Beruflich Dokumente
Kultur Dokumente
art ic l e i nf o
a b s t r a c t
Article history:
Received 9 July 2015
Accepted 24 September 2015
Background: Although patients with major depressive disorder (MDD) have dysfunctions in cognitive
behaviors and the regulation of emotions, the underlying brain dynamics of the pathophysiology are
unclear. Therefore, nonlinear techniques can be used to understand the dynamic behavior of the EEG
signals of MDD patients.
Methods: To investigate and clarify the dynamics of MDD patients' brains during different emotional
states, EEG recordings were analyzed using nonlinear techniques. The purpose of the present study was
to assess whether there are different EEG complexities that discriminate between MDD patients and
healthy controls during emotional processing. Therefore, nonlinear parameters, such as Katz fractal
dimension (KFD), Higuchi fractal dimension (HFD), Shannon entropy (ShEn), Lempel-Ziv complexity
(LZC) and Kolmogorov complexity (KC), were computed from the EEG signals of two groups under different experimental states: noise (negative emotional content) and music (positive emotional content)
periods.
Results: First, higher complexity values were generated by MDD patients relative to controls. Signicant
differences were obtained in the frontal and parietal scalp locations using KFD (po0.001), HFD
(po 0.05), and LZC (p 0.05). Second, lower complexities were observed only in the controls when they
were subjected to music compared to the resting baseline state in the frontal (p o0.05) and parietal
(p 0.005) regions. In contrast, the LZC and KFD values of patients increased in the music period compared to the resting state in the frontal region (po0.05). Third, the patients' brains had higher complexities when they were exposed to noise stimulus than did the controls' brains. Moreover, MDD
patients' negative emotional bias was demonstrated by their higher brain complexities during the noise
period than the music stimulus. Additionally, we found that the KFD, HFD and LZC values were more
sensitive in discriminating between patients and controls than the ShEn and KC measures, according to
the results of ANOVA and ROC calculations.
Conclusion: It can be concluded that the nonlinear analysis may be a useful and discriminative tool in investigating the neuro-dynamic properties of the brain in patients with MDD during emotional stimulation.
& 2015 Elsevier Ltd. All rights reserved.
Keywords:
EEG
Major depressive disorder
Complexity
Emotion
Music
Noise
Entropy
Fractal dimension
1. Introduction
Major depressive disorder (MDD) is a very common psychiatric
mood disorder that affects 1520% of the population [1]. The major
signs of MDD are loss of interest, energy and pleasure; a depressed
mood; disturbances in sleep; and recurrent suicidal thoughts [2].
Moreover, depressed patients exhibit some symptoms related to
cognition, such as low concentration, difculty in decision making
and focusing, according to the Diagnostic and Statistical Manual of
Mental Disorders (DSM-IV) diagnostic criteria for MDD [3].
http://dx.doi.org/10.1016/j.compbiomed.2015.09.019
0010-4825/& 2015 Elsevier Ltd. All rights reserved.
However, the underlying neural activities of these types of functional or cognitive impairments are still under investigation [4].
Therefore, there have been many electroencephalogram (EEG)
studies in groups of patients diagnosed with MDD to compare
them with healthy controls. Most of these studies have investigated resting state brain activity in MDD patients with the help of
conventional linear techniques, such as spectral domain analysis
or waveform investigations [5-8]. However, the complex dynamic
variations in an EEG time series cannot be discriminated by linear
techniques [9]. Moreover, because EEG is a complex and irregular
signal with nonlinear behaviors and without a linear relation
between cause and effect, a signicant number of complexity
estimators, such as largest Lyapunov exponents (L1), correlation
dimension (D2), mutual information, Shannon entropy (ShEn),
50
sample entropy, approximate entropy (ApEn), Lempel-Ziv complexity (LZC), fractal dimension (FD), and Kolmogorov complexity
(KC), have been proposed as more appropriate techniques for
understanding the underlying dynamics of brain activity with
unknown parameters [4]. These estimators are known as nonlinear measures because they reconstruct an attractor from an EEG
by characterizing its dynamic behaviors using the dimension of a
signal, which gives the degrees of freedom of system, or using
entropies that reect the unpredictability of the signals' dynamics
[10].Therefore, over the past 40 years, these measures have been
applied to EEG data for characterizing random-appearing series of
patterns across time in different physiological states, such as Alzheimer's disease [11-13], dementia [14], epilepsy [15-17], schizophrenia [18-20] and obsessivecompulsive disorder [21].
