Abstract
As findings on the neuropathological and behavioral components of Alzheimer’s disease (AD) continue to accrue, converging evidence suggests that macroscale brain functional disruptions may mediate their association. Recent developments on theoretical neuroscience indicate that instantaneous patterns of brain connectivity and metastability may be a key mechanism in neural communication underlying cognitive performance. However, the potential significance of these patterns across the AD spectrum remains virtually unexplored. We assessed the clinical sensitivity of static and dynamic functional brain disruptions across the AD spectrum using resting-state fMRI in a sample consisting of AD patients (n = 80) and subjects with either mild (n = 44) or subjective (n = 26) cognitive impairment (MCI, SCI). Spatial maps constituting the nodes in the functional brain network and their associated time-series were estimated using spatial group independent component analysis and dual regression, and whole-brain oscillatory activity was analyzed both globally (metastability) and locally (static and dynamic connectivity). Instantaneous phase metrics showed functional coupling alterations in AD compared to MCI and SCI, both static (putamen, dorsal and default-mode) and dynamic (temporal, frontal-superior and default-mode), along with decreased global metastability. The results suggest that brains of AD patients display altered oscillatory patterns, in agreement with theoretical premises on cognitive dynamics.
Highlights
A scanning session –the so-called functional connectivity
Based on established knowledge about the anatomical distribution of the pathophysiology and resting-state fMRI alterations in Alzheimer’s disease (AD), and considering theoretical concepts on the relevance of a wide set of time-varying connectivity, we hypothesized that patients with AD exhibit altered Statistical analysis of average coupling (sFC) and dynamic functional connectivity (dFC), both at the whole-brain level and at specific brain nodes implicating temporal, parietal and subcortical structures, reflecting a graded pattern of differences corresponding with disease severity
The present study evaluated the potential association between fMRI based neural oscillatory coupling disruptions and clinical severity across a phenotypical continuum related to cognitive status (AD, MCI and SCI)
Summary
A scanning session –the so-called (static) functional connectivity. For example, AD patients have been shown to exhibit stronger hippocampal connectivity within the default mode network and weaker hippocampal-cingulate co-activation[6]. Recent conceptual, theoretical and methodological advances may shed light on these mixed findings; among them, the observation that time-varying coupling and de-coupling of brain regions embeds information that may be important in clinical settings[10,11]. This novel and biologically feasible framework has been conceptualized in the communication through coherence theory, which postulates that cognition is linked to neural communication emerging from coherent oscillatory activity, and that cognitive functions require a flexible set of signaling processes occurring on top of the anatomical backbone of the brain[12,13,14]. Based on established knowledge about the anatomical distribution of the pathophysiology and resting-state fMRI alterations in AD, and considering theoretical concepts on the relevance of a wide set of time-varying connectivity, we hypothesized that patients with AD exhibit altered sFC and dFC, both at the whole-brain level and at specific brain nodes implicating temporal, parietal and subcortical structures, reflecting a graded pattern of differences corresponding with disease severity
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