KISEP
Original Article
Clinical Psychopharmacology and Neuroscience 2007; 5(1): 25-30
The Effect of Oxygen Inhalation on Cognitive Function and
EEG in Healthy Adults
Ho-Jun Seo, Won-Myong Bahk, Tae-Yun Jun, Jeong-Ho Chae
Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea
Oxygen is an essential component required for normal brain function. To explore the effect of oxygen on brain activity, we
evaluated the change in cognitive function and electroencephalographic patterns with and without added oxygen. Twenty
healthy subjects were enrolled for added oxygen, and twenty matched control subjects were selected. The K-Auditory Verbal
Learning Test and Learning Ability Diagnostic Examination including performance cognitive tasks was performed to assess
cognitive function in subjects and controls. For the 35% oxygen added group, verbal memory was significantly improved. In
addition, EEG testing showed that beta and gamma activity were decreased while delta activity increased in the oxygen added
group. These results suggest that oxygen supply may influence cognitive function and brain activity.
KEY WORDS： Brain; Cognitive function; Electroencephalography; Oxygen; Verbal memory; Performance cognitive task.
INTRODUCTION
brain activity consumes 20-30% of the energy usage for
the total body, and it requires approximately 200 liters
of oxygen per day for normal functioning.1) So, the brain
is very sensitive to oxygen, and a decrease of arterial
oxygen partial pressure (PO2) can alter brain function
such as attention and memory.7) Previous investigations
have concentrated on the effect of hypoxia on cognitive
function and a number of reports have demonstrated deterioration of cognitive function.8-12) In particular, it has
been reported that acute exposure to hypoxia appears to
have a larger negative impact on cognitive functioning
than chronic hypoxia over a longer period of time.13)
Little is known, however, about the exact effect of
oxygen supplementation on cognitive function. Some
researchers has been reported that variable changes of
cognitive function depend on the point of time and duration of inhalation of oxygen, and therefore, oxygen administration may differentially improve cognitive function
based on administration methods.14,15) But others reported
that the inhalation of oxygen alone was not effective,
and an enhanced effect on cognitive performance was
observed only when oxygen supply was combined with
glucose.16)
So, it has been suggested that the inhalation of oxygen
could improve cognitive function and increase brain activity, but how a variable concentration and duration of
inhalation of oxygen could affect brain activity has not
been demonstrated yet. In addition, there have been few
reports that evaluated the effect of oxygen inhalation on
The brain is the most metabolically active organ in the
human body, and accounts for up to 30% of basal energy
consumption; This energy is essentially dependent on
the oxidative breakdown of glucose,1) and converted to
neural activity which is variably distributed according to
the cognitive demands of specific tasks.2) Through the
various brain imaging techniques, it has been shown that
the brain increases the uptake of oxygen and glucose
into certain areas during variable cognitive tasks.3,4) Recently, it has been also suggested that supplemental glucose administration may enhance cognitive function. Some
researchers report that consumption of glucose containing drinks is particularly effective in enhancing performance on tests of declarative memory in older and
younger individuals,5) and glucose may also improve
performance on tests of non-mnemonic cognitive function, including reaction time.6) Although the brain accounts for only 2-3% of the total body weight in adults,
Address for correspondence: Jeong-Ho Chae, MD, Department
of Psychiatry, College of Medicine, The Catholic University of Korea,
#62 Yeouido-dong, Yeongdeungpo-gu, Seoul 150-713, Korea
Tel: +82-2-3779-1250, Fax: +82-2-780-6577
E-mail: [email protected]
This work was supported by grant from the Basic Research Program
of the Korea Science & Engineering Foundation (No. R01-2003000-10432-0) and supported by a grant of the Korean Health 21
R & D Project, Ministry of Health and Welfare, Republic of Korea
(A060273).
25
26·H.J. Seo, et al
neurophysiological markers such as the electroencephalography (EEG).
