From The Cover: An emotion-induced retrograde amnesia in humans is amygdala- and -adrenergic-dependent

Substantial evidence indicates that enhanced memory for emotional experience engages a β-adrenergic system (1). β-Adrenergic blockade with the β1β2-antatgonist propranolol selectively impairs long-term human episodic memory for emotionally arousing material without affecting memory for a neutral story (2). This modulation of emotional memory by propranolol is centrally mediated, because peripheral β-adrenergic blockade has no such effect on emotional memory function (3). Human amygdala lesions also produce emotional memory impairment (4, 5), suggesting that this structure may represent a critical locus for propranolol's influence on emotional memory. Although emotionality is strongly associated with enhancements in memory, there is evidence for emotion-induced memory decrements (6, 7). Human behavioral studies demonstrate enhanced memory for central details of an emotional event and memory suppression for peripheral details (8, 9). Ecological studies show that details of an event are less likely to be remembered if followed by an emotional event (10). In experimental contexts a weak, although unreliable, effect on words presented in close proximity to potentially emotional items is reported (11). By contrast to the extensive literature on emotional enhancements in memory, nothing is known regarding the neurobiological processes accounting for emotion-induced impairments in memory. In a series of related experiments, we present psychological (Exp. 1), psychopharmacological (Exp. 2) and neuropsychological (Exp. 3) data that characterize the psychological and neurobiological properties of emotion-induced forgetting. Our first aim was to establish a behavioral index of emotion-evoked memory enhancement and impairment. In an initial behavioral memory experiment (Exp. 1), nouns were presented serially, every 3 s, in semantically related lists, and recall was tested after each list presentation. Each list, in this and subsequent experiments, contained two “oddball” nouns: an emotionally aversive noun (E noun) and a perceptual oddball noun (P noun), presented in a novel font (Fig. 1a). In line with previous observations (1, 6), memory for emotional items is enhanced relative to control nouns. Critically, items preceding E nouns (E-1 nouns) are recalled less well than controls (see Results). Fig. 1. (a) Examples of presented nouns. (b) Recall performance (±SE) relative to control nouns (%) for deep and shallow encoding in Exp. 1. An encoding task (shallow, deep) × oddball type (emotional, perceptual) × position (oddball-1, . A previously reported blockade of enhanced memory for emotional stimuli by propranolol (2) indicates central noradrenaline/norepinephrine (NE) release in response to emotional stimuli. In animals, posttraining amygdala stimulation, electrically or with adrenergic agonists, typically leads to enhanced memory for previously learned tasks but can evoke memory impairment (12, 13). For example, retrograde amnesia in rodents for visual discrimination learning is produced by postlearning stimulation of the amygdala (14), an effect attenuated by pretreatment with propranolol. Hence amygdala stimulation-evoked adrenergic release, occurring after learning, may disrupt ongoing consolidation (14). We reasoned that NE release evoked by E nouns may affect consolidation of E-1 encoding. On this basis, we conducted further experiments to examine whether memory impairment for E-1 items, like the memory enhancement for E items, would be attenuated by propranolol. To test this prediction, we conducted a psychopharmacological study (Exp. 2), in which subjects received either propranolol or placebo in a double-blind experimental design. As in Exp. 1, nouns were presented serially in semantically related lists and recall tested after each list presentation. Both enhanced memory for E nouns, and memory impairment for E-1 items was abolished by propranolol (see Results). The adrenergic release that enhances memory for emotional events is thought to be mediated by the amygdala (2, 4, 5), because this memory enhancement is abolished by both β-adrenergic blockade (2) and amygdala lesions (4, 5). Our observation that β-adrenergic blockade abolishes the emotion-induced impairment of memory for E-1 nouns suggests that the same NE release that enhances memory for the E noun also impairs consolidation of E-1 items. Given that this NE release is thought to be amygdala-dependent (1), we hypothesized that human amygdala lesions would abolish emotion-induced E-1 memory impairment. We therefore tested a patient with selective bilateral amygdala damage (Exp. 3) on the paradigm used in Exp. 2.