We showed how cognitive, semantic information modulates olfactory representations in the brain by providing a visual word descriptor, “cheddar cheese” or “body odor,” during the delivery of a test odor (isovaleric acid with cheddar cheese flavor) and also during the delivery of clean air. Clean air labeled “air” was used as a control. Subjects rated the affective value of the test odor as significantly more unpleasant when labeled “body odor” than when labeled “cheddar cheese.” In an event-related fMRI design, we showed that the rostral anterior cingulate cortex (ACC)/medial orbitofrontal cortex (OFC) was significantly more activated by the test stimulus and by clean air when labeled “cheddar cheese” than when labeled “body odor,” and the activations were correlated with the pleasantness ratings. This cognitive modulation was also found for the test odor (but not for the clean air) in the amygdala bilaterally.

The aim of the event-related fMRI study described here was to measure the effects of cognitive (semantic) information on the neural responses to the (orthonasal) delivery of odors. The design consisted of presenting odors paired with descriptors (words) on a screen. A test odor (isovaleric acid combined with cheddar cheese flavor) was labeled on different trials as “cheddar cheese” or “body odor.” Thus, a particular test odor was associated with labels describing stimuli with different reward values. The same labels were paired with delivery of clean air in different trials. Alpha-ionone (pleasant, labeled “flowers”) and Octanol (unpleasant, labeled “burned plastic”) were used as reference pleasant and unpleasant stimuli for the psychophysics and neuroimaging. This design allowed us to assess how the semantic labels modulate responses to the delivery of test odor (and clean air) by performing correlation analysis with the subjective pleasantness ratings and by performing direct comparisons between different experimental conditions.

So far, little is known about how cognitive processing might modulate the neural representation of the affective value of odors. In a recent study,showed that activity in the human anterior hippocampus and medial orbitofrontal cortex is correlated with perceptual olfactory facilitation produced by presenting subjects with odors paired with semantically congruent pictures. In an earlier study using positron emission tomography (PET),showed that familiarity judgments were associated with activations in the right orbitofrontal and anterior cingulate cortices.reported that orbitofrontal cortex activation was related to hedonic judgements of a set of odors. However, none of these studies investigated the influences of cognitive information on the representations of pleasant and unpleasant odors in the human brain.

A central feature of odor perception is its hedonic or affective component. Most odors are labeled as “pleasant” (positive hedonic value) or “unpleasant” (negative hedonic value), and recent functional neuroimaging studies performed on humans have successfully demonstrated that the valence of odors is represented in particular in the orbitofrontal cortex. More specifically, pleasant odors preferentially activate medial orbitofrontal regions, whereas unpleasant odors activate more lateral regions (). In addition, the representation of the intensity of odors has been associated with activity in the piriform (primary olfactory) cortex () and in the amygdala (). Anatomical investigations in nonhuman primates have shown that connections from the olfactory bulb reach the piriform cortex, cortico-medial nucleus of the amygdala, and olfactory tubercle. From the piriform cortex, projections reach area 13a, a part of the caudal orbitofrontal cortex, and from there project on to area 13 of the caudal orbitofrontal cortex and then on to further orbitofrontal areas ().

To check whether differential sniffing induced by the word labels might have contributed to the results (), we performed a control study in 11 participants in which the sniffing was measured outside the scanner. Inhalation and exhalation were measured by both inductance plethysmography and by temperature changes (measured with a miniature thermistor) reflecting the air flow in the nostrils. The plethysmography (and temperature measurements) showed that in the 2 s period after the onset of the visual and olfactory stimuli, there was no influence on the inhalation of the stimulus by the visual word label. Further evidence that altered sniffing did not account for the effects described here is that if subjects had altered their sniffing differentially to the word labels, then this should have affected the intensity ratings given, and no such effect was found, as shown in the psychophysics section. In addition, as described above, the correlations of the BOLD signals with the pleasantness ratings were present when the intensity ratings were included as an effect of no interest, and the BOLD signals were not correlated with the intensity ratings. Thus, altered sniffing and intensity changes are very unlikely to account for the effects of the word labels on the pleasantness ratings or on the fMRI activations described in this paper.

