Neuronal generator patterns of olfactory event-related brain potentials in schizophrenia.
ABSTRACT To better characterize neurophysiologic processes underlying olfactory dysfunction in schizophrenia, nose-referenced 30-channel electroencephalogram was recorded from 32 patients and 35 healthy adults (18 and 18 male) during detection of hydrogen sulfide (constant-flow olfactometer, 200 ms unirhinal exposure). Event-related potentials (ERPs) were transformed to reference-free current source density (CSD) waveforms and analyzed by unrestricted Varimax-PCA. Participants indicated when they perceived a high (10 ppm) or low (50% dilution) odor concentration. Patients and controls did not differ in detection of high (23% misses) and low (43%) intensities and also had similar olfactory ERP waveforms. CSDs showed a greater bilateral frontotemporal N1 sink (305 ms) and mid-parietal P2 source (630 ms) for high than low intensities. N1 sink and P2 source were markedly reduced in patients for high intensity stimuli, providing further neurophysiological evidence of olfactory dysfunction in schizophrenia.
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ABSTRACT: The aim of this study was to investigate the usefulness of chemosensory event-related potentials (CSERPs) in response to both olfactory and intranasal trigeminal stimulation in the diagnosis of anosmia. Forty-four patients participated. Gaseous CO2 was used for trigeminal stimulation, vanillin and H2S were used as olfactory stimulants. Event-related potentials to olfactory stimuli could not be obtained in any of the anosmic patients, indicating the complete loss of the sense of smell. However, all patients responded to stimulation of the trigeminal nerve with CO2. These data clearly demonstrate the clinical significance of CSERPs in the assessment of anosmia.The Laryngoscope 08/1998; 108(7):1033-5. · 1.98 Impact Factor
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ABSTRACT: This paper addresses two questions related to the inherent association between breathing and odor perception: Does central nervous processing of odors change when an artificial breathing technique (velopharyngeal closure) is introduced and secondly, does odor processing vary with the oral breathing phase (inhalation or exhalation)? Chemosensory event-related potentials (CSERP) were obtained from eight female subjects while they were smelling an odor mixture (citral, eugenol, linalool, menthol and isoamylacetate). Each subject was required to perform spontaneous mouth breathing (120 trials) as well as the velopharyngeal closure technique (120 trials). Simultaneously, a thermistor monitored the phase of the respiratory cycle. The results reveal that the central nervous correlates of odor processing change with the breathing technique but not with the oral breathing cycle. The findings that early stimulus processing is faster (N1 latency) and late stimulus processing more pronounced (P3 amplitudes) when the subjects are breathing spontaneously are discussed with regard to attentional effects. The reduction of the N1 amplitude during the spontaneous breathing condition may be caused by larger latency variations and longer stimulus rise-times. Furthermore, it is concluded that the oral breathing cycle is less important than the nasal breathing cycle for olfactory information transmission.International Journal of Psychophysiology 07/1999; · 2.04 Impact Factor
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ABSTRACT: To determine how specific methodological choices affect "data-driven" simplifications of event-related potentials (ERPs) using principal components analysis (PCA). The usefulness of the extracted component measures can be evaluated by knowledge about the variance distribution of ERPs, which are characterized by the removal of baseline activity. The variance should be small before and at stimulus onset (across and within cases), but large near the end of the recording epoch and at ERP component peaks. These characteristics are preserved with a covariance matrix, but lost with a correlation matrix, which assigns equal weights to each sample point, yielding the possibility that small but systematic variations may form a factor. Varimax-rotated PCAs were performed on simulated and real ERPs, systematically varying extraction criteria (number of factors) and method (correlation/covariance matrix, using unstandardized/standardized loadings before rotation). Conservative extraction criteria changed the morphology of some components considerably, which had severe implications for inferential statistics. Solutions converged and stabilized with more liberal criteria. Interpretability (more distinctive component waveforms with narrow and unambiguous loading peaks) and statistical conclusions (greater effect stability across extraction criteria) were best for unstandardized covariance-based solutions. In contrast, all standardized covariance- and correlation-based solutions included "high-variance" factors during the baseline, confirming findings for simulated data. Unrestricted, unstandardized covariance-based PCA solutions optimize ERP component identification and measurement.Clinical Neurophysiology 01/2004; 114(12):2307-25. · 3.14 Impact Factor
Neuronal generator patterns of olfactory event-related
brain potentials in schizophrenia
JU¨RGEN KAYSER,a,bCRAIG E. TENKE,a,bDOLORES MALASPINA,cCHRISTOPHER J.
KROPPMANN,aJENNIFER D. SCHALLER,aANDREW DEPTULA,aNATHAN A. GATES,a
JILL M. HARKAVY-FRIEDMAN,bROBERTO GIL,b,dand GERARD E. BRUDERa,b
aDivision of Cognitive Neuroscience, New York State Psychiatric Institute, New York, New York, USA
bDepartment of Psychiatry, Columbia University College of Physicians & Surgeons, New York, New York, USA
cDepartment of Psychiatry, New York University School of Medicine, New York, New York, USA
dDivision of Translational Imaging, New York State Psychiatric Institute, New York, New York, USA
To better characterize neurophysiologic processes underlying olfactory dysfunction in schizophrenia, nose–referenced
30–channel electroencephalogram was recorded from 32 patients and 35 healthy adults (18 and 18 male) during
detection of hydrogen sulfide (constant-flow olfactometer, 200 ms unirhinal exposure). Event-related potentials
(ERPs) were transformed to reference–free current source density (CSD) waveforms and analyzed by unrestricted
Varimax–PCA. Participants indicatedwhen they perceivedahigh (10 ppm) or low (50% dilution) odor concentration.
Patients and controls did not differ in detection of high (23% misses) and low (43%) intensities and also had similar
olfactory ERP waveforms. CSDs showed a greater bilateral frontotemporal N1 sink (305 ms) and mid-parietal P2
source (630 ms) for high than low intensities. N1 sink and P2 source were markedly reduced in patients for high
intensity stimuli, providing further neurophysiological evidence of olfactory dysfunction in schizophrenia.
