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Predicting Modafinil-Treatment Response in Poststroke Fatigue Using Brain Morphometry and Functional Connectivity.

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Modafinil may reduce poststroke fatigue by improving fronto-striato-thalamic connectivity. Baseline fatigue severity and connectivity predict treatment response, suggesting alternative approaches for patients without these changes.

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Area of Science:

  • Neurology
  • Neuroimaging
  • Pharmacology

Background:

  • Poststroke fatigue significantly impacts survivors' quality of life.
  • Modafinil shows promise for reducing fatigue, but responses vary.
  • Predictors of modafinil efficacy in poststroke fatigue are not well understood.

Purpose of the Study:

  • To identify clinical and radiological predictors of fatigue reduction with modafinil in stroke survivors.
  • To explore the role of the fronto-striato-thalamic network in modafinil response.

Main Methods:

  • Twenty-six severe fatigue stroke survivors received 6-week daily modafinil (200 mg).
  • Baseline and post-treatment resting-state fMRI and structural MRI were acquired.
  • Functional connectivity within the fronto-striato-thalamic network and regional brain volumes were analyzed.

Main Results:

  • Higher baseline fatigue scores predicted greater fatigue reduction.
  • Reduced functional connectivity between the dorsolateral prefrontal cortex and caudate nucleus predicted better modafinil response.
  • The model explained 52% of the variance in fatigue reduction (adjusted r²=0.52).

Conclusions:

  • Fronto-striato-thalamic functional connectivity is a key predictor of modafinil response for poststroke fatigue.
  • Altered fronto-striato-thalamic network function may underlie poststroke fatigue, similar to other neurological conditions.
  • Patients with normal connectivity may require different treatment strategies.