Physiology & Behavior 103 (2011) 467–476
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Physiology & Behavior
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / p h b
Pre-learning stress differentially affects long-term memory for emotional words,
depending on temporal proximity to the learning experience
Phillip R. Zoladz a,⁎, Brianne Clark a, Ashlee Warnecke a, Lindsay Smith a, Jennifer Tabar a, Jeffery N. Talbot b
a
b
Department of Psychology & Sociology, Ohio Northern University, Ada, Ohio, 45810, USA
Department of Pharmaceutical & Biomedical Sciences, Ohio Northern University, Ada, Ohio, 45810, USA
a r t i c l e
i n f o
Article history:
Received 17 September 2010
Received in revised form 6 January 2011
Accepted 16 January 2011
Available online xxxx
Keywords:
Cortisol
Stress
Hippocampus
Amygdala
Learning
Memory
a b s t r a c t
Stress exerts a profound, yet complex, influence on learning and memory and can enhance, impair or have no
effect on these processes. Here, we have examined how the administration of stress at different times before
learning affects long-term (24-hr) memory for neutral and emotional information. Participants submerged
their dominant hand into a bath of ice cold water (Stress) or into a bath of warm water (No stress) for 3 min.
Either immediately (Exp. 1) or 30 min (Exp. 2) after the water bath manipulation, participants were
presented with a list of 30 words varying in emotional valence. The next day, participants' memory for the
word list was assessed via free recall and recognition tests. In both experiments, stressed participants
exhibited greater blood pressure, salivary cortisol levels, and subjective pain and stress ratings than nonstressed participants in response to the water bath manipulation. Stress applied immediately prior to learning
(Exp. 1) enhanced the recognition of positive words, while stress applied 30 min prior to learning (Exp. 2)
impaired free recall of negative words. Participants' recognition of positive words in Experiment 1 was
positively associated with their heart rate responses to the water bath manipulation, while participants' free
recall of negative words in Experiment 2 was negatively associated with their blood pressure and cortisol
responses to the water bath manipulation. These findings indicate that the differential effects of pre-learning
stress on long-term memory may depend on the temporal proximity of the stressor to the learning experience
and the emotional nature of the to-be-learned information.
© 2011 Published by Elsevier Inc.
1. Introduction
Stress exerts a profound, yet complex, influence on learning and
memory. Over the past few decades, a growing body of literature has
revealed that stress can enhance, impair or have no effect on learning
and memory, depending on several factors related to the stressor, the
information being learned and the organism under investigation [1–3].
For instance, the effects of stress on learning and memory appear to
depend, at least in part, on the particular stage of learning and memory
that is being affected by the stress, as well as the emotional nature of
the information that is being tested [4,5]. Research has shown that
stress generally exerts deleterious effects on memory retrieval [6–12]
(however, see [13], where stress enhanced retrieval), yet when stress
is administered after learning, it enhances consolidation [11,14,15],
thus boosting performance on subsequent memory assessments. Both
of these effects tend to be more pronounced for information that is
emotionally arousing in nature [8,9,11,12,14]. The effects of prelearning stress on long-term memory, however, have been less clear;
⁎ Corresponding author at: Ohio Northern University, Department of Psychology &
Sociology, 525 S. Main St. Hill 013, Ada, OH, 45810, USA. Tel.: +1 419 772 2142; fax: +1
419 772 2746.
E-mail address: p-zoladz@onu.edu (P.R. Zoladz).
0031-9384/$ – see front matter © 2011 Published by Elsevier Inc.
doi:10.1016/j.physbeh.2011.01.016
studies in humans and rodents have reported that pre-learning stress
can enhance, impair or have no effect on the storage of information
[6,16–24]. When significant effects of pre-learning stress have been
observed, the most common, but not unanimous, finding has been
enhanced memory for emotionally arousing information, at the cost of
(i.e., impaired memory for) emotionally neutral information.
With regards to pre-learning stress, the duration of the stress, in
addition to the temporal proximity of the stressor to the learning
experience, strongly influences the types of effects that are observed
on long-term memory [25]. Research has suggested that pre-learning
stress can enhance long-term hippocampus-dependent memory as
long as the stress is relatively brief and is in close temporal proximity
to the learning experience [1]. Indeed, studies have shown that brief
stress administered immediately or shortly before learning enhances
long-term memory [20,21,23–25], while the same brief stressor
administered 30 min before learning has no effect on subsequent
memory [25]. Moreover, if the duration of the stressor applied
immediately before learning is extended, to 30 min for instance, then
long-term memory can be impaired [6,16,18,19].
To explain how pre-learning stress affects learning, Diamond and
colleagues [25] developed a theory in which they speculated that
stress produces different temporal activation profiles for different
brain regions. A majority of their theory focused on an amygdala-
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induced biphasic response pattern of hippocampal function following
the initiation of stress [26,27]. According to this theory, acute stress
initially produces a rapid enhancement of hippocampal neuroplasticity, which facilitates the storage of new information; over time,
however, the hippocampus is forced into a refractory state, during
which learning and memory processes are impaired. Part of the basis
for this theory was electrophysiological work indicating that
glucocorticoids, as well as electrical stimulation of the amygdala,
could exert immediate excitatory, but delayed inhibitory, effects on
hippocampal synaptic plasticity [26–31]. According to the theory,
stress that is applied immediately before learning should enhance
memory storage, while stress that is applied a longer time before
learning should impair memory storage. In their manuscript,
Diamond and colleagues [25] provided support for the theory by
demonstrating that 2 min of cat exposure (i.e., predator stress)
applied immediately, but not 30 min, prior to learning enhanced longterm water maze memory in rats. The application of brief stress
30 min prior to learning should have theoretically impaired long-term
memory, but the training parameters did not allow for such a memory
impairment to be detected.
The temporal dynamics model of emotional memory processing is
based largely on findings from non-human animal studies. Few
human studies have examined the influence of pre-learning stress on
long-term memory, and to our knowledge, no studies in humans have
specifically examined how stress that is applied at different times
before learning differentially affects long-term memory processes.
