Modafinil alters the functional connectivity of distinct thalamic nuclei with the neocortex
Modafinil promotes wakefulness and enhances cognitive function through mechanisms and neural effects that are still partially unknown. Several studies have shown that the compound alters the functional cortical architecture. In contrast, its influence on subcortical regions and thalamocortical conne...
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Elsevier
2025-05-01
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| Series: | NeuroImage |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1053811925002459 |
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| author | Stefano Delli Pizzi Federica Tomaiuolo Carlo Sestieri Antonio Maria Chiarelli Francesco Gambi Antonio Ferretti Stefano L Sensi |
| author_facet | Stefano Delli Pizzi Federica Tomaiuolo Carlo Sestieri Antonio Maria Chiarelli Francesco Gambi Antonio Ferretti Stefano L Sensi |
| author_sort | Stefano Delli Pizzi |
| collection | DOAJ |
| description | Modafinil promotes wakefulness and enhances cognitive function through mechanisms and neural effects that are still partially unknown. Several studies have shown that the compound alters the functional cortical architecture. In contrast, its influence on subcortical regions and thalamocortical connections, which are crucial for modulating neocortical connectivity, remains unexplored. The acute modulation of thalamo-cortical connectivity was assessed in two groups of participants who received either a single 100 mg dose of modafinil (N = 25) or a placebo (N = 25). Magnetic Resonance Imaging (MRI) was used to parcel the thalamus into its constituent nuclei, which served as seeds for voxel-wise resting state functional connectivity analyses. Additionally, maps of nuclei-specific functional reorganization were compared to those of receptor/transporter expression to assess their spatial overlaps. Modafinil, but not placebo, altered the connectivity of three thalamic nuclei. Specifically, the medial pulvinar nuclei showed increased connectivity with cortical regions of the Sensorimotor and Salience/Ventral Attention (SVAN) Networks. These functional changes spatially overlapped with the distribution of the norepinephrine transporter (NET). Additionally, the anterior and inferior pulvinar complex exhibited enhanced connectivity with the insular and supramarginal regions of the SVAN and superior frontal area of the Default Mode Network (DMN). However, unlike the medial pulvinar, these effects were not spatially linked to the expression of any specific receptor or transporter. Finally, the ventro-lateral anterior complex exhibited increased connectivity with the posterior region of the DMN and the Fronto-Parietal Control Network, along with decreased connectivity to the premotor cortex. The topography of these functional modifications mainly overlaps with the distribution of glutamatergic and serotonergic receptors. In summary, our findings highlight modafinil's influence on thalamocortical circuits, emphasizing the role of higher-order pulvinar nuclei and ventro-lateral anterior complex. |
| format | Article |
| id | doaj-art-d86874d5dc504bfa8c7413686ffcf7ac |
| institution | DOAJ |
| issn | 1095-9572 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage |
| spelling | doaj-art-d86874d5dc504bfa8c7413686ffcf7ac2025-08-20T02:57:05ZengElsevierNeuroImage1095-95722025-05-0131212124210.1016/j.neuroimage.2025.121242Modafinil alters the functional connectivity of distinct thalamic nuclei with the neocortexStefano Delli Pizzi0Federica Tomaiuolo1Carlo Sestieri2Antonio Maria Chiarelli3Francesco Gambi4Antonio Ferretti5Stefano L Sensi6Department of Neuroscience, Imaging, and Clinical Sciences, University ''G. d'Annunzio'' of Chieti-Pescara, Italy; Institute for Advanced Biomedical Technologies (ITAB), University “G. d'Annunzio”of Chieti-Pescara, Italy; Molecular Neurology Unit, Center for Advanced Studies and Technology (CAST), University ''G. d'Annunzio'' of Chieti-Pescara, Italy; Corresponding authors at: Department of Neuroscience, Imaging, and Clinical Sciences, University ''G. d'Annunzio'' of Chieti-Pescara, Italy.Institute for Advanced Biomedical Technologies (ITAB), University “G. d'Annunzio”of Chieti-Pescara, Italy; Department of Engineering and Geology, University “G. d’Annunzio” of Chieti Pescara, ItalyDepartment of Neuroscience, Imaging, and Clinical Sciences, University ''G. d'Annunzio'' of Chieti-Pescara, Italy; Institute for Advanced Biomedical Technologies (ITAB), University “G. d'Annunzio”of Chieti-Pescara, ItalyDepartment of Neuroscience, Imaging, and Clinical Sciences, University ''G. d'Annunzio'' of