When the Sense of Smell Meets Emotion: Anxiety-State-Dependent Olfactory Processing and Neural Circuitry Adaptation

“Imaging data were preprocessed using AFNI (Cox, 1996), where images were slice-time corrected, spatially realigned and coregistered with the T1, and field-map corrected.”

“Normalization was based on Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra, a preferable approach relative to conventional normalization to achieve more precise spatial registration (Ashburner, 2007).”

“To some degree, this state-dependent process in olfaction also aligns with the embodied perception literature, demonstrating various perceptual alterations given different internal/bodily states (e.g., fatigue and affect) (Proffitt, 2006; Barsalou, 2008).”

“Finally, we further incorporated neural connectivity analysis (using dynamic causal modeling and psychophysiological interaction analysis; Friston et al., 1997, 2003; Gitelman et al., 2003) to unveil the neural circuitry subserving this dynamic, state-dependent process.”

“, 1994; Zelano and Sobel, 2005; Gottfried, 2010); and emotion areas—amygdala and anterior cingulate cortex (ACC), especially considering their close relationship with anxiety (Rauch et al., 2003; Bishop et al., 2004; Etkin et al., 2011).”

“Other ROIs were based on anatomical masks assembled in MRIcro (Rorden and Brett, 2000) and drawn on the mean T1 image, with reference to a human brain atlas (Mai et al., 1997).”

“Characterized by negative anticipation of the world and the future (Beck, 1976; Mathews and MacLeod, 2005), anxiety could negatively shift predictive codes in the APC to predominantly represent negative olfactory cues even when actual odor stimuli are affectively neutral.”

“Potentially unique to the olfactory system, this emotion encoding initiated in the sensory cortex presents an interesting alternative to prevalent accounts of emotion processing centered on the amygdala (LeDoux, 1995; Tamietto and de Gelder, 2010).”

“Human olfactory experience ties directly with the internal milieu, such that an invariant odorant elicits vastly disparate perception given different biological states, a phenomenon characterized as olfactory alliesthesia (Cabanac, 1971).”

“To confirm the main effects and to circumvent unrealistic correlations generated by rigid correction for multiple comparisons (Vul et al., 2009), we conducted a conjunction analysis between the main contrast and a regression test of this contrast on anxiety rating change (with threshold set at p 0.”

“A food odor thus becomes especially appetizing with decreasing metabolic energy reserve, promoting food seeking and consumption (O’Doherty et al., 2000; Gottfried et al., 2003).”

“Finally, we further incorporated neural connectivity analysis (using dynamic causal modeling and psychophysiological interaction analysis; Friston et al., 1997, 2003; Gitelman et al., 2003) to unveil the neural circuitry subserving this dynamic, state-dependent process.”

“…analysis focused on a set of a priori ROIs: the olfactory sensory cortex-anterior and posterior piriform cortex (APC and PPC) and olfactory OFC (Carmichael et al., 1994; Zelano and Sobel, 2005; Gottfried, 2010); and emotion areas—amygdala and anterior cingulate cortex (ACC), especially…”

“…olfactory sensory cortex-anterior and posterior piriform cortex (APC and PPC) and olfactory OFC (Carmichael et al., 1994; Zelano and Sobel, 2005; Gottfried, 2010); and emotion areas—amygdala and anterior cingulate cortex (ACC), especially considering their close relationship with anxiety (Rauch…”

“Anxiety has been associated with interpretational biases (Mathews and MacLeod, 2005), particularly for ambiguous/neutral cues (Eysenck et al., 1991; Clark and Wells, 1995).”

“A food odor thus becomes especially appetizing with decreasing metabolic energy reserve, promoting food seeking and consumption (O’Doherty et al., 2000; Gottfried et al., 2003).”

“, 1994; Zelano and Sobel, 2005; Gottfried, 2010); and emotion areas—amygdala and anterior cingulate cortex (ACC), especially considering their close relationship with anxiety (Rauch et al., 2003; Bishop et al., 2004; Etkin et al., 2011).”

“In light of the particular relevance of olfaction in fulfilling primitive biological needs, we thus posit that olfactory perception can be largely steered by the internal state to integrate hedonic value and biological utility with basic sensory encoding (Cabanac, 1971, 1979).”

“In fact, humans are notoriously poor at odor object identification, even if they are to name smells of household objects (Lawless and Engen, 1977; Cain, 1979; de Wijk et al., 1995).”

