The sequelae of stoke, including the loss and recovery of function, are strongly linked to the mechanisms of neuroplasticity. Rehabilitation and non-invasive brain stimulation (NIBS) paradigms have shown promise in modulating corticomotor neuroplasticity to promote functional recovery in individuals post-stroke. However, an important limitation to these approaches is that while stroke recovery depends on the mechanisms of neuroplasticity, those mechanisms may themselves be altered by a stroke.
Objective:
Compare Transcranial Magnetic Stimulation (TMS)-based assessments of efficacy of mechanism of neuroplasticity between individuals post-stroke and age-matched controls.
Methods:
Thirty-two participants (16 post-stroke, 16 control) underwent an assessment of mechanisms of neuroplasticity, measured by the change in amplitude of motor evoked potentials elicited by single-pulse TMS 10–20 minutes following intermittent theta-burst stimulation (iTBS), and dual-task effect (DTE) reflecting cognitive-motor interference (CMI). In stroke participants, we further collected: time since stroke, stroke type, location, and Stroke Impact Scale 16 (SIS-16).
Results:
Although there was no between-group difference in the efficacy of TMS-iTBS neuroplasticity mechanism (p = 0.61, η2 = 0.01), the stroke group did not exhibit the expected facilitation to TMS-iTBS (p = 0.60, η2 = 0.04) that was shown in the control group (p = 0.016, η2 = 0.18). Sub-cohort analysis showed a trend toward a difference between those in the late-stage post-stroke and the control group (p = 0.07, η2 = 0.12). Within the post-stroke group, we found significant relationships between TMS-iTBS neuroplasticity and time since stroke onset, physical function (SIS-16), and CMI (all rs > |0.53| and p-values < 0.05).
Conclusions:
In this proof-of-principle study, our findings suggested altered mechanisms of neuroplasticity in post-stroke patients which were dependent on time since stroke and related to motor function. TMS-iTBS neuroplasticity assessment and its relationship with clinical functional measures suggest that TMS may be a useful tool to study post-stroke recovery. Due to insufficient statistical power and high variability of the data, generalization of the findings will require replication of the results in a larger, better-characterized cohort.
Benjamin,E.J., Blaha,M.J., Chiuve,S.E., Cushman,M., Das,S.R., Deo,R., de Ferranti,S.D., Floyd,J., Fornage,M., Gillespie,C., Isasi,C.R., Jiménez,M.C., Jordan,L.C., Judd,S.E., Lackland,D., Lichtman,J.H., Lisabeth,L., Liu,S., Longenecker,C.T., ... & Muntner,P. (2017). Heart Disease and Stroke Statistics—2017 Update: A Report From the American Heart Association. Circulation, 135(10), e146–e603.
2.
Byblow,W.D., Stinear,C.M., Barber,P.A., Petoe,M.A., & Ackerley,S.J. (2015). Proportional recovery after stroke depends on corticomotor integrity. Annals of Neurology, 78(6), 848–859.
3.
Chang,W.H., Fried,P.J., Saxena,S., Jannati,A., Gomes-Osman,J., Kim,Y.H., & Pascual-Leone,A. (2016). Optimal number of pulses as outcome measures of neuronavigated transcranial magnetic stimulation. Clinical Neurophysiology, 127(8), 2892–2897.
4.
Cramer,S.C. (2008). Repairing the human brain after stroke: I. Mechanisms of spontaneous recovery. Annals of Neurology, 63(3), 272–287.
5.
Cramer,S.C., Nelles,G., Benson,R.R., Kaplan,J.D., Parker,R.A., Kwong,K.K., Kennedy,D.N., Finklestein,S.P., & Rosen,B.R. (1997). A functional MRI study of subjects recovered from hemiparetic stroke. Stroke, 28(12), 2518–2527.
6.
Duncan,P.W., Lai,S.M., Bode,R.K., Perera,S., & DeRosa,J. (2003). Stroke impact scale-16: A brief assessment of physical function. Neurology, 60(2), 291–296.
7.
Freitas,C., Perez,J., Knobel,M., Tormos,J.M., Oberman,L., Eldaief,M., Bashir,S., Vernet,M., Peña-Gómez,C., & Pascual-Leone,A. (2011). Changes in Cortical Plasticity Across the Lifespan. Frontiers in Aging Neuroscience, 3(APR), 1–8.
