Abstracts

Rationale: Patients with epilepsy (PWE) suffer cognitive deficits, which contribute to poor quality of life. There are ongoing efforts to develop treatments to improve cognition in PWE. This study assesses how adjunct treatment with a pharmaceutical formulation of cannabidiol (100 mg/ml CBD®) affects attention processing during fMRI in patients with intractable epilepsy who are part of the UAB CBD Program. Methods: 19 PWE (7 male; ages 16-62) underwent 3T fMRI (2 scanners) at 2 visits: before starting CBD treatment (OFF) and while on a stable intermediate dose of CBD (15, 20, or 25 mg/kg) for at least 2 weeks (ON). At each visit, each patient performed 2 fMRI runs of a modified Eriksen Flanker task to assess attention and inhibitory control (as recommended by NIH CDE). Each run consisted of 6 blocks each with congruent (CON) and incongruent (INCON) stimuli. For each stimulus, PWE were instructed to indicate via button press the direction the center fish was swimming relative to the surrounding fish. Standard fMRI image processing, statistical modeling and visualization were performed using AFNI software. Single-subject general linear modeling was performed to contrast fMRI response to CON vs. INCON conditions and assess attention processing, while accounting for head motion, MRI signal drift, and serial correlation of noise parameters. One-sample t-tests (covarying for scanner type and monthly seizure frequency) were performed to assess main effects of attention processing (CON vs. INCON contrast) for each visit. Regression analysis was then performed to compare OFF and ON visits (covarying for scanner type and monthly seizure frequency) and determine CBD-related changes in attention processing. Results: Average time between fMRI visits was 11.9 weeks and median percent change in seizure frequency was -61.9% (range -100% to 50%). The pattern of Flanker task attention processing differed between the OFF and ON visits, with patients only showing significant INCON>CON activation at the ON visit while also exhibiting CON>INCON activation at the OFF visit (p=0.05, corrected; voxelwise p=0.001, cluster threshold 18 voxels; Fig. 1A,B). Regression analysis showed a greater difference in fMRI response to CON vs. INCON conditions in the left middle frontal and superior frontal gyrus at the ON compared to OFF visit (p=0.01 uncorrected, cluster threshold 10 voxels; Fig. 2). Behavioral data was recorded for only 11 patients, which showed non-statistically significant improvement in task accuracy for both CON (33.2% to 43.2%; p=0.13) and INCON (31.8% to 38.3%; p=0.30) conditions from OFF to ON visits, respectively. Conclusions: PWE recruited less brain regions overall for attention processing at the ON visit when compared to the OFF visit, and specifically only increased activation at the ON visit to the more difficult INCON condition. Considering all analyses accounted for seizure frequency, the observed change in attention-related cortical activity is likely a result of CBD treatment. Funding: State of Alabama