Experimental Brain Research

, Volume 233, Issue 11, pp 3301–3311 | Cite as

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

  • B. Mercante
  • G. Pilurzi
  • F. Ginatempo
  • A. Manca
  • P. Follesa
  • E. Tolu
  • F. Deriu
Research Article


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.


Trigeminal nerve stimulation Transcranial magnetic stimulation Blink reflex Cortical excitability Brainstem excitability Sensorimotor integration 



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).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • B. Mercante
    • 1
  • G. Pilurzi
    • 2
  • F. Ginatempo
    • 1
  • A. Manca
    • 1
  • P. Follesa
    • 3
  • E. Tolu
    • 1
  • F. Deriu
    • 1
  1. 1.Department of Biomedical SciencesUniversity of SassariSassariItaly
  2. 2.Neurological Clinic, Department of Clinical and Experimental MedicineUniversity of SassariSassariItaly
  3. 3.Department of Life and Environmental SciencesUniversity of CagliariMonserratoItaly

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