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The Effects of L-theanine on Alpha-Band Oscillatory Brain Activity During a Visuo-Spatial Attention Task

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Abstract

Background/Objectives Ingestion of the non-proteinic amino acid l-theanine (γ-glutamylethylamide) has been shown to influence oscillatory brain activity in the alpha band (8–14 Hz) in humans during resting electroencephalographic (EEG) recordings and also during cognitive task performance. We have previously shown that ingestion of a 250-mg dose of l-theanine significantly reduced tonic (background) alpha power during a demanding intersensory (auditory-visual) attentional cueing task. Further, cue-related phasic changes in alpha power, indexing the shorter-term anticipatory biasing of attention between modalities, were stronger on l-theanine compared to placebo. This form of cue-contingent phasic alpha activity is also known to index attentional biasing within visual space. Specifically, when a relevant location is pre-cued, anticipatory alpha power increases contralateral to the location to be ignored. Here we investigate whether the effects of l-theanine on tonic and phasic alpha activity, found previously during intersensory attentional deployment, occur also during a visuospatial task. Subjects/Methods 168-channel EEG data were recorded from thirteen neurologically normal individuals while engaged in a highly demanding visuo-spatial attention task. Participants underwent testing on two separate days, ingesting either a 250-mg colorless and tasteless solution of l-theanine mixed with water, or a water-based solution placebo on each day in counterbalanced order. We compared the alpha-band activity when subjects ingested l-Theanine vs. Placebo. Results We found a significant reduction in tonic alpha for the l-theanine treatment compared to placebo, which was accompanied by a shift in scalp topography, indicative of treatment-related changes in the neural generators of oscillatory alpha activity. However, l-theanine did not measurably affect cue-related anticipatory alpha effects. Conclusions This pattern of results implies that l-theanine plays a more general role in attentional processing, facilitating longer-lasting processes responsible for sustaining attention across the timeframe of a difficult task, rather than affecting specific moment-to-moment phasic deployment processes.
ORIGINAL PAPER
The Effects of L-theanine on Alpha-Band Oscillatory Brain
Activity During a Visuo-Spatial Attention Task
Manuel Gomez-Ramirez Æ Simon P. Kelly Æ
Jennifer L. Montesi Æ John J. Foxe
Accepted: 16 September 2008
Springer Science+Business Media, LLC 2008
Abstract Background/Objectives Ingestion of the non-
proteinic amino acid
L-theanine (c-glutamylethylamide)
has been shown to influence oscillatory brain activity in the
alpha band (8–14 Hz) in humans during resting electro-
encephalographic (EEG) recordings and also during
cognitive task performance. We have previously shown
that ingestion of a 250-mg dose of
L-theanine significantly
reduced tonic (background) alpha power during a
demanding intersensory (auditory-visual) attentional cue-
ing task. Further, cue-related phasic changes in alpha
power, indexing the shorter-term anticipatory biasing of
attention between modalities, were stronger on
L-theanine
compared to placebo. This form of cue-contingent phasic
alpha activity is also known to index attentional biasing
within visual space. Specifically, when a relevant location
is pre-cued, anticipatory alpha power increases contralat-
eral to the location to be ignored. Here we investigate
whether the effects of
L-theanine on tonic and phasic alpha
activity, found previously during intersensory attentional
deployment, occur also during a visuospatial task. Subjects/
Methods 168-channel EEG data were recorded from thir-
teen neurologically normal individuals while engaged in a
highly demanding visuo-spatial attention task. Participants
underwent testing on two separate days, ingesting either a
250-mg colorless and tasteless solution of
L-theanine mixed
with water, or a water-based solution placebo on each day
in counterbalanced order. We compared the alpha-band
activity when subjects ingested
L-Theanine vs. Placebo.
Results We found a significant reduction in tonic alpha for
the
L-theanine treatment compared to placebo, which was
accompanied by a shift in scalp topography, indicative of
treatment-related changes in the neural generators of
oscillatory alpha activity. However,
L-theanine did not
measurably affect cue-related anticipatory alpha effects.
Conclusions This pattern of results implies that
L-theanine
plays a more general role in attentional processing, facili-
tating longer-lasting processes responsible for sustaining
attention across the timeframe of a difficult task, rather
than affecting specific moment-to-moment phasic deploy-
ment processes.
Keywords Alpha
L-Theanine EEG Tea
Oscillations High-density electrical mapping
With a history of consumption stretching over thousands of
years, tea is now the most commonly consumed beverage
in the world after water, and continues to grow in popu-
larity. Consumers often associate tea with subjective
effects on ‘state of mind’ and mood, as much as the
obvious factor of taste. Anecdotal testimony regarding
these effects has recently been borne out in experimental
investigations, with findings of increased relaxation ratings,
stress relief, and alertness resulting from placebo-con-
trolled tea studies (e.g. Hindmarch et al. 2000; Steptoe
et al. 2007). Several recent studies have focused their
investigation on the non-proteinic amino acid
L-theanine
M. Gomez-Ramirez S. P. Kelly J. L. Montesi
J. J. Foxe (&)
Program in Cognitive Neuroscience and Schizophrenia, The
Cognitive Neurophysiology Laboratory, Nathan S. Kline
Institute for Psychiatric Research, 140 Old Orangeburg Road,
Orangeburg, NY 10962, USA
e-mail: foxe@nki.rfmh.org
M. Gomez-Ramirez S. P. Kelly J. J. Foxe
Program in Cognitive Neuroscience, Department of Psychology,
City College of the City University of New York, 138th Street
and Convent Avenue, New York, NY 10031, USA
123
Brain Topogr
DOI 10.1007/s10548-008-0068-z
(c-glutamylethylamide), a substance found almost exclu-
sively in tea and known to elicit neurochemical effects in
the brain within 1 h of consumption (Terashima et al.
1999).
Previous studies in healthy humans have suggested that
ingestion of
L-theanine can affect oscillatory brain activity
in the so-called alpha band (8–14 Hz) when subjects are in
a passive resting state (Kobayashi et al. 1998; Juneja et al.