Descriptors: Olfaction, Schizophrenia, Event-related potential, ERP, Current source density, CSD, Principal com-
ponents analysis, PCA, Surface Laplacian
The study of olfactory event-related potentials (OERP) requires
a rapid onset of odor concentration (less than 50 ms rise time to
70% of maximum concentration; cf. Evans, Kobal, Lorig, &
Prah, 1993; Rombaux, Mouraux, Bertrand, Guerit, & Hummel,
2006) and recording of olfactory responses that avoid concom-
itant trigeminal nerve stimulation (Lorig, 2000) and, depending
on the research objective, potential confounds associated with
active inhalation (Sobel et al., 1998; however, see Lorig, Matia,
Peszka, & Bryant, 1996, for a balanceddiscussion onthe relative
merits of active vs. passive breathing techniques). This became
possible through the development of an olfactometer capable of
producing a rapid pulse of odor in a constant air stream (Kobal,
1982, 2003; cf. Rombaux et al., 2006). Using an olfactometer,
researchers have begun to advance the knowledge in basic mech-
anisms of olfactory perception (Lorig, 2000). The clinical sig-
nificance of OERPs is evident in that stimulation with vanillin or
hydrogen sulfide (H2S) yields no OERP components in anosmic
patients (Kobal & Hummel, 1998), and OERPs are closely as-
sociated with odor thresholds, odor discrimination, and odor
identification (Lo ¨ tsch & Hummel, 2006). Although there has
beensome disagreementabout the naming ofpeaks inthe OERP
waveforms, when using a combined lateral-inferior electroen-
cephalogram (EEG) recording reference (i.e., linked ears or
mastoids), healthy adults typically show as the first distinctive
deflection a negative peak at vertex between 300 and 500 ms,
labeled N1 (e.g., Rombaux et al., 2006). This is followed by one
or more positive deflections (e.g., P2, P3) peaking between 500
et al., 2003). Although significantly delayed compared to other
modalities (approximate N1 peak latencies range between 100
and 200 ms for auditory or visual stimuli) because of a longer
transduction time at the olfactory receptor level (e.g., Rombaux
et al., 2006), the N1 component may have similar modality-spe-
cific properties (Pause & Krauel, 2000; Olofsson, Ericsson, &
Nordin, 2008). The olfactory pathway, however, unlike all other
sensory systems, does not include a thalamic relay, and it is un-
known to what extent different anatomical structures and cor-
tical regions within the olfactory system (e.g., olfactory bulb,
orbital prefrontal cortex; cf. Martzke, Kopala, & Good, 1997)
The National Institute of Mental Health (NIMH) supported this
research through grants MH066428, MH066597, and MH082393. We
are grateful to Bruce Turetsky at the University of Pennsylvania for his
help when we initially established an olfactory laboratory at New York
State Psychiatric Institute. We thank Charles L. Brown, III, for devel-
oping a fine software for waveform plotting. Thanks are also due to
Raymond Goetz and Deborah Goetz for their help with this project. We
appreciate several constructive comments received during the review
process by Tyler Lorig, Dean Salisbury, and two anonymous referees.
Address reprint requests to: Ju ¨ rgen Kayser, New York State Psychi-
atric Institute, Division of Cognitive Neuroscience, Unit 50, 1051 Riv-
erside Drive, New York, NY 10032, USA. E-mail: email@example.com.
Psychophysiology, 47 (2010), 1075–1086. Wiley Periodicals, Inc. Printed in the USA.
Copyright r 2010 Society for Psychophysiological Research
contribute toearly olfactory components. Nevertheless,both N1
and P2 varywithexternal odor characteristics; for example,their
amplitudes increase with greater odor concentration (e.g., Tate-
yama, Hummel, Roscher, Post, & Kobal, 1998; Turetsky et al.,
2003). In contrast, the P3 component, as in other stimulus mo-
dalities, appears to change as a function of subjective signifi-
cance, stimulus probability, and emotional valence of odors
(Pauseetal., 1996, 2003; see also Laudien, Kuster, Sojka, Ferstl,
& Pause, 2006). However, a directcomparison ofchemosensory,
auditory, and visual N1, P2, and P3 peak deflections at midline
sites (Fz, Cz, Pz) revealed a clustering of chemosensory P2 and
P3, which were, in turn, clustered with auditory and visual P3,
suggesting that olfactory P2 may have functional properties typ-
ically attributed to P3 in other sensory systems (Olofsson et al.,
2008). OERP components in healthy adults vary with age and
gender, with younger adults or women having generally greater
amplitude and shorter latency when compared to older adults or
men (e.g., Covington, Geisler, Polich, & Murphy, 1999; Mor-
2000; Olofsson & Nordin, 2004; Stuck et al., 2006).
Very little is known about the current generators underlying
the olfactory ERP components. Kettenmann, Hummel, Stefan,
and Koba (1997), using magnetoencephalographic rather than
EEG recordings, localized equivalent current dipoles or sources
corresponding to P1, N1, and P2 components between the su-
periortemporalplane, theparainsularcortex, centralpartsofthe
insular, and the superior temporal sulcus. Furthermore, Daniels
et al. (2001) found that patients with right-sided lesions, primar-
discriminationanddecreasedamplitudesofP2 andP3 atparietal
scalp locations, independent of stimulation side (left or right
Olfactory Deficits in Schizophrenia
Evidence for olfactory dysfunction in schizophrenia has been
reported in multiple studies using psychophysical measures of
odor identification and detection thresholds. Studies have con-
sistently found reduced ability to name or identify odors in
schizophrenic patients compared to healthy controls, typically
yielding large effect sizes (for a review, see Moberg et al., 1999).
Findings for odor detection thresholds have been more mixed,
with some studies reporting poorer odor thresholds in schizo-
phrenia (Moberg et al., 1999) and others reporting normal or
even superior olfactory acuity (Martzke et al., 1997; Moberg et
al., 2006). Measuring unirhinal thresholds to n-butanol in 17
unmedicated patients and 17 well-matched healthy controls,
Purdon and Flor-Henry (2000) found asymmetric thresholds in
schizophrenia. Whereas controls revealed no nostril differences,
patients had a greater deficit for the left compared to the right
nostril, implicating a primarily left-lateralized impairment, given
the predominantly ipsilateral afferent projections from the ol-
factory bulb to piriform cortex within the medial temporal lobe
(e.g., Martzke et al., 1997; Moberg et al., 1999). Interestingly,
this threshold asymmetry was reversed in another 10 patients
after they received neuroleptic treatment, mostly because of left
nostril improvements, which suggested that the effects of anti-
psychotic medication may differentially affect the two hemi-
spheres (Purdon & Flor-Henry, 2000).
Few studies, however, have been directed at the neurophys-
iologic processes underlying olfactory dysfunction in schizo-
phrenia. In the first electrophysiologic study, Turetsky et al.
