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Modafinil alters intrinsic functional connectivity of the right posterior insula: a pharmacological resting state fMRI study.

ABSTRACT: Modafinil is employed for the treatment of narcolepsy and has also been, off-label, used to treat cognitive dysfunction in neuropsychiatric disorders. In a previous study, we have reported that single dose administration of modafinil in healthy young subjects enhances fluid reasoning and affects resting state activity in the Fronto Parietal Control (FPC) and Dorsal Attention (DAN) networks. No changes were found in the Salience Network (SN), a surprising result as the network is involved in the modulation of emotional and fluid reasoning. The insula is crucial hub of the SN and functionally divided in anterior and posterior subregions.Using a seed-based approach, we have now analyzed effects of modafinil on the functional connectivity (FC) of insular subregions.Analysis of FC with resting state fMRI (rs-FMRI) revealed increased FC between the right posterior insula and the putamen, the superior frontal gyrus and the anterior cingulate cortex in the modafinil-treated group.Modafinil is considered a putative cognitive enhancer. The rs-fMRI modifications that we have found are consistent with the drug cognitive enhancing properties and indicate subregional targets of action.ClinicalTrials.gov NCT01684306.

SUBMITTER: Cera N

PROVIDER: S-EPMC4169531 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Modafinil alters intrinsic functional connectivity of the right posterior insula: a pharmacological resting state fMRI study.

Cera Nicoletta N Tartaro Armando A Sensi Stefano L SL

PloS one 20140919 9

<h4>Background</h4>Modafinil is employed for the treatment of narcolepsy and has also been, off-label, used to treat cognitive dysfunction in neuropsychiatric disorders. In a previous study, we have reported that single dose administration of modafinil in healthy young subjects enhances fluid reasoning and affects resting state activity in the Fronto Parietal Control (FPC) and Dorsal Attention (DAN) networks. No changes were found in the Salience Network (SN), a surprising result as the network ...[more]

PMID: 25237810

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Project description:The emergence of flow is a situation of high salience because externally oriented attention on the task and access to resources for goal-directed behavior are enhanced, while internally oriented or self-related cognition is decreased. The right anterior insula has been reported as a causal out-flow hub of the salience resting-state network, orchestrating the engagement of the central executive network (CEN) and the disengagement of the default-mode network (DMN) during a functional challenge. In the present study, we employed a combined task-based activation and connectivity analysis to investigate the role of the right anterior insula during the emergence of flow. A sample of 41 healthy male subjects was confronted with a functional challenge that permitted the emergence of flow during BOLD-based functional magnetic resonance imaging. Comparing connectivity changes in the right anterior insula during the flow condition against connectivity changes associated with control conditions of boredom and overload, relatively increased couplings were observed with the left and right dorsolateral prefrontal cortex. Activation data for these regions did, however, not show the flow-typical inverted U-shaped (invU) response pattern. Relatively decreased functional couplings encompassed ventral aspects of the striatum, but neither the amygdala nor the medial prefrontal cortex (MPFC). For the ventral striatum, activation data were consistent with the flow-typical U-shaped activation pattern, which supports the notion that under the high salience of autotelic situations, the anterior insula is much less positively coupled with the ventral striatum than under boundary conditions of boredom and overload. Taken together, present functional connectivity results were in alignment with the assumed role of the right anterior insula under conditions of different salience. However, this particular region does not appear to mediate the most typical flow-associated activation patterns.

Project description:ObjectiveDaytime cognitive impairment is an essential symptom of primary insomnia (PI). However, the underlying neural substrate remains largely unknown. Many studies have shown that the right anterior insula (rAI) as a key node of salience network (SN) plays a critical role in switching between the executive control network (ECN) and the default mode network (DMN) for better performance of cognitively demanding tasks. Aberrant effective connectivity (directional functional connectivity) of rAI with ECN or DMN may be one reason for daytime cognitive impairment in PI patients. Up to now, no effective connectivity study has been conducted on patients with PI during resting state. Our aim is to investigate the effective connectivity between the rAI and the other voxels in the whole brain in PI.Materials and methodsFifty drug-naive patients with PI and forty age- and sex-matched healthy controls were scanned using resting-state functional MRI. Seed-based Granger causality analysis was used to examine effective connectivity between the rAI, including ventral and dorsal part, and the whole brain. The effective connectivity was compared between the two groups and was correlated with clinical characteristics.ResultsCompared with controls, patients showed decreased effective connectivity from the rAI to the bilateral precuneus, the left postcentral gyrus (extending to bilateral precuneus) and the bilateral cerebellum posterior lobe, and decreased effective connectivity from the bilateral orbitofrontal cortex (OFC) to the rAI (single voxel P < 0.001, AlphaSim corrected with P < 0.01). In addition, effective connectivity from the ventral rAI to the left postcentral gyrus and from the left OFC to the ventral rAI were significantly negatively correlated with Insomnia Severity Index scores (r = -0.28/P = 0.046 and r = -0.29/P = 0.038, respectively).ConclusionThe present study is the first to reveal aberrant effective connectivity between the SN hub (rAI) and the posterior DMN hub (precuneus) as well as decision-making region (OFC) and sensori-motor region in PI. These findings suggest an aberrant salience processing system of the rAI in PI patients.

Dataset Information

Modafinil alters intrinsic functional connectivity of the right posterior insula: a pharmacological resting state fMRI study.

Publications

Modafinil alters intrinsic functional connectivity of the right posterior insula: a pharmacological resting state fMRI study.

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