Since the effects of pre-learning stress on memory might differ
between humans and non-human animals, the present experiments
were designed to extend the temporal dynamics model of emotional
memory processing to humans by examining the effects of brief stress,
applied immediately or 30 min prior to learning, on long-term
memory in people. Our hypothesis was that stress applied immediately prior to learning would enhance long-term memory, while
stress applied 30 min prior to learning would impair long-term
memory. Since previous work has shown that the emotional nature of
the to-be-learned information also mediates the effects of stress on
learning, we varied the emotional valence of the information that
participants learned and expected that such information may be more
affected by the stress manipulations.
study. All of the methods for the experiments were approved by the
Institutional Review Board at Ohio Northern University.
2.2. Experimental procedures
The experimental timeline for each experiment is presented in
Fig. 1. To control for diurnal variations in cortisol levels, all testing was
carried out between 1200 and 1800 h.
2.2.1. Socially Evaluated Cold Pressor Test (SECPT)
Participants were asked to submerge their dominant hand, up to
and including the wrist, in a bath of water for 3 min. Those
participants who had been randomly assigned to a stress condition
(Experiment 1: N = 15; Experiment 2: N = 16) placed their hand in a
bath of ice cold (0–2 °C) water, while participants who had been
randomly assigned to a control condition (Experiment 1: N = 21;
Experiment 2: N = 20) placed their hand in a bath of warm (35–37 °C)
water. The water was maintained at the appropriate temperature by a
Lauda Brinkmann RMT6 circulating water bath. To maximize the
stress response, participants in each experiment were encouraged to
keep their hand in the water bath for the entire 3-min period.
However, if a participant found the water bath too painful, he or she
was allowed to remove his or her hand from the water and continue
with the experiment. From Experiments 1 and 2 combined, there was
only one participant who did not keep his or her hand in the water
bath for the entire 3 min.
Based on previous work [32], a social evaluative component was
added to the cold pressor manipulation. Participants in the stress
conditions were misleadingly informed that they were being
videotaped during the procedure for subsequent evaluation of their
facial expressions, and throughout the water bath manipulation, they
were asked to keep their eyes on a camera that was located on the
wall of the laboratory. Moreover, a confederate member of the
opposite sex was in the testing facility and stared at participants in the
stress conditions throughout the water bath manipulation.
2.1. Participants
2.2.2. Subjective pain and stress ratings
All participants were asked to rate the painfulness and stressfulness of the water bath manipulation at 1-min intervals on 11-point
scales ranging from 0 to 10, with 0 indicating a complete lack of pain
or stress and 10 indicating unbearable pain or stress. If a participant
removed his or her hand from the water before 3 min had elapsed, the
remaining data points were automatically scored as 10 s for each
measure.
Seventy-two healthy men and women (20 men, 52 women; age:
M = 19.68, SD = 2.94; body-mass-index (BMI): M = 23.40, SD = 3.77)
from Ohio Northern University volunteered to participate in the
experiments. Individuals were excluded from participating if they met
any of the following conditions: history of severe head injury; current
treatment with psychotropic medications, narcotics, beta-blockers,
steroids or any other medication that affects central nervous or
endocrine system function; medical illness within the 3 weeks prior
to participation; mental or substance use disorder; regular nightshift
work. Individuals who smoked were allowed to participate in the
study; information regarding individuals' smoking habits was
collected prior to the experiments via a short demographic survey.
From both experiments combined, there were only 3 participants who
reported smoking on a regular basis, and inclusion of the data from
these participants in the statistical analyses did not alter the results.
Participants were asked to refrain from using recreational drugs (e.g.,
marijuana) for 3 days prior to the experimental sessions; to refrain
from drinking alcohol or exercising extensively for 24 h prior to the
experimental sessions; and, to refrain from eating or drinking
anything but water for 2 h prior to the experimental sessions.
Participants were awarded class credit upon completion of the
2.2.3. Word presentation
Either immediately (Experiment 1) or 27 min (Experiment 2)
following the water bath manipulation, participants were presented
with a list of 30 words, composed of 10 neutral, 10 positive and 10
negative words. The words were chosen from the Affective Norms for
English Words [33] and, across emotional valence categories, were
balanced for word length and word frequency. As per the methods
employed by Schwabe and colleagues [20], participants were
instructed to read each word aloud and rate its emotional valence
on a scale from − 3 (very negative) to +3 (very positive) on a sheet of
paper containing the list of words. This manipulation was performed
to promote encoding of the words.
Two versions of the word list were used in the experiments. According
to the Affective Norms for English Words [33], the mean (±SEM) valence
and arousal ratings for the words that made up these lists were as follows:
word list 1 (positive words: valence=7.83±0.17, arousal=5.56±0.43;
negative words: valence=2.24 ±0.14, arousal =5.75 ±0.39; neutral
words: valence=5.12±0.21, arousal=4.28±0.28) and word list 2
(positive words: valence=7.64±0.12, arousal=5.25±0.48; negative
words: valence= 2.18 ± 0.15, arousal = 5.59 ± 0.28; neutral words:
valence=4.90±0.17, arousal=4.30±0.33).
2. Method
P.R. Zoladz et al. / Physiology & Behavior 103 (2011) 467–476
469
Fig. 1. Timeline for the methodology employed in Experiments 1 and 2. Participants were exposed to the water bath manipulation at time point 0. Participants in the stress conditions
placed their dominant hand in cold (0–2 °C) water while being observed by a confederate of the opposite sex and believing that they were being videotaped; participants in the no
stress conditions placed their dominant hand in warm (35–37 °C) water. Either immediately (Experiment 1) or 27 min (Experiment 2) following the water bath manipulation,
participants were presented with a list of 30 words (10 positive, 10 negative, 10 neutral). They were asked to read each word aloud and rate its emotional valence. To verify the
induction of a stress response, several saliva samples (S in the figure) and cardiovascular measurements (C in the figure) were obtained from participants throughout the first
experimental session. Twenty-fours hours later, participants returned to the laboratory to complete free recall and recognition tasks regarding the word list that was studied on the
previous day. Recognition memory was assessed 15 min following the free recall assessment.