1999). This brain rhythm has traditionally been associated
with a relaxed state (Pfurtscheller 1992), and has also been
linked to general states of mental alertness and/or arousal
(e.g. Klimesch et al. 1998). More recent research has
shown that alpha activity is not simply associated with
brain arousal states but indexes the operation of selective
attention mechanisms (Vanni et al. 1997; Foxe et al. 1998;
Worden et al. 2000; Fu et al. 2001; Bastiaansen and Brunia
2001; Bastiaansen et al. 2001; Kelly et al. 2005; Yamagi-
shi et al. 2005; Sauseng et al. 2005; Kelly et al. 2006; Thut
et al. 2006; Rihs et al. 2007; Kelly et al. 2008). For
example, several studies from our lab have shown that
alpha activity is highly involved in distracter suppression
mechanisms during visuo-spatial and intersensory atten-
tional deployments (see Worden et al. 2000; Fu et al. 2001;
Kelly et al. 2006). Furthermore, this oscillatory alpha
activity has been found to predict both the accuracy level
and reaction time in detecting a visual target stimulus (see
Thut et al. 2006; Kelly et al. 2007–Abstract Presentation at
the Cognitive Neuroscience Meeting in NY, 2007).
Following up on a series of experiments on alpha-
mediated attention mechanisms, we recently investigated
the effects of a 250-mg dose of
L-theanine on alpha activity
during a highly demanding intersensory attention task
(Gomez-Ramirez et al. 2007). In this study, a symbolic cue
stimulus instructed subjects to attend to either the auditory
or visual modality, thus preparing to preferentially process
an imperative stimulus that may appear *1 s later in that
modality, and to disregard any information emanating from
the uncued modality. Previous studies of this paradigm
revealed that attention deployments to the visual modality
result in a decrease in parieto-occipital alpha power in the
anticipatory period prior to imperative stimulus presenta-
tion, while deploying attention to the auditory modality
results in an increase (Foxe et al. 1998; Fu et al. 2001).
This differential in phasic (event-related) alpha-band
activity is proposed to reflect anticipatory gating of visual
processing by parieto-occipital structures known to be
involved in attentional switching and disengagement
within the visual modality. The data of Gomez-Ramirez
and colleagues (2007) showed an enhanced differential
alpha effect when subjects ingested
L-theanine compared to
placebo, suggesting that
L-theanine may have a specific
facilitatory effect on the brain’s attentional deployment
mechanisms. In addition to this effect on phasic
deployment processes, a significant overall drop in tonic
(background) alpha-band activity was observed, i.e. alpha
amplitude appeared reduced across all trial periods, in all
conditions.
The aims of the present study were twofold. First, we
wished to investigate whether a similar enhancement in the
cue-related, phasic alpha differential as seen in Gomez-
Ramirez et al. (2007) would be observed during a visuo-
spatial attention task, for which analogous, retinotopically
specific cueing effects are routinely observed (Worden
et al. 2000, Kelly et al. 2006; Thut et al. 2006). Second, we
wished to test for the finding of decreased tonic alpha on
L-theanine as was observed in our previous study (see
Gomez-Ramirez et al. 2007).
Methods
Participants
Thirteen (five females) neurologically normal, paid vol-
unteers (mean age = 23.5, SD = 3.25 years) participated.
Two participants were excluded from the analyses due to
excessive eye movements during the task. All participants
provided written informed consent, and the Institutional
Review Board of the Nathan Kline Institute approved the
procedures. All participants reported normal or corrected-
to-normal vision and all were right-hand dominant as
assessed by the Edinburgh handedness inventory (Oldfield
1971). Subjects were required to refrain from drinking any
caffeine-based products (such as soft drinks, soda, coffee or
tea) for at least 24 h before the day of testing. Subjects’
neurological status was assessed via a shortened version of
the Structured Clinical Interview for DSM-IV-TR (SCID).
Treatment
At the beginning of each experimental day, all participants
were given either a mixed solution of the
L-theanine sub-
stance or a placebo drink. The mixed drink solution
consisted of 250 mg of powdered clear
L-theanine with
200 ml of room-temperature water. The placebo drink
consisted only of the 200 ml of water (i.e. approximately
one cup). The day of drinking the
L-theanine solution was
counterbalanced across participants. Note that
L-theanine is
colorless and flavorless in a water solution. Anecdotally,
subjects were at chance in guessing whether they were
taking the active compound or simply water.
Experimental Paradigm
The sequence of events in a typical trial is illustrated in
Fig. 1. A trial commenced with the onset of a visual cue
Brain Topogr
123
stimulus (S1) indicating the location to which attention was
to be deployed in anticipation of an imperative stimulus
(S2) appearing 900 ms later. The inter-trial interval (ITI,
i.e. the time between S2 offset and following S1 onset) was
1,500 ms. A central fixation cross (white; 1 of visual
angle) remained on the screen throughout the experiment
and participants were instructed to maintain fixation at all
times. All visual stimuli were presented on an Iiyama
VisionMaster Pro502 21’ computer monitor, on a black
background.
The S1 (cue) consisted of a white arrow (duration
100 ms, 1 visual angle; see Fig. 1) pointing leftward or
rightward with equal probability toward one of two marked
peripheral locations in the upper hemifield. Cue stimuli
appeared in random order throughout the experiment.
The S2 (imperative stimulus) consisted of the letter T
rotated at either 0,90, 180 or 270 (white, 60 ms
duration, 0.66 visual angle) constructed from two
orthogonal line segments, and surrounded by four equally
spaced distracter circles (0.66visual angle). The S2
appeared inside a square outlined by 4 white dots (3.33,
centered at 4.1eccentricity) placed in the left and right
visual fields, which were permanently present throughout
the experiment (see Fig. 1).
At the beginning of each block, one specific ‘T’ orien-
tation was assigned as the target stimulus for that block. On
20% of trials the target stimulus appeared and subjects
were instructed to make a speeded button push if it
appeared at the cued location only. On 60% of the trials,
the orientation of the ‘T’ stimulus was different than the
target, and subjects were instructed to withhold any
response. The remaining 20% of trials were ‘catch trials’’,
where no S2 was presented. The subject was instructed to
attend to the stimuli appearing at cued location only, and to
ignore any information appearing in the uncued location.
Participants completed a minimum of 14 blocks of trials,
on each of the 2 days of testing. Each block contained a
total of 100 S1–S2 pairs, giving an average block run-time
of less than 5 min.
Data Acquisition
Continuous electroencephalographic (EEG) data, digitized
at 512 Hz, was acquired through the ActiveTwo Biosemi
electrode system from 168 scalp electrodes. With the
Biosemi system, every electrode or combination of elec-
trodes can be assigned as the ‘reference’’, and this is done
purely in software after acquisition. A detailed description
of the referencing conventions used by this active electrode
system can be found at the following website: http://www.
biosemi.com/faq/cms&drl.htm.
