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The neurophysiology of human touch and eye gaze and its effects on therapeutic relationships and healing: A scoping review

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Objective: The primary objective of this scoping review was to examine and map the range of neurophysiological impacts of human touch and eye gaze, and consider their potential relevance to the therapeutic relationship and to healing. Introduction: Clinicians, and many patients and their relatives, have no doubt as to the efficacy of a positive therapeutic relationship; however, much evidence is based on self-reporting by the patient or observation by the researcher. There has been little formal exploration into what is happening in the body to elicit efficacious reactions in patients. There is, however, a growing body of work on the neurophysiological impact of human interaction. Physical touch and face-to-face interaction are two central elements of this interaction that produce neurophysiological effects on the body. Inclusion criteria: This scoping review considered studies that included cognitively intact human subjects in any setting. This review investigated the neurophysiology of human interaction including touch and eye gaze. It considered studies that have examined, in a variety of settings, the neurophysiological impacts of touch and eye gaze. Quantitative studies were included as the aim was to examine objective measures of neurophysiological changes as a result of human touch and gaze. Methods: An extensive search of multiple databases was undertaken to identify published research in the English language with no date restriction. Data extraction was undertaken using an extraction tool developed specifically for the scoping review objectives. Results: The results of the review are presented in narrative form supported by tables and concept maps. Sixty-four studies were included and the majority were related to touch with various types of massage predominating. Only seven studies investigated gaze with three of these utilizing both touch and gaze. Interventions were delivered by a variety of providers including nurses, significant others and masseuses. The main neurophysiological measures were cortisol, oxytocin and noradrenaline. Conclusions: The aim of this review was to map the neurophysiological impact of human touch and gaze. Although our interest was in studies that might have implications for the therapeutic relationship, we accepted studies that explored phenomena outside of the context of a nurse-patient relationship. This allowed exploration of the boundary of what might be relevant in any therapeutic relationship. Indeed, only a small number of studies included in the review involved clinicians (all nurses) and patients. There was sufficient consistency in trends evident across many studies in regard to the beneficial impact of touch and eye gaze to warrant further investigation in the clinical setting. There is a balance between tightly controlled studies conducted in an artificial (laboratory) setting and/or using artificial stimuli and those of a more pragmatic nature that are contextually closer to the reality of providing nursing care. The latter should be encouraged.
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Neurophysiology of human touch and eye gaze in
therapeutic relationships and healing: a scoping review
Fiona Kerr
1,3, 4,5
Rick Wiechula
1,2
Rebecca Feo
1,2
Tim Schultz
1,2
Alison Kitson
1,2
1
Adelaide Nursing School, University of Adelaide, Adelaide, Australia,
2
Centre for Evidence-based Practice South Australia: a Joanna Briggs Institute
Centre of Excellence,
3
Faculty of the Professions, University of Adelaide, Adelaide, Australia,
4
The NeuroTech Institute Pty. Ltd., Adelaide, Australia,
and
5
South Australian Health and Medical Research Institute, Adelaide, Australia
ABSTRACT
Objective: The primary objective of this s coping review was to examine and map the range of neurophysiological impacts
of human touch and eye gaze, and consider their potential relevance to the therapeutic relationship and to healing.
Introduction: Clinicians, and many patients and their relatives, have no doubt as to the efficacy of a positive therapeutic
relationship; however, much evidence is based onself-reporting by the patient or observation by the researcher. There has
been little formal exploration into what is happening in the body to elicit efficacious reactions in patients. There is, however,
a growing body of work on the neurophysiological impact of human interaction. Physical touch and face-to-face
interaction are two central elements of this interaction that produce neurophysiological effects on the body.
Inclusion criteria: This scoping review considered studies that included cognitively intact human subjects in any
setting. This review investigated the neurophysiology of human interaction including touch and eye gaze. It
considered studies that have examined, in a variety of settings, the neurophysiological impacts of touch and eye
gaze. Quantitative studies were included as the aim was to examine objective measures of neurophysiological
changes as a result of human touch and gaze.
Methods: An extensive search of multiple databases was undertaken to identify published research in the English
language with no date restriction. Data extraction was undertaken using an extraction tool developed specifically for
the scoping review objectives.
Results: The results of the review are presented in narrative form supported by tables and concept maps. Sixty-four
studies were included and the majority were related to touch with various types of massage predominating. Only
seven studies investigated gaze with three of these utilizing both touch and gaze. Interventions were delivered by a
variety of providers including nurses, significant others and masseuses. The main neurophysiological measures were
cortisol, oxytocin and noradrenaline.
Conclusions: The aim of this review was to map the neurophysiological impact of human touch and gaze. Although
our interest was in studies that might have implications for the therapeutic relationship, we accepted studies that
explored phenomena outside of the context of a nurse-patient relationship. This allowed exploration of the
boundary of what might be relevant in any therapeutic relationship. Indeed, only a small number of studies included
in the review involved clinicians (all nurses) and patients. There was sufficient consistency in trends evident across
many studies in regard to the beneficial impact of touch and eye gaze to warrant further investigation in the clinical
setting. There is a balance between tightly controlled studies conducted in an artificial (laboratory) setting and/or
using artificial stimuli and those of a more pragmatic nature that are contextually closer to the reality of providing
nursing care. The latter should be encouraged.
Keywords Gaze; healing; neurophysiological; therapeutic relationship; touch
JBI Database System Rev Implement Rep 2019; 17(2):209 247.
Correspondence: Fiona Kerr, fiona.kerr@adelaide.edu.au
Conflict of interest: Author RW is an associate editor of the JBI Database of Systematic Reviews and Implementation Reports.
This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0
(CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way
or used commercially without permission from the journal.
DOI: 10.11124/JBISRIR-2017-003549
JBI Database of Systematic Reviews and Implementation Reports COPYRIGHT ß2018 THE AUTHORS. PUBLISHED BY 209
WOLTERS KLUWER HEALTH, INC. ON BEHALF OF THE JOANNA BRIGGS INSTITUTE.
SYSTEMATIC REVIEW
Introduction
The purpose of the review was to examine the
connection between two distinct research fields.
The first field is aligned to the social sciences and
examines the importance of human interaction and
positive therapeutic relationships for healing and the
delivery of fundamental care.
1
The second research
field is aligned to the natural sciences, and inves-
tigates the neurophysiological impact of touch and
eye gaze during human interaction. Although arising
from different research domains, both bodies of
work are strongly connected, with touch and gaze
being key elements of human interaction that have
the potential to influence therapeutic relationships,
healing and patients’ experiences of fundamental
care delivery. The connection of these bodies of
work is further emphasized by the shared variables
of trust and positivity as relevant mediators of the
impact of human interaction.
Fundamental care refers to the essential elements
of care that every patient requires regardless of their
clinical condition or the setting in which they are
receiving care. These elements of care can be physical
(e.g. nutrition, hydration, elimination and hygiene),
psychosocial (e.g. respect, dignity, privacy and cul-
tural safety) or relational in nature (e.g. empathy and
compassion).
1
Given the growing evidence that these
fundamentals are being poorly executed globally,
there is increasing emphasis on how they can best
be delivered in clinical practice.
2-10
Research is
beginning to acknowledge that a positive, trusting
nurse-patient relationship is integral to the delivery
of high-quality, person-centered fundamental
care.
1,11
However, the specific neurophysiological
mechanisms through which this positive relationship
impacts patient care and experiences is largely
unknown and unexplored.
In addition to work on fundamental care, there is
a large body of work on the importance of an
empathic, therapeutic relationship for healing,
patient health, resilience and hope.
12-14
This thera-
peutic relationship might involve multiple ‘‘actors’’,
given that patients can interact with multiple health
professionals in any healthcare episode. Specific
studies focusing on the therapeutic relationship
include studies on connectedness,
15
social influences
on healing and stress,
16,17
meta-analyses of noncon-
tact healing studies
18
and reviews of the effect
of interpersonal touch on patients
19,20
and specific
cells.
21
There are also studies and literature reviews on
the role of trust in health professional (particularly
nurse)-patient relationships
22,23
and the impact of
increasing technological interaction on this thera-
peutic relationship.
24,25
These studies demonstrate
the increased capacity for hope displayed by the
patient when there is a high trust relationship and
personal interaction between the patient and nurse/
medical practitioner.
26,27
The observed interactions
and interconnections that are considered to be rele-
vant for improving the healing capacity of patients in
these circumstances include the display of genuine
empathy, compassion, direct eye contact and physi-
cal touch.
Whilst clinicians, and many patients and relatives,
are in no doubt as to the efficacy of a positive
therapeutic relationship, much evidence is based
on self-reporting by the patient or observation by
the researcher.
23,24
There is, however, a growing
body of work on the neurophysiological impact of
human interaction. Physical touch and face-to-face
interaction, entailing eye gaze and retinal eye lock,
are two types of contact that produce neurophysio-
logical effects on the body.
20,28,29
There are a growing number of studies investigat-
ing the neurophysiological impact of physical touch.
Such studies have examined the cortical dynamics of
both discriminative (discrimination of stimuli) and
affective (pleasant, gentle stroking) touch,
30-34
and
the way in which the brain registers (codes) affective
touch.
35-38
The neurophysiological response to
touch includes the release of specific chemicals
and neurotransmitters that lead to neuroendocrine
effects; vagal stimulation; reduction of stress,
pain and depression; and enhancement of immu-
nity.
20,39-42
Affective touch also appears to lessen
allostatic load (i.e. stress) in critically ill patients,
20
due to the positive effects on pathophysiological
processes aggravated by stress, such as immune
and neuroendocrine derangements and inflamma-
tion.
28,39
There is recent evidence of an interoceptive
effect of affective touch that aids rehabilitation
through alterations to the insular cortex and limbic
system.
43
Affective touch is transmitted primarily through
stimulation of the nerve’s unmyelinated C-fibers, the
impact of which is beneficial to healing.
29
Affective
touch is represented in areas of the brain that are
closely related to the perception of emotion and
empathy, and this affective-emotional pathway runs
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in part through the spinomesencephalic tract, engag-
ing the amygdala, insula and anterior cingulate cor-
tex.
29
Resultant neurophysiological reactions can
mediate the perception of touch, and are shown to
be beneficial to the healing process, as well as having
a positive effect on a patient’s capacity for pain
management
29,44
and a number of physiological
outcomes, including changes to autonomic innerva-
tion through repetition of affective stimulation.
20
One of the most powerful human interactions is
face-to-face contact involving eye gaze. The interac-
tion between trusted individuals creates a neural
duet between brains due to the reciprocal firing of
the brain’s social networking areas, with a powerful
effect on the level of trust and empathy as well as a
positive attitudinal shift.
45
Face-to-face contact
involves the activation of mirror and spindle neu-
rons.
33,46-48
When interacting with trusted others a
number of chemicals are released including oxytocin
and vasopressin,
49,50
both of which help to lower the
physiological stress response and aid growth and
wound healing.
51
Social interaction becomes an
interactive process of positive feedback whereby
increased levels of oxytocin in turn encourage even
greater levels of gaze to the eye region of human
faces.
50
This dynamic further increases the level of
trust and empathy between the interacting parties.
When there is sufficient trust and positivity, a
positive feedback effect can occur, which stimulates
the parasympathetic nervous system and releases
immune system chemicals that enable neuroplastic-
ity and neurogenesis to occur.
52,53
These same chem-
icals are involved in immune system strength and
changes to hormonal responses triggered by stress,
pain signalling and integration. Each of these are
directly related to healing and resilience through
such mechanisms as modulating the interplay of
lymphocytes that produce antibodies
54
and trigger-
ing hormone and neuropeptide changes that mediate
emotions.
