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The precise role of the cortex in human anxiety is not well characterised. Previous imaging research among healthy controls has reported alterations in regional cerebral blood flow (rCBF) within the prefrontal and temporal cortices during periods of anxious anticipation; however, the temporal dynamics of this activity has yet to be examined in detail. The present study examined cortical Steady State Probe Topography (SSPT) changes associated with anticipatory anxiety (AA), allowing examination of the temporal continuity and the excitatory or inhibitory nature of AA activations. We recorded Steady State Visually Evoked Potentials (SSVEPs) at 64 scalp locations, skin conductance, and self reported anxiety among 26 right-handed males while relaxed and during the anticipation of an electric shock. Relative to the baseline condition, the AA condition was associated with significantly higher levels of self-reported anxiety and increased phasic skin conductance levels. Across the seven second imaging window, AA was associated with increased SSVEP latency within medial anterior frontal, left dorsolateral prefrontal and bilateral temporal regions. In contrast, increased SSVEP amplitude and decreased SSVEP latency were observed within occipital regions. The observed SSVEP latency increases within frontal and temporal cortical regions are suggestive of increased localised inhibitory processes within regions reciprocally connected to subcortical limbic structures. Occipital SSVEP latency decreases are suggestive of increased excitatory activity. SSVEP amplitude increases within occipital regions may be associated with an attentional shift from external to internal environment. The current findings provide further support for the involvement of frontal, anterior temporal, and occipital cortical regions during anticipatory anxiety, and suggest that both excitatory and inhibitory processes are associated with AA alterations.
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Cortical neurophysiology of anticipatory anxiety: an investigation
utilizing steady state probe topography (SSPT)
M. Gray, A.H. Kemp, R.B. Silberstein, and P.J. Nathan*
Neuropsychopharmacology Laboratory, Brain Sciences Institute, Swinburne University of Technology,
400 Burwood Road Hawthorn 3122, Victoria, Australia
Received 31 March 2003; revised 23 June 2003; accepted 30 June 2003
The precise role of the cortex in human anxiety is not well characterised. Previous imaging research among healthy controls has reported
alterations in regional cerebral blood flow (rCBF) within the prefrontal and temporal cortices during periods of anxious anticipation;
however, the temporal dynamics of this activity has yet to be examined in detail. The present study examined cortical Steady State Probe
Topography (SSPT) changes associated with anticipatory anxiety (AA), allowing examination of the temporal continuity and the excitatory
or inhibitory nature of AA activations. We recorded Steady State Visually Evoked Potentials (SSVEPs) at 64 scalp locations, skin
conductance, and self reported anxiety among 26 right-handed males while relaxed and during the anticipation of an electric shock. Relative
to the baseline condition, the AA condition was associated with significantly higher levels of self-reported anxiety and increased phasic skin
conductance levels. Across the seven second imaging window, AA was associated with increased SSVEP latency within medial anterior
frontal, left dorsolateral prefrontal and bilateral temporal regions. In contrast, increased SSVEP amplitude and decreased SSVEP latency
were observed within occipital regions. The observed SSVEP latency increases within frontal and temporal cortical regions are suggestive
of increased localised inhibitory processes within regions reciprocally connected to subcortical limbic structures. Occipital SSVEP latency
decreases are suggestive of increased excitatory activity. SSVEP amplitude increases within occipital regions may be associated with an
attentional shift from external to internal environment. The current findings provide further support for the involvement of frontal, anterior
temporal, and occipital cortical regions during anticipatory anxiety, and suggest that both excitatory and inhibitory processes are associated
with AA alterations.
© 2003 Elsevier Inc. All rights reserved.
Keywords: Anticipatory anxiety; Steady state probe topography; SSPT; BOLD; Electrophysiology; Electric shock; Healthy human participants
Human anxiety consists of a complex pattern of cogni-
tive, affective, physiological and behavioural changes in
response to threat, loss, or perceived negative outcome
(Beck and Clark, 1997). Anxiety reactions cross into the
spectrum of clinical disorders when they are situationally
inappropriate or excessive in duration or degree. Within any
one-year period, 5.7% of the Australian population meet the
DSM-IV criteria for an anxiety disorder, a level closely
matched in both UK and US samples (Andrews et al., 2001),
highlighting the importance of gaining a better understand-
ing of the neural underpinnings of anxious symptomatology.
Research within a range of anxiety disorders employing
symptom provocation, pharmacological or behavioural
challenges, and resting state comparison methodologies has
highlighted the fact that in addition to the activity of limbic
and brain stem structures, higher cortical areas are function-
ally significant to the pathophysiology of anxiety. The most
consistently reported cortical brain regions with functional
significance to anxiety are found within the prefrontal cor-
tex, the temporal cortex (particularly anteriorly) and insula,
and within the occipital lobes. Alterations in activity within
the prefrontal cortex have been observed amongst a range of
patient populations including social phobia (Davidson et al.,
* Corresponding author. Neuropsychopharmacology Laboratory, Brain
Sciences Institute, Swinburne University of Technology, 400 Burwood
Road Hawthorn 3122, Victoria, Australia. Fax: 61-3-92145525.
E-mail address: (P.J. Nathan).
NeuroImage 20 (2003) 975–986
1053-8119/$ – see front matter © 2003 Elsevier Inc. All rights reserved.
2000), simple phobia (SP) (Paquette et al., 2003; Johanson
et al., 1998; Fredrickson et al., 1995; Wik et al., 1993),
panic disorder (PD) (Boshuisen et al., 2002; Bremner et al.,
2000; Meyer et al., 2000; Malizia et al., 1998; Nordahl et
al., 1998, 1990; De Cristofaro et al., 1993), post traumatic
stress disorder (PTSD) (Shaw et al., 2002; Osuch et al.,
2001; Mirzaei et al., 2001; Semple et al., 2000, 1993;
Liberzon et al., 1999; Shin et al., 1999; Zubieta et al., 1999),
and obsessive compulsive disorder (OCD) (Rauch et al.,
2002; Lucey et al., 1997; Schwartz et al., 1996; Rubin et al.,
1992; Zohar et al., 1989; Baxter et al., 1987). The results of
the above studies are consistent with the hypothesis that
prefrontal cortical regions (particularly within the right
hemisphere) are involved with the regulation and control of
anxiety by regulating the activity of subcortical limbic areas
including the anterior cingulate and amygdala (Davidson,
2002; Davidson and Irwin, 1999).
Alterations in temporal lobe function associated with
anxious symptomatology have also been frequently re-
ported. Increased temporal lobe rCBF activity was reported
among patients with generalised anxiety disorder (GAD)
(Johanson et al., 1992; Wu et al., 1991), OCD (Breiter et al.,
1996), SP (Rauch et al., 1995; Davidson et al., 2000), PD
(Boshuisen et al., 2002) and PTSD (Shin et al., 1999).
Increased rCBF was observed within the right insula of SP
(Rauch et al., 1995) and OCD patients (Breiter et al., 1996)
and among SP, OCD and PTSD patients (Osuch et al., 2001;
Shin et al., 1999; Rauch et al., 1997). Decreased rCBF has
been reported within the parietotemporal cortex (Meyer et
al., 2000; Bisaga et al., 1998) and anterior insula (Boshuisen
et al., 2002) of PD patients, and within the temporal polar
cortices of SP patients (Fredrickson et al., 1995). Anxious
symptomatology has also been associated with alterations in
occipital lobe activity. Reduced rCBF within primary and
secondary visual cortical areas has been reported among SP
patients (Wik et al., 1996, 1993) and PTSD patients (Mir-
zaei et al., 2001). Increases in occipital rCBF have also been
reported among subjects with PTSD (Rauch et al., 1996), SP
(Paquette et al., 2003; Fredrikson et al., 1993 1997), GAD
(Wu et al., 1991) which were attenuated after benzodiaz-
epine treatment (Buchsbaum et al., 1987), and subjects with
OCD (Zohar, 1989).