It must be taken into account that all of these estimators reect
the complexity with different approaches, such as dimensional
complexity, regularity and predictability [22,23]. While the D2 and
Higuchi FD are related to dimensional complexity, the ApEn is a
statistical calculation of regularity of a signal. Some other complexity measures, such as the L1 and entropies, focus on determining the irregularity and predictability of signals. The randomness or degree of irregularity (chaoticness) of nite sequences can
be investigated by the LZC and KC. Among all of these complexity
estimators, traditional estimators (D2 and L1) are the oldest and
have limitations because of their requirement for a noise-free, long
and stationary time series [24]. Alternatively, entropy-based
complexity estimators calculated in either frequency domain
(spectral entropy) or a time series (ShEn, ApEn) have the advantage of anti-noise ability [25]. On the other hand, Katz fractal
dimension (KFD), Higuchi's fractal dimension (HFD) and Petrosian
FD algorithms simply and quickly estimate the self-similarity of a
time interval directly in the time series [26].
Although most of the attention has been paid to analyses of
EEGs in MDD patients based on linear techniques [5-8], there have
been a small number of studies on nonlinear EEG analysis of
patients [4,19,27-29]. To the best of our knowledge, Nandrino et al.
[27] conducted the rst nonlinear EEG analysis study of MDD
patients. They calculated the D2 and found a negative correlation
between the symptoms of MDD and its complexity. Li et al. [19]
reported that MDD patients exhibited increased LZC values in
anterior brain regions when the values were compared with corresponding values in controls. Ahmadlou et al. [28] applied HFD
and KFD analyses to both the full band and sub-bands of EEG data
in patients with depression and in controls. According to their
reports, elevated complexities in patients were particularly
observed in the beta and gamma sub-bands of the frontal area in
EEG recordings. The same authors proposed a new nonlinear
measure called spatiotemporal analysis of relative convergence
(STARC) for investigating brain dynamics based on relative EEG
convergence in different loci [29]. They found signicant STARC
differences between male and female MDD patients. Puthankattil
and Joseph [30] used signal entropy values to classify the EEG
signals of patients with depression and control subjects. In another
of their works, the ApEn values of MDD patients and healthy
controls were compared [31]. They reported decreased ApEn
values, indicating the predictability and regularity of EEG recordings in patients with depression. In another study, Hosseinifard
et al. [32] compared the performance of different classication
algorithms that used some EEG nonlinear features, such as
detrended uctuation analysis (DFA), HFD, D2, and L1 for discriminating MDD patients from controls. They reported high
classication accuracy when the linear discriminant analysis was
used with extracted nonlinear features. Similarly, probabilistic
neural network-based high classication accuracy in the discrimination of MDD patients and control subjects was obtained by
Faust et al. [33]. They used entropy values estimated from the EEG
2. Methods
2.1. Participants and experimental protocol
The groups in this study were healthy control subjects and
MDD patients. There were 15 control subjects, who had no history
of any neurological, psychiatric, or psychological disorder or
Table 1
Demographical and clinical features of participants.
N
Gender (male/female)
Age (years 7 std. deviation)
Education (years)
Age of onset
Baseline HAM-D Score
51
Healthy control
subjects
15
8/7
29.42 7 4.02
15.337 4.02
15
8/7
30.92 7 3.65
13.92 7 2.78
28.127 3.63
22.147 3.98
Statistical analysis
Fig. 1. The general block diagram of the procedure.
52
m
X
pxi lnpxi
i0
n-1
where
2.2.2. Katz fractal dimension
The FD of a signal can be calculated using Katz's algorithm in
the time domain. This method depends on a simple calculation of
the FD of a planar curve as follows [49]
FD
log L
log d
log L=a
log n
!
(
)
N1
XN m
k
Lm k
5
xm ik xm i 1k
N m
i1
k
k
where NNm1k is the normalization factor for the curve length of the
k
Lm k
m1
n
log 2n
10
11
Lk
bn
p:U p x
12
7
3. Results
8
53
Fig. 2. Comparison of LZC values using bar-graph representation during each experimental period (Abbreviations: R1 resting 1, M musical stimulus, R2 resting 2,
N noise stimulus, R3 resting 3) between control and MDD groups in frontal, central, parietal and temporal regions. * and ** indicate the statistical differences between
groups of p o0.05 and p o0.001, respectively.
54
4. Discussion
Table 2
The p-values (F-values) of estimated complexity features of frontal and central regions of EEG, in discriminating MDD and control groups. (Abbreviations: R1: resting 1,
M: music, R2: resting 2, N: noise, R3: resting 3).