2.2.4. Twenty-four hour free recall and recognition testing
One day following the first experimental session, participants
returned to the laboratory to have their memory for the list of words
assessed. Participants were given 5 min to write down as many words
as they could remember from the list of words that they studied on
the previous day (i.e., free recall). Then, participants sat quietly and
completed school work that they had brought to the laboratory. After
15 min had elapsed, participants were given a recognition test. They
were presented with a list of words containing 30 “old” words (i.e.,
words that were presented on the previous day) and 30 “new” words
(i.e., words that were not presented on the previous day) and were
instructed to label each word as “old” or “new.” The “new” words
were matched to the “old” words on emotional valence, word length
and word frequency. To assess participants' ability to discriminate
between “old” and “new” words, we calculated a sensitivity index
(d' = z[p(hit) − p(false alarm)]) for each category of word (i.e.,
positive, negative and neutral) to be used for statistical analysis [34].
2.3. Cardiovascular analysis
Heart rate (HR) and blood pressure (BP) measurements were
taken 2 min before (baseline), halfway through, 5 min after and
15 min after the water bath manipulation. Cardiovascular activity was
measured with the vital signs monitor (Mark of Fitness WS-820
Automatic Wrist Blood Pressure Monitor) placed on the wrist of each
participant's non-dominant hand.
2.4. Cortisol analysis
Saliva samples were collected from participants 2 min before
(baseline), 5 min after, 15 min after and 25 min after the water bath
manipulation to analyze salivary cortisol concentrations. The samples
were collected in a Salivette saliva collection device (Sarstedt, Inc.,
Newton, NC). Participants were asked to place a swab of cotton in
their mouths and chew on it so that it would easily absorb their saliva.
Following 1 min of chewing, the swab was collected and placed in the
Salivette conical tube and kept at room temperature until the
experimental session was completed. The samples were subsequently
stored at −20 °C until assayed for cortisol. Since salivary cortisol
levels do not rise immediately following stress onset, we did not assay
those samples collected 5 min after the water bath manipulation.
Saliva samples were thawed and extracted by low-speed centrifugation, and salivary cortisol levels were assayed by enzyme immuno
assay (EIA; Caymen Chemical Co., Ann Arbor, MI) according to the
manufacturer's protocol. The minimum detectable concentration of
cortisol was approximately 8 pg/ml, and the average inter- and intraassay percent coefficients of variation were less than 5.2% and 14%,
respectively.
2.5. Statistical analyses
Mixed-model ANOVAs were used to analyze the data from each
experiment. The between-subjects factor utilized in these analyses
was stress, and the within-subjects factor was word valence (for recall
and recognition analyses) or time (for physiological and subjective
ratings analyses). Sex was not included as a between-subjects factor
in these analyses because of (1) the uneven distribution of males and
females to the stress and no stress conditions in each experiment and
(2) the small number of males in some experimental cells.
Participants in the stress conditions from each experiment were
divided into “Responders” and “Non-Responders” based on their
cortisol responses to the SECPT. Those participants exhibiting a
cortisol increase of at least 1.5 nmol/l 15 min following the SECPT
were considered Responders; all other participants were considered
Non-Responders. The cutoff for dividing participants into Responder
and Non-Responder groups was based on previous work using a
similar criterion [20]. The Responders and Non-Responders were then
statistically compared on memory and, when deemed necessary, on
physiological measures. Bivariate correlations (Pearson's r) were
performed on the data from each experiment to examine the
relationship between participants' physiological stress responses
and their long-term memory performance. To limit the inflation of
Type I error rates, correlations were performed only for memory
measures affected by stress. Alpha was set at 0.05 for all analyses, and
Bonferroni-corrected post hoc tests were employed when necessary.
SPSS (version 18.0; SPSS, Inc.) was used to perform all statistical
analyses.
3. Results
3.1. Experiment 1: Stress immediately before learning
3.1.1. Cardiovascular and hormonal activity
The stress manipulation had no effect on HR (significant main
effect of time: F(3,99) = 4.35, p b 0.01, η2 = 0.12; no significant main
effect of stress: F(1,33) = 1.19, p N 0.05, η2 = 0.04; no significant
Time × Stress interaction: F(3,99) = 2.50, p N 0.05, η2 = 0.07). However,
the stress group exhibited significantly greater systolic (significant
main effect of time: F(3,99) = 55.73, p b 0.001, η2 = 0.63; significant
Time × Stress interaction: F(3,99) = 10.90, p b 0.001, η2 = 0.25; no
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significant main effect of stress: F(1,33) = 3.14, p N 0.05, η2 = 0.09) and
diastolic (significant main effect of time: F(3,99) = 50.98, p b 0.001,
η2 = 0.61; significant main effect of stress: F(1,33) = 5.65, p b 0.05,
η2 = 0.15; significant Time × Stress interaction: F(3,99) = 15.89,
p b 0.001, η2 = 0.33) BP during the water bath manipulation than the
control group (Table 1). The stress group also exhibited significantly
greater cortisol levels than the control group at 15 and 25 min following
the water bath manipulation (significant main effect of time: F(2,36)=
8.92, pb 0.001, η2 =0.33; significant main effect of stress: F(1,18)=7.67,
pb 0.01, η2 =0.30; significant Time×Stress interaction: F(2,36)=6.56,
pb 0.01, η2 =0.27; Fig. 2).
3.1.2. Subjective ratings of water bath manipulation
Relative to the control group, the stress group expressed significantly
greater overall pain ratings of the water bath manipulation (significant
main effect of stress: F(1,34) = 134.43, p b 0.001, η2 = 0.80), and the
ratings observed in the stress group significantly increased over time
(significant main effect of time: F(2,68) = 9.41, p b 0.001, η2 = 0.22;
significant Time x Stress interaction: F(2,68) = 8.07, p b 0.001, η2 = 0.19;
Table 2). The stress group also expressed significantly greater overall
stress ratings of the water bath manipulation than the control group
(significant main effect of stress: F(1,34) = 62.10, p b 0.001, η2 = 0.65;
no significant main effect of time: F(2,68) = 2.53, p N 0.05, η2 = 0.07; no
significant Time × Stress interaction: F(2,68) = 1.43, p N 0.05, η2 = 0.04).