(2003) measured OERPs in 21 patients with schizophrenia and
20 healthy controls to three concentrations of H2S. Patients and
controls did not differ significantly in ratings of the perceived
intensity of the odors, but, nonetheless, patients had reduced N1
and P2 amplitudes, with the largest difference for the strongest
odor intensity. Turetsky, Kohler, Gur, and Moberg (2008) also
found similar reductions of N1 and P2 amplitude in first degree
relatives of patients with schizophrenia, suggesting that this rep-
resents a vulnerability marker for this disorder. Using odorants
of different hedonic value (i.e., rose-like phenethyl alcohol and
rotten butter-like isobutyraldehyde), Pause, Hellmann, Goder,
Aldenhoff, and Ferstl (2008) reported shorter peak latencies
across several ERP components in nine schizophrenic compared
to nine depressed and nine healthy men, but these effects were
evidently most robust for N1 during the presentation of negative
odors. Unfortunately, no ERP waveforms were included in this
report, making it difficult to evaluate the exact meaning of these
findings or to relate them to other studies.
Methodological Issues in Olfactory ERP Research
Following early recommendations (Evans et al., 1993), most
OERP studies have relied on peak and latency measures of
‘‘prominent’’ deflections inselected OERP waveforms, mostly at
vertex (Cz) orneighboring midline (Fz, Pz) or lateral sites (C3/4)
and usually referenced to linked ear lobes or linked mastoids
(e.g., Kru ¨ ger, Frasnelli, Bra ¨ unig, & Hummel, 2006; Lundstro ¨ m,
Seven, Olsson, Schaal, & Hummel, 2006; Murphy et al., 2000;
Pause et al., 2003). The use of multichannel EEG montages has
largely been limited to mapping ERP or CSD1topographies
(Laudien et al., 2006, 2008) or showing LORETA source local-
source localization algorithms, such as LORETA or BESA, have
the potential for data simplification and clarification, these ap-
proaches provide genuinely model-dependent solutions that need
to be cautiously considered, pending independent validation.
Statistical analyses have relied on ERP component measures
employing a ‘‘region-of-interest’’ approach, in which the topo-
graphic ERP signal is reduced to a few spatially smeared sites,
and is also subject to experimenter bias in the selection or group-
ing of electrodes (Kayser & Tenke, 2005). Although the need to
systematically identify the olfactory ERP component structure
(i.e., how many major components with what temporal, spatial,
and functional characteristics) has long been recognized (Lorig,
2000), only preliminary efforts have been made to date. ERP
components are classically conceived as an electrophysiologic
correlate of the underlying neuronal generators associated with
information processes (cf. Kayser & Tenke, 2003). This concep-
tual definition implies that an ERP component is characterized
by (1) temporal (latency), (2) spatial (scalp topography), and (3)
functional (task or condition) specificity (e.g., Donchin et al.,
1977; Fabiani, Gratton, & Coles, 2000). However, the identifi-
cation and measurements of ‘‘obvious’’ peaks and troughs in the
ERP waveforms as meaningful entities can be misleading. Spec-
ifying peaks in noisy waveforms (a problem not resolved but
rather aggravated by using an automated computer algorithm)
1076J. Kayser et al.
1There appears to be considerable confusion about the meaning of
sources and sinks and their relationship to ERP waveforms. CSD esti-
scalp from the underlying brain tissue and are therefore equally impor-
tant in characterizing neuronal generator activity. As such, these esti-
mates must be fully compatible with the ERP topography from which
they are derived in order to be of empirical or descriptive value.
and determining area integration limits fordeflectionsthatinvert
and shift across scalp locations are subject to experimenter bias
and raise questions of statistical independence, which will cru-
cially affect their statistical analysis. Moreover, these ERP com-
ponent measures depend directly on the recording reference,
because the timing, topography, and amplitude of these ERP
deflectionswillchangewithanyotherreference (e.g., Dien, 1998;
Kayser, Fong, Tenke, & Bruder, 2003), thereby affecting com-
ponent interpretation (e.g., polarity, topography, generator).
Thus, the definition and measurement of appropriate ERP com-
ponents and the dependency of surface potentials on a reference
location (e.g., linked ears or mastoids, nose, average) are two
problemsthathaveplaguedERPresearch(e.g., Kayser &Tenke,
2003, 2005; Nunez & Srinivasan, 2006; Tenke & Kayser, 2005).
We have proposed that these limitations can be overcome
without sacrificing information by combining current source
density (CSD; surface Laplacian) and temporal principal com-
ponents analysis (PCA) to identify relevant, data-driven com-
ponents (Kayser & Tenke, 2006a, 2006b; Kayser et al., 2006,
& Bruder, 2009; Tenke et al., 2008; Tenke, Kayser, Stewart, &
Bruder, 2010). CSD provides a representation of current gener-
ators that underlie ERPs and represent the magnitude of radial
current flow entering (sink) and leaving (source) the scalp (e.g.,
Nunez & Srinivasan, 2006). CSD analysis is a reference-free
technique (any EEG recording reference scheme will yield the
same, unique CSD transform) that provides sharper topogra-
phies compared to those of scalp potentials while also reducing
redundant contributions due to volume conduction (e.g., Tenke
& Kayser, 2005). Often-raised concerns include the requirement
ofa high-density EEG montage for reliably computing CSDs, as
well as their presumed insensitivity to deep sources. We have
empirically addressed these concerns, demonstrating that no in-
formation is lost with the CSD transform when directly com-
paredtotheoriginal ERPs, and deepordistributedsources,such
as P3, are adequately and sufficiently represented (Kayser &
Tenke, 2006a). A low-density EEG montage may be as efficient
as a dense electrode montage in summarizing CSD activity for
group data, because group averages effectively impose a spatial
low-pass filter to the data (Kayser & Tenke, 2006b). In the spe-
cific context of olfactory ERPs, for which generators are pre-
sumably deep (i.e., with origins in olfactory, gustatory, or limbic
structures), the corresponding fields and CSDs will be more
diffuse at scalp, rendering a low–resolution surface Laplacian an
advantage, rather than a liability. Thus, these conventional con-
to be useful but may constitute an optimal analytic approach for
many practical ERP applications. Compared to more complex
EEG source localization methods (Michel et al., 2004), relying
on surface Laplacian estimates as an analytic strategy is more
conservative because it completely avoids additional (and un-
proven) biophysical assumptions (tissue conductivity and geom-
etry, laminar orientation, number and independence of
shown to be superior to more traditional ERP measures, for
instance, revealing more robust F statisticsand betterreliabilities
(i.e., internal consistency and temporal stability) when directly
compared with integrated time windows or baseline-to-peak
measures (e.g., Beauducel, Debener, Brocke, & Kayser, 2000;
Kayser et al., 1997; Kayser, Tenke, & Bruder, 1998). Often-cited
limitations, such as misallocation of variance because of latency
traditional component measures and more severely (e.g., Beau-
ducel& Debener,2003;Chapman &McCrary,1995;Donchin &
Heffley, 1978; Wood & McCarthy, 1984). With careful consid-
eration, temporal PCA can provide a concise and unbiased sum-
mary of ERP/CSD activity (Kayser & Tenke, 2003, 2006a)
associated with generator patterns underlying stimulus process-
ing, even for slow and long-lasting components (e.g., Kayser et
al., 2006), and could therefore provide an answer to the question
of relative statistical independence between putative olfactory
components (Lorig, 2000). Moreover, because the extracted
CSD factors are independent of the recording reference, they
have an unambiguous component polarity and topography.
