The Behavioral Neuroscience of Motivation: An Overview of Concepts, Measures, and Translational Applications

Abstract

Motivation, defined as the energizing of behavior in pursuit of a goal, is a fundamental element of our
interaction with the world and with each other. All animals share motivation to obtain their basic needs,
including food, water, sex and social interaction. Meeting these needs is a requirement for survival, but
in all cases the goals must be met in appropriate quantities and at appropriate times. Therefore
motivational drive must be modulated as a function of both internal states as well as external
environmental conditions. The regulation of motivated behaviors is achieved by the coordinated action
of molecules (peptides, hormones, neurotransmitters etc), acting within specific circuits that integrate
multiple signals in order for complex decisions to be made. In the past few decades, there has been a great deal of research on the biology and psychology of
motivation. This work includes the investigation of specific aspects of motived behavior using multiple
levels of analyses, which allows for the identification of the underpinning neurobiological mechanisms
that support relevant psychological processes. In this chapter we provide an overview to the volume
“The Behavioural Neuroscience of Motivation”. The volume includes succinct summaries of; The
neurobiology of components of healthy motivational drive, neural measures and correlates of
motivation in humans and other animals as well as information on disorders in which abnormal
motivation plays a major role. Deficits in motivation occur in a number of psychiatric disorders, affecting
a large population, and severe disturbance of motivation can be devastating. Therefore, we also include
a section on the development of treatments for disorders of motivation. It is hoped that the collection
of reviews in the volume will expose scientists to a breadth of ideas from several different subdisciplines,
thereby inspiring new directions of research that may increase our understanding of
motivational regulation and bring us closer to effective treatments for disorders of motivation.

Full text

The Behavioral Neuroscience
of Motivation: An Overview of Concepts,
Measures, and Translational Applications
Eleanor H. Simpson and Peter D. Balsam
Abstract Motivation, defined as the energizing of behavior in pursuit of a goal, is a
fundamental element of ourinteraction with the world and with each other. All
animals share motivation to obtain their basic needs,including food, water, sex and
social interaction. Meeting these needs is a requirement for survival, butin all cases
the goals must be met in appropriate quantities and at appropriate times.
Thereforemotivational drive must be modulated as a function of both internal states
as well as externalenvironmental conditions. The regulation of motivated behaviors
is achieved by the coordinated actionof molecules (peptides, hormones, neuro-
transmitters etc), acting within specific circuits that integratemultiple signals in
order for complex decisions to be made. In the past few decades, there has been a
great deal of research on the biology and psychology ofmotivation. This work
includes the investigation of specific aspects of motived behavior using multi-
plelevels of analyses, which allows for the identification of the underpinning
neurobiological mechanismsthat support relevant psychological processes. In this
chapter we provide an overview to the volume“The Behavioural Neuroscience of
Motivation”. The volume includes succinct summaries of; Theneurobiology of
components of healthy motivational drive, neural measures and correlates ofmoti-
vation in humans and other animals as well as information on disorders in which
abnormalmotivation plays a major role. Deficits in motivation occur in a number of
psychiatric disorders, affectinga large population, and severe disturbance of moti-
vation can be devastating. Therefore, we also includea section on the development
of treatments for disorders of motivation. It is hoped that the collectionof reviews in
the volume will expose scientists to a breadth of ideas from several different
E.H. Simpson (&)
Department of Psychiatry, New York State Psychiatric Institute,
Columbia University, New York, NY, USA
e-mail: es534@cumc.columbia.edu
P.D. Balsam
Department of Psychiatry, New York State Psychiatric Institute,
Psychology Departments of Barnard College and Columbia University,
New York, NY, USA
e-mail: Balsam@columbia.edu
©Springer International Publishing Switzerland 2015
Curr Topics Behav Neurosci
DOI 10.1007/7854_2015_402