3.1.3. Word list ratings and 24-hour memory
3.1.3.1. Word list ratings. The analysis of subjective valence ratings for
the different types of words verified that participants rated negative
words as negative (M = −2.17, SEM = 0.05), neutral words as neutral
(M = −0.08, SEM = 0.06) and positive words as positive (M = 2.10,
SEM = 0.06) (significant main effect of word valence: F(2,68) = 599.74,
p b 0.001, η2 = 0.95). This effect was not dependent upon group (no
significant main effect of stress: F(1,34) = 1.20, p N 0.05, η2 = 0.03; no
significant Word Valence × Stress interaction: F(2,68) = 0.45, p N 0.05,
η2 = 0.01).
3.1.3.2. Free recall. Participants exhibited significantly better recall
performance for emotional words (i.e., positive and negative words)
than for neutral words (significant main effect of word valence:
F(2,60) = 8.92, p b 0.001, η2 = 0.23). However, stress did not signifiTable 1
Cardiovascular activity before, during and after the water bath manipulation in
Experiments 1 and 2.
Condition
Pre
During
Post 1
Experiment 1: Stress immediately before learning
Heart rate (bpm)
Stress
76.47 (2.75)
75.87 (3.43)
68.27 (3.06)
No stress
79.20 (3.77)
77.60 (3.71)
77.20 (3.38)
Systolic blood pressure (mm Hg)
⁎
Stress
127.20 (3.33) 151.53 (3.83) 123.27 (5.26)
No stress
125.85 (2.24) 131.95 (1.97) 122.25 (1.77)
Diastolic blood pressure (mm Hg)
Stress
82.47 (3.10) 103.53 (3.09)⁎
76.67 (4.31)
No stress
78.30 (1.85)
83.60 (1.34)
77.15 (1.43)
Post 2
73.27 (3.81)
80.05 (3.31)
118.07 (3.05)
116.95 (1.48)
75.33 (2.06)
74.35 (1.37)
Experiment 2: Stress 30 min before learning
Heart rate (bpm)
Stress
81.44 (4.76)
85.00 (3.54)⁎
78.25 (4.54)
77.50 (3.49)
No stress
80.80 (3.83)
77.40 (3.30)
80.95 (3.26)
78.45 (3.03)
Systolic blood pressure (mm Hg)
Stress
128.88 (3.54) 153.56 (5.54)⁎ 127.69 (3.34)⁎ 119.19 (3.30)
No stress
123.10 (1.79) 129.85 (2.28) 119.15 (1.97) 113.95 (1.97)
Diastolic blood pressure (mm Hg)
Stress
84.13 (2.62)⁎ 104.38 (3.63)⁎
80.94 (4.01)
76.31 (2.17)
No stress
77.40 (1.71)
83.65 (2.02)
75.75 (1.63)
71.95 (1.60)
Data are presented as means ± SEM.
⁎ p b 0.05 relative to the no stress group.
Fig. 2. Cortisol levels before and after the water bath manipulation in Experiments 1 (top)
and 2 (bottom). In both experiments, exposure to the SECPT (Stress) led to significantly
greater salivary cortisol levels than those observed in the control group (No stress). Data
are presented as means± SEM; * = p b 0.05 relative to the no stress group.
cantly affect the recall of any type of word (no significant main effect
of stress: F(1,30) = 0.16, p N 0.05, η2 = 0.01; no significant Word
Valence × Stress interaction: F(2,60) = 1.00, p N 0.05, η2 = 0.03).
3.1.4. Recognition
Participants exhibited significantly better recognition of positive
and neutral words, relative to negative words (significant main effect
of word valence: F(2,64) = 5.02, p b 0.01, η2 = 0.14). In addition, the
stress group exhibited significantly better recognition of positive
words than the control group (significant Word Valence × Stress
interaction: F(2,64) = 4.69, p b 0.05, η2 = 0.13; Fig. 3). There was no
significant main effect of stress, F(1,32) = 0.34, p N 0.05, η2 = 0.01.
Table 2
Subjective ratings of the water bath manipulation in Experiments 1 and 2.
Condition
Minute 1
Minute 2
Minute 3
6.27 (0.60)⁎
0.05 (0.05)
6.67 (0.65)⁎
0.05 (0.05)
4.80 (0.67)⁎
0.29 (0.14)
5.07 (0.69)⁎
0.33 (0.13)
(0.62)⁎
(0.12)
5.38 (0.60)⁎
0.40 (0.22)
6.06 (0.56)⁎
0.40 (0.22)
(0.59)⁎
(0.15)
4.69 (0.69)⁎
0.50 (0.17)
4.75 (0.62)⁎
0.45 (0.20)
Experiment 1: Stress immediately before learning
Painfulness ratings (scale of 0–10)
Stress
5.33 (0.72)⁎
No stress
0.00 (0.00)
Stressfulness ratings (scale of 0–10)
Stress
4.40 (0.69)⁎
No stress
0.24 (0.17)
Experiment 2: Stress 30 min before learning
Painfulness ratings (scale of 0–10)
Stress
5.88
No stress
0.20
Stressfulness ratings (scale of 0–10)
Stress
4.19
No stress
0.30
Data are presented as means ± SEM.
⁎ p b 0.05 relative to the no stress group.
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471
pb 0.01, η2 =0.23, significant Time×Stress interaction: F(3,102)=12.28,
pb 0.001, η2 =0.27). Lastly, the stress group demonstrated significantly
greater overall levels of salivary cortisol, relative to the control group
(significant main effect of stress: F(1,24)=6.86, pb 0.05, η2 =0.22).
Despite there being no significant main effect of time, F(2,48) =
2.15, pN 0.05, η2 =0.08, and no significant Time×Stress interaction,
F(2,48)=2.32, pN 0.05, η2 =0.09, inspection of the data suggested that
the observed significant main effect of stress was driven by greater
salivary cortisol levels in the stress group, relative to the no stress group, at
15 and 25 min post-water bath manipulation, which was confirmed via
separate one-way ANOVAs for each time point (p'sb 0.05; Fig. 2).