All data were re-referenced to an electrode placed on the
nose (Nz) after acquisition. After each recording session,
before the electrode cap was removed, the 3D coordinates
of the electrodes with reference to anatomic landmarks on
the head (nasion, pre-auricular notches) were digitized
using a Polhemus Magnetic 3D digitizer. The average
location across all subjects was computed and used as the
‘electrode file location’ and supplied to the BESA software
for 3D voltage source mapping. EEG was recorded con-
tinuously and epoched and averaged off-line. Trials with
blinks and large eye movements, defined as continuous
deviations of 20 ms or more of at least ±15 lV on both
eye channels relative to a preceding 10-ms baseline period,
were rejected offline. Before epoching and averaging, the
continuous EEG of an electrode site was linearly interpo-
lated, using the data from the four nearest ‘good-standing’
electrodes, if the standard deviation of amplitude over the
whole block at that electrode was 50% greater than that of
at least three of the six neighboring channels. Thereafter,
epoched trials on which activity exceeded ± 100 lVonat
least four electrodes were rejected. In all subjects, an
acceptance rate of greater than 90% was observed.
Data Analysis
Accepted trials were epoched separately for the S1
(-300 ms pre-stimulus to 900 ms post-stimulus) and the
S2. Only the S1 stimuli were analyzed for the present
study. The baseline was defined as the mean voltage from
200 ms to 0 ms before the onset of S1 (i.e. two full cycles
Fig. 1 Schematic illustration of the paradigm. Each trial commenced
with the presentation of a visual symbolic cue (S1). The visual cues
were either a left or right pointing arrow, which indicated which side
of fixation to deploy attention. A delay period of 800 ms followed the
cue, after which the imperative stimulus appeared. Subjects were
required to respond with a button push to targets within the cued side
Brain Topogr
123
of a 10 Hz oscillation). Separate averages were made for
the two possible variants of the S1 stimulus (cue-Left and
cue-Right). We inspected oscillatory activity in the alpha
band (8–14 Hz
1
) during the cue-to-target interval (CTI).
Alpha-band activity was characterized in this period by the
temporal spectral evolution (TSE) technique, which pro-
vides an index of ‘induced’ alpha activity as a function of
time (see Foxe et al. 1998). All statistical analyses were
performed on these induced alpha oscillations. The TSE
waveforms are derived by the following method:
Individual (single trial) stimulus-locked epochs are
band-pass filtered after artifact rejection (3rd Order IIR-
Butterworth, zero-phase, 8–14 Hz).
Filtered epochs are then Hilbert transformed.
The absolute value of the Hilbert transformed epoch is
computed. This computation is equivalent to a full-
wave rectification and enveloping technique that results
in robust measures.
Enveloped waveforms are then averaged.
Two repeated-measures analyses of variance (ANOVA)
were used to statistically test for effects over the baseline
period (-200 to 0 ms) and the late-stage of the CTI (650–
800 ms) relative to the S1 cue. The first ANOVA tested
effects over the baseline period, with factors of Treatment
(Theanine vs. Placebo) and Region of Interest (ROI–Left,
Right, and Center). The ROIs were defined as 6 clustered
electrodes over the parieto-occiptal scalp region of both the
left and right hemispheres, and 5 clustered electrodes over
the centro-parieto region. The dependent measure was
calculated by integrating the amplitude across the baseline
period and averaging across electrodes in each ROI. We
collapsed across attention condition (attend left, attend
right), since there should be no differential activation
between these conditions prior to the onset of the cue.
The second ANOVA tested effects over the late-stage of
the CTI, with factors of attention condition (Left vs. Right),
Treatment (Theanine vs. Placebo) and Hemisphere (Left
vs. Right). The dependent measure was calculated by
averaging the integrated amplitude measures across a
cluster of six electrodes over the left and right parieto-
occipital scalp, respectively. SPSS for Windows (version
12.0) was used for all statistical analyses.
Results
Behavioral Performance
We calculated the d’ values for each participant and
computed a repeated-measures ANOVA with factors of
treatment (
L-theanine vs. Placebo) and attention (attend left
vs. attend right). The ANOVA did not reveal any main
effects of treatment or attention, as well as no interaction
effect of treatment by attention. The mean d’ values for the
L-theanine and placebo conditions were 0.66 and 0.73,
respectively.
Tonic Alpha-Band Activity (Baseline Period):
Illustrated in Fig. 2a are the average TSE waveforms
plotting the time course of alpha-band activity for both
treatment conditions, collapsed over both attention condi-
tions and within the ROIs chosen for statistical testing. The
baseline period (-200 to 0 ms) relative to the instructional
cue onset is highlighted by the gray-shaded area. Consis-
tent with the previous study of Gomez-Ramirez et al.
(2007), an overall drop in tonic alpha activity is evident
over posterior regions on ingestion of
L-theanine relative to
placebo.
A repeated-measures ANOVA conducted on tonic alpha
measured in the baseline period revealed a main effect of
treatment (F(1,10) = 5.57, P \ 0.05), driven by the
reduction of tonic alpha power for the
L-theanine condition
(see Fig. 2b). The ANOVA also revealed an interaction
effect of treatment 9 ROI (F(2,20) = 4.897, P \ 0.01)
which suggests that the overall drop in tonic alpha is
topographically specific. Planned comparison t-tests
revealed that this interaction was driven by a significant
drop in alpha over the right hemisphere for
L-theanine
(t(10) = 3.487, P = 0.006), but a trend towards greater
alpha for
L-theanine over the center ROI (t(10) =-1.957,
P = 0.07). No other significant differences were found.
Illustrated in Fig. 2b is the scalp distribution of tonic
alpha for both treatment conditions during the baseline
period. A topographical shift in the focus of tonic alpha is
apparent, with a more dorsal/superior focus in the
L-thea-
nine condition relative to placebo.
Phasic Alpha-Band Activity (Late-Phase CTI)
Illustrated in Fig. 3 is alpha-band activity during the period
between the instructional cue and the subsequent impera-
tive stimulus (-200 to 900 ms). Depicted are average
alpha-band TSE waveforms over left and right parieto-
occipital cortices for the
L-theanine and placebo conditions.