8.
French,B., Thomas,L.H., Leathley,M.J., Sutton,C.J., McAdam,J., Forster,A., Langhorne,P., Price,C.I.M., Walker,A., Watkins,C.L., Connell,L., Coupe,J., & McMahon,N. (2007). Repetitive task training for improving functional ability after stroke. In Cochrane Database of Systematic Reviews, John Wiley and Sons Ltd, 4, p. CD006073.
9.
Fried,P.J, Jannati,A, Davila-Pérez,P, & Pascual-Leone,A. (2017). Reproducibility of single-pulse, paired-Pulse, and intermittent theta-burst TMS measures in healthy aging, type-2 diabetes, and Alzheimer’s Disease. Frontiers in Aging Neuroscience, 9(August), 1–13.
10.
Fried,P.J., Schilberg,L., Brem,A.-K., Saxena,S., Wong,B., Cypess,A.M., Horton,E.S., & Pascual-Leone,A. (2016). Humans with type-2 diabetes show abnormal long-term potentiation-like cortical plasticity associated with verbal learning deficits. Journal of Alzheimer’s Disease, 55(1), 89–100.
11.
Gomes-Osman,J., Cabral,D.F., Hinchman,C., Jannati,A., Morris,T.P, & Pascual-Leone,A. (2017). The effects of exercise on cognitive function and brain plasticity - a feasibility trial. Restorative Neurology and Neuroscience, 35(5).
12.
Hafsteinsdóttir,T.B., Rensink,M., & Schuurmans,M. (2014). Clinimetric Properties of the Timed Up and Go Test for Patients With Stroke: A Systematic Review. Topics in Stroke Rehabilitation, 21(3), 197–210.
13.
Hao,Z., Wang,D., Zeng,Y., & Liu,M. (2013). Repetitive transcranial magnetic stimulation for improving function after stroke. Cochrane Database of Systematic Reviews, 2013(5).
14.
Hara,Y. (2015). Brain plasticity and rehabilitation in stroke patients. Journal of Nippon Medical School, 82(1), 4–13.
15.
Huang,Y.-Z., Chen,R.-S., Rothwell,J.C., & Wen,H.-Y. (2007). The after-effect of human theta burst stimulation is NMDA receptor dependent. Clinical Neurophysiology, 118(5), 1028–1032.
16.
Huang,Y.-Z., Edwards,M.J., Rounis,E., Bhatia,K.P., & Rothwell,J.C. (2005). Theta Burst Stimulation of the Human Motor Cortex. Neuron, 45(2), 201–206.
17.
Johnson,C.O., Nguyen,M., Roth,G.A., Nichols,E., Alam,T., Abate,D., Abd-Allah,F., Abdelalim,A., Abraha,H.N., Abu-Rmeileh,N.M., Adebayo,O.M., Adeoye,A.M., Agarwal,G., Agrawal,S., Aichour,A.N., Aichour,I., Aichour,M.T.E., Alahdab,F., Ali,R.,... & Murray,C.J.L. (2019). Global, regional, and national burden of stroke, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology, 18(5), 439–458.
18.
Kelly,V.E., Janke,A.A., & Shumway-Cook,A. (2010). Effects of instructed focus and task difficulty on concurrent walking and cognitive task performance in healthy young adults. Experimental Brain Research, 207(1–2), 65–73.
19.
Klapp,S.T., Maslovat,D., & Jagacinski,R.J. (2019). The bottleneck of the psychological refractory period effect involves timing of response initiation rather than response selection. In Psychonomic Bulletin and Review, SpringerNew York LLC, 26(1), pp. 29–47.
20.
Koch,S., Tiozzo,E., Simonetto,M., Loewenstein,D., Wright,C.B., Dong,C., Bustillo,A., Perez-Pinzon,M., Dave,K.R., Gutierrez,C.M., Lewis,J.E., Flothmann,M., Mendoza-Puccini,M.C., Junco,B., Rodriguez,Z., Gomes-Osman,J., Rundek,T., & Sacco,R.L. (2020). Randomized trial of combined aerobic, resistance, and cognitive training to improve recovery from stroke: Feasibility and safety. Journal of the American Heart Association, 9(10).
