Fundamentals of Health Neuroscience, 1st Edition

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xii Author biographies

particular, her research focuses on (1) understanding the neural mechanisms

underlying cognitive, psychological, and mental health in young and older
adulthood, (2) examining individual difference factors (e.g., personality, ge-
netics, and environment) contributing to interindividual variability in cogni-
tive, psychological, and mental health, as well as the trajectories of brain and
cognitive aging, (3) investigating and developing psychological interventions
to improve health and ameliorate the aging-related decline of health and brain
functions. Dr. Tang has published over 30 peer-reviewed journal articles on
cognitive, clinical, and health neuroscience and has coauthored the Elsevier
book The Neuroscience of Meditation: Understanding Individual Differences.
Chapter 1

Introduction
Abstract
Health neuroscience is a new interdisciplinary field encompassing research from
cognitive, affective, and social neuroscience, integrative health (e.g., physical, mental,
emotional, and cognitive health), health psychology, and the science of behavior
change. In this chapter, we will provide an overview of health neuroscience research
areas and representative topics. Major noninvasive research methodologies and tech-
niques widely used in health neuroscience research will also be discussed. We will also
discuss how knowledge obtained from these research areas could facilitate translational
applications in achieving and promoting integrative health, as well as health behavior
change. We propose that prevention and treatment of diseases should target the root
causesdthe dysfunction and imbalance of brain and body. We also propose that when
treating these diseases, evidence-based bodyemind interventions may be more effec-
tive than dealing with each symptom or disorder in isolation through various treatment
approaches. Finally, we will discuss the concept of precision health.

Keywords
Behavior change; Brainebody interaction; Health neuroscience; Integrative bodye
mind interventions; Integrative health; Precision health.

Health neuroscience
According to the definition of the National Institutes of Health (NIH) (NCCIH,
2022), integrative health is different from whole-person health and refers to
helping individuals, families, communities, and populations improve and restore
their health in biological, behavioral, social, and environmental domains.
Moreover, integrative health brings conventional and complementary ap-
proaches together and emphasizes multimodal interventions, such as medication
and physical rehabilitation from conventional approaches, as well as meditation
and acupuncture from complementary and alternative approaches. The focus of
integrative health is on treating the whole person rather than one organ or
symptom. It should be noted that whole-person health is not the same as whole
health, which is implemented by the Veteran’s Health Administration (Jonas &
Rosenbaum, 2021; VA, 2022). Here, we discuss health neuroscience within the
framework of integrative health with a focus on brainebody interventions.

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2 Fundamentals of Health Neuroscience

How the brain/mind and body affect our health behavior such as health
mindsets, decision-making, actions, and health outcomes across the lifespan
has been an important question for both the scientific community and the
society as a whole. However, some key questions remain largely unaddressed.
For instance, how the brain and body interact with each other to affect health
outcomes, and how to predict health outcomes through biomarkers that capture
the interaction between body and mind.
Health neuroscience is a new interdisciplinary field encompassing research
from (but not limited to) cognitive, affective, and social neuroscience, integrative
health (e.g., physical, mental, emotional, and cognitive health), health psy-
chology, and the science of behavior change. Health neuroscience focuses on
understanding the relationship between the brain, mind, and body (physiology),
and how they relate and contribute to overall health and well-being. Moreover,
health neuroscience seeks to explore how the brain and body interact or work
together to affect health mindsets, decision-making, and behavior. Health
neuroscience was first proposed in 2014 and included health psychology and
neuroscience, and then integrated with social, cognitive, and affective neuro-
science in 2020 (Erickson et al., 2014; Inagaki, 2020). Here we extend the
framework of health neuroscience (see Fig. 1.1) and discuss several key areas of
health neuroscience and its applications in achieving physical, mental,
emotional, and cognitive health, and promoting health behavior change.

FIGURE 1.1 The framework of health neuroscience. Health neuroscience encompasses research
from (but not limited to) cognitive, affective, and social neuroscience, integrative health (e.g.,
physical, mental, and cognitive health), health psychology, and the science of behavior change.
 Introduction Chapter | 1 3