The present study was formulated to test the effect of
35% oxygen on various cognitive tasks and EEG. In order
to determine the effect of oxygen inhalation on cognitive
function, the Learning Ability Diagnostic System (Laxtha,
Taejon, Korea) and the Korean-Auditory Verbal Learning Test (K-AVLT)17) were used to healthy subjects before and after supplying oxygen. Simultaneously, to evaluate the effect of oxygen on physiological functions of
the brain, we recorded EEG findings at baseline and after
the inhalation of oxygen. We postulated that lower than
100% oxygen which used in previous studies would be
also effective, and predicted that inhalation of 35% oxygen would improve cognitive function and affect EEG
patterns.
SUBJECTS AND METHODS
Subjects
This study was performed after the approval by the
Institutional Review Board of the St. Mary’s Hospital,
The Catholic University of Korea; written informed consent was obtained from all participants. Healthy volunteers
between the age of 20 and 35 years and with an education level higher than college were enrolled. Twenty
individuals were randomly assigned to the oxygen added
group and 20 individuals were assigned to the control
group. In both groups, (1) individuals with a history of
trauma to the head, epilepsy, encephalitis, cerebrovascular diseases, and other disorders of the central nervous
system, (2) individuals with a history of mental health
disorders or currently taking psychotropic medications,
(3) individuals with asthma, bronchitis, or other respiratory diseases, (4) individuals with a history of alcohol
consumption within two days of the experiment, (5) individuals with narcolepsy or day time hypersomnia, and
(6) individuals with other active medical diseases were
excluded.
The average age for the oxygen added group and the
control group was 25.9 and 27.2 years, respectively. In
regard to the ratio of males to females, seven males and
13 females were in the oxygen added group, and five
males and 15 females in the control group. There were
no statistical differences in these demographic variables
between the groups.
Cognitive tests
The Learning Ability Diagnostic System (Laxtha,
Taejon, Korea) and the Korean-Auditory Verbal Learning Test (K-AVLT) were used to evaluate cognitive func-
tion. The Learning Ability Diagnostic System was a computerized assessment system which included a number
of measures specific to memory, concentration, and reaction time, and used performance cognitive tasks similar
to Standard Progressive Matrices (SPM).18) K-AVLT,
which was translated form of AVLT, had been confirmed
in their reliability and validity in Korea, and used to
evaluate verbal learning ability, recall and recognition
functions of memory. K-AVLT consisted of repeated five
measures for immediate word recall ability and two measures for delayed recall and recognition ability which
needed twenty minutes time interval.
Study design
Before the process, all subjects took a rest for 15
minutes and then pulse oxymetry (Model 8500, Nonin
Medical, Inc. Seoul, Korea) and a two channel EEG
(QEEG-2, Laxtha, Taejon, Korea) were installed. Baseline measures were assessed by pulse oxymetry, and test
for immediate word recall ability was taken five times
using K-AVLT. Subsequently, the Learning Ability Diagnostic Test (Laxtha, Taejon, Korea) and EEG were
measured and then the remainder of K-AVLT, the test for
delayed recall and recognition ability, was done. Throughout the process, the oxygen saturation level and heart
rate were measured at 10 minutes interval.
After the trial, all subjects were allowed 10 minutes
for rest; during the rest, the oxygen added group was
supplied 35% oxygen by a personal oxygen generator
(Oligo, Oxycure, Kyunggi, Korea), while the control
group was supplied only air. After the rest, above processes were taken repeatedly, and oxygen or air was supplied throughout the test (Fig. 1).
Statistical analysis
A difference in the oxygen saturation level dependent
on clinical variables such as the time spent for tests was
compared by repeated measures analysis of variance;
the changes of K-AVLT scores, the Learning Ability Diagnostic System scores, and power spectrum of EEG before and after the oxygen supply were analyzed by an
unpaired t-test. Statistical significance was set as p<0.05.