Pharmacological challenges, whilst providing another
avenue for investigation of the neural basis of anxious
symptomatology, are somewhat difcult to synthesize be-
cause of the use of various panicogens (CCK-4, pentagas-
trin, yohimbine, lactate, and CO
inhalation) in both clinical
and normal groups. Although each of these agents may be
used to induce anxious symptomatology to varying degrees
within patients and controls, each has a differing inuence
on the adrenergic and vascular functioning of the central
nervous system. As a result, the specic results appear
somewhat contradictory, however regional cortical alter-
ations within PFC, temporal lobes and insula, and occipital
cortex are commonly reported (Boshuisen et al., 2002;
Cameron et al., 2000; Javanmand et al., 1999; Bremner et
al., 1997; Benkelfat et al., 1995; De Cristofaro et al., 1993;
Stewart et al., 1988; Gur et al., 1987), highlighting the
involvement of these cortical regions during periods of
While clinical anxiety represents an excessive or inap-
propriate response to perceived threat, the underlying neural
circuitry associated with the basic components of anxiety
reactions may be common to both healthy and pathological
anxiety. Research within healthy adults aims at delineating
the specic neural circuitry involved in the normal emo-
tional self regulation associated with the various aspects of
anxiety reactions, providing a baseline for comparison with
the disordered and excessive reactions observed within clin-
ical populations. Evidence suggests that although disorder
specic abnormalities are observed within unique systems,
there is a core system comprised of elements of the para-
limbic belt which is common to anxiety states within both a
range of clinical anxiety populations, and within physiolog-
ical or normal anxiety (Rauch et al., 1997). Cortical activa-
tions associated with anxiety within healthy control subjects
are generally consistent to those observed amongst clinical
populations. Experimentally induced anxiety has also been
associated with activity within the prefrontal cortex (Simp-
son et al., 2001; Liotti et al., 2000; Critchley et al., 2001;
Chua et al., 1999). The results of Simpson et al. (2001)
suggests a dynamic interrelationship between decreased
rCBF within the PFC, attentional focus and subjective lev-
els of anxiety. These authors propose that the ability to
remain relaxed during anxiety provocation was associated
with successful suppression of prefrontal cortical activity in
the face of threatening aversive environmental stimuli. Ac-
tivations within the temporal poles and within the right
superior temporal sulcus and bilateral insula have also been
reported within healthy anxious subjects, as have activa-
tions within occipital cortical regions (Paquette et al., 2003;
Liotti et al., 2000; Kimbrell et al., 1999; Reiman et al.,
Anticipatory Anxiety (AA) is one of the most basic
forms of anxiety, and while being experienced by normal
individuals, also occurs within a number of clinical anxiety
disorders such as PD and phobias. AA refers to human
anxiety that is focused on an imminent threat or danger and
is typically associated with sympathetic arousal and ght or
ight reactions. AA can be differentiated from the more
long term and distally focused anxiety, such as worry,
which may largely constitute disorders such as GAD in a
similar fashion to Heller et al.s (1997) differentiation of
Anxious Arousal from the more generalised Anxious Ap-
prehension. AA has previously been induced within healthy
male controls via the expectation of an unpleasant electric
shock (Simpson et al., 2001; Chua et al., 1999; Reiman et
al., 1989). AA is also associated with arousal of the central
autonomic nervous system, previously gauged by examina-
tion of electrodermal activity (Chua et al., 1999; Kopacz
and Smith, 1971). These previous investigations amongst
healthy controls have employed Positron Emission Tomog-
raphy (PET) to investigate the alterations in cerebral meta-
bolic function associated with AA. Whilst providing data
976 M. Gray et al. / NeuroImage 20 (2003) 975–986
with an exceptional spatial resolution, PET data is less able
to provide ne-grained information on when these changes
occur and insight into the temporal continuity of AA acti-
In the current study, we aimed to examine electrical brain
activity associated with AA using an electrophysiological
technique called Steady State Probe Topography (SSPT).
SSPT is a variant of EEG which allows the examination of
cortical electrical activity on a millisecond timescale. Pre-
vious studies also have indicated that SSVEP is relatively
insensitive to noise contamination from sources including
Electrocculargraphic (EOG), eye blink, 50 Hz mains, and
electromyographic (EMG) noise (Silberstein et al., 1998;
Regan 1989). Furthermore, studies within our laboratory
suggest that SSVEPs are sensitive to cognitive (Silberstein
et al., 1998, 1996) and emotional alterations (Kemp et al.,
2003, 2002, in press). In addition, the differing neural basis
of PET and SSVEP data may provide complementary in-
formation the metabolic demands and excitatory or inhibi-
tory nature of localized cortical activity.
Twenty-six healthy males (age 23.4 yrs, 4.0) par-
ticipated in the present study. Prior to inclusion in the study,
all subjects underwent a medical examination, screening for
physical illness, and past or present neuropsychiatric disor-
ders. Subjects were non-smokers and were free of psycho-
tropic or prescribed medications. All subjects were strongly
right handed as assessed by the Edinburgh Handedness
Inventory (Oldeld et al., 1971). Subjects were recruited via
university notice board advertisements, and were generally
well educated (education 15.2 years, 2.0 yrs). All
subjects gave written informed consent to take part in the
study, which was approved by the Swinburne University
Human Research Ethics Committee.
Behavioural measures
Upon arrival subjects completed the Stait Trait Anxiety
Inventory (STAI) State and Trait versions (Spielberger et
al., 1970), and the Beck Depression Inventory (BDI) to
assess levels of anxious and depressive symptomatology
(Beck et al., 1961). Subjects also completed a Visual Ana-
logue Scale (VAS) measure of anxiety prior to scanning,
after the baseline scan and again after the anxiety-inducing
scan. The VAS consisted of three 100 mm lines anchored at
each end with the words relaxed/anxious, calm/nervous, and
Experimental tasks
Subjects completed a simple computer based Continuous
Performance Task, the CPT-AX under two conditions; a
relaxed followed by an anticipatory anxiety condition. The
CPT-AX task, previously described in Silberstein et al.
(2000, 1998, 1996), was included in order to ensure a basic
level of cognitive activity which was consistent between
task conditions. Subjects were instructed to view a computer
monitor upon which a random letter appeared every 1.5 sec,
remaining on the screen for 1.2 sec after which it was
replaced by a central xation cross. Subjects held a button
box and were required to make a button press on the un-
predictable appearance of the letter X, only when this was
preceded by the letter A. The ratio of targets to non-targets
was set at 1:4. The letters subtended a vertical and horizon-
tal angle of approximately 1.2 degrees when viewed at the
xed distance of 2.3 meters. During the relaxed task con-
dition, a 1.2 cm blue border framed the stimulus presenta-
tion screen. Subjects were assured that they would not
receive any electric shocks during the baseline task. During
the anticipatory anxiety condition, SS performed the same
CPT-AX task. As in the control condition, this task began
with a blue-bordered screen. Every 25 sec, this border
changed from blue to red, for a period of 11 sec. This
occurred 11 times throughout the task. SS were informed
that during this task they may receive electric shocks at any
time during the red border display. Five shocks were ad-
ministered at varying latencies after red border onset, en-
suring that subjects could not predict the exact timing of
electrical stimulation.