Thus, overall, the results show that in human brain areas activated by olfactory stimuli, modulatory effects of the word labels are found. The cognitive modulation effects are clear in areas of the orbitofrontal cortex, amygdala, and anterior cingulate cortex and may include part but perhaps not all of the primary olfactory cortical areas such as the pyriform cortex.

An additional analysis was performed to identify olfactory areas. We compared the activations of two of the odors to their nonodor (clean air) controls as follows (in which CT refers to the test odor labeled as cheddar cheese). With the contrast [(CT + α-ionone] − (CT control + α-ionone control)], activations were found bilaterally in the amygdala (e.g., [20 4 −25], Z = 3.99, p < 0.001 FDR corrected), in a posterior part of the orbitofrontal cortex extending to the ventral part of the far anterior cingulate cortex (peak at [−2 18 −24], Z = 3.34 p < 0.001 FDR corrected), and in the piriform cortex region described above to respond to the main effects of odor. These activations extended anteriorly to reach the agranular part of the insular cortex (at Y = 14 at p < 0.001 uncorrected).

The time course of the activations in the pyriform cortex at Y = 8 is shown in Figure 6 E. The odor was on for the period 0–8 s. Comparison of Figure 6 with Figure 2 shows that the region where word labels modulate olfactory processing is within the region of primary olfactory cortex where main effects of odor are found. However, the center of the odor main effects cluster was further forward (at Y = 8 as shown in Figure 6 A) than the center of the region in which word labels modulated olfactory processing (at Y = 0 as shown in Figure 2 C), providing a suggestion that not all primary olfactory cortical areas were modulated by the effects of the word labels. We show in Figure 6 C a slice through Y = 0 for the main effects analysis, where Y = 0 was chosen because it is the center of the area with a correlation with the pleasantness ratings, as illustrated in Figure 2 C. It can be seen from Figure 6 C that the main effects (olfactory) contrast was located in an area that is probably the pyriform cortex, which is dorsal to the peak of the region in the amygdala shown in Figure 2 C where correlations with pleasantness were found. Figure 6 D shows that the main effects (olfactory) activation at the slice Y = 15 (in or near the agranular insula) is lateral to the region in Figure 2 D at Y = 15 (in or near to the olfactory tubercle) where the activations were correlated with the pleasantness ratings. Thus, Figure 6 shows that the main effects of odors are centered in areas such as the pyriform cortex ( Figures 6 A–6C) and agranular insula ( Figure 6 D), whereas the correlations with pleasantness shown in Figure 2 are centered in areas such as the ACC/medial orbitofrontal cortex, the amygdala, and a region in or close to the olfactory tubercle.

This main effects analysis shows (A and B) strong activations bilaterally in primary olfactory cortical areas in or close to the pyriform cortex (MNI coordinates [−22 8 −26], Z score = 4.69, p < 0.05 corrected for multiple comparisons). (C) shows a slice though Y = 0 for the main effects analysis with activation in the pyriform cortex ([−20 0 −12] Z = 3.23, p < 0.001 uncorrected), where Y = 0 was chosen because it is the center of the area with a correlation with the pleasantness ratings, as illustrated in Figure 2 C. (D) shows the main effects activation at the slice Y = 15 (in or near the agranular insula ([36 15 −26] Z = 3.06, p < 0.001 uncorrected), for comparison with the region in Figure 2 D at Y = 15 (in or near to the olfactory tubercle) where the activations were correlated with the pleasantness ratings. (E) shows that the peak of the main effects activations is at Y = 8 (means ± SEM are shown).