21.
Murphy,T.H., & Corbett,D. (2009). Plasticity during stroke recovery: From synapse to behaviour. Nature Reviews Neuroscience, 10(12), 861–872.
22.
Oberman,L. (2010). Transcranial magnetic stimulation provides means to assess cortical plasticity and excitability in humans with fragile X syndrome and autism spectrum disorder. Frontiers in Synaptic Neuroscience, 2(JUN).
23.
Ohzuno,T., & Usuda,S. (2019). Cognitive-motor interference in post-stroke individuals and healthy adults under different cognitive load and task prioritization conditions. Journal of Physical Therapy Science, 31(3), 255–260.
24.
Pascual-Leone,A., Freitas,C., Oberman,L., Horvath,J.C., Halko,M., Eldaief,M., Bashir,S., Vernet,M., Shafi,M., Westover,B., Vahabzadeh-Hagh,A.M., & Rotenberg,A. (2011). Characterizing brain cortical plasticity and network dynamics across the age-span in health and disease with TMS-EEG and TMS-fMRI. Brain Topography, 24(3–4), 302–315.
Pollock,A., Farmer,S.E., Brady,M.C., Langhorne,P., Mead,G.E., Mehrholz,J., & van Wijck,F. (2014). Interventions for improving upper limb function after stroke. Cochrane Database of Systematic Reviews, 2014(11).
28.
Rossi,S., Antal,A., Bestmann,S., Bikson,M., Brewer,C., Brockmöller,J., Carpenter,L.L., Cincotta,M., Chen,R., Daskalakis,J.D., Di Lazzaro,V., Fox,M.D., George,M.S., Gilbert,D., Kimiskidis,V.K., Koch,G., Ilmoniemi,R.J., Lefaucheur,J.P., Leocani,L., . . . & Hallett,M. (2021a). Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Clinical Neurophysiology, 132(1), 269–306.
29.
Rossi,S., Antal,A., Bestmann,S., Bikson,M., Brewer,C., Brockmöller,J., Carpenter,L.L., Cincotta,M., Chen,R., Daskalakis,J.D., Di Lazzaro,V., Fox,M.D., George,M.S., Gilbert,D., Kimiskidis,V.K., Koch,G., Ilmoniemi,R.J., Lefaucheur,J.P., Leocani,L., . . . & Hallett,M. (2021b). Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Clinical Neurophysiology, 132(1), 269–306.
30.
Sigman,M., & Dehaene,S. (2006). Dynamics of the central bottleneck: Dual-task and task uncertainty. PLoS Biology, 4(7), 1227–1238.
31.
Smith,T., Gildeh,N., & Holmes,C. (2007). The montreal cognitive assessment: Validity and tility in a memory clinic setting. The Canadian Journal of Psychiatry, 52(5), 329–332.
32.
Stinear,C.M., Barber,P.A., Petoe,M., Anwar,S., & Byblow,W.D. (2012). The PREP algorithm predicts potential for upper limb recovery after stroke. Brain, 135(8), 2527–2535.
33.
Suppa,A., Huang,Y.-Z., Funke,K., Ridding,M.C., Cheeran,B., Di Lazzaro,V., Ziemann,U., & Rothwell,J.C. (2016). Ten years of theta burst stimulation in humans: Established knowledge, unknowns and prospects. Brain Stimulation, 9(3), 323–335.
34.
Takeuchi,N., & Izumi,S.I. (2012). Maladaptive plasticity for motor recovery after stroke: Mechanisms and approaches. In Neural Plasticity, Hindawi Publishing Corporation, 2012.
35.
Tremblay,S., Vernet,M., Bashir,S., Pascual-Leone,A., & Théoret,H. (2015). Theta burst stimulation to characterize changes in brain plasticity following mild traumatic brain injury: A proof-of-principle study. Restorative Neurology and Neuroscience, 33(5), 611–620.
36.
Wischnewski,M., & Schutter,D.J.L.G. (2015). Efficacy and time course of theta burst stimulation in healthy humans. Brain Stimulation, 8(4), 685–692.
37.
Woollacott,M., & Shumway-Cook,A. (2002). Attention and the control of posture and gait: A review of an emerging area of research. Gait & Posture, 16(1), 1–14.
