Neuroscience of Desire and Desire Regulation

P A R T I I

Neuroscience of Desire and Desire Regulation

Hofmann_PsychologyOfDesire.indb 127 4/24/2015 5:33:35 PM


129

The pursuit of pleasure is ubiquitous throughout the animal kingdom,

suggesting that pleasure is a fundamental principle of brain function

that facilitates the survival of species and individuals. It helps us make

decisions optimizing the allocation of brain resources for efficient behav-

ior. Much progress has been made over the last 15 years in mapping the

functional neuroanatomy and neurochemistry of pleasure in mammals,

which has at least three major subcomponents: wanting, liking, and learn-

ing. This has brought clarity to earlier research that had confounded the

complex psychological components of pleasure, especially the difference

between wanting and liking and their intricate interplay over time in the

pleasure cycles. The new science of pleasure and motivation can help us

understand affective disorders including depression and addiction— and

may help to improve subjective well-being.

Over 60 years ago, the young scientists James Olds and Peter Milner

made a most remarkable discovery of what appeared at the time to be a

brain pleasure center: rats would repeatedly press a lever to receive tiny

jolts of electricity delivered through electrodes implanted deep within

their brains— even up to 2,000 times per hour (Olds, 1956; Olds & Milner,

1954). The discovery was a surprise, as the scientists intended to probe

brain areas of punishment. But one of the electrodes accidentally was

misplaced in a different site in the brain, revealing the existence of the

reward circuit.

These so- called “pleasure electrodes” were so powerful that rats

would sometimes pursue them over other rewards such as food. Even-

tually electrode pursuit could even result in gradual starvation, at least

under extreme conditions when all of the rat’s foraging efforts needed

to be devoted to food in order to survive (Berridge & Valenstein, 1991).

C H A P T E R 6

Motivation and Pleasure in the Brain

Morten L. Kringelbach

Kent C. Berridge


130 N E U R O S C IE N C E O F D E S IR E A ND D E S IR E R EG UL AT I O N

Under more lenient conditions, rats ate enough to thrive but then spent

much of their time pressing excessively for the brain electrode reward.

Almost immediately other scientists reproduced these effects, and made

similar findings in higher primates and humans (Heath, 1972; Sem-

Jacobsen, 1976; Valenstein, 1973).

Further research in the next decade demonstrated that brain dopa-

mine is one of the main chemicals conveying neural signals in these

regions (Yokel & Wise, 1975). Dopamine was found to be important to

the electrode reward effects and also to many addictive drugs. In the

minds of many scientists and the general public, dopamine consequently

became known as the brain’s chief “pleasure chemical” (Hoebel, Rada,

Mark, & Pothos, 1999; Shizgal, 1999; Wise & Bozarth, 1985).

The discovery of pleasure electrodes and dopamine seemed to solve

the question of how pleasure is produced in a brain, and even for some to

promise an easy fix to unhappiness. Writers began to envisage brave new

worlds where electrical brain stimulation and drugs could induce bliss.

In the 1960s, therapists began implanting electrodes into the brains of

human patients suffering from depression or other psychological disor-

ders (Heath, 1972).

Yet, the early “pleasure electrodes” did not lead to a breakthrough

in the treatment of mental illness, and may even have misled scientists

about how pleasure comes about in the brain. In fact, subsequent research

suggests that brain dopamine and most “pleasure electrodes” do not pro-

duce actual pleasure sensations at all (Berridge & Kringelbach, 2008).

Instead, these produce only a form of “wanting” or motivation to obtain

the electrode stimulation or another reward. The true pleasure generators

in the brain are much more restricted and rather fragile (Kringelbach &

Berridge, 2012; Berridge & Kringelbach, 2013).

This new view of pleasure has come from careful scientific analy-

ses of the brain networks involved in reward for humans and animals.

Pleasure- generating systems turn out to be more complex than earlier

thought. This new understanding of the pleasures of the brain may also

offer insights into the complexities of happiness, which may, someday,

hopefully lead to better ways to enhance the quality of life (Berridge &

Kringelbach, 2011).

The Basic Pleasures of Life

Pleasure is at the heart of many human experiences, and the capacity for

pleasure is important for healthy well-being. Conversely, a lack of plea-

sure, anhedonia, is a major component in mental illnesses such as depres-

sion and anxiety (see also Treadway, Chapter 15, this volume). Treatments

of mood disorders will benefit if brain mechanisms of pleasure can be

understood. But more than that, a better understanding of pleasure and


Motivation and Pleasure in the Brain 131

reward is essential to understanding fundamental biological principles

of how reward works. All animals including humans have to survive and

procreate, and reward is the common currency that makes this happen.

Pleasure can be thought of as evolution’s boldest trick for sustaining and

nourishing interest in the things most important to survival (Kringel-

bach, 2005, 2009).

Seen in this light, food and sex are important fundamental pleasures,

and in social species such as humans, there is in addition a strong motiva-

tion to interact with other conspecifics, perhaps most importantly when

bringing up children to reproductive age, which ensures the survival of

the species (Parsons, Stark, Young, Stein, & Kringelbach, 2013; Parsons,

Young, Murray, Stein, & Kringelbach, 2010). So the social and cultural

pleasures are as much a part of the human hedonic repertoire as basic

pleasures.