13,55
Eye gaze and retinal eye lock between an anxious
person and a trusted ‘‘other’’ has a direct effect on
the synchronization of the right brain hemi-
spheres
56,57
and the quietening of the sympathetic
nervous system and amygdala,
58
increasing the abil-
ity to deal with trauma. Thus, it enables the caregiver
or trusted ‘‘other’’ to ‘‘soothe’’.
49,58
This ‘‘eye con-
tact effect’’ modulates activity in structures in the
social brain network,
59
aiding communicative inten-
tion and affective arousal. There is growing evidence
of the link between these neurophysiological reac-
tions and a decreased level of morbidity and mortal-
ity through such changes as an increased capacity for
hope,
13,60
the capacity to reframe vulnerability and
deal with trauma,
61,62
and neurophysiological reac-
tions related to the placebo effect.
63
In summary, touch and face-to-face interaction
with trusted others have a number of neurophysio-
logical effects that are relevant to the therapeutic
relationship. These neurophysiological effects are
impacted by the quality of the relationship shared
by the individuals. Trust and empathy, in particular,
appear to be mediators given they have a profound
effect on the body’s generation and/or secretion of
beneficial chemicals, such as serotonin.
This review maps the research literature on inter-
ventions that directly or indirectly replicate aspects of
a therapeutic relationship using touch and/or eye
gaze. This research literature arguably complements
the existing body of research, indicating that thera-
peutic relationships can have a positive impact on
patients, particularly in relation to the delivery of
fundamental care. Research evaluating objective
neurophysiological measures might provide further
insight as to why and how this positive impact occurs.
A search of the Cochrane Library, the JBI Database
of Systematic Reviews and Implementation Reports
(JBISRIR) and PubMed revealed a very large number of
systematic reviews primarily concerned with the effects
of massage and other forms of touch. Typically these
reviews were condition specific such as the impact on
lower back pain
64
or prevention of pressure ulcers.
65
These, and many other systematic reviews, typically
examined clinical outcomes and not neurophysiologi-
cal outcomes. One Cochrane systematic review did
consider neurophysiological outcomes but was nar-
rowly focused on massage for mental and physical
health in infants under the age of six months.
66
One
scoping review was identified that mapped massage
studies that measured neurophysiological impacts, but
only in relation to blood pressure.
67
The objectives, inclusion criteria and methods of
analysis for this review were specified in advance and
documented in a protocol.
68
Review question/objective
The specific review question for this review was:
what are the neurophysiological impacts of human
touch and eye gaze that have the potential to influ-
ence healing and the therapeutic relationships?
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The objective of this scoping review was to exam-
ine and map the range of neurophysiological impacts
of human touch and eye gaze, and explore possible
links to and implications for the therapeutic rela-
tionship and healing. Touch and gaze are two central
components of human interaction. Understanding
the neurophysiological impact of touch and gaze
might provide insights in to how these components
of interaction can be used to enhance relationships in
a therapeutic context. Our intention was not to only
include studies that overtly stated a link between
touch or gaze and the impact on the therapeutic
relationship and healing. This would have been too
restrictive. Our objective was to look broadly at
studies that measured the neurophysiological impact
of touch and gaze and consider: the contexts in
which these occurred; who received the touch or
gaze and who provided it; what were the variants of
touch and gaze; and what was being measured. In
keeping with the purpose of a scoping review, this
information allowed us to explore and map this
emerging research field.
Inclusion criteria
Participants
This scoping review considered studies that included
cognitively intact human subjects of any age.
Patients who were heavily sedated or unconscious
were excluded.
Concept
This scoping review investigated a number of areas
related to the neurophysiology of human interaction
(e.g. touch, eye gaze) and their potential connection
to building a useful therapeutic relationship. The
concept/s examined included:
Neurophysiology of touch
Neurophysiology of eye gaze
Neurophysiological impacts on healing
Neurophysiology of care
Therapeutic relationship.
Specifically, we considered who received the
touch or gaze and who provided it; what the variants
of touch and gaze were; and what outcomes were
being measured.
Context
This scoping review considered studies that exam-
ined, in either clinical or laboratory settings, the
neurophysiological impacts of touch and eye gaze,
and which have potential links to the therapeutic
relationship. Clinical settings included acute care,
long-term care and community care, including
the home.
Types of studies
This scoping review considered both experimental
and quasi-experimental study designs including:
randomized controlled trials, non-randomized con-
trolled trials, before and after studies and inter-
rupted time-series studies. In addition, analytical
observational studies including but not limited to
prospective and retrospective cohort studies and
case-control studies were considered for inclusion.
Only quantitative studies were included as the
aim was to examine objective measures of neuro-
physiological changes as a result of human touch
and gaze.
Methods
This scoping review adopted the methodology for
Joanna Briggs Institute (JBI) scoping reviews as
described in the JBI Reviewers’ Manual.
69,70
Search strategy
A three-step search strategy was utilized for this
review. An initial limited search of Scopus, PubMed
and CINAHL was undertaken, followed by an anal-
ysis of the text words contained in the title and
abstract, and of the index terms used to describe
the articles. A second search using all identified
keywords and index terms was then undertaken
across all included databases. Thirdly, the reference
list of all identified reports and articles were searched
for additional studies. Only published studies in
English were considered for inclusion in this review.
The decision not to search for unpublished papers
was due to the large amount of results from search-
ing the databases of published studies, making addi-
tional imprecise searches in the gray literature
impractical. There were no date restrictions.
The databases searched included: CINAHL,
PubMed, Cochrane Central Register of Controlled
Trials (CENTRAL), Scopus, PsycINFO and Web
of Science. Results of all searches are provided in
Appendix I.
Initial keywords used were: gaze, healing, neuro-
physiological, therapeutic relationship, touch.
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Study selection
All searches were imported into Endnote X8 (Clar-
ivate Analytics, PA, USA) and all title and abstracts
were reviewed by two reviewers independently. Full-
text of studies were then retrieved and reviewed by
two reviewers independently. All discrepancies in
selection were resolved through discussion.
Extraction of results
Data were extracted from papers included in the
scoping review by two independent reviewers using
the data extraction tool specified in the review
protocol.
68
The data extracted included specific
details about the populations, concept, context
and study methods of significance to the scoping
review question and specific objectives. Any dis-
agreements that arose between the reviewers were
resolved through discussion.
Data mapping
The extracted data are presented in both diagram-
matic and tabular form as per scoping review guide-
lines, including mind-maps of the various aspects of
the study and how they interrelate. A narrative
summary accompanies the tabulated and diagram-
matic results.
Results
Description of studies
The initial search of all databases was conducted on
1213 November 2015 and updated in February
2017. The search strategy was deliberately sensitive
and therefore resulted in a large number of studies
identified. Database searches identified 18,734
records. Other sources, primarily reference lists of
included studies, provided a further 46 records. After
removal of duplicates and screening of title and
abstracts, 86 studies were retrieved in full text and
22 were then excluded based on inclusion criteria
(See Appendix II). A total of 64 studies have been
included in the review. The PRISMA flowchart in
Figure 1 describes the flow of decisions for inclusion
of studies.
Characteristics of included studies
Of the 64 studies included in the review (Table 1),
most (61%) were set in the clinical environment,
72-110
with the vast majority of studies conducted in
the US (39%),
42,79,80,83-90,93,95,97,98,104,106,108,111-117
Sweden (13%),
75,77,78,99,100,102,110,118
Japan
(9%),
82,91,109,119-121
South Korea
96,122-124
and the
UK (6% each).
72,103,107,125
Nearly half of the studies
were randomized controlled trials,
42,73,74,77,78,80,
84-90,95,98,99,101,105-108,112,115,116,120,123,124,126-128
and
there were slightly fewer studies involving patients
(45%)
72-75,77-80,82,84-87,89,90,92,95-99,101,103,106-108,110,
113,129
as opposed to healthy participants. The largest
group of patients were those with cancer.
77-79,
95,101,106,107
Fifty-seven studies (89%) investigated
‘‘touch’’ as an intervention,
42,72-93,95-124,126,127,
130,131
four (6%) investigated the effect of
‘‘gaze’’,
125,129,132,133
two (3%) investigated ‘‘touch
and gaze’’ combined
94,128
and one study (2%) investi-
gated touch and gaze with the addition of vocalization
and facial expression.
134
It should be noted, that
although our aim was to identify studies that addressed
the neurophysiological impact of touch and gaze in
relation to healing there were no studies identified that
addressed this directly.
The detailed characteristics of all included studies
are provided in Appendix III.
Review findings
Interventions and intervention sub-types
Figure 2 maps the included studies showing the
numbers of studies investigating each of the inter-
vention types, and for each of the intervention sub-
types. The sub-types were derived iteratively as part
of the mapping process.
For studies of touch, the most prominent sub-type
was ‘‘massage’’ (46 studies, 81% of touch stud-
ies),
42,72-75,77-79,81,82,84-92,95-101,105-110,113,115,116,
118-124,126,127,130,131
followed by ’’skin to skin’’ (also
known as ‘‘kangaroo care’’) (5 studies, 9%),
76,80,
93,103,104
‘‘warm affective touch/holding’’ (5 studies,
9%)
83,102,111,112,114
and ‘‘Reiki touch’’ (1 study,
2%).
117
In the ‘‘skin to skin’’ care studies most involvedpre-
term infants,
80,93,103,104
with only one study involv-
ing full-term infants;
76
all with the mother providing
the contact. The studies of ‘‘warm affective touch/
holding’’ included mother and infant dyads
83,102
or
couples in a relationship.
111,112,114
The ‘‘Reiki touch’’
study involved healthy participants with a trained
Reiki practitioner.
117
Characteristics of the massage
studies are provided in more detail later.
For studies of gaze, one intervention sub-type
(‘‘direct and averted’’) was represented by two stud-
ies,
129,132
others sub-types (‘‘direct, averted and
closed’’ and ‘‘still face’’)
125,133
were investigated in
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Articles excluded on
reading full-text
(N=22)
Full-text articles
assessed for
eligibility
(N=86)
Number of articles
included
(N=64)
Records excluded
(N=13,172)
Records identified
through database
searching
(N=18,734)
Additional records
identified through
other sources
(N=46)
Records after
duplicates removed
(N=13,258)
Records screened
(N=13,258)
IdentificationScreeningEligibilityIncluded
Figure 1: PRISMA flowchart for the scoping review process
71
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one study each. One study involved mothers and
infants.
125
The other three studies involved women
and men viewing the gaze of either the researcher,
129
or
of live models.
132,133
For the two studies of touch and
gaze (combined), the intervention sub-types were ‘‘free
play’’
94
and ‘‘still face and touch’’.
128
Both studies
involved parents and their children. One study focused
on the combined intervention of ‘‘touch, gaze, vocal-
isation and facial expression’’, and examined the inter-
vention sub-type of ‘‘social interaction’’. This study
Table 1: Overview of included studies
Category Variable n %
Setting Clinical (including acute, long term community and home care) 39 61
Laboratory 25 39
USA 25 39
Sweden 8 13
Japan 6 9
South Korea 4 6
UK 4 6
Israel 3 5
Australia 2 3
Country Finland 2 3
Germany 2 3
Iran 2 3
Brazil 1 2
Canada 1 2
Switzerland 1 2
Taiwan 1 2
Thailand 1 2
Turkey 1 2
Randomized Controlled Trials 31 48
Non-randomized controlled trials 17 27
Study design Pre-test post-test 7 11
Case-Series 7 11
Other 2 3
Population Healthy 35 55
Patients 29 45
Touch 57 89
Intervention Gaze 4 6
Touch and gaze 2 3
Touch, gaze, vocalisation, facial expression 1 2
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Figure 2: Mapping of intervention types and outcome measures (values correspond to the number of
studies as does the relative size of each component of the figure)
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included a variety of participants including couples and
parents with children.