Frontal
R1
M
R2
N
R3
Central
KFD
HFD
ShEn
LZC
KC
KFD
HFD
ShEn
LZC
KC
0.005* (10.498)
0.000* (55.595)
0.000* (52.841)
0.000* (62.291)
0.068 (3.801)
0.026* (5.930)
0.004* (10.720)
0.001* (15.189)
0.000* (18.455)
0.056 (4.216)
0.322 (1.042)
0.217 (1.641)
0.328 (1.015)
0.319 (1.054)
0.799 (0.067)
0.000* (25.495)
0.000* (125.07)
0.006* (9.999)
0.016* (7.121)
0.047* (4.608)
0.273 (1.285)
0.052 (4.371)
0.024* (6.180)
0.024* (6.099)
0.005* (10.266)
0.405 (0.728)
0.341 (0.961)
0.078 (4.321)
0.160 (2.162)
0.152 (2.249)
0.731 (0.122)
0.904 (0.015)
0.119 (2.695)
0.307 (1.109)
0.167 (2.086)
0.369 (0.852)
0.237 (1.500)
0.065 (4.390)
0.146 (2.317)
0.116 (2.742)
0.030* (5.600)
0.138 (2.423)
0.271 (1.295)
0.448 (0.604)
0.448 (0.604)
0.032* (5.454)
0.130 (2.553)
0.265 (1.312)
0.460 (0.518)
0.443 (0.596)
55
Table 3
The p-values (F-values) of estimated complexity features of temporal and parietal regions of EEG, in discriminating MDD and control groups (Abbreviations: R1: resting 1, M:
music, R2: resting 2, N: noise, R3: resting 3).
Temporal
R1
M
R2
N
R3
Parietal
KFD
HFD
0.801 (0.066)
0.690 (0.164)
0.588 (0.305)
0.451 (0.596)
0.058 (4.503)
0.898
0.942
0.080
0.320
0.065
ShEn
(0.017)
(0.006)
(3.455)
(1.049)
(4.321)
0.729
0.703
0.887
0.501
0.093
LZC
(0.124)
(0.150)
(0.021)
(0.473)
(3.163)
0.038
0.070
0.070
0.334
0.334
KC
(5.090)
(3.731)
(3.731)
(0.987)
(0.987)
0.032
0.072
0.071
0.332
0.330
(5.120)
(3.725)
(3.730)
(0.989)
(0.992)
KFD
HFD
ShEn
LZC
KC
0.002* (12.677)
0.000* (25.041)
0.033* (5.403)
0.002* (13.115)
0.058 (4.134)
0.042* (4.831)
0.005* (10.404)
0.264 (1.337)
0.805 (0.063)
0.921 (0.010)
0.700 (0.153)
0.572 (0.333)
0.443 (0.617)
0.518 (0.436)
0.403 (0.736)
0.024* (6.103)
0.037* (5.150)
0.098 (3.063)
0.007* (9.373)
0.133 (2.485)
0.030* (5.998)
0.074 (3.611)
0.074 (3.611)
0.074 (3.611)
0.108 (2.887)
knowledge, this is the rst study describing emotion-induced changes in EEG complexity in MDD patients.
The main ndings in the present work were that MDD patients
showed increased EEG complexities (KFD, HFD and LZC) compared
to controls both at rest and during emotional stimulation periods.
