Temporal characteristics of the human mirror neuron system. Research using transcranial magnetic stimulation

Background. Mirror neurons (MN) are integral to linking the perception of actions with their execution, activating during both action observation and execution. While extensive research has elucidated their functional roles, the temporal dynamics of MN responses in humans remain insufficiently understood.

Aim. To investigate the temporal profile of MN activity during hand movement observation using transcranial magnetic stimulation at at different time intervals (0, 320, 640, 1000, 1320, 1640 ms from the beginning of the demonstrated movement, time ranges from 1000 to 1640 ms correspond to the time interval after the end of the movement).

Materials and methods. Twenty right-handed participants underwent neuronavigated transcranial magnetic stimulation targeting the left primary motor cortex during the observation of hand movements. Motor evoked potentials were recorded from the first dorsal interosseous and abductor digiti minimi muscles at various time points relative to movement onset.

Results. A three-way interaction between movement type, muscle, and time was observed. Muscle-specific responses and intermuscular differences became prominent at 640 ms, extending into post-movement periods (1000, 1320, 1640 ms). Notably, excitatory responses were seen in muscles corresponding to the observed action, while unrelated muscles exhibited inhibitory patterns, intensifying over time.

Conclusion. These findings reveal a complex excitatory-inhibitory interplay in the MN system, resembling motor surround inhibition. The extended temporal activity of MN suggests their role in processing action completion and potential outcomes. This study provides novel insights into MN dynamics and underscores the relevance of these mechanisms for motor rehabilitation strategies. Further research is required to explore MN activity at extended time points.

1. Rizzolatti G., Craighero L. The mirror-neuron system. Ann Rev Neurosci 2004;27:169–92. DOI: 10.1146/annurev.neuro.27.070203.144230

2. Oztop E., Kawato M., Arbib M. Mirror neurons and imitation: A computationally guided review. Neural Netw 2006;19:254–71.

3. Umiltà M., Kohler E., Gallese V. et al. I know what you are doing. A neurophysiological study. Neuron 2001;31:155–65. DOI: 10.1016/S0896-6273(01)00337-3

4. Fogassi L., Gallese V., Di Pellegrino G. et al. Space coding by premotor cortex. Exp Brain Res 1992;89(3):686–90.

5. Di Pellegrino G., Fadiga L., Fogassi L. et al. Understanding motor events: A neurophysiological study. Exp Brain Res 1992;91(1):176–80.

6. Bianco G., Feurra M., Fadiga L. et al. Bi-hemispheric effects on corticospinal excitability induced by repeated sessions of imagery versus observation of actions. Restor Neurol Neurosci 2012;30:481–9. DOI: 10.3233/RNN-2012-120241

7. Catmur C., Walsh V., Heyes C. Sensorimotor learning configures the human mirror system. Curr Biol 2007;17:1527–31. DOI: 10.1016/j.cub.2007.08.006

8. Fadiga L., Fogassi L., Pavesi G. et al. (1995). Motor facilitation during action observation: A magnetic stimulation study. J Neurophysiol 1995;73:2608–11. DOI: 10.1152/jn.1995.73.6.2608

9. Strafella, A.P., Paus T. Modulation of cortical excitability during action observation: A transcranial magnetic stimulation study. Neuroreport 2000;11(10);2289–92.

10. Maeda F., Kleiner-Fisman G., Pascual-Leone A. Motor facilitation while observing hand actions: Specificity of the effect and role of observer’s orientation. J Neurophysiol 2002;87(3):1329–35.

11. Maeda F., Chang V.Y., Longson K. et al. Motor facilitation during action observation depends on viewer’s perspective: A TMS study. Neuroimage 2001;13(6):1224.

12. Maeda F., Aziz-Zadeh L., Persson A.M. et al. Modulation of cortico-spinal excitability by goal-oriented vs. non-goal-oriented hand actions. Neuroimage2001;6(13):1223.

13. Hill A.T., Fitzgibbon B.M., Arnold S.L. et al. Modulation of putative mirror neuron activity by both positively and negatively valenced affective stimuli: A TMS study. Behav Brain Res 2013;249:116–23.

14. Mehta U.M., Waghmare A.V., Thirthalli J. et al. Is the human mirror neuron system plastic? Evidence from a transcranial magnetic stimulation study. Asian J Psychiatry 2015;17:71–7.