Procedureexperimental design
Subjects sat in a quiet recording room 2.3 meters from the
task computer monitor. Brain electrical activity was recorded
through an electrode cap containing 64 electrodes (1020
international location system and other midpoint electrodes),
with linked ear electrodes as a reference and a nose electrode
as ground. Half-mirrored goggles were tted which emitted a
ickering mild white light (13 Hz) while allowing subjects to
see the computer monitor before them. Subjects completed the
baseline task while SSPT data was collected. An isolated
stimulator CMS1-200 (Dogwood scientic equipment) was
used to deliver electrical stimulation via electrodes applied to
the dorsal aspect of the subjectsright hand immediately prior
to completion of the AA condition. Shocks were set at a
predetermined level of 30 mA, 115 v (maximum).
SSPT signal processing
The key features of the SSPT signal processing em-
ployed is described in Silberstein et al. (1995, 1990). Brain
electrical activity was amplied and ltered with a 0.74 Hz
high pass lter and a 74 Hz low pass lter prior to digiti-
zation (16 bit accuracy). Electrical activity was recorded at
a sampling rate of 500 Hz. SSVEPs, induced via a spatially
uniform 13 Hz visual icker were extracted from the brain
electrical activity by calculating the sine and cosine Fourier
Transform (FT) coefcients at each stimulus cycle during
each task recording. FT coefcients were smoothed to re-
977M. Gray et al. / NeuroImage 20 (2003) 975986
duce noise by averaging overlapping blocks of 10 stimulus
cycles. All data were checked for artifact within each elec-
trode as described in Silberstein et al. (1995).
SSVEP data analysis
The SSVEP was rst epoched to provide measures of
cortical activity within the relaxed and AA conditions. Dur-
ing the relaxed condition, nine seven-second periods were
randomly selected and averaged to form an epoch of relaxed
task SSVEPs for each subject. Similarly, nine seven-second
epochs were selected during the AA condition. These ep-
ochs were chosen so that they began upon the presentation
of the red-bordered screen and ended before shock delivery.
Electrical stimulation was delivered within the rst 1.5 sec
of the red border presentation during the remaining AA
periods, and as a result these were not included as AA
SSVEP epochs. The task characteristics during the relaxed
and AA epochs were matched, so that each contained the
same number of A and X targets as well as the same number
of AX responses required. SSVEP data is comprised of both
amplitude; the size of the SSVEP signal recorded at each
electrode site, and phase components; alterations in the time
between sinusoidal steady state visual stimuli presentation,
and their expression as SSVEP within the cortex. SSVEP
amplitude was normalized by subtracting the average am-
plitude for all electrodes from each electrode time series
(discrete waveform) data, for each subject. SSVEP phase
was normalized by subtracting the mean phase for each
electrode from its time series for each subject. Cross subject
averages were then constructed for each task condition,
providing averaged SSVEP maps for each of the 91 data
cycles (13 Hz 7 sec) within both the relaxed baseline and
AA conditions.
Topographic mapping of SSVEP data
Difference maps, subtracting the relaxed condition SS-
VEP from the SSVEP obtained during the AA condition,
were generated to provide a measure of electro-cortical
activity observed during periods of anticipatory anxiety.
SSVEP phase variations are presented in millisecond (msec)
latencies; (change in phase/2
)(1000/13). Hotellings
T statistics indicating the statistical strength of differences
in amplitude and phase combined were also calculated.
Previous spatial component analysis of SSVEP data sug-
gests that 5 independent factors are represented in SSVEP
data (Silberstein et al., 1995). As a result, Hotellings T p
values (2-tailed) have been divided by 5 before being re-
ported. Hotellings T statistics are presented as topographic
maps illustrating the statistical signicance of differences in
amplitude and latency at each electrode. Contour lines il-
lustrate areas of statistical signicant at 0.05 and 0.01 and
0.001 alpha levels.
Statistical cluster plot & component mapping
A statistical cluster plot displaying Hotellings T data
across all electrodes (y-axis) and time-points (x-axis) was
generated to investigate the location and time course of
signicant SSVEP differences. One benet of statistical
cluster plots is their ability to display data at each time point
across all electrodes, providing a clear summary of temporal
patterns of signicance. While datasets comprised of nu-
merous point wise t-tests will contain randomly distributed
type 1 error, clusters of statistical signicance are likely to
reect real effects, and may provide a useful guide for
further examination (Murray et al., 2002; Guthrie and Buch-
wald, 1991). Electrodes are approximately separated into
frontal (electrodes 020, including Fp1, Fp2, F7, F3, Fz, F4,
and F8), parieto-temporal (electrodes 2152, including T3,
C3, Cz, C4, T4, T5, P3, Pz, P4, and T6) and occipital
(electrodes 5363, including O1, Oz, and O2) locations.
The two clusters of signicant differences within frontal/
temporal electrodes clearly evident in the statistical cluster
plot were further examined by generating early and late
epochs (each 1 sec at 13 Hz), applying the original normal-
isation routine, and averaging the resulting data sets to form
topographic maps.
Electrodermal data analysis
Electrodermal measures of skin conductance (SC) were
recorded throughout the baseline and AA conditions for 14
of the 26 subjects using the Psylab SC5-SA skin conduc-
tance and temperature coupler. Electrodes were located on
the distal phalanx of index and middle ngers, and a hy-
poallergenic gel ensured contact between the skin and elec-
trode. Skin conductance was recorded at 40 Hz and digitized
to 24-bit accuracy at the electrode site, producing SC data
with an absolute accuracy of 0.1 micro siemens. Mean Skin
Conductance Level (SCL) was chosen as an electrodermal
index of sympathetic nervous system arousal, as this mea-
sure is able to reect differences in both the amplitude and
the frequency of non-specic skin conductance responses,
as well as general phasic increases in galvanic SC. In order
to ensure SCLs were not articially inated by shock de-
livery, we selected the four red-bordered epochs during
which no shocks were actually delivered. These were aver-
aged together to provide a measure of AA SC for each
subject. Relaxed SC was constructed from the average of
the entire baseline condition.
EMG artifact investigation
In order to ensure the results from our study were not
contaminated by electromyographic (EMG) noise, we ex-
amined the inuence of EMG activity on SSVEP proles. A
subset of 15 subjects were quasi-randomly selected to com-
plete an EMG artifact condition immediately following the
recording of the baseline AX condition. Subjects instructed
to complete the baseline AX task a second time while
978 M. Gray et al. / NeuroImage 20 (2003) 975986
clenching their jaw every 2 to 3 sec. Apart from this, the
task instructions were identical, as were data analysis pro-
The BDI scores (M5.3, SD 5.7) indicated that no
subjects suffered from depressive symptomatology to any
discernable extent. These scores are within the normal BDI
range for male college students. Likewise the trait STAI
scores (M36.4, SD 7.6) also indicated that all subjects
were within the normal ranges (Spielberger et al., 1970).
State STAI scores (M32.3, SD 6.8) indicated that
subjects were reasonably relaxed before testing com-
menced. VAS scores indicated that subjects were signi-
cantly more anxious during the anxiety induction task t(21)
8.194, p0.001, see Fig. 1.
EMG artefact results
Mann-Whitney Unon-parametric tests for independent
samples indicated that the 15 subjects included in the EMG
control study were not signicantly different from the re-
maining 11 subjects in terms of STAI (state or trait mea-
sures), BDI scores, or VAS levels during either the relaxed
or anticipatory conditions. Hotellings T analysis failed to
reveal any signicant differences at any electrode site be-
tween SSPTs recorded during the baseline and the EMG
artifact condition.