This result is consistent with the ndings of past studies, which
reported increased complexities in the brain of patients in a
resting condition [4,28]. According to previous neuro-imaging
studies, this higher complexity has been reported to be related
to the changes in brain dynamics caused by decreased white
matter and increased gray matter in the frontal region of MDD
patients [28,60,61]. Moreover, the increased complexities in MDD
patients may be related to the increased variability, or irregularity, of their EEG data. Second, it has been found that the complexities are lower when only control subjects receive musical
stimulation compared to the resting baseline period. This means
that the EEG signals become less complex/random when the participant is subjected to musical stimulation. This decrease in EEG
dynamic complexities might be explained by strongly coupled
oscillators or the inactivation of previously active neurons and
interacting networks [14,62]. In other words, the displayed values
of KFD, HFD and LZC suggest that listening to CTM reduces the
related region complexities of EEG dynamics in controls in terms
of degrees of randomness or degrees of freedom. A similar conclusion was drawn by a previous study that investigated the effect
of Mozart's music in learning [63]. In that study, less complex EEG
activities were observed in healty controls who were solving
spatial rotation tasks while listening to Mozart's music. These
nding suggest that this type of music enhances the learning of
applied tasks by reducing the brain complexity. Furthermore,
Lamberts et al. [64] and Natarajan et al. [65] showed that subjects
had lower EEG complexities when their brains went to a passive or
relaxed state. Considering these ndings, it may be inferred that
the applied musical stimulation causes a decrease in the complexity level of healthy controls' brains, which indicates that the
subjects are more relaxed during this period. Furthermore, this
result can be explained by the self-rating scores of participants for
evaluating the emotional content of both stimuli after the
experiments. According to results of Pearson's Correlation analysis,
LZC complexities during the music stimulus showed a signicant
negative correlation with the self-rated emotion data of the control subjects (p o0.05). It means that brain complexities of subjects decrease signicantly as the subjects rate the music to be
more positive. On the other hand, we determined that as the
rating scores during noise stimulation decreased, the KFD complexities increased in the frontal cortex. This nding may be
related to the negative potentiation hypothesis, which suggests an
increased emotional reactivity to negative emotional stimuli in
MDD patients. According to the results of an extensive metaanalysis of fMRI studies in MDD patients [66], it is believed that
multiple levels of emotional processing, including the amygdale,
striatum, and prefrontal cortex, are altered in patients' brain. MDD
56
R1
1
M
1
0.9
0.9
0.8
0.8
0.7
0.7
0.6
0.6
0.5
0.5
0.4
0.4
0.3
0.3
0.2
0.2
0.1
0.1
R2
1
0.9
0.9
0.8
0.8
0.7
0.7
0.6
0.6
0.5
0.5
0.4
0.4
0.3
0.3
0.2
0.2
0.1
0.1
R3
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Fig. 5. Spatial distribution of average LZC values of the EEG in the control subjects during each period.
between the two groups during the resting period (R3). After the
emotional periods, the complexity values generally tended to revert
to the levels observed before the stimulation periods in both
57
R1
1
0.9
0.9
0.8
0.8
0.7
0.7
0.6
0.6
0.5
0.5
0.4
0.4
0.3
0.3
0.2
0.2
0.1
0.1
R2
1
1
0.9
0.9
0.8
0.8
0.7
0.7
0.6
0.6
0.5
0.5
0.4
0.4
0.3
0.3
0.2
0.2
0.1
0.1
R3
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Fig. 6. Spatial distribution of average LZC values of the EEG in the MDD patients during each period.
groups. That is, after the noise period, EEG complexities decreased.
Moreover, the EEG complexities particularly decreased in the frontal
(by KFD) and parietal (by HFD) regions when the results of the R1
D2: correlation dimension; LZC: Lempel-Ziv complexity; KFD: Katz's fractal dimension; HFD: Higuchi's fractal dimension; PNN: probabilistic neural network; RWE: relative wavelet energy; ANN: articial neural network; STARC:
spatiotemporal analysis of relative convergence; DFA: detrended uctuation analysis; L1: Lyapunov exponents; kNN: k-nearest neighbors; LDA: linear discriminant analysis; LR: logistic regression; WPD: wavelet packet
decomposition; WE: wavelet entropy; ApEn: approximate entropy; FD: fractal dimension; ShEn: Shannon entropy; KC: Kolmogorov complexity.
Statistical analysis and PNN Classication accuracy (91.3%) based on HFD values of EEG
ANN
Classication accuracy (98.11%)
Statistical analysis
Signicant differences between male and female MDD patients
KNN, LDA, and LR
Classication accuracy (90%)
Statistical analysis
A good sensitivity for detection of depression based on HFD
PNN
Classication accuracy (99.5%)
Statistical analysis
Controls had higher entropies
Statistical analysis
Signicant differences in LZC between MDD patients and controls
Statistical analysis
Signicant differences between patients and controls and between emotional
periods
KFD and HFD
RWE and entropy
STARC
HFD, D2, DFA, and L1
Spectral asymmetry and HFD
WPD and entropy
WE and ApEn
LZC
KFD, HFD, ShEn, LZC, and KC
Resting EEG
EEG at rest and performing a mental arithmetic
task
Ahmadlou et al. [28]
Resting EEG
Puthankattil and Joseph [30] Resting EEG
Ahmadlou et al. [29]
Resting EEG
Hosseinifard et al. [32]
Resting EEG
Bachmann et al. [34]
Resting EEG
Faust et al. [33]
Resting EEG
Puthankattil and Joseph [31] Resting EEG
Bachmann et al. [4]
Resting EEG
Our study
EEG at rest and during emotional periods
Comparison methods
Extracted features
Data recording
Authors
Table 4
A brief summary of nonlinear EEG studies in MDD patients.
values of the MDD and control groups were closer after the stimulation periods (R3) than at rst baseline (R1). This nding might
be related to increased complexities (LZC and HFD) in control
subjects during the noise stimulus.