We have identified, in the above analyses, areas of the human brain where the cognitive labels modulated the activations. To investigate further whether these are olfactory areas, Figure 6 shows a main effects analysis showing the activations revealed by the contrast odor − control. This main effects analysis shows for example strong activations bilaterally in primary olfactory cortical areas in or close to the pyriform cortex, as illustrated in Figures 6 A and 6B (coordinates [−22 8 −26], Z score = 4.69, p < 0.05 corrected for multiple comparisons). (The odors included in this analysis were the test odor in both conditions, the α-ionone, and the octanol, each minus their respective control.) These activations extended in the anterior-posterior axis from Y = 15 (agranular insula) to Y = 2 (periamygdaloid cortex). There was also a small area of activation in the right lateral orbitofrontal cortex (illustrated in Figure 6 B). Overall, the fact that strong activation of the orbitofrontal cortex and amygdala was not apparent in this main effects analysis is likely to be due to the fact that pleasant and unpleasant odors activate parts of these regions in opposite directions (), so that the effects partly cancel in the main effects analysis.

Generally similar effects were found for the amygdala/olfactory cortex (see Figure 5 B), except that the labels had smaller effects on the activations to clean air (compare CA and BA). It was also noticeable that in the amygdala, in most of the experimental conditions, activations above the baseline were found, as shown in Figure 5

(A) Anterior cingulate cortex ACC and medial orbitofrontal cortex OFC. (B) Amygdala/pyriform cortex under the different experimental conditions. C, “cheddar cheese” label; B, “body odor” label; T, test odor; A, clean air. (Thus, CT = cheddar cheese label and test odor delivery, etc.) Although the main statistical comparisons are those provided in the SPMs, supplementary statistical tests on the data shown in these histograms show the following, based on an ANOVA followed by post hoc corrected t test comparisons. For the ACC/medial OFC, CT > BT at p < 0.005; CA > BA at p < 0.01; α-ionone > octanol at p < 0.002. For the amygdala/pyriform cortex, CT > BT at p < 0.03; α-ionone > octanol at p < 0.03.

We show the BOLD signal in these regions under the different experimental conditions in Figure 5 . Activations in the anterior cingulate cortex/medial orbitofrontal cortex (ACC/medial OFC) were greater to the test odor (T) when labeled as “cheddar cheese” (C) than when labeled as “body odor” (B). In the clean air (A) condition, somewhat similar changes of activations, though of smaller magnitude, were produced when the label was cheese (C) versus body odor (B). In the clean air condition, the signal in these ACC/medial OFC regions could thus reflect effects of the word label in influencing the pleasantness of what was perceived even when there was no change in the olfactory stimulus at the time that the word label was given, as the air flow was clean air continuously throughout the trial. This interpretation, that the label is affecting the perceived pleasantness in the clean air condition, is supported by fact that the activations in the ACC/medial OFC to the (pleasant, flowery) α-ionone (FL) were greater than to the (unpleasant) octanol (see top right of Figure 5 ). In fact, the SPM analysis showed that this comparison was significant at p < 0.001 uncorrected in the medial orbitofrontal cortex at [8 42 −16], Z = 3.54.

(A) Activations in the medial orbitofrontal cortex (shown in a saggital slice) produced by the contrast [test odor when labeled “cheddar cheese” − test odor labeled “body odor”]. (B) The same activations shown in an axial slice, illustrating bilateral activations. (C) The time course of activations in this region for these conditions, across trials and subjects (mean ± SEM).

The word labels used (“cheddar cheese” versus “body odor”) are prima facie more likely to influence representations of the pleasantness than of the intensity of the odor, and to check this we repeated the above analyses using the intensity ratings as regressors. No significant correlations (p < 0.001 uncorrected in the group analysis) were found between the BOLD signal in any brain area and the intensity ratings. As described in the psychophysics section, the intensity ratings were not influenced by the word labels, and the intensities of the different odorants used in this study were quite similar, so that the absence of a correlation of the BOLD signal with the intensity ratings is as might be expected. Thus, the word labels did influence the brain activations related to pleasantness ratings, and this result could not be attributed to effects arising from a correlation with intensity. Further confirmation of this is that the correlations of the BOLD signals with the pleasantness ratings were still the same when the analysis was repeated with the intensity ratings as an effect of no interest.

