Stratifying chronic stroke patients based on the influence of contralesional motor cortices: An inter-hemispheric inhibition study

Abstract

Objective: A recent "bimodal-balance recovery" model suggests that contralesional influence varies based on the amount of ipsilesional reserve: inhibitory when there is a large reserve, but supportive when there is a low reserve. Here, we investigated the relationships between contralesional influence (inter-hemispheric inhibition, IHI) and ipsilesional reserve (corticospinal damage/impairment), and also defined a criterion separating subgroups based on the relationships.

Methods: Twenty-four patients underwent assessment of IHI using Transcranial Magnetic Stimulation (ipsilateral silent period method), motor impairment using Upper Extremity Fugl-Meyer (UEFM), and corticospinal damage using Diffusion Tensor Imaging and active motor threshold. Assessments of UEFM and IHI were repeated after 5-week rehabilitation (n = 21).

Results: Relationship between IHI and baseline UEFM was quadratic with criterion at UEFM 43 (95%conference interval: 40-46). Patients less impaired than UEFM = 43 showed stronger IHI with more impairment, whereas patients more impaired than UEFM = 43 showed lower IHI with more impairment. Of those made clinically-meaningful functional gains in rehabilitation (n = 14), more-impaired patients showed further IHI reduction.

Conclusions: A criterion impairment-level can be derived to stratify patient-subgroups based on the bimodal influence of contralesional cortex. Contralesional influence also evolves differently across subgroups following rehabilitation.

Significance: The criterion may be used to stratify patients to design targeted, precision treatments.

Keywords: Corticospinal; Diffusion Tensor Imaging (DTI); Inter-Hemispheric Inhibition (IHI); Motor function; Rehabilitation; Stroke; Transcranial Magnetic Stimulation (TMS); Upper limb.

Figure 1.

Example of the ipsilesional silent period (iSP) data used to characterize interhemispheric inhibition (IHI-iSP) from the contralesional motor cortex in a stroke patient, using transcranial magnetic stimulation (TMS). (A) Schematic describes how iSP is collected based on application of supra-threshold (150% contralesional resting motor threshold, RMT). TMS pulses to the contralesional hemisphere during contraction of the paretic first dorsal interosseous (FDI) muscle. (B) Example traces showing how TMS leads to transient suppression (silence) of ongoing paretic FDI activity in a patient with Upper Extremity Fugl-Meyer (UEFM) of 53. Onset and offset of iSP are marked (top). Onset is at 47 ms after the application of the TMS pulse in this example and 22 ms later than the onset of the contralateral motor evoked potential (MEP) (bottom). iSP lasted for 31 ms and showed a 72% reduction in EMG (relative to pre-stimulus EMG). The reduction was used to characterize IHI.

Figure 2.

All the relationships between baseline IHI-iSP and impairment/damage are quadratic. (A) The threshold regression model for UEFM was significant and the criterion UEFM level could be identified at 43 (95% conference interval: 40 to 46). (B) The change point of AMT is at 65% but the threshold regression model was not significant. (C) The change point of FA_Asymmetry is at 0.22 but the threshold regression model was not significant. (D) Patient with UEFM of 44 demonstrates stronger IHI-iSP (81% decrease in paretic FDI EMG) (left) than another patient with milder impairment (UEFM = 54) (61% decrease in paretic FDI EMG) (right). IHI-iSP, interhemispheric inhibition measured with the method of ipsilateral silent period; UEFM, Upper Extremity Fugl-Meyer; AMT, active motor threshold; iSP, ipsilateral silent period; FA_Asymmetry, fractional anisotropy asymmetry; FDI, first dorsal interosseous.

Figure 3.

(A) IHI-iSP of healthy control subjects and IHI-iSP at baseline and post-training for patients less affected and more affected than UEFM 43. At post-training, there is a significant difference in IHI-iSP between less-affected and more-affected patients. (B) Pre- to post-treatment change in IHI-iSP is compared a more-affected patient (UEFM = 36) (left) to a less-affected patient (UEFM = 60) (right). The more-affected patient shows more substantial reduction in IHI from pre-to post-treatment compared to the less affected patient (−12% vs. 3%). (C and D) Correlation between change in IHI-iSP and change in UEFM is not significant in the more-affected subgroup (p = 0.996) but is significant in less-affected subgroups (p = 0.009). IHI-iSP, interhemispheric inhibition measured with the method of ipsilateral silent period; UEFM, Upper Extremity Fugl-Meyer.