title: Differential influence of hippocampal subfields to memory formation: insights from patients with temporal lobe epilepsy.
abstract: To clarify the anatomical organization of human memory remains a major challenge in clinical neuroscience. Experimental data suggest dentate gyrus granule cells play a major role in memory acquisition, i.e. pattern separation and rapid pattern completion, whereas hippocampal CA1 neurons are implicated in place memory and autobiographical memory retrieval. Patients with temporal lobe epilepsy present with a broad spectrum of memory impairment, which can be assessed during clinical examination. Although long seizure histories may contribute to a pathophysiological reorganization of functional connectivity, surgical resection of the epileptic hippocampus offers a unique possibility to anatomically study the differential contribution of hippocampal subfields to compromised learning and memory in humans. Herein, we tested the hypothesis of hippocampal subfield specialization in a series of 100 consecutive patients with temporal lobe epilepsy submitted to epilepsy surgery. Memory profiles were obtained from intracarotid amobarbital testing and non-invasive verbal memory assessment before surgery, and correlated with histopathologically quantified cell loss pattern in hippocampal subfields obtained from the same patients using the new international consensus classification for hippocampal sclerosis proposed by the International League against Epilepsy (HS ILAE). Interestingly, patients with CA1 predominant cell loss (HS ILAE Type 2; n = 13) did not show declarative memory impairment and were indistinguishable from patients without any hippocampal cell loss (n = 19). In contrast, 63 patients with neuronal loss affecting all hippocampal subfields including CA1, CA4 and dentate gyrus (HS ILAE Type 1), or predominant cell loss in CA4 and partially affecting also CA3 and dentate gyrus (HS ILAE Type 3, n = 5) showed significantly reduced declarative memory capacities (intracarotid amobarbital testing: P < 0.001; verbal memory: P < 0.05). Our results suggested an alternative model of how memory processing can be organized amongst hippocampal subfields, and that CA1 pyramidal cells are less critically involved in declarative human memory acquisition compared to dentate gyrus granule cells or CA4/CA3 pyramidal cells.
authors.affiliation: 1 Department of Neuropathology, University Hospital Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Coras
authors.affiliation: 2 Epilepsy Centre, Department of Neurology, University Hospital Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pauli
authors.affiliation: 1 Department of Neuropathology, University Hospital Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany3 Department of Neurology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Jinmei
authors.initials: J
authors.lastname: Li
authors.affiliation: 2 Epilepsy Centre, Department of Neurology, University Hospital Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schwarz
authors.affiliation: 4 Department of Neurosurgery, University Hospital Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Rössler
authors.affiliation: 4 Department of Neurosurgery, University Hospital Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Buchfelder
authors.affiliation: 2 Epilepsy Centre, Department of Neurology, University Hospital Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany.
authors.forename: Hajo
authors.initials: H
authors.lastname: Hamer
authors.affiliation: 2 Epilepsy Centre, Department of Neurology, University Hospital Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Stefan
authors.affiliation: 1 Department of Neuropathology, University Hospital Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany bluemcke@uk-erlangen.de.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Blumcke
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D004833:Epilepsy, Temporal Lobe / Q000150:complications* / Q000473:pathology / Q000601:surgery; D005260:Female; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000209:etiology* / Q000473:pathology*; D008875:Middle Aged; D059906:Neuroimaging; D009474:Neurons / Q000145:classification / Q000378:metabolism / Q000473:pathology; D009483:Neuropsychological Tests; D019635:Neurosurgical Procedures / Q000379:methods; D010751:Phosphopyruvate Hydratase; D012598:Sclerosis / Q000209:etiology / Q000473:pathology; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014706:Verbal Learning; D055815:Young Adult
chemical_list: D010751:Phosphopyruvate Hydratase
keywords: brain; dentate gyrus; epilepsy; hippocampus; neuropathology; seizure