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Chemical Senses 2004 29(8):731-745; doi:10.1093/chemse/bjh067
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Chemical Senses Vol. 29 No. 8 © Oxford University Press 2004; all rights reserved

Lateralization of Olfactory Processes

Jean-Pierre Royet1,2 and Jane Plailly1

1 Neurosciences and Sensory Systems, Claude-Bernard University Lyon 1, CNRS UMR 5020, IFR 19, Institut Fédératif des Neurosciences, 69366 Lyon cedex 7, France and 2 CERMEP, 69003 Lyon, France

Correspondence to be sent to J.P. Royet, Neurosciences and Sensory Systems, Claude-Bernard University, Lyon 1, CNRS UMR 5020, IFR 19, Institut Fédératif des Neurosciences, 69366 Lyon cedex 7, France. e-mail: royet{at}olfac.univ-lyon1.fr


    Abstract
 Top
 Abstract
 Introduction
 The olfactory system: anatomical...
 Methods of cerebral imaging
 The orbitofrontal cortex
 The primary olfactory cortex...
 Lateralization of odour...
 Conclusions
 Acknowledgements
 References
 
Over the last ten years, methods of cerebral imaging have revolutionized our knowledge of cognitive processes in humans. An impressive number of papers dealing with cerebral imaging for olfaction have been published to date. Whereas the early works revealed those structures participating in the processing of odours presented passively to subjects, researchers later recorded brain activity when subjects performed specific olfactory tasks based on memory, emotion and identification. From these results, we suggest that there is a dissociation of olfactory processes, with involvement of the right hemisphere in memory processes and the left hemisphere in emotional processes. The review concludes with a summary of how these lateralized processes are consistent with the gestalt-nature of our olfactory perception.

Key words: emotion, familiarity, fMRI, hedonicity, judgement task, lateralization, olfactory processes, PET


    Introduction
 Top
 Abstract
 Introduction
 The olfactory system: anatomical...
 Methods of cerebral imaging
 The orbitofrontal cortex
 The primary olfactory cortex...
 Lateralization of odour...
 Conclusions
 Acknowledgements
 References
 
Human lesion studies since the 1970s have made a substantial contribution to our understanding of the neural substrate participating in the processing of olfaction (e.g. Gordon and Sperry, 1969Go; Gazzaniga et al., 1975Go; Mair and Engen, 1976Go; Risse et al., 1978Go; Abraham and Mathai, 1983Go; Eichenbaum et al., 1983Go; Eskenazi et al., 1983Go, 1986, 1988; Zatorre and Jones-Gotman, 1991Go), but it is only since the 1990s that functional imaging techniques have revealed large-scale activation patterns associated with cognitive processes and have thus allowed the identification of the neural networks specifically activated by odours. Since the first studies using cerebral imaging, more than 100 specific papers and several reviews have been published (Kobal and Kettenmann, 2000Go; Zald and Pardo, 2000Go; Zatorre and Jones-Gotman, 2000Go; Brand et al., 2001Go; Kettenmann et al., 2001Go; Savic, 2001Go, 2002).

The purpose of the current review is not to present an overview of this emerging literature, but to focus on a major finding of the data: the lateralization of olfactory processes as a function of the kind of task performed by the subjects. After a rapid presentation of the basic anatomical data, and the various methods of cerebral imaging, we shall present neuroimaging data acquired at the level of the orbitofrontal cortex (OFC) and amygdala, while attempting to respect the chronological order of both the findings and the evolution of the concepts and ideas. Briefly, findings indicate that most of the first studies showed activation in the right OFC, which has since been associated with the familiarity judgement task. Activation of the left OFC was simultaneously evidenced during both stimulation with emotional odours and when subjects performed a hedonicity judgement task. This lateralization of olfactory processes as a function of the type of olfactory task was further extended to the olfactory primary cortex and the amygdala. It was hypothesized that the familiarity and hedonicity of odours was consistent with our holistic perception of odours, and that the right–left dichotomy of olfactory processes facilitated or contributed to increased survival from an evolutionary point of view.


    The olfactory system: anatomical data
 Top
 Abstract
 Introduction
 The olfactory system: anatomical...
 Methods of cerebral imaging
 The orbitofrontal cortex
 The primary olfactory cortex...
 Lateralization of odour...
 Conclusions
 Acknowledgements
 References
 
A great deal of data has been accumulated on the neural basis of odour processing, both in humans and animals. We shall only give a brief report of this anatomical data, because a detailed description would be beyond the scope of the current paper. The reader may consult the following reviews for further information (Scott, 1986Go; Takagi, 1986Go; McLean and Shipley, 1992Go; Shipley et al., 1995Go; Shipley and Ennis, 1996Go).

From the olfactory receptors located in the superior region of the nasal cavity, axons lead to the olfactory bulb situated under the ipsilateral cerebral hemisphere. The olfactory bulb cells are connected to the primary olfactory cortex by the fibres of the lateral olfactory tract (Shipley and Reyes, 1991Go). The olfactory cortex comprises the anterior olfactory nucleus, tenia tecta, olfactory tubercle, piriform cortex (PC), anterior cortical amygdaloid nucleus, periamygdaloid and entorhinal cortices (Figure 1). These projections are primarily ipsilateral. Only a few controlateral connections between both sides of the olfactory system via the anterior commissure have been reported (Shipley and Ennis, 1996Go). The major subcortical projections of the PC are the thalamus, the hypothalamus and the ventral striatum (Price and Slotnick, 1983Go). The lateral entorhinal cortex is the major source of afferent input to the hippocampus (Van Hoesen and Pandya, 1975Go), and the nuclei of the thalamus has further connections towards the OFC and the insular cortex (Von Bonin and Green, 1949Go; Nauta, 1960Go; Mesulam and Mufson, 1985Go). It has also been reported that the PC possesses projections connecting directly with the OFC (Potter and Nauta, 1979Go; Price et al., 1991Go). A further characteristic of the olfactory system is that it has a very rich network of centrifugal fibres leading from the PC, the anterior olfactory nucleus, the amygdala, the lateral entorhinal cortex, the hypothalamus, the locus coeruleus and the raphe nuclei to the olfactory bulb (Shipley et al., 1995Go). These fibres enable the brain to control the incoming flow of olfactory signals.



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Figure 1 Schema illustrating the major efferent connections of the main olfactory system, and axial and sagittal sections from an anatomically normalized standard brain showing areas of olfactory projection. ACo nucleus, anterior cortical amygdaloid nucleus; Amy, amygdala; AON, anterior olfactory nucleus; hippoc, hippocampus, OFC, orbitofrontal cortex; PC, piriform cortex; Thal, thalamus; x, coordinate in mm along the horizontal line perpendicular to the intercommissural plane; z, coordinate in mm along the vertical line passing through the intercommissural plane (adapted from McLean and Shipley, 1992).

 
The OFC is heterogeneous and contains several distinct regions that deserve to be described because most cerebral imaging studies systematically activated them (Zald and Kim, 1996aGo,b; Öngür and Price, 2000Go; Petrides and Pandya, 2002Go). Briefly, this description is based on a brain mapping system initially proposed by Brodmann (1909Go), who parcelled the cerebral hemisphere into more than 50 areas (Brodmann’s area, BA). Cerebral imaging studies often refer to these numbered areas to indicate activated areas. Nowadays, the OFC is considered to be a region of cytoarchitectural transition between the agranular and granular cortices of the frontal lobe. Carmichael and Price (1994Go) proposed a detailed parcellation system to take into account these cytoarchitectural transitions. Very succinctly, the olfactory areas in humans were reported as being the anterior and posterior BA 11 areas corresponding to Walker’s areas 11 and 13 respectively, described in the monkey (Walker, 1940Go). The BA 47 area, just lateral to the BA 11 and also implicated in olfactory processes, was reported to correspond to Walker’s area 12.


    Methods of cerebral imaging
 Top
 Abstract
 Introduction
 The olfactory system: anatomical...
 Methods of cerebral imaging
 The orbitofrontal cortex
 The primary olfactory cortex...
 Lateralization of odour...
 Conclusions
 Acknowledgements
 References
 
Non-invasive functional neuroimaging methods are commonly classified into two broad groups: electromagnetic techniques, such as electro-encephalography (EEG), event-related potential (ERP) and magneto-encephalography (MEG); and haemodynamic techniques, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI).

Electromagnetic techniques

In the field of olfaction, classical methods utilizing EEG and ERP recordings in response to olfactory stimuli have been in use since the 1960s (e.g. Allison and Goff, 1967Go; Smith et al., 1971Go; Kobal, 1982Go; Lorig et al., 1988Go; Kobal and Hummel, 1991aGo,b; Kobal et al., 1992Go; Hummel et al., 1995Go; Pause et al., 1996Go; Castle et al., 2000Go). The MEG technique has been in use since the 1990s (e.g. Kobal and Hummel, 1991bGo; Tonoike and Kaetsu, 1995Go; Kettenmann et al., 1996Go; Sakuma et al., 1997Go; Kobal and Kettenmann, 2000Go; Hamada and Yamaguch, 2001Go). Electromagnetic techniques have excellent temporal resolution (a few milliseconds), but poor spatial resolution (several centimetres). Furthermore, although the magnetic techniques convey information about slightly deeper brain structures with less distortion than using scalp techniques, electromagnetic methods are mainly designed for recording superficial brain activity and are therefore unsuitable for recording small olfactory areas located deep in the brain. This limitation explains the small number of studies devoted to olfaction based on such techniques. Another special electrophysiological method is the stereo-EEG (SEEG) technique that consists in recording intracerebral EEG and ERP activities in epileptic patients using deep electrodes prior to surgical treatment for relief of intractable seizures. Since activity in olfactory areas can then be directly recorded in deep cerebral structures, this method is more suitable for our purposes than the previous ones, but only two studies have been performed to date (Hudry et al., 2001Go, 2003).

Haemodynamic techniques

In addition to the last method described above, haemodynamic techniques of cerebral imaging such as PET and fMRI are quite suitable for studying olfactory information processing. These techniques allow investigation of the neural activity and metabolism by measuring changes in the regional cerebral blood flow (rCBF) (Cabeza and Nyberg, 2000Go). rCBF is a good indicator of neural activity, but the resolution of haemodynamic measurements is limited both temporally and spatially. Temporal resolution is limited by the ‘sluggishness’ of the haemodynamic response: although a neural event lasts a few milliseconds, the rCBF can last for 10 s. In addition, whereas PET cameras possess a relatively good mapping resolution (5 mm), spatial resolution is limited by smoothing applied to the data to improve the signal-to-noise ratio (from 10 to 20 mm). Finally, PET does not usually allow an adequate signal to noise ratio to be obtained in <1 min, although Silbersweig et al. (1993Go) demonstrated detection of PET responses in only 30 s. To study cognitive processes, the radioactive tracer H215O, which has a half-life of 2 min, is commonly used. Its short half-life allows the planning of several experimental conditions in a single session, commonly up to 12 scans of 60 s each.

fMRI measures rCBF changes through changes in blood oxygenation. When a cerebral region is activated, the concentration of oxyhaemoglobin increases, while that of deoxyhaemoglobin decreases. Deoxyhaemoglobin contains uncoupled electrons responsible for magnetic interactions that do not exist in oxyhaemoglobin, causing a dephasing of the spins in the brain voxel. During activation, spin dephasing is slower and signal intensity is enhanced (a few percent) on a T2*-weighted image. This effect is called the ‘blood oxygenation level dependent (BOLD) contrast’ (Ogawa et al., 1990Go). The temporal resolution of fMRI is limited by the intrinsic time constant of the haemodynamic response, although images can commonly be acquired in 100 ms. Although epoch designs from 30 to 60 s (Yousem et al., 1997Go; Sobel et al., 1998bGo; Royet et al., 2003Go) are commonly used in olfaction, event-related designs may also be used (Gottfried et al., 2002aGo,b; Anderson et al., 2003Go; Gottfried and Dolan, 2003Go).