Behavioural self-report measures and SCL
Again, Mann-Whitney Uanalysis indicated that the 14
subjects for which SCL data was recorded were not signif-
icantly different from the remaining subjects in terms of
STAI (state or trait measures), BDI scores, or VAS levels
during either the relaxed or anticipatory conditions. Analy-
sis of SC data revealed signicant increases in sympathetic
nervous system arousal during the AA condition, relative to
the baseline t(13) 3.256, p0.006, see Fig. 1.
SSVEP data
We rst examined the SSVEP difference data across the
seven-second epoch as a whole. Fig. 2 (left) shows the mean
SSVEP maps specic to the AA condition. Hotellings T
data is presented as a topographic map illustrating the sta-
tistical signicance of AA specic differences in SSVEP
data (considering both amplitude and latency differences).
Across the entire 7 sec epoch, AA was associated with
signicant alterations in SSVEPs within the medial (mid-
line) anterior frontal cortex, left dorsolateral prefrontal cor-
tex, bilateral temporal lobes, and left occipital cortex. Fig. 2
also illustrates differences in both the amplitude and latency
components of the SSVEPs. Warmer colours indicate re-
duced SSVEP amplitude and latency in the AA condition
relative to the baseline scan. Signicant alterations within
frontal and temporal electrodes are associated predomi-
nately with increases in SSVEP latency. SSVEP amplitude
increases are evident only within the occipital cortex. Wide-
spread latency reductions are evident within bilateral occip-
ital lobes; however, only a smaller portion of the left oc-
cipital lobe reached statistical signicance.
In order to examine the temporal nature of the observed
alterations in SSVEPs, we generated a Hotellings T statis-
tical cluster plot which displays the signicant SSVEP dif-
ferences for all electrodes (y-axis) across time (x-axis) (see
Fig. 2, right). An examination of the statistical cluster plot
indicates that the majority of signicant frontal and tempo-
ral differences occur in two bursts, an initial early compo-
nent (6921692 ms) and a later component (50006000 ms)
indicated by the white banded regions in Fig. 2. The occip-
ital activations conversely are relatively stable and consis-
tent throughout the windowing period, and are therefore
reasonably illustrated within the 7 sec epoch mean topo-
graphic maps. In order to examine frontal and temporal
activations, we generated SSVEP mean topographic maps
for both these early and late components (see Fig. 3).
Within both the early (6921692 ms) and late (5000
6000 ms) epochs, signicant differences are again primarily
driven by alterations in SSVEP latency. During the early
component epoch (6921692 ms), SSVEP latency increases
reached signicance within midline prefrontal electrodes
and left dorsolateral prefrontal electrodes. Further examina-
tion reveals the largest latency increases within temporal
electrodes (particularly left hemisphere) and left dorsolat-
eral electrodes. As in the entire epoch mean (Fig. 2), occip-
ital latency reductions are evident, reaching signicance
within the left occipital lobe. SSVEP amplitude changes are
relatively modest, with minor amplitude reductions within
the left frontal lobe and amplitude increases within the right
frontal and temporal lobes and within bilateral occipital
lobes. During the later component epoch (50006000 ms),
signicant differences are observed within large regions of
the bilateral frontal lobes, within the right temporal lobe,
and bilateral occipital lobes. Occipital amplitude and la-
tency increases are more pronounced during the later com-
ponent. Relative to the early component, SSVEP latency
increases are attenuated within the temporal lobes, particu-
larly within the left hemisphere, whilst within prefrontal
electrodes, larger latency increases are evident, particularly
within bilateral anterior frontal electrodes.
Further examination of the temporal prole of SSVEP
latency changes within the temporal lobes revealed some
evidence of hemispheric differences. Fig. 4 displays the
SSVEP latency changes recorded at 3 temporal lobe elec-
trodes within each hemisphere across the entire 7 sec epoch.
During the early component, the left hemisphere latency
increases are larger, more uniform, and more sharply de-
ned than within the right hemisphere.
979M. Gray et al. / NeuroImage 20 (2003) 975986
The current study examined the temporal processing of
AA within healthy male subjects. Our ndings suggest that
AA is associated with two predominant electrophysiological
changes; (1) signicant SSVEP latency increases within
prefrontal and temporal cortical regions, and (2) signicant
SSVEP latency decreases and amplitude increases within
occipital regions. Whilst occipital SSVEP latency decreases
and amplitude increases were evident throughout the anx-
ious anticipatory epoch, frontal and temporal lobe latency
increases were more transitory, appearing within the rst
sec, and again within the fth sec of the imaging window.
These cortical activations were associated with concomitant
increases in self-reported anxiety and electrodermal activ-
In terms of regional cortical alterations, the present nd-
ings are consistent with a large amount of previous research
amongst both patient groups and healthy controls. Anxiety
associated prefrontal increases in rCBF have been fre-
quently reported by metabolic imaging studies (Paquette et
al., 2003; Rauch et al., 2002, 1997; Meyer et al., 2000;
Zubieta et al., 1999; Shin et al., 1999; Malizia et al., 1999;
Liberzon et al., 1999; Johanson et al., 1998; Nordahl et al.,
1998, 1990; Breiter et al., 1996; Semple et al., 1993; Rubin
et al., 1992; Wu et al., 1991; Swedo et al., 1989; Baxter et
al., 1987). Previously reported increased rCBF within ante-
rior temporal lobes and insula are also consistent with the
signicant SSVEP alterations we observed within temporal
lobe electrodes (Boshuisen et al., 2002; Osuch et al., 2001;
Meyer et al., 2000; Liotti et al., 2000; Chua et al., 1999;
Shin et al., 1999; Rauch et al., 1997, 1996, 1995; Breiter et
Fig. 1. Skin conductance and visual analogue scale (Anxiety) measures during baseline and anticipatory anxiety conditions.
Fig. 2. SSVEP amplitude and latency changes and Hotellings T values during anticipatory anxiety induction (left) and statistical cluster plot illustrating the
selection of the early and late epochs (right).
980 M. Gray et al. / NeuroImage 20 (2003) 975986
Fig. 3. Mean SSVEP amplitude, latency and Hotellings T during early and late components.
Fig. 4. SSVEP latency changes within temporal lobe electrodes across the seven second imaging epoch. Early and late components are indicated by red
banded regions.
981M. Gray et al. / NeuroImage 20 (2003) 975986
al., 1996; Johanson et al., 1992; Wu et al., 1991; Reiman et
al., 1989). Likewise, regional anxiety associated changes
within the occipital cortex previously reported are also ev-
ident in the present results (Paquette et al., 2003; Mirzaei et
al., 2001; Fredrikson et al., 1997; Rauch et al., 1996; De
Cristofaro et al., 1993; Wu et al., 1991, Zohar et al., 1989;
Stewart et al., 1988; Buchsbaum et al., 1987).
SSVEPs are comprised of both amplitude and latency
components, each of which reect different aspects of re-
gional cortical network activation. Variations in SSVEP
latency have been previously interpreted as an index of
variations in neural information processing speed, and are
likely to result from alterations in the loop transmission time
of local cortico-cortical feedback loops (Kemp et al., 2002;
Silberstein et al., 2001, 1995). Previous research within our
institute has illustrated correlations between reaction time
during a visual vigilance task and SSVEP latency (Silber-
stein et al., 1996). In addition, SSVEP latency reductions
within prefrontal electrodes observed within normal chil-
dren during attentional tasks are attenuated among children
with attention decit hyperactivity disorder (Silberstein et
al., 1998), further strengthening the association between
latency decreases and normal excitatory processes. Alter-
ations in SSVEP latency are understood to result from the
excitatory and inhibitory neuromodulation of regional cor-
tico-cortical resonances (Silberstein et al., 2000, Regan,
1989). The release of neurotransmitters such as acetylcho-
line (ACh) are believed to reduce the cortico-cortical loop
time in a similar way to the increases in thalamocortical
transmission speeds following cortical ACh release ob-
served within animal research (Metherate and Ashe, 1993).