134
Figure 3 presents a detailed analysis of the key
characteristics of ‘‘massage’’, the most frequently
measured intervention sub-type. Many studies failed
to provide various details of these characteristics;
therefore, the totals for some characteristics in
Figure 3 are less than 46.
Six aspects of massage apparent from the litera-
ture are presented:
(i) Body area: The different amounts/locations of
the body being massaged, including: full body
(n ¼28);
42,73-75,78,79,81,82,84-87,90,91,95,97-99,106,
108,110,113,116,119,120,124,126,131
back (n ¼4);
89,
115,118,121
back, neck and head (n ¼2);
101,105
limbs (n ¼3);
77,92,100
neck and shoulders
(n ¼1);
127
scalp (n ¼1);
123
trunk (n ¼1);
96
upper body and limbs (n ¼3);
72,88,109
acupres-
sure points (n ¼2);
122,130
and self-selected
(n ¼1).
107
(ii) Type: The style of massage being provided,
ranging from gentle/tactile (n ¼9),
72,75,
77,78,98,100,109,110
and Swedish (n ¼7),
88,90,
101,108,115,118,131
to other forms such as anma
Figure 3: Mapping of ‘‘massage’’ intervention study characteristics (values correspond to the number of
studies as does the relative size of each component of the figure)
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(n ¼3),
82,119,120
shantala,
81
Thai
126
and Yak-
son.
96
Nine studies used multiple types of
massage,
42,73,74,95,105-107,113,116
and a further
12 did not specify the type of massage
used.
79,84-87,89,91,92,121,123,127,130
(iii) Relationship to provider (where stated): The
provider was either a trained masseuse (n ¼27)
or researcher/research assistant (n ¼1) that
had no existing relationship with the recipi-
ent;
42,75,78,79,81,86-90,92,95,101,106,108,110,113,115,
116,118-120,122-124,126,130,131
a trained clinician
involved in the subject’s care (all nurses:
n¼9);
72,74,77,96,97,99,100,105,107
or a significant
other (a person in a relationship with the
receiver) (n ¼6).
73,84,85,91,109,127
(iv) Duration: The duration of the massage, ranging
from less than 20 minutes (n¼12),
81,87,
88,91,96,98,105,115,121,123,127,130
20– 40 minutes
(n ¼18)
72,77,79,82,85,86,89,90,92,95,99,101,107,109,
118,120,124
to greater than 40 minutes
(n ¼12).
42,73-75,78,97,100,108,113,116,126,131
(v) Frequency: Whether the massage was con-
ducted once (n ¼14)
42,72-74,99,100,107,115,118,
120,122,126,127,130
or multiple times
(n ¼31).
75,77-79,81,82,84-92,95-98,101,105,106,
108-110,113,116,119,123,124,131
(vi) Control: If a control group was used, the most
frequently occurring comparator was no mas-
sage (n ¼14),
72,73,84,91,92,95,97,98,105,109,113,
123,124,131
followed by rest (n ¼9)
82,99-
101,106,115,118,119,126
and then relaxation
(n ¼6).
79,85,86,88,90,110
A small number of
studies used gentle touch (n ¼3)
42,96,116
and
attentive discussion (n ¼3).
77,78,127
One study
used video viewing.
89
Due to study design,
three studies had no comparator.
75,81,121
Outcomes
Figure 2 also presents the outcomes measured for all
of the included studies. The most common outcome
measure was cortisol accounting for 83% (n ¼53) of
studies. This included salivary cortisol in 48%
(n ¼31),
42,76-78,80-84,86,88-94,100,104,106,112,113,116,117,
119-121,124,126,128
serum cortisol in 28%
(n ¼18)
42,72-75,80,97,99,101,103,105,107,111,116,122-124,
131
and urinary cortisol in 17% (n ¼11) of stud-
ies.
79,85-87,89,95,96,98,108,110,113
It should be noted
that in a number of studies, two sources of cortisol
were sampled. None of the studies with gaze as a
sole intervention measured cortisol. Oxytocin was
measured in 23% (n ¼15) of studies and this was
mostly serum oxytocin.
42,75,77,94,102,109,111,112,114-
116,118,125,127,134
The next most frequent group of
outcome measures were the catecholamines: dopa-
mine, epinephrine (adrenaline) and norepinephrine
(noradrenaline) in 19% (n ¼12) of stud-
ies.
72,79,85,87,89,95,96,98,110,111,113,123
Serotonin was
measured in only 8% (n ¼5) of studies.
79,85,87,95,101
Neural activity including EEG, amygdala response
and N170, a component of event related potential
(stimulus in response to viewing faces), were mea-
sured in a small number of studies involving
gaze
129,132
and massage.
88,124,130
It should be noted that the inclusion criteria also
addressed studies in regard to the neurophysiology of
healing, care and the therapeutic relationship.
Although many included studies made inferences
about the potential for the various neurophysiologi-
cal measures and we have explored this potential, no
studies were identified that directly measured the
neurophysiological impact on these concepts. This
issue is elaborated in the following discussion.
Discussion
As this is a scoping review, the included studies have
not been subjected to critical appraisal. There is
therefore no attempt to address the effectiveness
of the interventions.
The impetus for this review was the growing body
of work on the neurophysiological impact of touch
and eye gaze during direct human interaction and the
benefits of a positive, trusting therapeutic relation-
ship as the central element in the delivery of high-
quality, person-centered fundamental care.
11,135
This review, therefore, aimed to identify research
that evaluated neurophysiological measures as a
response to touch and gaze, given they are essential
elements of establishing and maintaining therapeutic
relationships. We considered the nature of the inter-
ventions in terms of what intervention was delivered,
who administered the intervention and who
received it.
Although we identified a large body of research,
arguably only a small number of studies measured
relevant neurophysiological responses and were
contextually specific to what could be described
as the development and maintenance of a
clinician-patient relationship. These studies
involved patients and clinicians (all nurses) in
the clinical setting.
72,74,77,96,97,99,100,105,107
However,
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to restrict the review to these studies alone would have
prevented exploration of a number of aspects of touch
and gaze. For example, the effect of gaze was not
addressed in any of the studies involving nurses.
The scoping review methodology allows, even
encourages, the exploration of the boundaries of a
concept. We would assert that therapeutic relation-
ships are not restricted to a nurse and patient. These
relationships can and often do include relatives of
patients, with nurses often including them in thera-
peutic activities. In the case of infants, this would
include encouraging mothers to have skin-to-skin
contact. We established our boundary at the point
where objective measurement of direct human to
human touch and gaze occurred. Regarding the types
of touch and the inclusion of massage, there is a
continuum from light or gentle affective touch to
firm even forceful touch of deep tissue massage.
There is no natural cut-off point within this range.
We recognize that gentle affective touch would occur
when a nurse is giving comfort to a patient. At the
other end of the spectrum nurses will touch patients
more firmly when technical care is provided and it is
this boundary which we aimed to explore.
The actions of nurses when caring for patients
involve a great deal of touch.
136,137
This includes
touch that would be intended to comfort (gentle
touch) and, as part of an intervention, technical or
instrumental touch.
138
In considering touch in the
context of nursing practice, a bed-bound patient
requiring washing by a nurse might also be provided
with gentle massage, which would closely approxi-
mate some studies in the current review where a back
massage was the intervention. There were a small
number of included studies involving holding; warm,
affective touch; and skin-to-skin contact, and
once again these studies would contextually relate
to the use of touch by nurses to comfort a
patient.
76,80,83,93,102-104,111,112,114
Other aspects
related to touch that were reflected in the studies
included the skill level of the masseur/therapeutic
provider and the relationship they had to the person
receiving touch.
Trust is considered foundational in any therapeu-
tic relationship.
23,135
A trusting relationship is
considered to be ‘‘dynamic and ongoing’’,
23(p506)
suggesting that those who form this relationship
are known to each other and have multiple inter-
actions. The majority of studies had massage pro-
vided by a trained masseuse, with the next largest
group massaged by a significant other, most often a
spouse or life partner, and half as many again from a
trained clinician. Whilst only four studies reported
clinicians providing touch on more than three occa-
sions,
77,96,97,105
the trust engendered by an ongoing
relationship with a nurse or other type of clinician
during therapy (either in a hospital or undergoing
regular treatment) might offer potential benefits in
regard to the therapeutic relationship and patient
recovery/healing.
In the present review, the decision was made to
only include studies with ‘‘live’’ gaze, and not the
presentation of photos or videos, due to the body of
evidence indicating a difference in the neurophysio-
logical reaction to ‘‘live’’ gaze as opposed to gaze
that is intermediated by technology (i.e. interaction
over a screen, images of faces).
132,133
As a result,
only seven studies addressing gaze (with or without
touch) were included.
94,125,128,129,132,134
These stud-
ies measured both the effect of direct and averted
gaze. This is relevant for the nurse-patient relation-
ship as a more intense physiological response from
the stimulus of direct gaze might result in a greater
level of cognitive social network engagement which
could lead to interpersonal neural synchronization
and an increase in empathy.
133
It might also result in
an increase in neuro-chemicals that strengthen the
endocrine system and modulate the stress response.
However, no studies that involved gaze between a
patient and nurse were identified in the search.
The majority of included studies measured a
single intervention, either touch or gaze. In the
studies that involved touch, it is reasonable to
assume that those providing touch might be making
eye contact with the subjects; however, only a small
number of studies noted the potential for, or effect
of, direct eye gaze as a mediating factor on results.
This appears to be due to the lack of awareness of the
potential neurophysiological impact of direct eye
gaze and therefore, the lack of recognition of its role
in moderating or mediating outcomes. Only three
studies explicitly involved interventions of both
touch and gaze.
94,128,134
Notably one recent study
included an intervention involving the synchrony
codes of touch, gaze, vocalization and facial expres-
sion, and its ‘‘pragmatic’’ design meant it was one of
the few studies to attempt to control for the reality of
the complexity of human-to-human interaction.
134
A number of different population groups received
interventions. Approximately half of the studies
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involved the intervention being administered to
patients with a variety of medical conditions; the
largest group being people with cancer.
77-
79,95,101,106,107
Many studies aimed to use touch to
reduce anxiety and stress, which is common in
patient population groups. A few of the studies
focusing on healthy individuals used a range of
mechanisms to induce stress in the subjects before
or after the intervention process, which included
touch, gaze and proximity to a trusted or significant
other.
99,114,127
A number of these studies reported
results that can potentially inform how to mediate
stress via the therapeutic relationship.
The environment in which the intervention was
provided was also a consideration in a number of the
studies. Approximately half of the studies were
undertaken in a non-clinical environment where
conditions could be well-controlled in terms of stim-
uli not directly related to the human-to-human inter-
action, such as light and noise. Although the studies
undertaken in a clinical setting might be considered
more relevant, there was no direct attempt to control
for such environmental stimuli.
For the majority of studies (n ¼53), the major
impact marker tested was cortisol,
42,72-101,103-
108,110-113,116,117,119-124,126-128,131
with 15 studies
measuring oxytocin.
42,75,77,94,102,109,111,112,114-116,
118,125,127,134
Cortisol levels were measured in
serum, saliva and/or urine. In the nine studies that
involved patients with nurses providing (gentle)
touch, cortisol levels were measured as an indicator
of stress.
72,74,77,96,97,99,100,105,107
In many cases, the
purpose of touch therapy was to reduce stress in
patients, and in some it was to explore beneficial
neurophysiological effects (including immunologi-
cal), particularly when the patient was undergoing
treatment. Direct eye gaze was also indicated as a de-
stressor in the studies that examined at it as an
intervention.
