NEONATAL ASPIRATION LESIONS OF THE HIPPOCAMPAL FORMATION
IMPAIR VISUAL RECOGNITION MEMORY WHEN ASSESSED BY PAIRED-
COMPARISON TASK BUT NOT BY DELAYED NONMATCHING-TO-SAMPLE TASK
Olivier Pascalis and Jocelyne Bachevalier
Department of Neurobiology and Anatomy
University of Texas Health Science Center, Houston, TX, USA
Published in Hippocampus. Volume 9, Issue 6, Pages: 609-616
Abbreviated Title: Hippocampal lesions and recognition memory
Number of text pages: 18
Number of figures: 4
Number of tables: 1
Corresponding author: Jocelyne Bachevalier, Department of Neurobiology and Anatomy,
University of Texas Health Science Center, 6431 Fannin Street, Houston, TX 77030, USA.
Phone: 713-500-5626, Fax: 713-500-0623, Email: [email protected]
Grant sponsor: NIMH, Grant number: IRP, MH54167, and MH58846
Grant Sponsor: John D. and Catherine T. MacArthur Foundation (JB) and the “Fondation
Fyssen” (OP)
Olivier Pascalis is now at The University of Sheffield, Department of Psychology, Sheffield S10
2TP, UK.
Key Words: preference for novelty – parahippocampal gyrus - monkeys
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ABSTRACT:
Previous experiments showed that neonatal aspiration lesions of the hippocampal formation in
monkeys yield no visual recognition loss at delays up to 10 min, when recognition memory was
assessed by a trial-unique delayed nonmatching-to-sample (DNMS) task. The present study
examined whether the neonatal hippocampal lesions will also have no effects on visual
recognition when assessed by a visual paired-comparison (VPC) task. In the VPC task, animals
are looking at visual stimuli and their preference for viewing new stimuli is measured. Normal
adult monkeys showed strong preference for looking at the novel stimuli at all delays tested. By
contrast, adult monkeys with neonatal hippocampal lesions, which included the dentate gyrus,
CA fields, subicular complex, and portions of parahippocampal areas TH/TF, showed preference
for novelty at short delays of 10 sec but not at longer delays of 30 sec to 24 hrs. This visual
recognition loss contrasts with the normal performance of the same operated animals when tested
in the DNMS task. The discrepancy between the results obtained in the two recognition tasks
suggest that, to perform normally on the DNMS task, the operated monkeys may have used
behavioral strategies that do not depend on the integrity of the hippocampal formation. In this
respect, the VPC appears to be a more sensitive task than DNMS to detect damage to the
hippocampal region in primates.
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INTRODUCTION
Monkeys with extensive damage to the medial temporal lobe (including hippocampus,
amygdala, and surrounding cortex) show severe impairment on the trial-unique delayed
nonmatching-to-sample task (DNMS) as soon as the delays were increased from 10 sec to 30 sec
(Mishkin, 1978; Squire, Zola-Morgan and Chen, 1988). Recent studies revealed that this
recognition memory deficit is due to damage to cortical areas adjacent to the hippocampal
formation (Zola-Morgan et al., 1989; Gaffan and Murray, 1992; Meunier et al., 1993). Thus,
selective lesions of either the entorhinal and perirhinal cortex (Gaffan and Murray, 1992), or the
perirhinal cortex and parahippocampal cortex (Zola-Morgan et al., 1989; Suzuki et al., 1993)
yielded severe recognition memory loss even at the short delays. [Conversely, selective
damage to the hippocampal formation resulted in either a mild impairment at the longest
delays only (Zola-Morgan et al., 1992; Alvarez et al., 1995), or no impairment (Murray and
Mishkin, 1998).] Similar results have now been reported in rodents (Mumby et al., 1992; Otto
and Eichenbaum, 1992a, b; Mumby and Pinel, 1994). This pattern of results seems also to apply
when the lesions are done in infancy, since neonatal damage restricted to the hippocampal
formation and sparing most of the entorhinal and perirhinal cortex yielded no impairment in the
DNMS even at long delays of 10 min (Bachevalier et al., 1999). These data suggest that the
DNMS task that has been used to assess hippocampal-dependent memory functions in primates
is in fact measuring memory processes of the cortical areas on the parahippocampal gyrus.
