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Trigeminal nerve stimulation modulates brainstem more than cortical excitability in healthy humans

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Abstract

Multiple sites in the central nervous system (CNS) have been hypothesized to explain the beneficial effects of transcutaneous trigeminal nerve stimulation (TNS) on several disorders. This work investigated the acute effects of TNS on the excitability of brainstem and intracortical circuits, as well as on sensorimotor integration processes at cortical level in physiological conditions. Brainstem excitability was evaluated in seventeen healthy subjects measuring the R1 and R2 areas of the blink reflex (BR) and its recovery cycle, with cortical excitability and sensorimotor integration assessed by probing short-interval (SICI) and long-interval (LICI) intracortical inhibition, with short-interval (SICF), intracortical facilitation (ICF), short-latency (SAI) and long-latency (LAI) inhibition measuring motor potentials evoked in the first dorsal interosseous muscle by TMS of the contralateral motor cortex. Neurophysiological parameters were assessed, in seventeen healthy subjects, before and after cyclic 20-min TNS delivered bilaterally to the infraorbital nerve. After TNS, the area of the R2 was significantly reduced (p = 0.018). By contrast, R1 area and R2 recovery cycle were unaffected. Similarly, SICI, ICF, LICI, SICF, SAI and LAI appeared unaltered after TNS. These data suggest that, in normal subjects, TNS mainly acts on brainstem polysynaptic circuits mediating the R2 component of the BR and plays a minor role in modifying the activity of higher-level structures involved in the R2 recovery cycle and in modulation of cortical excitability. A further investigation of a chronic TNS-induced effect may disclose a higher potential for TNS in producing measurable after effects on its CNS targets.

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Acknowledgments

The authors are grateful to Dr. Paolo Enrico for his critical revision of the manuscript, Mr. Paul Gottlieb for language revision. Drs Beniamina Mercante and Andrea Manca were funded by a doctoral research fellowship (XXVIII cycle) awarded by the Regione Autonoma della Sardegna and MIUR (Italy), respectively. Dr Francesca Ginatempo was supported by Fondazione Banco di Sardegna Sassari (Italy).

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    1. Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100, Sassari, Italy

      B. Mercante, F. Ginatempo, A. Manca, E. Tolu & F. Deriu

    2. Neurological Clinic, Department of Clinical and Experimental Medicine, University of Sassari, Viale San Pietro 10, 07100, Sassari, Italy

      G. Pilurzi

    3. Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria Monserrato, 09042, Monserrato, Italy

      P. Follesa

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    B. Mercante, G. Pilurzi and F. Ginatempo have contributed equally to this work.

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    Mercante, B., Pilurzi, G., Ginatempo, F. et al. Trigeminal nerve stimulation modulates brainstem more than cortical excitability in healthy humans. Exp Brain Res 233, 3301–3311 (2015). https://doi.org/10.1007/s00221-015-4398-2

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