subdisciplines,thereby inspiring new directions of research that may increase our
understanding ofmotivational regulation and bring us closer to effective treatments
for disorders of motivation.
Keyword Motivation Cost-benefit analysis Addiction Apathy Translational
research
Contents
1 Why Motivation Is Important to Understand..........................................................................
2 What We Mean by the Word Motivation ...............................................................................
3 A Simplified Overview of How Motivation Might Work in the Brain.................................
4 Cost–Benefit Computation as the Arbiter of Motivated Behavior.........................................
5 Research Approaches to Understanding Motivation...............................................................
6 Organismal Level Biology Is Critical to Understanding Motivation .....................................
7 Motivation Gone Wrong..........................................................................................................
8 Treatments................................................................................................................................
References ......................................................................................................................................
1 Why Motivation Is Important to Understand
Understanding what drives motivated behavior in humans is a truly fascinating
endeavor. But as important as our curiosity for knowing what drives us as indi-
viduals, and what supports individual differences in levels of motivation among our
friends and colleagues, is the critical question; why do motivational processes get
disrupted when the clinical and personal consequences can be so devastating? As
we will see across this volume, motivated behaviors involve biological and psy-
chological processes that have undergone evolution at numerous levels, from
individual molecules all the way to species-specific social organization. While
motivational processes represent heritable traits of fitness, humans suffer from a
number of disorders of motivation that can be organized into two distinct cate-
gories. The first category is composed of the apathy and pathological deficits in
motivation commonly seen in patients with schizophrenia and affective disorders.
The second category involves problematic excesses in behavior including addic-
tions, the pathological misdirection of motivation. Developing treatments for dis-
orders of motivation requires a detailed understanding of how motivated behavior
occurs, how it is dynamically regulated under normal conditions, and how it is
disrupted in disease. This volume provides reviews of recent research in each of
these areas.
E.H. Simpson and P.D. Balsam

2 What We Mean by the Word Motivation
The concept of motivation is a useful summary concept for how an individual’spast
history and current state interact to modulate goal-directed activity. In this book, the
authors examine the motivation to pursue many different goals. One general aspect
of motivated behaviors is that they lead to a goal and obtaining the goal is
rewarding. Thus, motivation, defined as the energizing of behavior in pursuit of a
goal, is a fundamental property of all deliberative behaviors. One of the earliest
psychological theories of motivation, Hull’s drive theory, posited that behaviors
occur to reduce biological needs, thereby optimizing the organism’s potential for
survival (Hull 1943). However in Hull’s theory, motivational drive functioned
solely to energize responding, drive was not responsible for initiating, or main-
taining the direction of action. Later, motivation was conceptualized to consist of
both a goal-directed, directional component and an arousal, activational component
(Duffy 1957; Hebb 1955). This is the framework of motivation still in use, such that
if motivation were a vector—its length would represent the amplitude, or intensity
of pursuit, and the angle of the vector would represent its focus on a specific goal.
In this analogy, a motivation vector affected by apathy might have a reduced length
in all directions and a motivation vector affected by addiction might have an
increased length and a less flexible direction. The chapters in this volume explicitly
acknowledge that motivation affects which responses occur as well as the vigor of
those responses. It appears that we are just beginning to understand that these two
aspects of motivation have both common and distinctive neural underpinnings. For
example, circadian factors may energize the general motive of seeking food or mate
(Antle and Silver, this volume), but the specific actions that occur in pursuit of these
goals are regulated by different substrates (see Caldwell and Alders, Woods and
Begg, Magarinos and Pfaff, all in this volume). Similarly, local cues that signal food
availability may energize many food seeking actions, signals for specific foods
differentially energize actions associated with obtaining the specific outcome.
Again, the neural substrates of the general and specific effects are somewhat dis-
tinctive. At each level, whole classes of specific actions are made more or less likely
by these factors (Neuringer and Jensen 2010). We suggest that there is generally a
hierarchical structure to motivation in the sense that general arousal factors such as
sleep–wake cycles will affect many different motives, that activation of specific
motives (e.g., hunger, thirst, social motives) can activate many specific actions that
could lead to many specific outcomes within a general class of goals, and that more
temporally and situationally specific factors determine the specific actions that
occur in pursuit of that goal (Timberlake 2001). With this in mind, it is clear that
disruptions in motivation can occur at multiple levels of control which suggests
there may be multiple interacting ways to attempt to treat disruptions.
The Behavioral Neuroscience of Motivation: An Overview …