RESULTS
The oxygen saturation level
At baseline and during the process before oxygen delivery, there was no difference in the oxygen saturation
level between the oxygen added group and the control
group. After the subjects of both groups received oxygen
or air, the oxygen saturation level measured three times
Effect of Oxygen on Brain·27
Oxygen added and Control group
(n=40)
Rest for 15 min
↓
K-AVLT
Trial-1
Trial-2
Trial-3
Trial-4
Trial-5
↓
Learning Ability Diagnostic Test, EEG
↓
K-AVLT
Trial-6
Trial-7
Oxygen added (n=20)
Control (n=20)
Rest for 10 min
Start O2 Supplement
(during the rest and the remaining
process)
Rest for 10 min
Start Air Supplement
(during the rest and the remaining
process)
↓
↓
K-AVLT
K-AVLT
Trial-1
Trial-1
Trial-2
Trial-2
Trial-3
Trial-3
Trial-4
Trial-4
Trial-5
Trial-5
↓
↓
Learning Ability Diagnostic Test, EEG
Learning Ability Diagnostic Test, EEG
↓
↓
K-AVLT
K-AVLT
Trial-6
Trial-6
Trial-7
Trial-7
at 10 minute intervals, and at 10 minutes after oxygen
supply, the oxygen saturation level in the oxygen added
group was significantly higher than that of the control
group (t=2.12, df=38, p=0.04).
K-AVLT
The K-AVLT score changes between the before and
after added oxygen are shown in Table 1. Among the
tests repeated five times to evaluate short-term memory,
In trial 1, trial 3 and trial 4, the oxygen added group
showed significantly greater improvement in verbal memory than the control group (Trial 1: t=-2.27, df=38,
p=0.02; Trial 3: t=-2.90, df=38, p=0.006; Trial 4:
t=-2.15, df=38, p=0.03).
However, in regards of delayed recall (Trial 6) and
Fig. 1. Overview of the study process.
delayed recognition (Trial 7), a significant difference
between the study and control groups was not found.
Learning ability test
As to changes in learning ability test scores before and
after added oxygen, the difference between the oxygen
added group and the control group are shown in Table 2.
In all categories of the learning ability test, a significant
difference was not found.
The change of EEG
As to changes in EEG components, the difference between the oxygen added group and the control group are
shown in Table 3. For the oxygen added group, delta
activity of the left and right brain were increased (t=-
28·H.J. Seo, et al
2.02, df=38, p=0.05; t=-2.32, df=38, p=0.026). In
addition, in the oxygen added group, alpha activity in
the left brain (t=2.37, df=38, p=0.023), and beta activity in the left and right brain (t=2.68, df=38, p=
0.011; t=2.80, df=38, p=0.009), and gamma activity
in the left and right brain were decreased (t=2.41, df=
38, p=0.021; t=3.26, df=38, p=0.003).
DISCUSSION
The results of this study demonstrate that the administration of 35% oxygen to healthy young adults significantly improves verbal learning ability and affects physiological functions of the brain. There has been controversy regarding the effectiveness of oxygen for improvement of cognitive function; results depend on the type
of cognitive tasks, the order of performance and the point
of time and duration of oxygen delivery. Previous work
that investigated the effect of various durations of oxygen
supplementation during cognitive tasks reported that cognitive enhancement appeared to be dependent on the type
of task and the duration of oxygen supplementation.15)
Table 1. Comparison of oxygen added group and control group,
in changes of K-AVLT scores between the before and after of
oxygen supply
Oxygen added
group (N=20)
Trial 1
5.80±1.90
Control
group (N=20)
4.25±2.38
t
-2.27
The strongest effects were observed in measures of attention and vigilance and long term memory, with no apparent improvement on tests of reaction time and working memory. Beyond expectation, cognitive enhancement
tended to show an “inverted U shape” rather than a direct
proportionality to the duration of the supply of oxygen;
these results suggested that constant and maximum oxygen supply would not be the most efficient method to
enhance cognitive function. To explain this downgrade
of functional efficiency and differential cognitive enhancement with respect to the type of task, the investigators
suggested that prolonged oxygen over-supply would affect
mitochondrial functions and the permeability of the bloodbrain barrier, and that recognition and recall might be
dependent on different neural mechanisms.19,20)
Other work designed to explore the relationship between the degree of cognitive enhancement and variable
Table 3. Comparison of oxygen added group and control group,
