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.

Decreased neuron loss and memory dysfunction in pilocarpine-treated rats pre-exposed to hypoxia

“…Studies with TLE patients have shown that neuron loss in specific hippocampal subfields can promote differential memory loss (Coras et al, 2014;Rodrigues et al, 2015). Besides, SRS might cause progressive cognitive decline (Sutula et al, 1995).…”

Short‐ and long‐term surgical outcomes of temporal lobe epilepsy associated with hippocampal sclerosis: Relationships with neuropathology

“…26 (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) 36 (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41) 85 (91) 62 (67) Type 1 70 (74) 33 (47) 38 (54) 27 (39) 13 (19) 6 (3-10) (25) 7 (30) 11 (48) 5 (22) 7 ( 42 (43) 58 (60) 22 (23) 19 (20) 8 (4-13)…”

“…26 (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37) 38 (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43) 61 (85) 49 (68) Type 2 24 (25) 8 (33) 16 (67) 7 (29) 6 (25) 7 ( 44-45% of the selected population, but only 11% were affected by DP. The distribution of HS types (74% type 1, 25% type 2, and only one patient with type 3) is slightly different from that reported in some studies, 12,14,15,22 but similar to the recent findings of Savitr Sastri et al, 25 and confirms that type 1 is the most frequent, whereas CA4-predominant type 3 is rare, accounting for no more than approximately 4% of the patients in some cohorts, 4,14,15 and none at all in others.…”

Novel genetic loci associated with hippocampal volume

“…Further, the cytoarchitectural subdivisions (or ‘subfields') of the hippocampus are associated with distinct functions. For example, the dentate gyrus (DG) and sectors 3 and 4 of the cornu ammonis (CA) are involved in declarative memory acquisition12, the subiculum and CA1 play a role in disambiguation during working memory processes13, and the CA2 is implicated in animal models of episodic time encoding14 and social memory15. The anterior hippocampus, which includes the fimbria, CA subregions and hippocampal -amygdaloid transition area (HATA), may be involved in the mediation of cognitive processes including imagination, recall and visual perception16 and anxiety-related behaviours17.…”