Likewise increases in latency are likely to be associated
with inhibitory neuromodulation of cortico-cortical feed-
back loops, possibly via inhibitory interneurons such as
golgi, basket and stellate cells (Attwell and Iadecola, 2002;
Koos et al., 1999). SSVEP amplitude is, in some respects,
analogous to EEG amplitude within the alpha bandwidth,
such that regional event related desynchronisation results in
relative EEG alpha and SSVEP amplitude reductions
(Pfurtscheller and Lopes da Silva, 1999). Conversely, in-
creases in the number of neurons recruited into synchro-
nously activated cortico-cortical rhythmic activity results in
cortico-cortical loop gain, or relative SSVEP amplitude
The present ndings of increased SSVEP latency within
frontal electrodes may be interpreted as evidence of an
increase in neurochemically modulated inhibitory cortical
activity. These results suggest that previously reported PFC
increases in rCBF may be associated with increased lo-
calised inhibition. Regions within the prefrontal cortex have
long been understood to have a role in the modulation and
inhibition of subcortical limbic structures including the
amygdala and cingulate (Carr et al., 2003; Quirk and Geh-
lert, 2003; Davidson et al., 2002; Cardinal et al., 2002;
Niemer and Goodfellow, 1966). The amygdala is well
known to be necessary for the development of conditioned
fear (LeDoux, 1996) and communicates with regions within
the prefrontal cortex including the orbitofrontal cortex via
direct excitatory efferents and the dorsolateral prefrontal
cortex through a smaller number of excitatory efferents as
well as pathways through the orbitofrontal cortex (Barbas,
2000). Glutamatergic projections from the PFC are believed
to project to GABAergic neurons which synapse on the
amygdala, allowing both the PFC and amygdala to modu-
late each other during cognitive-emotional processing (Da-
vidson et al., 2002; LeDoux, 1996). Disruption of this co-
modulation may underlie increased PFC activation observed
within clinical populations (Barbas, 2000). The increased
SSVEP latency within dorsolateral and anterior PFC elec-
trodes amongst our healthy subjects during AA may be
associated with increased inhibition within localised PFC
circuits occurring in response to increased excitatory input
from the amygdala, although without the ability to concur-
rently image amygdala activity, this interpretation must
remain speculative. The signicant SSVEP alterations
within the left dorsolateral PFC evident in the epoch mean
data and also within both the early and late frontal compo-
nents lies approximately over Brodmanns area 8, an area
which is known to receive robust projections from visual
association cortices within primates, and may be associated
with visual attentive aspects of the PFCs selection of emo-
tionally appropriate responding (Barbas, 2000). In addition,
anxiety induced increases in inhibitory activity within pre-
frontal regions accords well with decits in processes sub-
served by prefrontal information processing during anxiety,
including attentional biases and working memory decits
(Ninan and Berger, 2001; Mogg and Bradley, 1998; Beck,
Increases in localised inhibitory processes associated
with the observed signicant SSVEP latency increases
within the right temporal lobe are consistent with many
previous reports of anxiety associated rCBF increases
within the temporal lobes of both patients and healthy con-
trols (Paquette et al., 2003; Boshuisen et al., 2002; Liotti et
al., 2000; Meyer et al., 2000; Chua et al., 1999; Rauch et al.,
1997, 1995; Breiter et al., 1996; Johanson et al., 1992; Wu
et al., 1991; Reiman et al., 1989). The frequently reported
activity within temporal cortices observed during the imag-
ing of human anxiety has previously been related to visceral
processing by the agranular neurons within the medial wall
of the temporal lobe and insula (Chua et al., 1999; Mesulam
and Mufsom 1982a). The temporal poles and insula form
part of the paralimbic cortex, reciprocally connected to the
amygdala, orbitofrontal and dorsolateral PFC and cingulate
gyrus, and are thought to integrate internal and external
environmental information useful for selection of appropri-
ate responses during situations involving threat, helpless-
ness or danger (Barbas, 2000; Pandya, 1995, Reiman et al.,
1989; Mesulam and Mufsom, 1982b). Our ndings of in-
creased SSVEP latency within temporal lobe electrodes
suggests that within these regions AA is again associated
with increased localised inhibitory modulation of cortico-
cortical oscillatory activity. Our ndings of larger latency
increases and more frequently signicant right temporal
982 M. Gray et al. / NeuroImage 20 (2003) 975986
lobe alterations, relative to the left hemisphere within both
the later component and overall epoch means are consistent
with the more frequent reports of rCBF increases within the
right temporal lobe, relative to the left associated with
anxiety specically, and emotional processing generally
(Heilman, 1997; Heller et al., 1997; Ross, 1981). It is
interesting to note, however, that the largest SSVEP latency
increases were observed within the left hemisphere during
the early component. This is consistent with largest rCBF
increases within the left insula of healthy males anticipating
an electric shock reported by Chua et al. (1999). Davidson
et al. (2002) suggests that the left PFC particularly may be
involved with inhibitory control of amygdala activity. Our
results indicate that this latency increase was more clearly
dened within the left hemisphere, providing some evi-
dence of hemispheric differences in the temporal lobe in-
volvement during AA.
The results from the EMG artefact condition have par-
ticular relevance to the observed changes within the tempo-
ral lobes. Acute periods of anxiety are commonly associated
with increases in muscle tension, which signicantly in-
creases the risk of EMG artefact during electrophysiological
recordings of brain activity. Previous reports on anxiety
induced alterations in temporal lobe function have had to
defend against claims of EMG artefact (Benkelfat et al.,
1995; Drevets et al., 1992). Our ndings of no signicant
SSVEP differences between the baseline and EMG artefact
conditions suggest that the observed results are indeed re-
lated to temporal lobe function.
A signicant amount of research has reported increased
activation of the occipital cortex associated with both the
visual processing of emotionally valanced stimuli (Kemp et
al., 2002; Phan et al., 2002; Lane et al., 1999; Lang et al.,
1998; Morris et al., 1998), and with anxiety, within patient
groups and anxious controls (Paquette 2003; Fredrikson et
al., 1997, 1993; Rauch et al., 1996; Breiter et al., 1996; De
Cristofaro et al., 1993; Wik et al., 1993; Wu et al., 1991;
Zohar et al., 1989; Gur et al., 1987). Wik et al., (1996)
observed anxiety related decreases in rCBF within primary
visual cortical regions amongst phobics which may be as-
sociated with anticipatory coping. Within occipital elec-
trodes, we also observed signicant SSVEP alterations dur-
ing periods of anxious anticipation. These were generally
observed within the left hemisphere, and were localised
with decreases in SSVEP latency observed within occipital
electrodes. Regions of the limbic cortex including the ante-
rior temporal lobes, orbitofrontal and dorsolateral PFC and
the magnocellular portion of the basal nucleus of the amyg-
dala are reciprocally connected to the primary visual cortex
and widespread regions of the extra-striate cortex (Weller et
al., 2002; Linke et al., 1999; Barbas, 1995). This connec-
tivity is likely to underlie visual cortex alterations observed
not only during anxiety induction, but also more generally
during emotional processing (Phan et al., 2002; Davis and
Whalen, 2001; Lang et al., 1998; Morris et al., 1998; Breiter
et al., 1996). The decreased SSVEP latency observed within
occipital electrodes is consistent with an increase in lo-
calised excitatory processes, possibly associated with in-
creased modulation of visual processing by regions of the
limbic system including the amygdala (LeDoux, 1996). Our
previous studies have reported SSVEP amplitude decreases
within extra-striate visual areas associated with increased
visual vigilance during continuous performance attentional
tasks (Nield et al., 1998; Silberstein et al., 1990). In con-
trast, the present results indicate SSVEP amplitude in-
creases within extra-striate cortex during periods of AA. We
hypothesise that this may be due to a shift in attentional
focus away from the visual aspects of the task in the face of
intense emotional induction. This is consistent with previ-
ous ndings that while highly trait anxious controls shift
attention towards anxiety inducing stimuli, normal controls
tend to divert attention from anxiety inducing stimuli (Wil-
son and MacLeod, 2003; Mogg and Bradley, 2002; Clark,
1999; Vasey et al., 1996).