A repeated-measures ANOVA conducted on the
TSE amplitude integrated over the pre-target period
1
The exact band-pass that constitutes the alpha–band is not
consistent across the literature and could be considered somewhat
arbitrary. In fact, the centre frequency of alpha is quite variable across
individuals and for most it tends to be in the 10–12 Hz range (see e.g.
Doppelmayer et al. 1998). As such, the band-pass chosen here of 8–
14 Hz nicely spans this range.
Brain Topogr
123
650–800 ms revealed a main effect of treatment
(F(1,10) = 5.873, P \0.05), indicating that the reduction
in tonic alpha persists throughout the trial epoch. The
ANOVA also revealed a main effect of hemisphere
(F(1,10) = 7.507, P \ 0.05), driven by a substantial drop
in alpha power over right-hemisphere cortices. There was
also an attention 9 hemisphere interaction (F(1,10) =
7.030, P = 0.022), reflecting the typically-observed dif-
ferential attention effect across hemispheres (see 10,15,18).
Planned comparison t-tests revealed that this interaction
effect was mostly driven by differential attention-directing
effects over the left hemisphere; t(10) = 2.498, P \ 0.05.
That is to say, directing attention to the left visual field
evoked significantly greater alpha-band activity over the
left hemisphere than directing attention to the right visual
field. No other significant effects were observed.
Discussion
The present study set out to investigate the effects of a
250-mg dose of
L-theanine on alpha-band oscillatory
activity while subjects were engaged in a highly demand-
ing visuo-spatial attention task. Primarily, we conducted
this study to verify and extend the results of Gomez-
Ramirez et al. (2007), in which we uncovered effects
Fig. 2 Alpha-band oscillatory
activity baseline. a TSE
waveforms from six electrodes
averaged over the left and right
parieto-occipito scalp and five
electrodes over the central-
parieto scalp are plotted for the
placebo (blue trace) and
theanine conditions (red trace).
The factor of directing attention
is collapsed across both
treatment conditions. Alpha-
band activity during this
baseline period is significantly
reduced when subjects ingest
L-theanine compared to placebo.
b Topographical voltage maps
for both treatment conditions,
and their difference, during the
baseline period (-200–0 ms
relative to the instructional cue).
The maps show a difference in
the topographical distribution
between both treatment
conditions, suggesting that
L-
theanine can have differential
effects on specific brain regions
Brain Topogr
123
of L-theanine on two aspects of alpha-band activity that we
have here termed tonic and phasic. The distinction between
these forms of attention-related alpha activity deserves
further elaboration. Ongoing alpha oscillatory activity is
evident in the EEG regardless of the task in which a subject
is engaged at a given time. This so-called tonic alpha
activity varies over periods of many seconds to minutes,
with a typical topography over parietal and parieto-occip-
ital scalp. It represents the baseline level of activity that is
not immediately related to particular events and it is con-
sidered to be an EEG correlate of sustained attentional
processing or overall engagement in a given task (see
Dockree et al. 2007). Phasic alpha, in contrast, refers to
changes in activity over much shorter timeframes on the
order of 100–1,000 ms that occur in response to specific
stimuli. Of most relevance to the current discussion, phasic
alpha has been clearly related to selective deployments of
intersensory (e.g. Foxe et al. 1998) and visuo-spatial
attention (e.g. Kelly et al. 2006, 2008). In the case of vi-
suo-spatial attention, cued phasic increases in alpha are
observed over retinotopically-specific regions reflecting the
gating of irrelevant input, whereas phasic decreases are
observed over regions preferentially primed to process
relevant input. This differential alpha effect is proposed to
arise from posterior structures known to be involved in
attentional switching and disengagement within the visual
modality (e.g. Posner and Petersen 1990; Foxe et al. 1998;
Worden et al. 2000). Demonstrating its importance to
behavior, this mechanism has been shown to be positively
correlated with detection performance (Thut et al. 2006).
Thus, separately measuring tonic and phasic varieties of
alpha activity enables the assessment of both long-term
sustained attentional factors and short-term moment-to-
moment phasic deployments.
2
Gomez-Ramirez et al. (2007) found that L-theanine
enhanced the differential effect of cue information on
anticipatory phasic alpha activity compared to placebo, and
found an overall decrease in tonic background alpha, which
was evident even before the presentation of any cue and
throughout the trial period. This would suggest that
L-theanine brings about an enhancement in both sustained
attention across the timeframe of the task, and in the
effectiveness of phasic attentional deployments. In the
present study, however, we again find a substantial drop in
tonic alpha indicating facilitated sustained attention but
find no evidence of effects upon phasic alpha deployments.
The present data indicate that
L-theanine does not
globally reduce tonic alpha power but exerts its influence
more selectively over distinct brain regions. That is,
Fig. 3 Alpha-band oscillatory
activity during the late phase of
the CTI. TSE waveforms from
six electrodes averaged over the
left and right parieto-occipito
scalp separately are plotted for
the placebo (upper panel) and
theanine conditions (lower
panel). Red traces indicated
attention deployed to the Left
visual field, while blue traces
indicate attention deployed to
the right visual field. Alpha-
band activity is significantly
depressed when subjects ingest
L-theanine compared to placebo
2
Although phasic and tonic alpha mechanisms clearly relate to
separable attentional factors, it has not yet been explicitly tested
whether these mechanisms rely on the same or different neural
generators. Nonetheless, the scalp topography of tonic alpha typically
shows a distribution over central parieto-occipital scalp sites. In
contrast, the distribution of phasic alpha rhythm, observed in these
visual spatial-attention studies, shows a clear bilateral and lateralized
topography. That is, when deploying attention to the left visual field,
the alpha-power distribution is highly biased to right parieto-occipital
cortices, and conversely, when attention is deployed to the right visual
field, the distribution is biased to left parieto-occipital cortices. We
take this voltage topographical dissimilarity as evidence for at least
partially distinct neural generators although a subset of common
neural generators is still a likelihood.
Brain Topogr
123
L-theanine caused a substantial drop in tonic alpha power
over posterior visual regions, mostly right-lateralized,
whereas a trend towards enhancement was seen over
midline centro-parietal scalp. This may reflect specific
targeting of task-critical visual areas for sustained facili-
tation, rather than a nonspecific modulation of more
generalized aspects of arousal. In this context, it is inter-
esting that the sustained alpha modulation is lateralized to
the right hemisphere, where phasic processes appear to be
instantiated somewhat equally for attentional deployments
towards left and right hemifields. A fair degree of caution
is warranted, however, as this was an unexpected finding
and will bear replication.
