Abstracts

Rationale: Gender differences have been observed in the structure and connectivity of the human brain. Women with epilepsy, particularly left temporal lobe epilepsy (TLE), often have increased seizure severity and frequency during menarche, certain menstrual cycle phases, and perimenopause.1 Reproductive hormones have cyclic variations during the menstrual cycle and modulate brain excitability, and gender may influence patterns of neuronal communication.2 We evaluated gender differences in structure, connectivity, and neuropsychological test scores in the context of the Epilepsy Connectome Project (ECP). Methods: Participants included 60 TLE patients (32 female, mean age 39 years) and 64 controls (35 female, mean age 34 years). Among TLE participants, 2 males and 2 females were left-handed, the rest right-handed. Seizure laterality among males was as follows: 4 Right, 14 Left, 2 Bilateral, 8 Uncertain. Among females, there were 11 Right, 16 Left, 0 Bilateral, 5 Uncertain. Mean age of seizure onset for males was 22.5 years, for females 18 years (p = 0.15). Average seizure duration for males was 18.4 years, for females 21.5 years (p = 0.44). Neuropsychological tests were conducted in TLE and control groups. High resolution structural T1 and T2-weighted and resting state fMRI images were acquired on GE 3T MR750 scanners using Human Connectome Project protocols. Data were processed with FSL and FreeSurfer-based processing pipelines. Results: Bilateral white matter surface area (SA) and estimated total intracranial volume (eTIV) were generally smaller in females than males in both TLE and control groups (p < 0.0002). Female TLE participants (FP) showed decreased SA (p < 0.03) and reduced eTIV (p < 0.022) when compared to female controls. Male TLE participants (MP), however, showed no significant difference in SA or eTIV compared to male controls. MPs showed stronger functional connectivity than FPs in temporal lobe and insular regions (p < 0.0001), and overall stronger contralateral connections among various brain regions. No significant differences were observed between MPs and FPs in several traditional neuropsychological tasks, such as the Rey Auditory Verbal Learning Test (p = 0.36), Boston Naming Test (p = 0.27), Weschler Abbreviated Scale of Intelligence-2 Full Scale IQ (WASI-II FSIQ) (p = 0.32), or Semantic Fluency (p = 0.43). A trend toward significance was noted, however, in the Grooved Pegboard Test - Dominant Hand (p = 0.08), favoring FPs. Among the NIH Toolbox Cognitive Tests, Pattern Comparison Processing Speed also trended toward significance in favor of FPs (p = 0.095), but no differences were noted in Oral Reading Recognition (p = 0.65) or the Penn Computerized Neurocognitive Battery Emotion Recognition and Matrix Analysis Tests (p = 0.27). Conclusions: Distinct gender differences were observed in brain structure and connectivity of male and female TLE participants. A trend towards significance was observed in processing speed and hand motor coordination tasks during neuropsychological testing, favoring female TLE participants. Gender and handedness, as it relates to seizure laterality, may underlie cognitive, behavioral, and motor differences between males and females with TLE. ECP data collection is ongoing. References1. Quigg M, Smithson SD, Fowler KM, Sursal T, Herzog AG. NIH Progesterone Trial Study Group. Laterality and location influence catamenial seizure expression in women with partial epilepsy. Neurology. 2009;73(3):223–227. 2. Gong G, He Y, Evans AC. Brain connectivity: gender makes a difference. Neuroscientist. 2011;17:575–591. Funding: National Institute of General Medical Sciences TEAM 32 R25GM083252-10, National Institute of Neurological Disease and Stroke 1U01NS093650-01