Context effects on odor processing: An event-related potential study

www.elsevier.com/locate/ynimg NeuroImage 41 (2008) 1426 – 1436

Context effects on odor processing: An event-related potential study Joachim H. Laudien,a Sonja Wencker,b Roman Ferstl,b and Bettina M. Pause a,⁎ a

Department of Experimental Psychology, Heinrich-Heine-University of Düsseldorf, FRG Department of Psychology, Christian-Albrechts-University, Kiel, FRG

b

Received 1 December 2007; revised 13 March 2008; accepted 26 March 2008 Available online 7 April 2008

The present study aimed to investigate the effects of cognitive/ emotional bias on central nervous odor processing. Forty-five female participants were divided into three groups and were either led to believe the odor was a natural, healthy extract (positive bias), potentially hazardous (negative bias), or a common test odorant (control). The odor (isobornyl acetate) was presented via a constant-flow olfactometer and the EEG was recorded from 60 scalp locations. In the negative bias condition, participants reported reduced well-being and judged the odor as less pleasant. However, neither the thresholds nor the intensity ratings were changed by the context condition. Chemosensory event-related potential (CSERP) analysis revealed that the latencies of the N1 and P2 components were prolonged in the negative bias condition and shortened in the positive bias condition. Current source densities were most prominent in the frontal lobe in negatively biased participants. The findings show that expecting to perceive an emotionally significant odor affects the early encoding of odors. © 2008 Elsevier Inc. All rights reserved. Keywords: Chemosensory event-related potential (CSERP); Emotion; Odor perception; Context

Introduction It has been known for several years that the subjective quality and detectability of an odor are influenced by the expectation about the odor's source and the context of odor presentation (Engen, 1972). Accordingly, it has been reported that the hedonic quality of an odor is individually learned (Soussignan et al., 1997). Thus, the emotional valence of an odor can vary with personal and cultural background, which can be explained by different degrees of familiarity with the odor (Hudson, 1999) or the specific learning conditions (Robin et al., 1999). More recently, psychophysical rating studies point to the fact that the perceived intensity of an odor can ⁎ Corresponding author. Department of Experimental Psychology, Heinrich-Heine-University, Universitaetsstr. 1, 40225 Düsseldorf, FRG. Fax: +49 211 81 12019. E-mail address: [email protected] (B.M. Pause). Available online on ScienceDirect (www.sciencedirect.com). 1053-8119/$ - see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2008.03.046

also be modulated by the subject's experience and the context of presentation (Dalton, 1996; Distel and Hudson, 2001; Smeets and Dalton, 2005). Participants who were instructed that a certain odor could potentially be harmful reported less habituation to the odor (Dalton, 2000), more experienced irritation (Dalton et al., 1997a) and even diffuse health symptoms, such as memory loss, weakness, dizziness, headache, and pain (Dalton, 1999; Williams and Lees-Haley, 1997). However, chronic exposure to an odor reduces the perceived intensity of and irritation to a potentially harmful odor (Dalton et al., 1997b). The aim of the present study was to investigate how the cognitive/emotional context of odor presentation modulates central nervous stimulus processing. Chemosensory event-related potentials (CSERPs) were used to investigate odor processing in a highly time-sensitive manner. The latencies of CSERPs are especially reliable estimates of odor processing (Thesen and Murphy, 2002; Welge-Lüssen et al., 2003), and CSERPs can be used in the clinical assessment of olfactory functions (Lötsch and Hummel, 2006). However, numerous state-dependent psychological factors also affect the CSERP, which need to be considered before conclusions about physiological performance can be drawn: CSERPs vary with the subjective stimulus significance (Lorig et al., 1993; Morgan et al., 1999; Pause et al., 1996), the allocation of attentional resources (Geisler and Murphy, 2000; Krauel et al., 1998), and intentional (Livermore and Hummel, 2004; Pause et al., 1999b) or unintentional (Pause and Krauel, 1998) perceptual training. Just recently it has been shown that the CSERP exhibits prolonged latencies and reduced amplitudes in participants experiencing helplessness (Laudien et al., 2006), which is similar to the CSERP effects observed in clinically relevant mood disorders (Pause et al., 2003). These results indicate that olfactory stimulus processing might be an indicator of the affective state of the perceiver. In the present study, participants were lead to believe that the odor was either a natural extract, an industrial solvent, or a standard research odor. In order to obtain information about neocortical sources, the EEG was recorded from 60 scalp locations, and current source density (CSD) mapping could thus be used as a tool for event-related source localization (Junghöfer et al., 1997). Acting like a spatial high-pass filter, CSD analysis maximizes near-field

