Downloaded from learnmem.cshlp.org on October 6, 2021 - Published by Cold Spring Harbor Laboratory Press Impaired Declarative Memory for Emotional Material Following Bilateral Amygdala Damage in Humans Ralph Adolphs, 1'4 Larry Cahill, 2 Rina Schul, 1 and Ralf Babinsky 3 1Department of Neurology Division of Cognitive Neur0science University of I0wa College of Medicine I0wa City, I0wa 52242 2Center for the Neur0bi010gy of Learning and Memory University of Calif0mia Irvine, California 92717-3800 3Physi010gical Psychology University of Bielefeld, D-33501 Bielefeld, Germany Abstract salient information can often be enhanced by emo- tional arousal (Loftus 1979; Winograd and Neisser Everyday experience suggests that 1992). Recent laboratory studies have likewise highly emotional events are often the most shown that increased emotional arousal can facili- memorable, an observation supported by tate the encoding of material into long-term de- psychological and pharmacological studies clarative memory in both normal (Bradley et al. in humans. Although studies in animals 1992) and brain-damaged subjects (Hamann et al. have shown that nondeclarative emotional 1997a). Our aim was to test a hypothesis regarding memory (behaviors associated with the neuroanatomical structures by which emotion emotional situations) may be impaired by influences memory, using the same, standardized lesions of the amygdala, little is known stimuli that have been used in several other studies about the neural underpinnings of (Heuer and Reisberg 1990; Burke et al. 1992). emotional memory in humans, especially in Evidence from both humans and animals indi- regard to declarative memory (memory for cates that the amygdala may be important in the facts that can be assessed verbally). We acquisition of conditioned behavioral and auto- investigated the declarative memory of two nomic responses to stimuli that have been paired rare patients with selective bilateral previously with an intrinsically aversive event amygdala damage. Both subjects showed (LeDoux et al. 1990; Davis 1992; Bechara et al. impairments in long-tetan declarative 1995; LaBar et al. 1995), although the amygdala memory for emotionally arousing material. does not appear to be essential for the acquisition The data support the hypothesis that the of all such behaviors (e.g., Tranel and Damasio human amygdala normally enhances 1993). The clearest evidence for the amygdala's acquisition of declarative knowledge involvement in modulating memory comes from regarding emotionally arousing stimuli. studies in rats, which have shown that memory is modulated by multiple neurotransmitter systems acting within the amygdala (McGaugh 1989; Cahill Introduction and McGaugh 1996; McGaugh et al. 1996). For in- stance, direct post-training injections into the Naturalistic studies of memory for emotional amygdala of a variety of drugs that modulate GAB- events have suggested that memory for relevant, Aergic, noradrenergic, or opiate-mediated neuro- transmission influence long-term memory for in- 4Corresponding author. hibitory avoidance training (GaUagher et al. 1981; LEARNING & MEMORY 4:291-300 © 1997 by Cold Spring Harbor Laboratory Press ISSN1072-0502/97 $5.00 L E A R N I N G & M E M 0 R Y 291 Downloaded from learnmem.cshlp.org on October 6, 2021 - Published by Cold Spring Harbor Laboratory Press Adolphs et aL Brioni et al. 1989). Recent data suggest that the material in the story better than information about amygdala influences memory by modulating en- more neutral material in the story, as has been coding and consolidation by other brain structures, found in prior studies (Heuer and Reisberg 1990; such as the hippocampus and basal ganglia (Mc- Burke et al. 1992; Cahill and McGaugh 1995), but Gaugh 1989; Packard et al. 1994; M.G. Packard and that subjects with amygdala lesions would fail to L.A. Teather, unpubl.). show this effect. Thus, we expected that subjects A human subject who had sustained selective with amygdala damage would remember the neu- bilateral amygdala damage early in life showed a tral and the emotionally arousing material in the specific inability to judge the intensity of fear in story about equally well. facial expressions (Adolphs et al. 1994, 1995) but A previous study (Cahill et al. 1995) reported no comparable impairment was found in two sub- some data from the same experiment with one of jects who had sustained amygdala damage as adults the patients (B.P.) that we report here and showed (Hamann et al. 1996), suggesting the hypothesis that B.P. had impaired memory for the emotional that the amygdala may be most important in the phase of a story; however, data for individual acquisition (e.g., during development) but not in stimuli were not presented in that study. Both the the retrieval of declarative knowledge about emo- data and the analyses in the present paper are new tions (Adolphs et al. 1996; Hamann et al. 1996; and provide a much more detailed description of Phelps and Anderson 1997; A. Anderson, K.S. La- the patient's impairment. These data, together Bar, and E.A. Phelps, unpubl.). A PET study of nor- with entirely new findings from a second subject mal subjects showed that activation of the right with selective bilateral amygdala damage, provide amygdala at the time of encoding was highly cor- strong evidence that the human amygdala plays a related with how well emotionally arousing infor- pivotal role in influencing long-term declarative mation was subsequently recalled (Cahill et al. memory for emotional material. 