(A) Activations in the rostral anterior cingulate cortex, in the region adjoining the medial OFC, shown in a saggital slice. (B) The same activation shown coronally. No significant correlations were found with clean air (cf. Figure 2 ) in the amygdala (C) or primary olfactory cortex (D). The image was thresholded at p < 0.0001 uncorrected in order to show the extent of the activation. (E) Parametric plots of the data averaged across all subjects showing that the percentage BOLD change (fitted) correlates with the pleasantness ratings in the region shown in (A) and (B). PST, poststimulus time (s). (F) Parametric plots showing activation related to stimulus presentation but not related to the pleasantness ratings for the amygdala region shown in (C).

We also examined the extent to which these brain areas had activations that were correlated with the pleasantness ratings produced by the clean air when labeled as “cheddar cheese” or “body odor.” Figure 3 shows that the anterior cingulate and adjoining medial orbitofrontal cortex areas also had activations that were correlated with the pleasantness ratings given to clean air when it was labeled as “cheddar cheese” or “body odor” (MNI coordinates [10 38 −2], Z score = 3.95, p < 0.03 FDR corrected). The areas showing this correlation overlapped with the anterior cingulate areas showing a correlation with the rated pleasantness of the test odor. Significant correlations (even at the low threshold of p < 0.05 uncorrected) with the pleasantness ratings of the clean air were not found in the amygdala and adjoining olfactory areas.

(A) Activations in the rostral anterior cingulate cortex, in the region adjoining the medial OFC, shown in a saggital slice. (B) The same activation shown coronally. (C) Bilateral activations in the amygdala. (D) These activations extended anteriorly to the primary olfactory cortex. The image was thresholded at p < 0.0001 uncorrected in order to show the extent of the activation. (E) Parametric plots of the data averaged across all subjects showing that the percentage BOLD change (fitted) correlates with the pleasantness ratings in the region shown in (A) and (B). The parametric plots were very similar for the primary olfactory region shown in (D). PST, poststimulus time (s). (F) Parametric plots for the amygdala region shown in (C).

A correlation analysis was performed between the fMRI BOLD signal and the pleasantness ratings of the test odor when labeled as cheddar cheese and as body odor. Figures 2 A and 2B show that significant correlations were found in a far anterior part of the anterior cingulate cortex and the adjoining medial orbitofrontal cortex (MNI coordinates [16 46 −4], Z score = 4.35, p < 0.05 corrected for multiple comparisons). (Although the peak voxel was on the right [ Figure 2 B], activations were found in a corresponding region on the left at a lower statistical threshold of p < 0.001 uncorrected.) Significant positive correlations were also found in the amygdala bilaterally ( Figure 2 C) (MNI coordinates [22 −2 −20], Z score = 3.41, p < 0.05 FDR corrected; and [−18 0 −16], Z score = 3.15, p < 0.001 uncorrected), which extended anteriorly to olfactory regions in or close to the olfactory tubercle ( Figure 2 D) (MNI coordinates [26 10 −22], Z score = 3.50, p < 0.05 FDR corrected). Thus, the pleasantness of the test odor measured by the ratings being given during the scanning, and being influenced by the verbal labels as shown in Figure 1 , was correlated with the activations produced by the odors in the brain areas shown in Figure 2

The pleasantness ratings (obtained during the scanning on every trial) for the six stimulus conditions are shown in Figure 1 . The α-ionone (labeled as “flowers”) was rated as pleasant (mean ± SEM = 0.32 ± 0.06), and the octanol (labeled as “burned plastic”) was rated as being unpleasant (−0.49 ± 0.06). The test odor when labeled as “cheddar cheese” was rated as being close to neutral (−0.10 ± 0.08) and when labeled as “body odor” was rated as being unpleasant (−0.86 ± 0.07). Statistical analysis showed that the test odor was rated as being significantly more pleasant when labeled as “cheddar cheese” than when labeled as “body odor” (paired t = 6.68, df = 11, p << 0.001). Interestingly, the clean air when labeled as “cheddar cheese” was rated as being more pleasant (0.02 ± 0.06) than when it was labeled as “body odor” (−0.40 ± 0.06) (paired t = 4.1, df = 11, p < 0.001). In contrast, the labels produced no effect on the intensity ratings, which were α-ionone, −0.10 ± 0.10; octanol, 0.20 ± 0.09; test labeled as cheddar, 0.55 ± 0.08; test labeled as body odor, 0.64 ± 0.08; clean air labeled as cheddar cheese, −0.38 ± 0.10; clean air labeled as body odor, −0.31 ± 0.09.