When the two groups were compared, it was found that
patients with MDD showed signicantly higher KFD, HFD and LZC
values in the frontal and parietal areas. The importance of the
frontal lobes in the pathophysiology of depression has been well
documented by previous neuro-imaging studies [78-80]. It has
been found that the frontal cortex is dysfunctional in depression,
and patients have reduced prefrontal and frontal lobe volumes
[81]. Studies have also shown that the parietal lobes contribute to
the pathology of MDD [82-85]. Previous studies reported
decreased volumes of the parietal regions in patients [83,85,86]. In
addition, some of these studies found abnormalities in the white
matter structures of the parietal cortex in patients with MDD
[82,84]. Considering all of these ndings, it may be hypothesized
that the changes in brain dynamics found in the nonlinear EEG
analysis result from neurological variances among some cortical
regions of patients with MDD [28]. In a previous thesis study that
investigated the nonlinear dynamics of brain signals in healthy
musician and non-musician participants, higher complexity values
in musicians compared to non-musicians were reported [87]. The
author proposed a possible relationship between these ndings
and anatomical differences between the two groups, which were
observed as increased grey and white matter volumes in musicians
[88,89]. On the other hand, patients and control subjects did not
differ in terms of EEG complexities in the temporal and central
lobes (Tables 2 and 3). For example, Table 2 shows the p-values of
extracted ve EEG features (ShEn, KFD, HFD, LZC, and KC) of the
frontal and central regions for discriminating between the two
groups. As shown in this table, there is no signicant p-value in the
central region. Similarly, none of the obtained p-values are signicant in the temporal region (Table 3). Therefore, it can be
reported that, regardless of the nonlinear method applied, no
signicant complexity differences were found between the EEGs of
MDD patients and controls in the temporal and central regions.
In a previous comprehensive study on schizophrenia patients
[20], the successes of different complexity estimators, such as
ShEn, ApEn, spectral entropy, LZC, and HFD, were compared to
obtain an optimum discrimination between patients and control
subjects. These authors found that the LZC, ApEn, and HFD measures of EEG were more optimal for discrimination. In our study,
the high AUC values of the ROC curve conrmed the ability of the
Results
Fig. 7. ROC curve analysis of KFD and HFD values obtained in parietal and frontal
regions during emotional periods.
D2
LZC
58
KFD and HFD predictors in the frontal and parietal regions for
distinguishing between patients and controls.
59
Acknowledgments
This study was funded by TBTAK (The Scientic and Technical
Research Council of Turkey) under project number 112E317.
5. Conclusion
In this paper, we have calculated different EEG complexity
measures both at rest and during emotional states in MDD
patients and in control subjects to better understand the underlying brain dynamics. We found that the KFD, HFD and LZC values
were more sensitive in detecting EEG complexities and in discriminating between two groups than the ShEn and KC values,
according to the results of ANOVA. We conclude that there were
differences in the EEG complexities between resting and emotional stimulation periods; that both the groups presented an
increase in the EEG complexities while listening to noise; and that
there was a decrease in brain complexity when control subjects
receive musical stimulation compared to the resting baseline
period. In terms of EEG complexities, better discrimination rate
were obtained using the KFD, HFD and LZC algorithms than the KC
and ShEn methods. Therefore, it can be reported that the ShEn and
KC methods might not be good nonlinear features for the EEG data
in our study. It was found that the emotional processing in the
patients' brains were quantitatively more complicated and complex. The brains of MDD patients had higher complexities than
healthy controls when they were expose to noise stimulus as a
negative and stressful period. MDD patients' negative emotional
bias was shown in the nonlinear EEG analysis.
Although we found that the nonlinear EEG analysis showed
signicant differences between patients with MDD and controls
during both resting and emotional stimulation states, some limitations must be taken into account when planning future studies.
First, the sample size of the participants in our research was small.
To prove the usefulness of these complexity measures in EEG
signals as a diagnostic tool for MDD, these analyses should be
performed on much larger populations. Moreover, further studies
must be carried out to investigate whether the observed complexity variances in the EEG during different emotional periods are
specic to MDD patients. In particular, it will also be important to
compare observed ndings in different pathological or psychological disorders such as bipolar depression, schizophrenia, and
epilepsy. Moreover, the complexity changes produced by emotional periods should be studied by taking into account the
symptom severities, gender effects, and medication status of
patients with MDD.