94,125,128,129,132-134
This highlights
the potential for touch and eye gaze, as part of
the nurse-patient relationship, to positively impact
patients, as supported by findings showing an inte-
grative role of the oxytocinergic system in support-
ing social affiliation, and an associated rise in
immune biomarkers.
134
Cortisol was shown to be a complex indicator, as
a number of variables are involved, including rela-
tionship, gender, age, baseline/resting level, type of
touch, type of cortisol (salivary, plasma and urinary)
and collection method. For example, massage
involving firm pressure (such as Swedish massage)
was reported to increase cortisol (due to pressure
sensors in the skin); yet, it had other beneficial
physiological impacts such as stimulation of oxyto-
cin and immune system function. In many of the
studies that had oxytocin as an outcome measure, it
was used as an indicator of bonding and/or syn-
chrony. Though not part of this review’s objectives,
there was a consistent link reported between raised
oxytocin and an increase in immunological activity,
and this warrants further research in terms of the
potentially beneficial outcomes from direct interac-
tion with the clinician. It also raises the potential of
using oxytocin as a measure of the development of a
therapeutic relationship; however, in the studies
with nurses, only one measured oxytocin levels
and the rationale was that it was an anxiolytic.
77
A small number of studies measured neurological
changes including amygdala and other neural activ-
ity, changes in nervous system activity and vagal
tone, and the presence of various neurochemicals/
transmitters in response to study interventions.
128-
130,132,133
The reported results were consistent with
the body of research work regarding the beneficial
neurophysiological effects of direct human interac-
tion.
30-41
Nursing interventions are often complex with
many confounders. Qualitative research investigat-
ing touch as part of nurse-patient interaction reports
that gentle touch can result in comfort or distress
depending on a range of contextual issues, such as
the gender of the nurse, the environment in which the
touch is administered, and the simple but important
act of explaining what is happening before the touch
is administered.
136,138
Looking for objective evi-
dence about the impact of a good therapeutic rela-
tionship is challenging, confounded by the iterative
and synergistic neurophysiological nature of direct
interaction on both parties.
99
The majority of studies
that we identified aimed to measure the impact of a
single intervention, most commonly massage, often
ignoring the additional moderation/mediation of
direct eye gaze. The interventions were rarely within
the context of the nurse-patient relationship.
Limitations
One potential limitation of this review is that we
focused specifically on touch and gaze as central
elements of human interaction, including as part
of a therapeutic relationship, in studies that
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quantifiably measured neurophysiological outcomes
of such interaction. Human interaction is much
more complex than touch and gaze, as shown in
those studies that included related aspects such as
social synchrony, convergence of biomarkers during
bonding and affiliation, and the interplay of such
things as allostasis and trust. There are also many
studies that explore the neurophysiological impact
of other aspects of human interaction, either inclu-
sive or exclusive of touch and gaze, using qualitative
methodologies. Such studies, when robust, should
also inform this area of research as the complex
interplay cannot be measured by quantitative mea-
sures alone.
Regarding gaze, the decision was made to only
include ‘‘live’’ faces and this restricted the literature
we accessed. A further limitation is that, due to the
complexity of cultural differences in regard to direct
gaze and touch, this review has not included cultural
difference as a criterion. This was compounded by
only including English language studies. Future
research in this area would be valuable in terms of
informing nurses and other clinicians on the complex
mediating effects.
Finally, it should be noted that we did not search
for unpublished literature. In preparation for this
review we deemed a comprehensive search for
unpublished papers impractical. As this is a scoping
review without critical appraisal we make no specific
judgments of effect which would be an issue in
relation to publication bias.
Conclusion
The aim of this review was to identify studies that
evaluated two important elements of human inter-
action, touch and gaze, and their impact on a range
of neurophysiological measures. An important con-
sideration was the relevance of the studies in regard
to the nurse-patient relationship, interpreted
through the wider lens of the therapeutic relation-
ship. Although small in number, there were studies
that did involve nurses and patients, but most did not
address the complexity of human interaction as
would be seen in the clinical setting. However, there
was sufficient consistency in trends evident across
many studies regarding the beneficial impact of
touch and eye gaze to warrant investigation in the
clinical setting. There is a balance here between
studies that are tightly controlled and those of a
more pragmatic nature that are contextually closer
to the reality of providing nursing care. The latter
should be encouraged.
Recommendations for research
Given the growing evidence that fundamental care
is being poorly executed globally,
2-10
there is
increasing emphasis on understanding how such
care can be delivered effectively and safely and
on elucidating the positive impact for patients
when such care is delivered well. Fundamental care
involves multiple opportunities for touch (as part of
routine activities, such as bathing, or intended to
comfort) and gaze, and is positively influenced by a
trusting nurse-patient relationship. Systematic
reviews of effectiveness could help to elucidate
the specific neurophysiological mechanisms though
which nurses’ routine work and fundamental care
result in positive care experiences for patients and
improved patient healing. These reviews would
range from those considering the neurophysiologi-
cal effect of massage as a standalone intervention,
likely to include a large number of studies, to a
review on the effectiveness of comforting touch by
nurses, likely to include only a small number of
studies. There is also potential for reviews in a
number of other areas including neural engagement
and synchronization and immunological change.
In regard to primary research, most of the
included studies were designed to control for a single
stimulus. Very few studies were conducted in the
clinical setting with the multiple stimuli that would
represent the reality and complexity of nurse-patient
interaction. However, these studies demonstrated
the feasibility of this type of pragmatic research.
Studies in which nurses are the providers of the
intervention should be undertaken in the clinical
area, to further explore the impact of the relationship
between patient and nurse, and it would be relevant
to further explore such an impact on both parties, as
informed by studies regarding the reciprocal nature
of the neurophysiological impacts of direct human
interaction. The study by Ulmer-Yaniv et al.
134
pro-
vides a methodological example of quantifying mul-
tiple convergent elements and outcomes of human
interaction. Other studies have also used video and
accompanying software to code interactions
between individuals in both the clinical and simu-
lated environments, also demonstrating feasibility of
this approach.
139,140
In the early 1990 s, Estabrooks
and Morse used a grounded theory approach to
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investigate how intensive care nurses learn to
touch.
136
This raises the potential of using both
neurophysiological measures and technological
intermediation and/or imaging as interventions or
aids to teach nurses how to use touch and gaze in
order to develop therapeutic relationships.
This review has research implications for the
positive use of massage, and for differentiating the
type of massage dependent on the required thera-
peutic outcome desired, as well as controlling for
duration, timing, frequency, expertise, relationship
and amount of body.
A research area that is currently under-developed
is the inclusion of direct eye gaze as a contributing
variable in both research studies and practice.
Whilst there were only a small number of studies
directly related to the role of eye gaze, in a thera-
peutic context there was evidence that the opportu-
nity for, and effect of, eye gaze is also a potential
mediator for a positive interactive outcome, and
may have an additive effect when touching is
also involved.
The increase in technology in health care requires
decisions to be made about the level of human or
technological intervention in the care of patients.
However, there is currently very little research evi-
dence to guide these choices to maximize benefits to
patients, clinicians and the medical institution
involved. Recognizing the therapeutic impact of
touch and gaze may redefine the way nurses choose
to interact with their patients and the future delivery
of health care.
Acknowledgments
The authors would like to thank Dr Micah Peters
(Joanna Briggs Institute) who provided guidance on
the conduct of scoping reviews.
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Appendix I: Search strategies
All searches conducted in February 2017
Source Query Results
CINAHL (touch or massage or gaze or retinal or eye) AND (oxytocin or
vasopressin or cortisol or dopamine or serotonin or amygdala)
259
Cochrane
(CENTRAL)
(touch or massage or gaze or retinal or eye) AND (oxytocin or
vasopressin or cortisol or dopamine or serotonin or amygdala)
634
PubMed ((oxytocin[Title/Abstract] OR cortisol[Title/Abstract] OR dopamine[Ti-
tle/Abstract] OR serotonin[Title/Abstract] OR vasopressin[Title/Abstract]
OR amygdala[Title/Abstract])) AND ((touch[Title/Abstract] OR massa-
ge[Title/Abstract] OR gaze[Title/Abstract] OR retinal[Title/Abstract] OR
eye[Title/Abstract])
3932
JBISRIR (touch OR massage OR gaze OR retinal OR eye) AND (oxytocin OR
vasopressin OR cortisol OR dopamine OR serotonin OR amygdala)
36
Web of Science (touch or massage or gaze or retinal or eye) AND (oxytocin or
vasopressin or cortisol or dopamine or serotonin or amygdala)
5276
Scopus (touch or massage or gaze or retinal or eye) AND (oxytocin or
vasopressin or cortisol or dopamine or serotonin or amygdala)
6959
PsycINFO ((touch or massage or gaze or retinal or eye).mp. [mp ¼title, abstract,
heading word, table of contents, key concepts, original title, tests &
measures]) AND ((oxytocin or cortisol or dopamine or serotonin or
vasopressin or amygdala).mp. [mp ¼title, abstract, heading word, table
of contents, key concepts, original title, tests & measures])
1638
Note that MeSH (Medical Subject Headings) were not used in any of the searches.
SYSTEMATIC REVIEW F. Kerr et al.
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Appendix II: Excluded studies based on eligibility criteria
Busch M, Visser A, Eybrechts M, van Komen R, Oen I, Olff M, et al. The implementation and evaluation of
therapeutic touch in burn patients: an instructive experience of conducting a scientific study within a non-
academic nursing setting. Patient Educ Couns. 2012;89(3):439 –46.
Reason for exclusion: No skin-to-skin contact
Chatel-Goldman J, Congedo M, Jutten C, Schwartz JL. Touch increases autonomic coupling between
romantic partners. Front Behav Neurosci. 2014;8:95.
Reason for exclusion: No reporting of neurophysiological measures
Currin J, Meister EA. A hospital-based intervention using massage to reduce distress among oncology
patients. Cancer Nurs. 2008;31(3):214 21.
Reason for exclusion: No reporting of neurophysiological measures
Gordon I, Voos AC, Bennett RH, Bolling DZ, Pelphrey KA, Kaiser MD. Brain mechanisms for processing
affective touch. Hum Brain Mapp. 2013;34(4):914 22.
Reason for exclusion: No skin-to-skin contact
Groer M, Mozingo J, Droppleman P, Davis M, Jolly ML, Boynton M, et al. Measures of salivary secretory
immunoglobulin A and state anxiety after a nursing back rub. Appl Nurs Res. 1994;7(1):2 6.
Reason for exclusion: No reporting of neurophysiological measures
Helminen TM, Kaasinen SM, Hietanen JK. Eye contact and arousal: the effects of stimulus duration. Biol
Psychol. 2011;88(1):12430.
Reason for exclusion: Only measured skin conductance response
Henricson M, Berglund AL, Maatta S, Ekman R, Segesten K. The outcome of tactile touch on oxytocin in
intensive care patients: a randomised controlled trial. J Clin Nurs. 2008;17(19):262433.
Reason for exclusion: Patients semi-conscious or unconscious
Hodgson NA, Lafferty D. Reflexology versus Swedish Massage to Reduce Physiologic Stress and Pain and
Improve Mood in Nursing Home Residents with Cancer: A Pilot Trial. Evid Based Complement Alternat
Med. 2012;2012:456897.
Reason for exclusion: Some participants not capable of providing consent so surrogate was used
Kanitz JL, Reif M, Rihs C, Krause I, Seifert G. A randomised, controlled, single-blinded study on the impact
of a single rhythmical massage (anthroposophic medicine) on well-being and salivary cortisol in healthy
adults. Complement Ther Med. 2015;23(5):68592.
Reason for exclusion: No detailed reporting of salivary cortisol
Kujala MV, Carlson S, Hari R. Engagement of amygdala in third-person view of face-to-face interaction.
