TYPE Systematic Review
PUBLISHED 22 December 2022
DOI 10.3389/fnbeh.2022.1040719

OPEN ACCESSEDITED BY

Etsuro Ito,
Waseda University, Japan

fNIRS neuroimaging in olfactory
research: A systematic literature
review

REVIEWED BY

Sara Invitto,
University of Salento, Italy
Dalin Yang,
Washington University in St. Louis,
United States*CORRESPONDENCE

Natalie Gunasekara
natalie.gunasekara.20@ucl.ac.uk

Natalie Gunasekara1*, Giuliano Gaeta2 , Andrew Levy3,4 ,Eleanor Boot3 and Ilias Tachtsidis1,3
1

Department of Medical Physics and Biomedical Engineering, University College London, London,
United Kingdom, 2 Health and Well-being Centre of Excellence, Givaudan UK Limited, Ashford,
United Kingdom, 3 MetaboLight Ltd., London, United Kingdom, 4 Wellcome Centre for Human
Neuroimaging, University College London, London, United Kingdom

SPECIALTY SECTION

This article was submitted to
Emotion Regulation and Processing,a section of the journal
Frontiers in Behavioral Neuroscience
RECEIVED 09 September 2022
ACCEPTED 04 November 2022
PUBLISHED 22 December 2022
CITATION

Gunasekara N, Gaeta G, Levy A, Boot E
and Tachtsidis I (2022) fNIRS
neuroimaging in olfactory research: A
systematic literature review.
Front. Behav. Neurosci. 16:1040719.
doi: 10.3389/fnbeh.2022.1040719
COPYRIGHT© 2022 Gunasekara, Gaeta, Levy, Bootand Tachtsidis. This is an open-accessarticle distributed under the terms of
the Creative Commons Attribution
License (CC BY). The use, distribution
or reproduction in other forums ispermitted, provided the original
author(s) and the copyright owner(s)are credited and that the original
publication in this journal is cited, in
accordance with accepted academic
practice. No use, distribution or
reproduction is permitted which does
not comply with these terms.

There are a number of key features which make olfaction difficult to study;
subjective processes of odor detection, discrimination and identiﬁcation, andindividualistic odor hedonic perception and associated odor memories. In thissystematic review we explore the role functional near-infrared spectroscopy(fNIRS) has played in understanding olfactory perception in humans. fNIRS
is an optical neuroimaging technique able to measure changes in brain
hemodynamics and oxygenation related to neural electrical activity. Adheringto PRISMA guidelines, results of this search found that generally the majorityof studies involving healthy adult subjects observed increased activity inresponse to odors. Other population types were also observed, such as
infants, individuals with autism, attention deﬁcit hyperactivity disorder (ADHD),
post-traumatic stress disorder (PTSD), mild cognitive impairment (MCI) anddysosmia. fNIRS coverage heavily favored the prefrontal cortex, temporal andparietal regions. This review ﬁnds that odor induced cortical activation isdependent on multiple factors, such as odorant type, gender and population
type. This review also ﬁnds that there is room for improvement in areas such as
participant diversity, use of wearable fNIRS systems, physiological monitoringand multi-distance channels.
KEYWORDS

odor, olfaction, fragrance, essential oils, functional near-infrared spectroscopy(fNIRS), aromatherapy

Introduction
The roles of olfaction are diverse and numerous. Living creatures are able utilize
smell to evaluate the environment, locate mates and food, and cement familial bonds.
Though these are examples of innate uses of smell, odor has a long history of humanuse. Plague doctors in Europe used lavender pouches in their masks, believing thatthese fragrant smells would deter disease. Incense has been used for thousands of years
during religious ceremonies and prayer throughout the world (Smith, 2018). Similarly,
aromatherapy has been used as a treatment for ailments of both mind and body for sometime (Sowndhararajan and Kim, 2016). More recently, science and industry have taken
an interest in investigating the psychophysiological benefits of plant extracts, perfumes,
and essential oils to promote wellbeing, relaxation, and improve sleep quality.

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Like sound, odors are capable of traversing great distances,
and are highly emotionally influential stimuli. The additional
benefit of applicability to objects in our everyday environment
lends odor to be highly adaptable asset for promoting changes
in mood and state. Using fragrances in items to aid relaxation
has become a commonplace occurrence. Aside from the longtime use of incense, candles and essential oils, various household
items, such as fabric detergent and home fresheners are utilizing
the relaxing effects of odor for both marketing and wellbeing
purposes. For example, cleaning products tend to utilize citrus
essences such as orange and lemon, as these odors are very often
associated with feelings of cleanliness and sanitation (Holland
et al., 2005). Odors such as lavender and rose are notable for
their relaxant and sedative properties, and are commonly usedin cosmetic and laundry products, lending odor to be accessible
on-the-go and crucially, during sleep (Field et al., 2005; KiecoltGlaser et al., 2008; Sowndhararajan and Kim, 2016).

odor delivery, the subjectivity of olfactory experiences, and an
inability to describe or evaluate odors consistently.
Functional near-infrared spectroscopy (fNIRS) is a relative
newcomer to brain imaging and odor research. fNIRS, like
fMRI, investigates cerebral blood hemodynamics rather thanneural electrical activity. Utilizing optical properties of nearinfrared light, fNIRS is able to measure changes in brain activity
via a system known as neurovascular coupling. Neurovascular
coupling is a term used to describe the relationship between
neural electrical activity and the changes in cerebral blood flow
and oxygenation. In summary, metabolic demand in a particulararea increases when neurons in that region become active. As
a result, the concentration of oxygenated hemoglobin in the
blood around this region is depleted as oxygen is used duringneural metabolism. Simultaneously, deoxygenated hemoglobinin the region increases (Chen et al., 2020). To compensate
for reduced oxygenation, blood flow to this region increases,
causing a reversal in relative chromophore concentrations. At
this stage, there is greater oxygenated hemoglobin relative tothe deoxygenated hemoglobin in the area. Both chromophores
possess differing near-infrared light absorption spectra (NIR)(650–900 nm), enabling the use of NIR light to determine
relative concentrations of each. Additionally, the absorption
spectra for NIR light has been found to be minimally absorbed
by water, bone and tissue (e.g., skin, scalp), allowing NIR
light to reach the cortex relatively unimpeded. Utilizing thesecharacteristics and conversion equations such as the BeerLambert Law, fNIRS is able to measure relative changes inblood oxygenation and derive regions of neural activity. A
comprehensive description of fNIRS principles is beyond thescope of this review. For full coverage of fNIRS, please see thefNIRS publication by Pinti et al. (2020) and Neurophotonics
fNIRS publication by Ayaz et al. (2022). From now onwards, theconcentrations of oxygenated and deoxygenation hemoglobinin the brain will be referred to as fNIRS measurements. fNIRS
devices consist of sources producing NIR light at two or more
wavelengths, and detectors receiving NIR light. Based on the
proportion of light received by the detectors, and the differing
absorption spectra of oxyhaemoglobin and deoxyhaemoglobin
at both wavelengths, changes in brain activity are determined.
Comparatively, fNIRS has greater motion artifact
resistance than EEG and fMRI, allowing for less restrictive
and more versatile studies. If interested in the relaxant
effects of a fragrance, the non-invasive, quiet, small size, andportable features of fNIRS are highly suitable. The additional
development of wearable fNIRS systems can add significant
scope to odor related in-context studies. Although fNIRS
has many beneficial features, its disadvantages should be
carefully considered before opting for this modality. Similar
to fMRI, fNIRS does not directly measure neural electricalactivity, instead calculates activity via changes in hemodynamic
oxygenation. The coupling between neural activity andhemodynamic activity is known to have a slight delay, therefore

Physiological data in olfaction studies
Many studies have observed the effects of odors, particularly
essential oils, on mood and relaxation. These effects are also
supported by physiological data. Some studies have foundthat lavender decreases heart rate and skin conductance,
whereas a stimulating fragrance such as neroli has the opposite
effect (Sowndhararajan and Kim, 2016). Physiological changes
induced by lavender included decreased skin conductance,increased blood flow and decreased blood pressure (Saeki and
Shiohara, 2001). The distinctive odors of Hinoki and Meniki
essential oils studied by Chen et al. (2015) found increased
pleasant mood after inhalation. The effect of these odors on
relaxation was noted by decreased systolic blood pressureand heart rate. Ylang ylang essential oil inhalation has also
been found to increase relaxation and improve mood, as
demonstrated by decreased heart rate and blood pressure (Junget al., 2013). Conversely, some olfactants are understood toincrease blood pressure, respiratory rate and heart rate, suchas rosemary (Sayorwan, 2013). Rosemary has been found to bea stimulant, improving memory and attention, whilst relaxant
naturals such as lavender caused the opposite effect (Moss et al.,2003). Cortisol is a measure of stress and can be modulatedby the presence of an anxiolytic fragrance. In a study involving
university students during their exam period, Rose essential oil
inhalation was found to modulate cortisol levels, as well as skinconductance (Fukada et al., 2011).
Although studies have shown psychophysiological andbehavioral changes due to odor, the exact mechanisms of odor
action are not well-understood (Kiecolt-Glaser et al., 2008).
Despite being a fundamental contributor to so many facetsof daily life, the sense of smell is largely overlooked, bothgenerally and scientifically. This may be due to difficulties with

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10.3389/fnbeh.2022.1040719

extra care should be taken to determine task and analysis
properties. The predominant disadvantage of fNIRS is low
spatial resolution. fNIRS optodes at the standard distance of
3 cm apart are only able to image the cortex to a depth ofroughly 5–8 mm (Karim et al., 2012). If measurement of regionsthat lie deep within the brain are required, fNIRS will likely not
be suitable. fNIRS has a lot to offer in other aspects, such as
free movement and real-world applications. With populations
that may have difficulties remaining still (infants, autism
spectrum), fNIRS is an ideal alternative, providing non-invasive,
lightweight measurement.

respectively. Through this analysis, readers will be able tounderstand how fNIRS has been used in odor based researchfor different populations, odor types, olfactory delivery devices,and paradigms.

