Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Transcranial direct current stimulation reconstructs diminished thalamocortical connectivity during prolonged resting wakefulness: a resting-state fMRI pilot study


Reductions in the alertness and information processing capacity of individuals due to sleep deprivation (SD) were previously thought to be related to dysfunction of the thalamocortical network. Previous studies have shown that transcranial direct current stimulation (tDCS) can restore vigilance and information processing after SD. However, the underlying neural mechanisms of this phenomenon remain unclear. The purpose of this study was to investigate the neurocognitive mechanisms of tDCS following SD, by comparing changes in the brain network, especially the thalamocortical network, after tDCS and sham stimulation following 24 h of SD. Sixteen healthy volunteers were tested in a sham-controlled, randomized crossover design experiment. Resting-state functional magnetic resonance imaging was conducted during resting wakefulness and again after either active tDCS or sham stimulation to the right dorsolateral prefrontal cortex (1.0 mA, 20 min) immediately following 24 h of SD. Seed-based correlations and graph theory analysis were used to determine functional connectivity within the brain thalamocortical network. When tDCS was used, the functional connectivity of the thalamus with the temporal lobe and left caudate was higher than that when the sham stimulation was used. Analysis using graph theory showed that compared with sham stimulation, tDCS administration was associated with a significant improvement in not only the number of connections but also the global efficiency of the thalamus itself. Our study reveals a modulation of the activity of the intrinsic thalamus networks after tDCS. The effects may help explain earlier reports of improvements in the cognitive performance after anodal-tDCS.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. Akerstedt, T. (2003). Shift work and disturbed sleep/wakefulness. Occupational Medicine, 53(2), 89–94.

  2. Alexander-Bloch, A., Giedd, J. N., & Bullmore, E. (2013). Imaging structural co-variance between human brain regions. Nature Reviews. Neuroscience, 14(5), 322–336.

  3. Alonzo, A., Brassil, J., Taylor, J. L., Martin, D., & Loo, C. K. (2012). Daily transcranial direct current stimulation (tdcs) leads to greater increases in cortical excitability than second daily transcranial direct current stimulation. Brain Stimulation, 5(3), 208–213.

  4. Antal, A., Nitsche, M. A., Kincses, T. Z., Kruse, W., Hoffmann, K. P., & Paulus, W. (2004). Facilitation of visuo-motor learning by transcranial direct current stimulation of the motor and extrastriate visual areas in humans. The European Journal of Neuroscience, 19(10), 2888–2892.

  5. Arbon, E. L., Knurowska, M., & Dijk, D. J. (2015). Randomised clinical trial of the effects of prolonged-release melatonin, temazepam and zolpidem on slow-wave activity during sleep in healthy people. Journal of Psychopharmacology, 29(7), 764–776.

  6. Baschi, R., Sava, S. L., Salvia, V. L., Pasqua, V. D., Schoenen, J., & Magis, D. (2014). Transcranial direct current stimulation in chronic migraine: A pilot trial combining cathodal visual and anodal dlpfc stimulation. Journal of Headache & Pain, 15(1), 1.

  7. Behrens, T. E., Johansenberg, H., Woolrich, M. W., Smith, S. M., Wheelerkingshott, C. A., & Boulby, P. A., et al. (2003). Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging. Nature Neuroscience, 6(7), 750.

  8. Ben Simon, E., Maron Katz, A., Lahav, N., Shamir, R., & Hendler, T. (2017). Tired and misconnected: a breakdown of brain modularity following sleep deprivation. Biological Psychiatry, 38(6), 3300–3314.

  9. Bikson, M., Datta, A., & Elwassif, M. (2009). Establishing safety limits for transcranial direct current stimulation. Clinical Neurophysiology, 120(6), 1033–1034.

  10. Boonstra, T. W., Nikolin, S., Meisener, A., Martin, D. M., & Loo, C. K. (2016). Change in mean frequency of resting-state electroencephalography after transcranial direct current stimulation. Frontiers in Human Neuroscience, 10.

  11. Bullmore, E., & Sporns, O. (2009). Complex brain networks: Graph theoretical analysis of structural and functional systems. Nature Reviews. Neuroscience, 10(3), 186–198.

  12. Chengyang, L., Daqing, H., Jianlin, Q., Haisheng, C., Qingqing, M., Jin, W., Jiajia, L., Enmao, Y., Yongcong, S., & Xi, Z. (2017). Short-term memory deficits correlate with hippocampal-thalamic functional connectivity alterations following acute sleep restriction. Brain Imaging and Behavior, 11(4), 954–963.

