tDCS cranial nerve Co-stimulation: Unveiling brainstem pathways involved in trigeminal nerve direct current stimulation in rats

Background: The effects of transcranial direct current stimulation (tDCS) are generally thought to result from the polarization of cortical neurons by the weak electric fields it creates. However, recent evidence suggests that some tDCS effects may be mediated through co-stimulation of peripheral or...

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Main Authors: Alireza Majdi, Liyi Chen, Lars E. Larsen, Robrecht Raedt, Myles Mc Laughlin
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Brain Stimulation
Online Access:http://www.sciencedirect.com/science/article/pii/S1935861X25000312
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author Alireza Majdi
Liyi Chen
Lars E. Larsen
Robrecht Raedt
Myles Mc Laughlin
author_facet Alireza Majdi
Liyi Chen
Lars E. Larsen
Robrecht Raedt
Myles Mc Laughlin
author_sort Alireza Majdi
collection DOAJ
description Background: The effects of transcranial direct current stimulation (tDCS) are generally thought to result from the polarization of cortical neurons by the weak electric fields it creates. However, recent evidence suggests that some tDCS effects may be mediated through co-stimulation of peripheral or cranial nerves, particularly the trigeminal nerve (TN). The TN projects to key brainstem nuclei that regulate neurotransmitter release throughout the central nervous system, but the specific pathways involved are not yet well understood. Methods: In this study, we examined the effects of acute transcutaneous TN direct current stimulation (TN-DCS) on tonic (i.e. mean spike rate) and phasic (number of bursts, spike rate per burst, burst duration, and inter-burst interval) activities while simultaneously recording single-neuron activity across three brainstem nuclei in rats: the locus coeruleus (LC; phasic and tonic activities), dorsal raphe nucleus (DRN; tonic activity), and median raphe nucleus (MnRN; tonic activity). Results: TN-DCS significantly modulated tonic activity in the LC and DRN, with interactions between amplitude, polarity, and time affecting mean spike rates. It also influenced phasic activity in the LC, altering burst number, duration, and inter-burst intervals. In contrast, MnRN tonic activity was unchanged. Blocking TN with xylocaine eliminated the effects on tonic activity in both the LC and DRN. Conclusions: These results suggest that tDCS may modulate the TN, altering DRN and LC activity. Differential changes in tonic and phasic LC activity highlight their roles in TN-DCS effects on the cortex. This research offers insights to improve tDCS efficacy and understanding. Keywords: tDCS; trigeminal nerve; locus coeruleus; Dorsal raphe nucleus; median raphe nucleus.
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spelling doaj-art-a3c3a839a83643829f647f61dd6472262025-02-12T05:30:57ZengElsevierBrain Stimulation1935-861X2025-03-01182171184tDCS cranial nerve Co-stimulation: Unveiling brainstem pathways involved in trigeminal nerve direct current stimulation in ratsAlireza Majdi0Liyi Chen1Lars E. Larsen2Robrecht Raedt3Myles Mc Laughlin4Research Group Experimental Oto-rhino-laryngology, Department of Neuroscience, Leuven Brain Institute, KU Leuven, Leuven, 3000, Belgium; Leuven Brain Institute, KU Leuven, Leuven, 3000, BelgiumResearch Group Experimental Oto-rhino-laryngology, Department of Neuroscience, Leuven Brain Institute, KU Leuven, Leuven, 3000, Belgium; Leuven Brain Institute, KU Leuven, Leuven, 3000, Belgium4BRAIN, Department of Head and Skin, Ghent University, 9000, Ghent, Belgium; MEDISIP, Department of Electronics and Information Systems, Ghent University, 9000, Ghent, BelgiumMEDISIP, Department of Electronics and Information Systems, Ghent University, 9000, Ghent, BelgiumResearch Group Experimental Oto-rhino-laryngology, Department of Neuroscience, Leuven Brain Institute, KU Leuven, Leuven, 3000, Belgium; Leuven Brain Institute, KU Leuven, Leuven, 3000, Belgium; Corresponding author. Research Group Experimental Oto-rhino-laryngology, RK-Herestraat 49 - box 1036, 3000, Leuven, Belgium.Background: The effects of transcranial direct current stimulation (tDCS) are generally thought to result from the polarization of cortical neurons by the weak electric fields it creates. However, recent evidence suggests that some tDCS effects may be mediated through co-stimulation of peripheral or cranial nerves, particularly the trigeminal nerve (TN). The TN projects to key brainstem nuclei that regulate neurotransmitter release throughout the central nervous system, but the specific pathways involved are not yet well understood. Methods: In this study, we examined the effects of acute transcutaneous TN direct current stimulation (TN-DCS) on tonic (i.e. mean spike rate) and phasic (number of bursts, spike rate per burst, burst duration, and inter-burst interval) activities while simultaneously recording single-neuron activity across three brainstem nuclei in rats: the locus coeruleus (LC; phasic and tonic activities), dorsal raphe nucleus (DRN; tonic activity), and median raphe nucleus (MnRN; tonic activity). Results: TN-DCS significantly modulated tonic activity in the LC and DRN, with interactions between amplitude, polarity, and time affecting mean spike rates. It also influenced phasic activity in the LC, altering burst number, duration, and inter-burst intervals. In contrast, MnRN tonic activity was unchanged. Blocking TN with xylocaine eliminated the effects on tonic activity in both the LC and DRN. Conclusions: These results suggest that tDCS may modulate the TN, altering DRN and LC activity. Differential changes in tonic and phasic LC activity highlight their roles in TN-DCS effects on the cortex. This research offers insights to improve tDCS efficacy and understanding. Keywords: tDCS; trigeminal nerve; locus coeruleus; Dorsal raphe nucleus; median raphe nucleus.http://www.sciencedirect.com/science/article/pii/S1935861X25000312
spellingShingle Alireza Majdi
Liyi Chen
Lars E. Larsen
Robrecht Raedt
Myles Mc Laughlin
tDCS cranial nerve Co-stimulation: Unveiling brainstem pathways involved in trigeminal nerve direct current stimulation in rats
Brain Stimulation
title tDCS cranial nerve Co-stimulation: Unveiling brainstem pathways involved in trigeminal nerve direct current stimulation in rats
title_full tDCS cranial nerve Co-stimulation: Unveiling brainstem pathways involved in trigeminal nerve direct current stimulation in rats
title_fullStr tDCS cranial nerve Co-stimulation: Unveiling brainstem pathways involved in trigeminal nerve direct current stimulation in rats
title_full_unstemmed tDCS cranial nerve Co-stimulation: Unveiling brainstem pathways involved in trigeminal nerve direct current stimulation in rats
title_short tDCS cranial nerve Co-stimulation: Unveiling brainstem pathways involved in trigeminal nerve direct current stimulation in rats
title_sort tdcs cranial nerve co stimulation unveiling brainstem pathways involved in trigeminal nerve direct current stimulation in rats
url http://www.sciencedirect.com/science/article/pii/S1935861X25000312
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