Elsevier

Physiology & Behavior

Volume 95, Issue 3, 20 October 2008, Pages 282-289
Physiology & Behavior

The effects of acute stress on human prefrontal working memory systems

https://doi.org/10.1016/j.physbeh.2008.04.027Get rights and content

Abstract

We examined the relationship between acute stress and prefrontal-cortex (PFC) based working memory (WM) systems using behavioral (Experiment 1) and functional magnetic resonance imaging (fMRI; Experiment 2) paradigms. Subjects performed a delayed-response item-recognition task, with alternating blocks of high and low WM demand trials. During scanning, participants performed this task under three stress conditions: cold stress (induced by cold-water hand-immersion), a room temperature water control (induced by tepid-water hand-immersion), and no-water control (no hand-immersion). Performance was affected by WM demand, but not stress. Cold stress elicited greater salivary cortisol readings in behavioral subjects, and greater PFC signal change in fMRI subjects, than control conditions. These results suggest that, under stress, increases in PFC activity may be necessary to mediate cognitive processes that maintain behavioral organization.

Introduction

Working memory (WM) may be defined as the retention and/or manipulation of to-be-remembered information over brief time intervals. It is believed to underlie many higher cognitive processes [6], [59] including reasoning [51], planning [18] and problem solving [13], [50]. Research indicates that the prefrontal cortex (PFC) is a vital neural substrate for WM functions [10], [27]. Neuroimaging studies with humans have consistently demonstrated increased PFC activation during delayed-response tasks that require temporary storage of information [11], [55]. In particular, event-related fMRI studies indicate that dorsolateral PFC mediates WM processes at high WM demands [55], [57]. These results are consistent with primate WM studies showing sustained firing of PFC neurons during delay periods of WM tasks [19] and significant decreases in performance on delayed-response tasks following PFC lesions [17], [26]. Primates also show performance decrements with stress induced PFC catecholaminergic changes [5].

Stress-regulation exerts influences on cognition and behavior. The presence of an acute environmental stressor can modify cognitive functions in humans, including WM systems [1], [14], [23], [37], [38], [44], [48]. Furthermore, WM processes may be particularly susceptible to the effects of acute stress under high memory loads [7], [46] and during the resistance of interference from competing sources of information, especially for older adults [67]. Given the fundamental nature of relationships between WM and higher cognitive processes, delineating the underlying mechanisms of stress-related performance changes is critical, not only to a complete understanding of WM systems in particular, but to understanding the nature of stress–cognition relations generally.

Studies that have examined the effects of acute stress on WM have produced mixed results. Negative effects of acute stress on WM task performance have been observed in some studies [32], [35], [46], [48], [61]. Other studies, however, have not shown such effects [12], [42], [58]. Empirical discrepancies have been difficult to reconcile because, across studies, a variety of stress manipulations and WM measures have been used. Some stress manipulations may be more susceptible to individual reactivity differences than others [2], [68]. Some performance measures may also be more susceptible to individual reactivity differences than others. For instance, some studies suggest that gender mediates stress–WM performance relationships [35], [68]. Procedural differences between experiments may also lead to differences in results across studies. These include temporal relationships between stress-administration and cognitive assessment, cortisol collection methods, endogenous collection or exogenous cortisol administration, measured behavioral parameters (i.e., reaction time; RT and accuracy), and within- vs. between-subject stress manipulations.