Methods
The aim of this systematic review is to summarize thevarious methods and instruments used to research odour with
fNIRS, and compile findings related to the effect of odour on
brain activity. Other modalities that were generated via the
keyword combination were not included if fNIRS was not used.
Papers were identified using Web of Science and PubMed using
keywords (fNIRS, functional near-infrared spectroscopy; NIRS,
fragrance, odor, olfaction, essential oils, smell, aromatherapy).
Boolean operators “AND” and “OR” were used to develop
combinations for the search string. The PRISMA method wasused to search for literature (Figure 1). The literature search
for this review was completed in July 2022. Details regarding
author, publishing year, odors used, fNIRS device, channel
number, region of interest (ROI), and analysis method wereextracted and compiled by NG. Due to the inclusion of NIRS,
a substantial number of papers were returned based on nearinfrared mass spectroscopy. These were immediately removed.
Any studies not involving odor, or an aspect of odor werealso discarded.

Aims
Currently, the uses of fNIRS in odor research are highly
varied, as is processing and analysis of fNIRS data. This
literature review aims to summarize all applications offNIRS in odor research, and will cover (1) the various
protocols used and key experimental features such asfNIRS equipment, channel density, channel location,
odourant type, and hemodynamic response to odors. (2)The preprocessing and analysis protocols currently used
for odor based fNIRS data. (3) Areas that could benefit
from further study, with recommendations for future
research. This review will be separated by population
type: infants, atypical and healthy control participants,

FIGURE 1

PRISMA chart depicting literature review screening process, including number of papers found with keyword search, papers excluded andretained.

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10.3389/fnbeh.2022.1040719

Results

1[HbO2] only and two recorded 1[HbT] only. No studies
observed 1[HHb] only (Figure 4). Some papers depictedconcentration changes in graphs rather that explicitly stating
findings. Further analysis was predominantly conducted on
1[HbO2] results. Figure 4 shows the percentage of studies
reporting each hemodynamic parameter. For full parameter
reporting, including use in each study and direction ofactivation, see Table 1. When comparing an odor stimulus
to control, 1[HbO2] was shown to generally increase
with odor stimulus presentation, while, when reported,
1[HHb] decreased.
Channel numbers have generally increased since 2000,
however, a notable drop in channel density can be seen from2017 onwards (Figure 5). This reduction may coincide with theincreased development and use of smaller, simpler, wearable
systems in odor research, or use of small non-wearable systems
such as the Hamamatsu Photonics TRS-20 system and NIRO200, predominantly used in infant studies with 1-2 channels(Song et al., 2019; Tomono and Tomono, 2020; Muelbert et al.,2021). This is corroborated by the use of wearable devices infive studies, all conducted between 2017 and 2022. Devices used
included the NIRSport NIRx device (Gramlich et al., 2017),
the Pocket NIRS Duo, DynaSense, by Hamamatsu (Kunihiro
et al., 2017), the Hb133 by Astem Co. (Yamashita et al., 2022),
and the HOT-1000, WOT-100 by Neu Systems Inc (Rajagoplan,
2018; Tomono et al., 2021). The recent development of in-housecustom systems for odor research has also shown a tendency
toward low channel density, as in the case of Moein et al. (2020)
and Chen et al. (2021). The need to combine fNIRS with otherwearable systems, particularly virtual reality headsets, may also
contribute to lower channel numbers (Kaimal et al., 2021). It
should be noted that six studies did not report channel density
information, so were excluded from Figure 5.
In general, there is high preference for prefrontal cortex(PFC) coverage (Figure 6). The close associations to regions
involved in odor processing, as well as easy access for
optode placement, grants the PFC high suitability for odor
imaging. Other areas of interest include the primary andsecondary olfactory cortices, found within the temporal regionsof the brain, as well as the somatosensory cortex, foundwithin the parietal lobe. The somatosensory cortex, found at
Brodmann’s areas 1, 2, 3a, and 3b, is responsible for processing
sensory information, and has roles within odor processing
and integration. A breakdown of regions of interest can beseen in Figure 6, with emphasis on the PFC/frontal regions,parietal, temporal, and occipital areas. Only four studies opted
to register optode locations using digitization methods suchas the FASTRAK Polhemus and Nirtrack by Shimadzu Co(Takakura et al., 2011; Hucke et al., 2018; Onuma et al., 2018; Xuet al., 2020). Additionally, one study presented MNI coordinatesand AAL labels for all channel locations (Hucke et al., 2018).
Three studies show interest in the parotid gland, also known

Using the keywords and databases previously mentioned,
229 results in total were returned in Web of Science and
PubMed, between the years 2000–2022. Three additional papers
were identified from other sources. Due to overlap between
databases, 52 papers were removed. Seventy-five papers werethen screened at the initial stage using the inclusion/exclusion
criteria, and subsequently excluded from the total. Two hundred
twenty-nine papers were filtered through to remove 61 mass
spectrometry based papers due to the keyword “NIRS.” Reasonsfor exclusion can be seen in Figure 1. With more in-depth
reading, 56 further papers were excluded in the next stage. The
49 remaining results of this review are presented in Table 1.
To our knowledge, this is the first systematic review collatingodor and fNIRS studies. As can be seen in Figure 2A, thepopularity of odor stimuli in fNIRS studies has shown a steadyincrease over the last 10 years, with spikes during 2018 and 2021.
The drop in studies between 2019 and 2020 may potentiallybe attributed to the overall suspension of research during the
COVID-19 crisis. In comparison to fMRI and EEG based odor
related studies, fNIRS use is still in its infancy (Figure 2B),
however, with the additional benefits fNIRS can bring, suchas use in naturalistic settings, and the renewed interest in
olfaction due to widespread anosmia experienced as a COVID19 symptom, it is expected that odor research with fNIRS willcontinue to increase in popularity.
A total of 49 studies were included in this review, a summaryof which, including details about instrumentation and stimulus,
can be found in Table 1. With regards to the stimuli andtechnology used, all studies differed greatly. Overall, there wasa preference for passive inhalation paradigms, with few studies
implementing real-world designs. Of the real-world type studies
found, two studies utilized the relaxing effects of essential oil
aroma in a foot-care paradigm and one during a massage (Etoet al., 2014, 2015, 2016).
Five studies in total utilized a wearable device during testing,however, not all employed a real-world paradigm (Gramlich
et al., 2017; Kunihiro et al., 2017; Rajagoplan, 2018; Tomono
et al., 2021; Yamashita et al., 2022). The potential of wearable
fNIRS devices in in-context scenarios will be explored in greater
depth in the discussion sub-chapter.
As seen in Figure 3, many different fNIRS instruments
were utilized by the studies in this search, however thedominant manufacturers were Hitachi Medical and Hamamatsu
Photonics, with the most popular device being the Hitachi
Medical ETG-4000 fNIRS. This device allows for high density
optode coverage. Its maximum channel number, 52, was utilized
by three studies.
With regards to the fNIRS parameters 1[HbO2], 1[HHb],
and 1[HbT], five studies reported findings for all threeparameters, nine recorded 1[HbO2] and 1[HHb], 33 recorded

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TABLE 1 Literature review table summarizing fNIRS studies involving odor stimuli.

Participants

Yamashita et al.

5 (no age info)(2022)

Instrumentation fNIRS
channels

Areas ofinterest

ProtocolStimulifNIRS Hb133,

OFC

Wearable device. Cross-modal

Vanilla, mint, lime,

experiment, between scent and lightgrapefruit, cypress

2

Astem Co., Ltd.

HbO2

HbR

HbT

↑

Not reported

Not reported↑

Not reported

Not reported↑

Not reported

Not reported↑

Not reported

Not reported↓

Not reported

Not reported↑

Not reported

Not reported

Maternal odor↑

Not reported

Not reported

Grass, rose, mint,↓

No change

Not reported↓

Not reported

Not reported↑

Not reported

Not reported

No change

Not reported

Not reported↓

Not reported

Not reported

Gunasekara et al.

Frontiers in Behavioral Neuroscience

Referencescolor harmony
Xu et al. (2020)• 25 autistic, 20.5
years

ETG-7000, Hitachi

22

OFC

medical

et al. (2020)
Matsumoto et al.

system used
NIRScout, NIRx

6

PFC

USA
10, 30.5 ± 4.6 years(2012)

Controls

thresholds. Odor pulse ejection delivery

21.33 years
42, mean 29.43

Mint, roseparticipants of differing detection• 16 typical,
Casillas-Figueroa

Triangle odor test on autistic

ETG-4000, Hitachi

52

MedicalFrontal,HbO2 changes manual vs.