A primary goal of thisstudywasthereforetoemploythisnew
CSD-PCA approach for an improved characterization of
OERPs (i.e., N1, P2) in schizophrenia patients and healthy
adults. Following the findings of Turetsky et al. (2003), it was
predicted that schizophrenia patients would show reduced N1
and P2 amplitudes (i.e., their CSD equivalents) when compared
to healthy adults, and these OERP differences will be most ev-
ident at higher concentrations of H2S.
As part of a study of olfaction and social function in schizo-
phrenia, 35 healthy adults (ages 18–61 years, M ? SD5
31.7 ? 12.0; 18 men; 6 smokers) without current or past psy-
chopathology, neurological illness, or substance abuse (Nurn-
berger et al., 1994) were recruited for payment (US$10/h) from
the New York metropolitan area. These controls were compared
Institute (ages 18–54 years, M ? SD533.3 ? 9.6; 18 men; 5
smokers) meeting DSM-IV (American Psychiatric Association,
1994) criteria for schizophrenia (n526; 15 paranoid, 9 undiffer-
entiated, 1 catatonic, 1 residual) or schizoaffective disorder
(n56; 3 bipolar type, 3 depressive type). Diagnoses were based
on clinical interviews by psychiatrists and trained psychologists
and a semistructured interview (Nurnberger et al., 1994) includ-
ing items from commonly used instruments (e.g., Andreasen
1983, 1984). Symptom ratings were obtained using the Positive
andNegative SyndromeScale(PANSS;Kay, Opler, & Fishbein,
1992). The mean total Brief Psychiatric Rating Scale (BPRS)
score available for 31 patients was 28.1 ? 6.6, with about equal
scores for positive (10.8 ? 4.9) and negative (11.7 ? 3.9) symp-
toms (general 23.7 ? 5.8), indicating that patients were mildly
disturbed. Meanageofonsetavailablewas 23.7 ? 6.3 yearswith
an average illness duration of 9.8 ? 8.9 years. Most patients
(n529) were treated with antipsychotic medications (9 ari-
priprazole, 7 risperidone, 5 olanzapine, 4 ziprasidone, 2 per-
25–800 mg/day; Woods, 2003).
All participants were right-handed (Oldfield, 1971; laterality
quotient, controls vs. patients, 73.6 ? 29.2 vs. 84.0 ? 18.3). Pa-
this difference was of only marginal significance (14.2 ? 2.7 vs.
15.5 ? 1.7 years), F(1,63)53.77, p5.06. Participants were in-
structed to refrain from smoking on the day of test. OERP re-
cording sessions were scheduled between 9 a.m. and 5 p.m. and
lastedabout 1.5 h. Time of testing did not differ betweengroups,
F(1,63)o1.0, n.s., thereby controlling for putative circadian in-
Olfactory ERP generator patterns in schizophrenia1077
fluences on OERP amplitudes (Nordin, Lo ¨ tsch, Murphy, Hum-
mel, & Kobal, 2003). The experimental protocol had been ap-
proved by the institutional review board and was undertaken
with the understanding and written consent of each participant.
Stimuli and Procedure
Participants were seated in an IAC sound–attenuated booth us-
ing a chin and forehead rest, with a video camera monitoring
participants’ compliance and behavior. While focusing on a fix-
ation cross and breathing normally through the nose,2H2S stim-
uli (10 ppm, Scott Speciality Gases, Plumsteadville, PA) at high
(undiluted) and low (diluted to 50%) concentrations were deliv-
ered to the left or right nostril by a constant-flow olfactometer
(OM2s, Heinrich Burghart GmbH, Wedel, Germany) through a
Teflon tube inserted approximately 1 cm into the naris. Stimulus
duration was 200 ms (notmorethan 50 ms risetime according to
attheexitoftheolfactometerhad aconstantflowrate(about8 l/
min), temperature (the measured range was 381–391C at the ol-
factometers head to approximate 371C body temperature in the
nasal cavity), and relative humidity (above 80%). Odors were
presented in four blocks of 24 trials each, with a variable inter-
stimulus interval (15–25 s). White noise of approximately 75 dB
SPL was presented binaurally via Telephonics TDH–49P ear-
phones to preclude hearing the switching valves. Participants
responded as to whether they perceived a low or high intensity
odor by raising their left or right hand, which was visually mon-
itored and recorded by the experimenter. Therefore, the present
paradigm consisted of an active odor intensity detection task,
requiring conscious processing of and responding to perceived
hydrogen sulfide stimuli. Because the time of odor stimulation
was not cued, participants could fail to respond (miss). Nostril
order and response hand assignment were counterbalanced
across blocks and participants.
Data Recording and Artifact Procedures
All data recording and preprocessing closely followed the pro-
cedures detailed elsewhere (e.g., Kayser et al., 2007). Briefly,
nose-referenced EEG (30 channels) and bipolar EOG activity
were continuously recorded at 200 samples/s with a gain of 10k
(5k horizontal, 2k vertical EOG) within 0.1–30 Hz (?6 dB/
octave). Volume-conducted blink artifacts were removed from
the raw EEG by spatial PCA. Recording epochs of 2000 ms (250
ms prestimulus baseline) were extracted off-line, tagged for A/D
saturation, and low-pass filtered at 20 Hz (?24 dB/octave). A
by-channel and trial-by-trial basis (Kayser & Tenke, 2006d). A
trial was rejected if it contained artifact in more than eight chan-
nels; otherwise, artifactual data were replaced by spherical spline
interpolation (Perrin, Pernier, Bertrand, & Echallier, 1989) from
artifact-free channels. These procedures for artifact detection
and reduction were originally developed to optimize the signal-
to-noise ratio in problematic ERP recordings, such as those
stemming from artifact-prone psychiatric samples, but these
routines also help in reducing the problem of latency jitter in
olfactory ERPs (Lorig, 2000).