Brain serves as a predictor of health

Research has shown that measures of brain resting-state, functional and
structural changes can predict health outcomes and help elucidating the un-
derlying mechanisms and efficacy of various prevention and intervention
(Berkman & Falk, 2013; Gianaros & Jennings, 2018; Tang et al., 2012; Woo
et al., 2017). For example, the anterior cingulate cortex (ACC), a brain region/
structure, is involved in both cognitive and emotional processing and is sen-
sitive to both reward and pain. ACC supports self-regulation (self-control, also
called executive function) and exhibits functional and structural abnormalities
in individuals with behavioral problems and mental disorders including
ADHD, anxiety, depression, stress-related disorders, schizophrenia, addiction,
and neurodegenerative disorders (Posner et al., 2007; Tang et al., 2015; Zhang
& Peng, 2023). One study showed that ACC regulates blood pressure reactions
to behavioral stressors in humans (Gianaros et al., 2005). Another study
showed resting-state functional connectivity within the ACC predicts stressor-
evoked cardiovascular reactivity (Sheu et al., 2011). Pregenual or rostral ACC
has been implicated in depression, such that its activity correlates with
depression severity and may serve as a promising predictor of treatment
response in depression (Pizzagalli, 2011). Cognitive neuroscience research has
also revealed that brain resting-state functional connectivity can predict task
performance in human participants. Thus, various brain functional and struc-
tural measures can serve as reliable predictors for various aspects of health.
However, some questions remain to be investigated. For example, what health-
relevant physiological responses are predicted by or related to brain changes?
How to develop brain-based biomarkers for predicting differential responses to
established treatments of mental disorders? How to better inform individual-
level treatment selection (i.e., precision mental health/psychiatry) based on
brain biomarkers? These are some of the interesting questions in the field of
health neuroscience, which we will further discuss in Chapters 2, 4, 5, and 11
of this book.

Brain serves as an outcome of health

Brain is also an outcome of health. In fact, there is a lot of research across
different disciplines of neuroscience in which the brain is studied as an
outcome of health. For instance, research has shown that social determinants
of health such as socioeconomic status (SES) are associated with individual
differences in brain structure and function. For example, individuals with
childhood socioeconomic disadvantage (i.e., low SES) tend to have an earlier
and shortened period of brain development and maturation compared with
those with higher SES (Sydnor et al., 2021). Moreover, low childhood SES is
related to functional and structural brain abnormalities in children and ado-
lescents. Likewise, a wide range of investigations on psychopathology and
4 Fundamentals of Health Neuroscience

neurodegenerative disorders have uncover structural and functional abnor-

malities in the brain in patients relative to healthy control participants. Inter-
estingly, recent studies have begun to show that some of these abnormalities
seem to be common across disorders. For instance, prior neuroimaging studies
often investigate patients with major depressive disorder (MDD) and mild
cognitive impairment (MCI) separately to demonstrate unique brain changes
due to each disorder. However, both MCI and MDD have common deficits in
mental and social functioning, which may be reflected as shared volumetric
reductions in some brain areas. A meta-analysis of voxel-based morphometry
studies in MDD, MCI, and age-matched controls found that MDD and MCI
patients have shared volumetric reductions in the insula, inferior frontal gyrus,
superior temporal gyrus, amygdala, hippocampus, and thalamus (Zacková
et al., 2021). These results indicate that the brain itself can serve as an outcome
of health that is reflective of an individual’s current state of health. We have a
more in-depth discussion of the brain as an outcome of health in Chapters 5, 6,
7, 8, and 9 of this book.

Brainebody interaction and health

The brain/mind and body cannot be separated in a living system. Growing
evidence has shown that the brain/mind and body always work together to
affect health behavior and outcomes. For instance, recent research has shown a
close relationship between heart health and brain health, with cardiovascular
diseases potentially leading to brain diseases such as stroke, dementia, and
cognitive impairment (Zhao et al., 2023). Using longitudinal brain imaging
and physiological phenotypes from the UK Biobank, one recent study
demonstrated human aging involves the brain and multiple organs including
cardiovascular, pulmonary, musculoskeletal, immune, renal, hepatic, and
metabolic systems (Tian, Cropley, et al., 2023). Another study with a large
sample size (N ¼ 173,168) found that poor body health was a stronger indi-
cator of psychiatric illnesses relative to brain changes in individuals with
psychiatric disorders such as anxiety, depression, bipolar disorder, and
schizophrenia (Tian, Di Biase, et al., 2023). However, it was found that brain
health enabled a more accurate differentiation between distinct neuropsychi-
atric diagnoses than body health.
Can we detect the interaction (dynamic relationship) between the brain and
body? A randomized controlled trial (RCT) with a 5-session of mindfulness
versus relaxation training provided some evidence of a dynamic relationship
between the brain and body (Tang et al., 2009). Participants practiced either
30 min of mindfulness or relaxation training per session with their brain waves
recorded in the midline anterior cingulate cortex (ACC). To measure the body,
there were also physiological measures including respiratory rate and ampli-
tude, heart rate, heart rate variability (HRV), and skin conductance response
(SCR). Results showed that during and after the 5-session training, the
 Introduction Chapter | 1 5