Lemonade,ReminiScentia (delivery system)

chocolate mint

Test of odor vs. odorless broth

Bonito flakes

temporalflavor/odor,
odorless broth

Eto et al. (2016)

15, >65 years

ETG-4000, Hitachi

44

PFC

MedicalFoot massage with and without aroma

Blend: Lavandulaof essential oil

angustifolia, tea
tree, Ravensara,
Palmarosa,

05

Chamomile
Moein et al. (2020)

17, mean 28.5 ± 6In-house build

Frie et al. (2019)45 (3 groups: 37–41,

NIRScout, NIRx

33–36, 28–32

USA

4

Odor detection

TD-fNIRS

Garlic, strawberry,
water

4

Olfactory

Infant study during active sleep, odor

corticespresentation

16

PFC & parietal

Haptic study using 3D models andedible/non-edible odors

lemon, cinnamon

Not specified

PFC

Hinoki image, blank with Hinoki oil,

Hinoki tree oils

weeks)
Invitto et al. (2019)

10, mean 25 ± 5.2

Song et al. (2019)

21, mean 21.1 ± 1.0

NIRScout, NIRx
USA
TRS-20 system,
Hamamatsu

Hinoki image with oil, blank no oil

Odor & Audio

photonics
Takakura et al.

10, 30.4 ± 2.6(2011)NIRSTATION:

32

PFC

Shimadzu Co
5 (±2 days) 10 (±2

NIRO-200,(2021)

days)

Hamamatsu, Japan

Eto et al. (2015)

11, >65

ETG-4000, Hitachi

TPD, saline

Causes garlic odor sensation
2

PFC

Intervention group shown smell and

Milk odor, breast,

taste of milk before gastric feed. Control

or formulawith no exposure

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Medical44

PFC

Massages with and without essential oil

Lavandula

aroma

angustifolia, tea
tree, Ravensara,
Palmarosa, andChamomile(Continued)

10.3389/fnbeh.2022.1040719

Muelbert et al.

TPD used as an odourant, but injected.

TABLE 1 (Continued)

Participants

Instrumentation fNIRS
channels

Areas ofinterest

Nishitani et al.

38, no age info

OM-220, Shimadzu

PFC

Not specified

26 (2 groups) mean

ETG-4000, Hitachi

1 (26.43 ± 3.52) 2

Medical24(25.08 ± 4.30)

Stimuli

HbO2

HbR

HbT

↑

Not reported

Not reported

Not reported

Not reported

Mothers and non-mothers presented

Infant and adultwith infant and adult male odors

male odor

Olfactory.

Participants exposed to irritant odors,

acetic acid, ethyl

Frontal,effect on brain activity measured

acetate, air (control)

Acetic acid

Olfactory,

Infants were presented with 3 odorous

Pure hand cleaner,↑

No change

Not reported

frontal,substances and the control when in

diluted handsomato-active sleep

cleaner, adhesive↓

Not reported

Not reported↑

Not reported

Not reported

VariedNot reported

Not reported

Soy sauce↑

Not reported

Not reported

Multiplication and word generation

Green tea,

Not reported

Not reported

Not reported

tasks were performed before and after

transparent sugar

drink intake. One drink was used per

milk, lemon teas,

day

water

fNIRS was recorded on combat veterans,

Diesel fuel, rotten

VariedNot reported

Not reported

combat veterans w/PTSD and civilians

egg, n-butanol

Effect of Yomogi, lavender and Ylang

Yomogi, lavender,

VariedVariedNot reported

ylang essential oil on brain activity

Ylang ylang

Participants received different footcare

Lavandula

VariedNot reported

Variedtreatments, footbath, a massage, aangustifolia, tea

footbath with aroma oils, and an aroma

tree, ravensara,

oil massage. HbO2 measured

palmarosa, and(2014)
Hucke et al. (2018)

ProtocolMothers↑

Gunasekara et al.

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References

middle frontal
gyrus

Frie et al. (2017)41, 28–41 weeks

NIRscout, NIRx

8

USA

remover

sensory
Tanida et al. (2008)

12 (no age info)

NIRO-300,[Fragrance exposure for 4 weeks. HbO2]

Floral green tone

Hamamatsu

Not specified

PFC

changes during mental arithmetic task

spray

photonics

and sebum secretion measured before
and after intervention

Azuma et al. (2016)

16 (no age info)

LABNIRS,52

PFC

Shimadzu

Odor detection and recognition

Rose, caramel,threshold testing of multiple chemical

sweat, fruit,sensitivity cohort

vegetable, sweet,
fecal

06

Tomono et al.

10 (21–22 years)(2021)
Onuma et al. (2018)

WOT-100 by NeU

16

PFC, temporal

Corporation
44 (4 groups) mean

FOIRE-3000

ages (1) 20.3, (2a)WOT-S20 Hitachi

21.6, (2b), 21.3, (3)parotid glands

Food videos presented to ppts via a

Sukiyaki sauce

integrated scent dispersal display
34

TemporalParticipants tasted NaCl with andwithout MSG or soy sauce odor

21.3
Rajagoplan (2018)

6, 21–22

HOT-1000,

2

Frontal

NeuSystems Inc

48, mean 32.02 ±Gramlich et al.

NIRSport-88, NIRx

22

PFC

(2017)
Kunihiro et al.

18, 19–24 years(2017)

Pocket NIRS Duo,2

PFC

DynaSense,
Hamamatsu

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Eto et al. (2014)

4, >65FOIRE-3000,
Shimadzu

46

PFC

chamomile(Continued)

10.3389/fnbeh.2022.1040719

8.47

TABLE 1 (Continued)

Participants

Instrumentation fNIRS
channels

Areas ofinterest

ProtocolStimuli

Bartocci et al.

23, mean 48 h ±NIRO 300,

Left

Assess olfactory cortex activity in awake

Control, colostrum,(2000)

10.1

Hamamatsu

orbito-frontal

infants receiving olfactory stimuli.

vanillaphotonics

gyrus

Thirty second baseline, stimuli order:

1

HbO2

HbR

HbT

↑

Not reported

Not reported↑

Not reported

Not reported↑

Not reported

Not reported

Not specified

Not reported

Not reported↑

No change

Not reported↓

No change↓↑

No change

Gunasekara et al.

Frontiers in Behavioral Neuroscience

References

control, colostrum, vanilla
Saito-Iizumi et al.

7, mean 31.4 ± 4.5(2013)

ETG-4000, Hitachi

52

medicalSchecklmann et al.

27 ADHD, 22

ETG-4000, Hitachi(2011a)control

medical24

Frontal,Participants take part in two conditions,Odor: Ethymaltol

temporal,taste without odor, taste with odor, atTaste: Sucrose

parotid glanddifferent concentrations

dilutions 2–10%

Inferior frontal

Olfactory sensitivity, discrimination &2-phenylethanol& temporal

identification in ADHD with(rose)ADHD withmedication

medication, ADHD without andcontrols, using Sniffin’ Sticks
Maharjan et al.

20, 25.05 ± 2.36

(2019)

COVIDIEN INVOS

Not specified

OFC

OXIMETER, Model
5100C-PA

Ishimaru et al.

5, 32.69 ± 14.9

(2004)

PSA500; Biomedical

Odor intensity tests (food odor) before

Citrus, Banana,

and after low and high frequency nerve

cheese, mushroom

stimulation
2

OFC

Science, Kanazawa

OFC activity observed during odorb-phenyl ethyl

inhalation

alcohol, iso-valeric

07

acid
Bartocci et al.

20, 33.7 ± 2.3(2001)

NIRO 300,

2

OFC

Hamamatsu

15 infants exposed to disinfectant smell,

Disinfectant,

5 to detergent

detergent

Seated pasasive breathing throughIsovaleric acidphotonics
Kobayashi et al.

13, (1) 28.9, (2) 46.9

Unspecified

22

Frontal lobe

(2009)

olfactometer for 5 s, followed by 55 s

Normosmic↑
Normalrest. Repeated 5 times
Kokan et al. (2011)

Schecklmann et al.

14, 19.6 years

29 (no age info)(2011b)Omega Monitor,

4

OFC

Passive inhalation through olfactometer,

BOM-L1W,

participant pushed button when odor

OmegaWave Co

detected

ETG-4000, Hitachi

44

PFC

Olfactory function testing

medicalBPEA and citrus

Not reported

Not reported

Direction notstated2-phenylethanol,
linalool↑Not reported

Not reported

Not reported

Not reported

Controls &26, mean 5 days ±NIRO-200,(2010)

1.8

2

OFC

fNIRS during sleep. Two groups, breast

Maternal milk,

Hamamatsu

fed, bottle fed. All infants took part inbottle milk

photonics

both conditions. Odors presented via↑

frontiersin.org

gauze detection
Hasegawa et al.
(2013)

25, 27.0 ± 2.8

NIRO-200,
Hamamatsu

2

Frontal lobe

Participants chewed 3 gum types with

Gum with anddifferent taste/odor combinations

without lemon odor↑

Not reported

photonics(Continued)

10.3389/fnbeh.2022.1040719

ADHD
Aoyama et al.

