Evidence for a Window of Enhanced Plasticity in the Human Motor Cortex Following Ischemic Stroke

Abstract

Background In preclinical models, behavioral training early after stroke produces larger gains compared with delayed training. The effects are thought to be mediated by increased and widespread reorganization of synaptic connections in the brain. It is viewed as a period of spontaneous biological recovery during which synaptic plasticity is increased. Objective To look for evidence of a similar change in synaptic plasticity in the human brain in the weeks and months after ischemic stroke. Methods We used continuous theta burst stimulation (cTBS) to activate synapses repeatedly in the motor cortex. This initiates early stages of synaptic plasticity that temporarily reduces cortical excitability and motor-evoked potential amplitude. Thus, the greater the effect of cTBS on the motor-evoked potential, the greater the inferred level of synaptic plasticity. Data were collected from separate cohorts (Australia and UK). In each cohort, serial measurements were made in the weeks to months following stroke. Data were obtained for the ipsilesional motor cortex in 31 stroke survivors (Australia, 66.6 ± 17.8 years) over 12 months and the contralesional motor cortex in 29 stroke survivors (UK, 68.2 ± 9.8 years) over 6 months. Results Depression of cortical excitability by cTBS was most prominent shortly after stroke in the contralesional hemisphere and diminished over subsequent sessions ( P = .030). cTBS response did not differ across the 12-month follow-up period in the ipsilesional hemisphere ( P = .903). Conclusions Our results provide the first neurophysiological evidence consistent with a period of enhanced synaptic plasticity in the human brain after stroke. Behavioral training given during this period may be especially effective in supporting poststroke recovery.

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

“…This direct comparison may support the hypothesis of a window of neuroplasticity which renders the brain specifically susceptible to neuromodulatory intervention relatively early during the course of recovery. 35 Most imaging studies in post-stroke aphasia concur that a shift of task-induced brain activation is observed in the first weeks after the stroke and that a normalization of activity patterns occurs after several months. 36 – 38 It has been shown in combined imaging and brain stimulation studies, that this natural occurring process can be modulated with rTMS in the first 2–12 weeks and that such successful modulation correlates with therapy response.…”

Genetic and Neurophysiological Biomarkers of Neuroplasticity Inform Post-Stroke Language Recovery

“…Moreover, we found that BDNF polymorphism, a genetic biomarker of neuroplasticity, accounted for a substantial amount of variance in aphasia severity and improved estimates of aphasia severity from established predictors alone. In addition, BDNF polymorphism interacted with other metrics of plasticity, including age at stroke, 32,33 cortical excitability, 29,30 and stimulation-induced neuroplasticity 27,28 to predict aphasia severity. These findings and their implications are discussed below.…”

Genetic and neurophysiological biomarkers of neuroplasticity inform post-stroke language recovery

“…Moreover, we found that BDNF polymorphism, a genetic biomarker of neuroplasticity, accounted for a substantial amount of variance in aphasia severity and improved estimates of aphasia severity from established predictors alone. In addition, BDNF polymorphism interacted with other metrics of plasticity, including age at stroke [41,42], cortical excitability [29,30], and stimulation-induced neuroplasticity [27,28] to predict aphasia severity. These findings and their implications are discussed below.…”

“…In particular, we investigated MEP amplitudes at baseline to measure cortical excitability as well as cTBS-induced MEP suppression (difference between pre-vs post-cTBS MEP amplitudes) as a measure of neuroplasticity. Examining MEPs enables us to objectively assess propensity for response to non-invasive brain stimulation (NIBS) [25][26][27][28], which is critical to understanding the mechanisms of efficacy and inter-individual variability in NIBS responsiveness for post-stroke language recovery and aphasia rehabilitation.…”