Relative to PET scanning, fMRI presents several advantages. It is non-invasive and less expensive because it does not need an infrastructure with a radionuclide-producing cyclotron with its intendant specialized medical and paramedical personnel. fMRI provides both structural and functional information and enables event-related paradigms. Subjects can be scanned several times allowing single-subject analyses not easily conceivable using PET. Lastly, it is quicker to perform, and more commonly available. However, fMRI also has its disadvantages. It is very noisy and is more sensitive to both motion and susceptibility artefacts especially in the vicinity of air–tissue interfaces (Frahm et al., 1988Go). Because these artefacts are located in the olfactory regions, several methods have been developed to alleviate them (e.g. Liu et al., 1993Go; Yang et al., 1997Go; Zald and Pardo, 2000Go; Wilson et al., 2002Go). However, these techniques have had varying degrees of success, and at best have shown only moderate signal quality in the ventromedial prefrontal cortex.

To reveal activation patterns the analysis techniques commonly applied in PET and block-design fMRI are primarily based on the principle of the subtraction of images; for example, subtracting images obtained in the baseline condition from those acquired when the subject performs a cognitive task. Before performing analyses, several pre-treatment steps are performed on each subject data set including realignment, stereotactic normalization, and smoothing. Group statistical analyses based on the Generalized Linear Model are then performed (Friston et al., 1995aGo,b). The specific location of the activated regions is often expressed in the form of three-dimensional coordinates as defined in the atlas published by Talairach and Tournoux (1988Go). Other more recent atlases are, however, available to identify activation regions (Duvernoy, 1991Go; Mai et al., 1997Go).

Statistical maps of the whole brain are exploratory and are used when no a priori hypothesis has been made concerning the neural network involved. It is possible to limit analysis to small anatomical regions of interest (ROI) such as the amygdala or the PC (Zald and Pardo, 1997Go; Royet et al., 2000Go, 2001; Kareken et al., 2001Go; O'Doherty et al., 2001Go; Gottfried et al., 2002aGo,b). The analysis of these ROI is more sensitive than maps from a statistical viewpoint, and notably overcomes the problem of variability in location and size across subjects, but can more easily give false positive responses. Statistical maps and ROI are most often used as a complement to other methods of data acquisition.


    The orbitofrontal cortex
 Top
 Abstract
 Introduction
 The olfactory system: anatomical...
 Methods of cerebral imaging
 The orbitofrontal cortex
 The primary olfactory cortex...
 Lateralization of odour...
 Conclusions
 Acknowledgements
 References
 
The first noteworthy study using the bolus H2O technique to measure rCBF during PET scans in healthy subjects was described by Zatorre et al. (1992Go). They found that the two most significant foci were located at the junction of the temporal and inferior frontal lobes in both hemispheres, corresponding to the PC. The third focus was located in the right OFC (corresponding roughly to BA 11), and the fourth one in the left inferior medial frontal lobe (BA 25). They suggested that ‘the asymmetric activity in OFC is related to more complex analyses of stimulus properties that preferentially recruit right hemisphere mechanisms’.

Activation in the right OFC (or more activation in the right than left OFC) was corroborated in most subsequent studies using both PET and fMRI techniques (Koizuka et al., 1994Go; Levy et al., 1997Go, 1998; Small et al., 1997Go; Sobel et al., 1997Go, 1998a, 2000b;Yang et al., 1997Go; Yousem et al., 1997Go, 1999; Fulbright et al., 1998Go; Francis et al., 1999Go; O'Doherty et al., 2000Go; Savic and Gulyas, 2000Go; Zatorre et al., 2000Go). Such a consensus in results is striking, and is consistent with most of the data found in behavioural studies in healthy subjects and lobectomized patients (Toulouse and Vaschide, 1900Go; Rausch et al., 1977Go; Abraham and Mathai, 1983Go; Zucco and Tressoldi, 1988Go; Cain and Gent, 1991Go; Zatorre and Jones-Gotman, 1991Go, 2000; Jones-Gotman and Zatorre, 1993Go; Kobal et al., 2000Go; Bratko and Baruðic, 2002Go). It was additionally observed that the right OFC was activated independently of the stimulated side, although the right OFC rCBF was higher during right nostril stimulations (Savic and Gulyas, 2000Go; Zatorre et al., 2000Go). Savic and Gulyas (2000Go) concluded that ‘odours seem to be processed both ipsi- and controlaterally, with a right hemisphere preponderance irrespective of the stimulated nostril’. Rather than BA 11, it appears that the most likely location for the observed activation is a more posterior region (within area 13), strongly connected with the PC and amygdala (Zald and Pardo, 2000Go; Zatorre and Jones-Gotman, 2000Go). This cytoarchitecturally distinct area is not described in the Talairach and Tournoux atlas, but appears to be structurally homologous to Walker’s area 13 in the monkey (Walker, 1940Go) and has been identified as an olfactory area in humans by Beck (1949Go) and Petrides and Pandya (1994Go). If any, such an asymmetry of olfactory processes found in humans can be related to structural, morphological and neurochemical asymmetry previously evidenced in olfactory structures in animals (Prasadao Rao and Finger, 1984Go; Heine and Galaburda, 1986Go; Dluzen and Kreutzberg, 1996Go; Rodriguez-Gomez et al., 2000Go). Furthermore, it is not unique because lateral asymmetries in perception of complex stimuli have also been reported in the auditory, visual and somesthetic modalities (Bryden and Bulman-Fleming, 1994Go). While a left-hemispheric dominance is commonly observed for language function, stimuli such as musical sounds, faces or visuospatial material require processing mechanisms mainly involving the right hemisphere (McKeever and Hulling, 1971Go; Rizzolatti et al., 1971Go; Zatorre, 1979Go).

Zald and Pardo (1997Go) reported the first noteworthy exception to the strong asymmetry described above. Measuring rCBF with PET when exposing healthy subjects to highly aversive olfactory stimuli (i.e. dimethyl sulphide, ethanethiol, methanethiol), they observed strong rCBF increases in the left OFC, but also in both amygdalae. This result was the second outstanding finding in olfactory neuroimagery.

Parallel and hierarchical processing of odours

In the first studies using cerebral imaging, odours were passively presented to subjects. In addition, some authors selected odorants considered to be the most neutral, difficult to name, unfamiliar, and similar in intensity ratings (Zatorre et al., 1992Go; Savic et al., 2000Go). It has however been emphasized that ‘The presence of a "passive" task in an activation paradigm ignores the nature of the cognitive components of such a task and therefore obscures the interpretation of any observed between-task differences in brain activity’ (Démonet et al., 1993Go). From concepts deduced from cognitive psychology (Craik and Lockhart, 1972Go; Craik and Tulving, 1975Go; Kosslyn and Koenig, 1992Go), we suggested the use of various olfactory tasks to study different odour processings (Royet et al., 1999Go, 2001). Cognitive studies have shown that sensory stimuli can be analysed at different levels, ranging from simple sensory analysis to deep or semantic analysis. In his review of the literature on odour memory, Schab (1991Go) suggested that the process of olfactory identification varies ‘in informational specificity from pleasantness and familiarity judgements to single-label, object-name identification, with various intermediate steps’. We further assumed that the detection task requires a superficial judgement not involving stored representations of odours, that perceptual and semantic odour representations are stored in separate neural subsystems, and that edibility judgements can involve the activation of semantic odour representations. We have thus shown that superficial processing of odour detection induced only a weak rCBF increase in the right OFC of healthy subjects, whereas the familiarity task, requiring perceptual processing, showed more activity in this area. In contrast, activity was significantly higher in the left OFC during the hedonicity judgement task.

Furthermore, we have shown that high-level odour processing, namely the edibility and familiarity judgement tasks, involves the left inferior frontal gyrus (BA 47) for semantic associations (Royet et al., 1999Go). Given that both these judgements are strongly correlated with naming, we concluded that activation of this area is also likely to reflect naming. This interpretation has been corroborated by more recent studies showing activation of this area to be correlated with familiarity ratings (Savic and Berglund, 2004Go), and during odour identification (Kareken et al., 2003Go). Our work has further revealed the involvement of the visual cortex when subjects performed edibility judgements (Royet et al., 1999Go, 2001). Activation of visual areas has also been found by other authors (Qureshy et al., 2000Go; Suzuki et al., 2001Go; Gottfried, personal communication). Given the well-known difficulty of verbalizing and identifying odours, we claimed that visual areas might participate in the semantic processing of odours, in the sense that subjects might visualize the object evoked by the odour and determine, for example, if the odour evokes an edible item.

From our cerebral imaging data, we suggested that odour processing comprises both a serial processing of information from the primary to secondary olfactory cortices, and a parallel, distributed processing depending on the nature of the cognitive operations being performed (Royet et al., 1999Go, 2001). The pattern of activation in the left and right OFCs varied respectively depending on whether the odour processing was related to emotional response (hedonicity judgement) or recognition memory (familiarity judgement).

Other cerebral imaging studies have been based on the use of active tasks such as detection, discrimination, recognition memory and identification (Dade et al., 1998Go, 2002; Qureshy et al., 2000Go; Savic et al., 2000Go; Zatorre et al., 2000Go; Kareken et al., 2001Go; Suzuki et al., 2001Go). In many of the aforementioned studies, several structures have also been found to be activated in addition to the OFC, such as the amygdala, hypothalamus, entorhinal, cingulate gyrus, thalamus, insula and cerebellum. On the basis of the different olfactory tasks, Savic et al. (2000Go) thus showed that odour perception activates complex neural networks which include all these structures, but in a variable way depending on the task. For example, they showed a significantly higher activity in the lateral OFC, frontal operculum and brainstem during odour quality discrimination and memory than during single odour exposition and intensity discrimination, whereas all four tasks activated structures in the olfactory cortex and more closely related structures. They further showed a higher activity in the right temporal neocortex and right parietal cortex during odour memory than in odour quality discrimination. From these findings, Ivanka Savic and her colleagues suggested that olfactory functions are organized in both a parallel and hierarchical manner, depending on the character and complexity of the task

A lateralized and extensive emotional circuit

In their pioneer study, Zald and Pardo (1997Go) demonstrated that exposure to a highly aversive odorant produced strong rCBF increases in the left OFC and both amygdalae, whereas exposure to less aversive odorants produced rCBF increases only in the left OFC. Furthermore, the activity within the left amygdala was significantly correlated with subjective ratings of perceived aversiveness, but not with perceived intensity. In a subsequent noteworthy work, applying covariance analyses to their previously acquired PET data, Zald et al. (1998aGo) estimated the functional connectivity between the amygdala and OFC in both hemispheres. They found a significant correlation between rCBF increases in the left amygdala and OFC in response to aversive odorants relative to when attempting only detection of an odour. Only the left OFC and amygdala operated in unison when exposed to an unpleasant odorant. The authors interestingly added that ‘if functional coupling reflects an active process that facilitates the interaction or communication between regions, functional uncoupling may optimise neurocognitive functioning by isolating the processing in different regions’. These findings stressed for the first time the dynamic nature of connectivity between the amygdalae and OFCs in olfaction.