But how does one measure something as seemingly subjective as

pleasure? We can ask people to give pleasure ratings of how they feel,

but subjective ratings may not always fully capture underlying pleasure

reactions. Further, it may be difficult to see how any form of pleasure

can measured in other animals, where the causal role of particular brain

systems can best be studied.

One window into such unspoken pleasures can be found by observ-

ing how parents decide whether their newborn baby likes a sweet taste

or dislikes a bitter taste by watching affective facial expressions (Steiner,

1973). Tasty food pleasures can elicit related facial reactions in other ani-

mals too, from apes to rodents, which are evolutionarily homologous and

similar in brain mechanisms to expressions of humans (Steiner, Glaser,

Hawilo, & Berridge, 2001). Rats and mice will, for example, lick their lips

contentedly when given sweet tastes, while aversive tastes will lead to

gapes, head shakes, and frantic wiping of the mouth. By measuring the

numbers of facial expressions elicited by a taste, we have a good measure

of its hedonic impact or how much it is liked, which can then be linked to

brain activity (Figure 6.1, left panel).

Hedonic Hotspots: Pleasure Generators

Using these behavioral tools combined with precise targeting of specific

brain regions has allowed for a much more refined understanding of how

particular brain systems generate pleasure from sensations. In a set of

experiments on the neural causation of pleasure, we have found “hedonic

hotspots” deep below the cortex in the rat brain (Peciña & Berridge, 2005)

(Figure 6.1, left panel). These brain sites are capable of amplifying a sen-

sory pleasure to make it more “liked” when neurons in the hotspot are

neurochemically stimulated. In this way, a palatable sweet taste becomes

even nicer.



One pleasure- amplifying hotspot is in the nucleus accumbens, a

major structure within brain reward circuits, particularly in its subregion

near the center of the brain called the medial shell. Another hotspot lies

within the main output target of the nucleus accumbens, called the ven-

tral pallidum, which lies even deeper and near the bottom of the fore-

brain. Each hotspot is tiny, being only a cubic millimeter in volume in

the brains of rats and presumably about a cubic centimeter in a human

brain. Each hotspot constitutes only one-tenth to one-third of its brain

structure, indicating tight localization of pleasure- generating circuits.

FIGURE 6.1. Hedonic reactions for studying hedonic and motivational hotspots. On

the left are shown the positive and negative hedonic reactions to taste found in

humans and other animals. On the right are shown details of the hedonic hotspot

for pleasure generation in the nucleus accumbens (sagittal view of medial shell

and of neostriatum). This is a causation map: colors reflect hedonic or motiva-

tion consequences (on “liking” reactions or on food intake) of mu opioid ago-

nist microinjections at each site. Red/orange symbols in the rostrodorsal hotspot

show sites that caused doubling or higher levels of hedonic “liking” reactions to

sucrose taste. By comparison, at caudal sites the same opioid microinjections only

suppressed aversive “disgust” reactions to bitter quinine (purple; e.g., suppressed

gapes) or bivalently suppressed both “liking” and “disgust” reactions (blue). Green

sites denote increases in motivation “wanting” to eat without any hedonic change

in either “liking” or disgust (enhanced motivation also extended through all red/

purple/blue sites in the nucleus accumbens). Adapted from Richard, Castro, Dife-

liceantonio, Robinson, and Berridge (2013) and based on data from Peciña and

Berridge (2005). Copyright 2013 by Morten L. Kringelbach and Kent C. Berridge.

Adapted by permission. (Purchasers can download a color version of this figure

from www.guilford.com/p/hofmann2.)



Within the small brain hotspots, taste pleasure is amplified by neu-

rochemical stimulation via several neurotransmitters related to addic-

tive drugs or to natural appetite states. For example, pleasure “liking” is

enhanced when hotspots are stimulated by opioid neurotransmitters such

as enkephalins or endorphins, which are the brain’s natural version of the

drugs heroin or morphine. Another pleasure- enhancing neurotransmit-

ter is anandamide, a natural brain version of the psychoactive ingredient

in marijuana. Yet another may be orexin, which is released by the brain

during hunger and by acting in a hotspot helps to make food taste better.

Elevations of pleasure seem to require unanimous activation of an

entire network of hotspots together, and defection by any single hotspot

can prevent the hedonic enhancement. The stringency of a network

requirement may make intense pleasures relatively rare.

From this evidence, it is clear that actual reward pleasure lies in active

processes of the brain and mind as a reaction to a stimulus, rather than

any physical stimulus itself. Pleasure is thus never merely a sensation, but

rather something that the brain adds to sensations and experiences.

Return to Dopamine, False-Pleasure Electrodes, and Addictive “Wanting”

As mentioned earlier, dopamine has been the most famous reward-

associated neurochemical for over half a century (Hoebel et al., 1999;

Shizgal, 1999; Wise & Bozarth, 1985). But recent findings indicate dopa-

mine does not actually generate pleasure after all, as mentioned above,

but instead contributes something subtle to reward, more related to moti-

vation than to pleasure (Berridge, 2007).

This also means that pleasure fluctuates with brain state, and natu-

rally with hunger or fullness, and thus often occurs in short-term cycles

with phases of expectation, consummation, and satiety (see Figure 6.2). In

short, although reward was long thought to be a unitary process, it actu-

ally contains at least three major psychological components, each with

distinguishable neurobiological mechanisms: Liking is the actual pleasure

component or hedonic impact of a reward, which can be generated in the

hedonic hotspots. Wanting is the motivation for reward, often triggered

by reminders or by thinking about the reward, which can be changed by

modulating dopamine. Both contribute to learning, which help form the

associations, representations, and predictions about future rewards based

on past experiences (see also Papies & Barsalou, Chapter 2, this volume).