While the present study was designed to replicate our
previous findings (see Gomez-Ramirez et al. 2007), it is
important to point out that the reduction in tonic alpha
power observed in this and our previous study occurs while
subjects are engaged in a highly demanding cognitive task,
and not in a ‘passive resting state’ as in previous studies
purporting to show enhanced alpha power for
L-theanine
(Kobayashi et al. 1998; Juneja et al. 1999). Though our
tonic alpha measure was taken over an interval where no
attentional deployment was taking place, subjects were still
highly engaged in the task. Thus, it may well be the case
that our results are addressing completely different brain
processes from those in the Kobayashi et al. (1998) and
Juneja et al. (1999) studies.
Although the finding of modulated tonic alpha may be
taken to reflect an effect on sustained attention based on
previous work related to the alpha rhythm, the failure to
find an accompanying behavioral effect casts some doubt
on whether the result can be interpreted in a wholly posi-
tive light. However, in attempting to induce strong
attentional shifts, the task was titrated to a very high dif-
ficulty level, which may have compromised its sensitivity
to detect changes in performance across treatments due to a
floor effect. Thus, it remains to be seen whether
L-theanine
can exert effects on behavior, or whether it modulates
phasic attentional deployment within the visual modality,
during a less difficult task. Whatever the case, the current
pattern of results suggests that
L-theanine modulates the
activity of the attentional system when deploying attention
to different sensory modalities, but not when deploying
attention in space. In the latter case,
L-theanine may exert
its influence on attentional processing at a more general
level, facilitating longer-term sustained attentional pro-
cessing across the timeframe of a difficult task, rather than
affecting specific moment-to-moment phasic deployment
processes.
Acknowledgements This work was supported by a grant from the
Lipton Institute of Tea. We would also like to acknowledge the
support of Dr. Jane Rycroft and Dr. Gail Owen of the Unilever
Beverages Global Technology Centre in Colworth House, Sharn-
brook, United Kingdom.
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... L-theanine is often advertised with claims of enhancing alertness and attention [16,20,21]. Several single-dose, placebo-controlled trials have investigated the acute attentional effects of L-theanine on healthy human volunteers using behavioral, neurophysiological and functional neuroimaging indices of selective attention [23][24][25][26][27][28][29][30]. These studies have produced mixed results in behavioral outcome measures, but those that examined neurophysiological measures of selective attention have produced more consistent results. ...
... As for the complexity, it is possible that these selective attention tasks were not demanding enough, thus leading to a possible ceiling effect at the behavioral level (as shown by high accuracy rates) among healthy young participants of those studies. The complexity the tasks were particularly constrained by the abstract nature of the stimuli such as tones [24], colored flashes [28][29][30], directional arrows [26,27,43,44] that required lower order attentional processing than in real-life scenarios. Therefore, we believe further exploration of behavioral effects of L-theanine in the future could employ more demanding and ecologically valid stimuli and task paradigms. ...
Article
Objective: L-theanine, a non-proteinic amino acid found in tea, is known to enhance attention particularly in high doses, with no reported adverse effects. We aimed to determine whether oral administration of L-theanine acutely enhances neurophysiological measures of selective attention in a dose-dependent manner. Methods: In a double-blind, placebo-controlled, counterbalanced, 4-way crossover study in a group of 27 healthy young adults, we compared the effects of 3 doses of L-theanine (100, 200 and 400 mg) with a placebo (distilled water) on latencies of amplitudes of attentive and pre-attentive cognitive event-related potentials (ERPs) recorded in an auditory stimulus discrimination task, before and 50 min after dosing. Results: Compared to the placebo, 400 mg of theanine showed a significant reduction in the latency of the parietal P3b ERP component (p < 0.05), whereas no significant changes were observed with lower doses. A subsequent exploratory regression showed that each 100-mg increase in dose reduces the P3b latency by 4 ms (p < 0.05). No dose–response effect was observed in P3b amplitude, pre-attentive ERP components or reaction time. Discussion: The findings indicate L-theanine can increase attentional processing of auditory information in a dose-dependent manner. The linear dose–response attentional effects we observed warrant further studies with higher doses of L-theanine.
... In humans, L-theanine has been reported to modulate alpha activity and play a role in attentional tasks in electroencephalogram studies [28][29][30], as well as provide beneficial effects on mental state [31], including sleep quality [32]. To our knowledge, however, only its acute effects have been investigated in healthy individuals. ...
... For cognitive functions, BACS verbal fluency and executive function scores improved after four weeks L-theanine administration. These findings are consistent with previous preclinical studies [11,20,21] and our clinical trial for MDD [40], whereas they are inconsistent with the acute attentionimproving effects reported in healthy humans [28][29][30][36][37][38]. Considering the comparison to the placebo administration, the current study suggests that the score for the BACS verbal fluency, especially letter fluency, but not the Trail Making Test, Stroop test, or other BACS parameters, significantly changes in response to the 4 weeks effects of L-theanine. ...
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This randomized, placebo-controlled, crossover, and double-blind trial aimed to examine the possible effects of four weeks L-theanine administration on stress-related symptoms and cognitive functions in healthy adults. Participants were 30 individuals (nine men and 21 women; age: 48.3 ± 11.9 years) who had no major psychiatric illness. L-theanine (200 mg/day) or placebo tablets were randomly and blindly assigned for four-week administration. For stress-related symptoms, Self-rating Depression Scale, State-Trait Anxiety Inventory-trait, and Pittsburgh Sleep Quality Index (PSQI) scores decreased after L-theanine administration (p = 0.019, 0.006, and 0.013, respectively). The PSQI subscale scores for sleep latency, sleep disturbance, and use of sleep medication reduced after L-theanine administration, compared to the placebo administration (all p < 0.05). For cognitive functions, verbal fluency and executive function scores improved after L-theanine administration (p = 0.001 and 0.031, respectively). Stratified analyses revealed that scores for verbal fluency (p = 0.002), especially letter fluency (p = 0.002), increased after L-theanine administration, compared to the placebo administration, in individuals who were sub-grouped into the lower half by the median split based on the mean pretreatment scores. Our findings suggest that L-theanine has the potential to promote mental health in the general population with stress-related ailments and cognitive impairments.
