Individualized Functional and Structural Language Lateralities in Temporal Lobe Epilepsy and Their Impact on Memory

The basis and impact of functional asymmetries in the brain, particularly language lateralization, are not fully understood, and the relationship between functional and structural asymmetries remains largely untested. This study investigated the degree to which asymmetries in hemispheric language laterality are concordant with asymmetries in gray matter (GM) structure and whether the hemispheric organization of memory is influenced by functional language asymmetries. Structural and functional MR data was acquired from 261 individuals, including those with unilateral temporal lobe epilepsy (LTLE = 96, RTLE = 69) and matched with healthy participants (HPs = 96). Functional language laterality indices (LIs) were calculated using two methods: (1) standard LIs from the frontal, temporal, and parietal lobes and (2) targeted LIs (T-LIs) from individually defined activation peaks. Structural LIs (ST-LIs) were derived from the GM volumes underlying these functional LIs. We observed significant shifts in language laterality in LTLE compared to HPs in 8 out of 12 brain regions. Strong correlations were observed between functional LIs and their structural counterparts. Discriminant analyses demonstrated that targeted LIs and ST-LIs more effectively distinguished TLE patients from HPs, with ST-LIs being the most powerful discriminator. Partial least squares analyses showed verbal and visual memory have a direct dependence on targeted LIs in HPs and LTLE, with this effect more pronounced in HPs. In RTLE, verbal memory showed a similar dependency. These findings underscored the importance of individualized, region-specific measures for understanding language laterality, its relation to structural underpinnings, and its impact on the organization of other cognitive functions such as memory.