mindfulness group showed lower chest respiratory rate, heart rate, and SCR,
but greater belly respiratory amplitude than the relaxation control group. These
physiological changes indicated greater parasympathetic regulation of the
autonomic nervous system (ANS) (Tang et al., 2009). High-frequency HRV
(HF-HRV) is related to the parasympathetic activity of the ANS, and midline
ACC activation is often correlated with HF-HRV, suggesting that the ACC may
regulate parasympathetic autonomic activity. Compared with the same amount
of relaxation training, increased HF-HRV and frontal midline ACC theta power
were detected in the mindfulness group, suggesting greater involvement of the
ANS (particularly parasympathetic activity) during and after mindfulness.
Additionally, the study also found a stronger frontal midline ACC activity
following mindfulness, as well as a correlation between midline ACC theta
wave and HF-HRV, suggesting the ACC’s control over parasympathetic ac-
tivity. Together, these findings indicate that the body (indexed by HF-HRV)
and brain (indexed by midline ACC theta power) work together to support the
mindfulness state and change brain and body functioning. In some ways, the
findings are not surprising, as mindfulness training is often considered to be a
mindebody intervention that engages both the brain and the body. Moreover,
these findings are examples of how the body and brain often work together to
maintain our everyday functioning, even those that seem to involve just the
brain/mind for basic processing. Additional examples and discussion of brain
and body interaction can be found in Chapters 3, 5, 10, and 12 of the book.

Science of behavior change

Behavior change, or specifically health behavior change, is one of the most
important achievements in our lives. To maximize overall health, wellness, and
longevity, people need evidence-based strategies and tools to manage their
health behaviors and change behavior effectively when needed. Health
behavior change includes at least the changes in health mindsets, motivations,
decision-making, actions, and health outcomes. These major components of
health behavior change are consistent with the dual processes models of
behavior change, which include both automatic (implicit) and controlled
(explicit) processes (Kwasnicka et al., 2016; Miller & Rollnick, 2012; Pro-
chaska et al., 1994; Tang et al., 2013; Wood et al., 2022).
For example, mindset is a way of thinking, a set of beliefs and attitudes,
which are crucial for behavior change. A healthy mindset refers to (1) finding
ways to grow from our thoughts rather than letting them control our health and
life and (2) moving beyond negative thoughts or simply accepting them, rather
than focusing on them until they become overwhelming. Mindset shapes how
we make sense of the world and ourselves and influences how we think, feel,
and behave in any given situation. A longitudinal study tracked thousands of
people in the United States for years by asking them two questions: (1) how
much stress did you experience last year? and (2) do you believe that stress is
6 Fundamentals of Health Neuroscience

harmful to your health? Based on the public death records, the study examined
who died or not during the study period. It turned out that people who
experienced a lot of stress in the past year had a 43% increased risk of dying.
But that was only true for the people who believed that stress is harmful to
their health, and not for those who did not. These findings suggest that some
people died prematurely, not from stress, but from their beliefs that stress is
bad and harmful (Keller et al., 2012). Relatedly, other studies using nationally
representative samples also indicated that perceptions about health behaviors
(e.g., level of physical activity) play an important role in shaping health out-
comes (Zahrt & Crum, 2017). Although mindset is associated with processes
involving motivation, decision-making, actions, and health outcomes, these
processes are also important to initiate and maintain behavior change and form
habits (Dweck, 2017). A recent review suggested that behavior change is
supported by both central and autonomic nervous systems (CNS and ANS)
through dual processes (Tang et al., 2022). Future research is needed to
investigate several unsolved questions such as the brainebody biomarkers of
readiness and behavior change, and how to induce automatic (implicit) and
controlled (explicit) behavior change. We will discuss some of the questions
and related research in Chapters 6, 7, and 8 of this book.

