Self-modulation of motor cortex activity after stroke: a randomized controlled trial
Zeena-Britt Sanders, Melanie K Fleming, Tom Smejka, Marilien C Marzolla, Catharina Zich, Sebastian W Rieger, Michael Lührs, Rainer Goebel, Cassandra Sampaio-Baptista, Heidi Johansen-Berg, Zeena-Britt Sanders, Melanie K Fleming, Tom Smejka, Marilien C Marzolla, Catharina Zich, Sebastian W Rieger, Michael Lührs, Rainer Goebel, Cassandra Sampaio-Baptista, Heidi Johansen-Berg
Abstract
Real-time functional MRI neurofeedback allows individuals to self-modulate their ongoing brain activity. This may be a useful tool in clinical disorders that are associated with altered brain activity patterns. Motor impairment after stroke has previously been associated with decreased laterality of motor cortex activity. Here we examined whether chronic stroke survivors were able to use real-time fMRI neurofeedback to increase laterality of motor cortex activity and assessed effects on motor performance and on brain structure and function. We carried out a randomized, double-blind, sham-controlled trial (ClinicalTrials.gov: NCT03775915) in which 24 chronic stroke survivors with mild to moderate upper limb impairment experienced three training days of either Real (n = 12) or Sham (n = 12) neurofeedback. Assessments of brain structure, brain function and measures of upper-limb function were carried out before and 1 week after neurofeedback training. Additionally, measures of upper-limb function were repeated 1 month after neurofeedback training. Primary outcome measures were (i) changes in lateralization of motor cortex activity during movements of the stroke-affected hand throughout neurofeedback training days; and (ii) changes in motor performance of the affected limb on the Jebsen Taylor Test (JTT). Stroke survivors were able to use Real neurofeedback to increase laterality of motor cortex activity within (P = 0.019), but not across, training days. There was no group effect on the primary behavioural outcome measure, which was average JTT performance across all subtasks (P = 0.116). Secondary analysis found improvements in the performance of the gross motor subtasks of the JTT in the Real neurofeedback group compared to Sham (P = 0.010). However, there were no improvements on the Action Research Arm Test or the Upper Extremity Fugl-Meyer score (both P > 0.5). Additionally, decreased white-matter asymmetry of the corticospinal tracts was detected 1 week after neurofeedback training (P = 0.008), indicating that the tracts become more similar with Real neurofeedback. Changes in the affected corticospinal tract were positively correlated with participants neurofeedback performance (P = 0.002). Therefore, here we demonstrate that chronic stroke survivors are able to use functional MRI neurofeedback to self-modulate motor cortex activity in comparison to a Sham control, and that training is associated with improvements in gross hand motor performance and with white matter structural changes.
Keywords: motor cortex; neurofeedback; real-time fMRI; stroke; white matter.
© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.
Figures
References
- Veerbeek JM, Kwakkel G, Van Wegen EEH, Ket JCF, Heymans MW. Early prediction of outcome of activities of daily living after stroke: A systematic review. Stroke. 2011;42:1482–1488.
- Franceschini M, La Porta F, Agosti M, Massucci M. Is health-related-quality of life of stroke patients influenced by neurological impairments at one year after stroke? Eur J Phys Rehabil Med. 2010;46:389–399.
- Johansen-Berg H, Rushworth MFS, Bogdanovic MD, Kischka U, Wimalaratna S, Matthews PM. The role of ipsilateral premotor cortex in hand movement after stroke. Proc Natl Acad Sci U S A. 2002;99:14518–14523.
- Ward NS, Brown MM, Thompson AJ, Frackowiak RSJ. Neural correlates of motor recovery after stroke: A longitudinal fMRI study. Brain. 2003;126:2476–2496.
- Buetefisch CM. Role of the contralesional hemisphere in post-stroke recovery of upper extremity motor function. Front Neurol. 2015;6:214.
- Hummel FC, Cohen LG. Non-invasive brain stimulation: a new strategy to improve neurorehabilitation after stroke? Lancet Neurol. 2006;5:708–712.
- Grefkes C, Fink GR. Noninvasive brain stimulation after stroke: It is time for large randomized controlled trials! Curr Opin Neurol. 2016;29:714–720.
- Shibata K, Watanabe T, Sasaki Y, Kawato M. Perceptual learning incepted by decoded fMRI neurofeedback without stimulus presentation. Science. 2011;334:1413–1415.
- Caria A, Sitaram R, Veit R, Begliomini C, Birbaumer N. Volitional control of anterior insula activity modulates the response to aversive stimuli. A real-time functional magnetic resonance imaging study. Biol Psychiatry. 2010;68:425–432.
- DeBettencourt MT, Cohen JD, Lee RF, Norman KA, Turk-Browne NB. Closed-loop training of attention with real-time brain imaging. Nat Neurosci. 2015;18:470–475.