... A likely explanation for this finding is that cortisol is just one of the many factors that impacts alpha power, and it does not provide the full story. Indeed, alpha activity is not only associated with arousal state, but indexes the operation of selective attention [30]. With L-theanine supplementation, alpha amplitude has been demonstrated to be lower in the pre-response and in response to visual and auditory cues compared to placebo [31]. ...
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Introduction: Stress is a complex life occurrence essential for survival and goal achievement but can be damaging in excess. Because of the high prevalence of stress in North America, a safe supplement that effectively reduces stress is in demand. The objective of this study was to investigate the efficacy and safety of AlphaWave® L-Theanine on whole-scalp and frontal alpha power, midline theta power, and salivary cortisol in healthy, moderately stressed adults. Methods: This was a randomized, triple-blind, placebo-controlled, crossover study that consisted of two study periods with a 7-day washout. A single dose of AlphaWave® L-Theanine (200 mg) or placebo was administered. To induce stress, a mental arithmetic test (MAT) was administered before and after the dose. Electroencephalogram, salivary cortisol, blood pressure, heart rate, self-reported stress, adverse events, clinical chemistry, and hematology were assessed to evaluate efficacy and safety. Results: Increases in heart rate, blood pressure, and self-reported stress and state anxiety indicated that participants experienced stress during the MAT. AlphaWave® L-Theanine led to a greater increase in frontal region and whole-scalp alpha power 3 h post-dose compared to placebo (p ≤ 0.050). Within groups, there were increases in alpha power, at 3 h with AlphaWave® L-Theanine, over the whole recording and during the eyes-open portions (p ≤ 0.048) of the alpha task. The changes in alpha wave activity are supported by greater decreases in salivary cortisol 1 h post-dose (p < 0.001) with AlphaWave® L-Theanine compared to placebo. Conclusion: This study was conducted during the SARS-CoV-2 pandemic, which has had a rapid and significant effect on both physical and mental health around the world. A single dose of AlphaWave® L-Theanine significantly increased frontal region alpha power compared to placebo in response to an acute stress challenge. These changes are indicative of relaxation in the brain and suggest a calming response. AlphaWave® L-Theanine was found to be safe and well tolerated by participants. Trial registration: ClinicalTrials.gov identifier NCT04706494.
... The sample size was justified upon significant modification of EEG alpha activity following intake of a constituent of green tea. Ltheanine has been demonstrated to induce significant changes in EEG resting state and attentional performance related alpha power [23,[40][41][42]. The effect sizes of L-theanine on EEG alpha activity in these studies ranged from 0.803 to 1.141 (Cohen's d ). ...
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Background: Magnesium (Mg), green tea and rhodiola extracts have, in isolation, been shown to possess stress and anxiety relieving effects. Green tea and rhodiola have been shown to modulate EEG oscillatory brain activity associated with relaxation and stress perception. The combined capacity of these ingredients to confer protective effects under conditions of acute stress has yet to be examined. We tested the hypothesis that a combination of Mg (with B vitamins) + green tea + rhodiola would acutely moderate the effects of stress exposure. Methods: A double blind, randomised, placebo controlled, parallel group design was employed (Clinicaltrials.gov:NCT03262376; 25/0817). One hundred moderately stressed adults received oral supplementation of either (i) Mg + B vitamins + green tea + rhodiola; (ii) Mg + B vitamins + rhodiola; (iii) Mg + B vitamins + green tea; or (iv) placebo. After supplementation participants were exposed to the Trier Social Stress Test. The effects of the study treatments on electroencephalogram (EEG) resting state alpha and theta, subjective state/mood, blood pressure, heart rate variability and salivary cortisol responses after acute stress exposure were assessed. Results: The combined treatment significantly increased EEG resting state theta (p < .02) - considered indicative of a relaxed, alert state, attenuated subjective stress, anxiety and mood disturbance, and heightened subjective and autonomic arousal (p < .05). Conclusions: Mg, B vitamins, rhodiola and green tea extracts are a promising combination of ingredients that may enhance coping capacity and offer protection from the negative effects of stress exposure.Trial registration: ClinicalTrials.gov identifier: NCT03262376.
... Furthermore, a study that used a visuospatial task also showed that the intake of 250 mg of l-theanine contributed to sustained attention. 32 Although increased a-wave activity does not simply indicate wakefulness in the brain, l-theanine may affect selective or sustained attentional function. In this study, a significant decrease in reaction time was observed for ST (Part 1), which indicates sustained attention and provides further support for the effects of l-theanine on attentional function. ...
Article
l-theanine (γ-glutamylethylamide), an amino acid in green tea, has been shown to affect brain functions by relieving stress disorders, improving mood, and maintaining normal sleep. However, the cognitive functions for which theanine is effective are unclear. This study aimed to clarify which cognitive functions are positively affected by intake of l-theanine. A double-blind, randomized, placebo-controlled study was conducted. The subjects were Japanese men and women aged 50-69 years. Mini Mental State Examination-Japanese version score was 24 or higher. Cognitrax was used as a test battery for cognitive function. Evaluations were performed before the intervention, after a single dose of l-theanine, and after 12 weeks of regular intake. The single dose of l-theanine reduced the reaction time to attention tasks (Stroop test, Part 1), and it increased the number of correct answers and decreased the number of omission errors in working memory tasks (4-Part continuous performance test, Part 4). In conclusion, our study indicated that l-theanine may contribute to improving attention, thus enhancing working memory and executive functions. Clinical Trial No.: UMIN000033812.
... These findings are consistent with the results of prior electrophysiological and neuroimaging studies. For instance, in two placebo-controlled electroencephalography studies conducted on healthy adults, Gomez-Ramirez observed decreased background α oscillations during an intersensory attention task 35 and increased task-related α oscillations during a visuospatial attention task 74 with the intake of 250 mg of l-theanine. In a similar electroencephalography study, Kelley et al. 25 observed decreased background mean α amplitudes with a combination of 100 mg of l-theanine and 50 mg of caffeine among healthy adults engaged in a cued attention shift task along with concurrent improvements task performance indicative of sustained attention. ...