in changes of power spectra of elecroencephalography between the before and after of oxygen supply
EEG power Oxygen added
Control
spectra
group (N=20) group (N=20)
t
p
Left
δ
-2.97±12.08
-7.27±19.07
-2.02 0.05*
θ
-1.54±07.94
-0.25±06.33
-0.56 0.574
α
-0.98±01.90
-1.74±04.75
-2.37 0.023*
0.02*
β
-1.95±04.35
-3.31±07.59
-2.68 0.011*
γ
-1.59±04.57
-2.00±04.84
-2.41 0.021*
p
Trial 2
4.45±1.66
4.50±2.23
-0.08
0.93
Trial 3
3.40±2.18
1.60±1.69
-2.90
0.006**
Trial 4
2.60±1.93
1.20±2.16
-2.15
0.03*
δ
-3.98±14.46
-8.97±20.31
-2.32 0.026*
0.33
θ
-0.87±08.40
-0.89±06.06
-0.75 0.452
0.41
α
-0.83±02.26
-1.43±05.75
-1.63 0.110
1.00
β
-2.10±04.62
-5.05±10.43
-2.80 0.009**
γ
-1.91±03.67
-3.38±06.26
-3.26 0.003**
Trial 5
Trial 6
Trial 7
1.55±1.76
2.10±1.80
0.50±1.10
1.10±1.07
1.65±1.63
0.50±1.05
-0.97
-0.82
-0.00
Trial 1-5: immediate recall, Trial 6: delayed recall, Trial 7: delayed recognition Data are represented the differences between K-AVLT scores before and after oxygen supply.
All data are shown as mean±SD.
*: p<0.05 level of significance, **: p<0.01 level of significance
Right
Data are represented the differences between EEG spectra before and after oxygen supply.
All data are shown as mean±SD.
*: p<0.05 level of significance, **: p<0.01 level of significance
Table 2. Comparison of oxygen added group and control group, in changes of Learning Ability Diagnostic Examination scores between
the before and after of oxygen supply
SPM subtests
Oxygen added group (N=20)
Control group (N=20)
t
p
Success
-3.50±09.09
-0.16±08.74
-1.30
0.20
Error
-3.33±07.79
-0.33±07.71
-1.49
0.14
Cognitive strength
-0.59±11.48
-5.42±08.56
-1.87
0.06
Response
-8.06±12.06
-3.58±10.56
-1.24
0.21
Concentration
-0.18±10.39
-1.14±07.11
-0.34
0.73
Workload
-1.14±05.90
-0.61±05.00
-1.01
0.31
Left brain activity
-1.17±04.94
-0.38±04.04
-1.08
0.28
Right brain activity
-1.22±04.80
-0.37±04.04
-1.13
0.26
Data are represented the differences between Learning Ability Diagnostic Examination scores before and after oxygen supply.
All data are shown as mean±SD.
Effect of Oxygen on Brain·29
point of time of oxygen delivery showed that significantly
more words were recalled when oxygen was inspired
immediately prior to, and following word presentation;
the investigators suggested that cognitive enhancement
was affected more by oxygen delivery during the word
presentation period rather than during the recall period.14)
However, Andersson et al.3) revealed possible methodological problems of the previous studies, and designed
a new battery of tests in which all tasks were verbally
based with reducing all spatial processing to minimum,
which was in order to disentangle eventual effects of
oxygen; 100% oxygen was supplied immediately prior
to all cognitive tasks for one minute, which included not
only word encoding but word recall. Contrary to results
of previous studies, the investigators reported that not
only recognition and working memory, but also attention
and long-term memory were not affected by the supply
of oxygen. To explain these results, the authors suggested
the previous hypothesis that enhanced blood oxygen saturation levels may be important only in combination with
an increased glucose level.16)
In our study, non-verbal intelligence, verbal learning
ability, recall and recognition functions of memory were
assessed with EEG monitoring, supplying 35% oxygen
from 10 minutes before the test entrance and till the end
of the test; this was lower concentration and longer duration than used in previous studies. To rule out the possibility of learning effects by repetition of cognitive tasks,
a control group was used. Results of the present study
correspond with those of earlier studies that reported that
recall function, but not recognition functions of memory,
was improved by oxygen supplementation. However, not
consistent with previous reports, there were no significant effects of oxygen administration on long-term memory. Another important finding in our study was that
cognitive enhancement occurred in some verbal memory
tasks after supplying significantly lower concentration
of oxygen than reported in previous studies; this suggests that it is not necessary to supply 100% oxygen to
enhance cognitive function, and the ideal duration of oxygen supplementation is linked to other factors, such as
oxygen concentration; however, the optimal concentration and duration of oxygen supplementation were not
determined in the present study and should be further
explored in future studies.