In a more recent work, we examined the neural correlates of responses to emotionally valenced olfactory, visual and auditory stimuli using PET and found an extensive emotional network (Royet et al., 2000Go). For all three sensory modalities, emotionally valenced stimuli led to increased rCBF in the OFC, temporal pole and superior frontal gyrus in the left hemisphere. These findings suggested that pleasant and unpleasant emotional judgements call upon the same core network in the left hemisphere regardless of the sensory modality. This core network was, however, activated in addition to a number of circuits specific to individual sensory modalities. Emotionally valenced olfactory and visual, but not auditory stimuli thus produced additional rCBF increases in the hypothalamus and the subcallosal gyrus. Only emotionally valenced olfactory stimuli induced activation in the left amygdala, suggesting that such stimuli are more potent activators of the amygdala than visual and auditory stimuli.

A major result found in the three PET studies described above was the strong involvement of the left hemisphere in emotional processes. This finding was consistent with data found in other PET or fMRI studies of chemical senses (Zald et al., 1998bGo; Royet et al., 2001Go, 2003; Gottfried et al., 2002aGo; Anderson et al., 2003Go), but also with other types of emotional processing such as the subjective experience of anger, dysphoria and obsessive-compulsive symptoms (Drevets et al., 1992Go; Pardo et al., 1993Go; Rauch et al., 1994Go; Morris et al., 1996Go, 1998; Dougherty et al., 1999Go). Interestingly, hemispheric lateralization of olfactory-mediated affective processes is not restricted to human beings and has also been observed in rats. Left bulbectomized rats are impaired in their response to emotionally negative social odours (Dantzer et al., 1990Go). Such a lateralization has, however, never been reported by Rolls and his team in their numerous electrophysiological studies on the functions of the OFC in monkey (for review, see Rolls, 2004Go). Overall, this data indicates that left hemisphere structures play a more prominent role in emotional processing than could be explained by traditional accounts of the lateralization of emotions. It is indeed noteworthy that studies based on behavioural, lesion and electrophysical precepts have attributed a decisive role to the right hemisphere in emotion (Ahren and Schwartz, 1985Go; Gainotti, 1989Go; Jones and Fox, 1992Go; Wittling and Roschmann, 1993Go). This does not appear true when performing cerebral imaging studies. On the one hand, the previous works on behavioural, lesion and electrophysiological data were not devoted to the study of olfactory processes, and it is possible that the present results reflect a specific aspect of olfactory function. On the other hand, it is conceivable that methodological bias in neuroimaging could also explain the present data.

When a neural network implicated in an emotional response to odours is located in the left hemisphere, then the structures pertaining to this network do indubitably play a slightly different role. In a recent fMRI study, we demonstrated that actively performing the hedonicity judgement task for pleasant and unpleasant odorants compared to passively smelling these same odorants specifically induced more activation in the left OFC (Royet et al., 2003Go). It follows that this area is implicated in the conscious assessment of the emotional quality of odours and that the OFC activation in Zald and Pardo (1997Go) subjects, who passively detected mildly aversive or pleasant odorants, was probably evoked by spontaneous hedonicity judgements. In contrast, the piriform–amygdala region did not appear to participate in conscious evaluation but was activated in relation to the emotional intensity (faculty to cause arousal) of the odours. Several recent distinct findings in relation to the primary olfactory cortex and the amygdala however deserve a more detailed presentation.


    The primary olfactory cortex and the amygdala
 Top
 Abstract
 Introduction
 The olfactory system: anatomical...
 Methods of cerebral imaging
 The orbitofrontal cortex
 The primary olfactory cortex...
 Lateralization of odour...
 Conclusions
 Acknowledgements
 References
 
Although activation of the PC has been found in several studies in humans (Zatorre et al., 1992Go; Small et al., 1997Go; Sobel et al., 1998aGo, 2000b; O'Doherty et al., 2000Go; Savic et al., 2000Go; Kareken et al., 2001, 2003), several subsequent studies reported either no piriform activity (Yousem et al., 1997Go; Zald and Pardo, 1997Go; Dade et al., 1998Go, 2002; Fulbright et al., 1998Go; Royet et al., 1999Go, 2000, 2001; Zatorre et al., 2000Go; Suzuki et al., 2001Go), showed only inconsistent activation (Sobel et al., 1998aGo; Yousem et al., 1999Go) or associated these activations with sniffing (Sobel et al., 1998aGo). These discrepancies were partly explained by the finding that odorants induce sharp increases in PC activation which then rapidly habituates despite continued odorant presentation and detection (Sobel et al., 2000bGo; Poellinger et al. 2001). Since in previous fMRI studies the odorants were presented for a relatively long time, habituation limited responses in the PC. Despite this phenomenon, different roles were attributed to the piriform–amygdala region. We will successively examine the various propositions.

A memory and familiarity judgement processor?

Dade et al. (1998Go, 2002) examined human brain function using PET during different stages of olfactory memory processing: (i) encoding of new odours; (ii) recognition of odours after a short interval and (iii) recognition of odours after a long interval (24 h). They did not find PC activation in the encoding condition, but found a weak bilateral activity in the short-term recognition condition, and strong bilateral activity in the long-term recognition condition. They added that these findings were in agreement with the theory developed in several studies (Haberly and Bower, 1989Go; Bower, 1991Go; Hasselmo and Barkai, 1995Go), ‘which suggests that the primary olfactory cortex serves as a type of associative memory system, which allows for the association of odour stimuli with memory traces of previously experienced events’. Several findings lend support to the theory that the PC is involved in learning and memory. For example, long-term synaptic potentiation was shown to occur in the rat PC in vitro (e.g. Jung et al., 1990Go) and in vivo at the conclusion of learning (Roman et al., 1993Go; Litaudon et al., 1997bGo). The finding that PC activity changes in rats after odour learning may explain the greater piriform activation during recognition than in encoding. In Dade’s study, the greater piriform activity during long-term recognition could reflect increases related to memory consolidation processes.

It is well established that recognition of a repeated stimulus may depend on two different forms of memory processes (Mandler, 1980Go; Lehrner et al., 1999Go; Bogacz et al., 2001Go). According to the ‘dual process theory’, these forms are called ‘familiarity’, which is based on perceptual processing, and ‘recollection’, which includes the retrieval of contextual information. Familiarity judgements are made on the basis of a feeling, without specific information about the encoding episode, and thus relate to implicit or unconscious memory. In other terms, familiarity ratings to a large extent reflect the clarity of perceptual processing (Broman et al., 2001Go). Recollection is seen as a form of an elaborate or conceptually driven process, and thus relates to explicit or conscious memory. Since a familiarity judgement task is thus clearly associated with a memory recognition task, it was surprising that we did not observe any activation in the PC in our previous PET studies. In a recent fMRI study (Plailly et al., 2003Go), we were, however, able to show that the odour familiarity judgement task also specifically activated primary olfactory areas such as the right PC.

We further showed activation of the PC only in the right hemisphere. Although Dade et al. (2002Go) reported bilateral activation of the PC, careful examination of their data indicated a more substantial activation in the right than left PC and showed that the extent of this spread in the right OFC was fairly wide. Findings with brain-damaged patients are convergent with these data. For instance, findings on the recognition of abstract visuospatial designs in unilateral temporal lobe epilepsy patients indicated that left-lesioned patients give more ‘known’ (familiarity process) than ‘remembered’ (recollection process) responses, whereas right-lesioned patients depict the opposite pattern (Blaxton and Theodore, 1997Go). Lastly, it has been demonstrated that the right prefrontal cortex is specialized for familiarity-based traces, whereas the left prefrontal cortex is specialized for recollective memories (Kensinger et al., 2003Go).

A hedonic intensity and arousal processor?

In a recent fMRI work, we examined those networks separately activated by pleasant and unpleasant odours while subjects rated their degree of pleasantness or unpleasantness by using the ‘finger-span’ technique (Royet et al., 2003Go). Subjective intensities of odorants perceived by subjects were checked and found to be identical between pleasant and unpleasant conditions. When we subtracted images obtained in the pleasant condition from those obtained in the unpleasant condition, we mainly observed activation of the left amygdala–piriform region and ventral insula. No activation was observed with the ‘pleasant–unpleasant’ contrast. Electrodermal and plethysmography responses were also recorded to control for covert physiological manifestations of the emotional response. We demonstrated that subjective hedonic perception (rating of degree of pleasantness or unpleasantness) was stronger with unpleasant than pleasant odours and that individual subject variations in electrodermal amplitudes were correlated with finger-span ratings. Unpleasant odours therefore induced stronger emotional responses than did pleasant stimuli, independently of perceived subjective intensity. Other concomitant data have consistently shown that the BOLD signal in both the amygdala (Anderson et al., 2003Go) and the PC (Rolls et al., 2003Go) is related to odour intensity, but not to odour valence. Interestingly, a similar dissociation of the neural representation of intensity and affective valuations was found in gustation (Small et al., 2003Go; see also the preview by Anderson and Sobel, 2003Go). We have emphasized that, to manipulate odour valence, Anderson et al. (2003Go) had selected an intensity range that provided rather neutral odours and that their data then suffered from a restriction of affective range (Royet et al., 2003Go). In our study, the odours selected to be at the extremes of unpleasantness were therefore perceived as more intense and were more likely to evoke a much stronger emotional reaction than the pleasant odours (Royet et al., 2003Go). Although we agree with Anderson’s results that amygdala activation is independent of valence, the first point to be underlined is that the strength of the emotional response, i.e. emotional intensity (even more specific with unpleasant odours), is determinant for activation of the amygdala. The second point to be emphasized is the preferential involvement of the left amygdala in the negative emotional processing of olfactory stimuli. This result is consistent with previous findings (Zald and Pardo, 1997Go; Zald et al., 1998bGo) and has also recently been reported by Gottfried et al. (2002aGo). Specifically considering the PC, these same authors found bilateral activation elicited for all odours regardless of valence. It is also worth noting that in the visual domain, the responses of the amygdala to unpleasant stimuli are almost always left lateralized (e.g. Morris et al., 1996Go; Lane et al., 1997Go; Phillips et al., 1998Go; Taylor et al., 1998Go; Whalen et al., 1998Go; Pessoa et al., 2002Go). We explained the activation of the piriform–amygdala region observed for strongly emotional, so rather negative, stimuli in our study from the level of arousal that they induced. ‘Arousal refers to the extent to which stimuli are calming (low arousal) or activating (high arousal) and this dimension has been described as being orthogonal to the valence dimension’ (Zald, 2003Go). Preferential activation of the amygdala in response to negatively valenced stimuli further appears to be a general principle, since it is observed far more consistently than activations induced by positively valenced stimuli (Breiter et al., 1996Go; Hamann, 2003Go).