Excluding trials on which the participant ‘‘missed’’ the odor,
and disregarding the participant’s high versus low intensity re-
sponse, separate olfactory ERPs for high and low odor intensity
were averaged from correctly detected, artifact-free trials using
the entire 2-s epoch. To obtain more stable waveforms, ERPs
werepooled across nostrilsbecause of their blocked presentation
order, and preliminary analyses did not reveal any effects of
odor stimulation is of subordinate importance for measuring
OERPs (e.g., Olofsson et al., 2006; Stuck et al., 2006). Themean
number of trials (? SD) used to compute OERP averages were
30.7 ? 8.4 and 23.1 ? 8.9 (high vs. low intensity, respectively)
for healthy controls and 30.0 ? 8.0 and 23.6 ? 8.5 for patients.
averages, F(1,63)545.3, po.0001, but there were no differences
between patients and controls. Visual inspections of the individ-
ratio for each participant. ERP waveforms were screened for
electrolyte bridges (Tenke & Kayser, 2001), low-pass filtered at
100 ms preceding stimulus onset. ERPs were re-referenced to
linked mastoids (TP9/10) for comparison to prior OERP studies
using linked ear lobes or mastoids as reference.
CSD Transform, Temporal PCA, and Statistical Analyses
All OERP waveforms at each electrode were transformed into
reference-free CSD estimates (mV/cm2units; 10 cm head radius;
50 iterations; m54; smoothing constant l510?5) using a
spherical spline surface Laplacian (Perrin et al., 1989). To deter-
mine their common sources of variance, CSD waveforms were
submitted to temporal PCA derived from the covariance matrix,
followed by unrestricted Varimax rotation of the covariance
loadings (Kayser & Tenke, 2003, 2006c). The input data matrix
consisted of 401 variables (time interval ?250 to 1750 ms) and
4,154 observations stemming from 67 participants, two intensi-
ties, and 31 electrode sites, including the nose.
Data from two meaningful, high-variance CSD factors cor-
responding to N1 and P2 were submitted to repeated measures
analysis of variance (ANOVA) with group (patients, controls)
and gender (male, female) as between-subjects factors and odor
intensity (high, low) as a within-subjects factor. The ANOVA
designs also included subsets of lateral, homologous recording
sites over both hemispheres at which PCA factor scores were
largest and most representative of the associated CSD compo-
nents (cf. Kayser & Tenke, 2006a; Kayser et al., 2006), adding
hemisphere and site as within-subjects factors to the design.
However, because subsets were selected on the premise that they
collectively represent sink or source activity targeted in these
not be reported.
It appears to be a fairly common, although incorrect, as-
sumption that CSD methods necessarily identify equivalent cur-
rent dipoles. Because multiple, overlapping generators with
different geometries, time courses, and signal-to-noise ratios
likely contribute to the ERP signal, it is not clear whether a
1078 J. Kayser et al.
2Although OERP studies typically trained participants to perform
velopharyngeal closure as an active breathing technique to prevent in-
tranasal respiratory airflow and interference during odor presentation,
these potential benefitsmay beoffsetbythe dual-task demands, resulting
in divided attention that may alter odor processing. Comparisons of
different breathing conditions with rather small sample sizes yielded
conflicting results as to whether and how OERP amplitudes are affected
(Lorig et al., 1996; Pause, Krauel, Sojka, & Ferstl, 1999; Thesen &
Murphy, 2001). Given the likelihood of differences between healthy
adults and schizophrenia patients in compliance with and capability of
performing the velopharyngeal closure technique and that its associated
systematic confounds (vigilance, attention) are more likely to affect odor
detection and OERPs than the uncontrolled nasal air flow (cf. Laudien,
Wencker, Ferstl, & Pause, 2008; Mainland & Sobel, 2006), a natural,
spontaneous breathing condition seemed to be the preferred choice.
prominent sink–source pattern represents opposite poles of a
single dipole or several dipoles with different orientations. This
uncertainty is not resolved by inverse models that identify pu-
sinks and inferior-temporal sources having corresponding time
courses and spanning the Sylvian fissure, thereby matching the
orientationofthewell-knownunderlyinggenerator (e.g., Kayser
& Tenke, 2006a, 2006b; Kayser et al., 2007, 2009), the ventral
source may be larger than the central sink and subject to greater
EMG noise from the neck. Another example would be a midline
closed-field generator as described for a novelty vertex source
field cancellations. The point is that CSD does not provide a
single dipole measure, nor does it require one. For its quanti-
fication, we are adopting a pragmatic approach by analyzing
CSD activity at regions or sites associated with distinct sinks or
For analyses of the behavioral data, percentages of missed
responses were submitted to a similar repeated measures
ANOVA without the electrode factors. Sources of interactions
and main effects were explored with simple effects (BMDP-4V;
Dixon, 1992). When appropriate, Greenhouse–Geisser epsilon
correction was used to compensate for violations of sphericity
was applied for all effects.
The mean percentages of H2S stimuli that were missed (? SD)
were 23.4 ? 17.5 and 44.9 ? 19.3 (high vs. low intensity, respec-
tively) for healthy controls, and 22.5 ? 16.1 and 41.1 ? 20.2 for
patients, yielding a highly significant main effect of odor inten-
sity, F(1,63)577.2, po.0001, but no effects involving group, all
Average ERP and CSD Waveforms
To the best of our knowledge, no complete ERP waveform to-
pography for olfactory stimuli has yet been published, except for
selected midline ‘‘topographies’’ (Fz, Cz, Pz), probably because
of concerns about individual specificity (Lorig, 2000). By over-
laying individual ERPs and CSDs, we established that the grand
means accurately summarized temporal and spatial properties of
the observed OERP components. Figure 1 compares the grand
mean olfactory ERP and CSD component structure for all 67
participants at all 31 scalp locations (averaged across intensi-
ties).3The OERP waveforms (solid gray lines) showed a typical
negative–positive component sequence, including an N1 poten-
tial (approximate peak latency 300 ms) believed to reflect initial
(600 ms), which is comparable to those reported in prior studies
(Pause et al., 1996; Turetsky et al., 2003). By explicitly including
the mastoid reference sites (TP9/10), however, it becomes obvi-
ous that recording sites along the reference-dependent isopoten-
tial line (e.g., T7/8, FT9/10, P9/10) showed little or no ERP
activity. Thus, ERP activity at these sites is severely attenuated
& Tenke, 2006a, 2006b; Tenke & Kayser, 2005). In contrast, the
reference-free CSD waveforms (black dashed lines) identified
robustsinkactivityatthesesites, which wasnotcompromised by
the choice of reference. Although the observed N1 sink and P2
source in the CSD waveforms directly corresponded to the N1
and P2 potentials in the OERP waveforms, marked topographic
distinctions were evident, particularly with respect to the fronto-
temporal N1 sink and lateral frontal sinks associated with the
mid-parietal P2 source.4
N1 sink and P2 source amplitudes were greater to high- than
low-intensity H2S stimuli in both patients and healthy adults,
further confirming their relationship to olfactory processing
(Figure 2). Schizophreniapatients showed similarolfactory ERP
and CSD waveforms when compared to controls, but their N1
sink and P2 source amplitudes were smaller.