The means ± SEM across subjects are shown. The corresponding stimulus and label to each bar are listed in the lower part of the figure. Note that the test odor and clean air were paired in different trials with a label of either “cheddar cheese” or “body odor.”

Discussion

Rolls et al., 2003 Rolls E.T.

Kringelbach M.L.

de Araujo I.E.T. Different representations of pleasant and unpleasant odors in the human brain. Rolls et al., 2003 Rolls E.T.

Kringelbach M.L.

de Araujo I.E.T. Different representations of pleasant and unpleasant odors in the human brain. We also found that the ratings of the pleasantness of clean air could be influenced by the word label ( Figure 1 ). An influence of the cognitive label on the magnitude of the BOLD signals was found in the anterior cingulate/medial orbitofrontal cortex region illustrated in Figure 4 Figure 5 , and a less significant cognitive effect was also found in the amygdala (see Results and Figure 5 ). Further, the activations in the anterior cingulate/medial orbitofrontal cortex region were correlated with the pleasantness/unpleasantness ratings given when the label was “cheddar cheese” versus “body odor.” Clearly, when there is no odor present, the subjects may imagine a smell based on the word cue shown. Alternatively, the activations in the clean air condition might reflect an effect of the cognitive input on these areas that is independent of any imagined odor. However, in either case, the important new point being made in this paper is that high-level cognitive inputs, such as the sight of a word, can influence the activations in brain regions that are activated by olfactory stimuli such as the anterior cingulate and orbitofrontal cortex and the amygdala. Moreover, the high-level cognitive influence can modulate affective ratings of pleasantness and the brain regions such as the anterior cingulate/medial orbitofrontal areas where the activations are correlated with the pleasantness of odors (). The finding that the anterior cingulate/medial orbitofrontal region had activation correlated with the pleasantness ratings being given even in the clean air condition may indicate that this region is relatively close to the affective ratings being given. Given that the brain areas in which the word labels modulated the activations to the odors are areas where pleasant olfactory stimuli have been shown to produce activation (), it is likely that the modulations produced by the word labels in the present investigation reflect an altered perception of the pleasantness of the odors and not just a bias on the ratings being given.

Figure 3 shows that the BOLD change in the amygdala in the clean air condition does not correlate highly with the pleasantness ratings, and this is consistent with the evidence in Figure 5 that the magnitude of the activations in the amygdala are not affected greatly by the label in the clean air condition. In comparison, as just noted, even in the clean air condition, activations in the anterior cingulate/medial orbitofrontal cortex do correlate with the pleasantness ratings. When the test odor was present, the activations in both the amygdala and the cingulate/orbitofrontal cortex were modulated by semantic labels. The implication is that the activations in the amygdala are relatively closely coupled to effects on odor inputs, whereas the activations in the anterior cingulate/medial orbitofrontal cortex can be modulated even in the absence of the olfactory test stimulus.

Rolls et al., 2003 Rolls E.T.

Kringelbach M.L.

de Araujo I.E.T. Different representations of pleasant and unpleasant odors in the human brain. Rolls et al., 2003 Rolls E.T.

