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Rethinking the Emotional Brain

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I propose a reconceptualization of key phenomena important in the study of emotion-those phenomena that reflect functions and circuits related to survival, and that are shared by humans and other animals. The approach shifts the focus from questions about whether emotions that humans consciously feel are also present in other animals, and toward questions about the extent to which circuits and corresponding functions that are present in other animals (survival circuits and functions) are also present in humans. Survival circuit functions are not causally related to emotional feelings but obviously contribute to these, at least indirectly. The survival circuit concept integrates ideas about emotion, motivation, reinforcement, and arousal in the effort to understand how organisms survive and thrive by detecting and responding to challenges and opportunities in daily life.
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RETHINKING THE EMOTIONAL BRAIN
Joseph LeDoux
Center for Neural Science and Department of Psychology, New York University, New York, NY.
Emotional Brain Institute, New York University and Nathan Kline Institute, New York, NY and
Orangeburg, NY
Abstract
I propose a re-conceptualization of key phenomena important in the study of emotion — those
phenomena that reflect functions and circuits related to survival, and that are shared by humans
and other animals. The approach shifts the focus from questions about whether emotions that
humans consciously feel are also present in other animals, and towards questions about the extent
to which circuits and corresponding functions that are present in other animals (survival circuits
and functions) are also present in humans. Survival circuit functions are not causally related to
emotional feelings, but obviously contribute to these, at least indirectly. The survival circuit
concept integrates ideas about emotion, motivation, reinforcement, and arousal in the effort to
understand how organisms survive and thrive by detecting and responding to challenges and
opportunities in daily life.
Introduction
Emotion is a major research growth area in neuroscience and psychology today. A search of
PubMed citations for the 1960s yields just over 100 papers with the word “emotion” in the
title. With each subsequent decade, small increases resulted, until the last decade, when
emotion titles grew exponentially — more than 2000 hits. Emotion has happened.
But what exactly is it that has happened? What is being studied in all these papers on
emotion? Actually, the term “emotion” is not well-defined in most publications. Perhaps this
is not surprising since there is little consensus about what emotion is, and how it differs from
other aspects of mind and behavior, in spite of discussion and debate that dates back to the
earliest days in modern biology and psychology (e.g. Darwin, 1872; James, 1884; Cannon,
1927, 1931; Duffy, 1934, 1941; Tomkins, 1962; Mandler, 1975; Schachter, 1975; Ekman,
1980, 1984, 1992; Izard, 2007; Frijda, 1986; Russell, 2003;; Ekman and Davidson, 1994;
LeDoux, 1996; Panksepp, 1998, 2000, 2005; Rolls, 1999, 2005; Damasio, 1994, 1999;
Leventhal and Scherer, 1987; Scherer, 2000; Ortony and Turner, 1990; Öhman, 1986, 2009;
Johnson-Laird and Oatley, 1989; Ellsworth, 1994; Zajonc, 1980; Lazarus, 1981, 1991a, b;
Barrett, 2006a, b; 2007; Kagan, 2007; Prinz, 2004; Scarantino, 2009; Griffiths, 2004;
Ochsner and Gross, 2005; Lyons, 1980).
One point that many writers on this topic accept is that, while there are unique features of
human emotion, at least some aspects of human emotion reflect our ancestral past. This
conclusion is the basis of neurobiological approaches to emotion, since animal research is
essential for identifying specific circuits and mechanisms in the brain that underlie
emotional phenomena.
Progress in understanding emotional phenomena in the brains of laboratory animals has in
fact helped elucidate emotional functions in the human brain, including pathological aspects
of emotion. But what does this really mean? If we don’t have an agreed upon definition of
emotion that allows us to say what emotion is, and how emotion differs from other
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psychological states, how can we study emotion in animals or humans, and how can we
make comparisons between species?
The short answer is that we fake it. Introspections from personal subjective experiences tell
us that some mental states have a certain “feeling” associated with them and others do not.
Those states that humans associate with feelings are often called emotions. The terms
“emotion” and “feeling” are, in fact, often used interchangeably. In English we have words
like fear, anger, love, sadness, jealousy, and so on, for these feeling states, and when
scientists study emotions in humans they typically use these “feeling words” as guideposts
to explore the terrain of emotion.
The wisdom of using common language words that refer to feelings as a means of
classifying and studying human emotions has been questioned by a number of authors over
the years (e.g. Duffy, 1934, 1941; Mandler, 1975; Russell, 1991, 2003; Barrett, 2006a,
2006b; Kagan, 2007; Griffiths, 1997; Rorty, 1980; Dixon, 2001; Zachar, 2006). Whatever
problems might arise from using feeling words to study human emotion, the complications
are compounded many fold when such words are applied to other animals. While there are
certainly emotional phenomena that are shared by humans and other animals, introspections
from human subjective experience are not the best starting point for pursuing these. How,
then, should the aspects of emotion relevant to animals and humans alike be pursued?
In answering this question it is important to separate the phenomena of interest from the
overarching concept of emotion. One set of such phenomena includes responses that occur
when an organism detects and responds to significant events in the course of surviving and/
or maintaining well-being — for example, responses that occur when in danger or when in
the presence of a potential mate or in the presence of food when hungry or drink when
thirsty. These are fundamental phenomena that have always interested animal behavior
scientists, and would be of interest even if the terms “emotion” and “feelings” never existed.
The challenge for emotion researchers is to understand the relation of the phenomena to the
field of emotion without redefining them as fundamentally emotional phenomena, and thus
infusing the phenomena with confusing implications.