PCA Component Waveforms and Topographies
The first four PCA factors effectively explained all of the sys-
tematic CSD variance (82.6% after rotation). The time courses
of the factor loadings (Figure 3A) and the corresponding factor
score topographies (Figure 3B) identified two factors corre-
sponding to N1 sink (305 ms peak latency, lateral frontotempo-
ral maximum) and P2 source (630 ms peak latency, mid-parietal
maximum). Two later factors had a frontocentral (1015 ms) or
parietal (1750 ms) midline sink maximum, suggesting a close
correspondence to the response requirements in this task (i.e.,
raising left or right hand; cf. Kayser et al., 2007) and were there-
fore not further analyzed.
Both healthy adults and schizophrenia patients had bilateral
N1 sinks for the high odor concentration over the lateral tem-
poral sites (Figure 3B, top, first column) and a corresponding
mid-frontopolar source. Similarly, both controls and patients
showed a medial parietal P2 source topography to both low and
high odor concentrations, with current sinks maximal over lat-
eral frontotemporal regions (Figure 3B, bottom, Columns 1 and
2). The reduced amplitude of the N1 sink and P2 source in pa-
tients was most evident to the high concentration of H2S.
Repeated Measures ANOVA of PCA Factor Scores
N1 sink. At lateral centrotemporal sites (T7/8, C3/4, FC5/6,
CP5/6) for factor 305, there was a highly significant main effect
of intensity, F(1,63)5131.7, po.0001, confirming the presence
for detailed ANOVA means, see supplementary Table A1). A sig-
nificant Group ? Intensity interaction, F(1,63)56.11, p5.02,
high- but not low-intensity stimuli: simple group main effects at
high intensity, F(1,63)55.87, p5.02, at low intensity, F(1,63)
o1.0, n.s. There were also a significant interactions of Group ?
Gender, F(1,63)54.15, p5.05, and of Group ? Gender ?
Intensity, F(1,63)54.87, p5.03, which originated from greater
high intensity N1 sinks for healthy women compared to healthy
men (M ? SD, ?1.42 ? 1.57 vs. ?0.97 ? 0.92), with patients
showingthe opposite gender
?0.95 ? 1.02); simple Group ? Gender interaction effects, at
effect(?0.51 ? 0.95 vs.
p5.03, at lowintensity,
Olfactory ERP generator patterns in schizophrenia 1079
3The ERP/CSD component structure was highly comparable for
healthy adults and schizophrenia patients (see Figures A1 and A2 in the
4Animated ERP (linked-mastoids reference) and CSD topographies
comparing groups and intensities can be obtained at URL http://
The analysis for the frontopolar source (Fp1/2) accompany-
ing the bilateral centrotemporal sinks for factor 305 revealed
highly significantintensity, F(1,63)527.2, po.0001, and Group
? Intensity effects, F(1,63)57.71, p5.007, stemming from
a greater high-larger-than-low-intensity amplitude difference
for controls compared with patients (Figure 3B, top).
Across groups, this source was also greater over the right than
left frontopolar site: hemisphere main effect, F(1,63)54.28,
P2 source. At medial-lateral centroparietal sites (P3/4, P7/8,
CP5/6, C3/4) for factor 630, there was also a highly significant
main effect of intensity, F(1,63)574.5, po.0001, stemming
from a greater P2 source for high than low odor concentration
(Figure 3B, bottom; for detailed ANOVA means, see supple-
mentary Table A2). A significant group main effect, F(1,63)
56.48, p5.01, and a highly significant Group ? Intensity in-
teraction, F(1,63)514.0, p5.0004, indicated smaller P2 source
in patients compared to healthy adults, which was significant for
high (simple group main effect, F(1,63)516.3, p5.0001) but
not low intensity stimuli, F(1,63)o1.0, n.s. A significant hemi-
sphere main effect, F(1,63)55.99, p5.02, resulted from right-
larger-than-left P2 source across groups. A greater P2 source in
women compared with men for both controls (M ? SD,
0.71 ? 0.94 vs. 0.40 ? 0.81) and patients (0.38 ? 0.77 vs.
0.31 ? 0.72)
8) accompanying the parietal P2 for factor 630 revealed a highly
significant main effects of intensity, F(1,63)516.8, p5.0001,
hemisphere, F(1,63)513.2, p5.0006, andgender, F(1,63)514.1,
p5.0004, which resulted from greater sinks for high compared to
low intensity and right-larger-than-left hemisphere sinks (Figure
3B, bottom), and greater sinks in women than men (M ? SD,
?0.97 ? 0.89 vs. ?0.47 ? 0.84). However, there were no
significant effects involving group.
yieldedasignificantgender main effect,
1080J. Kayser et al.
0500 1000 1500
500 1000 1500
0 500 1000 1500
0500 1000 1500
0 500 1000 1500
0 500 1000 1500
0 500 1000 1500
0 500 1000 1500
T7 C3 CZ
Figure 1. Grand mean olfactory ERPs referenced to linked mastoids and reference–free CSD waveforms for the total sample (N567) at all 31 recording sites
concerns. Two prominent CSD components are labeled at sites T7 (N1 sink) and Pz (P2 source), where they closely corresponded to their ERP counterparts.
The application of the CSD-PCA approach identified factors
corresponding to the N1 and P2 potentials, which have been
consistently observed in OERP studies (Lorig, 2000; Pause &
Krauel, 2000). Schizophrenia patients and healthy controls
showed a prominent N1 sink over frontotemporal sites and a
corresponding mid-frontopolar source. This topography is fully
compatible with postulated generators within the medial tempo-
ral lobe and/or basal cortical regions (e.g., orbital frontal cortex;
cf. Martzke et al., 1997). In addition, the observed N1 sink to-
pography was distinctly unique, that is, it did not match gener-
atorpatternspreviouslydescribedforearly visual(e.g., Kayseret
al., 2006, 2007, 2009) or auditory components (e.g., Kayser &
Tenke, 2006a, 2006b; Kayser et al., 2007, 2009; Tenke et al.,
2008, 2010), which strongly suggests that the underlying neuro-
nal activity may indeed reflect an early, modality-specific pro-
cessing stage during odor perception. In contrast, the P2 source
had a mid-parietal topography, with current sinks over lateral
frontotemporal sites, which is compatible with the notion of a
close association of olfactory P2 with a classical P3b potential
(e.g., Lorig,2000; Olofssonetal., 2008). Moreover, theobserved
P2 source topography was highly similar to P3 source topogra-
phies repeatedly found during working and recognition memory
paradigms using visual or auditory word stimuli (e.g., Kayser et
al., 2006, 2007, 2009, 2010) or during auditory oddball para-
digms (e.g., Kayser & Tenke, 2006a, 2006b; Tenke et al., 2010).