3 A Simplified Overview of How Motivation Might Work
in the Brain
Many different factors influence motivation, including the organism’s internal
physiological states, the current environmental conditions, as well as the organism’s
past history and experiences. In order for all these factors to influence motivation,
information about them must be processed in a number of ways; it must be evaluated
and encoded, and unless the motives are novel, the valuation and encoding will be
affected by learning and retrieval processes. A simplified overview of how such
diversity of information must be processed and integrated to result in motivation
(both response selection and action vigor) is shown in Fig. 1. Here, we organize the
problem into a single, highest order concept that motivated behaviors represent the
actions associated with the highest net value that results from a cost–benefit analysis
that encompasses all of the potential influencing factors and processes.
Environment
(Availability of goal,
response opportunity)
Physiological State
(deprivation, stress,
time of day, health)
Past history
(experience of goals,
responses and stimuli)
BENEFITS
(meeting physiological and
psychological needs,
escaping harm)
Evaluation, encoding,
learning and retrieval
COSTS
(effort, time, discomfort,
lost opportunities, pain)
Evaluation, encoding,
learning and retrieval
Direction
Vigor
Goal
Fig. 1 A simplified diagram of the influencing factors and processes that are involved in
motivation. This framework of motivation places cost–benefit analysis central to the concept of
motivation. Three major categories of factors are known to influence motivation: the individual’s
physiological state, the environment, and the individual’s past history. Information about all 3
categories of factors will be subject to a number of processes (represented inside the blue oval),
including evaluation and encoding. In almost all circumstances, the motive, environment, and
physiological state will not be novel; therefore, information will also undergo learning and
retrieval processes. All of the combined processes result in weighting of all the costs and benefits
related to the motive, and the output of the cost–benefit calculation will impact upon the direction
and vigor of action that the individual takes toward the motive goal
E.H. Simpson and P.D. Balsam

4 Cost–Benefit Computation as the Arbiter
of Motivated Behavior
The costs associated with behavioral action may include physical effort, mental
effort, time, loss of potential opportunities, discomfort, and danger (the risk of pain
and potential death). The benefits associated with behavioral action might include
fulfilling physiological and psychological needs, obtaining reinforcement secondary
to those needs, escaping from harm, or avoidance of some of the costs listed above.
As mentioned above, information entering the cost–benefit computation for any
specific motive will be processed in several ways. The value of every cost and every
benefit must be calculated and encoded. The concept of encoding value and
experimental methods for measuring encoded value are discussed in detail by
Redish et al., in this volume. It is important to consider that value must be encoded
when a goal is obtained and then stored for future retrieval when obtaining that goal
again becomes relevant. When that happens in the current moment, the assessment
of value must be conditioned both on this past experience as well as the current
state and environmental conditions. Goals are likely to be obtained with some
temporal distance from the initiation, or even conclusion of behavioral output.
Single neuron activity in several brain regions including orbitofrontal cortex,
anterior cingulate, and basolateral amygdala has been shown to correlate with
reward prediction and this work is reviewed by Bissonette and Roesch in this
volume. The encoded values of costs and benefits do not belong in absolute scales
because the values of all costs and benefits are rendered relative to the animal’s
current physiological state as well as the current conditions of the surrounding
environment.
Much has been learned about the role of dopamine in reinforcement learning,
and its impact on motivated behavior from experimental manipulations of the
dopamine system in rodents. This work is comprehensively reviewed by Salamone
et al. in this volume. In addition to learning about the costs and benefits of a
particular action, subjects also learn about specific signals that are associated with
obtaining particular goals. Such signals can have an enormous influence on moti-
vated behavior, and several chapters in this volume provide details of when and
how environmental cues can influence response selection and response activation.
These include Corbit and Balleine’s chapter on learning and motivational processes
contributing to Pavlovian–instrumental transfer and John O’Doherty’s chapter on
the neural substrates of motivational control in humans. Cue learning is also dis-
cussed in the context of motivational disorder, in the chapters by Meyer et al. and
Barrus et al., that deal with substance abuse disorders and gambling.
Another aspect of the computation that energizes specific action has to do with
signals that a particular goal is currently available. These signals occur on multiple
timescales. Specific times of day can become associated with the opportunity to
obtain specific goals, and discrete cues can signal the opportunity to achieve a goal
as well as what specific ways there are to achieve it. For example, when meals occur
at a regular time of day, there are behavioral, hormonal, and neural changes that
The Behavioral Neuroscience of Motivation: An Overview …