Scalp recorded SSVEPs are generated by the synchro-
nised ring of pyramidal neurons lying within layers 2 and
3 of the cortex (Silberstein et al., 2001; Regan, 1989).
Alterations in rCBF measured by metabolic imaging meth-
odologies, such as PET and fMRI are understood to be
driven by the synaptic energy requirements of re-establish-
ing ionic concentrations and neurotransmitter repackaging
(Arthurs et al., 2002, Attwell and Iadecola, 2002, Attwell
and Laughlin, 2001; Jueptner and Weiller, 1995). Logoth-
etis and colleagues have recently shown in a fascinating
series of articles that rCBF as indexed by the BOLD re-
sponse is closely correlated with local eld potentials within
the occipital cortex, strengthening the association between
excitatory driven BOLD responses and cortical local eld
potentials (Logothetis et al., 2003, 2001; Logothetis, 2002).
A number of researchers have argued that both inhibitory
and excitatory activity is associated with increased rCBF
resulting from ion recycling and ion gradient restoration
(Arthurs et al., 2002, Jueptner and Weiller, 1995, Nudo and
Masterton, 1986, Ackermann et al., 1984). Although meta-
bolic imaging methodologies and electro-cortically re-
corded eld potentials gauge information processing within
cortical regions, the differing neurological basis of each
methodology may provide complementary perspectives on
regional cortical activity. Our ndings of region specic
excitatory and inhibitory processes in areas previously as-
sociated with rCBF increases suggests that further research
could benet from the simultaneous investigation of SSVEP
latency and rCBF alterations within the same region of the
In summary, the results from the present study support
alterations in regions previously found to undergo increases
in rCBF during anxious anticipation, including the anterior
and dorsolateral PFC, anterior temporal cortices, and the
extra-striate cortex. While previous research has reported
increases in rCBF within prefrontal, temporal and occipital
cortical regions, our results suggests an increase in localised
inhibitory processes within the PFC and anterior temporal
lobes, and an increase of localised excitatory processes
within regions of the extra-striate occipital cortex during
983M. Gray et al. / NeuroImage 20 (2003) 975986
anticipatory anxiety. These ndings may provide further
insight into the nature of the neurophysiological mecha-
nisms underlying anticipatory anxiety.
The authors would like to thank Cindy Van Roy, Peter
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... Moreover in extended interval of time, the discrete frequency components remain closely constant for SSVEP components, both in amplitude and phase [13]. In addition SSVEPs are also less susceptible to artifacts produced by blinks, eye movements and electromyographic noise contamination [14,15,16]. ...
... Rhythms originating at motor cortex as a result of cerebral activity and motor activity comprise this category. These rhythms consist of oscillations in the brain activity in the frequency band (7)(8)(9)(10)(11)(12)(13) and (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), which are generally known as Mu and Beta rhythms respectively [10]. These rhythms are used to control BCIs as one could be trained to generate these modulations voluntarily [36,37]. ...
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BCI (Brain computer interface) is a control and communication system which allows electrophysiological activity to control a computer or a peripheral device directly, without taking the natural route of peripheral nerves and muscles. The prime motive behind developing BCI technology was its ability to act as the only interactive link for people disabled by amyotrophic lateral sclerosis (ALS), cerebral palsy, spinal cord injury, stroke and similar neuromuscular disorders of high severity. However in the last decade, a gradual shift in BCI end-users from patients to casual (healthy) individuals has increased significantly. Because of this shift, BCI community has recognized the need for EEG based casual BCI to be more efficient and user friendly, keeping in mind the customized needs of healthy (Casual) user. So for increasing the performance of such BCIs, the selection of optimal control signal plays a very significant role. Hence, in this work, we evaluate various EEG control signals (CS) in accordance with considerations relevant to user-friendliness of casual BCIs and point up their neuro-physiological origins as well as their effectiveness in current applications. Finally, we recommend a set of parameters for selection of optimal EEG based control signal for casual BCIs and the best suitable option available among the present day control signals.
... In our study, the power spectrum could reflect decreased power spectral density at the occipital lobe in the gamma band under the condition of neutral music. A study provided further support for the involvement of anterior temporal and occipital cortical regions during anticipatory anxiety and suggested that both excitatory and inhibitory processes were associated with anticipatory anxiety alterations [65]. Our results were consistent with the study mentioned above, which demonstrated that low state anxiety was associated with a decrease in power spectral density in the temporal lobe and occipital lobe after neutral music intervention. ...
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Background: Some clinical studies have indicated that neutral and happy music may relieve state anxiety. However, the brain mechanisms by which these effective interventions in music impact state anxiety remain unknown. Methods: In this study, we selected music with clinical effects for therapy, and 62 subjects were included using the evoked anxiety paradigm. After evoking anxiety with a visual stimulus, all subjects were randomly divided into three groups (listening to happy music, neutral music and a blank stimulus), and EEG signals were acquired. Results: We found that different emotional types of music might have different mechanisms in state anxiety interventions. Neutral music had the effect of alleviating state anxiety. The brain mechanisms supported that neutral music ameliorating state anxiety was associated with decreased power spectral density of the occipital lobe and increased brain functional connectivity between the occipital lobe and frontal lobe. Happy music also had the effect of alleviating state anxiety, and the brain mechanism was associated with enhanced brain functional connectivity between the occipital lobe and right temporal lobe. Conclusions: This study may be important for a deep understanding of the mechanisms associated with state anxiety music interventions and may further contribute to future clinical treatment using nonpharmaceutical interventions.
... Firstly, unlike transient evoked potentials such as N200 or P3b, SST is well suited to the study of time extended cognitive tasks such as the ones described in the current study. In addition, the SST methodology is highly resistant to the common sources of EEG artifacts such as muscle activity, blinks and eye movements (Silberstein, 1995;Gray et al., 2003). Finally, the SST measures of brain activity appear to be suitably sensitive to cognitive processes such as visual attention and long-term memory encoding (Silberstein et al., 1990(Silberstein et al., , 2000aSilberstein and Nield, 2008). ...
