Escitalopram Decreases Cross-Regional Functional Connectivity within the Default-Mode Network

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.

Time related effects on functional brain connectivity after serotonergic and cholinergic neuromodulation

“…This does not imply that the partial (time specific) effects are meaningless. A decrease in connectivity at T  = 4.5 h between the default mode network and precuneus, PCC and ACC is in line with earlier results [Klaassens et al, 2015; McCabe and Mishor, 2011; McCabe et al, 2011; Van de Ven et al, 2013; Van Wingen et al, 2014] and in agreement with opposite features in depression, which is characterized by increased connectivity of DMN components [Sundermann et al, 2014]. Especially the posterior part of the DMN, where citalopram effects were most prevalent, has been implicated in SSRI efficacy in depression [Greicius et al, 2007; Li et al, 2013].…”

“…Disruptions of functional networks have been demonstrated in both depressed and demented patients, especially for the default mode network (DMN) [Hafkemeijer et al, 2012; Sundermann et al, 2014; Wang et al, 2006]. Several studies point to normalization of DMN connectivity in depression after SSRI administration [McCabe and Mishor, 2011; McCabe et al, 2011; Van de Ven et al, 2013; Van Wingen et al, 2014]. Yet, there is also proof of more extensive effects of SSRIs on brain connectivity [Klaassens et al, 2015; Schaefer et al, 2014].…”

Reduced Resting-State Functional Connectivity in Current and Recovered Restrictive Anorexia Nervosa

“…In addition, a number of participants had comorbid anxiety or depression diagnoses and, as such, were taking serotonergic antidepressants and/or antipsychotic medications. Antidepressant and antipsychotic medications have been shown to alter resting neural connectivity (84–86), and so the effects of these medications, or indeed comorbid diagnoses, on our results cannot be ruled out.…”

Differential activation of the frontal pole to high vs low calorie foods: The neural basis of food preference in Anorexia Nervosa?

“…In this patient population, comorbidities are common and several individuals were on psychotropic medications, which have been shown to alter neural connectivity (Lui et al, 2010, McCabe and Mishor, 2011, van de Ven et al, 2013), so the effects of these, on our results cannot be ruled out. In addition, as no differences were observed between the AN-R and HC groups, it was not possible to determine whether changes in the AN group result from malnutrition or acute illness.…”