Integrative health model

The integrative health model has three componentsdconventional medicine,
complementary and alternative medicine, and self-care. Conventional medi-
cine is the mainstream medical practice and treatments that focus on disease
treatment mainly using medications and surgeries. Conventional medicine has
made advancements in treating many disorders and specific symptoms.
However, conventional medicine also has its limitations. For example, it does
not always address the root causes of certain chronic diseases. In addition,
medical spending has significantly increased, such that in the United States,
prescription drug spending has been the fastest-growing goods/service cate-
gory. For instance, in the 1950s, about 2%e3% US GDP was used for
healthcare/medical spending, whereas in the 2000s, it increased to almost 20%
of GDP. Nonetheless, we have not received better and higher quality health-
care even with the higher costs. Recent data has shown that in 2022, the overall
pharmaceutical expenditures in the United States grew 9.4% compared with
2021, for a total of $633.5 billion. For 2023, the overall prescription drug
spending continues to increase compared with 2022 based on national trends
(Tichy et al., 2023). Given that medications often have side effects, in some
cases, conventional medicine has already incorporated certain aspects of
complementary and alternative therapies to achieve better health outcomes.
Indeed, there have been increasing numbers of individuals who prefer or
benefit from complementary and alternative approaches, which is the second
component of integrative health approaches. The third component of
 Introduction Chapter | 1 7

integrative health approaches is self-care, which includes behavior change and

lifestyle approaches (e.g., nutritional) to promote wellness and emphasize our
responsibilities, awareness, and care action (Jonas & Rosenbaum, 2021;
Tang et al., 2019). Compared with conventional medicine where patients often
have the mindset that physicians should fix their problems and symptoms, and
give their health back, self-care is more focused on prevention and health
promotion through our effort and action. Therefore, there is an urgent need to
apply integrative health approaches to prevent and treat diseases, not only to
ameliorate symptoms but also to address the root causes of diseases through
our efforts and actions.
The NIH’s Research Domain Criteria (RDoC) project is an example in
response to the growing awareness of the diagnosis and treatment issues
(NIMH, 2022). Traditionally, mental disorders are determined based on the
number and type of diagnosed symptoms and the presence of distress or
impairment. This approach and the resulting diagnostic systems provide
benefits but also have numerous trade-offs including problems with hetero-
geneity. For instance, an individual can qualify for a symptom-based disorder
diagnosis in varied ways, or two individuals can be diagnosed with the same
disorder despite having few symptoms in common. The second trade-off is
comorbidity. For instance, patients who meet the criteria for one disorder often
tend to meet the criteria for other disorders. These findings indicate that to
understand the full spectrum of mental health and disorders, dividing people
into groups based on symptom counts is not ideal, and may obscure important
information about how the disorders develop and gradually emerge and how
various risk factors interact with the individuals and their environment (NIMH,
2022). Therefore, targeting the common brainebody dysfunction and imbal-
ance may be a better approach, as dysfunction and imbalance may be the
precursor of symptoms and disorders. In contrast, targeting different symptoms
through symptom relief/reduction to prevent and treat disorders could not
directly address the root causes that give rise to these symptoms (Tang, 2017,
pp. 1e94). We will further discuss the integrative health model and its
application in Chapter 12 of this book.

Promoting integrative health through evidence-based integrative

bodyemind interventions
As mentioned before, the integrative health model has three componentsd
self-care, complementary and alternative medicine, and conventional medi-
cine. The self-care approach emphasizes that we should take an active role in
maintaining our health through intentional practices and behaviors. It recog-
nizes that we have the responsibility to act to promote physical, mental,
emotional, cognitive, and social health (e.g., harmony with others). Self-care
plays a crucial role in integrative health, as it affects the effectiveness of the
8 Fundamentals of Health Neuroscience

other two components. For example, it can change our passive attitudes,
mindsets, and actions in a positive and actionable way, rather than only waiting
for physicians to fix our problems through conventional care. Clearly, self-care
requires a high level of self-control (executive function) to continuously
support health behavior change and desired health outcomes (Tang et al., 2019;
Tang et al., 2022).
The human being is a complex living system that can self-regulate and self-
organize to maintain balance, stability, and integrative health. This can be
achieved through the active homeostatic process of adapting (also called
allostasis) during changing conditions or challenges, such as from healthy to
less healthy (symptoms), and to disease stages (Langevin, 2021; Tang, 2017,
pp. 1e94; Tang et al., 2022). Through efficient self-control, our self-organized
system can promote and restore health during the stages of the bidirectional
health and disease continuumdfrom disease to less healthy (symptoms) to
healthy. Research findings indicate strengthening self-control through the CNS
and ANS interaction, and optimization can help ameliorate diverse symptoms
and treat disorders (Tang, 2017, pp. 1e94; Tang et al., 2015). Moreover,
evidence-based integrative bodyemind interventions have shown huge
promises to effectively change the brainebody biomarkers, improve self-
control, and ameliorate brainebody dysfunction and imbalancedthe precur-
sor of symptoms and disorders (Tang & Tang, 2020; Tang, 2017, pp. 1e94;
Wielgosz et al., 2019). Based on our RCTs, we take one form of bodyemind
interventiondintegrative bodyemind training (IBMT) as an example to pro-
vide evidence regarding the positive effects of mindebody interventions on
self-control and integrative health. In addition to the positive behavior change
including stress reduction, improved emotion regulation, cognitive function,
immune function, and quality of life, we reveal one of the mechanisms by
which IBMT enhances the interaction and optimization between brain/mind
and bodyda process that involves both the CNS and ANS. As described
before, a 5-session of IBMT improves the body (indexed by HF-HRV) and
brain (indexed by midline ACC theta power) interaction to strengthen self-
control, regulate brain and body dysfunction and imbalance, and ameliorate
symptoms. Our findings also highlight the role of brain self-control
networksdincreased functional and structural brain plasticity, including the
ACC and adjacent medial prefrontal cortex, posterior cingulate cortex, and
striatum, as well as the parasympathetic activity of the ANS in improving
health and well-being (Tang et al., 2022). Our results suggest that bodyemind
intervention may be a promising approach that promotes the synergistic
engagement of mind/brain and body to achieve the desired behavior change
and health outcomes. Additional discussion of the integrative health model and
related health promotion interventions can be found in Chapters 10 and 12 of
this book.
 Introduction Chapter | 1 9