Future classication studies need to investigate and conrm
these results using different complexity estimators, such as sample
entropy, ApEn, Hurst's exponent, recurrence quantication analysis and higher-order spectra. The experimental results in this study
show the effectiveness of some nonlinear measures for investigating the dynamical behavior of patients' brains during emotional
periods. Because an increasing number of studies have investigated the diagnostic ability of different nonlinear EEG features in
MDD patients, all ndings, including ours, for clarifying the
underlying dynamical activity of the brain may provide objective
criteria in clinical practice.
References
[1] R.C. Kessler, E.E. Walters, The national comorbidity survey, in: M.T. Tsaung,
M. Tohen (Eds.), Textbook in Psychiatric Epidemiology, 2nd ed.,John Wiley &
Sons, New York, NY, 2002, pp. 343362.
[2] G. Andrews, Dimensionality and the category of major depressive episode, Int.
J. Methods Psychiatr. Res. 16 (2007) 4151.
[3] American Psychiatric Association (APA), Diagnostic and Statistical Manual of
Mental Disorders, 4th edition, APA, Washington, DC, 1994 DSM-IV.
[4] M. Bachmann, K. Kalev, A. Suhhova, J. Lass, H. Hinkrikus, Lempel Ziv Complexity of EEG in Depression, in: Proceedings of IFMBE, vol 45, 2015, pp. 5861.
[5] S.A. Reid, L.M. Duke, J.J.B. Allen, Resting frontal electroencephalographic
asymmetry in depression: inconsistencies suggest the need to identify mediating factors, Psychophysiology 35 (04) (1998) 389404.
[6] J.J.B. Allen, H.L. Urry, S.K. Hitt, J.A. Coan, The stability of resting frontal electroencephalographic asymmetry in depression, Psychophysiology 41 (2)
(2004) 269280.
[7] A. Sumich, A. Harris, G. Flynn, T. Whitford, N. Tunstall, V. Kumari, et al., Eventrelated potential correlates of depression, insight and negative symptoms in males
with recent-onset psychosis, Clin. Neurophysiol. 117 (8) (2006) 17151727.
[8] M. Bares, M. Brunovsky, M. Kopecek, P. Stopkova, T. Novak, J. Kozeny, et al.,
Changes in QEEG prefrontal cordance as a predictor of response to antidepressants in patients with treatment resistant depressive disorder: a pilot
study, J. Psychiatr. Res. 41 (2007) 319325.
[9] U.R. Acharya, V.K. Sudarshan, H. Adeli, J. Santhosh, J.E.W. Koh, A. Adeli,
Computer-aided diagnosis of depression using EEG signals, Eur. Neurol. 73
(2015) 329336.
[10] C.J. Stam, Nonlinear dynamical analysis of EEG and MEG: review of an emerging eld, Clin. Neurophysiol. 116 (2005) 22662301.
[11] C. Besthorn, R. Zerfass, C. Geiger-Kabisch, H. Sattel, S. Daniel, U. SchreiterGasser, et al., Discrimination of Alzheimer's disease and normal aging by EEG
data, Electroencephalogr. Clin. Neurophysiol. 103 (1997) 241248.
[12] D. Abasolo, R. Hornero, C. Gomez, M. Garcia, M. Lopez, Analysis of EEG background activity in Alzheimers disease patients with Lempel-Ziv complexity
and central tendency measure, Med. Eng. Phys. 28 (2006) 315322.
[13] D. Labate, F. La Foresta, G. Morabito, I. Palamara, F.C. Morabito, Alzheimer's
disease through a multivariate multiscale approach, IEEE Sens. J. 13 (2013)
32843292.
[14] J. Jeong, Nonlinear dynamics of EEG in Alzheimer's disease, Drug Dev. Res. 56
(2) (2002) 5766.
[15] R. Hornero, P. Espino, A. Alonso, M. Lpez, Estimating complexity from EEG
background activity of epileptic patients, IEEE Eng. Med. Biol. 18 (1999) 7379.
[16] S.F. Liang, H.C. Wang, W.L. Chang, Combination of EEG Complexity and Spectral Analysis for Epilepsy Diagnosis and Seizure Detection, EURASIP Journal on
Advances in Signal Processing (2010) 853434.
[17] P. Bob, R. Roman, M. Svetlak, M. Kukleta, J. Chladek, M. Brazdil, Preictal dynamics
of EEG complexity in intracranially recorded epileptic seizure: a case report,
Medicine 93 (23) (2014) 14, http://dx.doi.org/10.1097/MD.0000000000000151.