Although the findings imply that the hippocampal formation plays a relatively minor role
in recognition memory, they appear to contradict data in amnesic humans showing either mild
(Aggleton and Shaw, 1996) or enduring (Reed and Squire, 1997) visual recognition loss in
human subjects with damage to the hippocampal region. In a reinvestigation of the effects of
hippocampal damage on recognition memory in humans, Reed and Squire (1997) clearly
5
indicated that, for the same subject, a recognition memory deficit could be evident with one
recognition task but not another. They stressed the need to use several recognition tasks to
reveal the visual recognition memory deficit that follows hippocampal damage. Because only
one task, the DNMS, was used in all previous lesion studies in monkeys, it is possible that this
specific task failed to fully engaged the specific memory processing functions mediated by the
hippocampal formation, such that accurate performance might have been supported by alternate
strategies that are independent of the hippocampus (Ridley and Baker, 1991). The main goal of
the present study was to investigate such a possibility.
A visual recognition task widely used to assess memory in human infants is the visual
paired comparison (VPC) task (Fantz, 1964; Fagan, 1970). [The VPC task exploits the subject's
preference to look longer at novel stimuli]. The subject is first presented with a stimulus for a
brief familiarization period. Thereafter, a pair of stimuli, the familiar and a novel one, is
presented for viewing. The relevant parameter in this task is the amount of time spent looking at
both stimuli. Longer duration of looking to one stimulus, generally the novel one, indicates
recognition memory. This task has also been used to investigate the development of recognition
memory in infant monkeys (Gunderson and Sackett, 1984) and to measure long-term memory
(24 hours) in both human infants (Pascalis et al., 1998) and infant monkeys (Gunderson and
Swartz, 1985). Interestingly for the purpose of the present experiment, the ontogenetic studies
have provided different findings depending on the recognition tasks used. That is, in both human
infants (Diamond, 1990; Overman et al., 1993; Pascalis and de Schonen, 1994) and infant
monkeys (Gunderson and Sackett, 1984; Bachevalier et al., 1993), good performance on the
VPC task emerges earlier in life than that on the DNMS. This difference in the developmental
time table of these two recognition memory tasks is important because it suggests that the
DNMS task might require cognitive processes different than, or in addition to those required for
6
the VPC task (Bachevalier et al., 1993). These different cognitive processes may entail different
neural circuits subserving the two tasks, and, thus, the two recognition tasks may not be equally
sensitive to hippocampal damage.
As yet, few studies have employed the VPC to investigate the effects of hippocampal
lesions on recognition memory. Recognition memory loss was found in both infant and adult
monkeys with damage to the medial temporal lobe, including the hippocampal formation,
amygdala and surrounding tissue, with both the VPC (Bachevalier et al., 1993) and DNMS
(Bachevalier and Mishkin, 1994) tasks. Similarly, using the VPC task, McKee and Squire
(1993) demonstrated a recognition memory loss in amnesic subjects with hippocampal damage.
The VPC task was thus used in the present study to assess the contribution of the hippocampal
formation to recognition memory in adult monkeys with early nonselective hippocampal lesions
(Bachevalier et al., 1998) that had showed normal performance on the DNMS task.
METHOD
Subjects
Six rhesus monkeys (Macaca mulatta) of both sexes participated in the present study.
Three monkeys (2 males and 1 female) had received neonatal hippocampal lesions (Group H)
and three (2 males and 1 female) were unoperated controls (Group N). Subjects were 11 years of
age and weighing 3.8 – 7.1 kg at the beginning of the experiment.
A detailed description of their rearing conditions as infants and juveniles was given in an
earlier report (Bachevalier et al., 1999). Briefly, all monkeys were born at the breeding colony
of National Institute of Health Animal Center (Bethesda, MD) and raised in the primate nursery
of the Laboratory of Neuropsychology (National Institute of Mental Health, Bethesda, MD).
During the first year of life, they were tested on a series of cognitive tasks including the 24-hr
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ITI task at the age of 3 months, and the visual DNMS task at 10 months of age (Bachevalier et
al., 1999). In addition, their social interactions with peers were measured at 2 months, 6 months,
and 5 years (Bachevalier, 1994). Upon reaching adulthood, they were sent to the Department of
Neurobiology and Anatomy (University of Texas, Houston) where they received further
cognitive testing, which included re-tests on the 24-hr ITI and visual DNMS tasks at 6 and 7
years of age, respectively, and training on a DNMS for locations task at 9 years of age, before
participating in the present experiment. At the time of testing, they were housed in individual
cages and maintained on a diet of Purina Monkey Chow plus fresh food. Water was always
available, except for 5 hours prior to testing.