These components are linked to one another in the pleasure cycle.

In recent years many experiments by labs including ours have shown

that manipulations of brain dopamine levels cause changes in “wanting”

for a reward rather than “liking” for that reward. One example is gene-

manipulated mutant mice that have extra-high levels of dopamine in



their brain, via selective disruption of the molecular vacuum cleaner that

normally sucks dopamine out of a synapse (the dopamine transporter

molecule) (Robinson, Sandstrom, Denenberg, & Palmiter, 2005). The

high- dopamine mice do “want” sweet rewards more and try to get to

the reward much more quickly than normal rodents, but their pleasure-

elicited facial expressions of “liking” sweetness never increase and are

actually lower than normal.

Similar enhancement of “wanting” without “liking” is caused by

directly stimulating dopamine release in the nucleus accumbens of rats

via a painless microinjection of amphetamine (Tindell, Berridge, Zhang,

Peciña, & Aldridge, 2005; Wyvell & Berridge, 2000). The elevated dopa-

mine makes cues for a sweet reward trigger intense pulses of motivation

to obtain, but when they actually taste the sugary treat it is no more

pleasant than normal. Conversely, rats that have lost nearly all their brain

dopamine fail to “want” any rewards at all and will voluntarily starve

to death unless nursed and passively nourished. Yet the dopamine- free

rats that refuse to eat have completely normal “liking” for any taste put

in their mouth. Likewise, in humans, brain levels of dopamine appear

to more closely track people’s ratings of wanting for a tasty food or an

FIGURE 6.2. Pleasure cycles. The brain needs to optimize resource allocation for

survival, and individuals are limited in the number of concurrent behaviors

they can engage in. Survival depends on engagement with rewards and typically

follows a cyclical time course common to many everyday moments of positive

affect. Within this pleasure cycle rewards act as motivational magnets to initiate,

sustain, and switch states. Typically, rewarding moments go through a phase of

expectation or wanting for a reward, which sometimes leads to a phase of con-

summation or liking of the reward, which can have a peak level of pleasure (e.g.,

encountering a loved one, a tasty meal, sexual orgasm, a drug rush, winning a

gambling bet). This can be followed by a satiety or learning phase, where one

learns and updates predictions for the reward. (Purchasers can download a color

version of this figure from www.guilford.com/p/hofmann2.)

Ple

asu

re

Time

Set-point

Wanting Liking Learning

Reward

Computational

Expectation

Prediction

Consummation

Evaluation

Satiety

Prediction error



addictive drug such as cocaine than to track their liking ratings for the

same reward (Evans et al., 2006; Leyton et al., 2002; see also Franken,

Chapter 19, this volume).

Given this new knowledge, it now seems clear that “pleasure elec-

trodes” might not be so pleasurable as originally assumed, but perhaps

also instead linked to the psychological process of “wanting” that can

occur without “liking.” Indeed, the original electrodes that rats worked to

activate turned on brain dopamine and, if given freely, often motivated

avid eating during the stimulation. But food tastes do not become more

pleasant during brain electrode stimulation that makes a rat eat, unlike

during a hotspot opioid stimulation or during natural hunger. Instead,

the rats show more “disliking” facial reactions to sugar taste during the

stimulation as though the electrode had made sweetness become bitter or

disgusting— even though the same electrode makes them consume large

quantities of food whenever turned on.

Similarly in humans, classic brain electrode stimulation sometimes

made people thirstily want to drink fluids— or strongly wish to engage

in sex —as well as to press thousands of times on their buttons that acti-

vated the electrode (Heath, 1972). Yet exclamations of pleasure were typi-

cally not produced by electrode stimulations, and many reports of the

experience were often dominated more by undercurrents of anxiety than

by any pleasurable sensation.

In the past decade, new techniques of deep brain stimulation deliver

pulses of stimulation programmed by computer to electrodes implanted

in brain structures related to reward, in conditions ranging from depres-

sion or obsessive– compulsive disorder (OCD) to Parkinson’s disease

(Kringelbach, Green, & Aziz, 2011; Kringelbach, Jenkinson, Owen, &

Aziz, 2007b). Sometimes the stimulation has led to side effects where the

patients have experienced manic mood episodes characterized by nearly

compulsive energetic motivation to shop or engage in hobbies, become

romantically attracted to nearby strangers, or fall into fits of mirthful

laughter (Kringelbach, Green, Owen, Schweder, & Aziz, 2010). Yet these

states are not necessarily pleasant. The energetic motivation can become

dominated by anxiety and hostility, or even paranoia, and the electrode-

evoked laughter can become so unpleasant that the patient asks for help to

make it stop. All of these conditions may reflect activation of dopamine-

related brain systems of “wanting” that simply by pass the generators

of pleasure “liking” (Berridge & Valenstein, 1991). In our view, it still

remains unknown whether any of Olds and Milner’s electrodes indicated

true pleasure (Figure 6.2).

Something similar may happen in the brains of some drug addicts.