The corresponding generators of olfactory P2 are therefore con-
sistent with those of P3 in other modalities, rather than with
interpretation of the P2 source, the likeness of the olfactory N1
sink to N1 activity observed for other modalities may be chal-
lenged by the suggestion that the olfactory bulbs themselves may
be closer homologs to the primary sensory cortices of other mo-
dalities than are piriform cortex and related olfactory cortical
regions (Haberly, 2001). In this scenario, it is unlikely that neu-
ronal activity of primary olfactory processing, equivalent to ca-
lcarine or Heschl’s gyrus activation within the visual or auditory
pathways, will propagate to scalp and may therefore not register
as an ERP component. Another consideration is that the com-
thalamocortical projections, afferent and efferent projections of
N1 fromother modalities improbable. Rather, olfactory N1 sink
activity peaking around 300 ms may instead reflect functional
activation of secondary olfactory regions, including piriform
cortex, analogous to inferior-temporal visual association cortex
(see Figure 13 in Haberly, 2001). The implication of this prop-
osition is that N1 sink could be regarded as an olfactory N2,
analogous to an auditory or visual N2. In this case, the olfactory
N1 should be associated with stimulus categorization and clas-
the present odor detection paradigm would be the olfactory
equivalent of an N2/P3 complex typically observed during many
ERP paradigms, including an oddball task. Although it is not
observed bilateral temporal N1 sink pattern is not necessarily
inconsistent with this assumption, the preferential access of ol-
faction to evaluative (also limbic) processes would suggest a
The N1 sink and P2 source were greater to high than low
concentrations of H2S, which is in accord with prior studies
(Stuck et al., 2006; Turetsky et al., 2003) and supports their re-
lation to olfactory processing. It is also compatible with the idea
the N1 sink reflects N2-like categorization processes, although
future studies have to pursue this hypothesis with a more ap-
Olfactory ERP generator patterns in schizophrenia 1081
1000 15000 500
(n = 35)
(n = 32)
Figure 2. Grand mean olfactory CSDs for 35 healthy adults and 32 schizophrenia patients comparing low- and high-intensity H2S stimuli at sites T7
1082 J. Kayser et al.
0 250 500750
CSD Factor Score Topographies
High - Low
CSD Factor Loading Waveforms
High Low High - Low
Figure 3. (a) Factor loadings of the first four PCA factors (labels indicate peak latency [with variance explained]) extracted from olfactory CSD
waveforms (N567). (b) CSD factor score topographies corresponding to N1 sink (top) and P2 source (bottom) for 35 healthy controls and 32
schizophrenia patients comparing low- and high-intensity H2S stimuli. Margins show difference topographies for intensity (high minus low) and group
(controls minus patients).
propriate design, for instance, by includinga broader parametric
manipulation or different odors. Notably, as the current data
were based on 12–16 trials per intensity level, it is evident that
viable and meaningful olfactory ERP/CSD averages can be ob-
tained with a relatively small number of trials.
Schizophrenic patients had reduced N1 sink and P2 source
amplitudes to the higher concentration of H2S, replicating the
findings of Turetsky et al. (2003). The reduced OERPs in schizo-
phrenia patients were present in the absence of behavioral differ-
ences between patients and controls. Schizophrenia patients
showed considerable success in performing the olfaction task,
and their behavioral performance was on a par with that for
healthy controls. This indicates that the OERP reductions in
schizophrenia are not due to a failure to attend to stimuli or
overall poorer task performance. Instead, it is more parsimoni-
ous topresume that the OERP differencesreflect an abnormality
in obligatory processing of odors in cortical regions related to
olfaction. Similarly, the lack of an association of olfactory iden-
tification and neurocognitive test performance (Continuous Per-
formance Test and Wisconsin Card Sorting Test) has been cited
as evidence that reduced olfactory function in schizophrenia is
not secondary to deficits in attention or executive function (Seid-
man et al., 1997). It still remains to be demonstrated, however,
whether the OERP deficits in schizophrenia are specific to ol-
factory processing or stem from a frontotemporal dysfunction
that affects ERPs in multiple modalities. Given our N2-like in-
terpretation of the olfactory N1 sink, its marked reduction in
schizophrenia is in striking accordance with ERP evidence doc-
umenting profound reductions of N2 amplitudes across process-
ing modalities and paradigms (e.g., Alain, Bernstein, He,
Cortese, & Zipursky, 2002; Alain, Cortese, Bernstein, He, &
Zipursky, 2001; Bruder et al., 1998, 1999; Kayser et al., 1999,
2001, 2009; O’Donnelletal.,1993;Umbricht, Bates,Lieberman,
Kane, & Javitt, 2006).
The reduction of N1 sink over lateral temporal lobe sites and
P2 sourceovermedialparietal sites inschizophrenia patientswas
bilateral and not dependent on hemisphere. However, the P2
source accompanying N1, were greater over right than left hemi-
sphere sites across both patients and healthy adults. In this re-
deficits in higher-order odor processing (Jones-Gotman &
Zatorre, 1993), and patients with right-sided lesions of the fron-
tal or temporal lobe showed decreased amplitudes of P2 and P3
emission tomography (PET) studies measuring regional cerebral
intensity of odors have provided additional evidence supporting
the important role of right orbitofrontal cortex in olfactory pro-
cessing (Zatorre, Jones-Gotman, & Rouby, 2000). Malaspina et
al. (1998) measured rCBF (using SPECTscans) in 6 schizophre-
nia patients and 7 controls during an odor identification task,
and the patients showed hypometabolism in right cortical re-
gions, including the inferior frontal area, superior temporallobe,
evidence of lateralized olfactory processes suggested that olfac-
tory stimuli differentially activate left or right brain regions, in-
cluding medial temporal lobe and orbitofrontal cortex, but the
inconsistent nature of this asymmetry has prompted suggestions
that hemispheric differences depend on the cognitive or emo-
tional processing demands (Royet & Plailly, 2004). Also, a study
of laterality of OERPs during monorhinal stimulation with amyl
acetate in 28 healthy adults found generally larger N1/P2 am-
plitudes for left than right nostril stimulation and at left than
right hemisphere sites for left nostril stimuli (Olofsson et al.,
2006). A related issue that has attracted less attention in this
context is the potential confound of blocking left or right stim-
ulus presentations as mandated by use of an olfactometer, such
as the one used in the current study. Blocked unilateral odor
presentations could lead to corresponding contralateral shifts in
attention (cf. Kinsbourne, 1970), which may interfere with the
predominantly ipsilateral organization of the olfactory system
clarify the nature of hemispheric asymmetries of OERPs and
their relation to stimulus and task demands.
