Differential Effects of Speech and Language Therapy and rTMS in Chronic Versus Subacute Post-stroke Aphasia: Results of the NORTHSTAR-CA Trial

Abstract

Background & objective Contralesional 1-Hz repetitive transcranial magnetic stimulation (rTMS) over the right pars triangularis combined with speech-language therapy (SLT) has shown positive results on the recovery of naming in subacute (5–45 days) post-stroke aphasia. NORTHSTAR-CA is an extension of the previously reported NORTHSTAR trial to chronic aphasia (>6 months post-stroke) designed to compare the effectiveness of the same rTMS protocol in both phases. Methods Sixty-seven patients with left middle cerebral artery infarcts (28 chronic, 39 subacute) were recruited (01-2014 to 07-2019) and randomized to receive rTMS (N = 34) or sham stimulation (N = 33) with SLT for 10 days. Primary outcome variables were Z-score changes in naming, semantic fluency and comprehension tests and adverse event frequency. Intention-to-treat analyses tested between-group effects at days 1 and 30 post-treatment. Chronic and subacute results were compared. Results Adverse events were rare, mild, and did not differ between groups. Language outcomes improved significantly in all groups irrespective of treatment and recovery phase. At 30-day follow-up, there was a significant interaction of stimulation and recovery phase on naming recovery ( P <.001). Naming recovery with rTMS was larger in subacute (Mdn = 1.91/IQR = .77) than chronic patients (Mdn = .15/IQR = 1.68/ P = .015). There was no significant rTMS effect in the chronic aphasia group. Conclusions The addition of rTMS to SLT led to significant supplemental gains in naming recovery in the subacute phase only. While this needs confirmation in larger studies, our results clarify neuromodulatory vs training-induced effects and indicate a possible window of opportunity for contralesional inhibitory stimulation interventions in post-stroke aphasia. NORTHSTAR trial registration https://clinicaltrials.gov/ct2/show/NCT02020421 .

Narrative Review of Noninvasive Brain Stimulation in Stroke Rehabilitation

“…For some post-stroke unilateral neglect patients, the parietal cortex was generally stimulated [ 30 ]. Stimulation of the Broca area was used to treat motor aphasia [ 31 , 32 ], and stimulation of the Wernicke area was applied for sensory aphasia [ 33 ]. However, large-scale alterations at the network level emerge after the plastic effects of rTMS, which contribute to local and long-term changes in the stimulated network and interactions between the stimulated and other functional networks [ 34 , 35 ].…”

“…After applying LF-rTMS in the right posterior superior temporal gyrus, auditory comprehension and repetition improved significantly, while inhibition in the posterior inferior frontal gyrus contributed to a significant enhancement of spontaneous speech and repetition [ 129 ]. Recently, a randomized sham-controlled blinded study [ 32 ] first found that subacute aphasia patients received a better effect by 1 Hz subthreshold rTMS over the pars triangularis of the right inferior frontal gyrus compared with patients in the chronic phase. Now, more research is focusing on the effects of rTMS on functional communication, with the ultimate goal of restoring communication in everyday life.…”

Continuous theta burst stimulation-induced suppression of the right fronto-thalamic-cerebellar circuit accompanies improvement in language performance in poststroke aphasia: A resting-state fMRI study

“…Therefore, cTBS of the right pSTG may downregulate the activity of the right pars triangularis through structural or functional connections between the two major nodes, such as the arcuate fasciculus. The right pars triangularis, the homotopic area to Broca’s area frequently used as a stimulation target, was inhibited in most of the previous studies addressing interhemispheric imbalance by decreasing activity in the right hemisphere or increasing activity in the left hemisphere ( Thiel et al, 2013 ; Heikkinen et al, 2018 ; Lee et al, 2022 ; Zumbansen et al, 2022 ). Our fALFF results provided compelling evidence for cTBS-induced reduction in spontaneous neural activity not only in the right frontal language regions but also in subcortical regions, including the right thalamus and the left cerebellum, in aphasic patients compared with those who received sham treatment.…”

Noninvasive Brain Stimulation for Neurorehabilitation in Post-Stroke Patients

“…The use of NIBS techniques for aphasia rehabilitation has aroused wide interest, especially the application of TMS and tDCS. Growing evidence has verified their effectiveness in modulating cortical excitability [ 148 ], facilitating functional reorganization [ 149 ], and improving speech and language performance [ 150 ].…”