References

Participants

Instrumentation fNIRS
channels

Chen et al. (2021)

28 (no age info)

In-house built

2

PFC

Passive inhalation of odor

Lavender↑↓Not reported

Maharjan et al.

18, 24.55 ± 3.8

COVIDIEN INVOS

2

FrontalOdor Threshold Test (OTT) and

Snif test kit

No change

Not reported

Not reported

Apple, garlic,

No change

Not reported

Not reported

Not reported

Not reported(2018)

Areas ofinterest

OXIMETER, Model

ProtocolStimuli

HbO2

HbR

HbT

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TABLE 1 (Continued)

Supra-threshold test (STT) with fNIRS

5100C-PA
Ho et al. (2021)

12 (no age info)

ETG-4000, Hitachi

52

medicalFrontal,Sniffin sticks 12 identification test

temporalchocolate, sesameoil

Fujii et al. (2007)

20, (1) 30–65 years

Hitachi ETG-100

20

PFC

(2) 24–48 years

Prefrontal activity of Koh-Do experts

Wood chips

whilst discriminating incense

Changes inexpert group
only

Kaimal et al. (2021)

Harada et al. (2006)

17–54, M = 27.5

fNIRS Imager

year

2000S

13, 23–31 years

NIRO 300

16PFC

VR with and without fragrance. Twenty

Lavender, orange,

hours sessions 1 week apart. Fragrance

juniper berry,08↑

Not reported

Not reported↑

Not reported

Not reported

Not reported

Not reported↑

Not reported

Not reported↓

Not reported

Not reported↑

Not reported

Not reported↑

Not reported

Not reported

or on fragpatchouli

Frontal,Olfactory stimulation during odor

Vanilla, strawberry,

Hamamatsu

temporal,

exposure to pleasant and unpleasantscatol, distilled

Photonics

parietal,stimuliwater

Orbito-frontal

Cognitive impairment detection

Unscented,↑

cortexparadigm. CN (cognitively normal),

peppermint

Controls2

occipital
Kim et al. (2022)• CN: 55, 74.0

Unspecified

7• MCI: 26, 74.0
• AD: 16, 76.5

MCI (mild cognitive impairment), AD(Alzheimer’s disease)

Tomono and22, 21–24 years

Tomono (2020)

NIRO-2002

TemporalHamamatsu
photonics

Mitsukura et al.

17 (no age info)(2021)

FOIRE-3000,

Passive inhalation of odors whilst

Bergamot orange,

watching video clips of others eating

vanillafood
44

SHIMADZU Co.

Frontal,fNIRS baseline recording and typing

Olive oil, bread

occipital

task before and after olive oil

combo

consumption
26, 24 ± 1.8 years

OMM-2001,

47

Shimadzu,

Right

Odor exposure followed by POMS

Japanese plumhemispherequestionnaire

blossom, control air

Participants exposed to 4 ambient odors

3 floral odors, noover 4 days. Each day faces evaluatedodor

Finometer device
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Onuma et al. (2018)

12, mean 20

ETG-100, Hitachi
medical24

Frontalbased on femininity(Continued)

10.3389/fnbeh.2022.1040719

Jo et al. (2013)

No change
Uncertain
No change

video

Rose water, water
Drink rose water or water, fNIRS

recording for 20 min while watching

Infant studies
Due to the artifact resistance and portability exhibited by
fNIRS, many papers focused on infant studies. In this literaturesearch, six infant studies investigated odor with fNIRS. Most
studies reported observing multiple infant age groups. Threestudies investigated odor effects on preterm infants; pre-term,very pre-term (Frie et al., 2017, 2019; Muelbert et al., 2021).
The remaining three studies observed full-term infants (Bartocci
et al., 2000, 2001; Aoyama et al., 2010). Most papers observed
activity during sleep (Aoyama et al., 2010; Frie et al., 2017, 2019),
whilst three studies observed wakefulness (Bartocci et al., 2000,
2001; Muelbert et al., 2021). In terms of odors, four of the six
studies used maternal scents such as breast odor, breast milkodor and maternal colostrum as the stimulus (Bartocci et al.,
2000; Aoyama et al., 2010; Frie et al., 2019; Muelbert et al., 2021).
These odors were either collected and delivered on a cotton
pad, gauze or cotton bud. Other odor stimuli include unnatural
aromas experienced in hospital situations, such as disinfectant,detergent and hand cleaner. These odors were found to becapable of eliciting trigeminal pain responses (Bartocci et al.,
2001; Frie et al., 2017).
Two studies analyzed both 1[HbO2] and 1[HHb], three
analyzed 1[HbO2] only, and one analyzed all three parameters.
Apart from Bartocci et al. (2001) and Muelbert et al. (2021),
all studies found an increase in 1[HbO2] in the OFC region,↑ Indicates an increase in parameter, ↓ a decrease.

medical systems
23.3 years

Oxymon, Artinis• Water: 40,

photonics• Rose: 40, 23 years
Moss et al. (2018)12

Not specified
TRS-20 system,

Hamamatsu

13, 21.5 ± 1.0 years

photonics

Ikei et al. (2015)

Frontiers in Behavioral Neuroscienceas the salivary gland, found toward the temporal region of thebrain. This region is often activated in the presence of food
related odor stimuli. In this review, 3 studies utilize odor toenhance taste, e.g., ethylmaltol odor, soy sauce, and bonito
flake aroma (Saito-Iizumi et al., 2013; Onuma et al., 2018;
Tomono et al., 2021). The majority of studies were conducted onhealthy, neurotypical adults. Some studies observed infants, aswell as atypical populations with post-traumatic stress disorder(PTSD), attention deficit hyperactivity disorder (ADHD) andautism (Schecklmann et al., 2011a,b; Gramlich et al., 2017; Xu
et al., 2020). Figure 7b demonstrates a typical infant response
to odor stimuli, in this case a combination of hospital basedalien odors (Frie et al., 2017). Response to odor in healthy
adult controls can be seen in Figures 7a,c,d, highlighting thedifferent responses that can be induced depending on paradigm.
Paradigms involved in Figures 7c,d involve the intent to increase
relaxation, and show a gradual decrease in 1[HbO2] over time,
whilst (Figures 7a,b) shows a typical increase in 1[HbO2] inresponse to odor onset.
For the purposes of this review, the following sections are
separated by population type; infant, atypical and typical. Withineach section, details pertaining to odors used, demographics,
protocols and hemodynamic findings will be stated. If studies
show similarities or differences in any aspect of the protocol or
results, this will be highlighted.

Frontalair↓
Hinoki cypress oil,Presentation of odor for 90 s,
PFC

PFC
Not specified
TRS-20Hamamatsu

Photonics

20, 22.5 ± 1.6 years
Igarashi et al. (2014)

NIRO 300,

Hamamatsu

29, 56–79 years
Fladby et al. (2004)

2questionnaire following inhalation

3 odor stimuli presented for 90 sorange oil

Control, rose,↓

Not reported

Not reported

Not reported

Not reported

Not reported
Uncertain
Uncertain
Vanilla, water
TemporalInhalation of vanilla or sham water,

activation measured in termporal region

HbO2
ProtocolAreas ofinterest
Instrumentation fNIRS
channels
Participants
References

TABLE 1 (Continued)

10.3389/fnbeh.2022.1040719

Stimuli

HbR

HbT

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FIGURE 2(A) Number of papers published by year involving fNIRS with odor stimuli. (B) A comparison of the number of papers published by year involving
odor stimuli for fMRI, EEG, and fNIRS.

in response to odor stimuli. Muelbert et al. (2021) foundno significant change in 1[HbO2] after odor exposure, while
Bartocci et al. (2001) demonstrated a decrease in 1[HbO2]
and 1[HbT] in response to hospital odor stimuli. Activation
also varied within stimulus types. Interestingly, one study usingmaternal odors, found significantly higher activation in response
to maternal odor than a control (Aoyama et al., 2010), withthe other finding either a slight increase in 1[HbO2] or nochange at all (Bartocci et al., 2000). Findings are summarized in
Figure 8.

Frontiers in Behavioral Neuroscience

This contradiction may be due to age differences of theexperimental population, with Aoyama et al. (2010) opting touse infants with a mean age of 5 days ± 1.8, compared to 48 h
± 10.1 in Bartocci et al. (2000). fNIRS optode coverage ranged
from 1 to 8 channel configurations. Only one paper adopted asingle channel device (Bartocci et al., 2000). Both Bartocci et al.
(2001) and Muelbert et al. (2021) utilized Hamamatsu Photonics
dual channel oxygenation monitors. An example of an infant
fNIRS configuration can be seen in Figure 9a, in the study byFrie et al. (2017).