Surgery and Lesion assessment
A detailed description of the neonatal surgical procedures is available elsewhere
(Bachevalier et al., 1998). The two-stage neonatal aspiration lesions were performed aseptically
under anesthesia when the animals were approximately 7 and 20 days of age. The hippocampal
removal included the dentate gyrus, all CA fields, the subicular complex as well as the
underlying parahippocampal gyrus (cortical areas TH and TF) lying medial to the
occipitotemporal sulcus. The extent of the lesions was verified histologically in one case (see
case H-6, Bachevalier et al., 1998, Fig. 2) and through Magnetic Resonance Imaging in the two
remaining cases (cases H-1 and H-3, Bachevalier et al., 1998, Fig. 3) when the animals were 5-7
years old. MR images through the extent of hippocampal removal of one representative case (H-
3) are shown on Figure 1. In all cases, the lesions were as intended, including the hippocampus
proper, subicular complex, and portion of cortical areas TH and TF. The entorhinal cortical area
28 and perirhinal cortical areas 35 and 36 were spared, except for the most caudal dorsomedial
portion of the entorhinal cortex, bilaterally in cases H-3 and H-6, and unilaterally in case H-1.
8
Finally, small unintended damage was found in the inferior temporal cortical area TEO,
unilaterally in cases H-3 and H-6 and bilaterally in case H-1. This damage was judged to be
potentially significant only in case H-1 where it extended caudally on the ventromedial surface
of the right hemisphere to include the occipital cortex (see Fig. 3, Bachevalier et al., 1998).
Apparatus
Behavioral testing was carried out in a standard Wisconsin General Testing Apparatus
(WGTA), which was located inside a darkened sound-shielded room. Extraneous sound masking
was provided by a white-noise generator. As previously described (Pascalis and Bachevalier,
1998), a Plexiglas cage was used to constrain the monkey during behavioral testing. At the
center-front of the cage, a sipper tube was attached and delivered orange juice during training.
This procedure restrained the animal in front of the testing area while its eye movements were
videorecorded during stimulus presentation. The front of the cage was positioned 30 cm in front
of a translucent screen onto which the stimuli (slides of objects) were rear projected. A camera
mounted above the screen captured the monkey's eye movements during testing. Measures of
the cumulative looking time at the stimulus during the familiarization period were made during
testing by the experimenter. The time spent looking at each stimulus (novel or familiar) during
retention tests was measured with the aid of a frame by frame video-recording system which
allowed detailed analyses of the corneal reflection of the stimuli. Figure 2 illustrated the corneal
reflection of the stimuli when the monkey looked at the stimulus on its left (top), at the center
(middle), or on its right (bottom). Percent looking time at a stimulus was expressed by dividing
the looking time to one stimulus (novel or familiar) by the total looking time at both stimuli and
multiplying this ratio by 100.
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Black and white slides of objects were used as stimuli. The size and brightness of the
objects were kept uniform on each slide. When projected onto the screen, the size of the stimuli
was 15 cm X 10 cm, and when two stimuli were present, they were separated by a 12-cm gap.
Visual paired-comparison task
An adaptation period of 4-5 days was given to acclimate the monkey to sit quietly in the
front of the cage and to drink from the sipper tube while looking at stimuli. Thereafter, formal
training began. Each trial involved new stimuli and was made of two parts. In the
familiarization period, a sample stimulus was presented in the middle of the screen and remained
on until the monkey had looked at it for a total cumulative time of 20 sec. After a delay, two
retention tests separated by a 5-sec interval were given. In the retention tests, the familiar
stimulus and a new stimulus were simultaneously projected onto the screen and their left-right
positions were reversed from one retention test to the other. A retention test began when the
monkey started to look at one of the two stimuli and lasted 5 sec. Monkeys were first tested at
delays of 10 sec, 2 min, 10 min, and 24 hrs. During daily session, the left-right position of the
new stimulus in the first retention test and the delays were counterbalanced across trials. For the
24-hour delay, the familiarization period of one stimulus was given at the end of a daily session,
and the two retention tests for this stimulus were given the next day at the beginning of the daily
session. Monkeys were tested for a total of 10 trials at each delay. All monkeys, except case H-
6, were then tested with two additional delays (30 sec and 1 min) in the same manner as before.