[18] T. Elbert, W. Lutzenberger, B. Rockstroh, P. Berg, R. Cohen, Physical aspects of
the EEG in schizophrenics, Biol. Psychiatry 32 (7) (1992) 595606.
[19] Y. Li, S. Tong, D. Liu, Y. Gai, X. Wang, J. Wang, et al., Abnormal EEG complexity
in patients with schizophrenia and depression, Clin. Neurophysiol. 119 (2008)
12321241.
[20] M. Sabeti, S. Katebi, R. Boostani, Entropy and complexity measures for EEG
signal classication of schizophrenic and control participants, Artif. Intell.
Med. 47 (2009) 263274.
[21] S. Aydn, N. Arca, E. Ergl, O. Tan, Classication of obsessive compulsive disorder by EEG complexity and hemispheric dependency measurements, Int. J.
Neural Syst. 25 (3) (2015), http://dx.doi.org/10.1142/S0129065715500100.
[22] G. Tononi, G.M. Edelman, O. Sporns, Complexity and coherency: integrating
information in the brain, Trends Cogn. Sci. 2 (1998) 474484.
[23] A. Fernandez, C. Gomez, R. Hornero, J.J. Lopez-Ibor, Complexity and Schizophrenia, Prog. Neuro-psychopharmacol. Biol. Psychiatry 45 (2012) 267276,
http://dx.doi.org/10.1016/j.pnpbp.2012.03.015.
[24] S.A. Akar, S. Kara, F. Latifolu, V. Bilgi, Investigation of the noise effect on
fractal dimension of EEG in schizophrenia patients using wavelet and SSAbased approaches, Biomed. Signal Process. Control 18 (2015) 4248.
[25] Z. Liang, Y. Wang, X. Sun, et al., EEG entropy measures in anesthesia, Front.
Comput. Neurosci. 9 (2015), article 16, 1-17.
60
[59] J.D. Herrington, W. Heller, A. Mohanty, A.S. Engels, M.T. Banich, A.G. Webb, G.
A. Miller, Localization of asymmetric brain function in emotion and depression, Psychophysiology 47 (3) (2010) 442454.
[60] G.S. Alexopoulos, D.N. Kiosses, S.J. Choi, C.F. Murphy, K.O. Lim, Frontal white
matter microstructure and treatment response of late-life depression: a preliminary study, Am. J. Psychiatry 159 (2002) 19291932.
[61] M.J. Kim, J.P. Hamilton, I.H. Gotlib, Reduced caudate gray matter volume in
women with major depressive disorder, Psychiatry Res.: Neuroimaging 164 (2)
(2008) 114122.
[62] J. Jeong, D.J. Kim, J.H. Chae, S.Y. Kim, H.J. Ko, I.H. Paik, Non-linear analysis ofthe
EEG of schizophrenics with optimal embedding dimension, Med. Eng. Phys. 20
(1998) 669676.
[63] N. Jausovec, K. Jausovec, I. Gerlic, The inuence of Mozart's music on brain
activity in the process of learning, Clin. Neurophysiol. 117 (2006) 27032714.
[64] J. Lamberts, P.L.C. van den Broek, L. Bener, et al., Correlation dimension of the
human electroencephalogram corresponds with cognitive load, Neuropsychobiology 41 (2000) 149153.
[65] K. Natarajan, R. Acharya, F. Alias, et al., Nonlinear analysis of EEG signals at
different mental states, BioMed. Eng. Online 3 (2004) 111.
[66] N.A. Groenewold, E.M. Opmeer, P. Jonge, A. Aleman, S.G. Costafreda, Emotional
valence modulates brain functional abnormalities in depression: evidence
from meta-analysis of fMRI studies, Neurosci. Behav. Rev. 37 (2013) 153163.
[67] A. Papazacharias, M. Nardini, The relationship between depression and cognitive decits, Psychiatr. Danub. 24 (2012) 179182.
[68] P.B. Fitzgerald, et al., An fMRI study of prefrontal brain activation during
multiple tasks in patients with major depressive disorder, Hum. Brain Mapp.
29 (2008) 490501.
[69] S. Schoning, et al., Working-memory fMRI reveals cingulate hyperactivation in
euthymic major depression, Hum. Brain Mapp. 30 (2009) 27462756.
[70] R. Patterson, S. Uppenkamp, I. Johnsrude, T. Grifths, The processing of temporal
pitch and melody information in auditory cortex, Neuron 36 (4) (2002) 767776.
