Associations between repetitive negative thinking and segregation of the anterior salience network amongst healthy middle‐aged adults

Abstract

AbstractBackgroundRepetitive Negative Thinking (RNT) includes negative thoughts about the future (worry) and past (rumination), and has been associated with AD physiopathology (Marchant et al. Alzh&Dement 2020;16:1054). Prefrontal and anterior cingulate cortices play a major role in RNT (Demnitz‐King et al., Psychiatry Res Neuroimaging. 2021;316:111353). Nonetheless, RNT involves several brain regions within large‐scale networks (Makovac et al., Psychiatry Res Neuroimaging. 2020;295:111020), the efficiency of which depends on their ability to remain segregated (Tononi et al., PNAS, 1994;91:11). We investigated associations between RNT and system segregation (SyS) of the Anterior Salience Network (ASN), Default Mode Network (DMN) and Executive Control Network (ECN) in middle‐aged adults.Method248 healthy controls (mean age: 59.17 (SD 4.79), 50.61% women) from the Barcelona Brain Health Initiative (Cattaneo et al. Front Aging Neurosci. 2018;10:321) underwent resting‐state functional magnetic resonance imaging to compute SyS using a node‐based approach with the Shirer atlas (Shirer et al., Cereb Cortex. 2012;22:1). RNT was estimated from questionnaires as previously (Schlosser et al., BMC Psychiatry, 2020;20:1), and a global RNT score was computed. Regression analyses investigated associations between RNT and SyS of ASN, DMN and ECN, including age, depression and stress ratings, emotional stability and cognitive complaints.ResultRNT was positively predicted by cognitive complaints (t = 3.18, p = 0.002) and depression (t = 6.55, p<0.0001), and negatively by emotional stability (t = ‐4.77, p<0.0001). Likewise, RNT was negatively associated with SyS_ASN (t = ‐2.57, p = 0.011; Fig1). Post‐hoc analyses revealed increased connectivity between ASN and ventral DMN (vDMN, t = 2.57, p = 0.01) and the reverse for ASN‐dorsal DMN (dDMN, t = ‐2.03, p = 0.04; Fig2).ConclusionHigher levels of RNT amongst middle‐aged subjects were related to less segregation of the ASN. Results are of importance considering that declining brain segregation predicts dementia severity (Chan et al. Nat Aging 2021;1:1053). Specifically, the ASN presented higher coupling with the vDMN (medial temporal lobe and precuneus), linked to self‐processing and autobiographical processes (Bayley et al., J Neurosci. 2006;26:51), and lower coupling with the dDMN (medial prefrontal regions) associated with cognitive control (Piguet et al., Biol Psychol. 2014;103:195). This dissociative connectivity may partially explain poorer cognitive control and increased self‐referential processes characteristic of RNT (Piguet et al., Biol Psychol. 2014;103:195).