Transcutaneous vagal nerve stimulation to treat disorders of consciousness: protocol for a double-blind randomized controlled trial

• Marie M. Vitello ^[1] ; Marie-Michèle Briand ^[1] ; Didier Ledoux ^[3] ; Jitka Annen ^[1] ; Riëm El Tahry ^[2] ; Steven Laureys ^[1] ; Didier Martin ^[3] ; Olivia Gosseries ^[1] ; Aurore Thibaut ^[1]
  1. [1] University of Liège

     University of Liège

     Arrondissement de Liège, Bélgica

     
  2. [2] Université Catholique de Louvain

     Université Catholique de Louvain

     Arrondissement de Nivelles, Bélgica

     
  3. [3] University Hospital of Liège

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• Localización: International journal of clinical and health psychology, ISSN 1697-2600, Vol. 23, Nº. 2, 2023, págs. 131-140
• Idioma: inglés
• DOI: 10.1016/j.ijchp.2022.100360
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• Resumen

  • Background Patients with disorders of consciousness (DoC) are a challenging population prone to misdiagnosis with limited effective treatment options. Among neuromodulation techniques, transcutaneous auricular vagal nerve stimulation (taVNS) may act through a bottom-up manner to modulate thalamo-cortical connectivity and promote patients’ recovery. In this clinical trial, we aim to (1) assess the therapeutic clinical effects of taVNS in patients with DoC; (2) investigate the neural mechanisms underlying the effects of its action; (3) assess the feasibility and safety of the procedure in this challenging population; (4) define the phenotype of clinical responders; and (5) assess the long-term efficacy of taVNS in terms of functional outcomes.

    Methods We will conduct a prospective parallel randomized controlled double-blind clinical trial investigating the effects of taVNS as a treatment in DoC patients. Forty-four patients in the early period post-injury (7 to 90 days following the injury) will randomly receive 5 days of either active bilateral vagal stimulation (45 min duration with 30s alternative episodes of active/rest periods; 3mA; 200-300μs current width, 25Hz.) or sham stimulation. Behavioural (i.e., Coma Recovery Scale-Revised, CRS-R) and neurophysiological (i.e., high-density electroencephalography, hd-EEG) measures will be collected at baseline and at the end of the 5-day treatment. Analyses will seek for changes in the CRS-R and the EEG metrics (e.g., alpha band power spectrum, functional connectivity) at the group and individual (i.e., responders) levels.

    Discussion These results will allow us to investigate the vagal afferent network and will contribute towards a definition of the role of taVNS for the treatment of patients with DoC. We aim to identify the neural correlates of its action and pave the way to novel targeted therapeutic strategies.

    Clinical trial registration Clinicaltrials.gov n° NCT04065386.