[71] I. Peretz, R. Zatorre, Brain organization for music processing, Annu. Rev. Psychol. 56 (2005) 89114.
[72] J.W. Bruce, Fractal Physiology and Chaos in Medicine, World Scientic Publishing Co. Pte. Ltd, 1990.
[73] N. Kannathal, R. Acharya, F. Alias, T. Tiboleng, S.K. Puthusserypady, Nonlinear
analysis of EEG signals at different mental states, Biomed. Eng. Online 3 (2004) 7.
[74] S.A. Surguladze, A.W. Young, C. Senior, G. Brebion, M.J. Travis, M.L. Phillips,
Recognition accuracy and response bias to happy and sad facial expressions in
patients with major depression, Neuropsychology 18 (2004) 212218, http:
//dx.doi.org/10.1037/0894-4105.18.2.212.
[75] C. Bourke, K. Douglas, R. Porter, Processing of facial emotion expression in
major depression: a review, Aust. NZ J. Psychiatry 44 (2010) 681696, http:
//dx.doi.org/10.3109/00048674.2010.496359.
[76] A. Beck, The evolution of the cognitive model of depression and its neurobiological correlates, Am. J. Psychiatry 165 (2008) 969977, http://dx.doi.org/
10.1176/appi.ajp.2008.08050721.
[77] E. Bodner, I. Iancu, A. Gilboa, A. Sarel, A. Mazor, D. Amir, Finding words for
emotions: the reactions of patients with major depressive disorder towards
various musical excerpts, Arts Psychother. 34 (2007) 142150.
[78] A.L. Brody, M.W. Barsom, R.G. Bota, S. Saxena, Prefrontalsubcortical and
limbic circuit mediation of major depressive disorder, Semin. Clin. Neuropsychiatry 6 (2001) 102112.
[79] R.J. Davidson, J.B. Henriques, Regional brain function in sadness and depression, in: J. Borod (Ed.), The Neuropsychology of Emotion, Oxford University
Press, New York, NY, 2000, pp. 269297.
[80] D.A. Pizzagalli, J.B. Nitschke, T.R. Oakes, A.M. Hendrick, K.A. Horras, C.L. Larson,
et al., Brain electrical tomography in depression: the importance of symptom
severity, anxiety, and melancholic features, Biol. Psychiatry 52 (2002) 7385,
http://dx.doi.org/10.1016/S0006-3223(02)01313-01316.
[81] S. Bell-McGinty, M.A. Butters, C.C. Meltzer, et al., Brain morphometric
abnormalities in geriatric depression: long-term neurobiological effects of
illness duration, Am. J. Psychiatry 159 (2002) 14241427.
[82] F. Biver, S. Goldman, V. Delvenne, A. Luxen, V. De Maertelaer, P. Hubain,
J. Mendlewicz, F. Lotstra, Frontal and parietal metabolic disturbances in unipolar depression, Biol. Psychiatry 36 (1994) 381388.
[83] M. Ballmaier, A. Kumar, P.M. Thompson, K.L. Narr, H. Lavretsky, L. Estanol,
et al., Localizing gray matter decits in late-onset depression using computational cortical pattern matching methods, Am. J. Psychiatry 161 (2004)
20912099.
[84] N. Ma, L. Li, N. Shu, J. Liu, G. Gong, Z. He, Z. Li, L. Tan, W.S. Stone, Z. Zhang, L. Xu,
T. Jiang, White matter abnormalities in rst-episode, treatment-naive young
adults with major depressive disorder, Am. J. Psychiatry 164 (2007) 823826.
[85] M.A. Ikram, H.J. Luijendijk, M.W. Vernooij, A. Hofman, W.J. Niessen, A. van der
Lugt, et al., Vascular brain disease and depression in the elderly, Epidemiology.
21 (2010) 7881.
[86] W.C. Drevets, J.L. Price, J.R. Simpson, R.D. Todd, T. Reich, M. Vannier, M.
E. Raichle, Subgeual prefrontal cortex abnormalities in mood disorders, Nature
386 (6627) (1997) 827-827.
[87] S.M. Carpentier, Brain-Music Duet: MEG Signal Complexity and Auditory
Perception in Musicians and Nonmusicians, Department of Psychology, University of Toronto, 2011.
[88] G. Schlaug, The brain of musicians, Ann. NY Acad. Sci. 930 (2001) 281299.
[89] C. Gaser, G. Schlaug, Brain structures differ between musicians and nonmusicians, J. Neurosci. 23 (27) (2003) 92409245.