Health neuroscience methodologies

Health neuroscience research involves multimodal neuroimaging (e.g., fMRI,
EEG), physiological (e.g., cortisol, heart rate variability), interventional (e.g.,
cognitive training, mindfulness, exercise, neurofeedback, brain stimulation),
behavioral, and genetic methodologies. Here, we focus on multimodal neu-
roimaging techniques. Neuroscience research is particularly complex due to
the multiple scales (top) and dimensions (bottom) of recording and analysis
across the lifetime and in different situations (see Fig. 1.2). The multiple di-
mensions include, but are not limited to, neurophysiology, neurochemistry,
cellular signaling, morphology, molecular biology, genetics, behavior, and
disease. The multiple scales include intracellular, extracellular, single neurons,
groups of neurons, networks, systems of neurons, and whole brain (Koslow,
2002). We take neuroimaging (brain imaging) and modulation techniques as
two primary examples and techniques used in human neuroscience research.
Brain imaging techniques are used to record, visualize, and investigate the
structure and function of the brain. These techniques play a crucial role in both
clinical and research settings, helping neuroscientists, psychologists, and
medical professionals better understand the brain and its various functions. We

FIGURE 1.2 The complexity of neuroscience research. Neuroscience research is particularly

complex due to the multiple scales (top) and dimensions (bottom) of analysis across the lifetime
and in different situations. From Koslow, S. H. (2002). Sharing primary data: A threat or asset to
discovery? Nature Reviews Neuroscience, 3(4), 311e313. https://doi.org/10.1038/nrn787
10 Fundamentals of Health Neuroscience

will discuss some of the most common neuroimaging techniques in the

following, and these techniques have been widely used in scientific research
and clinical settings. Magnetic resonance imaging (MRI) is one of the
commonly used neuroimaging techniques. Structural MRI provides high-
resolution images of the brain’s anatomical structures in white and gray
matter. It is commonly used to detect structural abnormalities for clinical
purposes, but also allows researchers to study and quantify different brain
structures in terms of volume, thickness, and surface area. Diffusion-based
imaging is an MRI-based technique that tracks the diffusion of water mole-
cules in brain tissues. Diffusion tensor imaging (DTI) is primarily used to map
the brain’s white matter tracts, which are situated just beneath the gray matter
and are essential for information transfer and processing across the brain. Once
these white matter tracts are modeled across the brain, researchers can assess
brain white matter integrity. For example, fractional anisotropy (FA) is an
index indicating the integrity and efficiency of white matter and has been
commonly used to assess white matter changes due to interventions or dis-
orders. One study on mindfulness training showed that there were increases in
the FA of corona radiata, an important white matter tract connecting the
anterior cingulate cortex (ACC) to other brain structures. This finding suggests
that mindfulness training could improve white matter integrity in specific re-
gions related to self-control and self-regulation. These white matter tracts can
also be used to study brain structural connectivity. For instance, white matter
tracts can be thought of as physical connections between different brain re-
gions. The greater number of tracts passing through any of the two regions can
be thought of as more or stronger structural connections between the two
regions. Measures of structural connectivity between any pairs of regions can
thus be calculated across the brain. Different studies have examined structural
connectivity within the context of health and diseases. Some of the studies and
discussion of structural connectivity can be found in Chapters 2, 3, 8, 9, and 10
of this book.
In addition to brain structural MRI, there is also brain functional MRI (fMRI),
which measures changes in blood flow and oxygenation in the brain, allowing
researchers to map brain activity in different regions. For instance, there are
studies that look at which regions in the brain are highly active (i.e., high brain
activity) during a task performance. A region that is highly active and correlates
with the task demands is often related to or support the task performance.
Moreover, fMRI can also enable the study of brain functional connectivity.
Similar to structural connectivity, functional connectivity refers to the correla-
tions between the time series of brain activation of any pairs of regions in the
brain. If two brain regions are highly synchronized in terms of their brain activity
over a period of time, then they are functionally connected. The stronger the
correlation, the stronger the functional connectivity. Functional connectivity has
been widely used in human neuroscience research and has revealed unprece-
dented insights into the functional organization of the human brain.
 Introduction Chapter | 1 11