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FIGURE 3

Indicating the numbers of studies which used each brand of device.

processing systems. The atypical populations included thosewith autism spectrum disorders (ASD) (Xu et al., 2020), combat
related PTSD (Gramlich et al., 2017), Alzheimer’s Disease
and mild cognitive impairment in the elderly (Kim et al.,2022), dysosmia (Kobayashi et al., 2009), multiple chemicalsensitivity (MCI) (Azuma et al., 2016), and ADHD in children
and adults (Schecklmann et al., 2011a,b). There has also beeninterest olfactory changes due to COVID-19 contraction (Hoet al., 2021). Methods of odor delivery varied between studies,with 50% of papers opting for passive inhalation such as“Sniffin’ Sticks,” and the remaining using pulse ejection systems
or olfactometers.
All eight odor studies reported 1[HbO2]. Five studies
observed increased activity in the presence of an odor, however,this activity was significantly lower than activity observedin control participants. Using individuals with MCI, Azuma
et al. (2016) reported a significantly higher response to
low intensity household products when compared to control
participants, indicating heightened perception. Three studies
also reported 1[HHb].
Only one paper opted to report all three parameters,
however, did not find any significant differences in activity inresponse to odor in any parameter (Kobayashi et al., 2009).
Figure 10 shows a breakdown of parameter results. The fNIRS
optode coverage for these odor studies ranged from 7 to
52 channel configurations. Figure 9b demonstrates an optodeconfiguration for a study using persons on the autism spectrum(Xu et al., 2020). Optode coverage mostly inspected the PFC,
OFC, and some in temporal regions.
No papers mentioned the use of short-channels or extra
systemic measurements. One study utilized the mobile NIRx
device, NIRScout-88 (Gramlich et al., 2017). Behavioral data

FIGURE 4

Percentage of papers reporting each fNIRS parameter.

Atypical population studies
Eight studies investigated odor effects using atypical
populations, the majority of which investigating features suchas olfactory perception, discrimination and identification in
populations with underdeveloped, altered or damaged olfactory

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FIGURE 5

Indicates the average number of channels used per year between 2000 and 2022, excluding studies that did not provide channel number
information. Wearable system channel numbers are shown in orange, and indicated recent favor toward wearable systems from 2017 onwards.

was collected from various tasks and questionnaires, suchas the Somato-Sensory Amplification Scale (Azuma et al.,2016), Wechsler Intelligence Scale for Children, Wechsler Adult
Intelligence Scale, sensory profiles, olfactory measurement andChildhood Autism Rating Scale (Xu et al., 2020), odor andaudio hedonic and intensity ratings (Gramlich et al., 2017),
impulsivity, depression and intelligence scales (Schecklmann
et al., 2011a), and visual analog scales for valence and intensityof odor (Schecklmann et al., 2011b).

Healthy population studies
Studies involving healthy adult populations and odorantstimuli account for 35 studies of the 49 found, one of which
utilizes EEG with fNIRS (Invitto et al., 2019). Odor delivery
methods varied greatly between studies. Three studies opted
for olfactometer odor delivery (Kokan et al., 2011; Huckeet al., 2018; Invitto et al., 2019). Most studies opted for odor
containers, such as bottles (Saito-Iizumi et al., 2013; Maharjan
et al., 2019; Moein et al., 2020; Chen et al., 2021; Yamashita
et al., 2022), test tubes (Fladby et al., 2004), odor filled bags
(Igarashi et al., 2014; Ikei et al., 2015), climate controlled
room (Figures 11a,b) (Song et al., 2019) and pressure containers(Figure 11c) (Jo et al., 2013). Jo et al. (2013) incorporated
naturally found stimuli, e.g. fresh flower petals, collectedon the day of testing as a stimulus, allowing the odor todiffuse into the air within a pressure container. Five studies

Frontiers in Behavioral Neuroscience

FIGURE 6

Optode coverage of PFC, temporal, parietal and occipital areasin 49 studies found.

implemented odor delivery mechanisms aiming to diffuse odor
into the environment around the participant, including below
the participants nose with the use of a wearable odor tray
(Onuma and Sakai, 2018; Song et al., 2019; Tomono andTomono, 2020; Kaimal et al., 2021; Tomono et al., 2021).

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FIGURE 7(a) Shows an example of a typical increase in HbO2 concentration (blue line) in response to odour, (b) a typical infant response to odour, (c) and(d) show a typical decrease in HbO2 in response to odour. Figures adapted from: (a) Harada et al. (2006), (b) Frie et al. (2017), (c) Song et al.
(2019), and (d) Eto et al. (2014).

use a fragrances liquid, rose water, as a stimuli (Moss et al.,2018). A significant proportion of studies incorporated odor in
an in-context paradigm, e.g., foot massage using essential oils
(Eto et al., 2014, 2015, 2016), presentation with or in food or
drink (Matsumoto et al., 2012; Onuma et al., 2018; Rajagoplan,
2018; Mitsukura et al., 2021), chewing gum (Hasegawa et al.,2013), incense (Fujii et al., 2007), and household spray (Tanida
et al., 2008). One study aimed to develop a novel odor delivery
system. ReminiScentia, developed by Casillas-Figueroa et al.
(2020) dispenses an odor selected by the participant during
the task, by using the digital interface. The device was used
to run odor based paradigms, such as scent-guided navigation,by presenting odor from different directions to influence task
choices. Only one study did not directly involve odor exposure,but instead induced the perception of odor by other means.
Takakura et al. (2011) induced the presence of garlic odor on
participants via the injection of intravenous thiamine propyldisulphide, which is known to induce this effect unintentionally.
Some studies utilized tasks, e.g., perception, face rating, within

One of these studies, Tomono and Tomono (2020) expelled
odor vapor via a airflow generator toward the participant,whilst also measuring odor concentration produced to checkodor concentration consistency (Figure 11d). Unlike the atypicalresearch presented previously, the odor delivery mechanism,
Sniffin Sticks, was not used in studies involving healthy adult
populations. A similar instrument, known as the Snap and Sniff
Olfactory Test System, utilizes pen-like odor delivery devices,and was used in one study investigating olfactory improvement(Maharjan et al., 2018). Three studies utilized simple smelling
strips to investigate the effect of essential oils on brain activity,
as well as other unpleasant and pleasant odors such as isovalericacid and strawberry, respectively (Ishimaru et al., 2004; Haradaet al., 2006; Kunihiro et al., 2017). Two studies opted to use
odors on material substances such as t-shirts and odor pads
(Nishitani et al., 2014; Onuma et al., 2018). The cotton pads usedin Onuma et al. (2018) were soaked in soy-sauce odor and placed
out-of-sight within cups containing taste stimuli, to investigate
the influence of odor on taste perception. One study opted to

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FIGURE 8

Vertical axis shows the percentage of infant studies thatreported each parameter. Horizontal axis shows the percentageof papers within each parameter [HbO2 , HHb, and HbTotal(HbT)] reporting an increase, decrease or no change in activity inresponse to an odor, for infant studies only. For example, allpapers reported HbO2 , however, only 66.7% observed anincrease in HbO2, illustrated by an upwards arrow. Downwards
arrows indicate a decrease in parameter concentration, and ahorizontal line depicts no change in parameter concentration.

FIGURE 9

Depicts the fNIRS optode arrangements for 4 studies. (a)conﬁguration used to image full-term and pre-term infants in
response to maternal odours, targeting the primary olfactorycortex, found between the orbitofrontal cortex and piriform
cortex. (b) in the study of individuals with covid-19 induced
olfactory impairments, PFC and temporal coverage was utilised(Ho et al., 2021). (c) in a study of healthy participants, bilateralcoverage was implemented (Hucke et al., 2018). (d) a small
16-channel wearable system observed PFC activity in response
to food odours whilst watching food related videos Tomono
et al. (2021). Figures adapted from: (a) Frie et al. (2017), (b) Ho
et al. (2021), (c) Hucke et al. (2018), (d) Tomono et al. (2021).

the odor paradigm (Onuma and Sakai, 2018; Onuma et al.,2018; Rajagoplan, 2018; Invitto et al., 2019; Moein et al., 2020).
Another study investigated the effect of crossmodal haptic andolfactory stimulation combination with a paradigm involving
3D models (Invitto et al., 2019). Yamashita et al. (2022) alsoutilized a combinatory study, with visual light displays as wellas odor. Mitsukura et al. (2021) employed a cognitive typing
task prior to and after olive oil consumption. Similarly, Tanida
et al. (2008) tested mental arithmetic prior to and after exposing
participants to a floral fragrance for 4weeks. Virtual reality was
implemented in one study with and without a relaxant fragrance
to the influence of odor on creativity and the ability to free-draw(Kaimal et al., 2021). This study can be seen in Figure 11e.
Four studies analyzed both 1[HbO2] and 1[HHb] withvarying results. One study found decreased activity in response
to odor (Moein et al., 2020), increased 1[HbO2] and decreased
1[HHb] (Fladby et al., 2004; Saito-Iizumi et al., 2013) andincreased 1[HbO2] with no change in 1[HHb] (Invitto
et al., 2019). Three other studies reported findings for all
three parameters, finding increased 1[HbO2], 1[HbT], anddecreased 1[HHb] (Hasegawa et al., 2013; Eto et al., 2014)
and no significant effect of fragrance for all parameters (Mosset al., 2018). The vast majority of studies reported and analyzed
1[HbO2] only. Eleven studies observed increased 1[HbO2] inresponse to odor stimulus, however this was odor dependent.
For example, Ylang ylang odor increased 1[HbO2], however,within the same study, Lavender odor decreased 1[HbO2](Kunihiro et al., 2017). 1[HbO2] change was found to also
be dependent.
Nishitani et al. (2014) observed increased 1[HbO2] inmothers in response to infant odor, a finding which was not
replicated in non-mothers. Seven studies observed significant
decreases in 1[HbO2] in response to various odors, e.g., relaxing
essential oil odors during a massage (Eto et al., 2015, 2016), olive