3.1.5. Cortisol responders versus non-responders
The analyses revealed no significant differences between cortisol
Responders and Non-Responders on any memory measure (all p'sN 0.05);
therefore, no analyses were performed to compare these groups on
physiological measures.
3.1.6. Correlations between physiological stress response and long-term
memory
There was a significant positive correlation between participants'
recognition of positive words and their HR during the water bath
manipulation, r(34) = 0.38, p b 0.05 (Fig. 3).
3.2.2. Subjective ratings of water bath manipulation
Relative to the control group, the stress group expressed significantly
greater overall pain ratings of the water bath manipulation (significant
main effect of stress: F(1,34)=126.56, pb 0.001, η2 =0.79; no significant
main effect of time: F(2,68)=0.86, pN 0.05, η2 =0.03; no significant
Time×Stress interaction: F(2,68)=1.16, pN 0.05, η2 =0.03; Table 2). The
stress group also expressed significantly greater overall stress ratings of
the water bath manipulation than the control group (significant main
effect of stress: F(1,34)=59.68, pb 0.001, η2 =0.64; no significant main
effect of time: F(2,68)=1.51, pN 0.05, η2 =0.04; no significant Time×Stress interaction: F(2,68)=0.41, pN 0.05, η2 =0.01).
3.2. Experiment 2: Stress 30 min before learning
3.2.1. Cardiovascular and hormonal activity
The stress group exhibited significantly greater HR than the
control group during the water bath manipulation (significant
Time × Stress interaction: F(3,102) = 4.43, p b 0.01, η2 = 0.12; no
significant main effect of time, F(3,102) = 2.02, p N 0.05, η2 = 0.06, or
no significant main effect of stress: F(1,34) = 0.05, p N 0.05, η2 = 0.00;
Table 1). The stress group also displayed significantly greater systolic BP
than the control group during and 5 min after the water bath
manipulation (significant main effect of time: F(3,102) = 90.78,
pb 0.001, η2 =0.73; significant main effect of stress: F(1,34)=8.19,
p b 0.01, η2 = 0.19; significant Time× Stress interaction: F(3,102) =
15.27, pb 0.001, η2 =0.31). The stress group demonstrated significantly
greater diastolic BP than the control group before and during the water
bath manipulation (significant main effect of time: F(3,102)=60.88,
pb 0.001, η2 =0.64; significant main effect of stress: F(1,34)=10.31,
3.2.3. Word list ratings and 24-hour memory
3.2.3.1. Word list ratings. Analysis of the subjective valence ratings for the
different word types verified that participants rated negative words as
negative (M=−2.17, SEM=0.05), neutral words as neutral (M=−0.12,
Experiment 1: Stress Immediately Before Learning
Free Recall
3.0
No Stress
Discrimination Index (d')
% of Words Recalled
25
Recognition
Stress
20
15
10
5
0
Neutral
Positive
No Stress
2.5
1.5
1.0
0.5
Neutral
Word Type
Positive Word Recognition (d')
*
2.0
0.0
Negative
Stress
Positive
Negative
Word Type
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
40
60
80
r = 0.38, p < 0.05
100
120
140
Heart Rate (bpm) during Water Bath
Fig. 3. Long-term (24-hr) memory for positive, negative and neutral words (top) and the relationship between positive word recognition and HR during the water bath manipulation
(bottom) in Experiment 1. Exposure to the SECPT (Stress) immediately before learning had no significant effect on free recall but led to a significant enhancement of positive word
recognition 24 h later. There was also a significant positive correlation between participants' recognition of positive words and their HR during the water bath manipulation. In the
scatter plot, the black circles represent the Stress group, while the gray circles represent the No stress group. The memory data (top) are presented as means ± SEM; * = p b 0.05
relative to the no stress group.
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P.R. Zoladz et al. / Physiology & Behavior 103 (2011) 467–476
SEM=0.06) and positive words as positive (M=2.21, SEM=0.06)
(significant main effect of word valence: F(2,68)=509.31, pb 0.001,
η2 =0.94). This effect was not dependent upon group (no significant main
effect of stress: F(1,34)=0.93, pN 0.05, η2 =0.03; no significant Word
Valence×Stress interaction: F(2,68)=0.93, pN 0.05, η2 =0.03).
3.2.3.2. Free recall. Participants exhibited significantly better recall
performance for emotional words (i.e., positive and negative words)
than for neutral words (significant main effect of word valence: F(2,62)=
13.63, pb 0.001, η2 =0.31). The stress group recalled significantly fewer
negative words than the control group (significant Word Valence x Stress
interaction: F(2,62)=6.52, pb 0.01, η2 =0.17; Fig. 4). The stress group
also tended to recall more positive words than the control group, although
this effect did not attain statistical significance (p=0.07). There was no
significant main effect of stress, F(1,31)=0.36, pN 0.05, η2 =0.01.
3.2.3.3. Recognition. Participants exhibited significantly better recognition
of positive words than of negative and neutral words (significant main
effect of word valence: F(2,68)=3.11, p=0.05, η2 =0.08). However,
stress had no effect on the recognition of any type of word (no significant
main effect of stress: F(1,34)=1.21, pN 0.05, η2 =0.03; no significant
Word Valence x Stress interaction: F(2,68)=0.15, pN 0.05, η2 =0.00).
