The brain's orienting response is a biologically primitive, yet critical cognitive function necessary for survival. Though based on a wide network of brain regions, the lateral prefrontal cortex and posterior hippocampus are thought to play essential roles. Indeed, damage to these regions results in abnormalities of the novelty P3 or P3a, an event-related potential (ERP) sign of the orienting response. Like other ubiquitous markers of orienting, such as the galvanic skin response, the P3a habituates when novel events are repeated. Here, we assessed habituation of the P3a in patients who had undergone unilateral anteromedial resection of the medial temporal lobe (AMTL), including the entire hippocampus, for relief of pharmacologically intractable epilepsy. Eight left- and 8 right-AMTL patients and 16 age- and education-matched controls heard frequent standard tones, infrequent targets (requiring reaction times) and equally infrequent, unique novel, environmental sounds. The novel sounds repeated 2 blocks after their first presentation. In controls, novel repetition engendered a reduction in P3a amplitude, but this was not the case in either left- or right-AMTL patients. We conclude that bilaterally intact hippocampi are necessary for the brain to appreciate that a repetition of a novel sound has occurred, perhaps due to disruptions in ipsilateral hippocampal-prefrontal pathways and/or between the left and right hippocampi.
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