Deficient memory acquisition in temporal lobe epilepsy is predicted by hippocampal granule cell loss

Background: The hippocampal formation is essentially involved in the formation of conscious memories for facts and events and neurologic diseases affecting the hippocampus associate with severe memory deficits, i.e., temporal lobe epilepsies. Methods: We studied the degree of declarative memory dysfunction in 24 human subjects with unilateral mesial temporal lobe epilepsy, using the unique possibility to access memory performance of each isolated hippocampus by intracarotid amobarbital anesthesia. Subsequently, hippocampal specimens from the same patients were available for neuropathologic analysis following surgical treatment of intractable seizures. Results: Neuronal cell loss in the dentate gyrus and all hippocampal subfields correlated with memory performance with the exception of CA2. Moreover, multiple regression and partial correlation analyses identified neuronal cell loss within the internal limb of the dentate gyrus, a developmentally distinct subregion of the hippocampal formation known to generate new neurons throughout life, as highly significant predictor for the patient's ability to learn and recall memories. Conclusions: In accordance with animal studies, the dentate gyrus may play a critical role in the neuronal network associated with memory formation.