The percent looking time at the novel stimuli at each delay was then compared with the
percent choosing novel objects when the same animals were tested on the DNMS task earlier as
adults, using the same delays, except the longest delay of 24 hrs (Bachevalier et al., 1999,
Experiment 2).
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RESULTS
Familiarization
The total amount of time needed for the control and operated monkeys to reach the
criterion of 20 cumulative seconds of looking at the stimulus across all delays averaged 38.5 ±
15.8 sec for the control monkeys and 44.6 ± 17.7 sec for the operated animals. A two-way
ANOVA using group and delay as the main factors and with repeated measures for the second
factor revealed no significant effects of group [F(1, 3) = 4.76, ns] and delay [F(5, 5) = 4.04, ns]
and no significant interaction [F(5, 5) = 1.08, ns].
Total Looking time during the two retention tests
For each delay, the total looking time at the two stimuli during the two retention tests was
summed and then averaged across the 10 trials. As shown in Figure 3, both Groups N and H
explored the stimuli for the same amount of time at each delay (mean of 3.14 ± 1.1 sec and 3.14
± 0.95 sec for Group N and Group H, respectively).
Percent looking time at each stimulus during the two retention tests
[The mean percent looking time at novel stimuli at each delay is depicted in Figure 4A
for each group. A two-way ANOVA using Group and Delay as main factors and with repeated
measures for the Delay factor revealed that both main factors were significant [Group: F (1, 3) =
28.051, p < .02; Delay: F(5, 15) = 3.365, p < .03], as was their interaction [F(5, 15) = 4.52, p <
.01]. This significant interaction indicated that in operated monkeys preference for novelty was
not present at all delays tested. Thus, separate analyses of variance at each delay revealed
significant group differences at all delays, except delay of 10 sec [10 sec: F(1-4) = 1.03, p > .05;
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30 sec: F(1-3) = 11.2, p < .05; 1 min: F(1-3) = 13.14, p < .04; 2 min (F(1-4) = 64.68, p < .001);
10 min: F(1-4) = 12.56, p < .03; 24 hours: F(1-4) =11.57, p < .03]. In addition, while in the
normal controls percent looking at novelty at 10 sec did not differ from any other delays, in the
operated monkeys percent looking at novelty was significantly greater at the 10 sec delay than at
any other delays (all p < .05). This different pattern of results in the two groups of animals was
also demonstrated when analyzing the amount of looking time at the novel vs the familiar objects
for each delay (Table 1). Whereas monkeys in Group N spent significantly longer time looking
at the novel stimulus than the familiar one at all delays, monkeys in Group H looked
significantly longer at the novel than the familiar objects at the shortest delay of 10 sec, but not
at any of the longest delays. These findings demonstrate that normal monkeys displayed
significant preference for looking at the novel stimuli at all delays, whereas those with
hippocampal damage engaged in this behavior only at the shortest delay of 10 sec.
DNMS
The results obtained with the VPC task contrasts sharply with that obtained earlier for the
same animals in the DNMS task (Bachevalier et al., 1998). In the performance test of the DNMS
task, as shown in Fig. 4B, animals in both Groups N and H did not differ significantly and
displayed excellent recognition of objects even at the longest delay of 10 minutes [Groups: F(1,
3) = 0.122, p = .75; Delays: F(4, 12) = 0.999, p = 0.44; Groups * Delays: F(4, 12) = 0.31, p =
0.86].