Human and animal research suggests anatomic and neurochemical relationships between sub-cortical structures that respond to stress and affect PFC [21]. Rodent medial PFC is one target of the stress-related neurochemical response [8], [15], [16] via connections with amygdalar basolateral complex [41]. Additionally, lesions within these amygdalo–PFC pathways have been shown to attenuate catecholamine release within PFC [3], [5]. Stress-related catecholaminergic changes may affect PFC-based WM processes in primates [5]. In one study, for instance, monkeys performed a spatial delayed-response task with varying delay intervals [3]. On some occasions, WM performance followed sustained exposure to loud noise (100–110 db wide-band frequency). Noise-related performance decrements were greater with longer delay intervals. Performance decrements were attributed to a “hyperdopaminergic” stress response in PFC because the behavioral stress response was mediated by administration of dopamine-receptor antagonists. In humans, excitation of the hypothalamic–pituitary–adrenal (HPA) axis leads to corticosteroid (e.g., cortisol) hypersecretion due to stress exposure. These hormones exert global effects on the brain and body and also affect mental states [20], [22], [45]. Results from multiple studies converge to indicate that increases in glucocorticoid levels exert a profound influence over PFC structure and functioning, in both animals and non-human primates. For example, corticosterone (the central cortisol analogue in rodents) has been associated with a reorganization of PFC dendritic fibers in rats [8]. Additionally, injections of hydrocortisone (a synthetic form of cortisol) have been linked to impairment of medial PFC-based behavioral inhibitory capabilities in non-human primates [39]. By impairing PFC function, excessive levels of cortisol also appear to disinhibit HPA activation thus increasing sympathetic nervous system activity.

These studies are consistent with the notion that WM systems are especially susceptible to the deleterious effects of acute stress. They illustrate a plausible mechanism through which stress could affect PFC-dependent WM processes, through PFC–amygdala interactions. To observe this mechanism in humans, we had subjects perform a delayed-response WM task during behavioral performance and fMRI scanning. In behavioral (Experiment 1) and fMRI (Experiment 2) studies we periodically immersed subjects' hands in ice-cold water (4 °C) to induce acute stress. For Experiment 1, we hypothesized that there would be a significant difference in salivary cortisol levels during cold stress compared to control conditions. Specifically, we hypothesized that salivary cortisol levels would be higher when subjects' hands were immersed in cold water than when they were immersed in room temperature water. For Experiment 2, we predicted that PFC activity would be most affected by the application of cold stress, relative to non-cold stress conditions. It is our hypothesis that the cold press experience results in increased cortisol levels, and that these higher cortisol levels disrupt typical prefrontal functioning. Additionally we predicted that this increase, if present, may be mediated by amygdalar activity. Because behavioral results from studies of acute stress have been mixed [35], [42], [46], [49], [58], we were less certain about predictions regarding behavioral performance. By convolving the presence or absence of acute cold-pressor stress with high and low WM demand we sought to clarify the manner in which these factors interact with PFC activity, amygdala activity and WM performance. The current study sheds new light on the nature of the interaction of PFC areas underlying WM processes and the amygdala, and how these neural regions interact to regulate the effects of acute stress in order to maintain organized and goal-directed behavior.

Section snippets

Participants

Eighteen healthy young volunteers (mean age = 20.4; 6 men) were recruited from the undergraduate and medical campus of Rutgers University — Newark and UMDNJ. Participants were excluded if they had any medical (including type I or type II diabetes, hypertension, cardiac condition, significant weight loss or major surgery within the last 6 months), psychiatric (including depression, anxiety or substance abuse), or neurological (including epilepsy and migraine syndrome) conditions. Participants were

Participants

Twelve right-handed healthy volunteers (mean age 22.67, 6 men) were recruited from the undergraduate campus of Rutgers University — Newark. Only subjects determined to be free of psychotropic medications, substance abuse or addiction, medical, neurological or psychiatric illness via a screening interview were allowed permitted to participate. Subjects were told that they would be performing several computerized cognitive tasks during fMRI scanning. In addition they were informed of the water

Discussion

Experiment 1 was conducted to determine the effects of stress, as measured by salivary cortisol levels, on WM performance. Subjects performed a WM task with high and low WM demand trials, while their hands were immersed in either room temperature or cold water. We observed minimal stress-related performance differences. There were significant performance differences, however, as a function of WM demand. Subjects performed significantly slower on high WM demand as compared to low WM demand

Acknowledgements

This study was supported by NIH grants MH61636 and AG029523 (BR). We thank the staff at the UMDNJ—Rutgers Advanced Imaging Center who contributed to this project. We would also like to thank Dr. Dane Cook for assistance in the design of this project.

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