In layperson terms I have no clue what cortical excitability does for stroke recovery.
Effects of transcranial magnetic stimulation in modulating cortical excitability in patients with stroke: a systematic review and meta-analysis
Journal of NeuroEngineering and Rehabilitation volume 19, Article number: 24 (2022)
Abstract
Background
Transcranial magnetic stimulation (TMS) has attracted plenty of attention as it has been proved to be effective in facilitating motor recovery in patients with stroke. The aim of this study was to systematically review the effects of repetitive TMS (rTMS) and theta burst stimulation (TBS) protocols in modulating cortical excitability after stroke.
Methods
A literature search was carried out using PubMed, Medline, EMBASE, CINAHL, and PEDro, to identify studies that investigated the effects of four rTMS protocols—low and high frequency rTMS, intermittent and continuous TBS, on TMS measures of cortical excitability in stroke. A random-effects model was used for all meta-analyses.
Results
Sixty-one studies were included in the current review. Low frequency rTMS was effective in decreasing individuals’ resting motor threshold and increasing the motor-evoked potential of the non-stimulated M1 (affected M1), while opposite effects occurred in the stimulated M1 (unaffected M1). High frequency rTMS enhanced the cortical excitability of the affected M1 alone. Intermittent TBS also showed superior effects in rebalancing bilateral excitability through increasing and decreasing excitability within the affected and unaffected M1, respectively. Due to the limited number of studies found, the effects of continuous TBS remained inconclusive. Motor impairment was significantly correlated with various forms of TMS measures.
Conclusions
Except for continuous TBS, it is evident that these protocols are effective in modulating cortical excitability in stroke. Current evidence does support the effects of inhibitory stimulation in enhancing the cortical excitability of the affected M1.
Background
Extensive investigations by means of transcranial magnetic stimulation (TMS) have provided pivotal insights into the cortical neurophysiology of patients who have suffered a stroke. Immediately after a stroke, impaired motor function accompanies substantial changes within the affected primary motor cortex (M1)—specifically, decreased corticospinal excitability, which can be reflected by the absence of recordable motor evoked potentials (MEPs)/decreased MEP amplitudes and increased resting/active motor thresholds (rMT/aMT) [1]. Besides, it is also evident that persistent disinhibition is detectable, regardless of chronicity [1], which is believed to have a facilitatory role in motor recovery [2]. For instance, the effects of rehabilitation training correlate with reduced intracortical inhibition, reflected by reduced short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition [3, 4]. With respect to the cortical reorganization within the unaffected M1, as suggested by neuroimaging studies, the unaffected M1 in stroke patients became overactivated during movement execution of the affected hand [5]. Along with recovery of motor functions, stroke patients tend to regain the interhemispheric balance over the bilateral sensorimotor cortices [6]. However, meta-analyses found nonsignificant differences in a series of TMS measures, such as rMT, aMT and MEP amplitudes, compared to healthy controls [1].
In view of the association between cortical excitability and motor impairment of the hemiplegic arm, non-invasive brain modulation by repetitive TMS (rTMS) has attracted plenty of attention as it is effective in facilitating motor relearning and motor recovery after stroke. In accordance with the interhemispheric imbalance model, hemiparesis is caused not only by damaged corticospinal output from the affected M1, but also by excessive transcallosal inhibition from the unaffected to the affected M1 which can be measured by interhemispheric inhibition (IHI) and the ipsilateral silent period (iSP) [7]. Therefore, two unilateral modulatory approaches have been proposed—exciting or inhibiting the affected and unaffected M1—to counterbalance bilateral cortical excitability [8]. Early studies have revealed that both a single session of low frequency rTMS (LF-rTMS) and high frequency rTMS (HF-rTMS) were effective in improving the motor performance of the hemiparetic hand when they were applied to the unaffected and affected M1 [9, 10], respectively. From a neurophysiological perspective, LF-rTMS was shown to significantly reduce the MEPs of the unaffected M1 and the IHI from the unaffected to affected M1 [9, 10], while HF-rTMS had a direct facilitatory effect on the affected M1 [10].
Theta burst stimulation (TBS) is a unique form of rTMS that is usually delivered at subthreshold intensities over a short conditioning period [11, 12]. In healthy people, intermittent TBS (iTBS) was shown to enhance cortical excitability outlasting the stimulation period by almost 30 min, while opposite effects were shown after continuous TBS (cTBS) [13]. In stroke, iTBS to the affected M1 and cTBS to the unaffected M1 were shown to increase and decrease the MEPs, respectively [14]. Clinical studies suggested that both iTBS and cTBS were effective in modulating modulate the cortical excitability in patients with acute stroke [15]; iTBS, but not cTBS, was also able to change the cortical excitability in patients with chronic stroke [14, 16, 17].
Since the early introduction of TMS in the treatment of stroke [9], the clinical effects of various rTMS protocols have been well reviewed [18], and LF-rTMS to the unaffected M1 was shown to be the most effective form of treatment [19]. However, previous meta-analyses and reviews have generally focused only on clinical effects; effects from a neurophysiological perspective were less systematically and statistically reviewed [18]. Because of the inextricable relationship between cortical reorganization and motor recovery, it is necessary to consider how rTMS modulates cortical excitability, and whether the interhemispheric imbalance model is a valid hypothesis underlying the two therapeutic approaches. Therefore, the current systematic review and meta-analysis were conducted to evaluate the effects of four forms of rTMS (namely, LF-rTMS, HF-rTMS, iTBS, and cTBS) on a range of TMS measures of cortical excitability, including rMT, aMT, MEPs, SICI, intracortical facilitation (ICF), and iSP of bilateral M1s. Moreover, not only the accumulated effects of multiple sessions of rTMS, but also the effects of a single session of stimulation were evaluated. We also summarize the correlation between cortical excitability and motor improvement after multiple sessions of stimulation.
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