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31 Disorganization of language and working memory networks in frontal versus temporal lobe epilepsy
  1. Lorenzo Caciagli1,2,3,
  2. Casey Paquola4,
  3. Xiaosong He3,
  4. Christian Vollmar1,2,5,
  5. Maria Centeno1,2,6,
  6. Britta Wandschneider1,2,
  7. Urs Braun3,7,
  8. Karin Trimmel1,2,8,
  9. Sjoerd B Vos1,2,9,10,
  10. Meneka K Sidhu1,2,
  11. Pamela J Thompson1,2,
  12. Sallie Baxendale1,2,
  13. Gavin P Winston1,2,11,
  14. John S Duncan1,2,
  15. Dani S Bassett3,12,13,14,15,16,
  16. Matthias J Koepp2,3,
  17. Boris C Bernhardt4
  1. *Equal contribution as senior author
  2. 1Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  3. 2Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK
  4. 3MRI Unit, Epilepsy Society, Chalfont St Peter, Buckinghamshire, UK
  5. 4Multimodal Imaging and Connectome Analysis Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute, Quebec,Canada
  6. 5Department of Neurology, Ludwig-Maximilians-Universität, Marchioninistrasse 15, Munich, Germany
  7. 6Epilepsy Unit, Hospital Clínic de Barcelona,Barcelona, Spain
  8. 7Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim
  9. 8Department of Neurology, Medical University of Vienna, Vienna, Austria
  10. 9Centre for Medical Image Computing, University College London, London, UK
  11. 10Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology, University College London, London, UK
  12. 11Department of Medicine, Division of Neurology, Queen's University, Kingston, Ontario, Canada
  13. 12Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, Pennsylvania USA
  14. 13Department of Electrical and Systems Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  15. 14Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  16. 15Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  17. 16Santa Fe Institute, Santa Fe, New Mexico, USA

Abstract

Objectives/Aims Cognitive 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.

Methods We 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.

Results We 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.

Conclusions Our 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.

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