• Referencias bibliográficas
  • Adams, J. H., Graham, D. I., & Jennett, B. (2000). The neuropathology of the vegetative state after an acute brain insult. Brain : A...
  • Angelakis, E., Konstantinidi, M., & Sakas, D. (2018). Cognitive rehabilitation in disorders of consciousness with transcranial direct...
  • Annen, J., Filippini, M.M., Bonin, E., Cassol, H., Aubinet, C., Carri�ere, M., Gosseries, O., Thibaut, A., Barra, A., Wolff, A., Sanz,...
  • Ardesch, J. J., Buschman, H. P. J., van der Burgh, P. H., Wagener-Schimmel, L. J. J. C., van der Aa, H. E., & Hageman, G. (2007). Cardiac...
  • Aston-Jones, G., & Cohen, J. D. (2005). An integrative theory of locus coeruleus-noepinephrine function: Adaptive gain and optimal performance....
  • Badran, B. W., Dowdle, L. T., Mithoefer, O. J., LaBate, N. T., Coatsworth, J., Brown, J. C., DeVries, W. H., Austelle, C. W., McTeague, L....
  • Bagnato, S. (2022). The role of plasticity in the recovery of consciousness. Handbook of Clinical Neurology, 184, 375–395. doi:10.1016/B978-0-12-819410-2.00020-5.
  • Bai, Y., Xia, X., Wang, Y., Guo, Y., Yang, Y., He, J., & Li, X. (2018). Fronto-parietal coherence response to tDCS modulation in patients...
  • Bell, A. J., & Sejnowski, T. J. (1995). An information-maximization approach to blind separation and blind deconvolution. Neural Computation,...
  • Briand, M. M., Gosseries, O., Staumont, B., Laureys, S., & Thibaut, A. (2020). Transcutaneous auricular vagal nerve stimulation and disorders...
  • Bruno, M. A., Vanhaudenhuyse, A., Thibaut, A., Moonen, G., & Laureys, S. (2011). From unresponsive wakefulness to minimally conscious...
  • Caine, D., & Watson, J. D. G. (2000). Neuropsychological and neuropathological sequelae of cerebral anoxia: A critical review. Journal...
  • Cao, J., Lu, K. H., Powley, T. L., & Liu, Z. (2017). Vagal nerve stimulation triggers widespread responses and alters large-scale functional...
  • Chatelle, C., Majerus, S., Whyte, J., Laureys, S., & Schnakers, C. (2012). A sensitive scale to assess nociceptive pain in patients with...
  • Chatelle, C., Thibaut, A., Whyte, J., de Val, M.D., Laureys, S., & Schnakers, C. (2014). Pain issues in disorders of consciousness. 10.3109/02699052.2014.920518,...
  • Chen, M., Yu, L., Ouyang, F., Liu, Q., Wang, Z., Wang, S., Zhou, L., Jiang, H., & Zhou, S. (2015). The right side or left side of noninvasive...
  • Chennu, S., Annen, J., Wannez, S., Thibaut, A., Chatelle, C., Cassol, H., Martens, G., Schnakers, C., Gosseries, O., Menon, D., & Laureys,...
  • Claassen, J., Velazquez, A., Meyers, E., Witsch, J., Falo, M. C., Park, S., Agarwal, S., Michael Schmidt, J., Schiff, N. D., Sitt, J. D.,...
  • Dorr, A. E., & Debonnel, G. (2006). Effect of vagus nerve stimulation on serotonergic and noradrenergic transmission. The Journal of...
  • Edlow, B. L., Claassen, J., Schiff, N. D., & Greer, D. M. (2021). Recovery from disorders of consciousness: Mechanisms, prognosis and...
  • Estraneo, A., Pascarella, A., Moretta, P., Loreto, V., & Trojano, L. (2015). Clinical and electroencephalographic on�off effect of amantadine...
  • Estraneo, A., & Trojano, L. (2017). Prognosis in disorders of consciousness. Coma and Disorders of Consciousness: Second Edition, 17–36....
  • Faul, F., Erdfelder, E., Lang, A. G., & Buchner, A. (2007). G*Power 3: A flexible statistical power analysis program for the social,...