occur in anticipation of a meal time that give rise to the motivation to seek food
(Antle and Silver, in this volume). Encountering a restaurant can activate the
specific behavioral sequences that lead to the ordering of food and the specific foods
themselves can activate specific consummatory responses. All along this sequence
of temporally organized behavior, there are concomitant changes in hormonal and
neural states that energize and guide action (Woods and Begg in this volume).
After effective encoding of all the relevant costs and benefits, a computational
process (the cost–benefit computation) is required to resolve the appropriate
direction and vigor of action to be taken. This complex interplay of factors and
processes is schematized in Fig. 1.
How conceptually the cost–benefit computation is made is currently unclear. It is
still unknown whether the value of costs and benefits are calculated on the same
scale or not, whether their weights are integrated or subtracted such that, for
example, the amount of predicted effort reduces the value of the predicted reward.
Or perhaps, there is a circuit component that acts as a comparator of these two
component values. An additional complication is that for any given motive, there
are often multiple types of costs and potentially multiple types of benefits involved
because many different types of control systems and circuits are at play (e.g.,
neuroendocrine, circadian, Pavlovian). This leads to the question of how so much
diversity of information can all be used to make an appropriate response selection
and determine action vigor. Do all factors enter into a singular, highly complex
equation, as our simplified diagram (Fig. 1) may seem to imply? Or do some
systems continually run in parallel, with behavioral output as the result of a hier-
archical switching from one system to another? Or perhaps there is fluctuation in
the degree to which different factors influence the computation, e.g., the relative
weights of physical and mental costs depend on the energy state of the organism.
Furthermore, it is possible that these alternative regulatory schemes are not
mutually exclusive. For a detailed discussion on the potential mechanisms by which
multiple deliberative processes that are running in parallel may each influence
motivation (see Redish et al. in this volume). In the case of appetitive conditioning,
there is evidence to suggest that animals can rapidly switch between responding that
is driven by two different control systems, goal directed or habitual (Gremel and
Costa 2013). Audiovisual cues can trigger the rapid switching, implying that these
two alternate circuits are constantly online and available in parallel. On the other
hand, instead of a multi-tiered, hierarchical, or switching system, other work sug-
gests that all information enters a singular computation process, and the output of
this meta-computation is what drives motivation. This concept is favored by
Magarinos and Pfaff (this volume) whose work on the sexual motivation of female
rodents may suggest that for this specific motive, at least some factors may be
integrated into a single decision-making process.
Above we have described the complex situation of many different factors
influencing a single motive. It must also be recognized that at any given time, there
may be competition for multiple goals and that imbalances in the strength of the
motivations for each goal can cause conflict and dysfunctional behavior. The
chapter by Cornwell et al. describes how human well-being depends not only on
E.H. Simpson and P.D. Balsam

satisfying specific motives, but also on ensuring that motives work together such
that no individual motive is too weak or too strong. It is becoming clear that
different motivational systems have control elements that are unique to each system
but that there may also be common substrates, perhaps close to the final steps that
determine behavioral output. This is well illustrated in the chapter on defensive
motivation by Campese et al. and in the chapter on social motivation by Caldwell
and Alders. Again, the neurobiological mechanism whereby different motive sys-
tems interact is an important but not yet well-understood problem. Of particular
interest will be to understand how defensive motivations interact with appetitive
ones. The vast majority of modern work on motivation concerns itself with the
mechanisms of appetitive motivation. Campese et al. show how to leverage what is
now known about fear learning to understand the neurobiological mechanisms of
defensive motivations. In a similar vein, Cornwell et al. argue for the importance of
understanding how promotion/prevention motives in humans is an important
modulator of other motives. Hopefully, the future will include a greater focus on
understanding defensive motivations.
5 Research Approaches to Understanding Motivation
To increase our understanding of motivation in the brain, there are numerous
approaches that can be taken. In this volume, many different academic approaches
are represented as the research reviewed includes clinical, experimental, and
comparative psychology; and several neuroscience subfields including, cognitive,
molecular, cellular, behavioral, and systems neuroscience. This means that specific
questions or single hypotheses can be, and often are being, approached at multiple
levels of analysis. Indeed, it is when research programs combine a number of
techniques, or use information derived from a few different techniques to propose
(and test) new hypotheses that the most compelling results are obtained. For
example, the work described by O’Doherty in this volume includes the use of
human fMRI studies to investigate potential action-value signals that have been
proposed from rat electrophysiological recordings. The research described by
Redish et al. considers computational models of decision making and tests these
models by measuring neuronal activity during deliberative behavior. In the chapter
by Ward, the approach to testing motivational deficits in mice has very much been
informed by the data from molecular and clinical studies in humans. By pheno-
copying in mice the molecular changes that have been detected in patients using
PET imaging techniques, the behavioral consequences can be probed under
well-controlled conditions. In a similarly translational manner, the research
described by Robinson et al. in this volume applies electrophysiological and
optogenetic techniques in rodents to probe behaviors that are altered in people with
addictions. In the chapter by Barrus et al., the authors discuss the development of
rodent paradigms designed to test various psychological theories of substance use
and gambling disorders.
The Behavioral Neuroscience of Motivation: An Overview …