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local cortical brain activity and minimizes far-field, global contributions (Law et al., 1993). Threshold tests were carried out before and after the odor presentations, and subjective data on odor evaluations and well-being were sampled. In accordance with Dalton (1996), the subjective ratings were expected to change with the context condition, whereas the thresholds were expected to be independent of the context. In accordance with studies showing that all components of the CSERP can be modulated by psychological top–down processes (Pause, 2002), odor processing was expected to be modified by the context during early (N1, P2) and late stages (P3s). As CSERPs generally appear more pronounced in females than in males (Olofsson and Nordin, 2004), only female participants were investigated. Methods Participants Forty-five right-handed females participated in the study. According to self-reports, none of the participants had ever had any surgery of or trauma to the head, nose or throat, or any problems with their ability to smell. All of them stated that they did not suffer from any acute or chronic somatic or mental disease. All participants gave written informed consent to participate in an EEG-study which examined the psychological and physiological correlates of olfactory stimulation. According to the bias condition (positive, neutral, negative), the participants were randomly assigned to three experimental groups (N = 15 each). There were no group differences in age [range 18–46 years, M = 23.13, SD = 6.25, F (2, 44) = 1.28, p p N 0.25] or smoking habits [15 smokers, chi2 (2) = 1.76, p N 0.25 (Freeman– Halton-Test)]. At the end of the experiment all participants were informed about the true nature of the study. The study was carried out in accordance with the ethical guidelines of the American Psychological Association. Odors and odor presentation Isobornyl acetate (IBA, 93%, Symrise, Germany) dissolved in diethyl phthalate (phthalic-acid-diethylester, 98%, Fluka, Germany) was used as olfactory stimulus. IBA was chosen because it has been shown to be perceptually malleable (Dalton, 1996). Depending on the instructional context, it is perceived as being either hazardous or healthy. For the EEG recordings, the odor (1:10 v/v, IBA: diethyl phthalate) was presented 60 times (ISI = 20 s) for 300 ms within a constantly flowing air stream (100 ml/s) by an olfactometer (OM6b, Burghart, Wedel, Germany; see Kobal, 2003). The temperature of the gas flow at the exit of the olfactometer was 37 °C, and the relative humidity was above 80%. White noise of 85 dB (A) was presented binaurally by earphones (Earlink Ear Tips, Aearo Company Auditory Systems, USA) and prevented the participants from hearing the switching valves. Both nostrils were stimulated simultaneously, and accordingly, both airstreams were controlled by separate mass flow controllers. Due to the ultradian rhythm of the bilaterally reciprocal alternations of the nasal air flow between the two nostrils (Stoksted, 1952), olfactory sensitivity (Frye and Doty, 1992) and quality perception (Sobel et al., 1999) varies between the nostrils. Therefore, unilateral odor perception is always confounded with the cycle of the lateralized nasal air flow and may (Daniels et al., 2001; Kobal et al., 1992) or may not (Olofsson et al., 2006) result in lateralized scalp distributions of

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the CSERP. Bilateral psychophysical testing, however, has been shown to reflect the performance of the more sensitive nostril (Betchen and Doty, 1998; Hornung et al., 1990; Klimek et al., 1998). Thus, birhinal stimulus administration is preferable, especially in studies with small sample sizes (Stuck et al., 2006). It has been proposed that natural perception of odor intensity and quality necessarily requires nasal inhalation (Mainland and Sobel, 2006), which seems to prime several areas of the olfactory cortex for an optimum odor processing (e.g., cerebellum: Johnson et al., 2003; dentate gyrus: Vanderwolf, 2001; olfactory bulb: Freeman and Schneider, 1982; Philpot et al., 1998; piriform cortex: Sobel et al., 1998). Therefore, in the present study, the odors were presented during inhalation. However, compared to another administration method, which applies the odors non-synchronously to breathing (Kobal, 2003), CSERPs recorded during natural breathing show reduced amplitudes of the early potentials and shorter component latencies (Pause et al., 1999a; Thesen and Murphy, 2001). The appearance of a white cross on a screen indicated that the participants should inhale. After a variable interval of 2–3 s, IBA was delivered to the participant's nose for 300 ms. The white cross disappeared 2–3 s thereafter. Participants were instructed to avoid eye movements, to close their mouth and to inhale regularly through their nose while the cross was presented (forced sniffing was not required and had to be avoided). Eye movement control and the inhalation technique were practiced across 15 trials until every participant could follow the instructions perfectly. During the EEG recordings, adherence to the instruction was controlled by on-line monitoring of the respiratory cycle. Due to the extensive training, all odor presentations were embedded into the inspiratory phase of the breathing cycle. Prior to fixing the EEG-cap and following the EEG recordings, thresholds for IBA were determined using a two-alternative staircase forced-choice detection procedure (Doty and Laing, 2003). Beginning with a dilution of 1:2 (v/v, IBA:diethyl phthalate), 16 serial dilutions of half-decimal log steps were prepared. Within the detection procedure each trial consisted of the presentation of two 100-ml glass bottles. One contained the odorous solution whereas the other contained the solvent alone. The participants had to decide which of the bottles had the stronger odor. The first trial started at the − 6.0 log concentration step. According to the method, increasing and decreasing concentrations were presented (intertrialinterval = 20 s), and depending on the subject's performance, staircase reversals were carried out. Trials were repeated until seven reversal points were detected, and the geometrical mean of the last four staircase reversal points was used as the threshold estimate. Subjective ratings At the beginning of the experiment, both prior to introduction of the bias conditions and again after the EEG recordings, all participants were asked to judge their subjective well-being using the Self Assessment Manikin scale (SAM, Bradley and Lang, 1994), a questionnaire about general complaints (Beschwerden-Liste, BL, Zerssen and Koeller, 1976), and questions about various sensory irritations. The SAM-scale is a language-free self-report instrument for assessment of the emotional state on three pictographic dimensions (valence: happy–sad, arousal: aroused–relaxed, and dominance: dominant–submissive). Even though the dominance factor accounts for less variance in emotional experiences than the other two factors (Bradley and Lang, 1994), in the present study it was used as an indicator for the degree of helplessness the participants might have felt in the negative bias condition.