Chieti-Pescara, Italy; Institute for Advanced Biomedical Technologies (ITAB), University “G. d'Annunzio”of Chieti-Pescara, ItalyDepartment of Neuroscience, Imaging, and Clinical Sciences, University ''G. d'Annunzio'' of Chieti-Pescara, Italy; Molecular Neurology Unit, Center for Advanced Studies and Technology (CAST), University ''G. d'Annunzio'' of Chieti-Pescara, ItalyDepartment of Neuroscience, Imaging, and Clinical Sciences, University ''G. d'Annunzio'' of Chieti-Pescara, Italy; Institute for Advanced Biomedical Technologies (ITAB), University “G. d'Annunzio”of Chieti-Pescara, Italy; UdA-TechLab, Research Center, University “G. d’Annunzio” of Chieti-Pescara, ItalyDepartment of Neuroscience, Imaging, and Clinical Sciences, University ''G. d'Annunzio'' of Chieti-Pescara, Italy; Institute for Advanced Biomedical Technologies (ITAB), University “G. d'Annunzio”of Chieti-Pescara, Italy; Molecular Neurology Unit, Center for Advanced Studies and Technology (CAST), University ''G. d'Annunzio'' of Chieti-Pescara, Italy; Neurology Institute, SS Annunziata University Hospital, University “G. d’Annunzio” of Chieti-Pescara, Italy; Corresponding authors at: Department of Neuroscience, Imaging, and Clinical Sciences, University ''G. d'Annunzio'' of Chieti-Pescara, Italy.Modafinil promotes wakefulness and enhances cognitive function through mechanisms and neural effects that are still partially unknown. Several studies have shown that the compound alters the functional cortical architecture. In contrast, its influence on subcortical regions and thalamocortical connections, which are crucial for modulating neocortical connectivity, remains unexplored. The acute modulation of thalamo-cortical connectivity was assessed in two groups of participants who received either a single 100 mg dose of modafinil (N = 25) or a placebo (N = 25). Magnetic Resonance Imaging (MRI) was used to parcel the thalamus into its constituent nuclei, which served as seeds for voxel-wise resting state functional connectivity analyses. Additionally, maps of nuclei-specific functional reorganization were compared to those of receptor/transporter expression to assess their spatial overlaps. Modafinil, but not placebo, altered the connectivity of three thalamic nuclei. Specifically, the medial pulvinar nuclei showed increased connectivity with cortical regions of the Sensorimotor and Salience/Ventral Attention (SVAN) Networks. These functional changes spatially overlapped with the distribution of the norepinephrine transporter (NET). Additionally, the anterior and inferior pulvinar complex exhibited enhanced connectivity with the insular and supramarginal regions of the SVAN and superior frontal area of the Default Mode Network (DMN). However, unlike the medial pulvinar, these effects were not spatially linked to the expression of any specific receptor or transporter. Finally, the ventro-lateral anterior complex exhibited increased connectivity with the posterior region of the DMN and the Fronto-Parietal Control Network, along with decreased connectivity to the premotor cortex. The topography of these functional modifications mainly overlaps with the distribution of glutamatergic and serotonergic receptors. In summary, our findings highlight modafinil's influence on thalamocortical circuits, emphasizing the role of higher-order pulvinar nuclei and ventro-lateral anterior complex.http://www.sciencedirect.com/science/article/pii/S1053811925002459ModafinilThalamusfMRIPulvinarNorepinephrine transporter |
| spellingShingle | Stefano Delli Pizzi Federica Tomaiuolo Carlo Sestieri Antonio Maria Chiarelli Francesco Gambi Antonio Ferretti Stefano L Sensi Modafinil alters the functional connectivity of distinct thalamic nuclei with the neocortex NeuroImage Modafinil Thalamus fMRI Pulvinar Norepinephrine transporter |
| title | Modafinil alters the functional connectivity of distinct thalamic nuclei with the neocortex |
| title_full | Modafinil alters the functional connectivity of distinct thalamic nuclei with the neocortex |
| title_fullStr | Modafinil alters the functional connectivity of distinct thalamic nuclei with the neocortex |
| title_full_unstemmed | Modafinil alters the functional connectivity of distinct thalamic nuclei with the neocortex |
| title_short | Modafinil alters the functional connectivity of distinct thalamic nuclei with the neocortex |
| title_sort | modafinil alters the functional connectivity of distinct thalamic nuclei with the neocortex |
| topic | Modafinil Thalamus fMRI Pulvinar Norepinephrine transporter |
| url | http://www.sciencedirect.com/science/article/pii/S1053811925002459 |
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