Neural substrates of increased memory sensitivity for negative stimuli in major depression

Abstract

Background: Although memory biases for negatively valenced stimuli have been reliably associated with depression and have been postulated to play a critical role in the maintenance of this disorder, the neural bases of these biases have received little attention. In this study, we tested a model of heightened memory sensitivity for negative information in depression in which neural mechanisms that normally facilitate memory for affective material are over-recruited during encoding of negative material in depression.

Methods: We used functional magnetic resonance imaging to examine amygdala activity and functional connectivity with the hippocampus and caudate-putamen during successful encoding--as assessed by a recognition memory probe 1 week after scanning--of negative, neutral, and positive pictures by 14 depressed and 12 nondepressed individuals.

Results: Depressed individuals demonstrated greater memory sensitivity than nondepressed participants to negative but not to neutral or positive stimuli. The right amygdala was more active and showed greater functional connectivity with the hippocampus and caudate-putamen in depressed than in control participants during encoding of subsequently remembered negative but not neutral or positive stimuli. The degree of memory-related right amygdala responsivity in the depressed participants was significantly correlated with depressive severity.

Conclusions: These findings support the formulation that, in remembering negative information better than nondepressed persons, depressed individuals over-recruit a neural network involved more generally in enhancing memory for affective stimuli and that the degree to which they over-recruit this system is related to the severity of clinical symptomatology.

Figures

Figure 1

Schematic of individual fMRI memory encoding trials.

Figure 2

Mean intensity ratings with standard error bars for positive (POS), neutral (NEU) and negative (NEG) stimuli in depressed (MDD) and control (CTL) groups. Mean values connected by bars are significantly different.

Figure 3

Mean normalized memory sensitivity scores across levels of group and valence factors.

Figure 4

Mean contrast coefficient values from remembered (REM) versus forgotten (FOR) contrast across valence and group variables in peak left amygdala (A; −19, −4, −12) and right amygdala (B; 17, −5, −12) voxels, and REM versus fixation and FOR versus fixation for negative stimuli in each group (C).

Figure 5

Mean contrast coefficients from analysis of psychophysical interaction between right amygdala and right hippocampus for each level of group and valence. Values shown are from peak hippocampal voxel (22, −11, −12).

Figure 6

Mean contrast coefficients from analysis of psychophysical interaction between right amygdala and right caudate-putamen for each level of group and valence. Values shown are from peak caudate-putamen voxel (17, 5, 6).

Figure 7

Scatter plot showing positive correlation between BDI-II score in depressed participants and memory-related right amygdala responsivity to negative stimuli.