A gendereffect was found for the N1 sinkthat differedacross
groups. Namely, healthy women showed greater N1 for the high
concentration of H2S compared to healthy men, whereas schizo-
phrenia patients showed the opposite gender effect. P2 also
showed a gender effect, with women showing greater source and
sink activity than men, but this was not dependent on group.
that men with schizophrenia had greater olfactory impairment
than women for smell identification, more recent studies by this
and other groups have not replicated this gender effect (Kopala,
et al., 1997). Although we know of no reports examining gender
differences in OERPs of schizophrenia patients, Becker et al.
(1993) found larger P1/N1 and N1/P2 amplitudes for vanillin
and H2S odorants in women compared to men in a sample of
healthy and psychosis-prone subjects (i.e., gender differences
were unaffected by group classification), and Stuck et al. (2006)
also found larger P2 amplitudes to H2S in healthy women than
men. Lundstro ¨ m and Hummel (2006), measuring ERPs of
healthy adults topeppermint, which activates botholfactory and
trigeminal systems, did not find a gender effect for P2 amplitude
but did report that women had larger amplitude of N1 over the
left than right hemisphere, whereas men had larger P1 amplitude
over the right than left hemisphere. Although these studies sug-
gest possible gender effects in OERPs, the extent to which they
differ in schizophrenia patients and healthy adults needs further
There are several limitations of this study that should be
noted. First, participants responded to the odors by raising their
components (N1 or P2), it may have interfered with the mea-
surement of later components (cf. Kayser et al., 2007). Second,
subjects were not cued as to the time of odor presentation, and
there was also no control of their breathing technique (i.e., nat-
ural breathing through mouth and nose). Although this could
well have increased the variability of OERP measurements,
leading to overall reduced OERP amplitudes compared to con-
trolled breathing procedures (cf. Pause et al., 1999; Thesen &
Murphy, 2001), there is no reason to believe that it would have
differentially affected the schizophrenia patients and healthy
adults. Third, OERPs were measured only to the unpleasant
smelling odor of H2S. One of the distinguishing features of ol-
factory stimuli is their strong affective associations and the brain
regions mediating olfaction overlap with those mediating emo-
tional processing. The extent to which deficits in OERPs in
schizophrenia are related to the emotional valence ofthe odorsis
an important issue for future research (cf. Pause et al., 2008).
Fourth, although the lack of antipsychotic medication control is
Olfactory ERP generator patterns in schizophrenia1083
also a limitation, there is little evidence that medication status is
related to performance on psychophysical measures of olfactory
function (Moberg et al., 1999); however, the reported relation
of neuroleptic treatment to asymmetrical olfactory thresholds
(Purdon & Flor-Henry, 2000) may imply a more complex mod-
but there were marked individual differences in the OERPs
among patients, which raises the possibility that only a sub-
group of schizophrenia patients have OERP deficits. Further
study should be given to examining clinical, neurophysio-
logical, and neuroanatomical correlates of olfactory deficits in
Apart from replicating the original findings of Turetsky et al.
(2003) with a considerably larger sample, the current study ad-
vances olfactory ERP research by providing a complete, compar-
densities underlying reference-dependent surface potentials. The
PCA-based summary of orthogonal variance contributions iden-
tified a distinct, bilateral temporal N1 sink that appears to be
unique to olfactory stimuli. This PCA-CSD component has a
subtle ERP counterpart with similar topography that has not yet
been reported in the literature, presumably because the common
choice of a linked–mastoids reference attenuates the visibility of
this topographic effect. In contrast, the topography of P2 source,
the second prominent PCA-CSD component, was found to be
highly similar to P3 source topographies observed for other stim-
ulus modalities. The topographic CSD findings and insights for
olfactory N1 and P2 are unique and may help stimulate method-
ological and theoretical advancements in the field.
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The following supplementary material is available for this article
(all figures provided in PDF format):
Figure A1. Grand mean olfactory ERP (in mV) waveforms ref-
erenced to linked mastoids for 35 healthy adults and 32 schizo-
phrenia patients at all 31 recording sites (averaged across
intensity). Horizontal and vertical electrooculograms (EOG),
which are shown at a smaller scale before blink correction, in-
are labeled at sites T7 (N1) and Pz (P2).
Figure A2. Reference-free CSD (mV/cm2) waveforms for 35
healthy adults and 32 schizophrenia patients at all 31 recording
sites (averaged across intensity). Two prominent CSD compo-
nents are labeled at sites T7 (N1 sink) and Pz (P2 source).
Table A1. Means (? SD) of N1 sink (factor 305)
Table A2. Means (? SD) of P2 source (factor 630)
This material is available as part of the online article from:
2010.01013.x. (This link will take you to the article abstract).
Please note: Blackwell Publishing is not responsible for the
by the authors. Any queries (other thanmissingmaterial) should
be directed to the corresponding author for the article.
(Received August 25, 2009; Accepted November 13, 2009)
1086J. Kayser et al.
Olfactory ERP generator patterns in schizophrenia13
Table A1. Means (±SD) of N1 sink (factor 305)
Sink activity at lateral centrotemporal sites
(T7/8, C3/4, FC5/6, CP5/6)
Odor IntensityHigh Low
Hemisphere LeftRightLeft Right
(n = 35)
(n = 18)
(n = 17)
(n = 32)
(n = 18)
(n = 14)
Accompanying source activity at frontopolar sites
Odor Intensity HighLow
HemisphereLeft Right Left Right
(n = 35)
(n = 18)
(n = 17)
(n = 32)
(n = 18)
(n = 14)
14 J. Kayser et al.
Table A2. Means (±SD) of P2 source (factor 630)
Source activity at medial-lateral centroparietal sites
(P3/4, P7/8, CP5/6, C3/4)
Odor Intensity HighLow
Hemisphere LeftRightLeft Right
(n = 35)
(n = 18)
(n = 17)
(n = 32)
(n = 18)
(n = 14)
Accompanying sink activity at lateral frontotemporal sites
Odor Intensity HighLow
HemisphereLeft Right Left Right
(n = 35)
(n = 18)
(n = 17)
(n = 32)
(n = 18)
(n = 14)
Olfactory ERP generator patterns in schizophrenia 15
Figure A1. Grand mean
olfactory ERP [μV]
waveforms referenced to
linked mastoids for 35
healthy adults and 32
schizophrenia patients at all
31 recording sites (averaged
across intensity). Horizontal
and vertical electrooculo-
grams (EOG), which are
shown at a smaller scale
before blink correction,
indicate no eye artifact
concerns. Two prominent
ERP components are labeled
at sites T7 (N1) and Pz (P2).
Figure A2. Reference-free
CSD [μV/cm2] waveforms
for 35 healthy adults and 32
schizophrenia patients at all
31 recording sites (averaged
across intensity). Two
prominent CSD components
are labeled at sites T7 (N1
sink) and Pz (P2 source).