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The complaints-questionnaire measures the degree of subjective impairment through (mainly) somatic and global symptoms, such as headache, labored breathing, exhaustion, freezing, and discomfort. Additionally, 15 questions on sensory irritation had to be answered (e.g. throat irritation, eye fatigue, or chest pressure). These questions were constructed in accordance with Gamberale et al. (1989) and Smeets and Dalton (2002). After being instructed according to the bias condition and before the EEG recordings started, the odor was presented to the participants via the olfactometer. The participants then had to judge the intensity, pleasantness, unpleasantness, and familiarity of the odor on visual analog scales (offline conversion to 0–500 scales). Additionally, after each of the 60 odor presentations during the EEG recording, the participants were asked to judge the intensity of the odors (visual analog scale). All participants were told that the concentration of the odorous stimuli could either vary throughout the session or stay the same. In fact, the concentration of every presentation was the same throughout the experiment. Bias conditions The participants were randomly assigned to one of three groups, each of which received different biasing information about the nature of and consequences of exposure to the odorant (see Dalton, 1996). The positive bias group (PB) was told they would be exposed to a natural extract from balsam trees, which has been reported to have positive effects on physiological and psychological well-being. In contrast, the negative bias group (NB) was told they would be exposed to an industrial solvent, which has been reported to deteriorate physiological and psychological health after long-term exposure. The control group (C) was told they would be exposed to a standard odorant generally used in and recommended for olfactory research. At the end of the experiment, immediately before the participants were debriefed, an open interview was carried out in order to obtain information about the trustworthiness of the bias induction. None of the participants reported having any doubts as to the nature of the study. EEG recordings and data analysis EEG activity was recorded unipolarly from 60 scalp locations (10%-system, Ag/AgCl sintered ring electrodes, 12 mm outer, 8 mm inner diameter, Falk Minow Services, Herrsching-Breitbrunn, Germany) in reference to the left ear lobe. Offline, the EEG was rereferenced to both linked ear lobes. Two additional electrodes were placed near the right eye (3 cm above, outside the vertical pupil-axis and 1.5 cm below, inside the vertical pupil-axis) in order to record horizontal and vertical eye movements. The ground was connected at FCz. Electrode impedances were always below 11 kOhm. Signals were collected with a bandpass of 0–40 Hz and digitized at a rate of 200 Hz per channel (Aquire Software, Application 4.2, Neurosoft Inc.). The data analysis was carried out using the Vision Analyser Software (Version 1.05; Brain Products GmbH, Germany). After rereferencing, baseline-correction (baseline: −1000 ms–0 ms) and highpass filtering (Butterworth Zero Phase Filters, low cutoff: 0.2 Hz), trials with eye movement artifacts were corrected according to Gratton et al. (1983). Subsequently, trials contaminated by any further artifacts (amplitudes between −50 and +50 μV) within the first 1400 ms after odor presentation were eliminated from the analysis and a zero phase shift digital low pass filter (Butterworth-Filter, 7 Hz) was applied.

