjects matched 1:2 on age, gender, and education. We found that differences in connectivity we and others have previously observed in Alzheimer's disease can be explained by differences in dwell time in DMN sub-network configurations, rather than steady state connectivity magnitude. DMN dwell time in specific modular configurations may also underlie the TF-fMRI findings that have been described in mild cognitive impairment and cognitively normal subjects who are at risk for Alzheimer's dementia.
authors: Department of Neurology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors: David T
authors: DT
authors: Jones
authors: Prashanthi
authors: P
authors: Vemuri
authors: Matthew C
authors: MC
authors: Murphy
authors: Jeffrey L
authors: JL
authors: Gunter
authors: Matthew L
authors: ML
authors: Senjem
authors: Mary M
authors: MM
authors: Machulda
authors: Scott A
authors: SA
authors: Przybelski
authors: Brian E
authors: BE
authors: Gregg
authors: Kejal
authors: K
authors: Kantarci
authors: David S
authors: DS
authors: Knopman
authors: Bradley F
authors: BF
authors: Boeve
authors: Ronald C
authors: RC
authors: Petersen
authors: Clifford R
authors: CR
authors: Jack
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology; D001921:Brain / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male