Fluoxetine restores spatial learning but not accelerated forgetting in mesial temporal lobe epilepsy.

Learning and memory dysfunction is the most common neuropsychological effect of mesial temporal lobe epilepsy, and because the underlying neurobiology is poorly understood, there are no pharmacological strategies to help restore memory function in these patients. We have demonstrated impairments in the acquisition of an allocentric spatial task, in patients with unilateral hippocampal sclerosis. We also show that patients have accelerated forgetting of the learned spatial task and that this is associated with damage to the non-dominant hippocampal formation. We go on to show a very similar pattern of chronic allocentric learning and accelerated forgetting in a status epilepticus model of mesial temporal lobe epilepsy in rats, which is associated with reduced and abnormal hippocampal neurogenesis. Finally, we show that reversal of the neurogenic deficit using fluoxetine is associated with reversal of the learning deficit but not the accelerated forgetting, pointing to a possible dissociation in the underlying mechanisms, as well as a potential therapeutic strategy for improving hippocampal-dependent learning in patients with mesial temporal lobe epilepsy.

Selective temporal resections and spatial memory impairment: cue dependent lateralization effects.

Patients who had undergone a unilateral trans-sylvian selective amygdalohippocampectomy as treatment for chronic intractable epilepsy were tested in a virtual Morris Water Maze (MWM) task where they were required to locate a hidden platform as a measure of spatial learning. These individuals' performance on spatial tasks was compared to age-matched healthy controls and drug-matched healthy controls. Training occurred in two different maze environments, one with conventional cues such as windows and doors, and another with abstract cues, such as colours and patterns. Participants searched for a hidden platform in the virtual pool, guided by either the conventional or abstract cues. There was a significant impairment in the surgery group compared to the control groups in all environments, however in the abstract environment only the patients with right-sided lesions were significantly worse than the controls. There was no difference between the groups on a control egocentric navigation task. These results suggest that people who have had right-sided surgery are impaired in spatial tasks, and that the level of impairment on the spatial task may be dependent on the characteristics of the cues such as how easily the cues are verbalised. These results support the notion of the functional lateralization of specific elements of spatial memory and functional lateralization, and may shed light on previous inconsistencies in this area of research.