Journal of Psychiatric Research 36 (2002) 399–406

www.elsevier.com/locate/jpsychires

P300 subcomponents in obsessive-compulsive disorder

Paraskevi Mavrogiorgoua, Georg Juckela,*, Thomas Frodla, Jürgen Gallinata,
Walter Haukeb, Michael Zaudigb, Gerhard Dammannc, Hans-Jürgen Möllera,
Ulrich Hegerla
a
Department of Psychiatry, Section of Clinical Neurophysiology and Outpatient Clinic for Obsessive-Compulsive Disorder, Ludwig-Maximilians
University Munich, Germany
b
Psychosomatic Clinic, Windach, Germany
c
Institute for Psychosomatic Medicine, Technical University Munich, Germany

Received 4 March 2002; received in revised form 5 August 2002; accepted 7 August 2002

Abstract
Hyperactivity in the frontal cortex, leading to acceleration of attentional and cognitive processes, is discussed as pathogenetic
factor in obsessive-compulsive disorder (OCD), as supported by findings of neuroimaging studies. This dysfunction in patients with
OCD could be reflected by the auditory event-related P300 component, since one subcomponent of the P300, the so-called P3a, is
mainly generated in frontal regions. The P300 of 21 patients with OCD free of medication and 21 age- and sex-matched healthy
controls was studied, and dipole source analysis was used, allowing the separation of the subcomponents P3a and P3b with high
reliability. No difference concerning the P3a between OCD and healthy subjects was found. OCD patients, however, showed a
larger P3b amplitude and a shorter P3b latency (only right hemisphere) as well as a shorter reaction time to target tones as the
healthy controls. Since the P3b, generated mainly in the temporo-parietal junction, is related to attentional and higher cognitive
functions, whereas the P3a is more related to unspecific orienting reactions, the P3b abnormalities found in these patients could be
an electrophysiological correlate of overfocussed attention and faster cognitive processes in OCD, possibly due to higher arousal
and noradrenergic function. Regarding the findings with small P300 amplitudes and long latencies in most of the other psychiatric
patients, it is remarkable that OCD is one of the few psychaitric diseases being characterized by larger P3b amplitudes and shorter
latencies.
# 2002 Elsevier Science Ltd. All rights reserved.
Keywords: Obsessive-compulsive disorder; Event-related potentials; P300; Cognitive dysfunction; Neuroanatomy

1. Introduction disorders, including seizure disorders (Levine & Duch-

In the last 10 years, remarkable advances in the
understanding of the neurobiological underpinnings of
obsessive-compulsive disorder (OCD) as well as in the
development of effective therapeutic possibilities of this
former treatment-refractory disease have been made.
First hints for neuroanatomical abnormalities in OCD
were given by the well-known association between OCD
and some neurological disorders. It was often found
that OCD symptoms are associated with neurological
* Corresponding author. Present address: Department of Psy-
chiatry, Charite, Humboldt University, Schumannstrasse 20/21, 10117
Berlin, Germany. Tel.: +49-30-450-517-042/062 ; fax: +49-450-517-
962.
E-mail address: georg.juckel@charite.de (G. Juckel).
0022-3956/02/$ - see front matter # 2002 Elsevier Science Ltd. All rights reserved.
PII: S0022-3956(02)00055-9
owny, 1991), head trauma (McKeon et al., 1984) and
diseases with basal ganglia abnormalities like Syden-
ham’s chorea (Swedo et al., 1989), Huntington’s disease
(Cummmings and Cunningham, 1992) and Tourette’s
syndrom (Pauls et al., 1986). Further evidence for neu-
roanatomical abnormalities in OCD was supported by
findings that psychosurgical disconnection of orbito-
frontal regions from limbic, thalamic, and possibly
striatal structures, improved OCD-symptomatology in
severe-ill patients (Mindus et al., 1994). It has been,
therefore, suggested that disturbances in loops including
the orbitofrontal cortex could be responsible for symp-
toms of OCD.
