Modafinil-Induced Changes in Functional Connectivity in the Cortex and Cerebellum of Healthy Elderly Subjects

Abstract

In the past few years, cognitive enhancing drugs (CEDs) have gained growing interest and the focus of investigations aimed at exploring their use to potentiate the cognitive performances of healthy individuals. Most of this exploratory CED-related research has been performed on young adults. However, CEDs may also help to maintain optimal brain functioning or compensate for subtle and or subclinical deficits associated with brain aging or early-stage dementia. In this study, we assessed effects on resting state brain activity in a group of healthy elderly subjects undergoing acute administration of modafinil, a wakefulness-promoting agent. To that aim, participants (n = 24) were investigated with resting state functional Magnetic Resonance Imaging (rs-fMRI) before and after the administration of a single dose (100 mg) of modafinil. Effects were compared to age and size-matched placebo group. Rs-fMRI effects were assessed, employing a graph-based approach and Eigenvector Centrality (EC) analysis, by taking in account topological changes occurring in functional brain networks. The main finding of the study is that modafinil promotes enhanced centrality, a measure of the importance of nodes within functional networks, of the bilateral primary visual (V1) cortex. EC analysis also revealed that modafinil-treated subjects show increased functional connectivity between the V1 and specific cerebellar (Crus I, Crus II, VIIIa lobule) and frontal (right inferior frontal sulcus and left middle frontal gyrus) regions. Present findings provide functional data supporting the hypothesis that modafinil can modulate the cortico-cerebellar connectivity of the aging brain.

Modafinil treatment modulates functional connectivity in stroke survivors with severe fatigue

“…We mainly observed decreases in rsFC, which was in contrast to our a-priori hypothesis. Studies on rsFC after modafinil administration are scarce, however, those available indicate an increase of connectivity in areas such as the frontal cortex 51 , the posterior insula 52 , and the anterior cingulate cortex 20 . Our findings showed a decrease in rsFC in several brain networks, which may be indicative of post-stroke fatigue related hyper-connectivity, which normalizes after modafinil administration.…”

Особливості Когнітивних Порушень У Хворих На Розсіяний Склероз

“…виявлено, що модафініл покращує концентрацію уваги й вербальну пам'ять [56]. Згідно з даними літератури, модафініл, покращуючи дофамінергічну й норадренергічну передачі, сприяє посиленню нейрогенезу, Практикуючому неврологу /To Practicing Neurologist/ особливо в ділянці гіпокампа [57], що проявляється покращенням просторової орієнтації, уваги й функціонального стану білої речовини головного мозку [58]. Терапія бета-інтерферонами, згідно з даними деяких клінічних досліджень, приводить до покращення показників когнітивних функцій, особливо концентрації уваги й короткотривалої пам'яті [59], зокрема, застосування авонексу та ребіфу (інтерферон β-1a) має переваги перед бетафероном (інтерферон β-1b) [60].…”

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“…The half-life of the drug was approximately between 10-12 h range, which was differed by CYP-genotypes, functioning of liver and kidney. The drug is metabolized in the liver and resulting inactive metabolite is excreted in the urine [7][8][9] .…”