Other than brain function and structure, the brain also has molecular sys-
tems that support various processes and functions. For instance, the neuro-
transmitter systems are considered to be part of the brain chemoarchitecture.
Magnetic resonance spectroscopy (MRS) is a technique that measures the
chemical composition of tissues within the brain and produces spectra that
reveal the concentrations of specific chemical compounds in a region of in-
terest (ROI). For example, one can measure glutamate concentrations, one
excitatory chemical compound, in various regions of the brain (Lee et al.,
2017). In recent years, MRS has been increasingly used to assess different
biochemical processes within the brain for both clinical and research purposes.
Positron emission tomography (PET) imaging is another widely used
methodology in human neuroscience research and involves injecting a radio-
active tracer into the bloodstream, which can later be captured by the PET
scanner. Specifically, the scanner detects the positrons emitted by the tracer,
creating a 3D map of metabolic activity. PET is often used to study brain
function and metabolism, such as glucose metabolism and neurotransmitter
receptor density. For example, PET can detect early abnormalities in the
glucose metabolism of the posterior cingulate cortex (PCC) and prefrontal
cortex (PFC) in patients with Alzheimer’s disease (AD). Depending on the
radioactive tracers and where they bind to in the brain, PET imaging can serve
various purposes, including the most widely used PET imaging for detecting
AD pathologies. For example, amyloid and tau are two types of AD pathology
that can be separately detected using amyloid PET and tau PET. These two
approaches have become the gold standard for clinical diagnosis of AD and
other related dementia.
Single-photon emission computed tomography (SPECT) is similar to PET,
but it uses different radiotracers and gamma-ray detection. SPECT can also be
used to study brain function, blood flow, and metabolism. In general, PET
tends to offer better spatial resolution than SPECT, but SPECT is able to offer
longer scanning time if needed by the researchers or clinicians. This is because
the radiotracers used by SPECT typically have longer half-live than the ones
used by PET. Thus, depending on the purposes, either PET or SPECT can be
used to study the same questions. Computed tomography (CT) provides
detailed images of the brain at a low cost compared with MRI and PET. CT
scans are particularly useful for identifying structural abnormalities and in-
juries, but they involve ionizing radiation. Most of the time, CT is more widely
used in clinical settings than in research settings.
There are other neuroimaging approaches that do not focus on the high-
resolution visualization of brain structures, but focus more on the resolution
of brain functional activity. Electroencephalography (EEG) is a neuroimaging
technique that records electrical activity in the brain using electrodes that are
placed on the scalp. It is commonly used in research settings to study brain
function during the performance of various tasks and monitor brain activity
during sleep. Compared with fMRI which also assesses brain functional
12 Fundamentals of Health Neuroscience