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We examined the acute effects of l-theanine, caffeine and their combination on sustained attention, inhibitory control and overall cognition in boys with attention deficit hyperactivity disorder (ADHD). l-Theanine (2.5 mg/kg), caffeine (2.0 mg/kg), their combination and a placebo were administered in a randomized four-way repeated-measures crossover with washout, to five boys (8–15 years) with ADHD. Functional magnetic resonance imaging (fMRI) was performed during a Go/NoGo task and a Stop-signal task ~ 1 h post-dose. NIH Cognition Toolbox was administered ~ 2 h post-dose. Treatment vs. placebo effects were examined in multi-level mixed-effects models. l-Theanine improved total cognition composite in NIH Cognition Toolbox (p = 0.040) vs. placebo. Caffeine worsened and l-theanine had a trend of worsening inhibitory control (i.e. increased Stop-signal reaction time; p = 0.031 and p = 0.053 respectively). l-Theanine–caffeine combination improved total cognition composite (p = 0.041), d-prime in the Go/NoGo task (p = 0.033) and showed a trend of improvement of inhibitory control (p = 0.080). l-Theanine–caffeine combination was associated with decreased task-related reactivity of a brain network associated with mind wandering (i.e. default mode network). l-Theanine–caffeine combination may be a potential therapeutic option for ADHD-associated impairments in sustained attention, inhibitory control and overall cognitive performance.
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Artificial intelligence (AI) service failures are inevitable in hospitality companies; thus, how AI service recovery retains customers is an issue that cannot be ignored. This article focuses on AI service recovery, abandoning the traditional “intelligence quotient” thinking and exploring the recovery effect of empathy response from the perspective of emotional intelligence. Using four experimental scenarios, the results indicate that, in service recovery, a high-empathy AI response can increase customers’ continuous usage intention, and psychological distance and trust are sequential mediators in this process. Compared with mono-sensory stimulus interactions (text only), a high-empathy response that adopts multisensory stimulus interactions (text and voice) could strengthen the recovery effect of empathy responses. This paper extends the field of AI service research from a focus on time and phase to the continuing use of AI after service failure. It also moves beyond the traditional intelligence quotient improvement thinking and reveals the importance of using AI emotional intelligence to activate customer emotional response in AI service recovery. Finally, it provides a useful tool for resolving AI service failure problems autonomously in the service process, which is of great value to research and development and hospitality operators in the promotion and application of AI services.
Chapter
In recent decades, preclinical research into natural products has focused on the identification of pharmacologically active secondary metabolites produced by plants, often traditionally used as medicinal remedies. Beyond vitamins and minerals, plants contain other secondary metabolites recently defined as “nutraceuticals,” which are at the center of important scientific studies. The term nutraceutical is a portmanteau word, a combination of “nutrition” and “pharmaceutical,” and refers to “naturally derived bioactive compounds that are found in foods, dietary supplements, and herbal products and have health-promoting, disease-preventing, and/or medicinal properties.” Several nutraceuticals exhibit antiaging features by acting on the inflammatory status and on the prevention of oxidative reaction. This results in a significant reduction of all risk factors for age-related diseases, enhancing the attainment of healthy aging. In this context, the chapter will summarize the available clinical evidence supporting the use of selected botanicals and phytochemicals with confirmed activity on the human central nervous system and demonstrated effects in modulating cognitive decline as an example of age-related disease. In particular, the chapter will focus on data supporting the potential usefulness of Ginkgo biloba, Vitis vinifera, Camellia sinensis, Theobroma cacao, Bacopa monnieri, Crocus sativus, and Curcuma longa.
Chapter
Dementia is a chronic condition characterized by the decreased cognitive capacity, which is more severe than in case of normal aging. Cognitive impairment is a major social and economic problem of modern society, which affects about 47 million people worldwide. The first stage of dementia (mild cognitive impairment) is characterized by the decline of memory, executive function, attention, visuospatial skills and speech. Pathogenic links of cognitive impairment are represented by neuroinflammation, excessive amyloid-β protein deposition, oxidative stress, hyperphosphorylation etc. In the recent years, the interest in natural plant-derived compounds for the treatment of cognitive decline has increased. In this chapter, we summarize the available evidence supporting the benevolent action of some botanicals and phytochemicals on cognitive function. The most widely studied plants include Ginkgo biloba, Panax ginseng and Camellia sinensis (green tea), but there also some other promising ones like guarana, grape, soy etc. These nutraceuticals mostly influence memory, learning and attention. At the moment it is quite difficult to make a definite conclusion on the effects of nutraceuticals on cognitive decline, because human trials show significant discrepancies. This underpins the need of future trials and scientific analysis.
Chapter
Depression characterized as a mental disorder occupies the fourth position in the list of frequent global brain-related diseases. It is believed to occupy the second position in that list by 2030. Depression has been defined in terms of neurological disorders adversely influencing the physiological activities as well as functions of the brain. The disease manifests in the affected individual in the form of loss of sleep, appetite, attention, thinking, and concentration. Such persons develop a tendency of a feeling of being dejected and stay disappointed. As a result, they imbibe tendencies to suicide. Globally, this disease causes morbidity and mortality. The compounds used to treat depression are called antidepressants. These antidepressants have been shown to be useful in the treatment of pain and anxiety syndromes. Based on the mechanism of their actions, these antidepressants have been placed in five different groups: (i) the antidepressants with tricyclic chemical structure (tricyclic antidepressants – TCAs); (ii) the compounds selectively inhibiting serotonin reuptake (selective serotonin reuptake inhibitors); (iii) the molecules acting as inhibitors of the enzyme, monoamine oxidase (MAOIs); (iv) the chemical agents inhibiting the reuptake of serotonin norepinephrine (SNRIs); and (v) the non-TCA antidepressants. Many of these antidepressants are synthetic in nature and pose harmful effects on the health of users through many ways including generation of oxidative stress, which is responsible for brain dysfunction. In this regard, the phytochemicals and medicinal herbs are believed to offer most viable options because they possess enormous antioxidant potential, easy availability, low cost, least toxicity, and high therapeutic potential. The phytoconstituents have recently been utilized as a complementary therapeutic agent, which may help cure depression and check the recurrence of psychoneurotic disorders. The present chapter illustrates recent advances in research concerning phytochemicals acting as antidepressants. Also, their chemical structures, biological functions, mode of actions, role in regulation of pathophysiology, and toxicity, if any, have been included.
