Modulating cortical connectivity in stroke patients by rTMS assessed with fMRI and dynamic causal modeling

Abstract

Data derived from transcranial magnetic stimulation (TMS) studies suggest that transcallosal inhibition mechanisms between the primary motor cortex of both hemispheres may contribute to the reduced motor performance of stroke patients. We here investigated the potential of modulating pathological interactions between cortical motor areas by means of repetitive TMS using functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM). Eleven subacute stroke patients were scanned 1-3 months after symptom onset while performing whole hand fist closure movements. After a baseline scan, patients were stimulated with inhibitory 1-Hz rTMS applied over two different locations: (i) vertex (control stimulation) and (ii) primary motor cortex (M1) of the unaffected (contralesional) hemisphere. Changes in the endogenous and task-dependent effective connectivity were assessed by DCM of a bilateral network comprising M1, lateral premotor cortex, and the supplementary motor area (SMA). The results showed that rTMS applied over contralesional M1 significantly improved the motor performance of the paretic hand. The connectivity analysis revealed that the behavioral improvements were significantly correlated with a reduction of the negative influences originating from contralesional M1 during paretic hand movements. Concurrently, endogenous coupling between ipsilesional SMA and M1 was significantly enhanced only after rTMS applied over contralesional M1. Therefore, rTMS applied over contralesional M1 may be used to transiently remodel the disturbed functional network architecture of the motor system. The connectivity analyses suggest that both a reduction of pathological transcallosal influences (originating from contralesional M1) and a restitution of ipsilesional effective connectivity between SMA and M1 underlie improved motor performance.

Imaging human brain networks to improve the clinical efficacy of non-invasive brain stimulation

“…For example, inhibitory rTMS to the non-lesioned parietal cortex can induce long-lasting improvements in symptoms of spatial neglect (Brighina et al 2003;Shindo et al 2006). In the motor region, Grefkes and colleagues showed that inhibitory rTMS applied over contralesional M1 of patients with subacute stroke significantly improved motor performance of the affected hand (Grefkes et al, 2010). This improvement was related to functional reorganization of the sensorimotor system.…”

Bilateral Transcutaneous Electrical Nerve Stimulation Improves Lower‐Limb Motor Function in Subjects With Chronic Stroke: A Randomized Controlled Trial

“…The results of clinical studies have demonstrated that bilateral pinch gripping could enhance ipsilesional M1 excitability when compared with unilateral pinch gripping with either hand in subjects with stroke,24 which was shown by an increase in the motor evoked potential amplitude recorded from the first dorsal interosseous of the paretic hand 24. Moreover, Grefkes and colleagues23 demonstrated in a sample of 11 subjects with subacute and subcortical stroke that bilateral hand movements resulted in facilitatory neural coupling between the M1 and supplementary motor areas of the 2 cerebral hemispheres. Simultaneous activation of bilateral sensorimotor cortices via TENS might exert a similar effect of enhancing the interhemispheric interaction in both hemispheres via the corpus callosum, thus enhancing the effects of motor training.…”

“…Based on the findings of neuroanatomical48 and clinical23, 24 studies, the underlying mechanisms that mediate the effects of Bi‐TENS might include the enhancement of interhemispheric interaction, possibly via the corpus callosum, which is the white matter in the human brain that connects the 2 hemispheres via more than 200 million axonal connections 48. The motor areas of the 2 hemispheres have been shown with functional magnetic resonance imaging and diffusion tensor imaging to be connected via the posterior body of the corpus callosum 48.…”

“…Current evidence shows that bilateral intervention recruits spare neural substrates to enhance motor recovery17, 20, 21, 22, 23, 24, 25; we thus hypothesized that the application of TENS over both paretic and nonparetic legs (Bi‐TENS) might induce greater and earlier improvement in lower‐limb motor function than the use of Uni‐TENS in subjects with stroke. A literature search revealed that no study has compared the efficacy of Bi‐TENS+TOT and Uni‐TENS+TOT on motor recovery after stroke.…”

Optogenetic Approaches to Target Specific Neural Circuits in Post-stroke Recovery

“…Various strategies have been shown to enhance recovery in preclinical models and patients, including pharmacological treatment, rehabilitation (e.g., constraint-induced therapy) [32][33][34], stem cell transplantation [35,36], and brain stimulation [37][38][39][40][41][42][43]. In particular, brain stimulation is a promising area of research because it allows direct activation and manipulation of the target area's excitability.…”