EEG data were averaged separately for each electrode position. Afterwards, the 60 scalp electrode positions were merged into nine pools by averaging adjacent electrodes in anterior, central, and posterior areas for left and right hemispheres as well as for midline electrodes (3 [sagittal line: anterior (A), central (C), posterior (P)] * 3 [transversal line: left (L), midline (M), right (R)]: AL: Fp1, AF7, AF3, F7, F5, F3; AM: Fpz, F1, Fz, F2; AR: Fp2, AF4, AF8, F4, F6, F8; CL: FT7, FC5, FC3, T7, C5, C3, TP7, CP5, CP3; CM: FC1, FCz, FC2, C1, Cz, C2, CP1, CPz, CP2; CR: FC4, FC6, FT8, C4, C6, T8, CP4, CP6, TP8; PL: P7, P5, P3, PO7, PO3, O1; PM: P1, Pz, P2, POz, Oz; PR: P4, P6, P8, PO4, PO8, O2), which made another baselinecorrection necessary (baseline: − 1000 ms–0 ms). Finally, within these nine pools maximum negative and positive peaks were searched for in previously defined latency ranges: N1 (250–500 ms), P2 (300–550 ms), P3-1 (400–650) and P3-2 (600–900 ms). All local peaks of the CSERP were detected automatically, however, in case the peaks were not detected in the correct order (N1, P2, P3-1, P3-2), they were manually readjusted. Statistical calculations were made by analysis of variance (ANOVA, using SPSS). Accordingly, separate three way ANOVAs were calculated for the amplitude and latency of each peak, including the factors bias (PB, C, NB–between subject variable), sagittal line (anterior, central, posterior–within subject, repeated measures variable) and transversal line (left, midline, right–within subject, repeated measures variable). To correct for insufficient variance homogeneity in repeated measures ANOVAs, significance tests included the adjustment of the degrees of freedom according to Huynh and Feldt (1976). Subsequently, nested effects were calculated according to Levine (Page et al., 2003). In case of significant nested effects, single comparisons were analyzed by means of t-tests. Questionnaire-data as well as subjective ratings were analyzed accordingly. As an ISI of 20 s was used, habituation effects on the CSERP were to be expected (Morgan et al., 1997; Pause et al., 1996), and could possibly interact with the bias condition. Therefore, additional post-hoc analyses were calculated including the factors bias, sagittal line, transversal line and in addition the factor time (first 30 trials, last 30 trials—within subject, repeated measures variable). Current Source Density (CSD) maps were calculated in accordance with a spherical spline model (Perrin et al., 1989; order of splines: m = 4, maximal degree of Legendre polynominals: 20). Results Subjective well-being Before odor labeling and subsequent stimulation, the participants of the three groups felt equally happy, aroused and dominant (SAM ratings, see Fig. 1). However, after introducing the different contextual meaning of the odorous stimulus and after odor exposure, the participants in the PB-group felt significantly happier than the participants in the C- and NB-groups [Time × Bias: F (2, 42) = 9.11, p = 0.001; nested effects: bias within first measurement: F (2, 42) = 1.80, p = 0.18, bias within second measurement: F (2, 42) = 6.60, p b 0.01; single comparisons within second measurement: PB and NB: t (28) = 3.69, p b 0.001, PB and C: t (28) = 2.51, p b 0.01, NB and C: n.s.]. Additionally, participants who considered the odor to be potentially healthy or harmful were more aroused after exposure than participants who expected that they were perceiving a standard odor [Time × Bias: F (2, 42) = 8.92, p = 0.001; nested effects: bias within first measurement: F (2, 42) = 3.12, p = 0.054, bias within

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Fig. 2. Ratings of general complaints (BL-questionnaire; means, SD) before bias introduction and after odor exposure (higher values indicate more and stronger complaints). ⁎p b 0.05, ⁎⁎p b 0.01.

within first measurement: F (2, 42) = 0.21, p N 0.25, bias within second measurement: F (2, 42) = 5.15, p b 0.01; single comparisons within second measurement: NB and PB: t (28) = 3.03, p b 0.01, NB and C: t (28) = 2.24, p b 0.05, PB and C: n.s.; see Fig. 2]. Odor evaluations After bias introduction, the participants in the NB-group judged the odor to be less pleasant [Bias: F (2, 44) = 4.36, p b 0.05; single comparisons: NB and PB: t (28) = 3.15, p b 0.01, NB and C: n.s., PB and C: n.s.] and more unpleasant [Bias: F (2, 44) = 4.47, p b 0.05; single comparisons: NB and PB: t (28) = 3.14, p b 0.01, NB and C: t (28) = 1.79, p b 0.05, PB and C: n.s.] than the participants in the PBgroup. However, the degree of odor familiarity [Bias: F (2, 42) = 1.21, p N 0.25] and odor intensity [Bias: F (2, 42) = 0.17, p N 0.25] was perceived similarly between all bias groups. Accordingly, during EEG recording, the averaged intensity ratings were not significantly different between groups [Bias: F (2, 44) = 0.62, p N 0.25]. Fig. 1. Ratings of subjective well-being (SAM-scales) before bias introduction and after odor exposure (means, SD) on the dimensions “valence” (1 = sad, 9 = happy), “dominance” (1 = submissive, 9 = dominant) and “arousal” (1 = aroused, 9 = relaxed). ⁎⁎p b 0.01, ⁎⁎⁎p b 0.001.