Intense “wanting” may be triggered by drug- related cues, and the vul-

nerability to such urges may last a long time, creating an enduring

risk of relapse (see also Franken, Chapter 19, this volume). The reason

is that addictive drugs not only activate brain dopamine systems, but



in some people the drugs also may permanently change those systems.

The change is neural sensitization, which leaves the brain’s mesolimbic

systems hyperreactive to addictive drugs and associated cues in a way

that may generate intense “wanting.” This neural change, called incen-

tive sensitization, may well last years (Robinson & Berridge, 1993, 2001).

Persisting long after detox is finished and withdrawal feelings have gone

away, incentive sensitization would leave the person vulnerable to cue-

triggered urges to take the drug again despite sincere wishes not to do so,

especially at moments of stress or in other states that stimulate reactivity

of brain dopamine systems. Such elevated “wanting” could persist even

if tolerance left the addict no longer “liking” the drug as much as before.

Manipulating Hedonic Valence in the Brain

Positive (desire) and negative (dread) emotions can be controlled via

hedonic mechanisms. Recent studies have demonstrated existence of an

affective keyboard mechanism in the medial shell of the nucleus accumbens

for generating intense dread versus desire. This accumbens keyboard has a

remarkable anatomical orderliness in the arrangement of valence genera-

tors (Figure 6.3). Intense dread– desire motivations can be induced with

localized disruptions, arranged by valence along a rostrocaudal gradient

in the shell (Richard & Berridge, 2011, 2013). Just as a musical keyboard

generates many different notes according to key location, the affective

keyboard can generate many mixtures of desire versus fear, each mixture

triggered at a different anatomical location.

Furthermore, although anatomical location biases the valence of

desire versus dread released by the keyboard, valence at many sites can

be retuned by context and psychological factors. The presence of a stress-

fully overstimulating sensory environment such as bright lights and

loud music (e.g., Iggy Pop) remaps the accumbens bivalent keyboard by

expanding the fear- generating zone while shrinking the desire- generating

zone (Reynolds & Berridge, 2008). Conversely, a comfortable and quiet

homelike ambience remaps in opposite direction, expanding desire and

shrinking fear. Such psychological top-down remapping can retune a sin-

gle site in the nucleus accumbens so that it releases opposite motivations

in different situations, reversing its mode of operation.

The switch in operating mode may involve recruiting different neu-

robiological components. Fear generation demands endogenous dopa-

mine activity at D1 and D2 receptors simultaneously within a “key” site

(implicating roles for both a “direct” output path to the tegmentum and

an “indirect” path to the ventral pallidum and hypothalamus), whereas

positive desire generation by the same site requires only its D1 dopamine

signal (potentially indicating a more dominant role for neurons of its

“direct” path to the ventral tegmentum).



FIGURE 6.3. Affective keyboard for intense desire and dread in the nucleus accum-

bens. The keyboard pattern of intense motivated behaviors is revealed in the

consequences of drug microinjections at various rostrocaudal sites in the medial

shell. Microinjections of drugs that relatively inhibit accumbens neurons via

amino acid neurotransmitters (e.g., a GABA agonist or a glutamate antagonist)

may in turn disinhibit or release motivation- generating circuits in downstream

target structures. Rostral green sites released stimulation of eating by up to 600%

(desire only). Caudal red sites released purely increased fearful reactions at levels

up to 600% over normal (dread only; escape attempts, distress calls, defensive

bite attempts; spontaneous anti- predator treading/burying). Yellow sites released

both desire and dread in the same rats during the same 1-hour test. Just as a key-

board has many notes, the bars shown in the figure reflect the many graded mix-

tures of affective desire– dread released as microinjection sites move rostrocaudal

location in medial shell (appetitive desire to eat at top; fearful dread reactions at

bottom). Adapted from Berridge and Kringelbach (2013) and based on data from

Richard and Berridge (2011, 2013). Copyright 2013 by Kringelbach and Berridge.

Adapted by permission. (Purchasers can download a color version of this figure

from www.guilford.com/p/hofmann2.)

Appetitive

Defensive

Mixed

No effect

850

600

350

100

100

350

600

850

% Incre

ase

Eating

% Incre

ase

Fear



Neurochemical signals similarly switch the operating modes of an

accumbens microdomain to generate different affects and motivations.

For example, in the rostral nucleus accumbens hotspot, opioid stimula-

tion generates intense “liking” plus “wanting” for reward, while micro-

injection of dopamine or glutamate- related drugs generates “wanting”

alone. Conversely, in a caudal nucleus accumbens shell key, microin-

jections inducing opioid or dopamine stimulation generate “wanting,”

whereas glutamate AMPA blockade instead generates fear, and GABA sig-

nals add disgust to the fear. Thus, a variety of intense affective states can

be created by changing the manipulation of a single site.

Of Mice and Men: From Pleasure Causes to Pleasure Codes

While findings from brain studies of rodents have contributed enor-

mously to our fundamental understanding of how pleasure is generated,

it is also clear that the brain of a rodent is not much larger than a human

opposable thumb. How well do these important findings of animal plea-

sure relate to human pleasure— and in particular to those perhaps unique

higher- order pleasures such as friends and loved ones, or money, culture,

music, and dance?

Evolutionary forces have been busy since humans and rats shared a

common ancestor 100 million years ago. In terms of brain changes, the

perhaps most significant change has happened in the rapid proportional

expansion of the prefrontal cortex, while similar increases have not taken

place in the overall amount of, for example, gray matter in the rest of the

brain (Rakic, 2009).