- Young KD, Siegle GJ, Zotev V, et al. . Randomized clinical trial of real-time fMRI amygdala neurofeedback for major depressive disorder: Effects on symptoms and autobiographical memory recall. Am J Psychiatry. 2017;174:748–755.
- Mehler DMA, Sokunbi MO, Habes I, et al. . Targeting the affective brain—A randomized controlled trial of real-time fMRI neurofeedback in patients with depression. Neuropsychopharmacology. 2018;43:2578–2585.
- Emmert K, Breimhorst M, Bauermann T, Birklein F, Van De Ville D, Haller S. Comparison of anterior cingulate vs. insular cortex as targets for real-time fMRI regulation during pain stimulation. Front Behav Neurosci. 2014;8:350.
- Zhang S, Yoshida W, Mano H, et al. . Pain control by co-adaptive learning in a brain–machine interface. Curr Biol. 2020;30:3935–3944.e7.
- Zilverstand A, Sorger B, Sarkheil P, Goebel R. fMRI neurofeedback facilitates anxiety regulation in females with spider phobia. Front Behav Neurosci. 2015;9:148.
- Koizumi A, Amano K, Cortese A, et al. . Fear reduction without fear through reinforcement of neural activity that bypasses conscious exposure. Nat Hum Behav. 2016;1:0006.
- Wang T, Mantini D, Gillebert CR. The potential of real-time fMRI neurofeedback for stroke rehabilitation: A systematic review. Cortex. 2018;107:148–165.
- Linden DEJ, Turner DL. Real-time functional magnetic resonance imaging neurofeedback in motor neurorehabilitation. Curr Opin Neurol. 2016;29:412–418.10.1097/WCO.0000000000000340
- Mehler DMA, Williams AN, Whittaker JR, et al. . Graded fMRI neurofeedback training of motor imagery in middle cerebral artery stroke patients: A preregistered proof-of-concept study. Front Hum Neurosci. 2020;14:226.
- Sitaram R, Veit R, Stevens B, et al. . Acquired control of ventral premotor cortex activity by feedback training: An exploratory real-time fMRI and TMS study. Neurorehabil Neural Repair. 2012;26:256–265.
- Liew S-L, Rana M, Cornelsen S, et al. . Improving motor corticothalamic communication after stroke using real-time fMRI connectivity-based neurofeedback. Neurorehabil Neural Repair. 2016;30:671–675.
- Thibault RT, Macpherson A, Lifshitz M, Roth RR, Raz A. Neurofeedback with fMRI: A critical systematic review. Neuroimage. 2018;172:786–807.
- Jebsen RH, Taylor N, Trieschmann RB, Trotter MJ, Howard LA. An objective and standardized test of hand function. Arch Phys Med Rehabil. 1969;50:311–319.
- Rance M, Walsh C, Sukhodolsky DG, et al. . Time course of clinical change following neurofeedback. Neuroimage. 2018;181:807–813.
- Neyedli HF, Sampaio-Baptista C, Kirkman MA, et al. . Increasing lateralized motor activity in younger and older adults using real-time fMRI during executed movements. Neuroscience. 2018;378:165–174.
- Sampaio-Baptista C, Neyedli HF, Sanders ZB, et al. . fMRI neurofeedback in the motor system elicits bidirectional changes in activity and in white matter structure in the adult human brain. Cell Rep. 2021;37:109890.
- Lyle RC. A performance test for assessment of upper limb function in physical rehabilitation treatment and research. Int J Rehabil Res. 1981;4:483–492.
- Fugl-Meyer AR, Jääskö L, Leyman I, Olsson S, Steglind S. The post-stroke hemiplegic patient. 1. A method for evaluation of physical performance. Scand J Rehabil Med. 1975;7:13–31.
- Woolrich MW, Ripley BD, Brady M, Smith SM. Temporal autocorrelation in univariate linear modeling of FMRI data. Neuroimage. 2001;14:1370–1386.
- Woolrich MW, Behrens TEJ, Beckmann CF, Jenkinson M, Smith SM. Multilevel linear modelling for FMRI group analysis using Bayesian inference. Neuroimage. 2004;21:1732–1747.
- Seghier ML. Laterality index in functional MRI: Methodological issues. Magn Reson Imaging. 2008;26:594–601.
- Fernández G, De Greiff A, Von Oertzen J, et al. . Language mapping in less than 15 minutes: Real-time functional MRI during routine clinical investigation. Neuroimage. 2001;14:585–594.
- Jansen A, Menke R, Sommer J, et al. . The assessment of hemispheric lateralization in functional MRI-robustness and reproducibility. Neuroimage. 2006;33:204–217.
