Abstract
Pre-existing knowledge, a ‘schema’, facilitates the encoding, consolidation, and retrieval of schema-relevant information. Such schema-based memory is key to every form of education and provides intriguing insights into the integration of new information and prior knowledge. Stress is known to have a critical impact on memory processes, mainly through the action of glucocorticoids and catecholamines. However, whether stress and these major stress mediators affect schema-based learning is completely unknown. To address this question, we performed two experiments, in which participants acquired a schema on day 1 and learned schema-related as well as schema-unrelated information on day 2. In the first experiment, participants underwent a stress or control manipulation either immediately or about 25 min before schema-based memory testing. The second experiment tested whether glucocorticoid and/or noradrenergic activation is sufficient to modulate schema-based memory. To this end, participants received orally a placebo, hydrocortisone, the α2-adrenoceptor-antagonist yohimbine, leading to increased noradrenergic stimulation, or both drugs, before completing the schema-based memory test. Our data indicate that stress, irrespective of the exact timing of the stress exposure, impaired schema-based learning, while leaving learning of schema-unrelated information intact. A very similar effect was obtained after hydrocortisone, but not yohimbine, administration. These data show that stress disrupts participants’ ability to benefit from prior knowledge during learning and that glucocorticoid activation is sufficient to produce this effect. Our findings provide novel insights into the impact of stress and stress hormones on the dynamics of human memory and have important practical implications, specifically for educational contexts.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Alba JW, Hasher L (1983). Is memory schematic? Psychol Bull 93: 203–231.
Anderson R (1984). Some reflections on the acquisition of knowledge. Educ Res 13: 5–11.
Arnsten AF (2009). Stress signalling pathways that impair prefrontal cortex structure and function. Nat Rev Neurosci 10: 410–422.
Barlett FC (1932) Remembering: A study In experimental and social psychology. University Press: Cambridge.
Barsegyan A, Mackenzie SM, Kurose BD, McGaugh JL, Roozendaal B (2010). Glucocorticoids in the prefrontal cortex enhance memory consolidation and impair working memory by a common neural mechanism. Proc Natl Acad Sci USA 107: 16655–16660.
Buchanan TW, Lovallo WR (2001). Enhanced memory for emotional material following stress-level cortisol treatment in humans. Psychoneuroendocrinology 26: 307–317.
De Kloet ER, Reul JMHM, De Ronde FSW, Bloemers M, Ratka A (1986). Function and plasticity of brain corticosteroid receptor systems: action of neuropeptides. J Steroid Biochem 25: 723–731.
Diamond DM, Campbell AM, Park CR, Halonen J, Zoladz PR (2007). The temporal dynamics model of emotional memory processing: a synthesis on the neurobiological basis of stress-induced amnesia, flashbulb and traumatic memories, and the Yerkes-Dodson law. Neural Plast 2007: 1–32.
Elzinga BM, Roelofs K (2005). Cortisol-induced impairments of working memory require acute sympathetic activation. Behav Neurosci 119: 98–103.
Ghosh VE, Gilboa A (2014a). What is a memory schema? A historical perspective on current neuroscience literature. Neuropsychologia 53: 104–114.
Ghosh VE, Moscovitch M, Melo Colella B, Gilboa A (2014b). Schema representation in patients with ventromedial PFC lesions. J Neurosci 34: 12057–12070.
Heckers S, Zalesak M, Weiss AP, Ditman T, Titone D (2004). Hippocampal activation during transitive inference in humans. Hippocampus 14: 153–162.
Izquierdo A, Wellman CL, Holmes A (2006). Brief uncontrollable stress causes dendritic retraction in infralimbic cortex and resistance to fear extinction in mice. J Neurosci 26: 5733–5738.
Joels M, Fernandez G, Roozendaal B (2011). Stress and emotional memory: a matter of timing. Trends Cogn Sci 15: 280–288.
Joels M, Sarabdjitsingh RA, Karst H (2012). Unraveling the time domains of corticosteroid hormone influences on brain activity: rapid, slow, and chronic modes. Pharmacol Rev 64: 901–938.
Kumaran D (2013). Schema-driven facilitation of new hierarchy learning in the transitive inference paradigm. Learn Mem 20: 388–394.
Kumaran D, Melo HL, Duzel E (2012). The emergence and representation of knowledge about social and nonsocial hierarchies. Neuron 76: 653–666.
Liu RJ, Aghajanian GK (2008). Stress blunts serotonin- and hypocretin-evoked EPSCs in prefrontal cortex: role of corticosterone-mediated apical dendritic atrophy. Proc Natl Acad Sci USA 105: 359–364.
McEwen BS, De Kloet ER, Rostene W (1986). Adrenal steroid receptors and actions in the nervous system. Physiol Rev 66: 1121–1188.
