Tracing volitional recovery in post-stroke akinetic mutism using longitudinal microstructure imaging: Insights from a single case study

Lesions in the frontal-subcortical circuitry can lead to akinetic mutism (AM) characterized by diminished volition. However, the microstructural changes in the damaged network underlying its recovery remain unknown. Clinical examination and neuropsychological assessment were performed on a patient with post-stroke AM. Multimodal MRI scans were performed at baseline and follow-ups. We used diffusion MRI and biophysical models, specifically utilizing neurite orientation dispersion and density imaging for assessing gray matter microstructure, and fixel-based analysis for the evaluation of white matter. Longitudinal comparisons were performed between the patient and healthy controls. Pronounced recovery of volition was observed after dopamine agonist therapy combined with physical therapy. In addition to infarcts in the bilateral medial cortex, microstructure imaging detected reduced neurite density in extensive areas, specifically in temporal areas and subcortical nuclei, and decreased fiber density of white matter tracts (TFCE-corrected p < .05). Microstructural degeneration in the anterior cingulate cortex and cingulum was relatively persistent (Bonferroni-corrected p < .05). However, most tracts within the frontal-subcortical circuitry showed increased fiber density during the recovery stage. Microstructure of an extensive network may contribute to the disruption and recovery of volition. Fiber density within the frontal-subcortical circuitry could be a promising biomarker indicating volitional recovery.