  13. Clark, V. P., Coffman, B. A., Mayer, A. R., Weisend, M. P., Lane, T. D. R., Calhoun, V. D., Raybourn, E. M., Garcia, C. M., & Wassermann, E. M. (2012). Tdcs guided using fmri significantly accelerates learning to identify concealed objects. Neuroimage, 59(1), 117–128.

  14. Coffman, B. A., Clark, V. P., & Parasuraman, R. (2014). Battery powered thought: Enhancement of attention, learning, and memory in healthy adults using transcranial direct current stimulation. Neuroimage, 85(Pt 3), 895–908.

  15. Cummiford, C. M., Nascimento, T. D., Foerster, B. R., Clauw, D. J., Zubieta, J. K., Harris, R. E., & DaSilva, A. F. (2016). Changes in resting state functional connectivity after repetitive transcranial direct current stimulation applied to motor cortex in fibromyalgia patients. Arthritis Research & Therapy, 18, 40.

  16. De Havas, J. A., Parimal, S., Soon, C. S., & Chee, M. W. L. (2012). Sleep deprivation reduces default mode network connectivity and anti-correlation during rest and task performance. Neuroimage, 59(2), 1745–1751.

  17. Ebajemito, J. K., Furlan, L., Nissen, C., & Sterr, A. (2016). Application of transcranial direct current stimulation in neurorehabilitation: The modulatory effect of sleep. Frontiers in Neurology, 7.

  18. Elder, G. J., & Taylor, J. P. (2014). Transcranial magnetic stimulation and transcranial direct current stimulation: Treatments for cognitive and neuropsychiatric symptoms in the neurodegenerative dementias? Alzheimer's Research & Therapy, 6(9), 74.

  19. Frase, L., Piosczyk, H., Zittel, S., Jahn, F., Selhausen, P., Krone, L., Feige, B., Mainberger, F., Maier, J. G., Kuhn, M., Kloppel, S., Normann, C., Sterr, A., Spiegelhalder, K., Riemann, D., Nitsche, M. A., & Nissen, C. (2016). Modulation of total sleep time by transcranial direct current stimulation (tdcs). Neuropsychopharmacol, 41(10), 2577–2586.

  20. Fregni, F., Boggio, P. S., Nitsche, M., Bermpohl, F., Antal, A., Feredoes, E., Marcolin, M. A., Rigonatti, S. P., Silva, M. T. A., Paulus, W., & Pascual-Leone, A. (2005). Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory. Experimental Brain Research, 166(1), 23–30.

  21. Garc A-Larrea, L., Peyron, R., Mertens, P., Gregoire, M. C., Lavenne, F., Le Bars, D., Convers, P., Mauguière, F., Sindou, M., & Laurent, B. (1999). Electrical stimulation of motor cortex for pain control: A combined pet-scan and electrophysiological study. Pain, 83(2), 259–273.

  22. Goel, N. (2017). Neurobehavioral effects and biomarkers of sleep loss in healthy adults. Current Neurology and Neuroscience Reports, 17(11), 89.

  23. Grunblatt, E., Zehetmayer, S., Jacob, C. P., Muller, T., Jost, W. H., & Riederer, P. (2010). Pilot study: Peripheral biomarkers for diagnosing sporadic parkinson's disease. Journal of Neural Transmission (Vienna), 117(12), 1387–1393.

  24. Gujar, N., Yoo, S. S., Hu, P., & Walker, M. P. (2010). The unrested resting brain: Sleep deprivation alters activity within the default-mode network. Journal of Cognitive Neuroscience, 22(8), 1637–1648.

  25. Haber, S. N., & Calzavara, R. (2009). The cortico-basal ganglia integrative network: The role of the thalamus. Brain Research Bulletin, 78(2), 69–74.

  26. Hagenacker, T., Bude, V., Naegel, S., Holle, D., Katsarava, Z., Diener, H. C., & Obermann, M. (2014). Patient-conducted anodal transcranial direct current stimulation of the motor cortex alleviates pain in trigeminal neuralgia. The Journal of Headache and Pain, 15, 78.