Table 1 CSERP: analysis of variance of amplitudes (Amp) and latencies (Lat) Significant main effects, interactions, and single comparison

second measurement: F (2, 42) = 4.97, p b 0.05; single comparisons within second measurement: PB and C: t (28) = 2.84, p b 0.01, NB and C: t (28) = 2.85, p = 0.01, PB and NB: n.s.]. Feelings of dominance were not changed through the bias introduction [Time × Bias: F (2, 42) = 1.10, p N 0.25]. After odor exposure, the participants in the NB-group reported increased sensory irritation [averaged across all 15 items, Time × Bias: F (2, 35) = 5.00, p b 0.05; nested effects: bias within first measurement: F (2, 35) = 1.56, p N 0.20, bias within second measurement: F (2, 35) = 3.36, p b 0.05; single comparisons within second measurement: NB and C: t (23) = 2.16, p b 0.05, NB and PB: t (23) = 1.82, p b 0.05, PB and C: n.s.]. The group differences were mainly due to an increase in eight (out of 15) symptoms in the NB-group (throat irritation, unclear vision, tired eyes, irritated eyes, drowsiness, sleepiness, dazedness, bad taste, p b 0.05 each). Moreover, during the course of the experiment, general mental and somatic complaints increased in the NB-group [BL-questionnaire: Time × Bias: F (2, 42) = 6.94, p b 0.01; nested effects: bias

Detected peaks Sagittal N1 (Amp) N1 (Lat) P2 (Amp) P2 (Lat) P3-1 (Amp) P3-1 (Lat) P3-2 (Amp) P3-2 (Lat)

⁎⁎⁎ AbCbP ⁎⁎⁎ AbCbP ⁎⁎⁎ ANCNP ⁎⁎ A b (C = P) ⁎⁎⁎ AbCbP – ⁎⁎⁎ AbCbP ⁎⁎⁎ A b (C = P)

Transversal Sagittal by transversal Bias –

–

–

⁎ M b (L = R) in C –

⁎ PB b NB –

⁎ M N (R = L) – – ⁎⁎⁎ M N (R = L) – ⁎⁎⁎ M N (R = L) –

⁎⁎⁎ M N (R = L) – ⁎⁎⁎ M N (R = L) –

⁎ PB b NB – – – + PB b NB

Notes: Sagittal line: A = anterior, C = central, P = posterior. Transversal line: L = left, M = midline, R = right. Bias: PB = positive bias, NB = negative bias; + p b 0.10; ⁎p b 0.05; ⁎⁎⁎p b 0.001.

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Odor thresholds Odor thresholds were not significantly different between groups, neither before nor after EEG recording [Time × Bias: F (2, 42) = 1.12, p N 0.25]. Moreover, thresholds did not change from the first to the second measurement [Time: F (1, 42) = 0.67, p N 0.25]. CSERP amplitudes Potential features The scalp distribution of the CSERP showed a parietal dominance of the N1 [Sagittal: F (2, 84) = 20.34, p b 0.001] and a frontal dominance above midline electrodes of the P2 component [Sagittal: F (2, 84) = 52.85, p b 0.001; Transversal: F (2, 84) = 4.80, p b 0.05]. The P3-1 and P3-2 amplitudes showed a maximum over parietal positions with a midline dominance [P3-1: Sagittal: F (2, 84) = 86.91, p b 0.001; Transversal: F (2, 84) = 25.07, p b 0.001; Sagittal by transversal: F (4, 168) = 12.27, p b 0.001; P3-2: Sagittal: F (2, 84) = 82.08, p b 0.001; Transversal: F (2, 84) = 35.24, p b 0.001; Sagittal by transversal: F (4, 168) = 14.02, p b 0.001] (Table 1, Fig. 3). Effects of context The ANOVAs showed no overall effects (neither any main effects nor any interactions) of the bias conditions on the CSERP amplitudes.

Effects of habituation Whereas the amplitudes of the early CSERP components (N1 and P2) did not change during the course of the experiment, the amplitudes of the late positivities were reduced from the first half to the second half of the session. The amplitude reduction was most prominent for the P3-1 component [main effect Time: F (1, 42) = 7.93, p b 0.01] at central and parietal scalp areas [Time × Sagittal: F (2, 84) = 4.88, p b 0.05]. In comparison, the amplitude of the P3-2 was less prone to habituation effects, which occurred only above parietal scalp areas [Time × Sagittal: F (2, 84) = 6.05, p b 0.05]. However, all habituation effects observed were independent of the bias condition. CSERP latencies Potential features The latency of the N1 peak was shortest above anterior and longest above posterior electrode positions [Sagittal: F (2, 84) = 77.90, p b 0.001]. Furthermore, the N1 showed shortest latencies above midline electrodes within central positions [Sagittal by transversal: F (4, 168) = 3.44, p b 0.05]. The P2 and P3-2 components both appeared with shortest latencies at anterior positions [Sagittal: P2: F (2, 84) = 7.35, p = 0.001; P3-2: F (2, 84) = 12.72, p b 0.001] (Table 1, Fig. 3). Effects of context Descriptively, all components consistently showed the same pattern: the shortest latencies were detected in the PB-group, the

Fig. 3. CSERPs (grand averages across 15 participants in each condition) separated for each of the nine electrode pools (first line: anterior, second line: central, third line: posterior; first column: left, second column: midline, third column: right).

