Effects of acute psychosocial stress on working memory related brain activity in men

Abstract

Acute psychosocial stress in humans triggers the release of glucocorticoids (GCs) and influences performance in declarative and working memory (WM) tasks. These memory systems rely on the hippocampus and prefrontal cortex (PFC), where GC-binding receptors are present. Previous studies revealed contradictory results regarding effects of acute stress on WM-related brain activity. We combined functional magnetic resonance imaging with a standardized psychosocial stress protocol to investigate the effects of acute mental stress on brain activity during encoding, maintenance, and retrieval of WM. Participants (41 healthy young men) underwent either a stress or a control procedure before performing a WM task. Stress increased salivary cortisol levels and tended to increase WM accuracy. Neurally, stress-induced increases in cortical activity were evident in PFC and posterior parietal cortex (PPC) during WM maintenance. Furthermore, hippocampal activity was modulated by stress during encoding and retrieval with increases in the right anterior hippocampus during WM encoding and decreases in the left posterior hippocampus during retrieval. Our study demonstrates that stress increases activity in PFC and PPC specifically during maintenance of items in WM, whereas effects on hippocampal activity are restricted to encoding and retrieval. The finding that psychosocial stress can increase and decrease activity in two different hippocampal areas may be relevant for understanding the often-reported phase-dependent opposing behavioral effects of stress on long-term memory.

Figure 1

Working memory task. Each trial began with an instruction to either remember the faces and ignore the scenes or remember the scenes and ignore the faces or passively view both. This was followed by the encoding phase, where four stimuli (two faces, two scenes) were presented in a randomized order. After a variable maintenance interval, a probe stimulus was presented in the two active conditions and participants had to determine via button press whether it matched one of the previously shown sample stimuli, which was the case in 50% of the trials. In passive viewing trials, an arrow heading left or right was presented superimposed on a checkerboard with a decreasing luminance contrast gradient in the direction of the arrow, and participants had to press the button corresponding to the direction of the arrow. A variable baseline period followed before the onset of the next trial. The order of different trials was randomized.

Figure 2

Salivary cortisol data of the two groups of participants at three different times of measurement. Salivary levels of free cortisol were significantly increased in the stress group at t1 (after the TSST) and t2 (after the WM task) as compared to t0 (prior to stress) and to t1 and t2 in the control group. **p < 0.01 (paired and unpaired t‐tests, Bonferroni‐corrected).

Figure 3

Prefrontal and parietal activity differences between the stress and the control group during maintenance of memory. Middle row: 3D transparent “glass brain” renderings showing (in red) the sites of group differences in cortical activity within PFC and PPC (significance threshold: p ≤ 0.05, familywise error corrected for multiple comparisons). Shaded in yellow are the regions of interest (ROI) comprising prefrontal (BAs 9, 10, 11, 44, 45, 46, and 47) and posterior parietal cortical areas (BAs 7 and 40). Upper and lower row: Estimated betas of the peak voxels as a function of condition (active/passive) and group (stress/control). Error bars represent ±1 standard error. In all four areas, stressed participants show stronger activity during active as compared to passive trials, while this activity pattern is reversed in control participants.

Figure 4

Hippocampal activity differences between the stress and the control group during memory encoding (left side) and memory retrieval (right side): (a) Illustration of memory phase entering into analysis; (b) sagittal slices of an anatomical mean image of all participants depicting sites of hippocampal activity differences (significance threshold: p ≤ 0.05, familywise error corrected for multiple comparisons). Left side: bigger difference between the activity during the encoding phases of active and passive trials in the stress as compared to the control group in right anterior hippocampus (x = 33, y = −9, z = −21; Z = 3.58; 2 voxels). Right side: bigger difference between the activity during retrieval phases of active trials and baseline in the control as compared to the stress group in left posterior hippocampus (x = −21, y = −33, z = −9; Z = 3.61; 5 voxels). (c) Estimated betas of the peak voxels of the clusters shown in (b) as a function of condition (active/passive) and group (stress/control). Error bars represent ±1 standard error. During encoding, stress leads to a numeric increase in anterior hippocampal activity in active trials and a significant decrease in passive trials. During retrieval, stress leads to a significant decrease of posterior hippocampal activity during active trials. *p < 0.05, **p < 0.01 (unpaired t‐tests, Bonferroni‐corrected).