  27. Jacob, C. P., Nguyen, T. T., Dempfle, A., Heine, M., Windemuth-Kieselbach, C., Baumann, K., Jacob, F., Prechtl, J., Wittlich, M., Herrmann, M. J., Gross-Lesch, S., Lesch, K. P., & Reif, A. (2010). A gene-environment investigation on personality traits in two independent clinical sets of adult patients with personality disorder and attention deficit/hyperactive disorder. European Archives of Psychiatry and Clinical Neuroscience, 260(4), 317–326.

  28. Jamil, A., Batsikadze, G., Kuo, H. I., Labruna, L., Hasan, A., Paulus, W., & Nitsche, M. A. (2017). Systematic evaluation of the impact of stimulation intensity on neuroplastic after-effects induced by transcranial direct current stimulation. The Journal of Physiology, 595(4), 1273–1288.

  29. Kaida, K., Takahashi, M., Åkerstedt, T., Nakata, A., Otsuka, Y., Haratani, T., & Fukasawa, K. (2006). Validation of the karolinska sleepiness scale against performance and eeg variables. Clinical Neurophysiology, 117(7), 1574–1581.

  30. Kincses, T. Z., Antal, A., Nitsche, M. A., Bartfai, O., & Paulus, W. (2004). Facilitation of probabilistic classification learning by transcranial direct current stimulation of the prefrontal cortex in the human. Neuropsychologia, 42(1), 113–117.

  31. Kripke, D. F., Langer, R. D., & Kline, L. E. (2012). Hypnotics' association with mortality or cancer: A matched cohort study. BMJ Open, 2(1), e850.

  32. Martin, D. M., Liu, R., Alonzo, A., Green, M., & Loo, C. K. (2014). Use of transcranial direct current stimulation (tdcs) to enhance cognitive training: effect of timing of stimulation. Experimental Brain Research, 232(10), 3345–3351.

  33. McIntire, L. K., McKinley, R. A., Goodyear, C., & Nelson, J. (2014). A comparison of the effects of transcranial direct current stimulation and caffeine on vigilance and cognitive performance during extended wakefulness. Brain Stimulation, 7(4), 499–507.

  34. McIntire, L., Mckinley, R. A., Nelson, J., & Goodyear, C. (2017a). Transcranial direct current stimulation (tdcs) versus caffeine to sustain wakefulness at night when dosing at start-of-shift. New York: Springer International Publishing.

  35. McIntire, L. K., McKinley, R. A., Nelson, J. M., & Goodyear, C. (2017b). Transcranial direct current stimulation versus caffeine as a fatigue countermeasure. Brain Stimulation, 10(6), 1070–1078.

  36. Mckinley, R. A., Mcintire, L., Bridges, N., Goodyear, C., Bangera, N. B., & Weisend, M. P. (2013). Acceleration of image analyst training with transcranial direct current stimulation. Behavioral Neuroscience, 127(6), 936–946.

  37. Moliadze, V., Lyzhko, E., Schmanke, T., Andreas, S., Freitag, C. M., & Siniatchkin, M. (2018). 1 ma cathodal tdcs shows excitatory effects in children and adolescents: insights from tms evoked n100 potential. Brain Research Bulletin, 140, 43–51.

  38. Nelson, J. T., McKinley, R. A., Golob, E. J., Warm, J. S., & Parasuraman, R. (2014). Enhancing vigilance in operators with prefrontal cortex transcranial direct current stimulation (tdcs). Neuroimage, 85(Pt 3), 909–917.

  39. Park, C. H., Chang, W. H., Park, J. Y., Shin, Y. I., Kim, S. T., & Kim, Y. H. (2013). Transcranial direct current stimulation increases resting state interhemispheric connectivity. Neuroscience Letters, 539, 7–10.

  40. Robertson, G. J. (2010). Raven's progressive matrices. Hoboken: Wiley.

  41. Roy, A., Baxter, B., & He, B. (2014). High-definition transcranial direct current stimulation induces both acute and persistent changes in broadband cortical synchronization: a simultaneous tdcs-eeg study. IEEE Xplore: IEEE Transactions on Biomedical Engineering, 61(7), 1967–1978.

  42. Sanchez-Kuhn, A., Perez-Fernandez, C., Canovas, R., Flores, P., & Sanchez-Santed, F. (2017). Transcranial direct current stimulation as a motor neurorehabilitation tool: An empirical review. Biomedical Engineering Online, 16(Suppl 1), 76.

  43. Schoenborn, CA, Adams, PE. (2010). Health behaviors of adults: United States, 2005-2007. Vital and health statistics. Series 10, Data from the National Health Survey (245), 1-132.

