Review Article | Published:

Modulation of brain plasticity in stroke: a novel model for neurorehabilitation

Nature Reviews Neurology volume 10, pages 597608 (2014) | Download Citation

Abstract

Noninvasive brain stimulation (NIBS) techniques can be used to monitor and modulate the excitability of intracortical neuronal circuits. Long periods of cortical stimulation can produce lasting effects on brain function, paving the way for therapeutic applications of NIBS in chronic neurological disease. The potential of NIBS in stroke rehabilitation has been of particular interest, because stroke is the main cause of permanent disability in industrial nations, and treatment outcomes often fail to meet the expectations of patients. Despite promising reports from many clinical trials on NIBS for stroke recovery, the number of studies reporting a null effect remains a concern. One possible explanation is that the interhemispheric competition model—which posits that suppressing the excitability of the hemisphere not affected by stroke will enhance recovery by reducing interhemispheric inhibition of the stroke hemisphere, and forms the rationale for many studies—is oversimplified or even incorrect. Here, we critically review the proposed mechanisms of synaptic and functional reorganization after stroke, and suggest a bimodal balance–recovery model that links interhemispheric balancing and functional recovery to the structural reserve spared by the lesion. The proposed model could enable NIBS to be tailored to the needs of individual patients.

Key points

  • Noninvasive brain stimulation (NIBS) is a promising approach to enhance recovery after stroke, but its beneficial effect is limited and the technique is not yet ready for broad clinical use

  • We suggest that the disappointments in NIBS trials are related to over-reliance on the interhemispheric competition and vicariation models of recovery, which are oversimplified and do not apply to all patients with stroke

  • The concept of 'structural reserve' integrates the effects that interhemispheric inhibition and vicariation exert on the unlesioned residual network

  • We propose a unified 'bimodal balance–recovery model' that takes into account this individual residual network

  • The model could be used to tailor treatment for individual patients and increase the efficacy of NIBS in stroke rehabilitation

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Author information

Affiliations

  1. Institute of Neurology, Campus Bio-Medico University, Via Álvaro del Portillo 200, 00128 Rome, Italy.

    • Giovanni Di Pino
    • , Giovanni Pellegrino
    • , Giovanni Assenza
    • , Fioravante Capone
    • , Florinda Ferreri
    • , Federico Ranieri
    • , Mario Tombini
    •  & Vincenzo Di Lazzaro
  2. Laboratory of Biomedical Robotics and Biomicrosystem, Center for Integrated Research, Campus Bio-Medico University, Via Álvaro del Portillo 28, 00128 Rome, Italy.

    • Domenico Formica
  3. Department of Neurology & Stroke, and Hertie Institute for Clinical Brain Research, Eberhard Karls-University Tübingen, Hoppe-Seyler-Strasse 3, D-72076 Tübingen, Germany.

    • Ulf Ziemann
  4. Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.

    • John C. Rothwell

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Contributions

G.D.P. developed the model and wrote the article. G.P. searched the literature and wrote the section on the stimulation protocols and clinical trials. G.A. searched the literature and wrote the section on EEG and repetitive electric stimulation. F.C. searched the literature and participated in writing the section on predictors of recovery. F.F. searched the literature and wrote the section on TMS–EEG in the multimodal diagnostic approach. D.F. was involved in the computational development of the model. M.T. searched the literature and wrote the section on synaptic dysfunctions following stroke. F.R. provided substantial contributions to discussion of the content. U.Z., J.C.R. and V.D.L. guided the manuscript development and revised the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Vincenzo Di Lazzaro.

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DOI

https://doi.org/10.1038/nrneurol.2014.162

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