Functional heterogeneity within the PC and the amygdala

Attribution of a distinct function to the right and left PC and amygdala is made more complex by the fact that these structures are subdivided from an anatomical point of view, and therefore can also subtend different functions. Lateralization of olfactory processes could then involve only one part of these structures. In animals, a functional dissociation between the anterior and posterior parts of the PC has been shown by anatomical as well as optical and electrophysiological recording studies (Litaudon et al., 1997aGo,b; Mouly et al., 1998Go; Chabaud et al., 2000Go; Haberly, 2001Go). Notwithstanding the ‘sniffing versus smelling’ dichotomy evidenced by Sobel et al. (1998aGo), Gottfried et al. (2002aGo) were the first authors to show functional heterogeneity within the PC in humans. They showed that the posterior PC mediates basic odour perception (so neutral odour) and detection. In this regard, the posterior PC activations described in their study were situated close to those identified in previous imaging experiments using passive smelling (e.g. Zatorre et al., 1992Go; Savic et al., 2000Go; Sobel et al., 2000bGo; Poellinger et al., 2001Go). In contrast, they found that the anterior segment of the PC is receptive to hedonic quality, especially at extremes of odour valence. They also noted a difference in temporal processing according to whether odours were pleasant or unpleasant.

Although Anderson et al. (2003Go) found that the amygdala response is not specifically related to the dimensions of the positive and negative valences of olfactory experience, the amygdala comprises several subnuclei, and thus a ‘collapse’ across these subdivisions could have blurred the segregation of pleasantness coding. To guard against this possibility, they tested this, but did not find any functional heterogeneity within the amygdala for hedonic valence. The whole amygdala response profile appeared characteristic of smaller subdivisions. Functional segregation of the posterior amygdala was found by Gottfried et al. (2002bGo) with appetitive, but not aversive olfactory learning. As noted by the authors, these findings were intriguing and the reverse pattern of results could have been predicted. Gottfried et al. (2002bGo) suggested that the use of unpleasant odours could cause insufficient arousal to engage amygdala-dependent conditioning and/or that the reactions of disgust provoked by unpleasant odorants could activate the amygdala only poorly. These hypotheses, however, appear inconsistent with findings described in previous sections and data from a recent study in which disgusting odours induced strong activation in the amygdala (Wicker et al., 2003Go).

Regarding functional heterogeneity within the PC and amygdala, too little data has been published to be able to draw conclusions. The proximity of areas such as the PC and amygdala, and a fortiori of subregions of these areas, can in addition lead to the misinterpretation of activation patterns. The question is indeed whether the fMRI technique can allow the functional dissociation of small adjacent regions. To date, it seems that the event-related fMRI technique associated with analyses of small ROIs enables the examination of such subregions of the PC and amygdala. Recording of intracerebral EEG activity in these structures could also be an alternative method adapted to evoking responses. If subtle differences in function are implied in subregions of the PC and amygdala, it is likely that new investigations will soon allow us to elucidate their specific role.

Conclusions

Zatorre et al. (2000Go) claimed that ‘data suggest a need to revise the traditional view of PC as a simple sensory relay in a hierarchy’. However, neurophysiologists have long since established that the primary olfactory cortex is a cortex involved in highly integrated processes (see Haberly, 2001Go, for review). Cells in the PC do not respond to only olfactory input, but also fire vigorously in relation to the non-olfactory components of an odour discrimination task (Schoenbaum and Eichenbaum, 1995Go). The findings described above further subtend this assertion, and prove that the primary olfactory cortex in humans also participates in high levels of processing. It appears that the primary olfactory cortex has several roles and that these different functions can probably be ascribed to different subregions. With improvement in cerebral imaging techniques, it is likely that we may soon be able to distinguish activation patterns in substructures of this cortex such as the anterior olfactory nucleus, olfactory tubercle, frontal and temporal parts of the PC and the diagonal band nucleus as already shown by Sobel et al. (2000bGo). In summary, it was found that both odorants and sniffing activate the PC. This double function is coherent given that ‘sniffs may be regarded as the attentional spotlight of olfaction’ (Sobel et al., 2000bGo). In addition to this ‘zoom lens’ function, the PC further appears to participate in memory processes such as long-term recognition memory (Dade et al., 2002Go) and familiarity judgement (Plailly et al., 2003Go) and to the evaluation of hedonic intensity (Gottfried et al., 2002aGo; Royet et al., 2003Go). Furthermore, these processes seem lateralized with the preferential involvement of the right PC in memory processes and the left PC in hedonic intensity. The hedonic aspect (quality) further appears to be processed in the anterior part of PC, whereas odour detection seems to be processed in the posterior part (Gottfried et al., 2002aGo).


    Lateralization of odour processing
 Top
 Abstract
 Introduction
 The olfactory system: anatomical...
 Methods of cerebral imaging
 The orbitofrontal cortex
 The primary olfactory cortex...
 Lateralization of odour...
 Conclusions
 Acknowledgements
 References
 
Several theories have been proposed regarding the hemispheric asymmetry of cerebral processing. The HERA model, for instance, suggests that the left prefrontal cortical regions are more involved during the learning of new material (encoding), whereas the right prefrontal cortical regions are supposed to be more involved during subsequent recall or recognition (retrieval) (Tulving et al., 1994Go; Habib et al., 2003Go). However, the relevant anatomical regions within the extensive prefrontal cortex were not specified. It has been hypothesised that the right hemisphere is better at ‘holistic’ or ‘global’ processing, and the left hemisphere at ‘local’ processing (Fink et al., 1999Go). Regarding left–right lateralization of the amygdala activity, other hypotheses have been suggested such as unconscious versus conscious processing of stimuli (Morris et al., 1998Go), innate versus conditioned fearful stimuli (Dolan and Morris, 2000Go), and cognitively learned fear versus experimentally learned fear (Phelps et al., 2001Go), respectively.

Findings reported in the field of olfaction demonstrate that basic perceptual processes appear lateralized between the hemispheres, not only at the level of the OFCs, but also in primary olfactory regions including the PC and amygdala. It appears that the right hemisphere participates in the process of recognition memory, whereas the left hemisphere participates in the emotional processing of odours. First, these distinctions probably reflect more functional asymmetries than fully fledged dissociations. Second, since these two processes are closely related and difficult to dissociate, most studies simultaneously observe activation patterns in both hemispheres. Consistent with this, and although evidence suggests that each hemisphere can function independently (Gordon and Sperry, 1969Go), it is the interaction of the two that allows for optimal performance in more complex olfactory processing. The specificity of each hemisphere is all the more difficult to show as the airflow periodically reverses between both nostrils (Hasegawa and Kern, 1977Go) causing a slightly different image of the olfactory world to be conveyed to the brain (Sobel et al., 2000aGo), and that gender and handedness may also interact with hemispheric lateralization (Royet et al., 2003Go).

Several studies indicate that the right hemisphere is involved in the processing of pleasant odours. For instance, Zatorre et al. (2000Go) studying neural mechanisms involved in odour pleasantness and intensity judgements, demonstrated activation in the right OFC only. The lack of activation in the left OFC could, however, be explained by the use of moderately familiar odours. Intensity, hedonicity and familiarity have indeed been reported to be closely related, and less familiar odorants are rated as rather neutral and not intense (Distel et al., 1999Go; Royet et al., 1999Go). With the exception of pyridine, the odorants used in Zatorre’s study were not very intense and, since activation was summed on 60 s, the unpleasant dimension could then be eclipsed to the detriment of the pleasant dimension. Anderson et al. (2003Go) corroborated that activation in the left OFC showed greater responsiveness to unpleasant than pleasant odours, but also claimed that activation in the right medial OFC was greater for pleasant than unpleasant odours, regardless of intensity. The preferential activation of the right caudolateral OFC was subsequently replicated with pleasant tastes (Small et al., 2003Go). Activation of the right PC with pleasant odours was also reported by Gottfried et al. (2002bGo). Recent behavioural studies have finally indicated that subjects stimulated through the right nostril provided higher hedonic scores than those stimulated through the left nostril (Herz et al., 1999Go; Dijksterhuis et al., 2002Go) but it appears that the authors used rather neutral or pleasant odours. Briefly, from these data, we suggest that the right hemisphere is activated by pleasant odours because these are less emotionally arousing, and that cerebral processing of the familiarity rating is then engaged or prominent. This hypothesis could be tested by performing a comparative cerebral imaging study, in which subjects judge either hedonicity or familiarity of the same set of odours selected a priori as being rather neutral or pleasant. We suppose that activation patterns would be more lateralized in the right hemisphere for the familiarity than hedonicity judgement task.

The dichotomy of unpleasant versus pleasant emotional responses for odorous stimuli is not associated with the respective functions of left and right olfactory systems as has been suggested in several studies. Whereas the specialization of the left hemisphere for higher cognitive processes such as language is indubitably well established (Gazzaniga, 2000Go), it appears that the basic perceptual processing of odours is also lateralized between the hemispheres, with hedonic judgements (and emotional intensity) and familiarity judgements being lateralized in the left and right hemispheres respectively. Objections have been raised that the wide network activated in the left hemisphere for processing olfactory emotions (Royet et al., 2000Go) may be partly due to the influence of semantic processing. This viewpoint is supported if we refer to the OFC and superior frontal gyrus, but such an explanation cannot be corroborated by data concerning activation in the PC/amygdala, temporal pole and insula. Furthermore, it would be surprising that top-down semantic processes activate a wide neural network in the left hemisphere after stimulation only with emotional odours. Even when odours are presented passively and are not emotional, subjects are probably performing an implicit task of semantic processing. Interestingly, Zald (2003Go) also brilliantly pointed out the problem of emotional lateralization in a wider context by stressing that the neuroimaging data on the amygdala fails to support traditional models generally deduced from lesion data. He emphasized that role of the right amygdala was probably more important to the successful recognition of facial emotion. In other words, it appears that the right amygdala is more involved in recognition than emotional processes.

It appears that lateralization of the olfactory system hinges on three principles: one being based on ‘analytical’ processing (semantic), the second and third based on the ‘non-analytical’, basic perceptual processing, i.e. emotional and familiarity processings. The left brain would participate not only in analytical processing, but would also be processing the hedonic value of odours. The right brain would be ‘non-analytical’, ‘holistic’, and would process the familiarity of odours. Hedonic value as well as familiarity levels are crucial, decisive determinants of odour identity. A right-hemispheric advantage in processing odour familiarity and a left-hemispheric advantage in aversive or unpleasant odour processing enable a better and faster basic reaction of the ‘flight/fight/fear type’, because they can contribute to increased survival from an evolutionary viewpoint. A familiarity processing is unaware of the details of a stimulus and induces a feeling of ‘known’ before more semantic processing can be performed. Similarly, ‘emotional processing takes place irrespective of details of a stimulus, often before detailed properties can even be perceived or inferred’ (Kunst-Wilson and Zajonc, 1980Go; Zajonc, 1980Go). The ‘aversive’ term includes toxic food odours, stress odours that can be related to fear, odours of fire, dangerous fumes and polluted environments and natural gas leaks. If, in all these situations, the aversive or unpleasant aspect induces an arousal reaction, it also involves a very rapid decision as to whether or not an odour is familiar. It thus appears that temporal factor is a key component in hedonicity and familiarity judgements. It should be interesting to measure response times of subjects and take them into account in analyses. Activation patterns associated with these dimensions could then be strengthened.


