Olfactory function in psychotic disorders: Insights from neuroimaging studies

Table 1 Description of the olfactory methods used to examine different olfactory domains

Olfactory domain	Methods by which this domain is assessed
Passive smelling	Odorant is presented passively to the subject. Imaging done without response or overt cognitive appreciation
Olfactory detection	Similar to passive smelling, however, the subject must press a button to signal the onset of the odorant perception
Odour “sniffing”	Subjects are given instructions to inhale the odorant during presentation
Olfactory intensity	Rating the odorant as to its perceived strength. Can be done by a button press (Is the odour “strong”?)
	Intensity may be assessed by ratings of odorants (e.g., VAS) outside of the scanner and presenting odours that have been rated on opposite ends of the continuum (very strong vs very weak)
Olfactory familiarity	Recollect prior exposure without the exact autobiographical context and also without naming. Button press if odour is “familiar”
Olfactory hedonics (valence)	The determination of pleasantness of the odorant.
	Button press to rate whether an odorant is pleasant
	Pleasant/Unpleasant odorant rated (e.g., VAS) outside of the scanner and presenting odours that have been rated on opposite ends of the continuum (very unpleasant to very pleasant)
Olfactory identification	Correct identification- those items that are correctly labeled vs those for which label is incorrect
	Olfactory identification test score used to capture most impaired, compared with normal sense of smell
	Forced choice odour naming during scanning

Table 2 Olfactory studies

Ref.	AuthorsPassive smelling	Year	Modality	Subject group(s)	Finding
[46]	Zatorre et al	1992	PET	Healthy subjects	Piri (B) and OFC (RH)
[53]	Levy et al	1997	FMRI	Healthy subjects	P and UP: piri, amyg, hippocam, cing and post inf front cortex (laterality not specified)
[43]	Sobel et al	1998	FMRI	Healthy subjects	Passive smelling, lat OFC; Sniffing-piri (B) and post OFC (B)
[48]	Savic et al	2000	PET	Healthy subjects	OFC (RH), amyg/piri (RH), thal (RH), insula (LH), ant cing
[49]	Gottfried et al	2002	FMRI	Healthy subjects	P and UP: Amyg (B), post OFC (B), post piri (B), insula (RH)
[45]	Royet et al	2003	FMRI	Healthy subjects	UP and P odorants-piri/amyg, hypothal, sup temp, insula and OFC, ant cing
[44]	Kareken et al	2004	PET	Healthy subjects	Piri (B), amyg (B), insula (B); sniffing lateral OFC (B)
[47]	Kjelvik et al	2012	FMRI	Healthy subjects	Piri (B), amyg (B), OFC (B) and thal (B) cing (RH), insula (LH)
[25]	Plailly et al	2006	PET	Psychosis patients	HC > SZ Piri (LH) and inf front (LH)
					SZ > HC insula (RH)
	Good et al	Under review	FMRI	Psychosis patients	HC > SZ thal (RH), caud (B), ant cing, OFC (B only midly greater), mid temp gyrus (B)
	Hedonics (Valence)
[55]	Zald et al	1997	PET	Healthy subjects	Aversive odorant- amyg and OFC; less aversive- only OFC (LH)
[56]	Fulbright et al	1998	FMRI	Healthy subjects	Pleasant- BA 46/9 (RH), 32 (LH), 8 (B) 6 (RH) and insula (B); Unpleasant- 46/9 (RH), 32 (LH), 6 (B), insula (RH)
[57]	Royet et al	2000	PET	Healthy subjects	Hedonic judgement- ant cing, OFC (LH), sup front (LH), midd front gyrus (LH), inf midd temporal (LH)
[49]	Gottfried et al	2002	FMRI	Healthy subjects	UP: insula (RH), lat hypothal (LH), amyg (RH), post OFC (L); P: piri (RH), insula (RH), post OFC (RH)
[45]	Royet et al	2003	FMRI	Healthy subjects	Hedonic valence -UP > P: piri (LH), amyg (LH); P > U: cing (LH)
[58]	Rolls et al	2003	FMRI	Healthy subjects	P: med OFC; ant cing
[54]	Anderson et al	2003	FMRI	Healthy subjects
[72]	Crespo-Facorro et al	2001	PET	Psychosis patients	HC > SZ P vs UP: insula (LH), para hipp (LH), sup temp gyrus (LH), accumbens (RH), lingual gyrus (B), cb. vermis (LH) SZ > HC Med OFC (B), DLPFC (B), med front (LH), lat front (RH), lat front (LH), front operculum (LH), parahipp (RH), post cing (LH)
[25]	Plailly et al	2006	PET	Psychosis patients	HC > SZ Insula (LH) and Inf front (LH)
[27]	Schneider et al	2007	FMRI	Psychosis patients	HC > SZ UP: Midd temp gyrus (RH) Midd front gyrus (RH) Insula; P: thal (L) SZ > HC UP: Midd front (RH) ant cing (RH)
	Intensity
[54]	Anderson et al	2003	FMRI	Healthy subjects	Amyg (B)
[63]	Winsto et al	2005	FMRI	Healthy subjects	Amyg, (but only at the extremes of valence), OFC and piri
	Familiarity
[60]	Royet et al	1999	PET	Healthy subjects	Med frontal (RH), inf front (LH), sup front(LH) cingulate (B)
[57]	Royet et al	2000	PET	Healthy subjects	OFC (B), ant cing, sup front (LH) midd front (RH)
[25]	Plailly et al	2006	PET	Psychosis patients	HC > SZ piri (LH), sup temp gyrus(LH), gyrus rectus(RH), OFC (LH), inf OFC (LH)
	Identification
[47]	Kjelvik et al	2012	FMRI	Healthy subjects	Correctly identified entorhinal cortex (LH), Hippocam (RH), parahippocam gyrus (B), OFC and piriform cortices Incorrectly identified: OFC and piri cortices
[73]	Clark et al	1991	PET	Psychosis patients	HC > SZ front (B) parietal (B); Norm > Micro thal (RH) and basal ganglia
[33]	Malaspina et al	1998	SPECT	Psychosis patients	HC > SZ inf. Front (RH), sup temp (RH) supramarg/angular gyrus (RH) HC (but not SZ) hippocam(B), fusiform(RH)
	Genetic Trait
[27]	Schneider et al	2007	FMRI	Psychosis patients	HC > FDR UP: mid front gyrus(RH) FDR > HC P: ant cing(LH)

FMRI: Functional magnetic resonance imaging; PET: Positron emission tomography; SPECT: Single photon emission computed tomography; HC: Healthy controls; SZ: Schizophrenia patients; FDR: First-degree relatives; UP: Unpleasant; P: Pleasant; B: Bilateral; LH: Left hemisphere; RH: Right hemisphere; ant: Anterior; post: Posterior; lat: LAteral; inf: Interior; sup: Superior; midd: Middle; temp: Temporal; front: Frontal; Amyg: Amygdala; piri: Piriform cortex; hippocam: Hippocampus; OFC: Orbitofrontal cortex; ant cing: Anterior cingulate; thal: Thalamus; hypothal: Hypothalamus; parahippocam: Parahippocampal; DLPFC: Dorsolateral prefrontal cortex.