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While our experience of the world may appear continuous, recent evidence suggests that our experience is automatically segmented and encoded into long-term memory as a set of discrete events. Event segmentation is an important process in long-term memory encoding with evidence pointing to experiences occurring around event boundaries being better recognized subsequently. Neuroimaging studies have shown increased activity in the hippocampus and other nodes of the default mode network (DMN) when encountering an event boundary. We have previously demonstrated that the steady state topography (SST) measure of brain activity at a left inferior frontal scalp sites is correlated with the strength of long-term memory encoding. More recently, we have noted that event boundaries occurring in naturalistic stimuli such as television advertising trigger a transient drop in activity at the inferior frontal scalp sites, an effect we have termed Conceptual Closure. In this study, SST measures of brain activity were recorded in 50 male participants as they viewed a first-person journey through a 10-room virtual art gallery. We hypothesized that the transition from one room to another would serve as an event boundary which would triggers increased hippocampal and DMN activity while correspondingly decreasing activity in task positive networks in the vicinity of the inferior frontal cortex thus eliciting Conceptual Closure. A permutation test confirmed the hypothesis in that the appearance of the door between gallery rooms was associated with Conceptual Closure in that we observed a significant drop in brain activity at the left hemisphere inferior frontal scalp site at this point in time. Finally, we illustrate the real-world impact of Conceptual Closure by considering the commercial effectiveness of a television advertisement that exhibited Conceptual Closure at points of branding. The television advertisement was broadcast before and after it was re-edited to minimize Conceptual Closure at the time the advertising brand was being featured. Minimizing Conceptual Closure at the time of branding and key message was associated with significant increased commercial effectiveness of the advertisement.
... Steady-state probe topography is a variant of the EEG, which allows for the millisecond time scale to be studied in a cortical (centralized data analytics of the human brain) electrical activity (Gray et al., 2003). ...
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With the acceleration of technology, companies have to constantly renew also their marketing strategies in order to get closer to consumers, to encourage them to buy their products and to outperform their competitors. One of these marketing strategies is neuromarketing. Neuromarketing is a marketing activity that tries to find consumers' buying behavior towards a product in a subconscious way with rational data. This marketing method makes measurements on brain waves with devices such as Positron Emission Tomography (PET), functional Magnetic Resonance Imaging (fMRI), Electroencephalography (EEG), Steady State Probe Topography (SSPT), Galvanic Skin Response (GRS), Magnetoencepholography (MEG), Eye Tracking. It is thought that neuromarketing will directly affect research and its applications in sports marketing in the near future. Therefore, in this study, a comprehensive literature review has been performed and the concept of neuromarketing has been examined thoroughly with document analysis and its effects on sports marketing has been evaluated. Keywords: Neuromarketing, Sports Marketing, Consumer, Purchase Decision, Subconscious
Background: Homocysteine, a methionine metabolite, is a recognized risk factor for accelerated age-related cognitive decline and dementia. Objective: In the light of studies indicating increases in brain activity and brain functional connectivity in the early stages of age-related cognitive decline, we undertook a study to examine the relationship between plasma homocysteine levels and brain functional connectivity in a group of late middle-aged males at risk of cognitive decline due to high body mass index and a sedentary lifestyle. Methods: Brain functional connectivity was measured using the steady state visual evoked potential event related partial coherence while 38 participants performed a memory task where each trial comprised an object recognition task followed by a location memory task. Results: We observed a significant transient peak in the correlation between plasma homocysteine levels and fronto-parietal brain functional connectivity immediately before the presentation of the memory location component of the task. Significantly, this correlation was only apparent if the participant pool included individuals with homocysteine concentrations above 11μmole/L. Conclusion: Our findings suggest that the increased brain functional connectivity observed in the earlier stages of age-related cognitive decline reflects pathognomonic changes in brain function and not compensatory changes engaged to enhance task performance. Our findings also suggest that homocysteine interferes with the inhibition of cortical networks where this inhibition is necessary for optimum task performance. Finally, we observed that the effect of homocysteine on brain functional connectivity is only apparent at concentrations above 11μmol/L.
Background Many aspects of steady-state responses of the brain remain unclear in bipolar disorder (BD) due to the small number of auditory steady-state response (ASSR) studies and the lack of steady-state visual evoked potential (SSVEP) studies on this complex disorder. Therefore, we assessed the patterns of SSVEP and ASSR in adolescents with BD during an active task to detect possible deficits in these important brain responses compared to normal subjects. Methods 27 adolescents with BD and 30 healthy adolescents were assessed in this study. The blinking background of the monitor presented at 15 Hz and the tone signal stimulation at 40 Hz evoked SSVEPs and ASSRs, respectively. The phase and amplitude of the steady-state responses were calculated in the auditory and visual conditions. Results Patients exhibited a substantially worse performance in the motor control inhibition task during both auditory and visual modalities. Patients showed increased SSVEP amplitude and phase in the frontal region compared to control adolescents. Also, patients exhibited decreased ASSR amplitude in the prefrontal and increased ASSR amplitude in the right-frontal and centro-parietal areas compared to healthy adolescents. Conclusions impairments in the production and preservation of SSVEP and ASSR are evident in BD, implicating abnormalities in visual and auditory pathways. Neurophysiological deficits and worse performance in BD adolescents may imply that visual and auditory pathways cannot well transfer the pertinent information from arriving sensory data to the visual and auditory cortices, and the frontal cortex cannot well integrate incoming signals into a unified and coherent perceptual action.
Tea (Camellia sinensis) is widely considered to promote feelings of calming and soothing. This effect is attributed to L-theanine (L-γ-glutamylethylamide) in tea, a non-protein amino acid mainly derived from tea leaves. As a naturally occurring structural analogue of glutamate, L-theanine competes for the receptors with glutamate and is able to pass the blood-brain barrier to exert its relaxation effect. This review focuses on the relaxation effect of L-theanine, including animal models and the latest human trials as well as the potential molecular mechanisms regarding neuron stem cells. The biological efficacy of dietary L-theanine in the food matrix has been further discussed in this review in relation to the physiological changes in the gastrointestinal tract and bindings of L-theanine with other food components.
Brain-computer interfaces (BCIs) development is closely related to physics. In this paper, we review the physical principles of BCIs, and underlying novel approaches for registration, analysis, and control of brain activity. We analyse recent advances in BCI studies focusing on their applications for (i) controlling the movement of robots and exoskeletons, (ii) revealing and preventing brain pathologies, (iii) assessing and controlling psychophysiological states, and (iv) monitoring and controlling normal and pathological cognitive activity. After introducing the topic to the reader in chapter 1, in chapter 2 we consider the BCI as a hardware/software communication system that allows interaction of humans or animals with their surroundings without the involvement of peripheral nerves and muscles, using control signals generated from brain cerebral activity. Classifying BCIs into three main types (active, reactive and passive), we describe their functional models and neuroimaging methods, as well as novel techniques for signal enhancement and artifact recognition and avoidance, to improve BCI performance in real time. In this chapter, we also review different BCI applications, including communications, external device control, movement control, neuroprostheses, and assessment of human psychophysiological states. In chapters 3 and 4 we talk about the most common techniques for the analysis and classification of electroencephalographic (EEG) and magnetoencephalographic (MEG) data. Special attention is paid to modern technology based on machine learning and reservoir computing. Chapters 5–8 are devoted to main results on the creation and application of BCIs based on invasive and noninvasive EEG recordings. First, in chapter 5 we consider neurointerfaces for controlling the movement of robots and exoskeletons. Then, in chapter 6 we describe BCIs for diagnosis and control of pathological brain activity, in particular, epilepsy. We also discuss the results on the development of invasive BCIs for predicting and mitigating absence epileptic seizures. After that, in section 7 we focus on passive neurointerfaces for assessing and controlling a person’s psychophysiological states and cognitive activity. Chapter 8 is devoted to optogenetic brain interfaces using photostimulation to deliver intervention to specific cell types. We outline the basic principles of optogenetic neurocontrol and extracellular electrophysiology recording. At the end of this chapter, we describe the state-of-the-art of miniaturized closed-loop optogenetic devices to control normal and pathological brain activities. In chapter 9 we discuss the new emerging technological trend in the BCI development which consists in using neurointerfaces to improve the interaction between people, so-called brain-to-brain interfaces (BBIs). Such interfaces can increase the efficiency of collaborative processes when working in a group. We propose a BBI which distributes a cognitive load among all the team members working on a common task. This BBI allows sharing the workload among the participants according to their current cognitive performance, estimated from their electrical brain activity. The novel results of the brain-to-brain interaction are promising for the development of a new generation of communication systems based on the neurophysiological brain activity of interacting persons, where the BBI estimates the physical conditions of each partner and adapts the assigned task accordingly. Finally, in chapter 10 we trace the main historical epochs in BCI development and applications and highlight possible future directions for this research area, including hybrid BCIs.