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Fig. 4. Latency effects (means, SDs) between the three bias groups (PB = positive bias, NB = negative bias, C = control) for the N1, P2, P3-1 and P3-2 components of the CSERP. ⁎p b 0.05, + p b 0.10.

longest in the NB-group, and intermediate latencies in the control group (Fig. 4). This effect was significant for the N1 [Bias: F (2, 42) = 3.21, p b 0.05, single comparisons: NB and PB: t (28) = 2.36, p b 0.05, NB and C: n.s., PB and C: n.s.] as well as for the P2 component [Bias: F (2, 42) = 3.34, p b 0.05, single comparisons: NB and PB: t (28) = 2.31, p b 0.05, NB and C: n.s., PB and C: n.s.]. For the P3-2 amplitude this effect only approached the significance level [Bias: F (2, 42) = 3.00, p = 0.06] and was not further analyzed (Table 1). Effects of habituation The latencies did not significantly change from the first to the second half of the session. Current source densities In the PB-group, current density was increased in the left temporal area, with strongest and broadest activations in the latency range of the P3-1. The participants in the control group showed two separated neuronal sources at frontal regions in the time frame of the early CSERP components. Additionally, for the late positivities an occipital source could be observed in the control group. In the NB-group, the intensity of the electrical activation was more pronounced than in the two other groups. In NBparticipants, two distinct sources, one with a fronto-central, the other with an occipital dominance, were observed over the entire time frame of the CSERP (Fig. 5). Discussion In the present study, the subjective expectation that a potentially harmful odor was perceived resulted in a changed perception of the odor and affected mental and bodily well-being: the odor was perceived as being unpleasant, the participants felt less happy, their physiological complaints increased, and sensory irritations were reported. Opposite effects were observed in participants who expected to perceive a potentially healthy odor: they described the

odor as more pleasant, themselves as more happy, and did not experience significant bodily changes. Both groups, however, felt more aroused by the odor than participants who believed that they perceived a standard odor. The verbally reported changes were paralleled by changes in central nervous odor processing. Across all scalp areas the N1 and P2 components appeared later in participants expecting the odor to be harmful. During the time window of the entire CSERP these participants showed broad neuronal sources in the frontal and occipital lobe which were not lateralized. This effect contrasts the observation of only weak left temporal sources in participants who were told that they were perceiving a healthy odor. The findings of a changed subjective odor perception and a changed subjective well-being through semantic odor labeling are in accordance with other studies investigating the cognitive context of odor perception (Engen, 1972; Dalton, 1996; Distel and Hudson, 2001; Herz, 2003; Smeets and Dalton, 2005). In fact, similar effects of labeling on the perception of the chemical environment and on mood can even be observed if no odor is present, but participants are instructed accordingly (Knasko et al., 1990). However, in the present study, odor intensity perception was not influenced by the cognitive/ emotional bias. This finding is in contrast with reports of a reduced subjective habituation in study participants perceiving odors as harmful (Dalton, 1996, 1999, 2000). These effects are found when participants are constantly stimulated, and when habituation occurs in the control group. In the present study, the odors were presented briefly with relatively long ISIs in between the presentations. Therefore, no habituation was observed in the participants (psychophysically as measured by the threshold tests, verbally as measured by the intensity ratings, and physiologically as indexed by the amplitudes of the early CSERP components), and accordingly the intensity judgments did not differ between groups. In addition, the subjective belief of perception of a potentially harmful odor resulted in the experience of diffuse health symptoms such as throat irritation, unclear vision, and drowsiness. Again, these results are strongly supported by other studies (Dalton, 1999; Williams and Lees-Haley, 1997). When participants are made to

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Fig. 5. Current source density maps plotted for the time frames of the components' maximum amplitude. Blue colors represent a weaker signal (neuronal sinks), red colors represent a stronger signal (neuronal sources).

believe that odors can be potentially harmful, they will spontaneously report diffuse symptoms, whether or not they are asked to describe their well-being (Dalton, 1996). The scalp topography of the CSERP reflects different processing stages: the N1 showed a parietal maximum, which indicates that the odor was predominately processed olfactorily and not through the trigeminal system (Hummel and Kobal, 1992). The early positivity (P2) could be separated from the late positivities by its frontal dominance (Pause et al., 1996). According to Pause (2002) and Pause and Krauel (2000), both early components are sensitive to odor concentration and quality but also to attentional resources allocated during stimulus encoding. In contrast to the early positivity, the late positivities are most prominent above central (P3-1) and parietal (P3-2) scalp areas (Pause et al., 1996). Even though in the present experiment both components showed a parietal dominance, the P3-1 habituated much more strongly than the P3-2 during the course of the experiment. This finding is in line with earlier observations (Pause et al., 1996) and might reflect the relatedness of the P3-2 with the P300 component and of the P3-1 with the Novelty-P3 (see Pause, 2002). Therefore, the novelty of the stimulus information might have been reduced during the course of the session (P3-1 amplitude), and subjective stimulus