Modern neuroimaging techniques have allowed us to probe the

brain substrate of human pleasure, even though brain scanners are not

particularly friendly environments for inducing much pleasure. Yet, with

some ingenuity studies have managed to look at changes in brain activ-

ity related to both fundamental pleasures such as food (Kringelbach,

O’Doherty, Rolls, & Andrews, 2003; Rolls, Kringelbach, & de, 2003; Small

et al., 2003; Small, Zatorre, Dagher, Evans, & Jones- Gotman, 2001) and

sex (Georgiadis et al., 2006; Georgiadis & Kringelbach, 2012), and to

higher- order pleasures such as music (Gebauer, Kringelbach, & Vuust,

2012; Salimpoor, Benovoy, Larcher, Dagher, & Zatorre, 2011; Salimpoor et

al., 2013) and money (O’Doherty, Kringelbach, Rolls, Hornak, & Andrews,

2001).

Human brains notice, remember, think about, and plan for pleasure,

beyond causing the pleasant feeling at the moment. All of this can be con-

sidered a form of pleasure coding in the brain, for which the expanded

prefrontal cortex plays especially important roles. We have shown that

hedonic coding especially occurs in a specific part of the lower prefron-

tal cortex, the orbitofrontal cortex (OFC), hanging right above the eyes



(Kringelbach, 2005) (Figure 6.4). Particularly, a region located in the mid-

anterior subregion of OFC (roughly around 1 cubic centimeter in size) shows

neuroimaging activity tightly correlated with the subjective pleasantness

of a nice sensation, such as the taste of chocolate milk or of tomato juice

(Kringelbach et al., 2003).

These tasty sensations do not simply cause activity in the OFC in the

same way all the time, but rather vary in activity according to just how

pleasant the taste is at the moment. Taste pleasantness is modulated by

selective satiety, or what can be called the dessert stomach phenomenon.

Why do we always seem to have room for dessert even when we feel

FIGURE 6.4. Brain pleasure networks, “pleasure electrodes,” and the orbitofrontal

cortex. (A) Pleasure is processed in hedonic networks, where hedonic causation

has been identified in rodents as arising from interlinked subcortical hedonic

hotspots, such as in the nucleus accumbens and ventral pallidum, where neural

activation may increase “liking” expressions to sweetness. Similar pleasure cod-

ing and incentive salience networks have also been identified in humans. (B)

The so- called “pleasure” electrodes in rodents and humans were unlikely to have

elicited much true pleasure, but perhaps only incentive salience or desire. (C)

Subjective pleasure is faithfully coded by orbitofrontal cortex (OFC) activations

in people. Sensory pleasures appear to be most faithfully represented by a mid-

anterior OFC site (orange). Pleasant sensations are also coded by activation in a

medial strip of the OFC (green), but the medial strip may not as faithfully track

changes in pleasure as the orange mid- anterior site. Smaller symbols show results

of a large meta- analysis of 267 orbital areas, which indicated that a medial sub-

region of the OFC monitored learning and memory of reward values (green area

and round blue dots), whereas a lateral orbitofrontal subregion monitored pun-

ishers (purple and orange triangles) (Kringelbach & Rolls, 2004). Independently,

posterior subregions of the OFC represented complex or abstract reinforcers (such

as money), whereas anterior subregions represented sensory rewards such as taste.

(Purchasers can download a color version of this figure from www.guilford.com/p/

hofmann2.)



completely full from the main course? In part, it is because the dessert is

the only part of the meal that we haven’t tasted yet. From an evolution-

ary perspective, this has the clear advantage of helping to obtain a suf-

ficiently wide variety of nutrients.

Selective satiety is not just good for restaurants but is useful for

studying reward representation in the brain, because it provides a way

of altering the affective value of a stimulus without modifying the taste’s

physical attributes. As a result, any differences in brain activity can be

attributed to the change in the impact of the reward, or the reward value.

The important finding is that when people drink a large amount of

tomato juice to satiety, their mid- anterior site in the orbitofrontal brain

immediately afterwards stops activating to this taste, and they simultane-

ously report the tomato taste as no longer pleasant, whereas they still like

and have activity to the taste of chocolate milk. The converse was true

when people drank too much chocolate milk. These selective changes in

liking for tomato or chocolate tastes due to satiety effects are strong evi-

dence that the mid- anterior site of the OFC tracks the pleasure of a sensa-

tion, and not any simpler psychological or physical feature.

Similar orbitofrontal coding of pleasure has also been found for sex-

ual orgasm, in a study by Janniko Georgiadis of the University of Gron-

ingen in the Netherlands. Sexual pleasure was examined in women who

were either having real sexual orgasms or instead only faking an orgasm

and its expressions, as in the movie When Harry Met Sally (Georgiadis et

al., 2006b; Georgiadis & Kringelbach, 2012; Georgiadis, Kringelbach, &

Pfaus, 2012). In short, the pleasure of diverse rewards may be coded by

the OFC (Kringelbach, 2005).