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Brain signals are potential biometric markers in user authentication, complementing existing biometric authentication techniques (such as those based on fingerprint, iris and facial recognition). This paper proposes a novel EEG fusion method to examine the reliability and durability of EEG biometric markers across recording sessions. Our hypothesis is that models trained using EEG signals collected during various elicitation protocols can capture generalised brain patterns that pertain personalised information which can improve the durability of biometric systems. Different protocols are likely to produce different responses across brain regions, which can result in more identifiable responses from EEG. In our approach, an end-to-end convolutional neural network (CNN) model is adopted for feature extraction and classification of raw EEG data. The proposed method is evaluated on two EEG datasets which were collected over two separate sessions on different days using multiple different EEG elicitation protocols. Within-session and across-session experiments were conducted. Results for within session experiments showed that CNN models with protocol fusion can achieve similar if not better results than models trained with single protocol. In across-session scenarios, models trained with the proposed protocol fusion approach significantly outperformed single protocol based models. The obtained results illustrate the durability and reliability capabilities of the proposed fusion approach
Purpose: It has been shown that multifrequency stimulation with multifocal electroretinography can reduce recording time without a loss in signal-to-noise ratio. Here, we studied the applicability of multifrequency stimulations for steady-state visually evoked potential (VEP) recordings. Methods: Multifrequency VEPs were recorded monocularly from 10 healthy subjects using pattern-reversal stimuli. The reversal frequency varied between 5 and 30 Hz. Pattern-reversal checkerboard stimuli were generated using four square arrays, each containing 100 light-emitting diodes (LEDs), positioned in four quadrants. Each array had a temporal frequency that differed slightly from the nominal frequency. The long duration of the data acquisition ensured that the slightly different stimulus frequencies in the four LED arrays can be resolved and that the responses to the stimulus in each array can be distinguished (e.g., with a frequency resolution: 0.011 Hz at 12 Hz). The best response from the four recording electrode configuration, defined as the recording with the maximal signal-to-noise ratio, was used for further analysis. Algorithmic latencies were calculated from the ratio of phase data and frequencies in a range of 4 and 20 Hz. Results: Quadrant-VEPs with simultaneous pattern-reversal stimulation yielded a significant dependency on temporal frequency and stimulus location. The frequency range leading to the maximal response amplitude was between 10 and 12 Hz. Response phases decreased approximately linearly, with increasing temporal frequency suggesting a mean algorithmic latency between 112 and 126 ms. Conclusions: Multifrequency stimulation using LED arrays is an efficient method for recording pattern-reversal VEPs while all stimuli are presented at the same time. Translational relevance: Simultaneously recorded VEPs as performed by the multi-frequency method can be used for objective measurements of visual field defects.
Recently, there has been a convergence in lesion and neuroimaging data in the identification of circuits underlying positive and negative emotion in the human brain. Emphasis is placed on the prefrontal cortex (PFC) and the amygdala as two key components of this circuitry. Emotion guides action and organizes behavior towards salient goals. To accomplish this, it is essential that the organism have a means of representing affect in the absence of immediate elicitors. It is proposed that the PFC plays a crucial role in affective working memory. The ventromedial sector of the PFC is most directly involved in the representation of elementary positive and negative emotional states while the dorsolateral PFC may be involved in the representation of the goal states towards which these elementary positive and negative states are directed. The amygdala has been consistently identified as playing a crucial role in both the perception of emotional cues and the production of emotional responses, with some evidence suggesting that it is particularly involved with fear-related negative affect. Individual differences in amygdala activation are implicated in dispositional affective styles and increased reactivity to negative incentives. The ventral striatum, anterior cingulate and insular cortex also provide unique contributions to emotional processing.
The haemodynamic responses to neural activity that underlie the blood-oxygen-level-dependent (BOLD) signal used in functional magnetic resonance imaging (fMRI) of the brain are often assumed to be driven by energy use, particularly in presynaptic terminals or glia. However, recent work has suggested that most brain energy is used to power postsynaptic currents and action potentials rather than presynaptic or glial activity and, furthermore, that haemodynamic responses are driven by neurotransmitter-related signalling and not directly by the local energy needs of the brain. A firm understanding of the BOLD response will require investigation to be focussed on the neural signalling mechanisms controlling blood flow rather than on the locus of energy use.
Conference Paper
Objective: The purpose of this study was to determine whether anterior limbic and paralimbic regions of the brain are differentially activated during the recollection and imagery of traumatic events in trauma-exposed individuals with and without posttraumatic stress disorder (PTSD). Method: Positron emission tomography (PET) was used to measure normalized regional cerebral blood flow (CBF) in 16 women with histories of childhood sexual abuse: eight with current PTSD and eight without current PTSD. In separate script-driven imagery conditions, participants recalled and imagined traumatic and neutral autobiographical events. Psychophysiologic responses and subjective ratings of emotional state were measured for each condition. Results: In the traumatic condition versus the neutral control conditions, both groups exhibited regional CBF increases in orbitofrontal cortex and anterior temporal poles; however, these increases were greater in the PTSD group than in the comparison group. The comparison group exhibited regional CBF increases in insular cortex and anterior cingulate gyrus; increases in anterior cingulate gyrus were greater in the comparison group than in the PTSD group. Regional CBF decreases in bilateral anterior frontal regions were greater in the PTSD group than in the comparison group, and only the PTSD group exhibited regional CBF decreases in left inferior frontal gyrus. Conclusions: The recollection and imagery of traumatic events versus neutral events was accompanied by regional CBF increases in anterior paralimbic regions of the brain in trauma-exposed individuals with and without PTSD. However, the PTSD group had greater increases in orbitofrontal cortex and anterior temporal pole, whereas the comparison group had greater increases in anterior cingulate gyrus.
In-vivo neuroimaging allows the investigation of brain circuits involved in the experience of anxiety and of receptor changes associated with anxiety disorders. This review focuses on studies by research groups who have compared brain activation maps in different forms of anxiety and on binding studies of the benzodiazepine-GABA(A) receptor. Activation studies have revealed the involvement of many brain areas depending on the condition and the paradigm. However, the orbitofrontal cortex/anterior insula and the anterior cingulate are implicated in all the studies and may represent the nodal point between somatic and. cognitive symptoms of any form of anxiety. Most studies of binding at the benzodiazepine-GABA(A) receptor are not interpretable because of substantial methodological problems, however, regional and/or global reductions are the most consistent finding in panic disorder.
Conference Paper
Anxiety disorders are characterised by distorted beliefs about the dangerousness of certain situations and/or internal stimuli. Why do such beliefs persist? Six processes (safety-seeking behaviours, attentional deployment, spontaneous imagery, emotional reasoning, memory processes and the nature of the threat representation) that could maintain anxiety-related negative beliefs are outlined and their empirical status is reviewed. Ways in which knowledge about maintenance processes has been used to develop focussed cognitive therapy programmes are described and evaluations of the effectiveness of such programmes are summarized. Finally, ways of identifying the effective ingredients in cognitive therapy programmes are discussed.