6 Organismal Level Biology Is Critical to Understanding
Motivation
When multiple levels of analyses are used to investigate motivational processes, a
critically important concept becomes apparent. While the evolution of traits that
support motivation occurs at the level of molecules, proteins, cells, and circuits, it is
the entire organism, and its interaction with the environment that is selected. An
example of this concept is easily seen in the research on circadian modulation of
motivation (Antle and Silver) and in the work on motivation for eating (Woods and
Begg). For example, in the case of feeding we know many of the molecules and
circuits involved in both the intrinsic, homeostatic factors which drive the moti-
vational to eat, such as hormones and peptides, and we also know the neuromod-
ulators and circuits that are responsible for some of the extrinsic/environmental
influences on eating such as predictive cues. We are beginning to understand how
these signals are integrated in order for decisions to be made and behavioral
responses to occur; though as described above, understanding the mechanism of
integration is currently a critical area of research.
7 Motivation Gone Wrong
Patients with many different psychiatric diagnoses may experience deficits in
motivation, including depression, schizophrenia, bipolar disorder, PTSD, and
anxiety disorders. In this volume, we focus on the neurobiology of motivational
deficits in depression and schizophrenia primarily because these are the two ill-
nesses in which pathological deficits in motivation play a major role in patient
functioning and clinical outcome (Barch et al. 2014; Strauss et al. 2013). As such,
far more research has been done on motivation in depression and schizophrenia
than any other illness. In the last few decades, it has been recognized that the
motivational deficits in Schizophrenia and depression share similarities, but also
distinct differences. These differences occur because as mentioned above, there are
many components involved in motivated behavior and each of them represent
potential vulnerabilities that may be involved in different pathophysiological
mechanisms. An excellent review of the similarities and differences in mechanisms
underlying motivational deficits in depression and schizophrenia is provided by
Barch et al. in this volume. The central difference in these types of pathologies is
that many depressed patients suffer from impairments of in-the-moment hedonic
reaction. Such anhedonia can diminish an individual’s capacity for anticipation,
learning, and effort. In contrast, patients with schizophrenia demonstrate relatively
intact in-the-moment hedonic processing. Instead, patients suffer impairments in
other components involved in translating reward experience to anticipation and
action selection.
E.H. Simpson and P.D. Balsam

There are also separate chapters that go into more specific detail for each of these
pathophysiological conditions. An update on candidate pathomechanisms for
motivational deficits in depression is provided by Treadway’s chapter. This volume
devotes two chapters to the topic of motivation deficit in schizophrenia because this
area of research has been more active than it has been in depression. This is likely
because antipsychotic medications that successfully ameliorate the positive symp-
toms of schizophrenia (delusions, hallucinations, etc.) have been available for some
time, leaving patients with the residual negative symptoms, of which amotivation is
the primary driver of poor outcome and low quality of life (Kiang et al. 2003).
Current concepts of motivation deficits and how motivation is assessed in
patients with schizophrenia is reviewed by Reddy et al. Waltz and Gold extend
these concepts into the exploration of the relationship between amotivation and the
representation of expected value. The clinical research reviewed in the chapters that
deal with apathy and motivation in humans is complimented by a chapter on
methods for dissecting motivation and related psychological processes in rodents
(Ward). Research using animal models is critical for several obvious reasons,
including the availability of genetic manipulations, molecular modifications as well
as invasive in vivo monitoring procedures that are not possible in human subjects.
What hasn’t previously been obvious is how well we can use such animal models to
investigate the various components of motivation that are particularly relevant to
human disease. Ward describes such procedures and explains how best to leverage
our current clinical knowledge using state-of-the-art mouse models.
On the flip side of apathy may be when motivation for a specific goal can come
to dominate action in maladaptive ways as appears to be the case in addictions.
Excessive behavior for many types of rewards including drugs, food, gambling, and
sex can be problematic. In addiction, rapid and strong learning about what leads to
reward, excesses in experiencing the hedonic value of rewards, exaggeration in
representing those values, and dominance in being guided by those representations
can all lead to significant narrowing in the diversity of motives. Several theories
exist that attempt to explain the process of addiction in terms of disruption of
motivational processes. Each theory differs in the emphasis on which specific
aspects of motivation are primarily affected. The chapters by both Meyer et al. and
Robinson et al. describe the motivational processes underlying substance abuse
disorder. The chapter by Barrus et al. extends this discussion into the field of
gambling. Barrus et al. suggest that many of the processes affected in gambling are
the same as those affected in drug addiction, and therefore, the paradigms that have
been successfully used to study drug addiction in animal models can be success-
fully modified to identify neurobiological mechanisms related to gambling. The
central hypothesis in these analyses of addictions of drugs and gambling (as well as
addiction to food and other things) is that an aberration in reward processing and/or
in the control by cues associated with these rewards underlies the problematic
nature of addictive behavior and its resistance to change.
The Behavioral Neuroscience of Motivation: An Overview …