  • Forgacs, P. B., Frey, H. P., Velazquez, A., Thompson, S., Brodie, D., Moitra, V., Rabani, L., Park, S., Agarwal, S., Falo, M. C., Schiff,...
  • Frangos, E., Ellrich, J., & Komisaruk, B. R. (2015). Non-invasive access to the vagus nerve central projections via electrical stimulation...
  • Fridman, E. A., Beattie, B. J., Broft, A., Laureys, S., & Schif, N. D. (2014). Role of anterior forebrain mesocircuit dysfunction in...
  • Garcia, R. G., Lin, R. L., Lee, J., Kim, J., Barbieri, R., Sclocco, R., Wasan, A. D., Edwards, R. R., Rosen, B. R., Hadjikhani, N., &...
  • Giacino, J. T., Ashwal, S., Childs, N., Cranford, R., Jennett, B., Katz, D. I., Kelly, J. P., Rosenberg, J. H., Whyte, J., Zafonte, R. D.,...
  • Giacino, J. T., Fins, J. J., Laureys, S., & Schiff, N. D. (2014). Disorders of consciousness after acquired brain injury: The state of...
  • Giacino, J. T., Kalmar, K., & Whyte, J. (2004). The JFK coma recovery scale-revised: Measurement characteristics and diagnostic utility....
  • Giacino, J. T., Katz, D. I., Schiff, N. D., Whyte, J., Ashman, E. J., Ashwal, S., Barbano, R., Hammond, F. M., Laureys, S., Ling, G. S. F.,...
  • Giacino, J. T., Whyte, J., Bagiella, E., Kalmar, K., Childs, N., Khademi, A., Eifert, B., Long, D., Katz, D. I., Cho, S., Yablon, S. A.,...
  • Grillner, S., Hellgren, J., Menard, A., Saitoh, K.,&Wikstr€om, M. A. (2005). Mechanisms for selection of basic motor programs�roles...
  • Gusnard, D. A., & Raichle, M. E. (2001). Searching for a baseline: Functional imaging and the resting human brain. Nature Reviews Neuroscience,...
  • Hahn, A., Wadsak, W., Windischberger, C., Baldinger, P., Hoflich, A. S., Losak, J., Nics, L., Philippe, C., Kranz, G. S., Kraus, C., Mitterhauser,...
  • Hakon, J., Moghiseh, M., Poulsen, I., Øland, C. M. L., Hansen, C. P., & Sabers, A. (2020). Transcutaneous vagus nerve stimulation in...
  • Hamer, H. M.,& Bauer, S. (2019). Lessons learned from transcutaneous vagus nerve stimulation (tVNS). Epilepsy Research, 153, 83–84. doi:10.1016/j.eplepsyres.2019.02.015.
  • Jones, T. A., & Schallert, T. (1992). Overgrowth and pruning of dendrites in adult rats recovering from neocortical damage. Brain Research,...
  • Kondziella, D., Bender, A., Diserens, K., van Erp, W., Estraneo, A., Formisano, R., Laureys, S., Naccache, L., Ozturk, S., Rohaut, B., Sitt,...
  • Krahl, S. E., Clark, K. B., Smith, D. C., & Browning, R. A. (1998). Locus coeruleus lesions suppress the seizure-attenuating effects...
  • Kreisberg, E., Esmaeilpour, Z., Adair, D., Khadka, N., Datta, A., Badran, B. W., Bremner, J. D., & Bikson, M. (2021). High-resolution...
  • Laureys, S., Celesia, G. G., Cohadon, F., Lavrijsen, J., Leon-Carrion, J., Sannita, W. G., Sazbon, L., Schmutzhard, E., von Wild, K. R.,...
  • Leech, R., & Sharp, D. J. (2014). The role of the posterior cingulate cortex in cognition and disease. Brain, 137(1), 12–32. doi:10.1093/brain/awt162.
  • Levin, H. S., Boake, C., Song, J., McCauley, S., Contant, C., Diaz-Marchan, P., Brundage, S., Goodman, H.,& Kotrla, K. J. (2001). Validity...
  • Liu, P., Gao, J., Pan, S., Meng, F., Pan, G., Li, J.,& Luo, B. (2016). Effects of high-frequency repetitive transcranial magnetic stimulation...
  • Machetanz, K., Berelidze, L., Guggenberger, R., & Gharabaghi, A. (2021). Transcutaneous auricular vagus nerve stimulation and heart rate...
  • Manta, S., Dong, J., Debonnel, G., & Blier, P. (2009). Enhancement of the function of rat serotonin and norepinephrine neurons by sustained...