Kringelbach M.L.

de Araujo I.E.T. Different representations of pleasant and unpleasant odors in the human brain. The region shown in Figure 6 to be activated by the main effects contrast odor versus no odor includes the olfactory tubercle and extends to the pyriform/primary olfactory areas close to the medial amygdala. This was not the center of the region where cognitive influences had their effects, which were further posterior, as shown for example in Figure 2 C. This may mean that the olfactory tubercle/pyriform cortex, which are primary olfactory areas, are less modulated by the word label or that they do not represent affect (), and so are not modulated by word labels that influence affect. Indeed, the reason that other olfactory areas were not activated in the main effects analysis shown in Figure 6 may well be because pleasant and unpleasant odors produce opposite effects in the medial orbitofrontal/anterior cingulate cortex areas (), so that the activations may cancel. However, the amygdala region shown in Figure 2 C as being modulated by cognitive inputs did extend continuously to the region shown in Figure 2 D, and, given the spatial resolution of the methods, some effect of cognitive inputs on representations in the pyriform/olfactory tubercle areas cannot be firmly rejected by the present investigation.

Cain, 1979 Cain W.S. To know with the nose: keys to odor identification. Herz, 2003 Herz R.S. The effect of verbal context on olfactory perception. Herz and von Clef (2001) Herz R.S.

von Clef J. The influence of verbal labeling on the perception of odors: evidence for olfactory illusions?. It has been well established by psychophysical methods that olfactory discrimination is rather inefficient in humans, in that successful odor identification depends heavily on attributes such as familiarity and a long-standing connection between an odor and its name (). In particular, verbal or semantic information can strongly influence the perception of odor attributes (). For example,presented subjects with a set of odors (including menthol and pine oil) paired with different labels in separate sessions and found a significant label × odor interaction for pleasantness ratings. One of the odors used was an ambiguous mixture of isovaleric acid and butyric acid, which was judged significantly more unpleasant when labeled “vomit” than when labeled “parmesan cheese.” In the psychophysical part of the present study, we extended that observation by showing that semantic labels influence hedonic judgements even when clean air is paired with hedonically distinct labels.

Rolls et al., 2003 Rolls E.T.

Kringelbach M.L.

de Araujo I.E.T. Different representations of pleasant and unpleasant odors in the human brain. Anderson et al., 2003 Anderson A.K.

Christoff K.

Stappen I.

Panitz D.

Ghahremani D.G.

Glover G.

Gabrieli J.D.

Sobel N. Dissociated neural representations of intensity and valence in human olfaction. Gottfried et al., 2002 Gottfried J.A.

O’Doherty J.

Dolan R.J. Appetitive and aversive olfactory learning in humans studied using event-related functional magnetic resonance imaging. Rolls et al., 2003 Rolls E.T.

Kringelbach M.L.

de Araujo I.E.T. Different representations of pleasant and unpleasant odors in the human brain. Zatorre et al., 2000 Zatorre R.J.

Jones-Gotman M.

Rouby C. Neural mechanisms involved in odour pleasantness and intensity judgements. The region of the far anterior cingulate cortex/medial orbitofrontal cortex with activations found to correlate with the pleasantness ratings given to the test odor basically coincides with a region previously found to correlate with the pleasantness ratings given to three pleasant and three unpleasant odors (). In addition, the medial orbitofrontal cortex has been reported to respond preferentially to pleasant but not unpleasant odors (). Thus, the present findings are in agreement with current evidence that the medial part of the human orbitofrontal cortex represents the pleasantness of odors, but also provides evidence on the new finding that this representation holds even when the attributed hedonic properties are modulated by cognitive information. Moreover, this region has enhanced activity when subjects are making hedonic olfactory judgements about odors ().

Gottfried and Dolan (2003) Gottfried J.A.

Dolan R.J. The nose smells what the eye sees: crossmodal visual facilitation of human olfactory perception. Critchley and Rolls, 1996 Critchley H.D.

Rolls E.T. Hunger and satiety modify the responses of olfactory and visual neurons in the primate orbitofrontal cortex. Thorpe et al., 1983 Thorpe S.J.

Rolls E.T.

Maddison S. Neuronal activity in the orbitofrontal cortex of the behaving monkey. Morris and Dolan, 2001 Morris J.S.

