Elsevier

Clinical Neurophysiology

Volume 118, Issue 2, February 2007, Pages 333-342
Clinical Neurophysiology

Exploring Theta Burst Stimulation as an intervention to improve motor recovery in chronic stroke

https://doi.org/10.1016/j.clinph.2006.10.014Get rights and content

Abstract

Objective

To explore the effects of a single session of repetitive Transcranial Magnetic Stimulation, given as Theta Burst Stimulation, on behavioural and physiological measures of hand function in chronic stroke patients.

Methods

Six chronic stroke patients with incomplete recovery of the hand were tested under three conditions: excitatory TBS over the stroke hemisphere (iTBSSH), inhibitory TBS (cTBSIH) over the intact hemisphere and sham stimulation. Behavioural outcomes included simple and choice reaction time paradigms. Physiological effects were assessed using single pulse TMS on both sides. Changes were sought for up to 40 min after TBS.

Results

Immediately after iTBSSH simple reaction times in the paretic hands were decreased and, compared to sham stimulation, remained significantly shorter throughout the testing period. The amplitude of the MEPs at rest and during background contraction and the area under the Input–Output curves were also increased on the stroke side after iTBSSH. cTBSIH suppressed the MEPs evoked in the healthy hands but did not change motor behaviour or the electrophysiology of the paretic hands. No side effects were encountered.

Conclusions

TBS seems safe in chronic stroke patients. iTBS over the stroke hemisphere transiently improved motor behaviour and corticospinal output in the paretic hands.

Significance

Excitatory TBS may represent a useful rTMS protocol to apply to the stroke hemisphere in future longer term therapy trials.

Introduction

A number of reports have recently shown that non-invasive brain stimulation can transiently improve motor behaviour of the paretic hand in chronic stroke patients (Mansur et al., 2005, Takeuchi et al., 2005, Fregni et al., 2005, Hummel et al., 2005). The implication is that brain stimulation could enhance clinical outcome when added to behavioural interventions used in current rehabilitation protocols, probably by optimising plastic changes in the cortex. Whether this effect will prove sufficiently robust to be useful clinically remains to be clarified as do questions about the optimal stimulation site and paradigm, and which patients are most likely to benefit.

Two general approaches are currently being used in the motor system. They are based on a model of interhemispheric rivalry between the motor areas of the stroke and intact hemisphere (Ward and Cohen, 2004, Murase et al., 2004) in which the stroke hemisphere is doubly disabled both by its own damage and by interfering output from the intact hemisphere. Therefore low-frequency repetitive Transcranial Magnetic Stimulation (rTMS) (Mansur et al., 2005, Takeuchi et al., 2005) or cathodal Transcranial Direct Current Stimulation (TDCS) (Fregni et al., 2005) have been used in single-session designs to suppress excitability in the intact hemisphere (IH). Both appear to induce a transient functional benefit of 10–20%. Excitatory stimulation of the stroke hemisphere (SH) has mainly been tested in the form of anodal TDCS and seems to be equally effective in improving motor function in chronic stroke patients (Fregni et al., 2005, Hummel et al., 2005). To date, the role of high frequency rTMS on the stroke study has mainly been assessed in the form of changes in clinical outcomes after multiple sessions; (Uy et al., 2003, Khedr et al., 2005); little is known about the actual effects of rTMS on the injured corticospinal tract and its behavioural correlates. One recent study showed that motor behaviour and neurophysiological measures of chronically paretic hands improve during a short train of high frequency rTMS (Kim et al., 2006). However, the duration of the after effects was not reported.

