Influence of Corticospinal Tracts from Higher Order Motor Cortices on Recruitment Curve Properties in Stroke.

BACKGROUND: Recruitment curves (RCs) acquired using transcranial magnetic stimulation are commonly used in stroke to study physiologic functioning of corticospinal tracts (CST) from M1. However, it is unclear whether CSTs from higher motor cortices contribute as well. OBJECTIVE: To explore whether integrity of CST from higher motor areas, besides M1, relates to CST functioning captured using RCs. METHODS: RCs were acquired for a paretic hand muscle in patients with chronic stroke. Metrics describing gain and overall output of CST were collected. CST integrity was defined by diffusion tensor imaging. For CST emerging from M1 and higher motor areas, integrity (fractional anisotropy) was evaluated in the region of the posterior limb of the internal capsule, the length of CST and in the region of the stroke lesion. RESULTS: We found that output and gain of RC was related to integrity along the length of CST emerging from higher motor cortices but not the M1. CONCLUSIONS: Our results suggest that RC parameters in chronic stroke infer function primarily of CST descending from the higher motor areas but not M1. RCs may thus serve as a simple, in-expensive means to assess re-mapping of alternate areas that is generally studied with resource-intensive neuroimaging in stroke.

Challenges in Recruitment for the Study of Noninvasive Brain Stimulation in Stroke: Lessons from Deep Brain Stimulation.

OBJECTIVE: Noninvasive brain stimulation (NIBS) can augment functional recovery following stroke; however, the technique lacks regulatory approval. Low enrollment in NIBS clinical trials is a key roadblock. Here, we pursued evidence to support the prevailing opinion that enrollment in trials of NIBS is even lower than enrollment in trials of invasive, deep brain stimulation (DBS). METHODS: We compared 2 clinical trials in stroke conducted within a single urban hospital system, one employing NIBS and the other using DBS, (1) to identify specific criteria that generate low enrollment rates for NIBS and (2) to devise strategies to increase recruitment with guidance from DBS. RESULTS: Notably, we found that enrollment in the NIBS case study was 5 times lower (2.8%) than the DBS trial (14.5%) (χ(2) = 20.815, P < .0001). Although the number of candidates who met the inclusion criteria was not different (χ(2) = .04, P < .841), exclusion rates differed significantly between the 2 studies (χ(2) = 21.354, P < .0001). Beyond lack of interest, higher exclusion rates in the NIBS study were largely due to exclusion criteria that were not present in the DBS study, including restrictions for recurrent strokes, seizures, and medications. CONCLUSIONS: Based on our findings, we conclude and suggest that by (1) establishing criteria specific to each NIBS modality, (2) adjusting exclusion criteria based on guidance from DBS, and (3) including patients with common contraindications based on a probability of risk, we may increase enrollment and hence significantly impact the feasibility and generalizability of NIBS paradigms, particularly in stroke.

Reproducibility of transcranial magnetic stimulation metrics in the study of proximal upper limb muscles.

OBJECTIVE: Reproducibility of transcranial magnetic stimulation (TMS) metrics is essential in accurately tracking recovery and disease. However, majority of evidence pertains to reproducibility of metrics for distal upper limb muscles. We investigate for the first time, reliability of corticospinal physiology for a large proximal muscle - the biceps brachii and relate how varying statistical analyses can influence interpretations. METHODS: 14 young right-handed healthy participants completed two sessions assessing resting motor threshold (RMT), motor evoked potentials (MEPs), motor map and intra-cortical inhibition (ICI) from the left biceps brachii. Analyses included paired t-tests, Pearson's, intra-class (ICC) and concordance correlation coefficients (CCC) and Bland-Altman plots. RESULTS: Unlike paired t-tests, ICC, CCC and Pearson's were >0.6 indicating good reliability for RMTs, MEP intensities and locations of map; however values were <0.3 for MEP responses and ICI. CONCLUSIONS: Corticospinal physiology, defining excitability and output in terms of intensity of the TMS device, and spatial loci are the most reliable metrics for the biceps. MEPs and variables based on MEPs are less reliable since biceps receives fewer cortico-motor-neuronal projections. Statistical tests of agreement and associations are more powerful reliability indices than inferential tests. SIGNIFICANCE: Reliable metrics of proximal muscles when translated to a larger number of participants would serve to sensitively track and prognosticate function in neurological disorders such as stroke where proximal recovery precedes distal.