Exploring Theta Burst Stimulation as an intervention to improve motor recovery in chronic stroke☆
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)
Neurophysiological methods for studies of the motor system in freely moving human subjects
J Neurosci Methods
(1997)- et al.
Theta burst stimulation of the human motor cortex
Neuron
(2005) - et al.
Sham TMS: intracerebral measurement of the induced electrical field and the induction of motor-evoked potentials
Biol Psychiatry
(2001) Techniques and mechanisms of action of transcranial stimulation of the human motor cortex
J Neurosci Methods
(1997)- et al.
Arm function after stroke: neurophysiological correlates and recovery mechanisms assessed by transcranial magnetic stimulation
Clin Neurophysiol
(2006) - et al.
Muscle strengthening and physical conditioning to reduce impairment and disability in chronic stroke survivors
Arch Phys Med Rehabil
(1999) - et al.
The intra- and interrater reliability of the action research arm test: a practical test of upper extremity function in patients with stroke
Arch Phys Med Rehabil
(2001) - et al.
Cortical stimulation and epileptic seizure: a study of the potential risk in primates
Neurosurgery
(1999) - et al.
Maximal grip force in chronic stroke subjects and its relationship to global upper extremity function
Clin Rehabil
(1999) - et al.
Motor cortex stimulation for the enhancement of recovery from stroke: a prospective, multicenter safety study
Neurosurgery
(2006)
Assessing motor impairment after stroke: a pilot reliability study
J Neurol Neurosurg Psychiatry
Theta-burst repetitive transcranial magnetic stimulation suppresses specific excitatory circuits in the human motor cortex
J Physiol
Direct demonstration that repetitive transcranial magnetic stimulation can enhance corticospinal excitability in stroke
Stroke
Transcranial direct current stimulation of the unaffected hemisphere in stroke patients
Neuroreport
A sham-controlled trial of a 5-day course of repetitive transcranial magnetic stimulation of the unaffected hemisphere in stroke patients
Stroke
Multimodal imaging of brain reorganization in motor areas of the contralesional hemisphere of well recovered patients after capsular stroke
Brain
Multivariate analysis of improvement and outcome following stroke rehabilitation
Arch Neurol
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The work has taken place at the Institute of Neurology.