15. Andrews S.C., Enticott P.G., Hoy K.E. et al. Reduced mu suppression and altered motor resonance in euthymic bipolar disorder: Evidence for a dysfunctional mirror system? Soc Neurosci 2015;11:60–71. DOI: 10.1080/17470919.2015.1029140

16. Basavaraju R., Mehta U.M., Pascual-Leone Á. et al. Elevated mirror neuron system activity in bipolar mania: Evidence from a transcranial magnetic stimulation study. Bipolar Disord 2018;21(3):259–69. DOI: 10.1111/bdi.12723

17. Saito Y., Kubicki M., Koerte I. et al. Impaired white matter connectivity between regions containing mirror neurons, and relationship to negative symptoms and social cognition, in patients with first-episode schizophrenia. Brain Imaging Behav 2018;12(1):229–37. DOI: 10.1007/s11682-017-9685-z

18. Mitra S., Nizamie S.H., Goyal N. et al. Event related desynchronisation of mu-wave over right sensorimotor cortex at baseline may predict subsequent response to antipsychotics in schizophrenia.Asian J Psychiatr 2015;14:19–21. DOI: 10.1016/j.ajp.2015.01.013

19. Khalil R., Tindle R., Boraud T. et al. Social decision making in autism: On the impact of mirror neurons, motor control, and imitative behaviors. CNS Neurosci Ther 2018;24( 8):669–76. DOI: 10.1111/cns.13001

20. Sosic-Vasic Z., Eberhardt J., Bosch J. et al. Mirror neuron activations in encoding of psychic pain in borderline personality disorder. NeuroImage Clinical 2019;22:101737. DOI: 10.1016/j.nicl.2019.101737

21. Eggermont L., Swaab D.F., Hol E.M., Scherder E. Observation of hand movements by older persons with dementia: Effects on cognition. Dement Geriatr Cogn Disord 2009;27(4):366–74. DOI: 10.1159/000209311

22. Marco-Garcia S., Ferrer-Quintero M., Usall J. et al. Facial emotion recognition in neurological disorders: A narrative review. Rev Neurol 2019;69(5):207–19. DOI: 10.33588/rn.6905.2019047

23. Plata-Bello J. The study of action observation therapy in neurological diseases: A few technical considerations. InTech eBooks 2017. DOI: 10.5772/67651

24. Khrulev A.E., Kuryatnikova K.M., Belova А.N. et al. Modern rehabilitation technologies of patients with motor disorders at an early rehabilitation of stroke. Modern Technologies in Medicine 2022;14(6 (eng)):64–78.

25. Stoykov M.E., Madhavan S. Motor priming in neurorehabilitation. J Neurol Physical Ther 2015;39(1):33–42.

26. Kim K. Action observation for upper limb function after stroke: Evidence-based review of randomized controlled trials. J Phys Ther Sci 2015;27(10):3315–7. DOI: 10.1589/jpts.27.3315

27. Sale P., Ceravolo M.G., Franceschini M. Action observation therapy in the subacute phase promotes dexterity recovery in right hemisphere stroke patients. Biomed Res Int 2014;2014):457538. DOI: 10.1155/2014/457538

28. Celnik P., Webster B., Glasser D.M., Cohen L.G. Effects of action observation on physical training after stroke. Stroke 2008;39(6):1814–20. DOI: 10.1161/strokeaha.107.508184

29. Bhasin A., Srivastava M.P., Kumaran S. et al. Neural interface of mirror therapy in chronic stroke patients: A functional magnetic resonance imaging study. Neurol India 2012;60(6):570–6. DOI: 10.4103/0028-3886.105188

30. Michielsen M.E., Selles R.W., Van Der Geest J.N. et al. Motor recovery and cortical reorganization after mirror therapy in chronic stroke patients. Neurorehabil Neural Repair 2010;25(3):223–33. DOI: 10.1177/1545968310385127

31. Harmsen W.J., Bussmann J.B., Selles R.W. et al. A mirror therapy– based action observation protocol to improve motor learning after stroke. Neurorehabili Neural Rep 2015;29(6):509–16.