    Conclusions
 Top
 Abstract
 Introduction
 The olfactory system: anatomical...
 Methods of cerebral imaging
 The orbitofrontal cortex
 The primary olfactory cortex...
 Lateralization of odour...
 Conclusions
 Acknowledgements
 References
 
To date, cerebral imaging findings have shown that olfactory function involves a complex and extensive olfactory neural network. Odour processing appears to be based on two main modes of processing, a serial processing with successive involvement of the primary and secondary olfactory areas, and a parallel processing (right hemisphere versus left hemisphere) depending on the nature of the cognitive task. While areas located in the right hemisphere such as the OFC and PC are more involved in memory and familiarity ratings, those located in the left hemisphere, such as the OFC, insula, PC, amygdala, temporal pole and superior frontal cortex, participate more in the emotional response to odours. These different structures would, however, be involved at different levels of emotional olfactory processing. Whereas the piriform–amygdala region appears to be associated with the evaluation of emotional intensity and therefore more activated with unpleasant than pleasant odours, the caudolateral OFC appears to mediate a conscious assessment of these odours. The role of the superior frontal cortex would be to control one’s own emotional state in the making of personally relevant decisions.

In humans, our difficulty in verbalizing and/or identifying odours is consistent with the Gestalt-nature (i.e. unitary) of our olfactory perception, and the shortened olfactory input-to-cortex pathway of the olfactory system. Wilson and Stevenson (2003Go) claim ‘that early analytical processing of odors is inaccessible at the behavioral level and that all odors are initially encoded as "objects" in the piriform cortex’, i.e. that odour percepts are synthetic. Familiarity/novelty and hedonicity perceptions can represent components of this holistic perception and their rapidity of execution represents an unquestionable advantage for survival. The PC has been reported to involve a detector of novelty (Sobel et al., 2000bGo), and the familiarity-based signal may be similar to that required for determining whether an object is novel (Kensinger et al., 2003Go). The major finding reported in the current review from neuroimaging studies is likely right–left lateralization of these processes. Although rarely described in animal studies, this lateralization of perceptual processes appears highly consistent with data obtained from cerebral imaging studies in fields of research other as olfaction. In order to formally test these hypotheses that are only derived from neuroimaging results, it would nevertheless be of further value to study patients with lateralized lesions in olfactory regions by testing them on specific judgement tasks


    Acknowledgements
 Top
 Abstract
 Introduction
 The olfactory system: anatomical...
 Methods of cerebral imaging
 The orbitofrontal cortex
 The primary olfactory cortex...
 Lateralization of odour...
 Conclusions
 Acknowledgements
 References
 
The authors would like to thank Chemical Senses’s editor R. Hudson for suggesting this review on cerebral imaging. We are very grateful to anonymous referees for constructive and pertinent comments. We thank W. Lipski for correcting the English language of the paper. This work was supported by the Centre National de la Recherche Scientifique (CNRS) and the Claude Bernard University of Lyon.


    References
 Top
 Abstract
 Introduction
 The olfactory system: anatomical...
 Methods of cerebral imaging
 The orbitofrontal cortex
 The primary olfactory cortex...
 Lateralization of odour...
 Conclusions
 Acknowledgements
 References
 
Abraham, A. and Mathai, K.V. (1983) The effect of right temporal lobe lesions on matching of smells. Neuropsychologia, 21, 277–281.[CrossRef][Web of Science][Medline]

Ahren, G.L. and Schwartz, G.E. (1985) Differential lateralization for positive and negative emotion in the human brain: EEG spectral analysis. Neuropsychologia, 23, 745–755.[CrossRef][Web of Science][Medline]

Allison, T. and Goff, W.R. (1967) Human cerebral evoked responses to odorous stimuli. Electroencephalogr. Clin. Neurophysiol., 23, 558–560.[CrossRef][Web of Science][Medline]

Amoore, J.E. (1970) Molecular Basis of Odors. Charles C. Thomas, Springfield, IL.

Anderson, A.K., Christoff, K., Stappen, I., Panitz, D., Ghahremani, D.G., Glover, G., Gabrieli, J.D. and Sobel, N. (2003) Dissociated neural representations of intensity and valence in human olfaction. Nat. Neurosci., 6, 196–202.[CrossRef][Web of Science][Medline]

Anderson, A.K. and Sobel, N. (2003) Dissociating intensity from valence as sensory inputs to emotion. Neuron, 39, 581–583.[CrossRef][Web of Science][Medline]

Beck, E. (1949) A cytoarchitectural investiga-tion into the boundaries of cortical areas 13 and 14 in the human brain. J. Anat., 83, 147–157.[Web of Science][Medline]

Blaxton, T.A. and Theodore, W.H. (1997) The role of the temporal lobes in recognizing visuospatial materials: remembering versus knowing. Brain Cogn., 35, 5–25.[CrossRef][Web of Science][Medline]

Bogacz, R., Brown, M.W. and Giraud-Carrier, C. (2001) Model of familiarity discrimination in the perirhinal cortex. J. Comput. Neurosci., 10, 5–23.[CrossRef][Web of Science][Medline]

Bower, J.M. (1991) Piriform cortex and olfactory recognition. In Davis, J.D. and Eichenbaum, H. (eds), Olfaction: A Model System for Computational Neuroscience. MIT Press, Cambridge, MA, pp. 266–285.

Brand, G., Millot, J.L. and Henquel, D. (2001) Complexity of olfactory lateralization processes revealed by functional imaging: a review. Neurosci. Biobehav. Rev., 25, 159–166.[CrossRef][Web of Science][Medline]

Bratko, D. and Baruic, T. (2002) Functional asymmetries of hemispheres and perception of odours. Studia Psychol., 44, 295–303.

Breiter, H.C., Etcoff, N.L., Whalen, P.J., Kennedy, W.A., Rauch, S.L., Buckner, R.L., Strauss, M.M., Hyman, S.E. and Rosen, B.R. (1996) Response and habituation of the human amygdala during visual processing of facial expression. Neuron, 17, 875–887.[CrossRef][Web of Science][Medline]

Brodmann, K. (1909) Vergleichende Lokalisationslehre der Großhirninde. Barth, Leipzig.

Broman, D.A., Olsson, M.J. and Nordin, S. (2001) Lateralization of olfactory cognitive functions: Effects of rhinal side of stimulation. Chem. Senses, 26, 1187–1192.[Abstract/Free Full Text]

Bryden, M.P. and Bulman-Fleming, M.B. (1994) Laterality effects in normal subjects: evidence for interhemispheric interactions. Behav Brain Res., 64, 119–129.[CrossRef][Web of Science][Medline]

Cabeza, R. and Nyberg, L. (2000) Imaging cognition II: An empirical review of 275 PET and fMRI studies. J. Cogn. Neurosci., 2, 1–47.

Cain, W.S. and Gent, J.F. (1991) Olfactory sensitivity: reliability, generality, and association with aging. J. Exp. Psychol. Human Percept. Perform., 17, 382–391.[CrossRef][Web of Science][Medline]

Carmichael, S.T. and Price, J.L. (1994) Architectonic subdivision of the orbital and medial prefrontal cortex in the macaque monkey. J. Comp. Neurol., 346, 366–402.[CrossRef][Web of Science][Medline]

Castle, P.C., van Toller, S. and Milligan, G.J. (2000) The effect of odour priming on cortical EEG and visual ERP responses. Int. J. Psychobiol., 36, 123–132.

Chabaud, P., Ravel, N., Wilson, D.A., Mouly, A.M., Vigouroux, M., Farget, V. and Gervais, R. (2000) Exposure to behaviourally relevant odour reveals differential characteristics in rat central olfactory pathways as studied through oscillatory activities. Chem. Senses, 25, 561–573.[Abstract/Free Full Text]

Craik, F.I.M. and Lockhart, R.S. (1972) Levels of processing: a framework for memory research. J. Verbal Learn. Verbal Behav., 11, 671–684.[CrossRef]

Craik, F.I.M. and Tulving, E. (1975) Depth of processing and the retention of words in episodic memory. J. Exp. Psychol. Gen., 104, 268–294.[CrossRef][Web of Science]

Dade, L.A., Jones-Gotman, M., Zatorre, R.J. and Evans, A.C. (1998) Human brain function during odour encoding and recognition: a PET activation study. Ann. NY Acad. Sci., 855, 572–574.[CrossRef][Web of Science][Medline]

Dade, L.A., Zatorre, R.J. and Jones-Gotman, M. (2002) Olfactory learning: convergent findings from lesion and brain imaging studies in humans. Brain, 125, 86–101.[Abstract/Free Full Text]

Dantzer, R., Tazi A. and Bluthe, R.M. (1990) Cerebral lateralization of olfactory-mediated affective processes in rats. Behav. Brain Res., 40, 53–60.[CrossRef][Web of Science][Medline]

Démonet, J.F., Wise, R. and Frackowiak, R.S.J. (1993) Language functions explored in normal subjects by positron emission tomography: a critical review. Hum. Brain Mapp., 1, 39–47.[CrossRef]

Dijksterhuis, G.B., Møller, P., Bredie, W.L., Rasmussen, G. and Martens, M. (2002) Gender and handedness effects on hedonicity of laterally presented odours. Brain Cogn., 50, 272–281.[CrossRef][Web of Science][Medline]

Distel, H., Ayabe-Kanamura, S., Martinez-Gomez, M., Schicker, I., Kobayakawa, T., Saito, S. and Hudson, R. (1999) Perception of everyday odors—correlation between intensity, familiarity and strength of hedonic judgement. Chem. Senses, 24, 191–199.[Abstract/Free Full Text]

Dluzen, D.E. and Kreutzberg, J.E. (1996) Norepinephrine is lateralized within the olfactory bulbs of male mice. J. Neurochem., 66, 1222–1226.[Web of Science][Medline]

Dolan, R.J. and Morris, J.S. (2000) The functional anatomy of innate and acquired fear: perspective from neuroimaging. In Lane, R.D. and Nadel, L. (eds), Cognitive Neuroscience of Emotion. Oxford University Press, New York, pp. 225–241.

Dougherty, D.D., Shin, L.M., Alpert, N.M., Pitman, R.K., Orr, S.P., Lasko, M., Macklin, M.L., Fischman, A.U.J. and Rauch, S.L. (1999) Anger in healthy men: a PET study using script-driven imagery. Biol. Psychiat., 46, 466–472.[CrossRef][Web of Science][Medline]

Drevets, W.C., Vieen, T.O., Price, J.L., Preskorn, S.H., Carmichael, S.T. and Raichle, M.E. (1992) A functional anatomy study of unipolar depression. J. Neurosci., 12, 3628–3641.[Abstract]

Duvernoy, H.M. (1991) The Human Brain—Surface, Three Dimensional Sectional Anatomy and MRI. Springer Verlag, Wien.