PET (positron emission tomography) and SPECT
(single photon emission computed tomography) studies
revealed functional abnormalities in the orbitofrontal-
400 P. Mavrogiorgou et al. / Journal of Psychiatric Research 36 (2002) 399–406
basal ganglia-thalamic loop of patients with OCD.
Concerning the frontal lobe, an increased glucose
metabolism in PET was found in the orbitofrontal cor-
tex of OCD patients (Baxter et al., 1987; Swedo et al.,
1989). Corresponding to that, SPECT measurements
showed an enhanced blood flow in the frontal cortex
(Insel, 1992; Rubin et al., 1992). Regional blood flow in
orbitofrontal regions also increased after symptom pro-
vocation of patients with OCD (Rauch et al., 1994;
Cottraux et al., 1996). This hyperactivity in frontal
regions in OCD patients could be related to findings of
overfocussed attention as well as faster cognitive pro-
cesses in OCD (Cohen et al., 1997), since the frontal and
prefrontal cortex are well-known to be involved in
focussing attention and in performing a broad range of
cognitive processes.
In order to get a functional measure of cortical
hyperactivity in OCD patients, the P300 component of
auditory event-related potentials (ERP) is an interesting
tool, since P300 might be generated by several cortical
regions including the frontal cortex (Molnar, 1994), and
this wave is related to cognitive and attentional pro-
cesses (Donchin and Coles, 1988; Verleger, 1988). Only
few studies have investigate ERPs in patients with OCD
with conflicting results. Cielselski et al. (1981) and
Beech et al. (1983) recorded visual ERPs in a visuospa-
tial tasks of shape discrimination with increasing level
difficulty. They found reduced N200 and P300 ampli-
tudes as well as latencies in the OCD patients, especially
when the difficulty of the task increased. This in line
with the findings of Malloy et al. (1989). Using a audi-
tory oddball paradigm, Towey et al. (1990, 1993)
reported shorter N200 and P300 latencies in unmedi-
cated OCD patients than in healthy controls. Shorter
latencies of auditory event-related P300 were also found
by Morault et al. (1997), de Groot et al. (1997) and
Miyata et al. (1998) in patients with OCD. In contrast,
Sanz et al. (2001) found longer P300 latencies and lower
P300 amplitudes in drug-free OCD patients.
The relevance of P300 component for clinical and
research aspects is, however, limited by methodological
problems such as low reliability, which may be respon-
sible for conflicting results in P300 studies. One of the
reasons for low reliability of P300 could be the fact of
overlapping subcomponents (P3a, P3b) of P300 recor-
ded at the scalp. These may reflect functionally different
psychological and physiological processes. Only one of
these subcomponents, the P3b, might be closely related
to higher cognitive functions, while the P3a is associated
with unspecific orienting reactions. Furthermore, P3a
has been discussed in the literature as a component with
a more frontal distribution as P3b, which is generated in
the temporo-parietal junction and is the main P300
subcomponent (Ruchkin et al., 1987; Molnar, 1994;
Halgren et al., 1998). Thus, recent imaging studies
revealed frontal generators of P3a and temporo-parietal
generators of P3b (Menon et al., 1997, Linden et al.,
1999, Kirino et al., 2000). Dipole source analysis allows
to separate the overlapping P300 subcomponents and
clearly increases the reliability of P300 parameters as
compared to single channel analysis or principal com-
ponent analysis (Hegerl and Frodl-Bauch, 1997). While
doing this, the potential distribution at the scalp in the
time range of P300 can be explained by the activity of
two dipoles per hemisphere: the activity of a temporo-
superior dipole with a frontal orientation which reflect
the P3a subcomponent and the somewhat later activity
of a temporo-basal dipole reflects the P3b sub-
component (Tarkka et al., 1995; Hegerl and Frodl-
Bauch, 1997).
Purpose of the present study was to investigate the
P300 subcomponents, separated by dipole source ana-
lysis, in OCD patients, compared to healthy controls.
Investigation of the P300 subcomponents was never
performed in OCD patients. It was hypothezied that the
hyperactivity in the frontal cortex, leading to accelera-
tion of attentional and cognitive processes in OCD
patients is reflected by a large amplitude and a short
latency of subcomponent P3a, which is mainly gener-
ated in frontal regions.