significance is suspected to be mirrored by the electrophysiological features of the late P3-2 (Pause, 2002, Pause and Krauel, 2000). The early peaks of the CSERP, the N1 and the P2, occurred earliest when the participants expected that they were perceiving healthy odors and latest when they expected harmful stimuli. These latency differences similarly occurred in the late positivities, however, not significantly. As the same olfactory stimulus was presented to all groups, psychological processing mechanisms are necessarily responsible for these latency effects. At first glance this result strikingly parallels the observation of prolonged CSERP latencies in study participants who transiently experienced helplessness. These CSERP effects are considered to be related to a generally reduced olfactory sensitivity in participants experiencing a negative emotional state (healthy participants: Pollatos et al., 2007; depressive patients: Pause et al., 2001). However, a generally reduced mood can only partly account for the present results, because olfactory thresholds were not affected through the bias condition and the CSERP amplitudes were not reduced, as in helpless participants. In fact, the grand averages even suggest increased amplitudes in participants in the NB condition. Another explanation for the latency prolongation seems to be more appropriate for the present study and is related to a reduction

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of attentional resources allocated to stimulus processing. It has been demonstrated before that subtraction of attention results in prolonged latencies of the early CSERP components (Geisler and Murphy, 2000; Krauel et al., 1998). Thus, it could be speculated as to whether expecting to perceive potentially harmful odors results in a reduction of selective attention to the stimulus. This hypothesis will be discussed in more detail with regard to the CSD results. So far, effects of the emotional stimulus valence on the CSERP have been reported for the positive components only (Lundström et al., 2006; Pause and Krauel, 2000). However, in these studies the odors were emotionally valenced but were not perceived as threat-related or potentially harmful. For the visual modality, effects of the emotional stimulus content on early ERP components have been well documented, but seem to be related to the degree of arousal which is induced by the emotional slides (Schupp et al., 2006). However, early ERP components recorded during the presentation of facial expressions have been described as varying with the emotional valence (Pizzagalli et al., 1999). Similarly, in response to fearful facial expressions participants show an enhanced N2 amplitude (Liddell et al., 2004). However, if the stimulus threat content is increased and potentially harmful (shock-predicting cues), participants respond after only 60 ms with increased amplitudes of early sensory negativities (Baas et al., 2002). Thus, valence related effects on early sensory components seem to vary with the type of emotional stimulus (emotional scenes vs. facial expressions) as well as with the degree of threat. Recently is has been reported that expecting to perceive a painful stimulus in between two odor presentations results in shorter latencies of the early components of the CSERP (Bulsing et al., 2007). One of the main differences between the aforementioned study and the current one is that in the present study, the CSERPs were analyzed in response to the potentially harmful stimulus, whereas Bulsing and coworkers analyzed CSERPs in response to another (non-painful) stimulus. Accordingly, the opposite CSERP effects could be due to an inhibitory effect in response to the potentially harmful stimulus itself, and to a processing advantage of stimuli which represent a non-harmful (safe) experience within a train of painful stimuli. However, both the present study and the study from Bulsing et al. (2007) found that the CSERP latencies were affected more strongly than the amplitudes. These observations are in line with several other CSERP studies showing that external as well as internal effects are often most pronounced (Pause and Krauel, 2000) and most reliable (Thesen and Murphy, 2002; WelgeLüssen et al., 2003) for the peak latencies. For example in the visual or auditory modality, effects of stimulus intensity or stimulus significance predominantly affect the amplitudes of the ERP, whereas in the olfactory modality latency differences are observed. This phenomenon might be related to the fact that odor representations in the olfactory system are coded by spatiotemporal patterns (Schaefer and Margrie, 2007; Spors and Grinvald, 2002). It could be speculated as to whether the latency effects of the present study are confounded with the breathing technique. For example, one could question whether the inhalation strength varied between bias conditions and differently affected temporal odor processing. However, according to empirical studies comparing CSERPs from different breathing conditions this possibility is highly unlikely: Thesen and Murphy (2001) found the latencies of