Eichenbaum, H., Clergg, R.A. and Feeley, A. (1983) Reexamination of functional subdivisions of the rodent prefrontal cortex. Exp. Neurol., 79, 434–451.[CrossRef][Web of Science][Medline]

Eskenazi, B., Cain, W.S., Novelly, R.A. and Friend, K.B. (1983) Olfactory functioning in temporal lobectomy patients. Neuropsychologia, 21, 365–374.[CrossRef][Web of Science][Medline]

Eskenazi, B., Cain, W.S., Lipsitt, E.D. and Novelly, R.A. (1988) Olfactory function and callosotomy: a report of two cases. Yale J. Biol. Med., 61, 447–456.[Web of Science][Medline]

Eskenazi, B., Cain, W.S., Novelly, R.A. and Mattson, R. (1986) Odor perception in temporal lobe epilepsy patients with and without temporal lobectomy. Neuropsychologia, 24, 553–562.[CrossRef][Web of Science][Medline]

Fink, G.R., Marshall, J.C., Halligan, P.W. and Dolan, R.J. (1999) Hemispheric asymmetries in global/local processing are modulated by perceptual salience. Neuropsychologia, 37, 31–40.[CrossRef][Web of Science][Medline]

Frahm, J., Merboldt, K.D. and Hanicke, W. (1988) Direct FLASH MR imaging of magnetic field inhomogeneities by gradient compensation. Magn. Reson. Med., 6, 474–480.[Web of Science][Medline]

Francis, S., Rolls, E.T., Bowtell, R., McGlone, F., O’Doherty, J., Browning, A., Clare, S. and Smith, E. (1999) The representation of pleasant touch in the brain and its relationship with taste and olfactory areas. Neuroreport, 10, 453–459.[Web of Science][Medline]

Friston, K.J., Ashburner, J., Frith, C.D., Poline, J.B., Healther, J.D. and Frackowiak, R.S.J. (1995a) Spatial registration and normalization of images. Hum. Brain Mapp., 3, 165–189.

Friston, K.J., Holmes, A.P., Worsley, K.J., Poline, J.B., Frith, C.D. and Frackowiak, R.S.J. (1995b) Statistical parametric maps in functional imaging: a general linear approach. Hum. Brain Mapp., 2, 189–210.[CrossRef]

Fulbright, R.K., Skudlarski, P., Lacadie, C.M., Warrenburg, S., Bowers, A.A., Gore, J.C. and Wexler, B.E. (1998) Functional MR imaging of regional brain responses to pleasant and unpleasant odors. Am. J. Neuroradiol., 19, 1721–1726.[Abstract]

Gainotti, G. (1989) Disorders of emotions and affect in patients with unilateral brain damage. In Boller, F. and Grafman, J. (eds), Handbook of Neurophysiology, III. Elsevier, Amsterdam, pp. 345–361.

Gazzaniga, M.S. (2000) Cerebral specialization and interhemispheric communication: does the corpus callosum enable the human condition? Brain, 123, 1293–1326.[Abstract/Free Full Text]

Gazzaniga, M.S., Risse, G.L., Springer, S.P., Clark, A.B. and Wilson, D.H. (1975) Psychologic and neurologic consequences of partial and complete cerebral commissurotomy. Neurology, 25, 10–15.[Abstract/Free Full Text]

Gordon, H.W. and Sperry, R.W. (1969) Lateralization of olfactory perception in the surgically separated hemispheres of man. Neuropsychologia, 7, 111–120.

Gottfried, J.A. and Dolan, R.J. (2003) The nose smells what the eye sees: crossmodal visual facilitation of human olfactory perception. Neuron, 39, 375–386.[CrossRef][Web of Science][Medline]

Gottfried, J.A., Deichmann, R., Winston, J.S. and Dolan, R.J. (2002a) Functional heterogeneity in human olfactory cortex: an event-related functional magnetic resonance imaging study. J. Neurosci., 22, 10819–10828.[Abstract/Free Full Text]

Gottfried, J.A., O’Doherty, J. and Dolan, R.J. (2002b) Appetitive and aversive olfactory learning in humans studied using event-related functional magnetic resonance imaging. J. Neurosci., 22, 10829–10837.[Abstract/Free Full Text]

Haberly, L.B. (2001) Parallel-distributed processing in olfactory cortex: new insights from morphological and physiological analysis of neuronal circuitry. Chem. Senses, 26, 551–576. Review.[Abstract/Free Full Text]

Haberly, L.B. and Bower, J.M. (1989) Olfactory cortex: model circuit for study of associative memory. Trends Neurosci., 12, 258–264.[CrossRef][Web of Science][Medline]

Habib, R., Nyberg, L. and Tulving, E. (2003) Hemispheric asymmetries of memory: the HERA model revisited. Trends Cogn. Sci., 7, 241–245.[CrossRef][Web of Science][Medline]

Hamada, T. and Yamaguch, M. (2001) Evoked and oscillatory neuromagnetic responses to sniffing odor in human subjects. Behav. Brain Res., 123, 219–223.

Hamann, S. (2003) Nosing in on the emotional brain. Nat. Neurosci., 6, 106–108.[CrossRef][Web of Science][Medline]

Hasegawa, M. and Kern, E.B. (1977) The human nasal cycle. Mayo Clin. Proc., 52, 28–34.[Web of Science][Medline]

Hasselmo, M.E. and Barkai, E. (1995) Cholinergic modulation of activity-dependent synaptic plasticity in the piriform cortex and associative memory function in a network biophysical simulation. J. Neurosci., 15, 6592–6604.

Heine, O. and Galaburda, A.M. (1986) Olfactory asymmetry in the rat brain. Exp. Neurol., 91, 392–398.[CrossRef][Web of Science][Medline]

Herz, R.S., McCall, G. and Cahill, L. (1999) Hemispheric lateralization in the processing of odor pleasantness versus odor names. Chem. Senses, 24, 691–695.[Abstract/Free Full Text]

Hudry, J., Ryvlin, P., Royet, J.P. and Mauguière, F. (2001) Odorants elicit evoked potentials in the human amygdala. Cereb. Cortex, 11, 619–627.

Hudry, J., Perrin, F., Ryvlin, P., Mauguière, F. and Royet, J.P. (2003) Olfactory short-term memory and related amygdala recordings in patients with temporal lobe epilepsy. Brain, 126, 1851–1863.[Abstract/Free Full Text]

Hummel, T., Pauli, E., Schüler, P., Kettenmann, B., Stefan, H. and Kobal, G. (1995) Chemosensory event-related potentials in patients with temporal lobe epilepsy. Epilepsia, 36, 79–85.

Jones, N.A. and Fox, N.A. (1992) Electroencephalogram asymmetry during emotionally evocative films and its relation to positive and negative affectivity. Brain Cogn., 20, 182–198.

Jones-Gotman, M. and Zatorre, R.J. (1993) Odor recognition memory in humans: role of right temporal and orbitofrontal regions. Brain Cogn., 22, 182–198.

Jung, M.W., Larson, J. and Lynch G. (1990) Long-term potentiation of monosynaptic EPSPs in rat piriform cortex in vitro. Synapse, 6, 279–283.

Kareken, D.A., Doty, R.L., Moberg, P.J., Mosnik, D.M., Chen, S.H., Farlow, M.R. and Hutchins, G.D. (2001) Olfactory-evoked regional cerebral blood flow in Alzheimer’s disease. Neuropsychology, 15, 18–29.

Kareken, D.A., Mosnik, D.M., Doty, R.L., Dzemidzic, M. and Hutchins, G.D. (2003) Functional anatomy of human odor sensation, discrimination, and identification in health and aging. Neuropsychology, 17, 482–495.

Kensinger, E.A., Clarke, R.J. and Corkin, S. (2003) What neural correlates underlie successful encoding and retrieval? A functional magnetic resonance imaging study using a divided attention paradigm. J. Neurosci., 23, 2407–2415.[Abstract/Free Full Text]

Kettenmann, B., Hummel, T. and Kobal, G. (2001) Functional imaging of olfactory activation in the human brain. In Simon, S.A. and Nicolelis, M.A.L. (eds), Methods and Frontiers in Chemosensory Research. CRC Press, Boca Raton, FL.

Kettenmann, B., Jousmaki, V., Portin, K., Salmelin, R., Kobal, G. and Hari, R. (1996) Odorants activate the human superior temporal sulcus. Neurosci. Lett., 203, 143–145.[CrossRef][Web of Science][Medline]

Kobal, G. (1982) A new method for determination of the olfactory and the trigeminal nerve’s dysfunction: olfactory (OEP) and chemical somato-sensory (CSEP) evoked potentials. In Rothenberger, A. (ed.), Event-related Potentials in Children. Elsevier Biomedical Press, Amsterdam, pp. 455–461.

Kobal, G. and Hummel, T. (1991a) Human electro-olfactograms and brain responses to olfactory stimulation. In Laing, D.G., Doty, R.L. and Breipohl, W. (eds), The Human Sense of Smell. Springer Verlag, Berlin, pp. 135–151.

Kobal, G. and Hummel, T. (1991b) Olfactory evoked potentials in humans. In Getchell, T.V. et al. (eds), Smell and Taste in Health and Disease. Raven Press, New York, pp. 255–275.

Kobal, G., Hummel, T. and Van Toller, S. (1992) Differences in human chemosensory evoked potentials to olfactory and somatosensory chemical stimuli presented to left and right nostrils. Chem. Senses, 17, 233–244.[Abstract/Free Full Text]

Kobal, G. and Kettenmann, B. (2000) Olfactory functional imaging and physiology. Int. J. Psychophysiol., 36, 157–163.

Kobal, G., Klimek, L., Wolfensberger, M., Gudziol, H., Temmel, A., Owen, C.M., Seeber, H., Pauli, E. and Hummel, T. (2000) Multicenter investigation of 1,036 subjects using a standardized method for the assessment of olfactory function combining tests of odor identification, odor discrimination, and olfactory thresholds. Eur. Arch. Otorhinolaryngol., 257, 205–211.[CrossRef][Medline]

Koizuka, I., Yano, H., Nagahara, M., Mochizuki, R., Seo, R., Shimada, K., Kubo, T. and Nogawa, T. (1994) Functional imaging of the human olfactory cortex by magnetic resonance imaging. Oto-Rhino-Laryngology, 56, 273–275.

Kosslyn, S.M. and Koenig, O. (1992) Wet Mind. Free Press, New York.

Kunst-Wilson, W.R. and Zajonc, R.B. (1980) Affective discrimination of stimuli that cannot be recognized. Science, 207, 557–558.[Abstract/Free Full Text]

Lane, R.D., Reiman, E., Bradley, M.M., Lang, P.J., Ahern, G.L. and Davidson, R.J. (1997) Neuroanatomical correlates of pleasant and unpleasant emotion. Neuropsychologia, 35, 1437–1444.[CrossRef][Web of Science][Medline]

Lehrner, J.P., Walla, P., Laska, M. and Deecke, L. (1999) Different forms of human odor memory: a developmental study. Neurosci. Lett., 272, 17–20.[CrossRef][Web of Science][Medline]

Levy, L.M., Henkin, R.I., Hutter, A., Lin, C.S., Martin, D. and Schellinger, D. (1997) Functional MRI of human olfaction. J. Comput. Assist. Tomogr., 21, 849–856.[CrossRef][Web of Science][Medline]

Levy, L.M., Henkin, R.I., Hutter, A., Lin, C.S. and Schellinger, D. (1998) Mapping brain activation to odorants in patients with smell loss by functional MRI. J. Comput. Assist. Tomogr., 22, 96–103.[CrossRef][Web of Science][Medline]

Litaudon, P., Datiche, F. and Cattarelli, M. (1997a) Optical recording of the rat piriform cortex activity. Progr. Neurobiol., 52, 485–510.[CrossRef][Web of Science][Medline]

Litaudon, P., Mouly, A.M., Sullivan, R., Gervais, R. and Cattarelli, M. (1997b) Learning-induced changes in rat piriform cortex activity mapped using multisite recording with voltage sensitive dye. Eur. J. Neurosci., 9, 1593–1602.[CrossRef][Web of Science][Medline]

Liu, G., Sobering, G., Duyn, J. and Moonen, C. (1993) A functional MRI technique combining principles of echo-shifting with a train of observations (PRESTO) . Magn. Reson. Med., 30, 764–768.[Web of Science][Medline]

Lorig, T.S., Schwartz, G.E., Herman, K.B. and Lane, R.D. (1988) Brain and odor II. EEG activity during nose and mouth breathing. Psychobiology, 16, 285–287.[Web of Science]

Mai, J.K., Assheuer, J. and Paxinos, G. (1997) Atlas of the Human Brain. Academic Press, San Diego.