Other regions of the cortex also have been implicated in coding plea-

sure, though the evidence for selective hedonic coding is not yet quite as

convincing as for the mid- anterior site of the OFC. Those regions include

a more medial strip of OFC located in the middle of the prefrontal lobe,

parts of the anterior cingulate cortex, slightly higher in the central front

of the brain, and a site in the insular cortex that sits deep inside the lateral

surface of the prefrontal lobe. These results have implicated a network

of key brain regions involved in pleasure and reward (Figure 6.4). Activ-

ity is found in this pleasure network for a whole range of basic sensory

pleasures such as food, sex, or addictive drugs (Völlm et al., 2004), and

higher- order pleasures including money, music, empathy, and even com-

passion (Kringelbach & Berridge, 2010; Kringelbach & Phillips, 2014).

The very existence of a brain pleasure network raises some interest-

ing and challenging questions for understanding how a sense of well-

being comes about. Taken together, the current evidence from animals

and humans would suggest that the subcortical hotspot regions are per-

haps most important for generating core processes of pleasure, while cor-

tical regions may be more linked to coding and interfacing pleasure with

cognition and conscious appraisal. It is also clear that fine- grained neural



dynamics and oscillations within the pleasure system are important and

interact closely with the brain’s so- called resting state networks (Zhang

& Raichle, 2010).

Recently, the combination of brain imaging with therapeutic deep

brain stimulation in patients has shown some interesting results for relief

from suffering. For example, we found that some forms of chronic pain

can be relieved with deep brain stimulation, which is experienced as

pleasurable by the patient (Kringelbach, Pereira, Green, Owen, & Aziz,

2009). Simultaneous MEG (magnetoencephalography) scanning showed

activity in brain regions including the mid- anterior OFC (Kringelbach et

al., 2007a). Stimulation of specific parts of the pleasure system for treat-

ing severe depression is also being investigated by others (Mayberg et al.,

2005), although the long-term efficacy of such treatments still remains

an open question (Lozano et al., 2012).

Desire for a Science of Well-Being?

At a deeper level, how might understanding brain pleasure networks

apply to more general questions of human well-being or happiness? Plea-

sure has traditionally been thought of as providing one part of happi-

ness, though there has been debate about its relative contribution (see

also Oishi, Westgate, Tucker, & Komiya, Chapter 14, this volume). Since

Aristotle, for example, well-being or happiness has often been thought to

consist of at least two ingredients: hedonia (pleasure or positive affect)

and eudaimonia (cognitive appraisals of meaning and life satisfaction).

While some progress has been made in understanding brain hedonics,

as shown in this article, it is important not to overinterpret our findings.

In particular, hardly anything is known about how brain systems relate

to the eudemonia component of happiness. Therefore science has not yet

made substantial progress toward understanding the functional neurosci-

ence of broader feelings of well-being or happiness.

Still, we can imagine several possible ways to relate happiness to par-

ticular hedonic psychological processes discussed above. For example,

one way to conceive of hedonic happiness is as “liking” without “want-

ing.” That is, a state of pleasure without disruptive desires, a state of con-

tentment. Another possibility is that moderate “wanting,” matched to

positive “liking,” facilitates engagement with the world. A little incentive

salience may add zest to the perception of life and perhaps even pro-

mote the construction of meaning, just as in some patients therapeutic

deep brain stimulation may help lift the veil of depression by making life

events more appealing. However, too much “wanting” can readily spiral

into maladaptive patterns such as addiction, and is a direct route to great

unhappiness (see also Oishi, Westgate, Tucker, & Komiya, Chapter 14, this

volume).



Finally, all might agree that happiness springs not from any single

component but from the interplay of higher pleasures, positive apprais-

als of life meaning, and social connectedness, all combined and merged

by interaction between the brain’s networks of pleasure and meaningful-

ness. Achieving the right hedonic balance in such ways may be crucial to

keep one not just free of distress— but even to achieve a degree of bliss.

REFERENCES

Berridge, K. C. (2007). The debate over dopamine’s role in reward: The case for incentive salience. Psychopharmacology, 191, 391–431.

Berridge, K. C., & Kringelbach, M. L. (2008). Affective neuroscience of pleasure: Reward in humans and animals. Psychopharmacology, 199, 457–480.

Berridge, K. C., & Kringelbach, M. L. (2011). Building a neuroscience of pleasure and well-being. Psychology of Well-Being: Theory, Research and Practice, 1(1), 1–3.

Berridge, K. C., & Kringelbach, M. L. (2013). Neuroscience of affect: Brain mecha-nisms of pleasure and displeasure. Current Opinion in Neurobiology, 23, 294–303.

Berridge, K. C., & Valenstein, E. S. (1991). What psychological process mediates feeding evoked by electrical stimulation of the lateral hypothalamus? Behav-ioral Neuroscience, 105, 3–14.

Evans, A. H., Pavese, N., Lawrence, A. D., Tai, Y. F., Appel, S., Doder, M., et al. (2006). Compulsive drug use linked to sensitized ventral striatal dopamine transmission. Annals of Neurology, 59, 852–858.

Gebauer, L., Kringelbach, M. L., & Vuust, P. (2012). Ever- changing cycles of musi-cal pleasure: The role of dopamine and anticipation. Psychomusicology, Music, Mind and Brain, 22, 152–167.

Georgiadis, J. R., Kortekaas, R., Kuipers, R., Nieuwenburg, A., Pruim, J., Reinders, A. A., et al. (2006). Regional cerebral blood flow changes associated with cli-torally induced orgasm in healthy women. European Journal of Neuroscience, 24, 3305–3316.