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the early components of the CSERP (N1, P2) to be independent of the breathing technique, specifically whether the odors were applied during inhalation (natural breathing through mouth and nose) or non-synchronously to breathing (velopharyngeal closure technique, see Kobal, 2003). A small and non-significant trend of the P3 occurring earlier during the inhalation condition was discussed as being related to a higher stimulus expectancy during inhalation. Pause et al. (1999a) presented the odors during natural inhalation and exhalation through the mouth (which is always associated with a corresponding air flow through the nasal cavity) and non-synchronously to breathing (velopharyngeal closure technique). Independent of the breathing cycle, the N1 was found to occur earlier during the natural breathing condition. This effect was considered to be caused by a higher amount of attentional resources available in the natural breathing condition. In addition, this study found no systematic effect of the phase of the breathing cycle on component latencies (N1, P2, P3-1, P3-2). In summary, as nasal inhalation has no effects on the N1 and P2 latencies (Thesen and Murphy, 2001), and as even (weak) nasal air in- and out-flow does not affect the CSERP latencies (Pause et al., 1999a), it is concluded that attentional mechanisms are much more likely to affect the latencies than the nasal air flow. The changes in component latencies were accompanied by extensive neuronal activity in the frontal lobe (Fig. 5) during the entire time frame of the CSERP, more so in those participants who were made to believe that the odor was potentially harmful. The prefrontal cortex is considered to be part of the secondary olfactory cortex (orbitofrontal areas: Zatorre et al., 1992) and seems to be especially involved in odor valence coding (Anderson et al., 2003; Rolls et al., 2003). In general, and independent of the stimulus modality, neuronal networks within the prefrontal cortex seem to be responsible for the assignment of a specific emotional value to external stimuli in a highly flexible manner and related to the performance of goal-directed behavior (Schoenbaum and Setlow, 2001). Accordingly, it has recently been shown that the expectation of threat (pain stimuli) involves activity within the ventromedial prefrontal cortex (Mobbs et al., 2007). An associated activation of the anterior cingulate cortex is supposedly related to response conflict monitoring (e.g. the conflict between fleeing or staying). Notably, a similar pattern of brain activity has been observed during the (placebo mediated) expectation of anxiety relief (Petrovic et al., 2005: orbitofrontal cortex and anterior cingulate cortex). This finding highlights the valence-independent regulatory function of these brain structures. Finally, the anterior cingulate and other structures of the prefrontal cortex are involved in the inhibition of amygdala activity during self-regulated suppression of negative emotions (Ochsner et al., 2004). It is here hypothesized that the latency prolongation within the CSERP and the frontal activation as indicated in the CSD maps are related effects: the processing of highly emotional, threat-relevant stimuli may have recruited neuronal resources within the frontal lobe, in order to adjust mental activity to the specific situational requirements (however, due to the low spatial resolution of the CSD method and its low ability to detect scalp-distant activity, it remains speculative whether or not the cingulate cortex was also involved in this task). It is further concluded that through these higher-order regulatory mechanisms within the prefrontal cortex brain structures which are responsible for the processing of emotionally negative odors and/or negative emotions were inhibited. Due to the personal relevance of the odorous stimuli in the NB condition, attention might have been directed to the internal state of

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the body (see physical complaints and sensory irritations) and subtracted from the odors. Thereby, the structures which are responsible for attentional odor processing might have been inhibited. Because olfactory evoked potentials recorded from the amygdala appear more quickly when the odors are attended to (Hudry et al., 2001), the amygdala seems to be involved in attentional odor processing. As the amygdala is also part of the primary olfactory cortex (direct projections from the olfactory bulb to the rostromedial part and the N. corticalis of the amygdala; Carmichael et al., 1994), the inhibitory control might have resulted in prolonged latencies of the early potentials. Moreover, the piriform cortex is another structure supposedly associated with attentional odor perception (Zelano et al., 2005). Since the prefrontal and piriform cortices are also directly connected with each other (Carmichael et al., 1994) a similar inhibitory mechanism is suggested. However, as in the present study only olfactory stimuli were presented, a more general modality-independent and emotion-specific process could have also been responsible for the present results. Recently, it could be demonstrated that the experience of continual threat-related stress is associated with a deactivation of limbic structures, including the amygdala (Pruessner et al., 2008). This process could have been voluntarily initiated in order to reduce anxiety and to gain relief (Ochsner et al., 2004), or it may have been automatically guided in order to retain homeostasis (as discussed in Mobbs et al., 2007). The results of the present study seem to be specific to the perception of strongly valenced stimuli signaling threat or harm. A recent brain imaging study (De Araujo et al., 2005) showed that odor labeling (as neutral/cheese or as negative/body odor) affected the activity of the anterior cingulate cortex and the medial orbitofrontal cortex, which were less activated when the participants were lead to believe that they were perceiving body odor. However, in this study the labeling resulted only in weak emotional odor evaluations. Moreover, labels represented different odor categories, with different natural value. Thus, the stronger brain activation might have been related to the fact that food odor may convey information about a natural reward. In contrast, the reward value of body odor is less distinct. Still, both studies demonstrate top–down processes in central nervous odor processing, and are in line with numerous studies on the visual system showing that the internal representation of the world, acquired by experience, affects the brain's strategy of percept formation (Gilbert and Sigman, 2007). Further studies are needed to investigate how the cognitive/ emotional context affects the processing of auditory or visual stimuli. As only olfactory stimuli were used in the present study, it cannot be determined whether the observations are due to a general effect of stimulus emotionality or whether related hedonic effects are specific to chemosensory stimulation. In any case, the present findings support the view that, beginning with the earliest stages of central nervous stimulus processing, chemosensory perception can be understood as an internal construction dependent on both bottom–up (quality and quantity of ambient molecules) and top–down processes, such as context factors.

Acknowledgments The authors would like to thank Dipl.-Phys. Bernfried Sojka for his valuable technical assistance, Conny Staffend for her help during the data acquisition, and Rachael Cole and Katrin Lübke for language editing.

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