Meaney MJ, Aitken DH, Bodonoff SR, Iny LJ, Tatarewicz JE, Sapolsky RM (1985). Early postnatal handling alters glucocorticoid receptor concentrations in selected brain regions. Behav Neurosci 99: 765–770.
Moench KM, Maroun M, Kavushansky A, Wellman C (2016). Alterations in neuronal morphology in infralimbic cortex predict resistance to fear extinction following acute stress. Neurobiol Stress 3: 23–33.
Morris RG (2006). Elements of a neurobiological theory of hippocampal function: The role of synaptic plasticity, synaptic tagging and schemas. Eur J Neurosci 23: 2829–2846.
Ramos BP, Arnsten AF (2007). Adrenergic Pharmacology and cognition: Focus on the prefrontal cortex. Pharmacol Therapeut 113: 523–546.
Roozendaal B, Hernandez A, Cabrera SM, Hagewoud R, Malvaez M, Stefanko DP et al (2010). Membrane-associated glucocorticoid activity is necessary for modulation of long-term memory via chromatin modification. J Neurosci 30: 5037–5046.
Roozendaal B, McEwen BS, Chattarji S (2009). Stress, memory and the amygdala. Nat Rev Neurosci 10: 423–433.
Schwabe L, Haddad L, Schachinger H (2008). HPA axis activation by a socially evaluated cold-pressor test. Psychoneuroendocrinology 33: 890–895.
Schwabe L, Hoffken O, Tegenthoff M, Wolf OT (2011). Preventing the stress-induced shift from goal-directed to habit action with a beta-adrenergic antagonist. J Neurosci 31: 17317–17325.
Schwabe L, Joels M, Roozendaal B, Wolf OT, Oitzl MS (2012a). Stress effects on memory: an update and integration. Neurosci Biobehav Rev 36: 1740–1749.
Schwabe L, Tegenthoff M, Hoffken O, Wolf OT (2010a). Concurrent glucocorticoid and noradrenergic activity shifts instrumental behavior from goal-directed to habitual control. J Neurosci 30: 8190–8196.
Schwabe L, Tegenthoff M, Hoffken O, Wolf OT (2012b). Simultaneous glucocorticoid and noradrenergic activity disrupts the neural basis of goal-directed action in the human brain. J Neurosci 32: 10146–10155.
Schwabe L, Wolf OT (2009). Stress prompts habit behavior in humans. J Neurosci 29: 7191–7198.
Schwabe L, Wolf OT (2010b). Socially evaluated cold pressor stress after instrumental learning favors habits over goal-directed action. Psychoneuroendocrinology 35: 977–986.
Schwabe L, Wolf OT (2012c). Stress modulates the engagement of multiple memory systems in classification learning. J Neurosci 32: 11042–11049.
Tse D, Langston RF, Kakeyama M, Bethus I, Spooner PA, Wood ER et al (2007). Schemas and memory consolidation. Science 316: 76–82.
Tse D, Takeuchi T, Kakeyama M, Kajii Y, Okuno H, Tohyama C et al (2011). Schema-dependent gene activation and memory encoding in neocortex. Science 333: 891–895.
Valentin VV, Dickinson A, O'Doherty JP (2007). Determining the neural substrates of goal-directed learning in the human brain. J Neurosci 27: 4019–4026.
van Kesteren MT, Beul SF, Takashima A, Henson RN, Ruiter DJ, Fernandez G (2013). Differential roles for medial prefrontal and medial temporal cortices in schema-dependent encoding: from congruent to incongruent. Neuropsychologia 51: 2352–2359.
van Kesteren MT, Rijpkema M, Ruiter DJ, Fernandez G (2010). Retrieval of associative information congruent with prior knowledge is related to increased medial prefrontal activity and connectivity. J Neurosci 30: 15888–15894.
van Kesteren MT, Ruiter DJ, Fernandez G, Henson RN (2012). How schema and novelty augment memory formation. Trends Neurosci 35: 211–219.
Acknowledgements
We gratefully acknowledge the assistance of Sonja Timmerman, Olivia Bendlin, Mewes Muhs, Michaela Christoph, Sandra Weber, and Irmak Bagirsakci during data collection. This study was supported by funding received from the German Research Foundation (DFG; grants SCHW 1357/5-3 and 1357/14-1).
Author information
Authors and Affiliations
Corresponding author
Additional information
Supplementary Information accompanies the paper on the Neuropsychopharmacology website
Supplementary information
Rights and permissions
About this article
Cite this article
Kluen, L., Nixon, P., Agorastos, A. et al. Impact of Stress and Glucocorticoids on Schema-Based Learning. Neuropsychopharmacol 42, 1254–1261 (2017). https://doi.org/10.1038/npp.2016.256
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/npp.2016.256