Hum Brain Mapp. 2012;33(8):175362.
Reason for exclusion: Subject not directly involved in interaction but observing others
Lee MS, Rim YH, Kang CW. Effects of external qi-therapy on emotions, electroencephalograms, and plasma
cortisol. Int J Neurosci. 2004;114(11):1493 502.
Reason for exclusion: No skin-to-skin contact
Lee YH, Park BN, Kim SH. The effects of heat and massage application on autonomic nervous system.
Yonsei Med J. 2011;52(6):9829.
SYSTEMATIC REVIEW F. Kerr et al.
JBI Database of Systematic Reviews and Implementation Reports COPYRIGHT ß2018 THE AUTHORS. PUBLISHED BY 228
WOLTERS KLUWER HEALTH, INC. ON BEHALF OF THE JOANNA BRIGGS INSTITUTE.
Reason for exclusion: No skin-to-skin contact
Listing M, Krohn M, Kim I, Reisshauer A, Peters E, Liezmann C, et al. The Influence of Classical Massage
Therapy on Stress Perception, Mood Disturbances, Body Image, Cortisol and Oxytocin Levels 2011. 389- p.
Reason for exclusion: Conference paper unable to access full-text
Okvat HA, Oz MC, Ting W, Namerow PB. Massage therapy for patients undergoing cardiac catheterization.
Altern Ther Health Med. 2002;8(3):68 70, 2, 4 5.
Reason for exclusion: Cortisol only raised in discussion
Peled-Avron L, Wagner S, Perry A, Shamay-Tsoory S. Get in touch: the role of oxytocin in social touch2013.
S90-S p.
Reason for exclusion: Conference paper unable to access full-text
Pierno AC, Becchio C, Turella L, Tubaldi F, Castiello U. Observing social interactions: the effect of gaze. Soc
Neurosci. 2008;3(1):519.
Reason for exclusion: Not live faces
Ponkanen LM, Hietanen JK, Peltola MJ, Kauppinen PK, Haapalainen A, Leppanen JM. Facing a real person:
an event-related potential study. Neuroreport. 2008;19(4):497 501.
Reason for exclusion: Unable to access full-text
Rapaport M, L. Hale K, Koury M, Shubov A, J. Bresee C. The role of oxytoncin, vasopressin and cortisol in
the beneficial effects of massage therapy 2008. 1S-S p.
Reason for exclusion: Conference paper unable to access full-text
Sato W, Kochiyama T, Uono S, Toichi M. Neural mechanisms underlying conscious and unconscious
attentional shifts triggered by eye gaze. Neuroimage. 2016;124(Pt A):118 26.
Reason for exclusion: Not live faces
Sato W, Kochiyama T, Uono S, Yoshikawa S. Amygdala integrates emotional expression and gaze direction
in response to dynamic facial expressions. Neuroimage. 2010;50(4):165865.
Reason for exclusion: Not live faces
Sato W, Yoshikawa S, Kochiyama T, Matsumura M. The amygdala processes the emotional significance of
facial expressions: an fMRI investigation using the interaction between expression and face direction.
Neuroimage. 2004;22(2):100613.
Reason for exclusion: Not live faces
Sauer A, Mothes-Lasch M, Miltner WH, Straube T. Effects of gaze direction, head orientation and valence of
facial expression on amygdala activity. Soc Cogn Affect Neurosci. 2014;9(8):1246 –52.
Reason for exclusion: Not live faces
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Appendix III: Characteristics of included studies
Citation Study aims Setting Study Type Population (N ¼) Intervention Outcomes Key findings
Acolet et al.
(1993)
72
To assess the bio-
chemical and clini-
cal response to
massage in preterm
infants
UK, Clinical Non-RCT Stable pre-term
infants (16)
Gentle massage of the
trunk and limbs using
arachis oil for approxi-
mately 20 minutes (only
one massage)
Provider: massage
trained clinician (nurse)
Comparator(s)
Control (no massage)
Cortisol
(plasma) Epi-
nephrine
Norepinephrine
Cortisol concentrations were
consistently reduced after
massage. No significant differ-
ence detected between the
change in cortisol concentra-
tion in the group receiving
massage and in the control
group.
Adib-Hajbagh-
ery, Rajabi-
Beheshtabad &
Abasi (2013)
73
To evaluate the
effect of whole body
massage performed
by a patient’s com-
panion on the level
of blood cortisol
among patients
admitted in the
CCU
Iran, Clinical RCT Male patients in
CCU (60)
60-min. whole body
massage. Techniques
used included static mas-
sage, superficial stretch-
ing technique, stretching
massage, lymph vacuum-
ing technique, latitudinal
rubbing technique, and
myofacial releasing tech-
nique, accompanied with
effleurage using almond
oil.
Provider: patient’s com-
panion
Comparator(s)
Control (no massage,
routine care)
Cortisol
(plasma)
In the group massaged by the
patients’ companions, the
mean of blood cortisol was
323.6 162.6 nanomoles,
which decreased to
268.4 141.1 after the inter-
vention (P <0.102). The mean
of blood cortisol in the con-
trol group did not change
significantly.
Adib-Hajbagh-
ery, Rajabi-
Beheshtabad,
Ardjmand
(2015)
74
To compare the
effect of massage
applied by a nurse
specialist and
patients’ relatives on
blood cortisol level
among patients
admitted in CCU
Iran, Clinical RCT Male patients in
CCU (90)
One 60-minute, whole
body massage. The tech-
niques used were static
massage, superficial
stretching technique,
stretching massage,
lymph vacuuming tech-
nique, latitudinal rub-
bing technique and
myofascial releasing
technique, which were
accompanied with effleu-
rage of almond oil.
Provider: massage
trained clinician (nurse)
Comparator(s)
(1) One session of 60-
minute, whole body
massage by patients’
relatives (2) Control (no
massage, routine care)
Cortisol
(plasma)
In the nurse group, the
median blood cortisol level
was decreased after the inter-
vention (P <0.007). The
median blood cortisol level for
the patients’ relatives and con-
trol group did not change
significantly. There was no
significant difference between
the cortisol level in the three
groups either before or after
the intervention.
Andersson,
Wa
¨ndell &
To
¨rnkvist
(2004)
75
To investigate how
TM, short term and
over time, affects
blood glucose, stress
hormones and well-
being in women
with type 2 diabetes
mellitus
Sweden, Clin-
ical
Pre-test post-
test
Women with
Type 2 diabetes
(11)
Whole-body massage for
60 minutes 1/week for
10 weeks. Tactile mas-
sage (TM): pain-free but
deliberate, gentle and
superficial massage of
the skin without manip-
ulation of the underlying
muscles. Odourless vege-
table oil. Quiet music is
played during the mas-
sage. Three measurement
times: before massage,
one week after and
twelve weeks after.
Provider: trained mas-
seuse
Cortisol
(plasma) Oxy-
tocin (plasma)
No statistically significant dif-
ferences were found regarding
oxytocin, however, the oxyto-
cin measurements did show
tendencies to decline over
time, with the lowest value
measured on occasion 3. The
S-cortisol value on occasion 2
showed a statistically signifi-
cant reduction (p <0.05).
Bennett et al.
(2016)
126
To examine the
acute effects of
TTM on cortisol
level, blood pres-
sure, heart rate and
stress perception in
academic stress
Thailand,
Lab
RCT Physiotherapy stu-
dents with self-
perceived stress
score equal to or
greater than 3 on
a 5-point scale
(rated by 1 ¼not
stressed at all and
5¼extremely
stressed) (36)
Whole body TTM was
applied to participants in
the TTM group for 90
minutes.
Provider: trained mas-
seuse
Comparator(s)
Participants were awake
resting in the supine
position for 90 minutes
Salivary cortisol
collected
between 10:00
and 12:00 and
then after the
procedure
No evidence to indicate that
single TTM could decrease
saliva cortisol when compared
with rest in the supine posi-
tion.
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Citation Study aims Setting Study Type Population (N ¼) Intervention Outcomes Key findings
Bigelow et al.
(2012)
76
To investigate the
effect of mother/
infant SSC on
mothers’ postpar-
tum depressive
symptoms during
the first 3 postpar-
tum months and
their physiological
stress during the
first postpartum
month
Canada,
Home Visits
Non-RCT Mothers and their
full-term infants
(90)
Mothers in the SSC
group provided approxi-
mately 5 hours per day
of SSC with their infants
in the infants’ first week
and then more than
2 hours per day until the
infants were age one
month. Saliva samples
were taken from the
mothers when the
infants were one week
and one month.
Provider: mothers
Comparator(s)
Control (mothers pro-
vided little or no SSC)
Cortisol (sali-
vary)
Mean values for salivary corti-
sol for the one-week visit were
.340 mg/dL (SD ¼.163) for the
SSC group and .278 mg/dL
(SD ¼.128) for the control
group. The mean values for
the one-month visit were
.234 mg/dL (SD ¼.095) for the
SSC group and .244 mg/dL
(SD ¼.161) for the control
group. Over their infants’ first
month, mothers in the SSC
group had a greater reduction
in their salivary cortisol than
mothers in the control group.
Billhult et al.
(2008)
77
To examine the
effect of repeated
effleurage massage
treatments com-
pared with a visit
control group on
circulating lympho-
cytes, levels of corti-
sol in saliva and
oxytocin in plasma
as well as degree
anxiety, depression
and quality of life,
in women with
breast cancer
Sweden, Clin-
ical
RCT Women with
breast cancer
undergoing radia-
tion therapy (22)
Effleurage massage ther-
apy (20 minutes of
effleurage on ten occa-
sions), directly after the
scheduled radiation. The
patients could choose
between massage on
either both feet/lower
legs or both hands/lower
arms. Cold-pressed vege-
table oil was used, and
the limb was wrapped in
a towel after the mas-
sage.
Provider: massage
trained clinician (nurse)
Comparator(s)
The control group was
given the same amount
of attention as the mas-
sage group but did not
receive massage.
Cortisol (sali-
vary) Oxytocin
(plasma)
Lymphocytes
No significant changes
between groups were detected
on cortisol and oxytocin con-
centrations.
Billhult et al.
(2009)
78
To examine the
short-term effects of
light pressure effleu-
rage on circulating
lymphocytes, sali-
vary cortisol levels,
heart rate and blood
pressure in patients
with breast cancer
Sweden, Clin-
ical
RCT Women with
breast cancer
undergoing radia-
tion therapy (30)
A single 45 min. full-
body light pressure
effleurage massage.
Cold-pressed vegetable
oil was used. The effleu-
rage technique used was
strokes with both hands,
palms and fingers, using
light pressure (in average
0.0090 kg/cm2).
Provider: massage
trained clinician (nurse)
Comparator(s)
The control group was
given the same amount
of attention as the mas-
sage group but did not
receive massage.
Cortisol (sali-
vary) Lympho-
cytes
No significant differences
were seen between groups in
changed cortisol levels.
Boylan (2005)
79
In a pilot study
massage resulted in
women with breast
cancer reporting
reduced anxiety,
depression and
anger, increased uri-
nary dopamine and
serotonin, increased
natural killer {NK)
cells and lympho-
cytes. Thus, this
study was designed
to determine
whether it was
indeed massage, or
just simple relaxa-
tion, that provided
the benefits in the
pilot study.
USA, Clinical Non-RCT Women diagnosed
in the previous 3
years with early
stage (I-III) breast
cancer. Women
were not admitted
into the study
until 3 months
post-surgery and/
or had completed
their last radia-
tion and/or che-
motherapy ses-
sion. (58)
The massage sessions (3
x 30 minutes each week
for 5 weeks). The thera-
pists were instructed to
restrict any talking dur-
ing the sessions to only
questions concerning
pressure and tender
points. The massage was
a full body massage.