Frontiers in Behavioral Neuroscience

FIGURE 10

Figure depicts number of papers reporting 1[HbO2], 1[HbT],and 1[HHb] (vertical axis) for atypical studies only. The
percentage of papers reporting each response (horizontal axes)
is denoted by arrows, e.g., upwards indicates increase inconcentration. A number of studies included here did observe
increased activity in response to odor in atypical populations,however, this response was signiﬁcantly diminished compared
to controls.

oil odor (Mitsukura et al., 2021), forest odor (Song et al., 2019),
Hinoki oil (Ikei et al., 2015), rose and orange oil (Igarashi et al.,2014), and floral spray (Tanida et al., 2008). It is important tonote that some studies observed no significant effect of odor
on cerebral hemodynamics (Maharjan et al., 2018; Onuma andSakai, 2018; Kaimal et al., 2021; Tomono et al., 2021). Two

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FIGURE 11

Depicts fNIRS task set-ups for four studies, two include viewing videos, one using virtual reality. Figures adapted from: (a,b) Song et al. (2019), (c)Jo et al. (2013), (d) Tomono et al. (2021), and (e) Kaimal et al. (2021).

Tomono, 2020; Tomono et al., 2021), and muscle movement
via electromyogram (Hasegawa et al., 2013). Most studies
included some element of behavioral data collection. Two usedsemantic differential methods to determine thoughts on theodor stimuli presented (Jo et al., 2013; Song et al., 2019). Somestudies included questionnaires relating to perceptions of odors,
utilizing visual analog scales and ratings of saltiness, sweetness,
comfort and relaxation, as well as the Profile of Mood Statesquestionnaire. The Standard Trait Anxiety Index to measuretransient stress levels was used in Tanida et al. (2008) to measurestress during a cognitive task, before and after a 4 week period offragrance exposure.

studies reported 1[HbT] only (Fujii et al., 2007; Kokan et al.,2011). A summary of all parameter results can be seen in
Figure 11.
Only three studies mentioned the use of multi-distance
optode configurations in the experimental paradigm, however,details regarding the short-channels were unclear (Kokan
et al., 2011; Maharjan et al., 2019; Song et al., 2019). All
studies but one (Bartocci et al., 2000) incorporated at least
two channels within the multi-channel configurations. Two
examples of fNIRS device used in healthy participant studies
can be seen in Figures 9c and d, one of which being a 16channel wearable system (Tomono et al., 2021). In total, fourof the healthy population studies utilized wearable devices,e.g., HOT-1000 by Neu Systems Inc for a study involving
consumption of green tea (Rajagoplan, 2018), Pocket NIRS Duo,
DynaSense, Hamamatsu to investigate essential oils (Kunihiro
et al., 2017), WOT-100 NeU Corporation for investigatingodor effect whilst watching food related videos (Tomono et al.,2021) and fNIRS Hb133, Astem Co., Ltd. to observe effectsof odor and light on activity (Yamashita et al., 2022). Not
all studies utilized physiological monitoring along with fNIRS.
Only eight studies included systemic measurements in theirinvestigations, including heart rate and heart rate variability(Tanida et al., 2008; Jo et al., 2013; Igarashi et al., 2014;
Ikei et al., 2015; Song et al., 2019; Tomono et al., 2021),
respiration rate, blood pressure (Jo et al., 2013), facial skintemperature (Tanida et al., 2008), saliva flow (Tomono andFrontiers in Behavioral Neuroscience

Discussion
Interpreting studies involving fNIRS andolfaction
To our knowledge, this is the first systematic review
collating odor based fNIRS research. The results of this search
produced 49 papers, information from which has been extracted
and discussed above. This review briefly introduces fNIRS
experimental paradigms used for studies involving odor, forexample, the odor detection, identification and evaluation
methodologies used in atypical studies, effect of odor on corticalactivity in passive paradigms, as well as during cognitive

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and discrimination ability was significantly reduced as theseverity cognitive impairment increased, as measured by abattery of cognitive function tests. Similarly to other fNIRS
studies involving infants, the results have found differencesin response to odors between infants of different ages, evenin the case of the same odor type being used, highlighting
the importance of considering participant age carefully whenrecruiting from infant populations. No significant differences
between ages of adult populations were reported in the papers.
The odor differences between males and females has been
investigated in recent years, finding increased sensitivity tosmells in females than males (Sorokowski et al., 2019). Within
this review, differences have also been found in corticalactivity between males and females. Multiple studies observed
significant interactions of fragrance with gender, predominantly
indicating lower activity in response to an odor in females
than in males, in both adults and infants (Eto et al., 2016;
Frie et al., 2019; Kaimal et al., 2021; Muelbert et al., 2021).
Interestingly, differences within a gender were also found when
exposed to certain odor stimuli. Nishitani et al. (2014) observed
significantly higher activity in women who were mothers, than
women who were not, in response to infant odor on t-shirts.
These subtle, but significant differences between participants
should be kept in mind during the recruitment process andexperiment design phase.
One significant limitation of the majority of odor based
studies is the population size used. Interestingly, infant andatypical population studies involved generally larger population
sizes compared to research using healthy populations, withan average population size of 32 and 37 participants per
study, respectively. On average, healthy studies only used
17 participants per study. To increase generalizability andreliability, studies should consider incorporating significantly
larger sample sizes. Due to the highly personal and emotional
nature of odor, larger sample sizes will also reduce the effectof individual differences in age, gender, past experiences
and odor hedonics on subsequent results. Odor hedonic
perception is an umbrella term encompassing the pleasant orunpleasant character of an odor, known as hedonic valence,and liking toward said odor. Collecting such information
during recruitment or experiment can allow variations between
groups with different hedonic characteristics to be determined.
Additionally, during the recruitment period, screening
participants for olfactory dysfunction should be considered,as underlying or unknown olfactory deficiencies or deviations
from normal function have the potential to skew results. The
majority of atypical studies in this review have used various tests
to do this, whilst most studies involving healthy populations
have not done so. Multiple olfactory function techniques havebeen discussed in this review, including the methodology
implemented by Azuma et al. (2016), wherein odor detection
and recognition were assessed using an olfactometer forindividuals with heightened olfactory sensitivity. Presented at

FIGURE 12

Figure depicts number of papers reporting 1[HbO2], 1[HbT],and 1[HHb] (vertical axis) for typical studies only. Note thatsome studies did not report ﬁndings.

performance tasks. Despite the varied experimental paradigms,
population groups and stimuli, overall there appears to besome agreement between studies. For example, odor studies
used different odor delivery methods, however, most opted for
passive inhalation paradigms, e.g., diffusion, within containers
such as bottles and test tubes, smelling strips, and scented
cotton pads. Only a few studies opted to use olfactometers,
perhaps due to ecological invalidity. Generally, in the presenceof odor, a significant effect on activity can be found, however
the direction of this effect varies depending on factors suchas participant type, odor family and concentration. The use ofmultichannel configurations in almost all studies can confirm
that the presentation of an odor elicits a change in activity,
most often an increase in HbO2 concentration, in specificregions such as the orbitofrontal cortex. This is in line withthe understanding that the orbital cortex receives direct axonal
connections from the primary olfactory cortex (Chen et al.,2021).

Population differences and size
Differences between population types can also be identified
using fNIRS and odor. In cases of atypical populations,diminished activity was seen in atypical populations in
response to odor compared to controls, suggesting altered odor
processing in atypical populations. In the case of Kim et al.
(2022), the possibility of using fNIRS and odor as a combinatory
diagnostic tool was explored, based on the understanding that
discrimination between odors is significantly diminished inpersons with cognitive impairment or Alzheimer’s disease. The
method was found to be an effective measure of decline insuspected impaired participants, as odor induced oxygenation

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increasing concentrations, the detection threshold is determinedas the point at which the participant notices the scent, but does
not recognize. Identification of the odor is labeled as therecognition threshold. The averaging of information from thistest gives researchers an indication of olfactory acuity for eachparticipant. Other testing measures include the University ofPennsylvania Smell Identification Test (UPSIT), a commerciallyavailable olfactory function test. This test comes in the formof a booklet, with scratchable strips containing odor alongside
related multiple choice questions. The UPSIT is commonlyused in studies involving Parkinson’s disease and Alzheimer’s,
however, in this review, it was used to test for and recruit
Normosmic participants (Moein et al., 2020). It is important
to note that there are various versions of this test available foruse with different geographic demographics, including versions
for Britain, France, Italy, Korea, and China. One potential
drawback of the current cohort of research in fNIRS and odor isthe large portion of participants belonging to the same or similar
participant demographics in East Asia (Figure 13). Currently,
no research was found investigating odor in South Asian
regions, despite the known long history with odor in relaxation
practices. Additionally, no research has been using participantsfrom Africa or South America, both vast and culturally diverse
regions, with different odor palettes depending on environment,
lifestyle and food.