The hypothesis that glucose utilization of the brain is
responsible for enhanced cognitive performance and it is
dependent on a regular supply of oxygen has been supported by the results of recent studies using newer brain
imaging techniques,4,21) but it has not been shown how
oxygen could affect brain activity. In our EEG record-
ings, a trend towards decrease in beta and gamma activity, and an increase in delta activity were observed in
the oxygen added group. Excessive frontal beta activity
has been linked to anxiety and posttraumatic stress disorder, and can be observed in healthy subjects under
stress during induced tonic pain.22,23) In addition, frontocentral theta activity has been associated with states of
focused attention such as working memory tasks and
meditative concentration. And besides, in regard to affective aspects, frontal theta activity has been associated
with feelings of well-being, relief from anxiety and reduced sympathetic autonomic activation.24-27) From these
results, additional studies whether learned modulation of
electrocortical activity, by neurofeedback application,
could control symptoms of various mental disorders have
been investigated;28) in these studies, it was reported that
additional biofeedback applications, aimed at increasing
theta over alpha activity levels, could be used as a complementary therapeutic tools in posttraumatic stress disorder, alcoholism and similar problems.29) In addition,
with respect to psychological and physical well-being,
these findings have important implications for healthy
subjects in a stressful environment that it may contribute
to significant enhancement of performance by alleviating
excessive worry about the performance.30) Therefore, the
decrease of fast frequency EEG activity, by oxygen supplementation, appears to correlate with the relief of anxiety and tension, improves feelings of well-being and
enhancement of performance skills. The results that besides regulating glucose utilization, oxygen can mediate
physiologic changes in the brain such as EEG activities,
implies that oxygen supplementation can provide an alternative relaxation method in addition to meditation and
breathing control. Furthermore, in contrast to previous
neurofeedback methods, which require long training periods and hard labor, inhalation of oxygen can be easily
applied; therefore it may be a prominent alternative method for enhancing relaxation and learning.
In summary, the present study shows that supplying
35% oxygen affects performance enhancement on some
cognitive tasks as well as EEG changes. But this study
has several limitations: In present study, though the oxygen saturation level in the oxygen added group was
significantly higher than that of the control group at 10
minutes after the supply, at the other two assessments,
20 and 30 minutes after the supply, it did not show any
significant difference. Because in the lung, the oxygen
hemoglobin saturation curve favors near-100% hemoglobin saturation around normal alveolar oxygen tensions,
35% oxygen supply in current study may influence scarcely in increasing PO2 level of cerebral artery and brain,
30·H.J. Seo, et al
which creating the driving force for oxygen delivery.1)
However our results are worthy of notice because, as
even with our current knowledge, there is no single
definite model adequately describing oxygen transport
from the vasculature to cerebral tissue,31) and the relationship between oxygen supply and PO2 of cerebral
artery, ultimately the mitochondria of brain, is not known
exactly. And besides, small sample size, a young study
population with high education level and the fact that
neurophysiologic changes were assessed only using a
two-channel EEG could be other limitation. Future studies
will be required to ascertain the effect of oxygen on cognitive function, with a larger sample size, controlling
glucose, oxygen concentration, and duration of oxygen
supplementation. In addition, functional neuroimaging
techniques are needed for further assessment of neurophysiologic change and studies for normal physiologic
condition should be accompanied to clear up the relationship between oxygen supply and oxygen delivery,
especially to brain.
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