Dolan R.J. Involvement of human amygdala and orbitofrontal cortex in hunger-enhanced memory for food stimuli. presented odors with congruent and incongruent pictures and found that activations in the anterior medial orbitofrontal cortex and the anterior hippocampus correlate with whether the picture is congruent with the odor. In the present investigation, knowing that pictures of food and similar stimuli can produce activation of orbitofrontal neurons in macaques () and orbitofrontal cortex and amygdala in humans (), we chose to use a much more high-level, semantic, cognitive cue, simply a word presented on a screen at the same time that the odor was presented. Moreover, it was affect in particular that was modulated by the type of label we used, as shown for example by the pleasantness ratings shown in Figure 1 . Thus, the study described here is not of congruence, but instead of whether cognitive inputs can influence brain activations produced by affective properties of one and the same odor.

Zatorre et al. (2000) Zatorre R.J.

Jones-Gotman M.

Rouby C. Neural mechanisms involved in odour pleasantness and intensity judgements. Deco and Rolls, 2003 Deco G.

Rolls E.T. Attention and working memory: a dynamical model of neuronal activity in the prefrontal cortex. Rolls and Deco, 2002 Rolls E.T.

Deco G. Computational Neuroscience of Vision. McClure et al., 2004 McClure S.M.

Li J.

Tomlin D.

Cypert K.S.

Montague L.M.

Montague P.R. Neural correlates of behavioural preference for culturally familiar drinks. The study described here is also very different from the study described by, who found more activation of the orbitofrontal cortex when subjects were making hedonic as contrasted with intensity judgements of a set of odors. In that study, there was no attempt to influence olfactory processing by a top-down biased competition cognitive influence, which is the framework investigated by Rolls and Deco (), in which we understand the effects produced in the present investigation. The present study with olfactory stimuli is also very different from a recent investigation of flavor produced by drinks in which it was found that the rated preference of unlabeled drinks (i.e., without cognitive influences) was reflected in activations of a ventromedial part of the prefrontal cortex and that pictures of Coca-Cola versus Pepsi cans influenced activations in areas that are more cognitive than flavor-related areas, including the hippocampus and dorsolateral prefrontal cortex (). They were unable to image the medial orbitofrontal cortex. In contrast, the present study used olfactory stimuli and showed that a more cognitive label, a word, could influence hedonic-related olfactory activations in the medial orbitofrontal/adjoining cingulate cortex ( Figure 2 Figure 4 ) and also in the amygdala and adjoining part of the olfactory tubercle as illustrated in Figures 2 C and 2D.

Anderson et al. (2003) Anderson A.K.

Christoff K.

Stappen I.

Panitz D.

Ghahremani D.G.

Glover G.

Gabrieli J.D.

Sobel N. Dissociated neural representations of intensity and valence in human olfaction. Small et al., 2003 Small D.M.

Gregory M.D.

Mak Y.E.

Gitelman D.

Mesulam M.M.

Parrish T. Dissociation of neural representation of intensity and affective valuation in human gustation. O’Doherty et al., 2001 O’Doherty J.

Kringelbach M.L.

Rolls E.T.

Hornak J.

Andrews C. Abstract reward and punishment representations in the human orbitofrontal cortex. Hamann et al., 2004 Hamann S.

Herman R.A.

Nolan C.L.

Wallen K. Men and women differ in amygdala response to visual sexual stimuli. The finding that modulation of activity in the amygdala by cognitive information depends on presentation of a detectable olfactory stimulus is in partial agreement with thestudy, in which it was found that activity in the human amygdala represents the intensity dimension of olfactory perception. This finding has also been found to hold with respect to taste processing in humans (). However, we also provide evidence that activity in the amygdala correlates with the subjective pleasantness of odors at least when subjective pleasantness judgements are under the influence of semantic information. Thus, it is possible that the human amygdala is also involved in encoding some hedonic properties of olfactory stimuli () and sexually related visual stimuli (). However, to what extent this covariation of amygdalar activity with hedonic judgements depends on a cognitive top-down type of influence remains to be determined by further studies.