Relationship between cognitive functioning and diffusion tensor imaging analysis along perivascular spaces as a diffusion magnetic resonance imaging marker of perivascular directional diffusivity in functional seizures after traumatic brain injury

Abstract Objective Patients with functional seizures (FS) frequently exhibit deficits in cognitive and functioning measures (CFM) similar in magnitude to those present in epilepsy. An association between glymphatic system function and CFM in various neuropsychiatric conditions has been reported. Our objective was to investigate the relationships between CFM and diffusion tensor imaging analysis along perivascular spaces (DTI‐ALPS) index as a measure of perivascular directional diffusivity related to neurofluid dynamics in FS after traumatic brain injury (TBI‐FS), TBI without functional seizures (TBI‐only), and healthy controls (HCs). Methods A total of 173 participants (40 HCs, 74 TBI‐FS, 59 TBI‐only) underwent diffusion magnetic resonance imaging at 3 T to establish their DTI‐ALPS index. CFM acquired in patient groups were Montreal Cognitive Assessment, Quality of Life in Epilepsy‐31 (total score and cognitive subscale), and Global Assessment of Functioning (GAF). Group differences were analyzed using linear mixed models with hemisphere as a within‐subject factor. The primary group comparison was adjusted for age and sex. Correlations between CFM and DTI‐ALPS index were examined in patient groups. Results CFM were significantly worse in TBI‐FS than TBI‐only on all measures. GAF showed a significant positive correlation with DTI‐ALPS index in the combined patient sample ( r = .228, p = .009). In the primary analysis, there was a significant main effect of group on DTI‐ALPS index ( F 2, 330 = 3.51, p = .031, η 2 p = .021). DTI‐ALPS index was lower in TBI‐FS than in TBI‐only ( p = .026), and biological sex was a significant covariate ( F 1, 330 = 5.71, p = .017; females higher). A significant hemispheric asymmetry was found, with right hemisphere DTI‐ALPS index values lower than left ( F 1, 340 = 35.30, p < .001, η 2 p = .094). Significance TBI‐FS participants showed reduced CFM across all measures, with lower global functioning associated with lower DTI‐ALPS index values in the combined patient sample, suggesting a positive relationship between perivascular directional diffusivity related to neurofluid dynamics and global functioning. Patients with TBI‐FS showed reduced DTI‐ALPS index compared to TBI‐only participants, suggesting potential differences in perivascular function.