Provider: trained mas-
seuse
Comparator(s)
(1) Relaxation group
practised progressive
muscle relaxation, 3 ses-
sions each week for 5
weeks.
(2) Control group only
seen at the start and the
end of the 5 weeks
study.
Cortisol (uri-
nary) Serotonin
(urinary) Epi-
nephrine (uri-
nary) Norepi-
nephrine (uri-
nary) Dopa-
mine (urinary)
There were large variances in
the urine results. Positive
changes (increases) were bene-
ficial for dopamine and sero-
tonin. Only the increases in
dopamine and serotonin in the
massage group were statisti-
cally significant.
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(Continued)
Citation Study aims Setting Study Type Population (N ¼) Intervention Outcomes Key findings
Chang et al.
(2012)
130
To investigate a
subject’s EEG per-
formance under
massage treatment
applied by hand and
treatment applied
by mechanical
devices
Taiwan, Lab Non-RCT Healthy volun-
teers, mainly col-
lege students (24)
Hand massage. Three
minute circular massage
for each of 4 acupoints
in the mid shoulder area.
Provider: trained mas-
seuse
Comparator(s)
The same as the inter-
vention but subjects
massaged themselves
with a mechanical
device.
Neural activity
(EEG)
There are was a comparison
around EEG coherence during
massage sessions between the
hands-on group and mechani-
cal massage group. The coher-
ence value is higher when
channel pair distance is
greater. This is valid for both
groups. Second, the coherence
value of the hands-on group is
averagely higher than that of
the same channel pairs for the
mechanical massage group.
The hands-on group’s coher-
ence does not change signifi-
cantly during the massage
session, but the mechanical
massage group’s coherence
becomes lower, especially with
regard to alpha and beta
rhythms. Massage by hand
seems to maintain EEG chan-
nel coherence, while massage
by mechanical may interrupt
the original brain interaction
between different brain
regions. For left-right symme-
try coherence, P3-P4 pair is
the lowest coherence value
pairs for both groups. Similar
with around coherence, there
were more significant varia-
tions on theta, alpha, and beta
rhythms for mechanical mas-
sage than for hands-on mas-
sage, and there was a
significant massage stage-type
interaction on beta rhythm.
Cong, Luding-
ton-Hoe &
Walsh (2011)
80
This study tested
KC effects on bio-
behavioral responses
to heel stick in pre-
term infants (30– 32
weeks’ gestational
age, 2– 9 days old)
measured by Prema-
ture Infant Pain Pro-
file and salivary and
serum cortisol. The
paper reports two
pilot studies.
USA, Clinical RCT Male and female
preterm infants at
30– 32 weeks’ GA
and 2– 9 days’
postnatal age (28)
Study 1 KC for 80 min-
utes, after 60 minutes
baseline data was col-
lected and then KC con-
tinued for 20 minutes
Study 2 KC for 30 min-
utes, after 10 minutes
baseline data was col-
lected and then KC con-
tinued for 20 minutes
Provider: mother
Comparator(s)
Control group: Infants
remained in the Incuba-
tor for the procedure.
They were left undis-
turbed for the same time
as the KC.
Cortisol (sali-
vary and
serum)
30 minutes of KC before and
throughout heel stick
appeared to be effective in
reducing bio-behavioural pain
responses and cortisol levels in
preterm infants. Changes in
these outcomes were not seen
for 80 minute KC.
de Ca
´ssia
Fogac¸aet al.
(2005)
81
To evaluate the
levels of salivary
cortisol before and
after Shantala mas-
sage therapy on
healthy infants
Brazil, Clini-
cal
Pre-test post-
test
Healthy infants
aged 4– 6 months
(9)
Infants received two
standard 15 minute
Shantala massages on
two consecutive days
and then after a one
week interval in the
morning and the after-
noon
Provider: researcher
Cortisol (sali-
vary)
Cortisol levels increased after
the two consecutive days and
were still raised after one
week. The differences were
only statistically significant
for the afternoon measures.
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Citation Study aims Setting Study Type Population (N ¼) Intervention Outcomes Key findings
Ditzen et al.
(2007)
127
The authors hypoth-
esized that standard-
ized physical
partner contact
(neck and shoulder
massage) results in
attenuated responses
of the hypotha-
lamic– pituitary–
adrenal axis and the
autonomic nervous
system to acute psy-
chosocial stress in
women.
Switzerland,
Lab
RCT Healthy, hetero-
sexual women,
aged 20– 37 years,
who had been
married or coha-
biting with a sig-
nificant other for
at least 12
months (67)
Standardized physical
contact (i.e., instructed
neck and shoulder mas-
sage, no conversation)
for 10 minutes from
spouse 5 minutes prior
to Trier Social Stress
Test (5 minute public
speaking task and then 5
minute mental arithmetic
task in front of a panel).
Provider: spouse
Comparator(s)
(1) Social support (i.e.,
only verbal support from
spouse) for 10 minutes
from spouse 5 minutes
prior to Trier Social
Stress Test (2) No spou-
sal support (left alone)
for 10 minutes 5 minutes
prior to Trier Social
Stress Test
Cortisol (sali-
vary) Oxytocin
(plasma)
Women with positive physical
partner contact before stress
exhibited significantly lower
cortisol and heart rate
responses to stress but no
different plasma oxytocin
levels compared to women
who received social support or
no social interaction. Verbal
social support alone was not
associated with reduced stress
responsiveness.
Donoyama,
Munakata &
Shibasaki
(2010)
119
To use scientifically
valid parameters to
determine the effect
of Anma therapy on
both the body and
mind
Japan, Lab Non-RCT Fifteen healthy
female volunteers
in their fifth
decade (15)
40-minute Anma therapy
session after a 15 minute
rest and assessment.
Standard therapy of
kneading, stroking and
pressing, with comfort-
able intensity over whole
body. Five sessions over
2 and a half consecutive
weeks.
Comparator(s)
same as for the Anma
therapy group, but parti-
cipants rested for 40
minutes instead.
Cortisol (sali-
vary)
Salivary cortisol concentration
was reduced only marginally
after Anma therapy sessions.
Donoyama &
Shibasaki
(2010)
120
To examine how
differences in mas-
sage practitioners’
proficiency impacted
clients physically
and psychologically,
as measured by cor-
tisol, pain (visual
analogue score),
anxiety (State-Trait
Anxiety Inventory)
Japan, Lab RCT Females in the
fifth decade of life
with chronic mus-
cle stiffness
around the neck
and shoulders. (8)
40 minutes Anma Ther-
apy (whole body
through clothing, using
kneading, stroking and
pressing).
Provider: trained mas-
seuse
Comparator(s)
(1) Intervention adminis-
tered by 1st year student
of massage and acupunc-
ture (2) Intervention
administered by 2nd
year student (3): Rest on
massage table
Cortisol (sali-
vary)
For concentration levels of
salivary cortisol, post-inter-
vention values were signifi-
cantly lower than those
obtained pre-intervention;
however, there were no signif-
icant differences among the
four interventions.
Donoyama,
Shoji & Muni-
kata (2005)
82
To determine the
effect of Anma ther-
apy on both the
body and mind.
Impact on Cortisol
s-IgA, Pain (visual
analogue score),
anxiety (State-Trait
Anxiety Inventory).
Japan,
Clinical
Non-RCT Intervention¼3
patients, 51– 74
years with a vari-
ety of diagnosis
Non-inter-
vention ¼3
‘healthy’ college
students, 22– 43
years with a mus-
culoskeletal (MS)
injury (6)
15 minute rest followed
by 40 minutes Anma
Therapy (whole body
through clothing, using
kneading, stroking and
pressing), twice a week
for 2 and half weeks.
Five sessions in total.
Provider: not stated
Comparator(s)
Same as for intervention
group except Anma was
replaced with resting on
the bed for the same
period.
Cortisol (sali-
vary)
Marginal decreases for corti-
sol in Anma group. Results
were considered inconclusive
due to study design, particu-
larly differences between
groups and small sample size.
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Citation Study aims Setting Study Type Population (N ¼) Intervention Outcomes Key findings
Elverson et al.
(2012)
83
To explore relation-
ships between
selected social regu-
lation behaviors
(holding and feed-
ing) and the transi-
tional newborn
infant’s cortisol
response during the
first 6 hours after
birth.
USA, Clinical Correlational
study
Mothers and their
term transitional
newborn infants
(46 dyads)
Behaviors of 46 mothers
and their term transi-
tional newborn infants
were measured with the
Index of Mother-Infant
Separation. For each
infant, eight unique ran-
dom times for Index of
Mother– Infant Separa-
tion observations during
each of the 6 hours after
birth (total of 48 obser-
vations) were under-
taken. The first saliva
sample was collected at
15 to 45 minutes of age,
except after cesarean
births when saliva was
collected as soon as pos-
sible after the mother
and infant returned to
the labor– delivery–
recovery room (n ¼10,
22% of sample, oldest
was 82 minutes of age).
Subsequent saliva sam-
ples were obtained at
2 hours (15 minutes)
and 6.5 hours (15 min-
utes) after birth. In addi-
tion, saliva samples were
collected before the bath
(after admission to the
nursery) and 20 to 30
minutes after the begin-
ning of the initial bath.
Cortisol (sali-
vary)
A higher percentage of obser-
vations in which mother was
holding infant was related to
lower infant total cortisol dur-
ing the first 6 hours after
birth.
Feldman, Singer
& Zagoory
(2010)
128
To measure the
effects of touch on
infant stress reactiv-
ity during simulated
maternal depriva-
tion
Israel, Lab RCT Mothers and their
infants (53 dyads)
Fifty-three dyads were
tested in two paradigms:
still-face (SF) and still-
face with maternal touch
(SFþT). Maternal and
infant cortisol levels
were sampled at base-
line, reactivity, and
recovery and mother’s
and infant’s cardiac
vagal tone were mea-
sured during the free
play, still-face, and
reunion episodes of the
procedure.
Cortisol (sali-
vary) Vagal
tone (Vna)
Oxytocin
(serum)
Cortisol reactivity was higher
among infants in the SF con-
dition. In the recovery phase,
cortisol decreased for infants
in the SFþT, and it markedly
increased for those in the SF.
Vagal tone showed a greater
suppression when SF was not
accompanied by maternal
touch. In reunion phase, Vna
in touch condition recovered
to free play level, but in no-
touch, remained same as SF.
Touch synchrony during free
play was associated with
higher infant vagal tone, not
cortisol. Touch myssynchrony
– maternal tactile stimulation
while the infant gaze averts
correlated with higher mater-
nal and infant cortisol and
higher gaze aversion, and
lower infant Vna during free
play.
Field et al.
(1992)
89
To examine the
independent effects
of massage on the
behaviors of chil-
dren and adoles-
cents hospitalized
for depression or
adjustment disorders
USA, Clinical RCT Children and ado-
lescents hospital-
ized for
depression or
adjustment disor-
ders (72)
52 subjects received a 30
minute back massage per
day for 5 days.
Provider: psychology stu-
dents
Comparator(s)
20 subjects received a
videotape viewing for
the equivalent time
Cortisol
(saliva), Corti-
sol (urine), nor-
epinephrine,
epinephrine and
dopamine
In the short term, to 30 min-
utes follow-up there was a
decrease in salivary cortisol
only. Salivary cortisol did not
change over the 5 day period
but both urinary cortisol and
urine norepinephrine did
decrease over the 5 day
period.
