Abstract
The default-mode network (DMN), which comprises medial frontal, temporal and parietal regions, is part of the brain’s intrinsic organization. The serotonergic (5-HT) neurotransmitter system projects to DMN regions from midbrain efferents, and manipulation of this system could thus reveal insights into the neurobiological mechanisms of DMN functioning. Here, we investigate intrinsic functional connectivity of the DMN as a function of activity of the serotonergic system, through the administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram. We quantified DMN functional connectivity using an approach based on dual-regression. Specifically, we decomposed group data of a subset of the functional time series using spatial independent component analysis, and projected the group spatial modes to the same and an independent resting state time series of individual participants. We found no effects of escitalopram on global functional connectivity of the DMN at the map-level; that is, escitalopram did not alter the global functional architecture of the DMN. However, we found that escitalopram decreased DMN regional pairwise connectivity, which included anterior and posterior cingulate cortex, hippocampal complex and lateral parietal regions. Further, regional DMN connectivity covaried with alertness ratings across participants. Our findings show that escitalopram altered intrinsic regional DMN connectivity, which suggests that the serotonergic system plays an important role in DMN connectivity and its contribution to cognition. Pharmacological challenge designs may be a useful addition to resting-state functional MRI to investigate intrinsic brain functional organization.
Highlights
The brain’s functional organization includes a network of medial frontal and parietal cortex and hippocampal areas [1,2,3,4]
The spatial independent component analysis (sICA) results were used as input to the dual-regression analysis to estimate global functional connectivity of the default-mode network (DMN) for the escitalopram and placebo functional timeseries of RS1 and RS2
Functional connections showed no significant effects of Time or of the interaction between Drug and Time, which suggests that escitalopram-related changes in functional connectivity between DMN ROIs was similar for both resting states RS1 and RS2
Summary
The brain’s functional organization includes a network of medial frontal and parietal cortex and hippocampal areas [1,2,3,4]. This network has been termed the ‘‘default mode’’ network (DMN) [5] because it typically shows increased metabolic activity during resting baseline compared to periods of goal-directed cognitive behaviour. The DMN is thought to play a role in a number of cognitive and affective behaviours, including social and self-referential perception [6,7,8], internal mental representation [9] and memory [4,10,11,12,13]. Impaired medial frontal, parietal or temporal connectivity may respectively contribute to affective processing deficits in major depression (MD) [17,18], and psychotic symptoms in schizophrenia [19,20]
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