to different odor classes and families. Each family can evoke
unique responses in both brain and behavior. Some fragrances
are able to increase activity and invigorate mental state, suchas peppermint or rosemary, whereas others have more sedativeand calming effects like lavender and chamomile. The odor
chosen for each study can therefore dramatically impact the
hemodynamics measured. Additionally, individual preference
toward each odor may also contribute to the diverse 1[HbO2],
1[HHb], and 1[HbT] results shown in this search. This should
be taken into consideration when interpreting fNIRS data fromthese studies. A few papers did address the differences between
odors rather than vs. control substances, however, currently
there does not seem to be enough odor based fNIRS studies tobe able to group papers by odor family for wider interpretation.
Additionally, no mention was made by any papers regarding
specific odor families used, any underlying known effects, orthe specific reasons why odors were selected. This may indicate
a limited understanding of odors or fragrances selected. Moreresearch involving specific odor families would be beneficial inthis field, not only for industry and marketing benefits, but also
for the collective improvement of general wellbeing.
Essential oils have been found to have significant effects
on brain activity, as well as behavior and mood, however,
only a few studies utilized essential oils with fNIRS. Threestudies utilized a blend of Lavendula angustifolia, tea tree,
Ravensara, Palmarosa, and chamomile essential oils (Eto et al.,2014, 2015, 2016). Three studies utilized the essential oils ofnative trees and plants in the regions, such as in Japan withthe use of cypress tree and Yomogi essential oil in studies
relating to the effect of Cypress oil on forest related visual
stimuli (Ikei et al., 2015; Song et al., 2019) the interaction
between colored light and odor (Yamashita et al., 2022) andthe stress relieving effects of Yomogi oil (Kunihiro et al., 2017).
One further study utilized a blend of essential oils; lavender,orange, juniper berry, patchouli and Ylang ylang (Kaimal et al.,2021). This particular study investigated the effect of thevarious fragrances mentioned on rote tracing and creative selfexpression using a virtual reality device. Although no significant
effect of fragrance was found in this case, differences in genderand age of the 16 participants in response to fragrance werenoted. This indicates that more research is needed using larger
population sizes to determine the hemodynamic effects ofessential oils and aromatherapy with fNIRS. Wearable fNIRS
systems should be utilized to a greater extent within such studies
to alleviate restriction further, broadening the scope of odor
related contextual research.

Odor types

Study design

Another contributor toward the varied results producedis the varying responses elicited between odors, causing theinterpretation of cerebral responses of odors in fNIRS studies
to be complicated. As mentioned previously, odors can belong

The most common fNIRS odor paradigm involved passive
inhalation whilst in a seated and comfortable position(Bartocci et al., 2000, 2001; Fladby et al., 2004; Ishimaru et al.,
2004; Harada et al., 2006; Kobayashi et al., 2009; Aoyama

FIGURE 13

A graphical representation of country contributions toward odor
based fNIRS studies, generated from the data in Table 1. The ﬁrst
author and affiliation for each study was used to create thisgraph. Darker blue shades indicate a higher number of papers
generated from a region. Purple shades indicate no fNIRS odor
papers. From this ﬁgure it can be seen that a signiﬁcant portionof fNIRS odor studies are conducted in Japan.

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photoelectrical sensor (Tanida et al., 2008), and pulse oximetryby Hewlett-Packard, Germany (Bartocci et al., 2001). Jo et al.
(2013) measured heart rate, as well as blood pressure and heart
rate variability using a finometer device and electrocardiogram,
AC-301A; GMS Corp., Japan. Heart rate variability gives anindication of variations in heart rate rhythm. Any changes
observed in heart rate can be due to changes in mental andemotional state.
Another measure utilized by one study in the review
observed pupil dilation. Pupillary diameter can be used as ameasure of participant mental state, able to reflect behaviors
such as level of interest. Used in a paradigm involving
food videos, the eye recorder EMR ACTUS by nac Image
Technology Corporation was used by Tomono et al. (2021) tomonitor participant pupil dilation and line-of-sight. Generally,
individuals tend to look toward an object or person ofparticular interest, which can give an indication of a particularsubjects preferences.
Interestingly, no studies utilized galvanic skin response(GSR) as a measure of relaxation or stress. The GSR signal isa direct measure of the action of sympathetic nerves on thesweat glands of the skin. An increase in arousal, due to fear,
joy or stress causes the heightened activity of sweat glands.
The increased production of sweat on the surface of the skinelevates electrical conductivity, which in turn can be detected
GSR monitors. Due to the nature of arousal, the exact identityof the emotion experienced cannot be determined from galvanic
skin response alone, only the presence and intensity of it.
The incorporation of extra physiological measures such as
facial sebum secretion, cortisol testing, blood pressure and eye
tracking, galvanic skin response, and dilation should be usedin future studies aiming to investigate the influence of odor on
mental state and behavior.

et al., 2010; Frie et al., 2017, 2019; Hucke et al., 2018; CasillasFigueroa et al., 2020; Ho et al., 2021). Some studies also utilized
questionnaires during or after the fNIRS recording phase tomeasure odor stimuli hedonic value and intensity for each odor
presented (Kokan et al., 2011; Jo et al., 2013; Nishitani et al.,2014; Azuma et al., 2016; Gramlich et al., 2017; Kunihiro et al.,2017; Chen et al., 2021; Tomono et al., 2021). A few studies
implemented tasks requiring the participant to identify the
moment of odor detection and recognition during testing, either
verbally, or using a button (Kokan et al., 2011; Moein et al., 2020;
Xu et al., 2020). Other studies used olfactory function tests as
the basis for odor stimuli implementation (Schecklmann et al.,2011a,b; Azuma et al., 2016; Kim et al., 2022). Multiple studies
employed food or drink as a means to introduce odor stimuli(Matsumoto et al., 2012; Hasegawa et al., 2013; Onuma et al.,2018; Rajagoplan, 2018; Tomono and Tomono, 2020; Mitsukura
et al., 2021; Muelbert et al., 2021; Tomono et al., 2021).
Overall, most studies utilized block design paradigms to
implement odor stimuli. Odor stimuli presentation durations
varied greatly between studies, however, most opted to add
sufficient lengths of rest between odor stimuli to reduce carryover effects. Rest periods were most often between 20 and 40 s
long, with odor stimuli periods most commonly between 10 and
30 s. Odor stimuli repeats and block designs were not always
included, particularly in cases where odors were diffused into thetesting environment over time rather than delivered on various
materials (Onuma and Sakai, 2018; Song et al., 2019; Kaimal
et al., 2021) or in infant studies. One study of import used alongitudinal design, testing cognitive performance before andafter a 4 week fragrance intervention using a floral spray (Tanida
et al., 2008). One study utilized a climate controlled cubicle,
displaying images of Hinoki cypress trees with and without
Hinoki essential oil (Song et al., 2019). Although this method
did find significantly reduced HbO2 in the trial with Hinoki oil,
it would be interesting to replicate some aspects of this study
within a natural Hinoki tree environment during a peacefulforest walking paradigm.

Regions of interest
The olfactory bulb and deeper associated olfactory
structures, such as the amygdala, are not within reach of fNIRS
devices, however, other brain regions can be influenced by odor
stimuli, and are penetrable by fNIRS. Studies in this review
designed configurations to predominantly cover the prefrontal
cortex (PFC), which is known to be structurally connectedto the olfactory pathway (Yamaguchi, 2017). Many studies inthis review observed significant changes in PFC activation in
response to an odor.
Tanida et al. (2008) observed significantly decreased HbO2
after a 4 week fragrance intervention, indicating the connection
between the PFC and the effect of fragrances on stress. The
orbitofrontal cortex (OFC), temporal and parietal areas werealso favored. The OFC is associated with odor perception andidentification, whilst the temporal region, involved with some
aspects of olfactory memory, is often imaged to capture olfactory

Physiological measurements
Tanida et al. (2008) also utilized facial sebum secretionmeasures as an indicator of stress levels, finding decreased
sebum production after 4 weeks of floral fragrance exposurecompared to controls. Kunihiro et al. (2017) tested salivary αamylase before and after inhalation of Yomogi essential oil. αamylase is a strong indicator of stress levels, and in this case, wasfound to be lower in participants inhaling Yomogi oil than incontrols, although not significant.
Some studies included additional measures of heart rate,
breathing rate and oxygen saturation using external devices
such as the Radical 7 (Masimo) and GE DASH-4000 monitor(GE Healthcare) (Frie et al., 2017) the Tsuyama MGF KK,

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FIGURE 14

Summarized preprocessing and analysis pipeline for odor based fNIRS data, generated from papers in Table 1. It depicts commonly usedfunctions and processes when handling fNIRS data.

2019). If optode space is available, future studies should aim toutilize short channels in the experimental design.

cortex and parotid gland activity (Savage et al., 2002). The
olfactory pathway is also closely linked to regulatory areas
within the brain associated with emotion, memory, and learning.
This interconnectivity allows for a multitude of paradigms
and channel configurations to be applicable to fNIRS andodor studies.

