Non-invasive brain stimulation as add-on therapy for subacute post-stroke aphasia: a randomized trial (NORTHSTAR)

Abstract

Introduction: Non-invasive brain stimulation (NIBS) with speech therapy might improve recovery from post-stroke aphasia. This three-armed sham-controlled blinded prospective proof-of-concept study tested 1 Hz subthreshold repetitive transcranial magnetic stimulation (rTMS) and 2-mA cathodal transcranial direct current stimulation (ctDCS) on the right pars triangularis in subacute post-stroke aphasia.

Patients and methods: Sixty-three patients with left middle cerebral artery infarcts were recruited in five hospitals (Canada/United States/Germany, 01-2014/03-2018) and randomized to receive rTMS (N = 20), ctDCS (N = 24) or sham stimulation (N = 19) with ST for 10 days. Primary outcome variables were Z-score changes in naming, semantic fluency and comprehension tests and adverse event frequency. Secondary outcome variable was the percent change in the Unified Aphasia Score. Intention-to-treat analyses tested between-group effects at days 1 and 30 post-treatment with a pre-planned subgroup analysis for lesion location (affecting Broca's area or not).

Results: Naming was significantly improved by rTMS (median = 1.91/interquartile range = 0.77/p =.01) at 30 days versus ctDCS (median = 1.11/interquartile range = 1.51) and sham stimulation (median = 1.02/interquartile range = 1.71). All other primary results were non-significant. The rTMS effect was driven by the patient subgroup with intact Broca's area where NIBS tended to improve UnAS (median = 33.2%/interquartile range = 46.7%/p =.062) versus sham stimulation (median = 12.5%/interquartile range = 7.9%) at day 30. Conversely, in patients with infarcted Broca's area, UnAS tended to improve more with sham stimulation (median = 75.0%/interquartile range = 86.9%/p =.053) versus NIBS (median = 12.7%/interquartile range = 31.7).Conclusion: We found a delayed positive effect of low-frequency rTMS targeting the right pars triangularis on the recovery of naming performance in subacute post-stroke aphasia. This intervention may be beneficial only in patients with morphologically intact Broca's area.

Keywords: Aphasia; language therapy; randomized control trial; speech therapy; stroke; transcranial direct current stimulation; transcranial magnetic stimulation.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

© European Stroke Organisation 2020.

Figures

Figure 1.

Participant flow.

Figure 2.

Unified Aphasia Score (UnAS) percent change: Panel A: rTMS (Mdn = 18.3, IQR = 53.5), ctDCS (Mdn = 7.4, IQR = 25.8), sham (Mdn = 5.6, IQR = 6.5), p = .789; Panel B: rTMS (Mdn = 3.0, IQR = 5.9), ctDCS (Mdn = 17.5, IQR = 27.4), sham (Mdn = 23.6, IQR = 36.7), p = .042; Post-hoc tests show sham > rTMS (χ2(1) = 7.244; p = .021; ϕ = 0.65, large effect); Panel C: rTMS (Mdn = 33.2, IQR = 46.8), ctDCS (Mdn = 26.8, IQR = 47.5), sham (Mdn = 12.5, IQR = 7.9), p = .009; post-hoc tests show rTMS > sham (χ2(1) = 11.733; p = .002; ϕ = 0.73, very large effect); Panel D: rTMS (Mdn = 6.7, IQR = 27.5), ctDCS (Mdn = 24.7, IQR = 87.1), sham (Mdn = 75.0, IQR = 86.9), p = .007; post-hoc tests show sham > rTMS (χ2(1) = 13.442; p = .001; ϕ = 0.89, very large effect).

Figure 3.

Lesion overlap maps spatially normalized to MNI-stereotaxic space for subgroups of patients with affected (Panel A) or non-affected (Panel B) Broca’s area. Color scale represents the percentage of patients who had infarcted tissue at that voxel.