activity, EEG has a better temporal resolution and allows researchers to more
precisely link certain changes in brain electrical activity to task stimuli. EEG is
also portable, unlike MRI scanner. In addition to research purposes, EEG can
also be used in clinical settings for diagnosing conditions such as epilepsy,
which involves abnormal and excessive brain activity.
Magnetoencephalography (MEG) is another neuroimaging approach that
focuses on brain function rather than structure. MEG measures the magnetic
fields generated by neuronal activity within the brain using a dewar that in-
cludes multiple sensor coils and does not touch the scalp or the head. MEG is
often used in human neuroscience research to study brain functional activity.
Compared with EEG, MEG also has relatively better spatial resolution.
For different neuroimaging methodologies and techniques, it is important
to compare their time versus spatial resolutions and the associated hardware
complexity and price. Although the EEG technique has a temporal resolution
similar to the actual neuronal activity (in the range of 1 ms), its spatial reso-
lution is the worst among all techniques. The SPECT and PET do not provide
resolution advantages and are more expensive. In contrast, fMRI has a better
spatial resolution (around 1 mm3). However, compared with EEG and CT,
MEG and fMRI are more expensive, making them not practical for a wide
range of applications (Georgieva et al., 2013).
There are also other methodologies that are not discussed. For example,
functional near-infrared spectroscopy (fNIRS) is a technique that measures
changes in blood oxygenation in the cortex and has good temporal resolution.
fNIRS is portable and noninvasive, making it suitable for studying brain
function in various settings, including infant research. Compared with fMRI,
fNIRS has better temporal resolution but is limited in terms of the brain areas
it can measure since its detectors determine the amount of coverage. fMRI can
achieve whole-brain coverage, whereas the same is not true for fNIRS.
Neuromodulation techniques, such as neurofeedback, transcranial direct
current stimulation (tDCS), and transcranial magnetic stimulation (TMS), are
not neuroimaging techniques, but rather methodologies that use electrical or
magnetic currents/fields to temporarily disrupt or stimulate brain activity.
Depending on the behavioral outcomes of the neuromodulation, researchers
can examine the processes and functions a brain region supports. For example,
a neuromodulation of the visual cortex of the brain may induce changes in the
visual processes. Both tDCS and TMS have been used in research and clinical
applications to investigate and optimize brain function and treat behavioral
problems and clinical conditions. Neurofeedback is one type of biofeedback
that focuses on self-regulating one’s own brain activity based on EEG or fMRI
signals. An individual could be inside an MRI scanner and be given a screen
with his or her real-time brain activity. The individual is typically asked to
learn to control (inhibit or stimulate) their brain activity and optimize brain
function. For instance, researchers have speculated that ACC is crucial for
self-control such as emotion regulation. They could use neurofeedback to ask a
 Introduction Chapter | 1 13

participant to inhibit his or her ACC brain activity and then measure the in-
dividual’s emotion regulation ability. If the results show reduced emotion
regulation after a participant successfully inhibits his or her ACC activity, then
the researchers would have evidence supporting the ACC’s role in emotion
regulation. EEG neurofeedback is also widely used, as EEG is portable, cost-
effective, and convenient. However, EEG has low spatial resolution and cannot
target deep brain areas for neurofeedback, such as the hypothalamus, amyg-
dala, and striatum. In contrast, these deep brain areas or subcortical regions
can be modulated using real-time fMRI neurofeedback. In the following, we
will briefly discuss several key topics in the EEG and fMRI neurofeedback
field. Additional discussion can be found in Chapter 10 of the book.

EEG and fMRI neurofeedback

What factors affect the neurofeedback learning process and
outcomes?
The neurofeedback learning process involves achieving self-regulation of
brain activity. The learning process often involves various processes and can
be affected by different factors, such as the type of feedback, reward, strategy,
and duration of training. To enhance and accelerate the learning process,
instructing participants to use mental imagery and providing participants with
monetary rewards for successful regulation of brain activity are often used in
real-time fMRI neurofeedback. However, it remains unclear as to what the
optimal strategy is for improving the control of brain activity during neuro-
feedback. One study focuses on training healthy participants to increase their
brain activity in the supplementary motor area (SMA) using real-time fMRI.
The study examined whether different kinds of feedback, explicit instructions,
and monetary rewards may lead to differences in participants’ control of their
brain activity. Four groups were trained with a 2-day neurofeedback protocol:
(1) neurofeedback only, (2) neurofeedback þ explicit instructions (motor im-
agery), (3) neurofeedback þ monetary reward, and (4) neuro-
feedback þ explicit instructions (motor imagery) þ monetary reward.
Interestingly, the study found that the neurofeedback þ monetary reward
group showed the highest functional activity in the SMA during the neuro-
feedback training relative to other groups. The two groups that were instructed
to use motor imagery did not show a significant learning effect during the 2-
day training protocol (Sepulveda et al., 2016). Whole-brain univariate and
functional connectivity analyses revealed common patterns of brain activity
across the four groups but also found distinct patterns in each of the four
groups, which reflect the different effects of feedback, reward, and instructions
on the brain. These findings indicated that the inclusion of explicit instructions
(performing motor imagery) does not improve the regulation of brain activity
during neurofeedback training, which may seem surprising given that this is
14 Fundamentals of Health Neuroscience

