Tailoring Brain Stimulation to the Nature of Rehabilitative Therapies in Stroke: A Conceptual Framework Based on their Unique Mechanisms of Recovery

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Key points

  • Noninvasive brain stimulation is typically paired with unilateral therapies of the upper limb.

  • Many recent clinical trials have failed to augment rehabilitative outcomes, especially for patients with greater motor impairments.

  • Bilateral therapies may offer a more feasible and neurophysiologic advantage over unilateral therapy to augment rehabilitative outcomes for patients with greater motor impairments.

  • Based on mechanisms of recovery, this article discusses how to create noninvasive brain

Mechanisms of recovery underlying unilateral therapy

Typically, coordination between limbs requires modulating motor overflow, where motor overflow refers to facilitation from the “moving” cortices to the opposing “resting” hemisphere. During unilateral movement of a limb, mirror movements can occur in the opposite resting limb if motor overflow is not regulated. Interhemispheric interactions conducted via transcallosal pathways between both hemispheres help regulate overflow. Specifically, the hemisphere contralateral to the moving limb imposes

Combining noninvasive brain stimulation with unilateral therapy based on theory of underlying mechanisms

In accordance with the interhemispheric competition model, present-day NIBS approaches aim to upregulate excitability of the affected hemisphere but inhibit that of the unaffected hemisphere to enhance rehabilitative outcomes. Toward this end, multiple research groups have used high-frequency rTMS or anodal tDCS to excite the affected hemisphere or low-frequency rTMS or cathodal tDCS to inhibit the unaffected hemisphere (Fig. 2; for a full review see Hoyer and Celnik46 or Sandrini and Cohen47).

Limitations of unilateral therapies and associated noninvasive brain stimulation approaches

Larger clinical trials have had limited success when replicating the early promise of pairing NIBS with unilateral therapies.15, 16, 22, 23, 24, 25, 51 One possible reason for the disappointing results is that the groups were less homogenous and included patients with a wider range of impairment than in earlier smaller studies. Previous studies have discussed that pairing NIBS with unilateral therapy is less effective for the more impaired chronic stroke patients.15, 26 An important question to

Bilateral therapy as an alternative approach

Bilateral approaches differ from unilateral therapies because they require moving both limbs simultaneously, either independently or in a linked manner. For example, bilateral isokinematic training28 requires patients to move both limbs, but actions of one are not dependent or controlled by actions of the other. In contrast, Stinear and Byblow’s69 APBT, Whitall and colleagues’s27 BATRAC, and Knutson and colleagues’s29 CCFES link movements of both limbs. Using external instrumentation, such as

Noninvasive brain stimulation approaches during bilateral therapy

The framework we have summarized regarding mechanisms of bilateral therapies could supply a basis for creating augmentative NIBS approaches. Bradnam and colleagues82 previously suggested that because of the potential impact of the indirect ipsilateral corticospinal pathways, one alternative NIBS approach would be to facilitate the unaffected hemisphere to improve paretic upper-limb function. NIBS has typically been used to facilitate the affected hemisphere and inhibit the unaffected hemisphere

Summary

This article discusses early evidence that bilateral therapy may be feasible and offer an alternative therapeutic advantage to unilateral therapy at least for patients with greater motor impairments. However, to date, no study has demonstrated superiority for either approach. Advances in research have demonstrated a notable shift in how scientists and therapists interpret mechanisms of recovery between patients. Many groups have begun to suggest alternative NIBS protocols and therapies

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    This work was supported by the National Institutes of Health (1K01HD069504) and American Heart Association (13BGIA17120055) to E.B. Plow and by the Clinical & Translational Science Collaborative (RPC2014-1067) to D.A. Cunningham.

    Conflicts of Interest: A.G. Machado has the following conflicts of interest to disclose: ATI, Enspire, and Cardionomics (distribution rights from intellectual property); Spinal Modulation and Functional Neurostimulation (consultant).

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