  44. Shao, Y., Wang, L., Ye, E., Jin, X., Ni, W., Yang, Y., Wen, B., Hu, D., & Yang, Z. (2013). Decreased thalamocortical functional connectivity after 36 hours of total sleep deprivation: Evidence from resting state fmri. PLoS One, 8(10), e78830.

  45. Shao, Y., Lei, Y., Wang, L., Zhai, T., Jin, X., Ni, W., Yang, Y., Tan, S., Wen, B., Ye, E., & Yang, Z. (2014). Altered resting-state amygdala functional connectivity after 36 hours of total sleep deprivation. PLoS One, 9(11), e112222.

  46. Simon, E. B., Oren, N., Sharon, H., Kirschner, A., Goldway, N., Okon-Singer, H., Tauman, R., Deweese, M. M., Keil, A., & Hendler, T. (2015). Losing neutrality: The neural basis of impaired emotional control without sleep. The Journal of Neuroscience, 35(38), 13194–13205.

  47. Stagg, C. J., Lin, R. L., Mezue, M., Segerdahl, A., Kong, Y., Xie, J., & Tracey, I. (2013). Widespread modulation of cerebral perfusion induced during and after transcranial direct current stimulation applied to the left dorsolateral prefrontal cortex. The Journal of Neuroscience, 33(28), 11425–11431.

  48. Thakrar, C., Patel, K., D'Ancona, G., Kent, B. D., Nesbitt, A., Selsick, H., Steier, J., Rosenzweig, I., Williams, A. J., Leschziner, G. D., & Drakatos, P. (2017). Effectiveness and side-effect profile of stimulant therapy as monotherapy and in combination in the central hypersomnias in clinical practice. Journal of Sleep Research, 27, e12627.

  49. Tomasi, D., Wang, R. L., Telang, F., Boronikolas, V., Jayne, M. C., Wang, G. J., Fowler, J. S., & Volkow, N. D. (2009). Impairment of attentional networks after 1 night of sleep deprivation. Cerebral Cortex, 19(1), 233–240.

  50. Turi, Z., Mittner, M., Opitz, A., Popkes, M., Paulus, W., & Antal, A. (2015). Transcranial direct current stimulation over the left prefrontal cortex increases randomness of choice in instrumental learning. Cortex, 63, 145–154.

  51. Van, M. C., Daniels, N., de Beeck, H. O., & Baeck, A. (2001). Effect of tdcs on task relevant and irrelevant perceptual learning of complex objects Journal of Vision, 16(6), 13.

  52. Weber, M. J., Messing, S. B., Rao, H., Detre, J. A., & Thompson-Schill, S. L. (2014). Prefrontal transcranial direct current stimulation alters activation and connectivity in cortical and subcortical reward systems: A tdcs-fmri study. Human Brain Mapping, 35(8), 3673–3686.

  53. Wesensten, N., Belenky, G., Kautz, M. A., Thorne, D. R., Reichardt, R. M., & Balkin, T. J. (2002). Maintaining alertness and performance during sleep deprivation: Modafinil versus caffeine. Psychopharmacology, 159(3), 238–247.

  54. Zaehle, T., Sandmann, P., Thorne, J. D., Janccke, L., & Herrmann, C. S. (2011). Transcranial direct current stimulation of the prefrontal cortex modulates working memory performance: Combined behavioural and electrophysiological evidence. BMC Neuroscience, 12, 2.

  55. Zhao, H., Qiao, L., Fan, D., Zhang, S., Turel, O., Li, Y., Li, J., Xue, G., Chen, A., & He, Q. (2017). Modulation of brain activity with noninvasive transcranial direct current stimulation (tdcs): Clinical applications and safety concerns. Frontiers in Psychology, 8.

Download references


This work was supported by the National Military Science Foundation of China, No. AWS14J011 and No.AWS16J028, Science Foundation of the 309 hospital, No. 2015MS-018, and National Science Foundation of Beijing Brain Plan of China, No. Z161100002616019.

Author information

Correspondence to Hou Yanhong or Shao Yongcong.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Dalong, G., Jiyuan, L., Ying, Z. et al. Transcranial direct current stimulation reconstructs diminished thalamocortical connectivity during prolonged resting wakefulness: a resting-state fMRI pilot study. Brain Imaging and Behavior 14, 278–288 (2020).

Download citation


  • Sleep deprivation
  • Transcranial direct current stimulation
  • Resting-state fMRI
  • Functional connectivity
  • Graph theory