- Bates D, Mächler M, Bolker BM, Walker SC. Fitting linear mixed-effects models using lme4. J Stat Softw. 2015;67:1–48.
- Gueorguieva R, Krystal JH. Move over ANOVA: Progress in analyzing repeated-measures data and its reflection in papers published in the archives of general psychiatry. Arch Gen Psychiatry. 2004;61:310–317.
- Quené H, Van den Bergh H. On multi-level modeling of data from repeated measures designs: A tutorial. Speech Commun. 2004;43:103–121.
- Matuschek H, Kliegl R, Vasishth S, Baayen H, Bates D. Balancing type I error and power in linear mixed models. J Mem Lang. 2017;94:305–315.
- Kuznetsova A, Brockhoff PB, Christensen RHB. Lmertest package: Tests in linear mixed effects models. J Stat Softw. 2017;82:1–26.
- Luke SG. Evaluating significance in linear mixed-effects models in R. Behav Res Methods. 2017;49:1494–1502.
- Pek J, Flora DB. Reporting effect sizes in original psychological research: A discussion and tutorial. Psychol Methods. 2018;23:208–225.
- Van Breukelen GJP. ANCOVA versus change from baseline had more power in randomized studies and more bias in nonrandomized studies. J Clin Epidemiol. 2006;59:920–925.
- Hummel FC, Heise K, Celnik P, Floel A, Gerloff C, Cohen LG. Facilitating skilled right hand motor function in older subjects by anodal polarization over the left primary motor cortex. Neurobiol Aging. 2010;31:2160–2168.10.1016/j.neurobiolaging.2008.12.008
- Shin JH, Kim MY, Lee JY, et al. . Effects of virtual reality-based rehabilitation on distal upper extremity function and health-related quality of life: A single-blinded, randomized controlled trial. J Neuroeng Rehabil. 2016;13:17.
- Lee SH, Lee JY, Kim MY, Jeon YJ, Kim S, Shin JH. Virtual reality rehabilitation with functional electrical stimulation improves upper extremity function in patients with chronic stroke: A pilot randomized controlled study. Arch Phys Med Rehabil. 2018;99:1447–1453.e1.
- Stinear CM, Barber PA, Smale PR, Coxon JP, Fleming MK, Byblow WD. Functional potential in chronic stroke patients depends on corticospinal tract integrity. Brain. 2007;130 (Pt 1):170–180.
- Lindenberg R, Renga V, Zhu LL, Betzler F, Alsop D, Schlaug G. Structural integrity of corticospinal motor fibers predicts motor impairment in chronic stroke. Neurology. 2010;74:280–287.
- Lioi G, Butet S, Fleury M, et al. . A multi-target motor imagery training using bimodal EEG-fMRI neurofeedback: A pilot study in chronic stroke patients. Front Hum Neurosci. 2020;14:37.
- Matarasso AK, Rieke JD, White K, Yusufali MM, Daly JJ. Combined real-time fMRI and real time fNIRS brain computer interface (BCI): Training of volitional wrist extension after stroke, a case series pilot study. PLoS One. 2021;16:e0250431.
- Alkoby O, Abu-rmileh A, Shriki O, Todder D. Can we predict who will respond to neurofeedback ? A review of the inefficacy problem and existing predictors for successful EEG neurofeedback learning. Neuroscience. 2018;378:155–164.
- Haugg A, Sladky R, Skouras S, et al. . Can we predict real-time fMRI neurofeedback learning success from pretraining brain activity? Hum Brain Mapp. 2020;41:3839–3854.
- Haugg A, Renz FM, Nicholson AA, et al. . Predictors of real-time fMRI neurofeedback performance and improvement—A machine learning mega-analysis. Neuroimage. 2021;237:118207.
- Lemon R. Cortical control of the primate hand. Exp Physiol. 1993;78:263–301.
- Kuypers HGJM. Anatomy of the descending pathways. Handbook of Physiology—The Nervous System II. V. Brooks, Ed. (American Physiological Society, Bethesda, MD) 1981:56–59.
- Lawrence DG, Kuypers HGJM. The functional organization of the motor system in the monkey I. The effects of bilateral pyramidal lesions. Brain. 1968;91:15–36.
- Ward NS. Non-invasive brain stimulation for stroke recovery: Ready for the big time? J Neurol Neurosurg Psychiatry. 2016;87:343–344.
- Subramanian L, Hindle J V, Johnston S, et al. . Real-time functional magnetic resonance imaging neurofeedback for treatment of Parkinson’s disease. J Neurosci. 2011;31:16309–16317.
- Allman C, Amadi U, Winkler AM, et al. . Ipsilesional anodal tDCS enhances the functional benefits of rehabilitation in patients after stroke. Sci Transl Med. 2016;8:330re1.
