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

Neurorehabil Neural Repair. 2022 Jun;36(6):371-380. doi: 10.1177/15459683221096391. Epub 2022 Apr 15.


Background: There is high variability in post-stroke aphasia severity and predicting recovery remains imprecise. Standard prognostics do not include neurophysiological indicators or genetic biomarkers of neuroplasticity, which may be critical sources of variability.

Objective: To evaluate whether a common polymorphism (Val66Met) in the gene for brain-derived neurotrophic factor (BDNF) contributes to variability in post-stroke aphasia, and to assess whether BDNF polymorphism interacts with neurophysiological indicators of neuroplasticity (cortical excitability and stimulation-induced neuroplasticity) to improve estimates of aphasia severity.

Methods: Saliva samples and motor-evoked potentials (MEPs) were collected from participants with chronic aphasia subsequent to left-hemisphere stroke. MEPs were collected prior to continuous theta burst stimulation (cTBS; index for cortical excitability) and 10 minutes following cTBS (index for stimulation-induced neuroplasticity) to the right primary motor cortex. Analyses assessed the extent to which BDNF polymorphism interacted with cortical excitability and stimulation-induced neuroplasticity to predict aphasia severity beyond established predictors.

Results: Val66Val carriers showed less aphasia severity than Val66Met carriers, after controlling for lesion volume and time post-stroke. Furthermore, Val66Val carriers showed expected effects of age on aphasia severity, and positive associations between severity and both cortical excitability and stimulation-induced neuroplasticity. In contrast, Val66Met carriers showed weaker effects of age and negative associations between cortical excitability, stimulation-induced neuroplasticity and aphasia severity.

Conclusions: Neurophysiological indicators and genetic biomarkers of neuroplasticity improved aphasia severity predictions. Furthermore, BDNF polymorphism interacted with cortical excitability and stimulation-induced neuroplasticity to improve predictions. These findings provide novel insights into mechanisms of variability in stroke recovery and may improve aphasia prognostics.

Keywords: aphasia; brain-derived neurotrophic factor; cortical excitability; language recovery; neuroplasticity; neurostimulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aphasia* / genetics
  • Biomarkers
  • Brain-Derived Neurotrophic Factor / genetics
  • Humans
  • Language
  • Neuronal Plasticity / genetics
  • Stroke* / complications
  • Stroke* / genetics
  • Transcranial Magnetic Stimulation


  • Biomarkers
  • Brain-Derived Neurotrophic Factor