2. Materials and methods
2.1. Subjects
Twenty-one patients (12 men, 9 women, aged 17–57
years, mean 33.9  12.0) hospitalized in a special ward
for OCD (Psychosomatic Clinic Windach) were inclu-
ded in the study. They met the DSM-IV and ICD-10
criteria for OCD and had no additional major psychia-
tric disorders, drug or ethanol addiction or neurological
impairment. The OCD patients were included after a 2-
week period free of psychotropic drugs. No serious
depressive symptoms were found in these patients
[10.7  7.0 points on the 17-item Hamilton Depression
Rating Scale (HDRS)]. OCD symptomatology was in
the middle range, as assessed by the Yale-Brown
Obsessive Compulsive Scale (Y-BOCS) (17.7  8.2
points).
As controls, 21 healthy subjects (12 men, 9 women,
mean aged 36.4  10.9) matched by age and sex to the
patients were studied. They had no history of any psy-
chiatric, addiction or neurological disorder.
Possible auditory dysfunctions in the OCD patients
and in the healthy subjects were excluded by measuring
hearing thresholds. Each group consisted of 20 right
and one left handed subjects according to the Edin-
burgh Handedness Scale (Oldfield, 1971).
All subjects gave their informed consent after the
study design and the procedures had been fully
explained to them. The study was approved by the local
 P. Mavrogiorgou et al. / Journal of Psychiatric Research 36 (2002) 399–406
ethic committee and was carried out in accordance with
the Declaration of Helsinki. (Somerset West 1996)
2.2. P300 method
A detailed description of the P300 method is given in
Hegerl and Frodl-Bauch (1997). Shortly, an oddball
paradigm with 80% non-target stimuli (400 sinus tones,
500 Hz) and 20% target stimuli (100 sinus tones, 1000
Hz) presented binaurally through headphones in
pseudo-randomized order was used (80 dB SPL, 40 ms
duration with 10 ms rise and fall time, interstimulus
interval 1.5 s). Subjects were seated with their eyes
closed in a reclining chair and had to press a button
with their dominant hand after target stimuli without
any instruction about speed. There was no differences of
correct and erroneous motor responses between healthy
and OCD subjects.
Evoked responses were recorded with 32 electrodes
(29 Zn-electrodes of an electrocap and three additional
Zn-electrodes at nasion and the mastoids, all referenced
to Cz). Electrodes were positioned according to the
international 10–20 system. A coronal line of four elec-
trodes was added between frontal and central electrodes
locations, another coronal line of four electrodes was
added between central and parietal electrode locations,
and one electrode was added at inion. The electro-
encephalogram was amplified with bandpass filters of
0.16–70 Hz (sampling rate=256 Hz). The electro-
oculogram was recorded with Fp1, Fp2 and at the
nasion. For artifact rejection, trials were excluded if
their voltage exceeded  50 mV in any one of the 31
channels at any time point during the averaging epoch
(from 200 ms pre-stimulus to 800 ms post-stimulus).
The epochs were averaged separately for the target and
non-target stimuli. The averaged data were digitally fil-
tered (0.5–20 Hz). Target P300 values were transformed
to average reference data so that they could be eval-
uated with BESA (Brain Electrical Source Analysis). In
BESA, prestimulus baseline correction ( 200 to 0 ms)
and data reduction from 256 to 97 data points took
place.