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Citation Study aims Setting Study Type Population (N ¼) Intervention Outcomes Key findings
Field & Grizzle
(1996)
86
To compare the
effects of massage
and relaxation ther-
apies on anxiety
and depression in a
sample of depressed
adolescent mothers
USA, Clinical RCT Depressed adoles-
cent mothers who
had recently given
birth at a large
inner-city hospital
and were
recruited from the
hospital’s mater-
nity ward (32)
The massage therapy
subjects (N ¼16)
received a 30-minute
massage per day on two
consecutive days per
week for five consecutive
weeks (10 massages).
Provider: trained
masseuse
Comparator(s)
The relaxation therapy
subjects (N ¼16) spent
the same amount of time
in relaxation therapy as
the massage therapy sub-
jects spent in MT. The
first 15 minutes con-
sisted of yoga exercises.
The second 15-minute
segment consisted of
progressive muscle
relaxation.
Cortisol
(salivary and
urinary)
Lower salivary cortisol levels
after massage therapy (no
effect for the relaxation
group); and lower urine corti-
sol levels on the last day
versus the first day of massage
therapy (no effect for the
relaxation group). Only the
massage therapy group
showed lower stress hormone
(cortisol) levels after their ses-
sions. In addition, only the
massage therapy group experi-
enced a reduction in depres-
sion and in stress (as
manifested by their lower uri-
nary cortisol levels) across the
course of the study.
Field et al.
(2009)
84
To assess the effects
of pregnancy mas-
sage by significant
others on prenatal
measures as well as
perinatal outcomes
USA, Clinical RCT Depressed women
recruited between
16 and 20 weeks
gestation from
two ultrasound
clinics. Primarily
low socioeco-
nomic status.
20% met criteria
for major depres-
sive disorder.
(129)
Massage group received
2 moderate pressure
massages per week for a
period of 12 weeks.
Provider: significant
others who were taught
the massage by a mas-
sage therapist and were
given DVDs for at-home
coaching in the massage
procedure.
Comparator(s)
Control group: standard
treatment
Newborn corti-
sol (salivary)
Maternal corti-
sol (salivary)
Massage group neonates had
lower cortisol levels. The mas-
sage group mothers had lower
cortisol levels (M ¼128.6
versus 2328.8,
F¼4.17,p ¼.05). Newborns
of the massaged mothers also
had lower cortisol levels than
the newborns of the control
mothers.
Field et al.
(2004)
85
To assess a more
cost-effective form
of massage therapy,
namely having the
‘‘significant other’’
instead of a massage
therapist provide
the massage
USA, Clinical RCT Depressed preg-
nant women 8–
24 weeks gesta-
tion recruited
from obstetric
and gynaecology
clinics. Of middle
socio-economic
status (112)
Two 20-minute massages
per week over 16 weeks.
Provider: Trained mas-
sage therapists taught
the massage to the ’’sig-
nificant others’’ of the
women.
Comparator(s)
(1) Progressive muscle
relaxation comparison
group
(2) Standard prenatal
care only group (3)
Group of 28 non-
depressed women
Cortisol (uri-
nary) Catecho-
lamines (norepi-
nephrine, epi-
nephrine, dopa-
mine) (urinary)
Serotonin (uri-
nary)
A group by first/last day inter-
action effect showed that the
massage therapy group experi-
enced the following effects: i)
increased serotonin levels; ii)
decreased cortisol levels; iii)
increased dopamine levels;
and iv) decreased norepineph-
rine levels.
Field, Grizzle
et al. (1996)
87
To evaluate the
potential benefits of
massage therapy for
healthy infants who
were born to
depressed mothers
USA, Clinical RCT 40 full-term I-to-
3-month old
infants born to
depressed adoles-
cent mothers (40)
Massage-therapy infants
were provided a 15 min-
ute massage midway
between morning feed-
ings 2 days per week for
6 weeks. The therapist
placed a small amount
of mineral baby oil on
the palms of her warm
hands and placed her
hands on the infant’s
chest then worked on six
regions of the infant’s
body.
Provider: researcher
Comparator(s)
The rocking group: Dur-
ing this condition, the
infant was held in a
cradled position by the
researcher and rocked in
a rocking chair.
Cortisol (sali-
vary and uri-
nary) Norepi-
nephrine (Uri-
nary) Epineph-
rine (urinary)
Serotonin (uri-
nary)
Salivary cortisol levels
decreased in the massage
group during the massage
unlike the rocking group
infants whose cortisol levels
remained the same. Over time
(comparing day 1 and day
12), the massage group expe-
rienced decreases in urinary
catecholamine and cortisol
levels and increased serotonin
levels. Increased soothability
and decreased stress levels, as
suggested by lower cortisol
and catecholamine levels, may
have contributed to the
infants’ enhanced responsivity.
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Citation Study aims Setting Study Type Population (N ¼) Intervention Outcomes Key findings
Field, Ironson
et al. (1996)
88
To investigate the
effects of massage
on alertness as mea-
sured by EEG and
by speed and accu-
racy of performance
on math computa-
tions. In addition,
anxiety, depression
and cortisol levels
were expected to
decrease.
USA, Clinical RCT Medical faculty
and staff members
(80% females, M
age ¼26). (50)
Chair massage: 15 min-
utes a day, 2 days a
week for 5 weeks, and
the sessions were sched-
uled at noon each day.
Standard Swedish mas-
sage procedure (knead-
ing of muscles) was
used.
Provider: trained mas-
seuse
Comparator(s)
Relaxation control
group: The subjects were
asked to relax by tight-
ening and relaxing the
same body parts as those
that were massaged for
the massage therapy
group (and in the same
sequence).
Cortisol (sali-
vary)
Neural activity
(EEG)
Salivary cortisol levels were
lower following the massage
but not the control sessions
but only on the first day (a
repeated measures by group
interaction effect revealed a
decrease in salivary cortisol
levels on the first day for the
massage group and an
increase on the last day for
the relaxation control group).
No effect on cortisol was
observed after 5 weeks of
massage.
Field et al.
(1998)
90
Massage therapy
was expected to
reduce stress hor-
mones in patients
with burns injuries
before debridement
USA, Clinical RCT Patients with burn
injuries at a Burn
Center (28)
Standard care and a 20
minute massage once a
day for 1 week. Massage
took place just before
debridement. Massage
was delivered in a supine
then prone position.
Provider: trained mas-
seuse
Comparator(s)
Usual care plus 20 min-
utes of sitting and relax-
ing.
Cortisol (sali-
vary)
On both days the salivary
cortisol levels decreased after
massage in the massage group
but there was no difference in
the control group. Salivary
cortisol (measured before the
massage) was lower after the
5 day period than before.
Fujita et al.
(2006)
91
To evaluate the
effects of baby mas-
sage on mothers’
mood status and
salivary cortisol
level within 3
months after deliv-
ery
Japan, Clini-
cal
Non-RCT Mothers who had
just given birth
(39)
Baby massage (stroke
and/or massage each
area of the babies’ body;
legs, belly, chest, arms,
and back). At least 10
minutes/day until 3
months after delivery.
Provider: mother
Comparator(s)
Control group (no mas-
sage)
Cortisol (sali-
vary)
No significant differences in
salivary cortisol levels between
groups, however, salivary cor-
tisol did increase in the con-
trol group and decrease in the
massage group over time.
Garner et al.
(2008)
92
To examine the
effectiveness of a
relaxation massage
therapy programme
in reducing stress,
anxiety and aggres-
sion on a young
adult psychiatric
inpatient unit.
Australia,
Clinical
Non-RCT Young adult psy-
chiatric inpatients
aged 15– 25 years
(32)
MT consisted of a 20
minute massage therapy
session offered daily to
patients during their
period of hospitalization.
Natural massage balm
containing no essential
oils or scent, was applied
to forearms and hands.
Measures were taken at
baseline and follow-up
(after conclusion of 7
weeks) and just before
and immediately follow-
ing both the first and
last massage sessions.
Provider: trained mas-
seuse
Comparator(s)
Treatment as usual
Cortisol (sali-
vary)
No differences in cortisol
levels between groups over-
time. There were some imme-
diate effects of massage on
cortisol. Following the 20
minute massage therapy ses-
sion there was a significant
reduction in saliva cortisol
levels at both the initial and
final massage therapy session.
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Citation Study aims Setting Study Type Population (N ¼) Intervention Outcomes Key findings
Gitau et al.
(2002)
93
To determine the
effects of a 20 min-
ute intervention of
maternal skin-to-
skin contact, mas-
sage, or a control
period, on stress (as
measured by sali-
vary cortisol) of
pre-term babies
USA, Clinical Non-RCT Clinically stable
preterm babies no
longer requiring
intensive care sup-
port and within 4
weeks of birth in
a low dependency
unit (40)
20 minute skin-to-skin
over 2 consecutive days.
The mother was seated
on a standard rocking
chair, tilted at an angle
of approximately 608.
Provider: mother
Comparator(s)
(1) 20 minute massage
consisted of gentle mas-
sage of the trunk and
limbs using rachis oil.
Massage was carried out
at a particular time of
day, independent of the
state of the baby. (2)
Control group
Cortisol
(salivary)
Control: No significant
change in cortisol over time
Massage group: no significant
change overall Skin-to-skin
contact: there was a reduction
in saliva cortisol, and the
overall reduction for the
whole group was highly
significant.
Gordon et al.
(2010)
94
To determine
impact of oxytocin
(OT) and salivary
cortisol (CT) on tri-
adic synchrony.
Israel, Home Correlational
study
Cohabitating par-
ents and their
healthy firstborn
infant (37)
Families were visited at
home twice during the
evening hours (4– 8 PM).
Interactions were video-
taped between each par-
ent and the child. On
the second home visit,
families were videotaped
in a free-play triadic
interaction. Parents were
instructed that the two
of them play together
with the infant as they
normally do and no spe-
cific position or toys
were required.
Triadic syn-
chrony:
Moments of
coordination
between physi-
cal proximity
and affectionate
touch between
the parents as
well as between
parent and
infant while
both parent
and child are
synchronizing
their social gaze
Among mothers, OT was an
independent positive predictor
and cortisol (CT) was an inde-
pendent negative predictor of
triadic synchrony. For fathers,
only OT independently pre-
dicted triadic synchrony and
no relations were found
between paternal CT and syn-
chrony in the family triad,
indicating that higher paternal
OT predicted higher levels of
triadic synchrony
Grewen et al.
(2005)
111
To examine whether
the magnitude of
plasma oxytocin
(OT), norepineph-
rine (NE), cortisol,
and blood pressure
(BP) responses
before and after a
brief episode of
warm contact (WC)
with a spouse/part-
ner may be related
to the strength of
perceived partner
support.
USA, Lab Pre-test post-
test
Healthy couples
living with their
current spouse or
monogamous
partner for at
least 1 year (76)
Baseline: Partners were
seated in comfortable
chairs in separate rooms.
Warm contact: Couples
were seated on a love-
seat in a quiet room and
instructed to sit close
together, holding hands
if they felt comfortable
doing so. They were
asked to talk about a
time they had spent
together that made them
feel closer as a couple (2
minutes). They then
watched a 5-minute seg-
ment of a romantic
video they had previ-
ously seen. They then
were instructed to talk
for 2 minutes about a
time when they felt close
as a couple. At the end
of this session, partners
stood for a 20-second
hug.
Provider: partner Post-
contact: Subjects were
moved to separate cham-
bers to rest quietly alone
for 10 minutes.
Oxytocin
(plasma) Corti-
sol (plasma)
Norepinephrine
(plasma)
Cortisol levels were lower
after WC than before it in
both men and women. How-
ever, there were no differences
in cortisol between subjects
reporting high versus low
partner support.