- Mottaz A, Corbet T, Doganci N, et al. . Modulating functional connectivity after stroke with neurofeedback: Effect on motor deficits in a controlled cross-over study. Neuroimage Clin. 2018;20:336–346.
- Mawase F, Cherry-Allen K, Xu J, Anaya M, Uehara S, Celnik P. Pushing the rehabilitation boundaries: Hand motor impairment can be reduced in chronic stroke. Neurorehabil Neural Repair. 2020;34:733–745.
- Ward NS, Brander F, Kelly K. Intensive upper limb neurorehabilitation in chronic stroke: Outcomes from the Queen Square programme. J Neurol Neurosurg Psychiatry. 2019;90:498–506.
- Stinear CM, Barber PA, Petoe M, Anwar S, Byblow WD. The PREP algorithm predicts potential for upper limb recovery after stroke. Brain. 2012;135:2527–2535.
- Wahl AS, Omlor W, Rubio JC, et al. . Asynchronous therapy restores motor control by rewiring of the rat corticospinal tract after stroke. Science. 2014;344:1250–1255.
- Marins T, Rodrigues EC, Bortolini T, Melo B, Moll J, Tovar-Moll F. Structural and functional connectivity changes in response to short-term neurofeedback training with motor imagery. Neuroimage. 2019;194:283–290.
- Ishibashi T, Dakin KA, Stevens B, et al. . Astrocytes promote myelination in response to electrical impulses. Neuron. 2006;49:823–832.
- Xiao L, Ohayon D, Mckenzie IA, et al. . Rapid production of new oligodendrocytes is required in the earliest stages of motor-skill learning. Nat Neurosci. 2016;19:1210–1217.
- Sampaio-Baptista C, Johansen-Berg H. White matter plasticity in the adult brain. Neuron. 2017;96:1239–1251.
- Wahl AS, Büchler U, Brändli A, et al. . Optogenetically stimulating intact rat corticospinal tract post-stroke restores motor control through regionalized functional circuit formation. Nat Commun. 2017;8:1187.
- Gu Z, Kalamboglas J, Yoshioka S, et al. . Control of species-dependent cortico-motoneuronal connections underlying manual dexterity. Science. 2017;357:400–404.
- Krakauer JW, Carmichael ST, Corbett D, Wittenberg GF. Getting neurorehabilitation right: What can be learned from animal models? Neurorehabil Neural Repair. 2012;26:923–931.
- Ruddy K, Balsters J, Mantini D, et al. . Neural activity related to volitional regulation of cortical excitability. Elife. 2018;7:e40843.
- Zhao Z, Yao S, Zweerings J, et al. . Putamen volume predicts real-time fMRI neurofeedback learning success across paradigms and neurofeedback target regions. Hum Brain Mapp. 2021;42:1879–1887.
- Emmert K, Kopel R, Sulzer J, et al. . Meta-analysis of real-time fMRI neurofeedback studies using individual participant data: How is brain regulation mediated? Neuroimage. 2016;124:806–812.
- Sitaram R, Ros T, Stoeckel L, et al. . Closed-loop brain training: the science of neurofeedback. Nat Rev Neurosci. 2017;18:86–100.
- Shibata K, Lisi G, Cortese A, Watanabe T, Sasaki Y, Kawato M. Toward a comprehensive understanding of the neural mechanisms of decoded neurofeedback. Neuroimage. 2019;188:539–556.
- Koralek AC, Jin X, Long JD, Costa RM, Carmena JM. Corticostriatal plasticity is necessary for learning intentional neuroprosthetic skills. Nature. 2012;483:331–335.
- Koralek AC, Costa RM, Carmena JM. Temporally precise cell-specific coherence develops in corticostriatal networks during learning. Neuron. 2013;79:865–872.
- Murray SO, Wojciulik E. Attention increases neural selectivity in the human lateral occipital complex. Nat Neurosci. 2004;7:70–74.
- Wood G, Kober SE. EEG Neurofeedback is under strong control of psychosocial factors. Appl Psychophysiol Biofeedback. 2018;43:293–300.
- Daeglau M, Zich C, Kranczioch C. The impact of context on EEG motor imagery neurofeedback and related motor domains. Curr Behav Neurosci Rep. 2021;8:90–101.
- Kadosh KC, Staunton G. A systematic review of the psychological factors that influence neurofeedback learning outcomes. Neuroimage. 2019;185:545–555.
- Ward NS, Carmichael ST. Blowing up neural repair for stroke recovery: Preclinical and clinical trial considerations. Stroke. 2020;51:3169–3173.
- Boyd LA, Hayward KS, Ward NS, et al. . Biomarkers of stroke recovery: Consensus-based core recommendations from the stroke recovery and rehabilitation roundtable. Neurorehabil Neural Repair. 2017;31:864–876.
Source: PubMed