Dipole source analysis was performed with BESA
(Scherg and von Cramon, 1985, distributed by MEGIS),
which can be used to distinguish temporally overlapping
activities recorded from scalp electrodes. The scalp-
recorded data are calculated in the dipole source activity
of a given a number of dipoles using a four-shell head
model. The dipoles are thought to represent the activity
of circumscribed cortical areas. Therefore, they change
dipole strength over time, but not location or orienta-
tion. The optimal location and orientation of the
dipoles are found by an iterative process (simplex algo-
rithm) optimizing the residual variance (variance of the
measured scalp-recorded data unexplained by the dipole
model), whereas the dipole source potentials are deter-
401
mined by a direct linear approach, as described by
Scherg and Picton (1991). Dipole source analysis was
performed for the individual data using a dipole con-
figuration calculated on the basis of a grand average
data set of healthy subjects (Hegerl and Frodl-Bauch,
1997) without individually fitting this dipole configur-
ation. The P300 interval was defined starting 40 ms after
the individual P2 peak and with a length of 166 ms. The
P300 dipole amplitudes were defined as the most posi-
tive peak. The latency was measured as the time
between stimulus onset and the most positive peak
within the P300 time window. The magnitude of the
dipole activity (source potential) was measured in units
of nano-Ampere-meters (nAm). Since there was no dif-
ference between P300 dipole amplitudes and latencies
from left and right hemisphere, mean values were cal-
culated and further analyzed. Reaction times were cal-
culated as mean time between appearance of the target
stimulus and the reaction of the volunteers by pressing
the button. It has to be mentioned that the dipole ana-
lysis is well suited for separating overlapping sub-
components and combine the information of many
channels. However, the dipole localization do not
necessary indicate the localization of P300 generators.
2.3. Statistical analysis
The statistical analyses were implemented using the
SPSS/PC package. Student t-test (two-tailed) were used
for comparing group means. Values are expressend as
means  standard deviation. For correlating electro-
physiological with clinical variables, Pearson and
Spearman correlation coefficients were calculated.
MANOVA was used for covariance analyses. P-values
less than 0.05 were considered as statistically significant.
3. Results
The subcomponents of the auditory event-related
P300, the P3a and the P3b, were separated by the dipole
source analysis in the OCD patients as shown in Fig. 1.
94,31% of the variance of the P300 (unexplained var-
iance 5.69%) recorded at the scalp could be explained
by two dipoles per hemisphere. The temporo-superior
dipole represents activity corresponding to the P3a
(frontal generator), and the temporo-basal dipole
represents that of the P3b (temporo-parietal generator).
There was no significant influence of covariables like
sex, duration of illness, or education level on the elec-
trophysiological variables (amplitudes and latencies of
P3a and P3b) in either the patients or the healthy sub-
jects. In the healthy subjects, there were no significant
correlation coefficients between age and the P3a and
P3b latencies (P3a latency: r= 0.31, n.s.; P3b latency:
r=0.25, n.s.), but significantly positive coefficients were
402 P. Mavrogiorgou et al. / Journal of Psychiatric Research 36 (2002) 399–406
Fig. 1. Dipole source potential model of the auditory event-related
P300 for the grand average data in 21 OCD-patients. Dipole solutions
were computed for the time interval of 269–435 ms. With two dipoles
per hemisphere, a temporo-basal (1+2) and a temporo-superior dipole
(3+4), 94.31% of the variance of the P300 recorded at the scalp could
be explained (unexplained variance 5.69%).
found in the OCD patients (P3a latency: r=0.48,
P=0.03; P3b latency: r=0.63, P=0.002).
3.1. Amplitude and latency of the temporo-superior
dipole (P3a)
Concerning the amplitude of the temporo-superior
dipole (P3a), there was no difference between the OCD
patients (3.2  1.9 nAm) and the healthy subjects
(3.2  3.1 nAm, n.s.). Similarly, the latency of the tem-
poro-superior dipole did not differ between OCD
patients (310.5 35.1 ms) and controls (311.7  28.2 ms;
n.s.).
3.2. Amplitude and latency of temporo-basal dipole
(P3b)
The amplitude of the temporo-basal dipole (P3b) were
significantly larger in OCD patients (7.5  2.9 nAm) as
in healthy controls (5.8  2.0 nAm; P=0,033; Fig. 2).
The latency of this dipole (P3b) was shorter in the OCD
patients (310.2  32.5 ms) as in the controls (323.0 25.0
ms; P=0.16), but this was statistically significant only
for the right hemisphere (OCD patients: 299.8  34.7
ms, controls: 321.5  29.1 m, P=0.034; Fig. 3). In the
covariance analyses, these differences between OCD
patients and healthy controls remained statistically sig-
nificant (P3b ampitude: F1/41=4.2, P=0.048; P3b
latency (right hemisphere: F1/41=4.2, P=0.047). There
was no significant correlation coefficients between the
severity of OCD symptomatology (Y-BOCS) and the
P3b amplitude (r= 0.29) or the P3b latency (right
hemisphere, r=0.22). Severity of depressed symptoms
(HDRS) were also not significantly correlated to the
P3b amplitude (r= 0.19) and latency (r=0.25).