3.2.4. Cortisol responders versus non-responders
When comparing the performance of cortisol Responders and NonResponders on long-term memory, we found that there was a significant
Word Valence×Group interaction for 24-hr free recall, F(4,54)=3.50,
Experiment 2: Stress 30 Minutes Before Learning
Free Recall
Recognition
Stress
Stress
No Stress
3.0
β
Discrimination Index (d')
% of Words Recalled
25
20
15
*
10
5
0
Neutral
Positive
No Stress
2.5
2.0
1.5
1.0
0.5
0.0
Negative
Neutral
Positive
35
30
r = -0.36, p < 0.05
25
20
15
10
5
0
100
120
140
160
180
200
220
35
30
r = -0.47, p < 0.01
25
20
15
10
5
0
60
70
80
90
100 110 120 130 140
Diastolic Blood Pressure (mmHg)
during Water Bath
Systolic Blood Pressure (mmHg)
during Water Bath
% of Negative Words Recalled
Negative
Word Type
% of Negative Words Recalled
% of Negative Words Recalled
Word Type
35
30
r = -0.38, p < 0.05
25
20
15
10
5
0
-20
-10
0
10
20
30
40
Change in Cortisol after Water Bath (nmol/l)
Fig. 4. Long-term (24-hr) memory for positive, negative and neutral words (top) and the relationship between negative word free recall and cardiovascular (middle)/cortisol
(bottom) activity during or after the water bath manipulation in Experiment 2. Exposure to the SECPT (Stress) 30 min prior to learning significantly impaired free recall of negative
words and marginally enhanced free recall of positive words 24 h later. However, exposure to the SECPT had no effect on recognition memory. There were significant negative
correlations between participants' free recall of negative words and their systolic BP during the water bath manipulation, their diastolic BP during the water bath manipulation and
their change in cortisol levels after the water bath manipulation. In the scatter plots, the black circles represent the Stress group, while the gray circles represent the No stress group.
The memory data (top) are presented as means ± SEM; * = p b 0.05 relative to the no stress group; β = p = 0.07 relative to the no stress group.
P.R. Zoladz et al. / Physiology & Behavior 103 (2011) 467–476
pb 0.05, η2 =0.21. Post hoc tests indicated that Responders, but not NonResponders, recalled significantly fewer negative words than the control
group (Fig. 4). We also found significant Time x Group interactions for
systolic, F(3,87) = 10.49, η2 = 0.42, and diastolic, F(3,87) = 7.20,
η2 =0.33, BP (p'sb 0.001). These effects revealed that, during the SECPT,
the Responders exhibited significantly greater systolic and diastolic BP
than the Non-Responders, who in both cases exhibited statistically
equivalent BP to the control group.
3.2.5. Correlations between physiological stress response and long-term
memory
There were significant negative correlations between participants'
free recall of negative words and their systolic BP during the water
bath manipulation, r(34) = −0.36, their diastolic BP during the water
bath manipulation, r(34) = − 0.47, and their change in cortisol levels
after the water bath manipulation, r(28) = −0.38 (p's b 0.05; Fig. 4).
4. Discussion
The purpose of the present experiments was to determine whether
acute stress applied immediately versus 30 min prior to learning would
exert differential effects on long-term (24-hr) memory. Based on the
available experimental evidence from rodent and human studies
[20,21,23–25], we hypothesized that stress applied immediately prior to
learning would enhance long-term memory, while stress applied 30 min
prior to learning would impair long-term memory. From a general
standpoint, the present data supported our hypotheses. However, the
observed effects were scattered across free recall and recognition testing
of words differing in emotional valence, and there were several drawbacks
of the experimental design of the present studies that limit the conclusions
one can make about the general nature of pre-learning stress effects on
long-term memory. Nonetheless, the present studies do provide a wellneeded extension to humans of the assessments of the temporal dynamics
model of emotional memory processing that have previously been
performed in rodents. They also provide insight, however preliminary,
into the nature of pre-learning stress effects on long-term memory that
could be useful for future investigators developing studies to further
advance our knowledge in this area of scientific inquiry.
When participants in the present experiments were stressed
immediately prior to learning, they exhibited enhanced recognition of
positive words 24 h later; yet, when participants were stressed
30 min prior to learning, they exhibited impaired free recall of
negative words 24 h later. Interestingly, participants' recognition of
positive words in Experiment 1 was positively correlated with their
HR during the water bath manipulation, while participants' free recall
of negative words in Experiment 2 was negatively correlated with
their systolic and diastolic BP during the water bath manipulation, as
well as with their increase in salivary cortisol levels following the
water bath manipulation. Although these correlations do not afford
one to make causal inferences, they could be suggestive of an
involvement of different mechanisms in the differential effects of prelearning stress on long-term memory.
Previous work has provided some support for this view, showing
that the pre-learning stress-induced enhancement, but not impairment, of long-term (24-hr) memory is dependent upon β-adrenergic
receptor activity [17]. In this particular study, rats were exposed to a
cat (i.e., predator stress) for 2 or 30 min prior to being trained in a
water maze. As the authors had shown previously [25], 2 min of cat
exposure enhanced, while 30 min of cat exposure impaired, 24-hr
memory retrieval. More importantly, however, peripheral administration of the β-adrenergic receptor antagonist propranolol blocked
the effects of 2 min, but not 30 min, of cat exposure on long-term
memory. These findings suggested that while blockade of β-adrenergic receptor activity was sufficient to prevent the pre-learning stressinduced enhancement of long-term memory, other mechanisms, such
as the delayed genomic effects of glucocorticoids, could have been
473
more important for the pre-learning stress-induced impairment of
long-term memory. Fittingly, we found that the impairment of
negative word free recall in Experiment 2 was observed only in
participants who demonstrated a significant increase in salivary
cortisol levels following the SECPT; however, such a relationship was
not observed for the memory effects observed in Experiment 1. This
suggests that there was potentially a greater involvement of cortisol in
the observed pre-learning stress-induced impairment of memory,
relative to the pre-learning stress-induced enhancement of memory.
On the other hand, that cortisol Responders and Non-Responders in
Experiment 2 also differed on measures of BP during the SECPT could
imply that concomitant actions of glucocorticoids and sympathetic
nervous system activity are necessary for the memory impairment that
was observed. Future work will be needed to explore this possibility,
particularly in the context of the present experiments' methodologies.
It would be useful, for instance, to include additional measures of
central sympathetic nervous system activity (e.g., salivary alphaamylase) to correlate with memory performance or to administer
pharmacological agents that block β-adrenergic and/or glucocorticoid
receptor activity prior to the pre-learning stress manipulations to
ascertain the importance of these mechanisms in the observed effects.