Georgiadis, J. R., & Kringelbach, M. L. (2012). The human sexual response cycle: Brain imaging evidence linking sex to other pleasures. Progress in Neurobiol-ogy, 98, 49–81.

Georgiadis, J. R., Kringelbach, M. L., & Pfaus, J. G. (2012). Sex for fun: A synthesis of human and animal neurobiology. Nature Reviews Urology, 9, 486–498.

Heath, R. G. (1972). Pleasure and brain activity in man: Deep and surface electro-encephalograms during orgasm. Journal of Nervous and Mental Disease, 154, 3–18.

Hoebel, B. G., Rada, P. V., Mark, G. P., & Pothos, E. N. (1999). Neural systems for reinforcement and inhibition of behavior: Relevance to eating, addiction, and depression. In D. Kahneman, E. Diener, & N. Schwarz (Eds.), Well-being: The foundations of hedonic psychology (pp. 558–572). New York: Russell Sage Foundation.

Kringelbach, M. L. (2005). The orbitofrontal cortex: Linking reward to hedonic experience. Nature Reviews Neuroscience, 6, 691–702.

Kringelbach, M. L. (2009). The pleasure center: Trust your animal instincts. New York: Oxford University Press.



Kringelbach, M. L., & Berridge, K. C. (2010). Pleasures of the brain. New York: Oxford University Press.

Kringelbach, M. L., & Berridge, K. C. (2012). A joyful mind. Scientific American, 307, 40–45.

Kringelbach, M. L., Green, A. L., & Aziz, T. Z. (2011). Balancing the brain: Resting state networks and deep brain stimulation. Frontiers of Integrative Neurosci-ence, 5, 8.

Kringelbach, M. L., Green, A. L., Owen, S. L. F., Schweder, P. M., & Aziz, T. Z. (2010). Sing the mind electric: Principles of deep brain stimulation. European Journal of Neuroscience, 32, 1070–1079.

Kringelbach, M. L., Jenkinson, N., Green, A. L., Owen, S. L. F., Hansen, P. C., Cornelissen, P. L., et al. (2007a). Deep brain stimulation for chronic pain investigated with magnetoencephalography. NeuroReport, 18, 223–228.

Kringelbach, M. L., Jenkinson, N., Owen, S. L. F., & Aziz, T. Z. (2007b). Transla-tional principles of deep brain stimulation. Nature Reviews Neuroscience, 8, 623–635.

Kringelbach, M. L., O’Doherty, J., Rolls, E. T., & Andrews, C. (2003). Activation of the human orbitofrontal cortex to a liquid food stimulus is correlated with its subjective pleasantness. Cerebral Cortex, 13, 1064–1071.

Kringelbach, M. L., Pereira, E. A. C., Green, A. L., Owen, S. L. F., & Aziz, T. Z. (2009). Deep brain stimulation for chronic pain. Journal of Pain Management, 3, 301–314.

Kringelbach, M. L., & Phillips, H. (2014). Emotion: Pleasure and pain in the brain. Oxford, UK: Oxford University Press.

Kringelbach, M. L., & Rolls, E. T. (2004). The functional neuroanatomy of the human orbitofrontal cortex: Evidence from neuroimaging and neuropsy-chology. Progress in Neurobiology, 72, 341–372.

Leyton, M., Boileau, I., Benkelfat, C., Diksic, M., Baker, G., & Dagher, A. (2002). Amphetamine- induced increases in extracellular dopamine, drug wanting, and novelty seeking: A PET/[11C]raclopride study in healthy men. Neuropsy-chopharmacology, 27, 1027–1035.

Lozano, A. M., Giacobbe, P., Hamani, C., Rizvi, S. J., Kennedy, S. H., Kolivakis, T. T., et al. (2012). A multicenter pilot study of subcallosal cingulate area deep brain stimulation for treatment- resistant depression. Journal of Neurosurgery, 116, 315–322.

Mayberg, H. S., Lozano, A. M., Voon, V., McNeely, H. E., Seminowicz, D., Hamani, C., et al. (2005). Deep brain stimulation for treatment- resistant depression. Neuron, 45, 651–660.

O’Doherty, J., Kringelbach, M. L., Rolls, E. T., Hornak, J., & Andrews, C. (2001). Abstract reward and punishment representations in the human orbitofrontal cortex. Nature Neuroscience, 4, 95–102.

Olds, J. (1956). Pleasure centers in the brain. Scientific American, 195, 105–116.Olds, J., & Milner, P. (1954). Positive reinforcement produced by electrical stimu-

lation of the septal area and other regions of rat brain. Journal of Comparative and Physiological Psychology, 47, 419–427.

Parsons, C. E., Stark, E. A., Young, K. S., Stein, A., & Kringelbach, M. L. (2013). Understanding the human parental brain: A critical role of the orbitofrontal cortex. Social Neuroscience, 8, 525–543.

Parsons, C. E., Young, K. S., Murray, L., Stein, A., & Kringelbach, M. L. (2010). The functional neuroanatomy of the evolving parent– infant relationship. Progress in Neurobiology, 91, 220–241.



Peciña, S., & Berridge, K. C. (2005). Hedonic hot spot in nucleus accumbens shell: Where do mu- opioids cause increased hedonic impact of sweetness? Journal of Neuroscience, 25, 11777–11786.