1996). Similarly, recent case studies of patients with bilateral amygdala damage indicated that memory for emotional stimuli was disproportion- ately impaired (Babinsky et al. 1993; Cahill et al. Experiment 1 1995). A patient with Urbach-Wiethe disease (the sibling of subject B.P. reported in this paper) was Materials and Methods impaired on a word-stem completion task for emo- tional but not for neutral words and likewise SUBJECTS showed impaired recognition memory for emo- tional but not for neutral pictures. Although this We tested subject SM046, who has bilateral evidence from studies in humans remains quite damage to the amygdala, six brain-damaged con- limited, it suggests that the amygdala may play a trois without amygdala damage, and seven normal modulatory role in the acquisition of declarative control subjects who overlapped with SM046 in memories concerning emotionally arousing mate- regard to their education, age, and IQ. rial. SM046 is a 32-year-old woman with a high- On the basis of the above findings, we hypoth- school education who suffers from a rare genetic esized that the human amygdala would be required disease, Urbach-Wiethe disease, which has led to to facilitate encoding of declarative knowledge re- bilateral destruction of the amygdala. Her brain garding emotionally arousing stimuli but that it is damage is restricted to the amygdala, with the ex- not required for encoding knowledge of emotion- ception of minimal damage to left anterior entorhi- ally neutral stimuli. We tested this hypothesis in nal cortex (Fig.lA). Her neuroanatomy has been two rare subjects with selective bilateral amygdala described in detail (Tranel and Hyman 1990; Nahm damage. Subjects were presented with a short au- et al. 1993; Adolphs et al. 1994, 1995). SM046's IQ, diovisual story that contained both neutral and visuoperception, and language abilities are all in emotionally arousing material, and their declarative the normal range (Tranel and Hyman 1990; Ado- memory was assessed at a later time using a stan- lphs et al. 1995). dardized multiple-choice questionnaire that asked SM046 and the six brain-damaged controls had several questions about the story. all been selected from the Patient Registry of the We expected that normal subjects would re- Division of Behavioral Neurology and Cognitive member information about emotionally arousing Neuroscience at the University of Iowa and had L E A R N / N G & M E M O R Y 292 Downloaded from learnmem.cshlp.org on October 6, 2021 - Published by Cold Spring Harbor Laboratory Press EMOTIONAL MEMORY FOLLOWING AMYGDALA DAMAGE The seven normal controls included individu- als whose age, education, and IQ were matched to that of SM046 (age: SM046 = 32, control mean = 36 --- 8.5; IQ: SM046 = 86, control mean = 98 --. 10; education: SM046 = 12 years, control mean = 12 years). EXPERIMENTAL TASK To study the modulation of declarative memory by emotion, we used a task that has been administered to normal human subjects in several studies, with reliable findings (Heuer and Reisberg 1990; Burke et al. 1992; Reisberg and Heuer 1992; Cahill and McGaugh 1995). The task consists of a set of 12 slides that are shown in sequence, accom- panied by a narrative. Together, the slides and nar- rative tell a story about a boy and his mother who visit the father at the hospital. The story can be divided into three phases: phase 1 (the first four slides) consists of material that is normally judged not to be very emotional (the boy and mother are on their way to the hospital), phase 2 (the middle four slides) contains emotionally arousing material (scenes of surgery at the hospital), and phase 3 (the last four slides) consists again of relatively nonemo- tional material (the mother leaves the hospital to Figure 1 : Imagesof the brains of SM046 and B.P. at the make a phone call and goes home). The verbatim level of the amygdala. (A) Tl-weighted magnetic reso- narrative that accompanied the slides is given in nance (MR) image of SMO46's brain showing bilateral the Appendix. amygdala lesions (arrows, dark regions on the MR scan). Subjects were told to pay close attention to the (B) CT scan of B.P.'s brain showing bilateral amygdala lesions (arrows, white radio-opaque regions on CT stimuli, because they would subsequently be asked scan). The amygdala pathology in both SM046 and B.P. about their emotional reaction; subjects were not is due to calcification of tissue.