Wearable fNIRS
Despite having limited penetration depth and spatial
resolution when compared to fMRI, fNIRS has the advantage ofartifact resistance and portability, creating immense scope for
future odor based research. Using lightweight, wearable fNIRS
devices, such as those used by Gramlich et al. (2017), Kunihiro
et al. (2017), Rajagoplan (2018), Tomono et al. (2021), andYamashita et al. (2022), experimental paradigms can be designed
to take place in the context of particular smells, e.g., in a forest,
car or a perfume store, heightening applicability of subsequentfindings, and allowing participant to have more natural andunregulated responses to stimuli. To support a more eventrelated paradigm, analysis methods such as AIDE, Automatic
IDentification of functional Events, have been developed, andcan be used in the place of conventional analysis (Pinti et al.,2017).

Channel conﬁguration andmulti-distance channels
The use of multichannel configurations provides more brain
coverage and increases the ability to localize induced activity.
Almost all studies in this review opted to use multichannel
probe designs, with only one study using a one channel design(Bartocci et al., 2000).
In addition to multichannel configurations, studies may
make use of multi-distance channel configurations. Using
various source-detector distances allows the probing of various
depths of the human head. At present, the optimal sourcedetector distance 30 mm. This distance allows the interrogationof the cortical areas of the brain. Shorter distance separations canbe utilized to record scalp hemodynamics, which can interferewith measurements of cortical areas. Using short channels,
scalp hemodynamics can be removed from the measured fNIRS
data, with the intention of the remaining data being corticalactivations only. This technique also improves the signal to noise
ratio (SNR) of the data. This regression technique is becoming
increasingly common in fNIRS research, however, only one
study included in this literature review mentioned the use of an
fNIRS device with multi-distance channel capabilities. Although
short channels were mentioned, no information regarding
their implementation or regression was provided in the data
preprocessing or analysis segments of the paper (Maharjan et al.,Frontiers in Behavioral Neuroscience

Pre-processing and analysis
As with the experimental paradigms and findings described
previously, preprocessing and analysis methods also differ
greatly between papers. Note that all studies pre-processed
fNIRS data, but not all reported the pre-processing steps applied.
Where reported, fNIRS data was filtered to remove systemic andequipment interferences, such as heart rate and breathing rate.
The low-pass and high-pass filter values varied greatly between
studies. To remove signal drift and slow oscillations, the studies
reported here use low pass, high pass, and band pass filters toremove both high and low frequency noise and artifacts. The

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parameters used for these filters are dependent on study design,
therefore block length should be considered before deciding
this. One papers used a Finite Impulse Response filter (Kaimal
et al., 2021). For signal smoothing, multiple studies implemented
a moving average smoothing technique which removed shortterm artifacts from the data (Schecklmann et al., 2011a,b; Etoet al., 2014; Frie et al., 2017, 2019; Ho et al., 2021). Other
artifact identification, removal or correction techniques include
using the MARA correction algorithm, Correlation based signal
improvement (CBSI), visual inspection and epoch removal,
removal with Principle Components Analysis, correction withlinear interpolation, and spline interpolation.
Prior to statistical analysis, it is often standard practice
to average time-series data between specified time windows
of interest. The windows vary depending on task paradigm,
however a common occurrence is to average data before andafter odor stimulus onset. Frie et al. (2019) and Onuma andSakai (2018) use an analysis window of 10 s prior to and 20 post
stimulus onset. Hucke et al. (2018) average multiple windows
of interest in intervals of 5 s following onset. Other common
methodologies involve averaging whole task blocks (Xu et al.,2020). Statistical analysis was conducted for all fNIRS data,
predominantly consisting of ANOVAs’, t-tests and correlation
analysis, e.g., Pearson’s correlation analysis. In instances of
non-parametric data, analysis was generally conducted using
Wilcoxon’s Test or the Friedman’s Test. One paper utilized
the General Linear Model to conduct analysis (Gramlich et al.,2017). Seven studies opted to use multiple corrections methods,
predominantly Bonferroni’s correction, with one using Tukey’s
and one using Dunnett’s methods. If additional corrections wereused, they were not stated in the articles. Future research should
aim to both use and report multiple corrections. Processing andstats are summarized in Figure 14.
This review highlights the relatively low presence of odor
fNIRS studies that exist in this field, but also the potential
and applicability of fNIRS to odor. The limited availabilityof research currently in this area may be due to a lack ofstandardized protocols with regards to odor stimuli, or the
wildly variable individual experiences with odors, which is
known to have an impact on both brain and behaviour. In
these instances, results may be analyzed in conjunction withquestionnaires rating hedonic fragrance properties such as“liking” or “dislike,” as has been done with some studies foundin this review.
With regards to standardized protocols, the results of thisreview suggest that passive and more natural inhalation ispreferred over the use of olfactometers. This in combination
with fNIRS, and in particular, wearable fNIRS devices, could
allow for a diverse range of in-context olfactory studies in the
future, e.g., fNIRS during a forest walk, whilst cooking, browsing
a perfume isle. Some research has been conducted using
behavioral measures and EEG to investigate odor properties,
providing a knowledge pool from which to carefully select odors

Frontiers in Behavioral Neurosciencebased on desired characteristics and expected responses. The
use of therapeutic essential oils such as Ylang ylang, Hinoki
cypress tree, lavender, and rose have been discussed in a few
papers, providing information regarding their odor properties,
however more can be done to develop this research area further
with fNIRS, including but not limited to significantly larger
population sizes and the inclusion of specifically chosen odors
based on known properties or odor families. Studies may wish
to investigate the properties of particular odors on sleep qualityand duration with portable fNIRS, as is being investigatedon a larger scale with EEG in recent years (Chandharakool
et al., 2020; Ko et al., 2021; Kwangjai et al., 2021). There ispotential here for invigorating odors to be used as a counterto fatigue and sleep onset during driving, to promote cognitive
performance under sleep deprived conditions, and for the
sleep delaying efficacy of specific odors to be tested using thisestablished paradigm. Similarly, the invigorating effects of someessential oils may be utilized in situations requiring enhanced
and prolonged attention, such as during study or in school.
The diversity of odor in daily life leads there to be many
avenues of study possible with the use of fNIRS, in particular,
wearable systems.

Conclusion
To finalize the results of this review, the presented studies
have been summarized to identify common characteristics andfindings between studies, in addition to areas to improvefor future odor research. In answer to the queries of thisarticle, due to the interconnectivity of odor within the brain,
fNIRS is able to measure cerebral changes in oxygenation in
response to odors despite having limited depth penetration.
The ability to use fNIRS in odor research rather than thestatic and costly alternative of fMRI, provides immense scopefor odor research in the future, which increases further withthe use of wearable fNIRS devices. The ability to move freely
and unconfined without risk of significant signal loss is aunique asset of fNIRS that has the potential to expand odor
research into a multifaceted and vibrant field, encompassing
elements of daily life that cannot be explored within laboratory
settings, or in confined paradigms involving fMRI or EEG.
The use of fNIRS in odor in wellbeing research is addressin some studies within this review. There is significant
potential here for odor, and in particular, essential oils, tobe used to promote wellbeing through sleep and relaxation.
The various paradigms presented here involving odor may
be adapted or replicated in the future to utilize specificessential oils and wearable fNIRS systems more effectively, withthe aim of increasing ecological validity. Short channels andphysiological measurements were not commonly used in thestudies presented, however, if available can provide an additional
method of removing physiological systemics in future studies

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and understanding the effects of odor further. In this particularfield, the strengths of this modality over its counterparts areevidently clear. With the continual development of new fNIRS
technologies as well as standardized protocols, the scope forstudy will only continue to increase, bringing the ambition of
improved odour understanding and general wellbeing for all
ever closer.

Imaging in Healthcare (i4health) (grant code EP/S021930/1),
and Givaudan UK Ltd.

Conﬂict of interest
Author GG was employed by the company Givaudan; AL
and EB were employed by the company Metabolight Ltd.; ITis full time employed at University College London, is thefounder of Metabolight Ltd. and a consultant to Givaudan; NG
is partially funded by EPSRC and Givaudan. The authors declarethat this study received funding from Givaudan. The funder only
had involvement during the conception of this literature review,and the decision to publish. The funder had no involvement
during data collection, analysis, interpretation or the writing of
this article.
The remaining authors declare that the research was
conducted in the absence of any commercial or financial
relationships that could be construed as a potential conflict ofinterest.

Data availability statement
The raw data supporting the conclusions of thisarticle will be made available by the authors, without
undue reservation.

Author contributions
NG, IT, and GG contributed to the conception of this work.
NG completed all data collection, analysis, and writing andediting. IT, GG, AL, and EB contributed toward manuscript
feedback and improvement. IT approved the submitted versionof the manuscript. All authors contributed to the article andapproved the submitted version.

Publisher’s noteAll claims expressed in this article are solely those of theauthors and do not necessarily represent those of their affiliatedorganizations, or those of the publisher, the editors and thereviewers. Any product that may be evaluated in this article, or
claim that may be made by its manufacturer, is not guaranteedor endorsed by the publisher.

Funding
This work was jointly supported by the EPSRC-funded
UCL Center for Doctoral Training in Intelligent, Integrated

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