“Along this line, recent evidence further promotes the idea that affective valence represents the dominant dimension in olfactory perception, and affective experience is the primary behavioral correlate of odorant chemical properties (Khan et al., 2007; Yeshurun and Sobel, 2010).”

“OFC, olfactory OFC; pgACC, pregenual ACC; PPC, posterior piriform. hancement is likely to represent high-order, cognitive appraisal/ interpretation of the newly instilled negativity in the odors (Kalisch et al., 2006; Rushworth et al., 2007).”

“In fact, humans are notoriously poor at odor object identification, even if they are to name smells of household objects (Lawless and Engen, 1977; Cain, 1979; de Wijk et al., 1995).”

“Neuroimaging results Because air reliably activates the olfactory system, particularly when attentive sniffs are required as in the odor detection task here (Adrian, 1942; Macrides and Chorover, 1972; Sobel et al., 1998; Fontanini et al., 2003; Zelano et al., 2005), we set the air condition as the primary experimental…”

“…were all right-lateralized, in keeping with the notion of right-hemisphere dominance in olfactory processing and (negative) emotion processing (Jones-Gotman and Zatorre, 1988, 1993; Borod et al., 1998; Davidson and Irwin, 1999), we only included the right hemisphere in the model to reasonably…”

“Neuroimaging results Because air reliably activates the olfactory system, particularly when attentive sniffs are required as in the odor detection task here (Adrian, 1942; Macrides and Chorover, 1972; Sobel et al., 1998; Fontanini et al., 2003; Zelano et al., 2005), we set the air condition as the primary experimental…”

“The olfactory OFC ROI was based on a 6 mm sphere centered on the right or left putative olfactory OFC (x, y, z: 24, 36, 12; 22, 32, 16) (Gottfried and Zald, 2005).”

“Evidence accrues that this process concerns not only the physical/chemical properties of the input (e.g., stimulus quality and intensity) but also its affective value (Young, 1959; Craig, 2003; Barrett and Bar, 2009).”

“We also note that this choice adhered to pertinent previous studies (Plailly et al., 2008; Dima et al., 2011).”

“This measure is commonly used in clinical settings to assess online self-reports of anxiety and discomfort (Edelman and Chambless, 1993; Muhlberger et al., 2001).”

“, 2007) and emotional disorders (Lombion-Pouthier et al., 2006; Atanasova et al., 2010; Naudin et al., 2012), in support of mood-state-related olfactory alliesthesia.”

“Neuroimaging results Because air reliably activates the olfactory system, particularly when attentive sniffs are required as in the odor detection task here (Adrian, 1942; Macrides and Chorover, 1972; Sobel et al., 1998; Fontanini et al., 2003; Zelano et al., 2005), we set the air condition as the primary experimental…”

“Given the role of PPC in quality encoding and olfactory OFC in hedonic evaluation and conscious experience of odors (Gottfried and Zald, 2005; Li et al., 2006, 2010a,b), direct amygdala influxes to these regions would enable emotion infusion into basic olfactory processing, thereby underpinning…”

“However, human fMRI research also indicates that this structure can exhibit response adaptation to psychological influences such as attention (Zelano et al., 2005) and expectation (Zelano et al., 2011).”

“These anxietyrelated changes add to previous reports of olfactory perceptual changes in negative affective states (Chen and Dalton, 2005; Pollatos et al., 2007) and emotional disorders (Lombion-Pouthier et al., 2006; Atanasova et al., 2010; Naudin et al., 2012), in support of mood-state-related…”

“, 2007) and emotional disorders (Lombion-Pouthier et al., 2006; Atanasova et al., 2010; Naudin et al., 2012), in support of mood-state-related olfactory alliesthesia.”

“, 2007) and emotional disorders (Lombion-Pouthier et al., 2006; Atanasova et al., 2010; Naudin et al., 2012), in support of mood-state-related olfactory alliesthesia.”

“discomfort (Edelman and Chambless, 1993; Muhlberger et al., 2001).”

“We suspect this slight increase in pleasantness was related to “hedonic contrast” (Zellner et al., 2003) as neutral odors turned clearly negative.”

“As the amygdala3 PPC projection plays an important role in integrative processing of odors (Small et al., 2013), this circuitry reorganization in anxiety promotes emotion– olfaction integration by incorporating amygdala as an integral step in olfactory sensory progression.”

“These areas also transmit “top-down” reciprocal axons (Krusemark et al. 2013).”

“This anxiety-induced change in odor perception is associated with enhanced PCX and OFC odor-evoked activity, and enhanced functional connectivity between the amygdala and olfactory cortex (Krusemark et al., 2013).”