Independent of condition, participants in the present experiments
demonstrated greater long-term memory for emotional words, as
compared to neutral words. Moreover, stress exerted greater effects
on long-term memory for information that was emotional in nature,
as it enhanced the recognition of positive words in Experiment 1 and
impaired the recall of negative words in Experiment 2. As indicated
above, when previous work has reported significant effects of prelearning stress on long-term memory, the most common, but not
unanimous, finding has been enhanced memory for emotionally
arousing information, at the cost of (i.e., impaired memory for)
emotionally neutral information. Indeed, Payne and colleagues
[23,24] reported that exposing participants to the Trier Social Stress
Test (TSST) immediately prior to learning enhanced long-term
memory for emotional information while impairing long-term
memory for neutral information. On the other hand, Schwabe et al.
[20] found that exposing participants to the SECPT 10 min prior to
learning a list of words led to enhanced long-term recall of neutral
words but had no effect on the recall of emotional words. It is likely
that differences in methodology explain why we, as well as Schwabe
et al., did not observe effects similar to the ones reported by Payne and
colleagues. For instance, Payne and colleagues examined the influence
of a different stressor (i.e., the TSST), which lasted significantly longer
(i.e., approximately 20 min) than the stressor employed in the present
experiments and that of Schwabe et al., on learning. In addition, Payne
and colleagues examined the effects of stress on participants' learning
of complex auditory and visual slideshows, as opposed to a list of
words, which were employed here and in the study by Schwabe et al.
Why we did not observe effects in the present studies that were
similar to those of Schwabe et al. could be explained by the different
number of words used in each study (30 words per list here vs. 85
words per list in Schwabe et al.) and/or by the difference in temporal
proximity of the stressor to the learning experience in each study
(immediately or 30 min before learning here vs. 10 min before
learning in Schwabe et al.). One important implication of the
differences between these three studies might be that pre-learning
stress does not straightforwardly enhance long-term memory for
emotional information, while impairing long-term memory for
neutral information; rather, the effects of pre-learning stress on
long-term memory may be much more complex and depend on
several factors including the type and duration of stress, the temporal
proximity of the stressor to the learning experience and the type of
information (e.g., words vs. pictures, emotional vs. neutral) that is
being acquired by the individual/organism.
That the memory effects detected in the present studies were
greater for emotional words than neutral words is consistent with
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P.R. Zoladz et al. / Physiology & Behavior 103 (2011) 467–476
much of the research literature and implicates an involvement of
amygdala activity in the observed modulation of long-term memory
[35–40]. Previous work has shown that an intact amygdala is essential
for enhanced memory of emotional information, as well as for the
stress-induced effects on hippocampus-dependent learning and
synaptic plasticity [18,19,41–43]. The differential effects of stress on
long-term memory that were observed in the present experiments
could possibly be explained by a biphasic modulatory effect of
amygdala activation on hippocampal function. Electrophysiological
studies have reported that when electrical stimulation of the
amygdala immediately precedes attempts to induce synaptic plasticity in the hippocampus, such plasticity is significantly enhanced
[26,27]. However, when there is a substantial delay between electrical
stimulation of the amygdala and attempts to induce synaptic plasticity
in the hippocampus, such plasticity is impaired (however, see [44] for
a description of how these effects may depend on hippocampal
subregion). Since the presentation of the word list in Experiment 1
immediately followed cessation of the stressor, the biological
mechanisms responsible for learning the word list would theoretically
be enhanced due to an amygdala-induced enhancement of hippocampal plasticity. Likewise, since the presentation of the word list in
Experiment 2 did not occur until 30 min following cessation of the
stressor, the biological mechanisms responsible for learning the word
list would theoretically be impaired due to an amygdala-induced
impairment of hippocampal plasticity. Exactly why the observed
memory enhancement and impairment depended on the emotional
valence (i.e., positive vs. negative) of the words will need to be
explored in future research.
The amygdala-induced modulation of hippocampal function
appears to be associated with concurrent time-dependent actions of
specific neurochemical substances that are released following the
onset of stress. Early neurochemical responses to stress, such as rapid
glucocorticoid actions and the massive increase in levels of corticotropin-releasing hormone (CRH), norepinephrine and glutamate,
seem to favor hippocampal plasticity and the storage of new
information [29,30,45–58]. Indeed, recent electrophysiological work
has shown that glucocorticoids exert rapid non-genomic enhancing
effects on hippocampal synaptic plasticity that involve a mineralocorticoid receptor-dependent increase in glutamate transmission. The
delayed effects of stress, however, involve a suppression of hippocampal plasticity and an impairment of information storage, primarily
as a result of genomic glucocorticoid activity and NMDA receptor
desensitization [59–65]. When learning immediately follows stress,
the massive presence of plasticity-enhancing neurochemicals (e.g.,
glucocorticoids, CRH, norepinephrine, glutamate), combined with
amygdala-induced stimulation of hippocampal function, would
theoretically facilitate the storage of new information. However,
when there is a substantial delay between stress and learning, the
presence of the aforementioned neurochemicals would be ineffective
in enhancing hippocampal plasticity due to the genomic actions of
glucocorticoids suppressing hippocampal function and rendering the
storage of new information much more difficult.
The above interpretations of the present data should be considered
with caution. Although the observed statistically significant effects in
the present study (i.e., stress applied immediately before learning
enhanced recognition of positive words, while stress applied 30 min
prior to learning impaired free recall of negative words) did support
our general hypotheses associated with the temporal dynamics model
of emotional memory processing, they were scattered across different
types of memory assessments (i.e., free recall vs. recognition) for
words in different emotional valence categories (i.e., positive vs.
negative words). Moreover, in Experiment 2, we observed a trend
suggesting that stress applied 30 min prior to learning marginally
enhanced 24-hr free recall of positive words. The differential effects of
stress applied 30 min prior to learning on the free recall of positive
(marginally enhancing) and negative (significantly impairing) words
could be attributable to different levels of arousal generated by the
words [20], which we did not assess in participants. It could also imply
that the effects of pre-learning stress on long-term memory depend
on a much more complex interaction between the temporal proximity
of the stressor to the learning experience and the emotional nature of
the to-be-learned information. On the other hand, that the effect of
pre-learning stress on positive word free recall in Experiment 2 did
not attain statistical significance could mean that our speculation is
unwarranted. Nevertheless, we are currently studying how arousal
level of positive and negative words mediates the effects of prelearning stress on long-term memory.