Mair, R.G. and Engen, T. (1976) Some effects of aphasic lesions on odor perception. Sens. Processes, 1, 33–39.[Web of Science][Medline]

Mandler, G. (1980) Recognizing: the judgment of previous occurrence. Psychol. Rev., 87, 252–271.[CrossRef][Web of Science]

McKeever, W.F. and Hulling, M.D. (1971) Lateral dominance in tachistoscopic word recognition performances obtained with simultaneous bilateral input. Neuropsychologia, 9, 15–20.[CrossRef][Web of Science][Medline]

McLean, J.H. and Shipley, M.T. (1992) Neuroanatomical substrates of olfaction. In Serby, M.J. and Chobor, K.L. (eds), Science of Olfaction. Springer-Verlag, New York, pp. 126–171.

Mesulam, M.M. and Mufson, E.J. (1985) The insula of Reil in man and monkey. Architectonics, connectivity, and function. In Peters, A. and Jones, E.G. (eds), Cerebral Cortex, Vol. 4: Association and Auditory Cortices. Plenum Press, New York and London, pp. 179–226.

Morris, J.S., Frith, C.D., Perrett, D.I., Rowland, D., Young, A.W., Calder, A.J. and Dolan, R.J. (1996) A differential neural response in the human amygdala to fearful and happy facial expressions. Nature, 383, 812–815.[CrossRef][Medline]

Morris, J.S., Ohman, A. and Dolan, R.J. (1998) Conscious and unconscious emotional learning in the human amygdala. Nature, 393, 467–470.[CrossRef][Medline]

Mouly, A.M., Litaudon, P., Chabaud, P., Ravel, N. and Gervais, R. (1998) Spatiotemporal distribution of a late synchronized activity in olfactory pathways following stimulation of the olfactory bulb in rats. Eur. J. Neurosci., 10, 1128–1135.[CrossRef][Web of Science][Medline]

Nauta, W.J.H. (1960) Anatomical relationships between the amygdaloid complex. The dorsomedial thalamic nucleus and the orbitofrontal cortex in the monkey. Anat. Record, 136, 251.

O’Doherty, J., Rolls, E.T., Francis, S., Bowtell, R., McGlone, F., Kobal, G., Renner, B. and Ahne, G. (2000) Sensory-specific satiety-related olfactory activation of the human orbitofrontal cortex. Neuroreport, 11, 399–403.[Web of Science][Medline]

O’Doherty, J., Rolls, E.T., Francis, S., Bowtell, R. and McGlone, F. (2001) Representation of pleasant and aversive taste in the human brain. J. Neurophysiol., 85, 1315–1321.

Ogawa, S., Lee, T.M., Kay, A.R. and Tank, D.W. (1990) Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc. Natl Acad. Sci. USA, 87, 9868–9872.[Abstract/Free Full Text]

Öngür, D. and Price, J.L. (2000) The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cereb. Cortex, 10, 206–219.

Pardo, J.V., Pardo, P.J. and Raichle, M.E. (1993) Neural correlates of self-induced dysphoria. Am. J. Psychiatry, 151, 784–785.

Pause, B., Sojka, B., Krauel, K. and Ferstl, R. (1996) The nature of the late positive complex within the olfactory event-related potential (OERP) . Psychophysiology, 33, 376–384.[Web of Science][Medline]

Pessoa, L., McKenna, M., Gutierrez, E. and Ungerleider, L.G. (2002) Neural processing of emotional faces requires attention. Proc. Natl. Acad. Sci. USA, 99, 11458–11463.[Abstract/Free Full Text]

Petrides, M. and Pandya, D.N. (1994) Comparative architectonic analysis of the human and macaque frontal cortex. In Boller, F. and Grafman, J. (eds), Handbook of Neuropsychology, Vol. 9. Elsevier, Amsterdam, pp. 17–58.

Petrides, M. and Pandya, D.N. (2002) Comparative cytoarchitectonic analysis of the human and the macaque ventrolateral prefrontal cortex and corticocortical connection patterns in the monkey. Eur. J. Neurosci., 16, 291–310.[CrossRef][Web of Science][Medline]

Phelps, E.A., O’Connor, K.J., Gatenby, J.C., Gore, J.C., Grillon, C. and Davis, M. (2001) Activation of the left amygdala to a cognitive representation of fear. Nat. Neurosci., 4, 437–441.[CrossRef][Web of Science][Medline]

Phillips, M.L., Young, A.W., Scott, S.K., Calder, A.J., Andrew, C., Giampietro, V., Williams, S.C., Bullmore, E.T., Brammer, M. and Gray, J.A. (1998) Neural responses to facial and vocal expressions of fear and disgust. Proc. R. Soc. Lond. B Biol. Sci., 265, 1809–1817.[Medline]

Plailly, J., Bensafi, M., Pachot, M., Delon-Martin, C., Rouby, C., Segebarth, C. and Royet, J.P. (2003) Functional anatomy of the task of odor familiarity judgement: influence of handedness. Chem. Senses, 28, E45.

Poellinger, A., Thomas, R., Lio, P., Lee, A., Makris, N., Rose, B.R. and Kwong, K.K. (2001) Activation and habituation in olfaction—an fMRI study. Neuroimage, 13, 547–560.[Web of Science][Medline]

Potter, H. and Nauta, W.J. (1979) A note on the problem of olfactory associations of the orbitofrontal cortex in the monkey. Neuroscience, 4, 361–367.[CrossRef][Web of Science][Medline]

Prasadao Rao, P.D. and Finger, T.E. (1984) Asymmetry of the olfactory system in the brain of the winter flounder, Pseudopleuronectes americanus. J. Comp. Neurol., 225, 492–510.[CrossRef][Web of Science][Medline]

Price, J.L. and Slotnick, B.M. (1983) Dual olfactory representation in the rat thalamus: an anatomical and electrophysiological study. J. Comp. Neurol., 215, 63–77.[CrossRef][Web of Science][Medline]

Price, J.L., Slotnick, B.M. and Revial, M.F. (1991) Olfactory projections to the hypothalamus. J. Comp. Neurol., 306, 447–461.[CrossRef][Web of Science][Medline]

Qureshy, A., Kawashima, R., Imran, M.B., Sugiura, M., Goto, R., Okada, K., Inoue, K., Itoh, M., Schormann, T., Zilles, K. and Kukuda, H. (2000) Functional mapping of human brain in olfactory processing: a PET study. J. Neurophysiol., 84, 1656–1666.[Abstract/Free Full Text]

Rausch, R., Serafetinides, E.A. and Crandall, P.H. (1977) Olfactory memory in patients with anterior temporal lobectomy. Cortex, 13, 445–452.[Web of Science][Medline]

Rauch, S.L., Jenike, M.A., Alpert, N.M., Baer, L., Breiter, H.C., Savage, C.R. and Fischman, A.J. (1994) Regional cerebral blood flow measured during symptom provocation in obsessive-compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography. Arch. Gen. Psychiatry, 51, 62–70.[Abstract/Free Full Text]

Risse, G.L., LeDoux, J., Springer, S.P., Wilson, D.H. and Gazzaniga, M.S. (1978) The anterior commissure in man: Functional variation in multisensory system. Neuropsychologia, 16, 23–31.[CrossRef][Web of Science][Medline]

Rizzolatti, G., Umilta, C. and Berlucchi, G. (1971) Opposite superiorities of the right and left cerebral hemispheres in discriminative reaction time to physiognomical and alphabetical material. Brain, 94, 431–442.[Free Full Text]

Rodriguez-Gomez, F.J., Rendon-Unceta, M.C., Sarasquete, C. and Munoz-Cueto, J.A. (2000) Localization of tyrosine hydroxylase-immunoreactivity in the brain of the Senegalese sole, Solea senegalensis. J. Chem Neuroanat., 19, 17–32.[CrossRef][Web of Science][Medline]

Rolls, E.T. (2004) The functions of the orbitofrontal cortex. Brain Cogn., 55, 11–29.[CrossRef][Web of Science][Medline]

Rolls, E.T., Kringelbach, M.L. and Araujo, I.E. (2003) Different representations of pleasant and unpleasant odours in the human brain. Eur. J. Neurosci., 18, 695–703.[CrossRef][Web of Science][Medline]

Roman, F.S., Chaillan, F.A. and Soumireu-Mourat, B. (1993) Long-term potentiation in rat piriform cortex following discrimination learning. Brain Res., 601, 265–272.[CrossRef][Web of Science][Medline]

Royet, J.P., Koenig, O., Gregoire, M.C., Cinotti, L., Lavenne, F., Le Bars, D., Costes, N., Vigouroux, M., Farget, V., Sicard, G., Holley, A., Mauguière, F., Comar, D. and Froment, J.C. (1999) Functional anatomy of perceptual and semantic processing for odors. J. Cogn. Neurosci., 11, 94–109.[CrossRef][Web of Science][Medline]

Royet, J.P., Zald, D., Versace, R., Costes, N., Lavenne, F., Koenig, O. and Gervais, R. (2000) Emotional responses to pleasant and unpleasant olfactory, visual, and auditory stimuli: a positron emission tomography study. J. Neurosci., 20, 7752–7759.[Abstract/Free Full Text]

Royet, J.P., Hudry, J., Zald, D.H., Godinot, D., Grégoire, M.C., Lavenne, F., Costes, N. and Holley, A. (2001) Functional neuroanatomy of different olfactory judgments. Neuroimage, 13, 506–519.[Web of Science][Medline]

Royet, J.P., Plailly, J., Delon-Martin, C., Kareken, D.A. and Segebarth, C. (2003) Functional anatomy of the emotional response to odors: influence of hedonic valence, hedonic judgment, handedness, and gender. Neuroimage, in press.

Sakuma, K., Kakigi, R., Kaneoke, Y., Hoshiyama, M., Koyama, S., Nagata, O., Takeshida, Y., Ito, Y. and Nagashima, K. (1997) Odorant evoked magnetic fields in humans. Neurosci. Res., 27, 115–122.[CrossRef][Web of Science][Medline]

Savic, I. (2001) Processing of odorous signals in humans. Brain Res. Bull., 54, 307–312.[CrossRef][Web of Science][Medline]

Savic, I. (2002) Imaging of brain activation by odorants in humans. Curr. Opin. Neurol., 12, 455–461.

Savic, I. and Gulyas, B. (2000) PET show that odors are processed both ipsilaterally and contralaterally to the stimulated nostril. Neuroreport, 11, 2861–2866.[Web of Science][Medline]

Savic, I. and Berglund, H. (2004) Passive perception of odors and semantic circuits. Hum. Brain Mapp., 21, 271–278.[CrossRef][Web of Science][Medline]

Savic, I., Gulyas, B., Larsson, M. and Roland, P. (2000) Olfactory functions are mediated by parallel and hierarchical processing. Neuron, 26, 736–745.