  • Naro, A., Russo, M., Leo, A., Bramanti, P., Quartarone, A., & Calabr�o, R. S. (2015). A single session of repetitive transcranial magnetic...
  • Noe, E., Ferri, J., Colomer, C., Moliner, B., O’Valle, M., Ugart, P., & Rodriguez, C. (2019). Feasibility, safety and efficacy of transauricular...
  • Peraza, L. R., Asghar, A. U. R., Green, G., & Halliday, D. M. (2012). Volume conduction effects in brain network inference from electroencephalographic...
  • Rappaport, M., Hall, K. M., Hopkins, K., Belleza, T., & Cope, D. N. (1982). Disability rating scale for severe head trauma: Coma to community....
  • Schiff, N. D. (2009). Recovery of consciousness after brain injury : A mesocircuit hypothesis. Cell Press, 33(1), 1–9. doi:10.1016/j.tins.2009.11.002.
  • Schiff, N. D. (2010). Recovery of consciousness after brain injury: A mesocircuit hypothesis. Trends in Neurosciences, 33(1), 1–9. doi:10.1016/J.TINS.2009.11.002.
  • Schiff, N. D. (2016). Mesocircuit mechanisms underlying recovery of consciousness following severe brain injuries: Model and predictions....
  • Schiff, N. D., Nauvel, T., & Victor, J. D. (2014). Large-scale brain dynamics in disorders of consciousness. Current Opinion in Neurobiology,...
  • Steriade, M., Timofeev, I., & Grenier, F. (2001). Natural waking and sleep states: A view from inside neocortical neurons. Journal of...
  • Straudi, S., Bonsangue, V., Mele, S., Craighero, L., Montis, A., Fregni, F., Lavezzi, S., & Basaglia, N. (2019). Bilateral M1 anodal...
  • Thibaut, A., Bruno, M. A., Ledoux, D., Demertzi, A., & Laureys, S. (2014). tDCS in patients with disorders of consciousness. Neurology,...
  • Thibaut, A., Piarulli, A., Martens, G., Chatelle, C., & Laureys, S. (2019). Effect of multichannel transcranial direct current stimulation...
  • Thibaut, A., Schiff, N., Giacino, J., Laureys, S., & Gosseries, O. (2019). Therapeutic interventions in patients with prolonged disorders...
  • Turgeon, A. F., Lauzier, F., Simard, J.-F., Scales, D. C., Burns, K. E. A., Moore, L., Zygun, D. A., Bernard, F., Meade, M. O., Dung, T....
  • Voss, H. U., Ulug, A. M., Dyke, J. P., Watts, R., Kobylarz, E. J., McCandliss, B. D., Heier, L. A., Beattie, B. J., Hamacher, K. A., Vallabhajosula,...
  • Williams, S. T., Conte, M. M., Goldfine, A. M., Noirhomme, Q., Gosseries, O., Thonnard, M., Beattie, B., Hersh, J., Katz, D. I., Victor,...
  • Xia, X., Bai, Y., Zhou, Y., Yang, Y., Xu, R., Gao, X., Li, X., & He, J. (2017). Effects of 10 Hz repetitive transcranial magnetic stimulation...
  • Yakunina, N., Kim, S. S., & Id, E. N. (2018). BOLD fMRI effects of transcutaneous vagus nerve stimulation in patients with chronic tinnitus....
  • Yap, J. Y. Y., Keatch, C., Lambert, E., Woods, W., Stoddart, P. R., & Kameneva, T. (2020). Critical review of transcutaneous vagus nerve...
  • Yu, Y., Yang, Y., Wang, L., Fang, J., Chen, Y., He, J., & Rong, P. (2017). Transcutaneous auricular vagus nerve stimulation in disorders...
  • Yuan, H., & Silberstein, S. D. (2016). Vagus nerve and vagus nerve stimulation, a comprehensive review: Part II. Headache, 56(2), 259–266....
  • Zeman, A. (2005). The boundaries of consciousness: Neurobiology and neuropathology. Progress in brain research: 150Elsevier. doi:10.1016/S0079-6123(05)50001-3.
  • Zhang, Y., & Song, W. (2018). Transcranial direct current stimulation in disorders of consciousness: A review. International Journal of...