one of the most widely used approaches in previous neurofeedback studies to

improve one’s control over the brain activity. Thus, it is crucial to reevaluate
some of the established approaches in neurofeedback training, as monetary
reward is a more effective feedback approach to enhance the success of
regulating one’s brain activity. Additionally, it is worth examining the un-
derlying neural mechanisms that lead to better regulation of brain activity
using neurofeedback. It is possible that such process may involve the brain
reward circuitries or networks.
Interestingly, participants in the previous studies reported that they did use
mental imagery (i.e., not necessarily motor imagery) during the training to
regulate their brain activity even though they were not told to do so. This raises
an important question for neurofeedback training, which seems to prompt
participants to incorporate some form of mental strategy to learn to control
their brain activity, suggesting that implicit processes may also be engaged
during the learning process. According to the dual-process theory, we have
both conscious and unconscious (explicit and implicit) learning abilities.
Therefore, unconscious learning could also happen during neurofeedback
training. Taken together, factors such as reward, instruction, and feedback can
differentially influence the learning process during neurofeedback training.
Moreover, it appears that monetary reward is an effective approach for
inducing successful control of brain activity during neurofeedback training,
suggesting that motivation may also be a key player in the neurofeedback
training process. Additionally, both conscious and unconscious learning pro-
cesses seem to be involved in the learning of neurofeedback training.

Implicit learning during neurofeedback training

As previously shown, real-time fMRI neurofeedback can succeed without an
explicit strategy or instruction (Scharnowski et al., 2012; Shibata et al., 2011).
One study examined whether neurofeedback training effects can be achieved
in the absence of participants’ awareness that they are being trained. Specif-
ically, participants were informed that they were participating in a task aimed
at mapping the brain’s reward networks. Participants received auditory feed-
back with each positive and each negative reward, but these rewards were
provided based on their brain activity from two classic visual-related regions,
the fusiform face area and the parahippocampal place area. However, partic-
ipants were not informed of this brain activity and reward coupling and
thought that the rewards were given out randomly. Interestingly, the results
showed that most participants were able to modulate their brain activity to
enhance the likelihood of positive rewards. The finding was remarkable as the
participants were not explicitly instructed to modulate their brain activity or
told that such modulation would change the rate of positive rewards. However,
they somehow managed to achieve modulation of brain activity without having
any awareness or intention of learning. Furthermore, the study showed changes
 Introduction Chapter | 1 15

in resting-state connectivity during the neurofeedback, which were correlated

with an individual’s ability to implicit their brain activity to obtain more
positive rewards (Ramot et al., 2016).
Overall, this study demonstrated that volitional control of brain activations
could be learned even when participants were unaware of the learning or the
fact that they were undergoing neurofeedback training. Moreover, the study is
a good example of how brain activity can be modified even in the complete
absence of intention and conscious awareness of learning. These findings lead
to interesting questions regarding the possibilities of unconscious clinical in-
terventions through neurofeedback training. Relatedly, it has been suggested
that during neurofeedback training, unconscious reward processing involves
the ventral striatum, whereas the dorsal striatum is linked to learning processes
(Sitaram et al., 2017). Thus, the striatum may play an important role in the
unconscious learning. The idea of unconscious learning and information
processing has been previously discussed and proposed (Shea & Frith, 2016),
which suggests important clinical implications for future research and clinical
practices. Taken together, both conscious and unconscious learning are
involved in neurofeedback training, which is consistent with the dual-process
theory.
These findings seem to reveal a new type of neurofeedbackdimplicit
neurofeedback. In explicit neurofeedback (i.e., participants are informed of the
purpose of the training), participants are explicitly told what the neurofeed-
back signal represents, what brain function is to be trained, what brain area(s)
are intended to be changed, and/or what behavioral changes are expected to
occur. In contrast, participants in implicit neurofeedback are not aware of the
meaning of the feedback provided to them or the purpose of the neurofeedback
training. However, recent studies have demonstrated that neurofeedback
training can be highly effective even when participants do not know what
behavior is being trained. Although implicit neurofeedback studies have
demonstrated robust effects, it remains unclear whether implicit or explicit
neurofeedback is more effective. It is possible that implicit feedback is more
effective in certain types of learning. For instance, learning does not require
much conscious effort to achieve the learning outcomes. Nonetheless, there is
a need for additional systematic investigations that compare potential differ-
ences in neural mechanisms and training effectiveness between implicit and
explicit neurofeedback (Watanabe et al., 2017).

Simultaneous real-time fMRI and EEG neurofeedback

EEG and fMRI can be assessed together and can also be used to provide
neurofeedback at the same time. Simultaneous fMRI and EEG recordings have
both high spatial and temporal resolution for neuroscience research. Is it
possible to simultaneously self-regulate fMRI and EEG brain activity? There
was one study that implemented a real-time neurofeedback system, which