DISCUSSION
The results show that visual recognition memory, as assessed by VPC, is abolished in
animals with neonatal hippocampal lesion for delays of 30 sec or longer. These findings confirm
12
those of McKee and Squire (1993) indicating that human amnesics have impaired recognition
memory, as assessed by VPC, when delays were increased from 5 sec to 2 minutes. The visual
recognition loss found in hippocampectomized monkeys can not be attributed to a more general
deficit in visual exploration since these operated animals displayed a mean total fixation time at
the two stimuli during the retention tests similar to that found in control monkeys (see Fig. 3). In
addition, the memory loss after hippocampectomy can not result from a lack of preference for
novelty since the operated animals demonstrated good preference for novelty at the shortest
delay of 10 sec. Finally, the additional training that the monkeys received prior to VPC testing
(e.g. tactual DNMS) is unlikely to have caused the recognition loss. Given the extensive
experience the animals gained in purposely selecting novel objects in the past (visual and tactual
DNMS), one would expect that these animals had developed greater interest towards novelty,
which was not the case. Therefore, the data indicate that the VPC is a recognition memory task
sensitive to hippocampal lesions in primates. This conclusion should still be considered with
caution, however, since the hippocampal lesions in the present study were done by aspiration and
thereby included not only the hippocampal formation but also the parahippocampal cortical
areas. While the additional damage to these cortical areas could be responsible by itself for the
visual recognition loss (Zola-Morgan et al., 1989; Gaffan and Murray, 1992; Meunier et al.,
1993, 1997), recent findings suggest otherwise. Thus, selective hippocampal lesions, performed
by injections of excitotoxins (Nemanic, Alvarado, and Bachevalier, unpublished results) or by
radiofrequency (Clark et al., 1996), resulted in a loss of preference for novelty at long delays but
not at the short ones. Yet, whether restricted damage to the parahippocampal cortex alone could
result in a loss of visual recognition as well remains to be directly tested.
The visual recognition loss found in hippocampectomized animals with the VPC task
contrasts sharply with the remarkable visual recognition performance that the same operated
13
animals obtained earlier when tested in the DNMS task (Bachevalier et al., 1999). One possible
explanation for the normal performance of monkeys with neonatal hippocampal lesions on the
delay condition of the DNMS task could have resulted from overtraining on the task. Indeed, all
animals had received training on the DNMS task first when they were 10 months of age and then
when they reached adulthood (i.e. 7 years of age). Nevertheless, at both ages, their performance
on the task did not differ significantly from that of unoperated controls, indicating that their
normal performance at 7 years of age was not simply due to an effect of experience on the task.
Thus, the discrepancy in the results of the two recognition tasks suggests that processes required
for good performance on the VPC differ from those required to perform on the DNMS task. One
important difference between the two tasks relies on the behavioral responses required to solve
them. In the VPC task, visual orientation to the stimuli is the only behavioral response required
to perform on the task. Recognition of the familiar stimulus is inferred by a significantly longer
duration of looking time to the novel stimulus. The VPC, thus, involves an incidental or
automatic learning of stimuli naturally occurring in the visual field, and no rule learning is
necessary. In the DNMS, by contrast, the subject is not only required to visually orient towards
stimulus objects, but to also displace them in order to retrieve food rewards. Furthermore, the
animals must associate a positive reinforcement with an object during the sample presentation
and must effortfully remember this rewarded stimulus during the delay, to avoid it in favor of the
novel object being rewarded during the choice test. Hence, in DNMS, the subject must first
learned the rule to displace the novel objects on any given trial to a 90% criterion and, then,
perform when memory demands are increased with longer delays. Given this difference between
the two tasks, it could be possible that hippocampectomized monkeys with poor recognition
memory could purposely used a different behavioral strategy to solve the DNMS at delays up to
10 min (Ridley and Baker, 1991).
14
Performance on delayed matching (or nonmatching) tasks requires the subject to engage
in retrospective processing (Colombo et al., 1996), i.e. in remembering aspects of the sample
stimulus during the delay period. Since the animal is eager to retrieve the food reward and, thus,
is highly motivated, it may use a strategy that helps in remembering the stimulus it just saw. We
can postulate that the operated animals may be able to use such a strategy to solve the DNMS
task at the short delays usually tested. By contrast, in the VPC task, the animal does not know
that it has to remember the stimuli and, thus, it will not make use of that specific strategy to
remember them. In fact, in the presence of poor recognition memory, the hippocampectomized
animals may rely on a working memory buffer to maintain normal performance on the DNMS
task at delays up to 10 min. Such a proposal is easily testable by introducing during the delay
interval of the DNMS trials a manipulation that will interfere with the strategy that the animals
use to maintain the memory trace of the sample object. The performance of monkeys with
neonatal hippocampal lesions in the list conditions of the DNMS task (Bachevalier et al., 1999)
seems to support this view. In the list conditions, the animal is first presented with a series of
sample objects, varying from 3 to 10 objects, and, at the end of the list, each sample object is
then paired with a new one. Thus, in this version of the task, they have to maintain a larger
amount of visual information into a working memory buffer and, in addition, they have to
disentangle possible similarities between perceptual attributes of multiple objects. Scores of
monkeys with neonatal hippocampal lesions dropped of an average of 7% from the delay
conditions to the list conditions as compared to a drop of only 2 % in the normal controls.