A very recent study showed that daily applications of inhibitory rTMS over the IH for 5 days may lead to consolidation of the benefits measured as simple motor reaction time, although the changes in a stroke-specific measure of hand function were less impressive and not clearly sustained after the end of the stimulation period (Fregni et al., 2006). These findings provide further support for the model of interhemispheric rivalry, but other recent evidence suggests that it may be an oversimplistic concept as in some circumstances the intact hemisphere may contribute to, rather than interfere with, control of the affected limbs. For example, brief functional disruption of contralesional motor areas impairs complex movements made with the paretic hand (Lotze et al., 2006). Aphasic patients may also perform worse after suppression of the right language area homologues (Martin et al., 2004, Winhuisen et al., 2005). To date only one study, using TDCS, has compared the effectiveness of suppressing the IH with facilitation of SH in patients with motor stroke; both approaches were found to be equally effective, with slightly greater improvement after suppression of the IH (Fregni et al., 2005). It is not yet known whether this is also true for rTMS, or whether application of excitatory rTMS protocols to the stroke hemisphere increases the risk of provoking a seizure.

Theta Burst Stimulation (TBS) is a novel form of rTMS that employs very low intensity to increase or decrease motor cortical excitability in healthy subjects for up to 20 min after the end of stimulation (Huang et al., 2005). The nature of the effect depends on the stimulation pattern (see Section 2). Bezard et al. showed that the seizure risk from motor cortical stimulation in healthy baboons results from high stimulation intensities (Bezard et al., 1999). TBS could thus represent a good rTMS option for treating stroke patients: it has a robust effect that lasts long enough to be clinically useful and a theoretically safer profile. The present study was conducted to test this hypothesis by evaluating the effect of a single session of TBS in a small population of unselected chronic stroke patients. We aimed to investigate if TBS can safely induce immediate improvements in the motor behaviour of the paretic hand, to identify power/duration differences between two interventions, excitation of the SH vs inhibition of the IH, and to study physiological equivalents of any behavioural effects.

Section snippets

Patients

Six patients (mean age 61.2 ± 13.6, 2 females 4 males) with a history of a single infarct within the Middle Cerebral Artery (MCA) territory initially causing hand weakness were recruited at least 1 year after the ictus. The National Institute of Health Stroke Scale (NIHSS) (Lyden et al., 1999), the arm section of the Motricity Index (MI) (Collin and Wade, 1990), the Action Research Arm Test (ARAT) (van Der Lee et al., 2001) and the 9-hole peg test (Heinemann et al., 1987) were employed to

Results

There were no major adverse events. TBS was well tolerated by all patients.

The main results are summarized in Fig. 3. In summary, iTBS over the stroke hemisphere (iTBSSH) was the only condition that significantly improved the motor behaviour and the physiological measures of the paretic hand.

Discussion

This study was designed to pilot the safety and efficacy of TBS in a small number of unselected chronic stroke patients. The lack of adverse events supports our hypothesis that TBS, which employs low stimulation intensities, is unlikely to be epileptogenic, at least when the lesion does not involve the whole MCA territory. Excitatory TBS over the stroke hemisphere (iTBSSH) transiently improved simple motor behaviour of the paretic hand in chronic stroke patients. In particular, iTBSSH shortened

Disclosure

The authors have reported no conflicts of interest.

References (36)

  • C. Collin et al.

    Assessing motor impairment after stroke: a pilot reliability study

    J Neurol Neurosurg Psychiatry

    (1990)
  • V. Di Lazzaro et al.

    Theta-burst repetitive transcranial magnetic stimulation suppresses specific excitatory circuits in the human motor cortex

    J Physiol

    (2005)
  • V. Di Lazzaro et al.

    Direct demonstration that repetitive transcranial magnetic stimulation can enhance corticospinal excitability in stroke

    Stroke

    (2006)
  • F. Fregni et al.

    Transcranial direct current stimulation of the unaffected hemisphere in stroke patients

    Neuroreport

    (2005)
  • F. Fregni et al.

    A sham-controlled trial of a 5-day course of repetitive transcranial magnetic stimulation of the unaffected hemisphere in stroke patients

    Stroke

    (2006)
  • C. Gerloff et al.

    Multimodal imaging of brain reorganization in motor areas of the contralesional hemisphere of well recovered patients after capsular stroke

    Brain

    (2006)
  • A.W. Heinemann et al.

    Multivariate analysis of improvement and outcome following stroke rehabilitation

    Arch Neurol

    (1987)
  • Huang YZ. Theta burst stimulation of the human motor cortex. Thesis. University of London;...
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    The work has taken place at the Institute of Neurology.

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