31 Disorganization of language and working memory networks in frontal versus temporal lobe epilepsy

Objectives/AimsCognitive impairment is a common comorbidity of epilepsy, and can be more burdensome than seizures themselves. Temporal and frontal lobe epilepsy (TLE, FLE) are accompanied by multi-domain cognitive impairment. While the underlying neural substrates have been extensively investigated in TLE, functional imaging studies in FLE are scarce. Here, we aimed to: (i) investigate systems-level neural processes accounting for cognitive dysfunction in FLE; (ii) directly compare FLE and TLE patients, establishing commonalities and differences; and (iii) decode the potential influence of clinical characteristics on cognitive network architecture.MethodsWe capitalized on a large, single-centre sample of 172 adult participants (56 with FLE, 64 with TLE, 52 with controls) who were investigated via: (i) an extensive neuropsychological test battery that included attention, psychomotor speed, language, working memory, executive function, and episodic memory tests; and (ii) four functional MRI tasks probing expressive language (verbal fluency, verb generation) and working memory (verbal and visuo-spatial). Patient groups were comparable in age of epilepsy onset, disease duration, and antiseizure medication load. We mapped task-related brain activation and deactivation using a novel multiscale approach, and tracked reorganization in FLE and TLE. We complemented voxel-based maps with profiling of task effects across established motifs of functional brain organization: (i) canonical resting-state functional networks, and (ii) the principal functional connectivity gradient, that encodes a continuous transition from lower-level (sensory) to higher-order (transmodal) brain areas.ResultsWe find that cognitive impairment in FLE is accompanied by broadly reduced activation across frontoparietal attentional and executive networks, and reduced default-mode network deactivation, indicating large-scale disorganization of task-related recruitment, particularly during working memory. Patterns of dysfunction in FLE and TLE are broadly similar, but some traits are syndrome-specific: impaired task-related deactivation of the default-mode network is more prominent in FLE, while impaired recruitment of posterior language areas is more marked in TLE. More severe epilepsy, as tracked by age at onset, epilepsy duration, seizure frequency, time since last seizure, and propensity for focal-to-bilateral tonic-clonic seizures, relates to more marked cognitive network disorganization both in FLE and TLE.ConclusionsOur study elucidates neural processes underlying cognitive impairment in the most common focal epilepsies, identifies frontoparietal executive alterations as a shared biological signature, irrespective of seizure focus localization, and shows that temporal lobe language alterations are TLE-specific. The highlighted systems-level behaviour may be amenable to future remediation strategies, including neurostimulation.