Mechanisms of Verbal Fluency Impairment in Stroke: Insights From “Strategic Indices” Derived From a Study of 337 Patients

Verbal fluency provides a unique index of the functional architecture of control functions because it reflects the interactions between executive processes and lower-level language processes. However, an evaluation of the number of correct words alone does not enable one to determine precisely which processes are impaired. This study investigates post-stroke fluency impairments, focusing on previously unexplored indices and their neuroanatomical correlates using voxel-based lesion symptom mapping (VLSM). In total, 337 patients and 851 controls performed letter and semantic fluency tests. Analyses included overall performance (correct responses) and strategic indices (errors, time course, frequency, switches, and cluster size). Stroke patients produced fewer correct responses, more rule-breaking errors, fewer words after 15″, fewer infrequent words, fewer switches, and smaller clusters in letter fluency. Switching was strongly associated with letter fluency, while clustering was more related to semantic fluency. VLSM identified left-hemisphere structures, particularly frontal tracts (e.g., anterior thalamic and frontostriatal tracts), associated with switching, and a smaller set of left-hemisphere structures linked to clustering. Conceptually, the findings suggest stroke-related fluency disorders primarily arise from impairments in executive strategic search, as indicated by switching impairments, with weaker impairment on lexicosemantic abilities. The rarity of rule-breaking and perseverative errors indicates that inhibition and working memory deficits do not significantly contribute to poor fluency. The patients' production of infrequent words and fluency worsened over time, although the precise contributions of the three core processes to these additional changes require further investigation. Our results highlight the importance of detailed fluency evaluations in stroke patients for optimized rehabilitation.