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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.

PurposeFunctional magnetic resonance imaging (fMRI) has previously demonstrated functional reorganisation of memory representations in people with Temporal Lobe Epilepsy (TLE). Less is known about the changes in functional connectivity within the memory network.MethodsWe studied 77 patients with unilateral TLE (37 left) and 27 controls. All participants performed a memory encoding fMRI paradigm of faces and words. Psychophysiological Interaction (PPI) analysis was conducted to examine brain regions that were time-correlated with activations in the left and right hippocampi.ResultsDuring word encoding, left TLE patients showed reduced connectivity from the left hippocampus to the prefrontal cortex, compared to controls. During face encoding, right TLE patients showed reduced connectivity from the right hippocampus to the ipsilateral lateral temporal lobe and bilateral fusiform gyri. However, left and right TLE patients showed greater connectivity to posterior hippocampi bilaterally during word and face encoding.ConclusionTLE is increasingly recognised as a network disease and correspondingly we demonstrate widespread memory network reorganisation in people with epilepsy. The reorganisation of eloquent functions has important implications in the planning of epilepsy surgery and a network approach may be helpful in the prediction of memory outcome after epilepsy surgery.