Schab, F.R. (1991) Odor memory: taking stock. Psychol. Bull., 109, 242–251.[CrossRef][Web of Science][Medline]

Schoenbaum, G. and Eichenbaum, H. (1995) Information coding in the rodent prefrontal cortex. I. Single-neuron activity in orbitofrontal cortex compared with that in pyriform cortex. J. Neurophysiol., 74, 733–750.[Abstract/Free Full Text]

Scott, J.W. (1986) The olfactory bulb and central pathways. Experientia, 42, 223–232.[CrossRef][Web of Science][Medline]

Shipley, M.T. and Reyes, P. (1991) Anatomical of the human olfactory bulb and central olfactory pathways. In Laing, D.G., Doty, R.L. and Breipohl, W. (eds), The Human Sense of Smell. Springer-Verlag, Berlin, pp. 29–60.

Shipley, M.T. and Ennis, M. (1996) Functional organization of olfactory system. J. Neurobiol., 30, 123–176.[CrossRef][Web of Science][Medline]

Shipley, M.T., McLean, J.H. and Ennis, M. (1995) Olfactory system. In Paxinos, G. (ed.), Rat Nervous System. Academic Press, San Diego, pp. 899–926.

Silbersweig, D.A., Stern, E., Frith, C.D., Cahill, C., Schnorr, L., Grootoonk, S., Spinks, T., Clark, J., Frackowiak, R. and Jones, T. (1993) Detection of thirty-second cognitive activations in single subjects with positron emission tomography: a new low-dose H2(15)O regional cerebral blood flow three-dimensional imaging technique. J. Cereb. Blood Flow Metab. 13, 617–629.[Web of Science][Medline]

Small, D.N., Jones-Gotman, M., Zatorre, R.J., Petrides, M. and Evan, A.C. (1997) Flavor processing: More than the sum of its parts. Neuroreport, 8, 3913–3917.[Web of Science][Medline]

Small, D.M., Gregory, M.D., Mak, Y.E., Gitelman, D., Mesulam, M.M. and Parris, T. (2003) Dissociation of neural representation of intensity and affective valuation in human gustation. Neuron, 39, 701–711.[CrossRef][Web of Science][Medline]

Smith, D.B., Allison, T., Goff, W.R. and Princitato, J.J. (1971) Human odorant evoked responses: Effects of trigeminal or olfactory deficit. Electroencephalogr. Clin. Neurophysiol., 30, 313–317.[CrossRef][Web of Science][Medline]

Sobel, N., Prabhakaran, V., Desmond, J.E., Glover, G.H., Sullivan, E.V. and Gabreli, J.D.E. (1997) A method for functional magnetic resonance imaging of olfaction. J. Neurosci. Methods, 78, 115–123.[CrossRef]

Sobel, N., Prabhakaran, V., Desmond, J.E., Glover, G.H., Goode, R.L., Sullivan, E.V. and Gabrieli, J.D.E. (1998a) Sniffing and smelling: separate subsystems in the human olfactory cortex. Nature, 392, 282–286.[CrossRef][Medline]

Sobel, N., Prabhakaran, V., Hartley, C.A., Desmond, J.E., Zhao, Z., Glover, G.H., Gabrieli, J.D.E. and Sullivan, E.V. (1998b) Odorant-induced and sniff-induced activation in the cerebellum of the human. J. Neurosci., 18, 8990–9001.[Abstract/Free Full Text]

Sobel, N., Khan, R.M., Hartley, C.A., Sullivan, E.V. and Gabrieli, J.D. (2000a) Sniffing longer rather than stronger to maintain olfactory detection threshold. Chem. Senses, 25, 1–8.[Abstract/Free Full Text]

Sobel, N., Prabhakaran, V., Zhao, Z., Desmond, J.E., Glover, G.H., Sullivan, E.V. and Gabrieli, J.D.E. (2000b) Time-course of odorant-induced activation in the human primary olfactory cortex. J. Neurophysiol., 82, 537–551.

Suzuki, Y., Critchley, H.D., Suckling, J., Fukuda, R., Williams, S.C., Andrew, C., Howard, R., Ouldred, E., Bryant, C., Swift, C.G. and Jackson, S.H. (2001) Functional magnetic resonance imaging of odor identification: the effect of aging. J. Gerontol. A Biol. Sci. Med. Sci., 56, 756–760.

Talairach, J. and Tournoux, P. (1988) Co-planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Propertional System: An Approach to Cerebral Imaging. Thieme Medical Publishers, New York.

Takagi, S.F. (1986) Studies on the olfactory nervous system of the Old World monkey. Progr. Neurobiol., 27, 195–250.[CrossRef][Web of Science][Medline]

Taylor, S.F., Liberzon, I., Fig, L.M., Decker, L.R., Minoshima, S. and Koeppe, R.A. (1998) The effect of emotional content on visual recognition memory: a PET activation study. Neuroimage, 8, 188–197.[CrossRef][Web of Science][Medline]

Tonoike, M. and Kaetsu, I. (1995) Measurements of olfactory event related magnetic fields using 122 channel whole-cortex type biomagnetometer. J. Japan Biomagn. Bioelect. Soc., 8, 14–21.

Toulouse, E. and Vaschide, N. (1900) L’asymétrie sensorielle olfactive. Rev. Philos., 49, 176–186.

Tulving, E., Kapur, S., Craik, F.I.M., Moscovitch, M. and Houle, S. (1994) Hemispheric encoding/retrieval asymmetry in episodic memory: Positron emission tomography findings. Proc. Natl Acad. Sci. USA, 91, 2016–2020.[Abstract/Free Full Text]

Van Hoesen, G.W. and Pandya, D.N. (1975) Some connections of the entorhinal (area 28) and perirhinal (area 35) cortices of the rhesus monkey—1. Temporal lobe afferents. Brain Res., 95, 1–24.[CrossRef][Web of Science][Medline]

Von Bonin, G. and Green, J.R. (1949) Connections between orbital cortex an diencephalon in the macaque. J. Comp. Neurol., 92, 243–254.

Walker, A.E. (1940) A cytoarchitectural study of the prefrontal area of the macaque monkey. J. Comp. Neurol., 73, 59–86.[CrossRef][Web of Science]

Whalen, P.J., Rauch, S.L., Etcoff, N.L., McInerney, S.C., Lee, M.B. and Jenik, M.A. (1998) Masked presentations of emotional facial expressions modulate amygdala activity without explicit knowledge. J. Neurosci., 18, 411–418.[Abstract/Free Full Text]

Wicker, B., Keyser, C., Plailly, J., Royet, J.P., Gallese, V. and Rizzolatti, G. (2003) Both of us disgusted in my insula: the common neural basis of seeing and feeling disgust. Neuron, 4, :655–664.

Wilson, D.A. and Stevenson, R.J. (2003) The fundamental role of memory in olfactory perception. Trends Neurosci., 26, 243–247.[CrossRef][Web of Science][Medline]

Wilson, J.L., Jenkinson, M., de Araujo, I., Kringelbach, M.L., Rolls, E.T. and Jezzard, P. (2002) Fast, fully automated global and local magnetic field optimization for fMRI of the human brain. Neuroimage, 7, 967–976.

Wittling, W. and Roschmann, R. (1993) Emotion-related hemisphere asymmetry: Subjective emotional responses to laterally presented films. Cortex, 29, 431–448.[Web of Science][Medline]

Yang, Q.X., Darzinski, B.J., Li, S., Eslinger, P.J. and Smith, M.B. (1997) Multi-gradient echo with susceptibility inhomogeneity compensation (MGESIC): demonstration of fMRI in the olfactory cortex at 3.0 T. Magn. Reson. Med., 37, 331–335.[Web of Science][Medline]

Yousem, D.M., Williams, S.C.R., Howard, R.O., Andrew, C., Simmons, A., Allin, M., Geckle, R.J., Suskind, D., Bullmore, E.T., Brammer, M.J. and Doty, R.L. (1997) Functional MR imaging during odor stimulation: preliminary data. Neuroradiology, 204, 833–838.

Yousem, D.M., Maldjian, J.A., Siddiqi, F., Hummel, T., Alsop, D.C., Geckle, R.J., Bilker, W.B. and Doty, R.L. (1999) Gender effects on odor-stimulated functional magnetic resonance imaging. Brain Res., 818, 480–487.[CrossRef][Web of Science][Medline]

Zajonc, R.B. (1980) Feeling and thinking: preferences need no inferences. Am. Psychol., 35, 151–175.[CrossRef]

Zald, D.H. (2003) The human amygdala and the emotional evaluation of sensory stimuli. Brain Res. Rev., 41, 88–123.[CrossRef][Medline]

Zald, D.H. and Kim, S.W. (1996a) Anatomy and function of the orbital frontal cortex, I: Anatomy, neurocircuitry, and obsessive-compulsive disorder. J. Neuropsychiat., 8, 125–138.

Zald, D.H. and Kim, S.W. (1996b) Anatomy and function of the orbital frontal cortex, II: Function and relevance to obsessive-compulsive disorder. J. Neuropsychiat., 8, 249–261.

Zald, D.H. and Pardo, J.V. (1997) Emotion, olfaction, and the human amygdala: Amygdala activation during aversive olfactory stimulation. Proc. Natl. Acad. Sci. USA, 94, 4119–4124.[Abstract/Free Full Text]

Zald, D.H., Donndelinger, M.J. and Pardo, J.V. (1998a) Elucidating dynamic brain interactions with across-subjects correlational analyses of positron emission tomographic data: the functional connectivity of the amygdala and orbitofrontal cortex during olfactory tasks. J. Cereb. Blood Flow Metab., 18, 896–905.[CrossRef][Web of Science][Medline]

Zald, D.H., Lee, J.T., Fluegel, K.W. and Pardo, J.V. (1998b) Aversive gustatory stimulation activates limbic circuits in humans. Brain, 121, 1143–1154.[Abstract/Free Full Text]

Zald, D.H. and Pardo, J.V. (2000) Functional neuroimaging of the olfactory system in humans. Int. J. Psychophysiol., 36, 165–181.[CrossRef][Web of Science][Medline]

Zatorre, R.J. (1979) Recognition of dichotic melodies by musicians and nonmusicians. Neuropsychologia, 17, 607–617.[CrossRef][Web of Science][Medline]

Zatorre, R.J. and Jones-Gotman, M. (1991) Human olfactory discrimination after unilateral frontal or temporal lobectomy. Brain, 114, 71–84.[Web of Science][Medline]

Zatorre, R.J. and Jones-Gotman, M. (2000) Functional imaging of the Chemical Senses. In Toga, A.W. and Mazziotta, J.C. (eds), Brain Mapping: The Systems. Academic Press, San Diego, pp. 403–424.

Zatorre, R.J., Jones-Gotman, M., Evans, A.C. and Meyer, E. (1992) Functional localization and lateralization of human olfactory cortex. Nature, 360, 339–340.[CrossRef][Medline]

Zatorre, R.J., Jones-Gotman, M. and Rouby, C. (2000) Neural mechanisms involved in odor pleasantness and intensity judgments. Neuroreport, 11, 2711–2716.[Web of Science][Medline]

Zucco, G.M. and Tressoldi, P.E. (1988) Hemispheric differences in odour recognition. Cortex, 25, 607–615.

Accepted July 5, 2004


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