3.3. Reaction time
The reaction time (measured as time until the pressing
of the button to the target tone) was significantly
shorter in the OCD patients (295.3 48.8 ms) as in the
healthy subjects (359.7  66.2 ms, P=0.001). This was
also true in the covariance analysis with the factor age
(F1/41=11.9, P=0.001).
4. Discussion
Our hypothesis that unmedicated OCD patients were
characterized by a large amplitude and short latency of
P3a subcomponent, which mainly reflects the frontal
hyperactivity, could not be confirmed since we found no
difference in P3a component between patients and
healthy controls. This negative finding could have sev-
eral explanations. The orbitofrontal cortex, whose
activity was mainly found to be changed in OCD
patients, is located deeply in the ventromedial anterior
part of the brain. Neuronal activity of the orbitofrontal
cortex can probably not be recorded by scalp electrodes.
Thus, the temporo-superior dipole (P3a), which is cal-
culated for the scalp data, is unable to reflect activity
from this brain area. On the other hand, it is not unli-
kely in general that the P3a component is generated by
other parts of the frontal cortex, for example, the dor-
solateral prefrontal cortex or cingulate gyrus, but not
the orbitofrontal cortex. Furthermore, it can not be
excluded, that the temporo-superior dipole in our dipole
solution is more related to activity of the upper tem-
poral lobe than to that of the frontal lobe. And possibly,
this negative finding could result from the relatively
small variance explained by the temporo-superior dipole
(Hegerl and Frodl-Bauch, 1997). Finally, the negative
result concerning the P3a could also mean that the gen-
eral orienting reaction to a target stimulus, reflected by
the P3a, is not disturbed in OCD patients.
The main result of this study is, however, that only
one subcomponent of the P300, the P3b (temporo-basal
dipole), indicates certain abnormalities in OCD
patients. Since the P3b subcomponent is related to
higher cognitive functions, larger P3b amplitudes and
shorter P3b latencies (right hemisphere) as well as
shorter reaction times in OCD patients as in healthy
subjects (even controlled for the possible covariable age)
could be an electrophysiological correlate of over-
focussed attention and faster cognitive processes.
Our finding of larger P3b amplitudes in OCD patients
compared to normals is noteworthy for several reasons.
 P. Mavrogiorgou et al. / Journal of Psychiatric Research 36 (2002) 399–406 403

Fig. 2. Comparison of the P3b amplitude (temporo-basal dipoles) in OCD patients and healthy controls.

Fig. 3. Comparison of the P3b latency (temporo-basal dipoles) in OCD patients and healthy controls.
404 P. Mavrogiorgou et al. / Journal of Psychiatric Research 36 (2002) 399–406
Firstly, such a finding in the auditory modality has not
been reported for OCD patients previously. Enhanced
amplitudes were found for other auditory ERP compo-
nents as the P300, especially for the N200 (Towey et al.,
1990, 1993; de-Groot et al., 1997; Miyata et al., 1998).
Only Sanz et al. (2001) reported smaller P300 ampli-
tudes in unmedicated OCD patients as in healthy con-
trols, but they did not used subcomponent analysis. As
mentioned earlier, reduced P300 amplitudes of the
visual modality in OCD patients were found in three
studies (Cielselski et al., 1981; Beech et al., 1983; Malloy
et al., 1989). This is in contrast to our finding, but dif-
ferences in modality should be taken into account.