32. Jaywant A., Ellis T.D., Roy S.H. et al. Randomized controlled trial of a home-based action observation intervention to improve walking in Parkinson disease. Arch Phys Med Rehabil 2016;97(5):665–73. DOI: 10.1016/j.apmr.2015.12.029

33. Pelosin E., Bove M., Ruggeri P. et al. Reduction of bradykinesia of finger movements by a single session of action observation in Parkinson disease. Neurorehabil Neural Rep 2013;27(6):552–60. DOI: 10.1177/1545968312471905

34. Pelosin E., Avanzino L., Bove M. et al. Action observation improves freezing of GAIT in patients with Parkinson’s disease. Neurorehabil Neural Rep 2010;24(8):746–52. DOI: 10.1177/1545968310368685

35. Bek J., Gowen E., Vogt S., et al. Observation and imitation of object-directed hand movements in Parkinson’s disease. Sci Rep 2023;13(1):18749. DOI: 10.1038/s41598-023-42705-x

36. Buccino G., Arisi D., Gough P.M. et al. Improving upper limb motor functions through action observation treatment: A pilot study in children with cerebral palsy. Dev Med Child Neurol 2012;54(9):822–8. DOI: 10.1111/j.1469-8749.2012.04334.x

37. Tekkuş B., Mutluay F. Effect of community-based group exercises combined with action observation on physical and cognitive performance in older adults during the COVID-19 pandemic: A randomized controlled trial. PLoS One 2023;18(12):e0295057. DOI: 10.1371/journal.pone.0295057

38. Catmur C., Walsh V., Heyes C. Associative sequence learning: the role of experience in the development of imitation and the mirror system. Philos Trans R Soc Lond B Biol Sci 2009;364(1528):2369–80.

39. Barchiesi G., Cattaneo L. Early and late motor responses to action observation. Soc Cogn Affect Neurosci 2013;8(6):711–9.

40. Ubaldi S., Barchiesi G., Cattaneo L. Bottom-up and top-down visuomotor responses to action observation. Cerebral Cortex 2015;25(4):1032–41.

41. Feurra M., Blagovechtchenski E., Nikulin V.V. et al. State-dependent effects of transcranial oscillatory currents on the motor system during action observation. Sci Rep 209;9:12858. DOI: 10.1038/s41598-019-49166-1

42. Rossini P.M., Barker A.T., Berardelli A. et al. Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee. Electroencephalogr Clin Neurophysiol 1994;91(2):79–92.

43. Rossini P.M., Rossi S., Pasqualetti P. et al. Corticospinal excitability modulation to hand muscles during movement imagery. Cerebral Cortex 1999;9(2):161–7.

44. Jahanshahi M., Obeso I., Rothwell J.C. et al. A fronto-striatosubthalamic-pallidal network for goal-directed and habitual inhibition. Nat Rev Neurosci 2015;16(12):719–32.

45. Kaji R. Basal ganglia as a sensory gating devise for motor control. J Med Invest 2001;48(3/4):142–6.

46. Mink J.W. The basal ganglia: focused selection and inhibition of competing motor programs. Prog Neurobiol 1996;50(4):381–425.

47. Mink J.W. The basal ganglia and involuntary movements: Impaired inhibition of competing motor patterns. Arch Neurol 2003;60(10):1365–8.

48. Rodriguez-Sabate C., Gonzalez A., Perez-Darias J.C. et al. The causal interaction in human basal ganglia. Sci Rep 2021;11(1):2989.

49. Sohn Y.H., Hallett M. Surround inhibition in human motor system. Exp Brain Res 2004;158:397–404.

50. Wessel J.R., Aron A.R. On the globality of motor suppression: Unexpected events and their influence on behavior and cognition. Neuron 2917;93(2):259–80.

51. Marceglia S., Fiorio M., Foffani G. et al. Modulation of beta oscillations in the subthalamic area during action observation in Parkinson’s disease. Neuroscience 2009;161(4):1027–36.

52. Alegre M., Rodríguez-Oroz M.C., Valencia M. et al. Changes in subthalamic activity during movement observation in Parkinson’s disease: Is the mirror system mirrored in the basal ganglia? Clin Neurophysiol 2010;121(3):414–25.

53. Abdelhaleem N., Tawfek A., Abouamra H.S. et al. Combined effect of non-invasive brain stimulation with mirror therapy for improving motor function in patients with stroke: A systematic review with meta-analysis. Curr Phys Med Rehabil Rep 2024;1–15.