Individuals reporting high
versus low partner support
exhibited greater OT across
the protocol (between sub-
jects). There were significantly
greater mean OT levels in the
high versus low partner sup-
port groups at all measure-
ment times. The link between
greater partner support and
higher OT values was
observed in men and women
at baseline and was present
after WC with partner in
women (postcontact rest alone
minute 4). When baseline OT
was examined by partner sup-
port quartiles, a consistent
pattern of increasing OT with
increasing partner support
was seen.
Although there were no links
between greater partner sup-
port and lower diastolic blood
pressure, heart rate, NE, or
cortisol, correlations of higher
OT with lower systolic blood
pressure, diastolic blood pres-
sure, and NE were obtained.
These associations were seen
in women but not men.
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Citation Study aims Setting Study Type Population (N ¼) Intervention Outcomes Key findings
Hernandez-Reif
et al. (2004)
95
To examine massage
therapy for women
with breast cancer
for i) improving
mood and biological
measures associated
with mood enhance-
ment (serotonin,
dopamine), ii)
reducing stress and
stress hormone
levels, and iii)
boosting immune
measures
USA, Clinical RCT Women with
Stage 1 or 2
breast cancer
diagnosis within
the past 3 years
and at least 3
months post-sur-
gery, chemother-
apy, and/or
radiation therapy
(34)
Received 15 massages
during the study period
(three massages each
week for 5 weeks). Each
massage was 30 minutes
long and consisted of
Swedish, trager, and acu-
pressure techniques. The
massages were con-
ducted in a quiet and
private room on a mas-
sage table.
Provider: trained mas-
seuse
Comparator(s)
Control group: standard
medical care alone.
Norepinephrine
(urinary) Epi-
nephrine (uri-
nary) Cortisol
(urinary) Dopa-
mine (urinary)
Urinary 5-
Hydroxyindo-
leacetic acid (a
metabolite of
serotonin)
Cortisol stress hormone, nor-
epinephrine, and epinephrine
levels did not decrease follow-
ing massage therapy. How-
ever, for the massage therapy
group there was an increase in
(1) dopamine, and (2) seroto-
nin levels, from the first to the
last day. The control group
showed a significant increase
in norepinephrine.
Hietanen et al.
(2008)
132
We aimed to deter-
mine whether seeing
another person’s
direct vs. averted
gaze has an influ-
ence on the obser-
ver’s neural
approach-avoidance
responses. We also
examined whether it
would make a dif-
ference if the parti-
cipants were
looking at the face
of a real person or a
picture.
Finland, Lab Non-RCT Adults with nor-
mal or corrected-
to-normal vision
(20)
Participants viewed a
face/gaze stimulus and a
control object (a radio)
in four different condi-
tions factorially manipu-
lating the gaze/object
direction (direct and
averted) and the stimu-
lus– presentation mode
(picture and live). The
pictures were presented
on a computer monitor,
whereas the live stimuli
were presented through
a liquid crystal shutter.
Provider: researchers
Comparator(s)
Two small, portable
radios (presented in pic-
ture and live)
EEG activity
(power in the
alpha band)
Skin conduc-
tance responses
Measurements of hemispheric
asymmetry in the frontal EEG
activity indicated that another
person’s direct gaze elicited a
relative left-sided frontal EEG
activation (indicative of a ten-
dency to approach), whereas
averted gaze activated right-
sided asymmetry (indicative of
avoidance). Skin conductance
responses were larger to faces
than to control objects and to
direct relative to averted gaze.
Gaze direction also influenced
subjective ratings of emotional
arousal and valence. However,
all these effects were observed
only when participants were
facing a real person, not when
looking at a picture of a face.
Holt-Lundstad,
Birmingham &
Light (2008)
112
To investigate the
impact of warm
touch enhancement
on plasma oxytocin,
24-hour ambulatory
blood pressure, and
salivary cortisol and
alpha amylase
USA, Lab RCT Healthy married
couples (68)
Couples underwent one
session of training in lis-
tening-touch based on
the types of touch used
in Rosen Method Body-
work and one training
session in head, neck,
and shoulder massage.
The intervention couples
then practiced these
warm touch techniques
for 30 minutes 3 times
per week for 4 weeks.
Provider: partners
Comparator(s)
Behaviour monitoring
control group: Subjects
were told not to change
anything about their
normal behaviour with
their spouse and to sim-
ply keep a diary of their
physical affection and
mood.
Oxytocin
(plasma and
salivary) Corti-
sol (salivary)
Alpha amylase
There was no main effect of
the intervention on salivary
cortisol, or plasma OT, how-
ever, there was a significant
effect of the intervention for
salivary OT obtained at home
during the month of treat-
ment/monitoring. Even as
early as intervention week 1,
salivary OT levels were signif-
icantly higher in the interven-
tion group than the control
group. Both men and women
in the intervention condition
continued to have higher OT
levels than those in the moni-
toring control condition dur-
ing the final week. This effect
remained significant after
adjusting for pre-treatment
plasma OT and even after
adjusting for their higher
week 1 OT levels, indicating
that further significant albeit
modest increases in OT activ-
ity occurred with greater
exposure to the warm touch
intervention. After controlling
for pre-treatment levels, post-
treatment alpha amylase was
significantly lower among hus-
bands and wives in the inter-
vention group than those in
the control group.
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Citation Study aims Setting Study Type Population (N ¼) Intervention Outcomes Key findings
Im & Kim
(2009)
96
To test the effect of
Yakson and Gentle
Human Touch
(GHT) on preterm
infants’ stress and
behaviours com-
pared to usual nurs-
ing care
South Korea,
Clinical
Non-RCT Pre-term infants
with a gestational
age of 26– 34
weeks at birth
(59)
Yakson: 15 minutes
twice a day for 15 days.
Yakson consists of three
5-minute phases: resting
the hand on the infant,
gentle caressing, and
resting the hand again.
Provider: massage
trained clinicians (nurse)
Comparator(s)
(1) GHT: 15 minutes
twice a day for 15 days.
GHT consists of hand
resting for 15 minutes.
(2) Control group: usual
care.
Cortisol (uri-
nary) Norepi-
nephrine (uri-
nary)
Following the intervention
period, infants in the Yakson
and GHT groups had signifi-
cantly lower stress hormone
levels compared to the control
group infants. No significant
difference was found in stress
hormone levels between Yak-
son and GHT group infants.
Ironson et al.
(1996)
113
To examine the
effects of daily mas-
sage for one month
on the immune
function of HIVþ
and HIV- gay men
USA, Lab Mixed design
including pre-
test post-test
and crossover
for part of the
sample
HIVþand HIV-
gay men with no
AIDS-defining
symptoms. If on
Antiretroviral
therapy, had to
have been on
them for at least
3 months. (29)
45 minute daily mas-
sage.
Provider: trained mas-
seuse
Comparator(s)
Control (no massage)
Cortisol (uri-
nary and sali-
vary) Norepi-
nephrine (uri-
nary) Epineph-
rine (urinary)
There was a significant
decrease in urinary cortisol,
during the massage period and
a marginally significant
increase during the control
period. For catecholamines
during the massage period, the
change was not significant.
Jung et al.
(2006)
122
To evaluate differ-
ences in the effects
of Qi therapy with-
out touching or
with touching on
anxiety, mood, neu-
rohormones, and
cellular immune
function
South Korea,
Lab
RCT Men aged 20– 35
years (women
were not included
because of their
hormonal varia-
tions) (24)
Qi no touching (QTN):
The subjects received
QTN for 10 minutes
according to the proce-
dures described in the
standard sequence. The
Qi master’s hand is
moved about 3 –10 cm
from the body in a pat-
tern from the head to
the toes. When a subject
arrived for the experi-
ment, he was taken to
the experimental room
and seated on a bed.
After 5 minutes rest
(Pre), the subject
received Qi. Qi therapy
was followed by 10 min-
utes of rest (Post I).
Provider: trained mas-
seuse
Comparator(s)
Qi touching (QTT):
Administered by the
same Qi master, who
pressed several impor-
tant acupoints with
effort or intention to
insert Qi through them.
Cortisol
(plasma)
No significant differences
between the effects of Qi ther-
apy with and without touch-
ing. There were significant
effects on anxiety, alertness,
depression, fatigue, tension,
cortisol levels, and NK cell
cytotoxicity for both QTN
and QTT, and on neutrophil
function for QTN only. These
findings suggest that there are
few differences between the
effects of QTN and QTT.
Kim et al.
(2014)
125
To examine the
relationship between
maternal oxytocin
response and
mother-to-infant
gaze during periods
of infant non-dis-
tress as well as dis-
tress. Two patterns
of maternal gaze,
maternal gaze
toward and gaze
shifts away from the
infant, were micro-
coded while mothers
interacted with their
7-month-old infants
during a modified
still-face procedure.
USA, Lab Pre-test post
test
Non-clinical sam-
ple of first-time
mothers (50)
The Modified Still Face
Procedure (MSFP) is a
three-phase procedure,
during which the mother
interacts freely with the
infant in Phases 1 and 3,
but is instructed to
maintain a neutral ‘still
face’ during Phase 2,
suddenly depriving the
infant of maternal con-
tingency and inducing
stress in the infant. The
MSFP thereby offers an
opportunity to examine
the mother’s behavior in
the absence and presence
of signals of infant dis-
tress.
Oxytocin
(plasma)
The mother’s oxytocin
response was positively associ-
ated with the duration of time
her gaze was directed toward
her infant, while negatively
associated with the frequency
with which her gaze shifted
away from her infant. Impor-
tantly, these associations were
more pronounced under con-
ditions of infant distress than
non-distress. Mothers who
showed low/average oxytocin
response demonstrated a sig-
nificant decrease in their
infant gaze during periods of
infant distress, while such
change was not observed in
mothers with high oxytocin
response.
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Citation Study aims Setting Study Type Population (N ¼) Intervention Outcomes Key findings
Kim, Kim &
Ko (2016)
123
A scalp massage
was conducted on
female office work-
ers divided into a
15 minute group
and 25 minute
group and its effect
on stress hormone,
blood pressure and
heart rate was ana-
lyzed in order to
provide a theoretical
rationale to apply
scalp massage as
stress therapy
South Korea,
Lab
RCT Female office
workers, aged
between 20– 49
years (34)
Scalp massage was per-
formed for 15 minutes/
session for experimental
group (I)
Provider: trained
masseuse
Comparator(s)
(1) 25 minutes/session
for experimental group
(II), twice a week, for a
total of 20 times over 10
weeks in both groups.
(2) Control group: no
massage
Epinephrine
(plasma) Nor-
epinephrine
(plasma) Corti-
sol (plasma)
In this study, 15-minute and
25-minute scalp massages had
a significant effect on norepi-
nephrine and cortisol while
the 25-minute scalp massage
had a significant effect on
epinephrine. This suggests that
a scalp massage decreases the
activation of the sympathetic
nerve while increasing the
activation of the parasympa-
thetic nerve, resulting in a
decrease in the secretion of
norepinephrine and cortisol,
or in other words, stabiliza-
tion of hormone levels.
Kramer et al.
(1975)
97
To ascertain
whether touch, in
the form of extra
tactile stimulation,
would result in
more rapid physical
and social develop-
ment and a greater
degree of social
development of the
premature infant
USA, Clinical Non-RCT Premature infants
with a gestational
age of 38 weeks
or less (14)
Extra tactile stimulation:
gentle, non-rhythmic
stroking of the greatest
possible area of skin sur-
face of the infant’s body
by the nurse’s hand for a
total of 48 minutes a
day and for a minimum
of two weeks while the
infant was confined to
an isolette (the 48 min-
utes was additional to
other tactile stimulation
provided in the usual
course of premature
infant care)
Provider: massage
trained clinician (nurse)
Comparator(s)
Control group: no extra
tactile stimulation
Cortisol
(plasma)
Plasma cortisol levels revealed
no significant difference
between the two groups. An