Glucocorticoids, Noradrenergic Arousal, and the Control of Memory Retrieval

Abstract

Glucocorticoids and noradrenaline can enhance memory consolidation but impair memory retrieval. Beyond their effects on quantitative memory performance, these major stress mediators bias the engagement of multiple memory systems toward “habitual” control during learning. However, if and how glucocorticoids and noradrenaline may also affect which memory system is recruited during recall, thereby affecting the control of retrieval, remain largely unknown. To address these questions, we trained healthy participants in a probabilistic classification learning task, which can be supported both by cognitive and habitual strategies. Approximately 24 hr later, participants received a placebo, hydrocortisone, yohimbine (an α2-adrenoceptor antagonist increasing noradrenergic stimulation), or both drugs before they completed a recall test for the probabilistic classification learning task. During training, all groups showed a practice-dependent shift toward more habitual strategies, reflecting an “automatization” of behavior. In the recall test, after a night of sleep, this automatization was even more pronounced in the placebo group, most likely due to offline consolidation processes and with beneficial effects on recall performance. Hydrocortisone or yohimbine intake abolished this further automatization, preventing the shift to a more efficient memory system and leading, in particular in the hydrocortisone group, to impaired recall performance. Our results suggest that glucocorticoids and noradrenergic stimulation may modulate the engagement of different strategies at recall and link the well-known stress hormone-induced retrieval deficit to a change in the system controlling memory retrieval.

How representative are neuroimaging samples? Large-scale evidence for trait anxiety differences between fMRI and behaviour-only research participants.

“…Therefore, we set out to gather a large dataset of existing trait anxiety scores from labs across multiple institutions who routinely collect trait anxiety measures in their behavioural and MRI studies 1,25,[41][42][43][44][45][46][47][48][49][50][51][52][53][54] . In order to control for possible confounds and examine interaction effects, we additionally collected the following variables: gender, age, whether and how participants were screened for affective/psychiatric disorders, and whether the study involved the presence of a stressor and/or pharmacological manipulation (see Methods for details).…”

Stress‐induced cortisol modulates the control of memory retrieval towards the dorsal striatum

“…Thus, although our data suggest a relevant role of cortisol, we cannot rule out a potential influence of noradrenaline. In fact, a role of noradrenaline in the modulation of multiple memory systems during retrieval has been suggested in pharmacological studies both in rodents (Elliott & Packard, 2008) and in humans (Zerbes et al., 2019). In particular, in a recent behavioural study from our lab (Zerbes et al., 2019), we used the same experimental paradigm as in the present study.…”

“…In fact, a role of noradrenaline in the modulation of multiple memory systems during retrieval has been suggested in pharmacological studies both in rodents (Elliott & Packard, 2008) and in humans (Zerbes et al., 2019). In particular, in a recent behavioural study from our lab (Zerbes et al., 2019), we used the same experimental paradigm as in the present study. In this study, we showed that both hydrocortisone and the α2‐adrenoceptor antagonist yohimbine, leading to increased noradrenergic stimulation, affected the memory strategy used during retrieval.…”

“…Participants were pseudorandomly assigned to a stress ( N = 36) or a control ( N = 36) group, ensuring an equal number of men and women per group. Nineteen participants had to be excluded from the analysis because they did not acquire the learning task (successful learning criterion: ≥ 60% correct trials in the second half of learning, see Zerbes et al., 2019), which was a prerequisite for testing stress effects on the engagement of multiple memory systems during retrieval. Thus, the final sample included 53 participants (stress: 12 women, 12 men; control: 14 women, 15 men; age (mean ± SD ): 25.2 ± 3.8).…”

“…Initial evidence in rats showed that the injection of anxiogenic drugs into the basolateral amygdala before retention testing induced a preference for striatal “habit” memory (Elliott & Packard, 2008). Furthermore, recent evidence in humans suggested that elevated glucocorticoid or noradrenergic activity before retrieving previously learned associations may bias the engaged memory system during retrieval (Zerbes, Kausche, Müller, Wiedemann, & Schwabe, 2019). However, whether stress modulates the engagement of multiple memory systems during retrieval and how such a stress effect on the control of memory retrieval is represented in the human brain is completely unknown.…”