8 Treatments
Given the modern emphasis on reward processes as a fundamental component of
motivation, it is encouraging that modern cognitive/behavioral approaches to
treating motivational disturbances focus on creating reward contingencies that
modify deficits or excesses in behavior. Saperstein and Medalia describe how in
schizophrenia patients motivation enhancing techniques are critical to
treatment-related improvements within cognitive remediation therapy. In the case of
addictions, Walter and Petry provide an overview of research indicating that con-
tingency management is a demonstrably effective psychosocial treatment for sub-
stance use disorders. The central concept of contingency management is that
extrinsic motivators are used to change patients’behaviors. Specifically, rein-
forcement is provided when patients demonstrate abstinence. In the descriptions of
both treatment approaches, the chapters consider the important role that intrinsic
motivation may play in clinical success.
We are hopeful that the great progress in understanding the neurobiology of
motivation described in this book will influence new ideas that will lead to novel
pharmacological, physiological and psychological/psychosocial approaches to
treatments for disorders of motivation. The identification of novel pharmacological
treatments is dependent on the ability of preclinical researchers to investigate
potential targets and screen potential candidate compounds using truly meaningful
endophenotypic assays. The chapters in this volume that describe clinical studies of
patient with disorders of motivation describe how motivation has been dissected
into a number of component processes and the specific processes that are selectively
disrupted in disease have been identified (Reddy et al., Barch et al., Waltz and
Gold). To identify drugs that will be effective for disorders of motivation, pre-
clinical assays must focus on the same specific processes affected in humans (see
Ward in this volume). A recent example of the development of the kind of research
tools that are needed for the purpose of investigating potential treatment targets is
the strategy of dissecting goal-directed action from arousal by modifying previously
existing rodent behavioral tasks (Bailey et al. 2015a). These new tools can then be
used to assay specific effects of drugs that affect novel treatment targets (Simpson
et al. 2011) and Bailey et al. (2015b). This novel approach was directly inspired by
the literature on the selectivity of processes disrupted in humans with disorders of
motivation.
In addition to pharmacological treatments, there is also the possibility that
electrophysiological treatments for disorders of motivation may be developed. Deep
brain stimulation (DBS) is currently used to treat a number of neurological and
psychiatric conditions (Kocabicak et al. 2015; Kringelbach et al. 2007; Udupa and
Chen 2015). DBS has been used to treat essential tremor, Parkinson’s disease,
treatment refractory major depression, severe obsessive–compulsive disorder, and
chronic pain for several years. Several other applications are in experimental stages,
including clinical trials for pervasive addiction and symptoms of schizophrenia.
Such an invasive procedure requires many successive small-scale clinical trials
E.H. Simpson and P.D. Balsam

before optimal procedures can be successfully developed. A significantly less
invasive procedure used to modulate brain activity is transcranial magnetic stim-
ulation (TMS). While the mechanism(s) by which TMS alters neuronal function and
network activity is not understood, due to its noninvasiveness, hundreds of clinical
trials have been conducted for a long list of neuropsychiatric conditions, including
schizophrenia, and craving/addiction. A comprehensive review of studies of
repetitive TMS has recently been published (Lefaucheur et al. 2014).
Lastly, we are also hopeful that the emerging understanding that there are
multiple systems driving motivation on an organismal level will lead to the
development of treatment schemes that are more comprehensive than those that
have been developed in the past. It may be that subtle adjustments in several of the
factors that are involved in disorders of motivation (the endocrine system, circadian
system, neurotransmitter function, etc.) can result in greater improvements and less
side effects than treatments that focus on a single system.
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