Modulation of cerebellar-cortical connectivity induced by
modafinil and its relationship with receptor and transporter
expression

J 2025

Modulation of cerebellar-cortical connectivity induced by modafinil and its relationship with receptor and transporter expression

PIZZI, Stefano Delli; Federica TOMAIUOLO; Antonio FERRETTI; Giovanna BUBBICO; Valeria ONOFRJ et al.

Základní údaje

Originální název

Modulation of cerebellar-cortical connectivity induced by modafinil and its relationship with receptor and transporter expression

Autoři

PIZZI, Stefano Delli; Federica TOMAIUOLO; Antonio FERRETTI; Giovanna BUBBICO; Valeria ONOFRJ; Stefania Della PENNA; Carlo SESTIERI a Stefano L SENSI

Vydání

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, AMSTERDAM, ELSEVIER, 2025, 2451-9022

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30103 Neurosciences

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.800 v roce 2024

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/25:00140494

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

Modafinil; cerebellum; fMRI; receptors; crus; vermis

Štítky

14110127, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 10. 4. 2026 10:30, Mgr. Tereza Miškechová

Anotace

V originále

Background Modafinil is primarily employed to treat narcolepsy but also as an off-label cognitive enhancer. Functional Magnetic Resonance Imaging (fMRI) studies indicate that modafinil modulates the connectivity of neocortical networks primarily involved in attention and executive functions. However, much less is known about the drug's effects on subcortical structures. Following preliminary findings, we evaluated modafinil’s activity on the connectivity of distinct cerebellar regions with the neocortex. We assessed the spatial relationship of these effects with the expression of neurotransmitter receptors/transporters. Methods Patterns of resting-state fMRI (rs-fMRI) connectivity were estimated in 50 participants from scans acquired pre- and post-administration of a single (100 mg) dose of modafinil (n=25) or placebo (n=25). Using specific cerebellar regions as seeds for voxel-wise analyses, we examined modafinil’s modulation on cerebellar-neocortical connectivity. Next, we conducted a quantitative evaluation of the spatial overlap between the modulation of cerebellar-neocortical connectivity and the expression of neurotransmitter receptors/transporters obtained by publicly available databases. Results Modafinil increased the connectivity of Crus I and Vermis IX with prefrontal regions. Crus I connectivity changes were associated with the expression of dopaminergic D2 receptors. The Vermis I-II showed enhanced coupling with the dorsal anterior cingulate cortex and matched the expression of histaminergic H3 receptors. The Vermis VII-VIII displayed increased connectivity with the visual cortex, an activity associated with dopaminergic and histaminergic neurotransmission. Conclusion Our study reveals modafinil's modulatory effects on cerebellar-neocortical connectivity. The modulation mainly involves Crus I and the Vermis and spatially overlaps the distribution of dopaminergic and histaminergic receptors and serotonin transporters.

Citovat

PIZZI, Stefano Delli; Federica TOMAIUOLO; Antonio FERRETTI; Giovanna BUBBICO; Valeria ONOFRJ; Stefania Della PENNA; Carlo SESTIERI a Stefano L SENSI. Modulation of cerebellar-cortical connectivity induced by modafinil and its relationship with receptor and transporter expression. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. AMSTERDAM: ELSEVIER, 2025, roč. 10, č. 3, s. 304-313. ISSN 2451-9022. Dostupné z: https://doi.org/10.1016/j.bpsc.2024.11.010.

@article{2468497,
   author = {Pizzi, Stefano Delli and Tomaiuolo, Federica and Ferretti, Antonio and Bubbico, Giovanna and Onofrj, Valeria and Penna, Stefania Della and Sestieri, Carlo and Sensi, Stefano L},
   article_location = {AMSTERDAM},
   article_number = {3},
   doi = {https://doi.org/10.1016/j.bpsc.2024.11.010},
   keywords = {Modafinil; cerebellum; fMRI; receptors; crus; vermis},
   language = {eng},
   issn = {2451-9022},
   journal = {Biological Psychiatry: Cognitive Neuroscience and Neuroimaging},
   title = {Modulation of cerebellar-cortical connectivity induced by modafinil and its relationship with receptor and transporter expression},
   url = {https://www.sciencedirect.com/science/article/pii/S2451902224003471},
   volume = {10},
   year = {2025}
}

TY  - JOUR
ID  - 2468497
AU  - Pizzi, Stefano Delli - Tomaiuolo, Federica - Ferretti, Antonio - Bubbico, Giovanna - Onofrj, Valeria - Penna, Stefania Della - Sestieri, Carlo - Sensi, Stefano L
PY  - 2025
TI  - Modulation of cerebellar-cortical connectivity induced by modafinil and its relationship with receptor and transporter expression
JF  - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
VL  - 10
IS  - 3
SP  - 304-313
EP  - 304-313
PB  - ELSEVIER
SN  - 24519022
KW  - Modafinil
KW  - cerebellum
KW  - fMRI
KW  - receptors
KW  - crus
KW  - vermis
UR  - https://www.sciencedirect.com/science/article/pii/S2451902224003471
N2  - Background Modafinil is primarily employed to treat narcolepsy but also as an off-label cognitive enhancer. Functional Magnetic Resonance Imaging (fMRI) studies indicate that modafinil modulates the connectivity of neocortical networks primarily involved in attention and executive functions. However, much less is known about the drug's effects on subcortical structures. Following preliminary findings, we evaluated modafinil’s activity on the connectivity of distinct cerebellar regions with the neocortex. We assessed the spatial relationship of these effects with the expression of neurotransmitter receptors/transporters. Methods Patterns of resting-state fMRI (rs-fMRI) connectivity were estimated in 50 participants from scans acquired pre- and post-administration of a single (100 mg) dose of modafinil (n=25) or placebo (n=25). Using specific cerebellar regions as seeds for voxel-wise analyses, we examined modafinil’s modulation on cerebellar-neocortical connectivity. Next, we conducted a quantitative evaluation of the spatial overlap between the modulation of cerebellar-neocortical connectivity and the expression of neurotransmitter receptors/transporters obtained by publicly available databases. Results Modafinil increased the connectivity of Crus I and Vermis IX with prefrontal regions. Crus I connectivity changes were associated with the expression of dopaminergic D2 receptors. The Vermis I-II showed enhanced coupling with the dorsal anterior cingulate cortex and matched the expression of histaminergic H3 receptors. The Vermis VII-VIII displayed increased connectivity with the visual cortex, an activity associated with dopaminergic and histaminergic neurotransmission. Conclusion Our study reveals modafinil's modulatory effects on cerebellar-neocortical connectivity. The modulation mainly involves Crus I and the Vermis and spatially overlaps the distribution of dopaminergic and histaminergic receptors and serotonin transporters.
ER  -

PIZZI, Stefano Delli; Federica TOMAIUOLO; Antonio FERRETTI; Giovanna BUBBICO; Valeria ONOFRJ; Stefania Della PENNA; Carlo SESTIERI a Stefano L SENSI. Modulation of cerebellar-cortical connectivity induced by modafinil and its relationship with receptor and transporter expression. \textit{Biological Psychiatry: Cognitive Neuroscience and Neuroimaging}. AMSTERDAM: ELSEVIER, 2025, roč.~10, č.~3, s.~304-313. ISSN~2451-9022. Dostupné z: https://doi.org/10.1016/j.bpsc.2024.11.010.

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