That stress applied immediately prior to learning significantly affected
recognition memory, while stress applied 30 min prior to learning
significantly affected free recall might seem to imply that pre-learning
stress exerts differential effects on brain regions involved in recall versus
recognition, depending upon the temporal proximity of the stress to the
learning experience. Some investigators have contended that recall is
dependent primarily on the hippocampus, while recognition is more
reliant on the perirhinal cortex (although, this depends on whether
recollection or familiarity is being assessed) [66–69]. However, this
dissociation is not agreed upon by the entire scientific community [70,71].
A number of investigators have proposed that, even if the perirhinal cortex
is involved in and primarily responsible for recognition memory, the
hippocampus is still necessary for the task. Thus, it is difficult to speculate
as to why stress exerted differential effects on recall versus recognition in
the present experiments. It is possible that stress applied immediately
prior to learning affected different brain regions than stress applied
30 min prior to learning; however, it is also possible that the observed
effects on 24 h memory were simply different manifestations of similar
stress-induced alterations of encoding and/or memory consolidation.
An additional concern with regards to the present studies is the
poor free recall performance exhibited by participants in each
experiment. The maximum average percent of recalled words,
which was observed in Experiment 2, was just below 20% (or
approximately 2 words out of a possible 10 words per valence
category). To inform the reader of the memory patterns demonstrated
by participants in each experiment, we have included the raw number
of words recalled, in addition to the raw number of hits and false
alarms exhibited during recognition testing, in Table 3. Based on these
numbers, it is clear that we may not have observed any group
differences on some free recall measures because of floor effects,
which could have resulted from not informing participants that their
memory for the list of words would subsequently be tested (i.e., we
examined incidental learning) and/or not including a measure of
immediate free recall, which could have strengthened participants'
storage of the information. The possibility that we encountered floor
effects in the present studies certainly limits, at least to some degree,
the confidence that can be placed in any conclusions drawn from the
present data set, and future studies, perhaps those assessing explicit
learning and utilizing immediate free recall tests for word lists
containing more or less words than the number used here, will need
to be employed to corroborate the effects observed in the present
experiments.
Lastly, the sample sizes utilized in each of the present studies were
relatively small. This could have led to insufficient statistical power to
detect significant effects in some places. On the other hand, given a
relatively modest sample size, it is encouraging that we still observed
significant effects of pre-learning stress on the aforementioned
measures of long-term memory. There were also more females who
participated in the study than males, and there was an uneven
distribution of males and females to the stress and no stress
conditions in each experiment. This problem was most likely a
consequence of the significantly skewed gender distribution at the
university from which the sample was acquired. It is well known that
sex is a factor that mediates the effects of stress on learning. Moreover,
various stages of the female menstrual cycle, which were not
P.R. Zoladz et al. / Physiology & Behavior 103 (2011) 467–476
Table 3
Free recall and recognition raw data from Experiments 1 and 2.
Condition
Neutral words
Experiment 1: Stress immediately before learning
Free recall
Stress
0.93 (0.25)
No stress
0.90 (0.18)
Recognition — hits
Stress
8.60 (0.29)
No stress
8.76 (0.24)
Recognition — false alarms
Stress
2.00 (0.31)⁎
No stress
1.24 (0.23)
Experiment 2: Stress 30 min before learning
Free recall
Stress
0.50 (0.13)
No stress
0.65 (0.17)
Recognition — hits
Stress
7.63 (0.45)
No stress
7.80 (0.35)
Recognition — false alarms
Stress
1.38 (0.20)
No stress
1.95 (0.34)
Positive words
Negative words
1.47 (0.22)
1.60 (0.23)
1.40 (0.25)
1.55 (0.20)
8.67 (0.29)
8.33 (0.28)
7.87 (0.41)
8.19 (0.25)
1.07 (0.30)
1.48 (0.29)
2.00 (0.32)
1.90 (0.37)
1.88 (0.31)a
1.16 (0.23)
1.00 (0.22)⁎
1.84 (0.18)
8.31 (0.33)
8.25 (0.30)
8.06 (0.42)
8.10 (0.16)
1.25 (0.31)
1.65 (0.26)
1.75 (0.39)
2.40 (0.36)
Data are presented as means ± SEM.
⁎ p ≤ 0.05 relative to the no stress group.
a
p = 0.07 relative to the no stress group.
controlled for in these experiments, also differentially affect stressinduced alterations of learning. Therefore, it is not known whether or
not these variables played a role in the observed results.
5. Conclusions
In summary, we have shown that pre-learning stress exerts effects
on long-term (24-hr) memory that depend, at least in part, on the
temporal proximity of the stressor to the learning experience and the
emotional nature of the to-be-learned information. Specifically, in the
present studies, stress applied immediately prior to learning enhanced recognition of positive words, while stress applied 30 min
prior to learning impaired free recall of negative words. Correlational
analyses revealed that participants' recognition of positive words in
Experiment 1 was associated with their HR responses to the water
bath manipulation, while participants' recall of negative words in
Experiment 2 was associated with their BP and cortisol responses to
the water bath manipulation. These data, though preliminary in
nature, are in general agreement with the recently proposed temporal
dynamics model of emotional memory formation and suggest the
possibility of different biological mechanisms contributing to the
differential effects of pre-learning stress on memory. However, since
the observed effects were scattered across different types of memory
assessments for words differing in emotional valence and were
potentially limited by the presence of floor effects, additional research
will need to be performed in order to validate the findings reported
here.
Acknowledgements
The authors would like to thank Dan Chido and Brandon Pritchard
for their assistance in the social evaluative component of the stress
procedure.
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