Dynamic states of resting‐state connectivity in patients with mild cognitive impairment

Abstract

AbstractBackgroundResting‐state functional connectivity (rsFC) has demonstrated promise as a biomarker for Alzheimer’s disease. Traditional rsFC assumes that brain connectivity is unvarying during the entire acquisition window. However, recent studies show that brain connection patterns or states are dynamic and change within a few seconds. We modified existing analyses of dynamic functional connectivity to identify differences between patients with Mild Cognitive Impairment (MCI) and controls.Method50 MCI patients (22 males, 74±8 years old) and 55 controls (35 males, age=75±8 y.o.) from ADNI3 with T1 and fast BOLD fMRI (TR=600ms) images were analyzed. Preprocessing consisted of motion correction, despiking, physiological noise correction, and registration to MNI space. Sliding windows had a stride length of 1 TR and contained 50 TRs. Correlation matrices were generated between brain regions of the default mode (DMN), salience (Sal), dorsal attention (DAN), and frontoparietal (FPN) networks. The data was then harmonized using ComBat to remove scanner‐related differences. Distinct brain connectivity patterns or states were extracted with Davies‐Bouldin optimized k‐means clustering. Dwell time (i.e., the number of TRs for which a state is sustained) and transition probability (i.e., the probability of changing state) were calculated. Significant differences were assessed using a t‐test without correcting for multiple comparisons.ResultWe identified eight states (Figure 1). No significant differences were discovered in dwell time (Figure 2). Six transition probabilities had p<0.05 (Figure 3). These included the transition from 2 to 5 (p=0.03), 2 to 6 (p=0.04), 2 to 7 (p=0.04), 4 to 3 (p=0.005), 6 to 3 (p=0.01), 8 to 4 (p=0.05), and 8 to 7 (p=0.05).ConclusionOur study showed MCI patients were less likely to transition from state 4 to 3 compared to controls. State 4 is characterized by positive rsFC within the DMN and FPN as well as between the networks. Compared to state 4, state 3 had decreased rsFC within the DMN and FPN and between the networks. State 3 also shows increased positive rsFC within and between Sal and DAN. Interaction between the 4 networks has been implicated in AD. The inability to perform this transition could explain cognitive deficits observed in MCI.