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Recent neuropharmacological research has suggested that certain constituents of tea may have modulatory effects on brain state. The bulk of this research has focused on either L-theanine or caffeine ingested alone (mostly the latter) and has been limited to behavioral testing, subjective rating, or neurophysiological assessments during resting. Here, we investigated the effects of both L-theanine and caffeine, ingested separately or together, on behavioral and electrophysiological indices of tonic (background) and phasic (event-related) visuospatial attentional deployment. Subjects underwent 4 d of testing, ingesting either placebo, 100 mg of L-theanine, 50 mg of caffeine, or these treatments combined. The task involved cued shifts of attention to the left or right visual hemifield in anticipation of an imperative stimulus requiring discrimination. In addition to behavioral measures, we examined overall, tonic attentional focus as well as phasic, cue-dependent anticipatory attentional biasing, as indexed by scalp-recorded alpha-band (8-14 Hz) activity. We found an increase in hit rate and target discriminability (d') for the combined treatment relative to placebo, and an increase in d' but not hit rate for caffeine alone, whereas no effects were detected for L-theanine alone. Electrophysiological results did not show increased differential biasing in phasic alpha across hemifields but showed lower overall tonic alpha power in the combined treatment, similar to previous findings at a larger dosage of L-theanine alone. This may signify a more generalized tonic deployment of attentional resources to the visual modality and may underlie the facilitated behavioral performance on the combined ingestion of these 2 major constituents of tea.
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: The concept of attention as central to human performance extends back to the start of experimental psychology, yet even a few years ago, it would not have been possible to outline in even a preliminary form a functional anatomy of the human attentional system. New developments in neuroscience have opened the study of higher cognition to physiological analysis, and have revealed a system of anatomical areas that appear to be basic to the selection of information for focal (conscious) processing. The importance of attention is its unique role in connecting the mental level of description of processes used in cognitive science with the anatomical level common in neuroscience. Sperry describes the central role that mental concepts play in understanding brain function. As is the case for sensory and motor systems of the brain, our knowledge of the anatomy of attention is incomplete. Nevertheless, we can now begin to identify some principles of organization that allow attention to function as a unified system for the control of mental processing. Although many of our points are still speculative and controversial, we believe they constitute a basis for more detailed studies of attention from a cognitive-neuroscience viewpoint. Perhaps even more important for furthering future studies, multiple methods of mental chronometry, brain lesions, electrophysiology, and several types of neuro-imaging have converged on common findings.
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L-Theanine is an amino acid found in green tea leaf and in its infusion, and is known to control excitement caused by caffeine. It is also known that the oral administration of L-theanine to rats results in a decrease of serotonin and increase of catecholamines in their brain. L-Theanine has been confirmed to be safe in animal experiments. We found recently that oral intake of L-theanine caused a feeling of relaxation among the human volunteers examined. These observations led us to do experiments on the effects of administration of L-theanine on the brain electric waves. Eight female university students were selected as volunteers. Four of them were ranked to be Grade I (the highest anxiety) and the remaining four, Grade V (the lowest anxiety) in an investigation done by the manifest anxiety scale method. A dose of oral administration of 200 mg of L-theanine dissolved in 100 ml of water resulted in the generation of α-electric waves in the occipital and parietal regions of the brains of the subjects. The emission intensity of α-brain waves (integrated as a function of investigation times and area) was significantly greater in the group of Grade I than that of Grade V. These results indicate the possibility for L-theanine to be applied to foods and beverages as a new type of functional food ingredient for its relaxation effect.
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HIGH-DENSITY EEG recordings revealed sensory specific modulation of anticipatory parieto-occipital ∼10 Hz oscillatory activity when visually presented word cues instructed subjects in an intermodal selective attention paradigm. Cueing attention to the auditory features of imminent compound audio-visual stimuli resulted in significantly higher ∼1 0 Hz amplitude in the period preceding onset of this stimulus than when attention was cued to the visual features. We propose that this parieto-occipital ∼1 0 Hz activity reflects a disengaged visual attentional system in preparation for anticipated auditory input that is attentionally more relevant. Conversely, lower ∼1 0 Hz activity during the attend—visual condition may reflect active engagement of parieto-occipital areas in the anticipatory period. These results support models implicating parieto-occipital areas in the directing and maintenance of visual attention.
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Since ancient times, it has been said that drinking green tea brings relaxation. The substance that is responsible for a sense of relaxation, is theanine. Theanine is a unique amino acid found almost solely in tea plants and the main component responsible for the exotic taste of ‘green’ tea. It was found that L-theanine administered intraperitoneally to rats reached the brain within 30 min without any metabolic change. Theanine also acts as a neurotransmitter in the brain and decreased blood pressure significantly in hypertensive rats. In general, animals always generate very weak electric pulses on the surface of the brain, called brain waves. Brain waves are classified into four types, namely α,β,δ and θ-waves, based on mental conditions. Generation of α-waves is considered to be an index of relaxation. In human volunteers, α-waves were generated on the occipital and parietal regions of the brain surface within 40 min after the oral administration of theanine (50–200 mg), signifying relaxation without causing drowsiness. With the successful industrial production of L-theanine, we are now able to supply Suntheanine™ (trade name of L-theanine) which offers a tremendous opportunity for designing foods and medical foods targeting relaxation and the reduction of stress. Taiyo Kagaku Co., Ltd, Japan won the 1998 ‘Food Ingredient Research Award’ for development of Suntheanine™ at Food Ingredients in Europe (Frankfurt). The judges felt it was a particularly well-documented and fascinating piece of research.
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Induced alpha power (in a lower, intermediate and upper band) which is deprived from evoked electroencephalograph (EEG) activity was analyzed in an oddball task in which a warning signal (WS) preceded a target or non-target. The lower band, reflecting phasic alertness, desynchronizes only in response to the WS and target. The intermediate band, reflecting expectancy, desynchronizes about 1 s before a target or non-target appears. Upper alpha desynchronizes only after a target is presented and, thus, reflects the performance of the task which was to count the targets. Thus, only slower alpha frequencies reflect attentional demands such as alertness and expectancy.
Oscillations in the alpha and beta bands can display either an event-related blocking response or an event-related amplitude enhancement. The former is named event-related desynchronization (ERD) and the latter event-related synchronization (ERS). Examples of ERS are localized alpha enhancements in the awake state as well as sigma spindles in sleep and alpha or beta bursts in the comatose state. It was found that alpha band activity can be enhanced over the visual region during a motor task, or during a visual task over the sensorimotor region. This means ERD and ERS can be observed at nearly the same time; both form a spatiotemporal pattern, in which the localization of ERD characterizes cortical areas involved in task-relevant processing, and ERS marks cortical areas at rest or in an idling state.