Furthermore, we have directly tested this possibility by introducing a distractor during the delay
trials of the standard DNMS task. While scores of unoperated controls did not differ between
standard trials and distraction trials, those of monkeys with neurotoxic hippocampal lesions
dropped significantly on distraction trials as compared to standard trials (Nemanic et al., 1999).
15
These data thus suggest that the standard DNMS task may not be sensitive enough to detect
recognition memory impairment resulting from damage to the hippocampal formation.
The pattern of results thus suggests that hippocampectomized monkeys used alternative
strategies to perform normally on the DNMS task. These alternative strategies may recruit
additional brain areas, such as the perirhinal cortex and orbital prefrontal cortex, which have
already been shown to be crucial for normal performance on the DNMS task (Zola-Morgan et
al., 1989; Gaffan and Murray, 1992; Meunier et al., 1993, 1997).
16
Figure Legends
Figure 1: Coronal MR images (left) through the extent of hippocampal lesions in case H-3 and
coronal sections (right) through a normal monkey brain at levels corresponding to the MR
images. The gray shading on the coronal sections of the right column depicts the extent of
damage seen on the MR images. Abbreviations: amt, anterior medial temporal sulcus; ERh,
entorhinal cortex; ot, occipitotemporal sulcus; PRh, perirhinal cortex; rh, rhinal sulcus; st,
superior temporal sulcus; TE, anterior inferior temporal cortical area (from von Bonin and
Bailey, 1947); TF/TH, parahippocampal cortical area (from von Bonin and Bailey, 1947).
Figure 2: Videoframes (3/100 sec) of a monkey’s eye movements during the retention tests of the
VPC task. From top to bottom, the corneal reflections of the two stimuli (two white bars inside
the monkey’s pupils) indicate that the animal looked at the stimulus on its left, then, at the center,
and finally at the stimulus on the right.
Figure 3: Mean total fixation time (sec) at the two stimuli during the two retention tests at each
delay of the VPC. Vertical bars for each data point indicate standard deviation from the mean.
Abbreviations: Group N: normal controls; Group H: adult animals with neonatal hippocampal
lesions.
Figure 4: Percent looking time at the novel object during each delay conditions of the VPC task
(A) and percent correct choices at corresponding delay conditions of the DNMS task (B).
Vertical bars for each data point indicate standard deviation from the mean. Abbreviations as in
Fig. 3.
17
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Table 1: Mean (±) percent fixation time at the novel and familiar stimuli at each delay
Groups Delays Novel Stimulus Familiar Stimulus Two-tailed Paired T-test
10 sec 60.84 ± 1.99 39.16 ± 1.98 t = 5.4, df = 29, p < .001
30 sec 61.46 ± 2.35 38.54 ± 1.89 t = 4.8, df = 29, p < .001
Group N 1 min 61.83 ± 2.62 38.17 ± 2.62 t = 4.5, df = 29, p < .001
2 min 62.31 ± 2.11 37.69 ± 2.11 t = 5.8, df = 29, p < .001
10 min 62.38 ± 1.95 37.62 ± 1.95 t = 6.3, df = 29, p < .001
24 hr 61.40 ± 2.24 38.60 ± 2.24 t = 5.1, df = 29, p < .001
10 sec 62.31 ± 1.89 37.69 ± 1.89 t = 6.4, df = 29, p < .001
30 sec 51.00 ± 3.89 49.00 ± 3.89 t = 0.27, df = 29, p > .05
Group H 1 min 51.66 ± 2.78 48.34 ± 2.78 t = 0.59, df = 29, p > .05
2 min 54.73 ± 2.72 45.27 ± 2.72 t = 1.74, df = 29, p > .05
10 min 52.05 ± 2.64 47.95 ± 2.64 t = 0.77, df = 29, p > .05
24 hr 52.81 ± 2.30 47.19 ± 2.30 t = 1.22, df = 29, p > .05
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