An emotion-induced retrograde amnesia in humans is amygdala- and beta-adrenergic-dependent

Abstract

The influence of emotion on human memory is associated with two contradictory effects in the form of either emotion-induced enhancements or decrements in memory. In a series of experiments involving single word presentation, we show that enhanced memory for emotional words is strongly coupled to decrements in memory for items preceding the emotional stimulus, an effect that is more pronounced in women. These memory effects would appear to depend on a common neurobiological substrate, in that enhancements and decrements are reversed by propranolol, a beta-adrenergic antagonist, and abolished by selective bilateral amygdala damage. Thus, our findings suggest that amygdala-dependent beta-adrenergic modulation of episodic encoding has costs as well as benefits.

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, oddball, oddball + 1) 2 × 2 × 3 ANOVA revealed a significant main effect of position (F_{1.3, 11.8} = 12.7 P < 0.005) and a significant oddball × position interaction (F_{1.9, 16.9} = 3.8 P < 0.05). Mean recall of control nouns (%; SE) after deep encoding was 58.8 (2.8) and after shallow encoding was 48.1 (3.6). E, emotional oddball; P, perceptual oddball; E-1, E + 1, P-1, P + 1, nouns presented before and after emotional and perceptual oddballs.

Fig. 2.

Emotion-induced memory impairment is β-adrenergic-dependent. (a) Recall performance relative to control nouns (%) is plotted after shallow encoding for placebo and propranolol groups in Exp. 2. A group (placebo, drug) × oddball type (emotional, perceptual) × position (oddball-1, oddball, oddball + 1) 2 × 2 × 3 ANOVA revealed a significant main effect of position (F_{1.8, 19.5} = 17.6 P < 0.001), a significant group × position interaction (F_{1.7, 18.6} = 34.5 P < 0.001), and a significant group × oddball type × position interaction (F_{1.5, 16.0} = 30.4 P < 0.001). A group × position 2 × 3 ANOVA restricted to the emotional factor revealed a significant main effect of group (F_1,11 = 9.3 P < 0.05) and position (F_{1.6, 18.1} = 5.2 P < 0.05) and a significant group × position interaction (F_{1.3, 14.6} = 42.4 P < 0.001). Post hoc t tests demonstrated that E-2 nouns are recalled significantly worse than control nouns in the placebo group (P < 0.001 one-tailed one-sample t test) and worse at trend level for placebo relative to drug groups (P = 0.08 one-tailed two-sample t test). The decrement for E-1 nouns was significantly greater than for E-2 nouns in the placebo group (P < 0.05 one-tailed paired t test). Memory for control nouns was not significantly different between groups; mean recall (%; SE) for placebo: 45.2 (1.9); drug: 43.5 (2.4). (b) Reciprocal codependency of memory for E and E-1 nouns demonstrated by contingency tables and plots of the percentage (±SE) of remembered (R) and forgotten (F) E nouns, split according to memory for the corresponding E-1 nouns. Memory decrement for E-1 and memory enhancement for E nouns show a strong item-by-item codependency in the placebo group (χ² = 4.7; P < 0.05). Propranolol modulated this codependency, evident as a significant difference between placebo (expected) and drug (observed) groups (χ² = 93.1; P < 0.001). (c) Reciprocal codependency of memory for E and E-2 nouns as for b except that E nouns are now split according to memory for the corresponding E-2 nouns. The item-by-item codependency for memory decrement for E-2 and memory enhancement for E nouns in the placebo group is abolished by propranolol (χ² = 32.2; P < 0.001). (d) Mean blood pressure (BP; mmHg), at the time of drug/placebo administration (0) and at the start of the experiment (+90 min), and drug serum concentrations ([propranolol]; μg/liter). Propranolol produced the expected decrease in BP (P < 0.001 in a two-tailed paired t test).

Fig. 3.

Emotion-induced memory impairment is amygdala-dependent. (a) Recall performance relative to control nouns (%) is plotted for the German control group and patient A.M. in Exp. 3. (Right) Coronal and transverse T₁ MRI images demonstrating patient A.M.'s bilateral amygdala lesion are shown. A group (patient, control) × oddball type (emotional, perceptual) × position (oddball-1, oddball, oddball + 1) 2 × 2 × 3 ANOVA (assumes variance in patient population is equal to that in normals) revealed a significant group × oddball interaction (F_{1.0, 1.0} = 196.6 P < 0.05) and a trend for the group × oddball × position interaction (F_{1.0, 1.0} = 60.0 P = 0.08). A group × position 2 × 3 ANOVA restricted to the emotional factor revealed a significant group × position interaction (F_{1.0, 1.0} = 256.4 P < 0.05). Post hoc independent t tests revealed a significant difference between patient and controls only for recall of E-1 (P < 0.01 two-tailed) and E (P < 0.005 two-tailed) nouns. Recall of control nouns was not significantly different between patient and controls; mean recall of control nouns (%; SE) for patient A.M. 44.7; controls 47.6 (2.1). (b) Reciprocal codependency of memory for E nouns and E-1 nouns for controls and patient A.M., as for Fig. 2b. The control group demonstrates the same reciprocal effects as the placebo group in Exp. 2 (Fig. 2b). The presence of bilateral amygdala lesions abolishes this codependency, evident as a significant difference between controls (expected) and patient (observed) (χ² = 113.8; P < 0.001). (c) The reciprocal codependency of memory for E nouns and E-2 nouns present for controls is abolished in patient A.M. (χ² = 74.6; P < 0.001).

Fig. 4.

Women display greater emotion-induced memory impairment than men. (a) Recall performance relative to control nouns (%) is plotted for male and female subjects collapsing across the placebo group in Exp. 2 and the control group in Exp. 3. A gender (male, female) × oddball type (emotional, perceptual) × position (oddball-1, oddball, oddball + 1) 2 × 2 × 3 ANOVA across these two groups from Exps. 2 and 3 revealed a significant main effect of position (F_{1.9, 21.3} = 72.8 P < 0.001), a significant gender × oddball type interaction (F_{1.0, 11.0} = 9.1 P < 0.05), a significant oddball type × position interaction (F_{1.4, 15.5} = 31.6 P < 0.001), and a significant gender × oddball type × position interaction (F_{1.4, 15.6} = 4.7 P < 0.05). A gender × position 2 × 3 ANOVA restricted to the emotional factor revealed a significant main effect of gender (F_1,11 = 6.1 P < 0.05) and position (F_{1.4, 15.9} = 64.7 P < 0.001) and a significant gender × position interaction (F_{1.6, 18.1} = 4.4 P < 0.05). Post hoc independent t tests revealed a significant gender difference only for the E-1 nouns (P < 0.005 two tailed). (b and c) Reciprocal codependency of memory for E nouns and E-1 nouns (b) and E and E-2 nouns (c) for males and females, as for Fig. 2b. A significant female vs. male difference for codependency between E/E-1 memory (χ² = 6.1; P < 0.05) and E/E-2 memory (χ² = 23.0; P < 0.001) was observed, with women showing a greater remembered E and forgotten E-1 (RE FE-1) and RE FE-2 effect.