Hippocampal damage abolishes the cortisol response to psychosocial stress in humans

Abstract

The hippocampus (HC) is necessary for learning and memory, but it also plays a role in other behaviors such as those related to stress and anxiety. In support of the latter idea, we show here that bilateral HC damage abolishes the cortisol response to psychosocial stress. We collected salivary cortisol, heart rate, and affective responses to the Trier Social Stress Test (TSST) from 7 participants with bilateral HC lesions, 12 participants with damage outside the HC, and 28 healthy normal comparison participants matched to the HC participants on age and sex. HC participants showed elevated pre-stress cortisol, but no cortisol response to the TSST. Heart rate and affective responses in the HC group were similar to those of the comparison groups. Participants with brain damage outside the HC showed stress responses that were comparable to those of the healthy comparison group. These findings support the idea that the functions of the human HC extend beyond learning and memory, and suggest that the HC is necessary for producing the cortisol response to psychosocial stress.

Figure 1

a: Neuroanatomy of 4 participants with hippocampal lesions and from a representative healthy brain from MR scans. Red outlines indicate hippocampal region-of-interest traced on each representative slice. Note that the right hippocampus in participant 2607 was not visible in this slice. b: Neuroanatomy of 3 participants with hippocampal lesions and one from a representative healthy brain from CT scans.

Figure 2

Cortisol levels across groups. Data show mean (± SEM) of cortisol levels before, 10 min, and 30 min after the Trier Social Stress Test (TSST) in the hippocampal group (HC), the brain damage comparison group (BDC), and normal comparison group (NC).

Figure 3

Cortisol levels from all participants in the HC group. Data show cortisol levels before, 10 min, and 30 min after the Trier Social Stress Test (TSST).

Figure 4

Cortisol levels across testing sessions for 3 hippocampal lesion patients tested twice on the TSST. Data show cortisol levels before, 10 min, and 30 min after the Trier Social Stress Test (TSST) from both testing session for each individual.

Figure 5

Heart rate across groups. Data show mean (± SEM) of heart rate during baseline, Trier Social Stress Test (TSST) preparation, and during the TSST in the hippocampal group (HC), the brain damage comparison group (BDC); and normal comparison group (NC).