Rakic, P. (2009). Evolution of the neocortex: A perspective from developmental biology. Nature Reviews Neuroscience, 10, 724–735.

Reynolds, S. M., & Berridge, K. C. (2008). Emotional environments retune the valence of appetitive versus fearful functions in nucleus accumbens. Nature Neuroscience, 11, 423–425.

Richard, J. M., & Berridge, K. C. (2011). Nucleus accumbens dopamine/glutamate interaction switches modes to generate desire versus dread: D1 alone for appetitive eating but D1 and D2 together for fear. Journal of Neuroscience, 31, 12866–12879.

Richard, J. M., & Berridge, K. C. (2013). Prefrontal cortex modulates desire and dread generated by nucleus accumbens glutamate disruption. Biological Psy-chiatry, 73, 360–370.

Richard, J. M., Castro, D. C., Difeliceantonio, A. G., Robinson, M. J., & Berridge, K. C. (2013). Mapping brain circuits of reward and motivation: In the footsteps of Ann Kelley. Neuroscience and Biobehavioral Reviews, 37, 1919–1931.

Robinson, S., Sandstrom, S. M., Denenberg, V. H., & Palmiter, R. D. (2005). Dis-tinguishing whether dopamine regulates liking, wanting, and/or learning about rewards. Behavioral Neuroscience, 119, 5–15.

Robinson, T. E., & Berridge, K. C. (1993). The neural basis of drug craving: An incentive- sensitization theory of addiction. Brain Research Reviews, 18, 247–291.

Robinson, T. E., & Berridge, K. C. (2001). Incentive- sensitization and addiction. Addiction, 96, 103–114.

Rolls, E. T., Kringelbach, M. L., & de Araujo, I. E. T. (2003). Different representa-tions of pleasant and unpleasant odors in the human brain. European Journal of Neuroscience, 18, 695–703.

Salimpoor, V. N., Benovoy, M., Larcher, K., Dagher, A., & Zatorre, R. J. (2011). Anatomically distinct dopamine release during anticipation and experience of peak emotion to music. Nature Neuroscience, 14, 257–262.

Salimpoor, V. N., van den Bosch, I., Kovacevic, N., McIntosh, A. R., Dagher, A., & Zatorre, R. J. (2013). Interactions between the nucleus accumbens and audi-tory cortices predict music reward value. Science, 340, 216–219.

Sem- Jacobsen, C. W. (1976). Electrical stimulation and self- stimulation with chronic implanted electrodes: Interpretation and pitfalls of results. In A. Wauquier & E. T. Rolls (Eds.), Brain- stimulation reward (pp. 505–520). Amster-dam: Elsevier- North Holland.

Shizgal, P. (1999). On the neural computation of utility: Implications from stud-ies of brain stimulation reward. In D. Kahneman, E. Diener, & N. Schwarz (Eds.), Well-being: The foundations of hedonic psychology (pp. 500–524). New York: Russell Sage Foundation.

Small, D. M., Gregory, M. D., Mak, Y. E., Gitelman, D., Mesulam, M. M., & Parrish, T. (2003). Dissociation of neural representation of intensity and affective valuation in human gustation. Neuron, 39, 701–711.

Small, D. M., Zatorre, R. J., Dagher, A., Evans, A. C., & Jones- Gotman, M. (2001). Changes in brain activity related to eating chocolate: From pleasure to aver-sion. Brain, 124, 1720–1733.

Steiner, J. E. (1973). The gustofacial response: Observation on normal and anen-



cephalic newborn infants. Symposium on Oral Sensation and Perception, 4, 254–278.

Steiner, J. E., Glaser, D., Hawilo, M. E., & Berridge, K. C. (2001). Comparative expression of hedonic impact: Affective reactions to taste by human infants and other primates. Neuroscience and Biobehavioral Reviews, 25, 53–74.

Tindell, A. J., Berridge, K. C., Zhang, J., Peciña, S., & Aldridge, J. W. (2005). Ventral pallidal neurons code incentive motivation: Amplification by mesolimbic sensitization and amphetamine. European Journal of Neuroscience, 22, 2617–2634.

Valenstein, E. S. (1973). Brain control: A critical examination of brain stimulation and psychosurgery. London: Wiley- Interscience.

Völlm, B. A., de Araujo, I. E. T., Cowen, P. J., Rolls, E. T., Kringelbach, M. L., Smith, K. A., et al. (2004). Methamphetamine activates reward circuitry in drug naïve human subjects. Neuropsychopharmacology, 29, 1715–1722.

Wise, R. A., & Bozarth, M. A. (1985). Brain mechanisms of drug reward and euphoria. Psychiatric Medicine, 3, 445–460.

Wyvell, C. L., & Berridge, K. C. (2000). Intra- accumbens amphetamine increases the conditioned incentive salience of sucrose reward: Enhancement of reward “wanting” without enhanced “liking” or response reinforcement. Journal of Neuroscience, 20, 8122–8130.

Yokel, R. A., & Wise, R. A. (1975). Increased lever pressing for amphetamine after pimozide in rats: Implications for a dopamine theory of reward. Science, 187, 547–549.

Zhang, D., & Raichle, M. E. (2010). Disease and the brain’s dark energy. Nature Reviews Neurology, 6, 15–28.


Documents

Neuroscience of Desire and Desire Regulation