Additionally, the patients in these two studies using
visual ERP were medicated with unknown types of
medication, while we studied unmedicated patients, as
well as severity of illness was not reported. Secondly, the
finding of larger P300 amplitudes in OCD patients is
noteworthy, because most of the other psychiatric
patients, such as schizophrenic or depressive patients,
exhibit smaller P300 amplitudes as normal subjects
(Strik et al., 1993; Juckel et al., 1996; Wagner et al.,
1997). There are also several studies reporting reduced
P300 amplitudes in patients with Alzheimer’s disease
(Pfefferbaum et al., 1990; Polich et al., 1990), with Par-
kinson‘s disease (Raudino et al., 1997) and with alcohol
addiction (Hesselbrock et al., 1993, Polich et al., 1994,
Cohen et al., 1995). Large P300 amplitudes do not seem
to be fully specific for OCD, since it was found that
patients with panic disorder and cycloid psychosis also
exhibited larger P300 amplitudes than healthy volun-
teers (Clark et al., 1996; Strik et al., 1997). However,
this was only true in the patients with panic disorder for
the P3a subcomponent. Finally, a high P3b amplitude
indicates an enhanced level of arousal in OCD patients
which fits very well to the clinical symptoms of these
patients, expressing overfocussed attention. Hyperar-
oused states are related to a highly activated nora-
drenergic system (Foote et al., 1993). Interestingly, the
noradrenergic system is mainly involved in the genera-
tion of P300 waves (Pineda et al., 1989; Swick et al.,
1994) that its activation leads to enlarged P300 ampli-
tudes (O’Neill et al., 2000)
Our finding of shorter P3b latencies in OCD patients
as in normal subjects corresponds to the results of pre-
vious ERP studies, mentioned earlier, in such patients
having short latencies of the P300 component. Using an
auditory oddball paradigm, Towey et al. (1990, 1993)
found that P300 latencies became longer in healthy
subjects with increasing task difficulty, but not in OCD
patients. Morault et al. (1997) found shorter P300
latencies in OCD as in normal subjects during an audi-
tory oddball task with verbal stimuli. These findings are
supported by the studies of de Groot et al. (1997) and
Miyata et al. (1998). Only Sanz et al. (2001) found
longer P300 latencies in OCD as in normal subjects.
Recording visual ERP in visuospatial tasks of shape
discrimination with increasing difficulty, shorter P300
latencies were found by Cielselski et al. (1981) and
Beech et al. (1983). The difference between OCD
patients and healthy controls was more marked, when
the difficulty of the task increased. In both auditory and
visual modality, short P300 latencies were observed in
OCD patients, independently whether difficulty or
complexity of the task increased. As well as in the case
of large P3b amplitudes in OCD, the finding of shorter
P300 latencies in these patients is interesting, since
patients with schizophrenia, depression or dementia
show, if there was any difference, longer P300 latencies
than healthy subjects (Roth et al., 1981; Gordon et al.,
1986; Patterson et al., 1988; Kalayam et al., 1998). This
pattern of short P300 latencies, which could be specific
for OCD, is also supported by shorter reaction times
found in our patients, as compared to the controls.
Reaction times were often found to be prolonged in
psychiatric patients, for example, schizophrenic patients
(Frodl et al., 1998).
Furthermore, it can not be excluded that the abnorm-
alities in P3b amplitude and latency, found here in OCD
patients, reflect structural or functional disturbances in
temporo-parietal or temporo-basal areas in these
patients. This is supported by several neuroimaging stud-
ies showing hyperperfusion or activation in the medial
temporal lobe of OCD patients (Horwitz et al., 1991;
Rauch et al., 1997) and by neuropsychological and EEG
studies (Christensen et al., 1992; Perros et al., 1992).
To sum up, the electrophysiological characteristics of
a large P3b amplitude, a short P3b latency and a short
reaction time in OCD is remarkable since OCD seems
to be one of the few psychaitric diseases being char-
acterized by larger P3b amplitudes and shorter latencies.
The finding of higher P3b amplitudes in OCD should be
replicated. It can be speculated whether auditory ERP,
analyzed by dipole source analysis, is an useful tool to
answer certain diagnostic questions as, for example, to
distinguish between OCD and mild schizophrenia with
motor stereotypes, as well as to have an objective
measure of the response to pharmacological or beha-
vioral therapy in OCD. The present ERP study finally
give further functional evidence for the hypothesis of
cortical hyperactivity associated with faster cognitive
processes and overfocussed attention in OCD.
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