In this Perspectives I, therefore, describe a way of conceiving phenomena important to the
study of emotion, but with minimal recourse to the terms emotion or feelings. The focus is
instead on circuits that instantiate functions that allow organisms to survive and thrive by
detecting and responding to challenges and opportunities. Included, at a minimum, are
circuits involved in defense, maintenance of energy and nutritional supplies, fluid balance,
thermoregulation, and reproduction. These survival circuits and their adaptive functions are
conserved to a significant degree in across mammalian species, including humans. While
there are species-specific aspects of these functions, there are also core components of these
functions that are shared by all mammals.
By focusing on survival functions instantiated in conserved circuits, key phenomena
relevant to emotions and feelings are discussed with the natural direction of brain evolution
in mind (by asking to what extent are functions and circuits that are present in other
mammals also present in humans) rather than by looking backwards, and
anthropomorphically, into evolutionary history (by asking whether human emotions/feelings
have counterparts in other animals).
Emotion, motivation, reinforcement and arousal are closely related topics and often appear
together in proposals about emotion. Focusing on survival functions and circuits allows
phenomena related to emotion, motivation, reinforcement and arousal to be treated as
components of a unified process that unfolds when an organism faces a challenge or
opportunity
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What follows is
not
an attempt at explaining or defining emotion. Instead, the aim is to offer
a framework for thinking about some key phenomena associated with emotion (phenomena
related to survival functions) in a way that is not confounded by confusion over what
emotion means. Stepping back from the over-arching concept of emotion and focusing
instead on key phenomena that make emotion an interesting topic may be the best way out
of the conceptual stalemate that results from endless debates about what emotion is.
Why Do We Need to Rethink the Relation of Emotion to Survival?
The relation of innate survival functions to emotions is hardly novel, and goes back at least
to Darwin (1872). As a result, neuroscientists have long assumed that specific emotional/
motivational circuits are innately wired into the brain by evolution, and that these mediate
functions that contribute to survival and well-being of the organism (e.g. Cannon, 1929;
MacLean, 1949, 1952; Hess, 1954; Stellar, 1954; von Holst and von Saint Paul, 1962;
Flynn, 1967; Olds, 1977; Siegel and Edinger, 1981; Panksepp, 1982, 1998, 2005; Blanchard
and Blanchard, 1972; Bolles and Fanselow, 1980; Damasio, 1994, 1999; Berridge, 1999;
McNaughton, 1989; Swanson, 2000; Ferris et al, 2008; Choi et al, 2005; Motta et al, 2009;
Lin et al, 2011; Öhman, 2009). That certain emotions are wired into the brain is also a major
tenet of evolutionary psychology (e.g. Tooby and Cosmides, 1990; Pinker, 1997; Nesse,
1990). If many researchers in the field (past and present) believe this, why do we need to
bother with another discussion of the topic?
A major controversy in the field of emotion research today is, in fact, about the issue of
whether there are innate emotion circuits in the human brain. This debate is centered on the
question of whether emotions are “natural kinds,” things that exist in nature as opposed to
being inventions (constructions) of the human mind (e.g. Panksepp, 2000; Griffiths, 2004;
Barrett, 2006a; Izard, 2007; Scarantino, 2009). Much of the discussion is focused the
question of whether so-called “basic emotions” are natural kinds. Basic emotions are those
that area said to be universally expressed and recognized in people around the world,
conserved in our close animal ancestors, and supposedly hard-wired into brain circuits by
evolution (Darwin, 1872; Tomkins, 1962; Ekman, 1972, 1980, 1984, 1992, 1999a, b; Izard,
1992, 2007; Damasio, 1994, 1999; Panksepp, 1998, 2000, 2005; Prinz, 2004). Contemporary
theories recognize between 5 and 7 of these basic or primary emotions. Ekman’s (1972) list
of six basic emotions is the canonical example, and includes fear, anger, happiness, sadness,
disgust, and surprise. This list of putative hardwired basic emotions in fact serves as the
foundation for much research on the neural basis of emotional functions in the human brain
— a recent review uncovered 551 studies between 1990 and 2008 that used Ekman’s basic
emotions faces or variants of these to study functional activity related to emotion in the
human brain (see Fusar-Poli et al, 2009).
In spite of being well known and widely applied in research, the basic emotions point of
view has been challenged on various grounds (e.g. Averill, 1980; Ortony and Turner, 1990;
Russell, 1980, 2003; Barrett, 2006a; Barrett et al, 2007). For one thing, different theories
have different numbers of basic emotions, and even different names for similar emotions. In
addition, questions have been raised about the methods used to identify basic emotions (e.g.
forced choice rather than free labeling of the emotion expressed in a face). Basic emotions
theory has also been challenged on the basis of a lack of coherence of the phenomena that
constitute individual emotions, and the diversity of states to which a given emotion label can
refer. Others argue that emotions, even so-called basic emotions, are psychological/social
constructions, things created by the mind when people interact with the physical or social
environment, as opposed to biologically determined states. Also relevant is the fact that the
main basic emotions theory based on brain research in animals (Panksepp, 1998, 2005) lists
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emotions that do not match up well with those listed by Ekman or otherS as human basic
emotions.
Of particular relevance here is Barrett’s recent challenge to the natural kinds status of basic
emotions, and particularly to the idea that the human brain has evolutionarily conserved
neural circuits for basic emotions (Barrett, 2006a; Barrett et al, 2007). Her argument is
centered on several points: that much of evidence in support of basic emotions in animals is
based on older techniques that lack precision (electrical brain stimulation), that basic
emotions identified in animals do not map onto the human categories, and that evidence
from human imaging studies show that similar brain areas are activated in response to
stimuli associated with different basic emotions. I disagree with Barrett’s conclusion that the
similarity of functional activation in different emotions is an argument against basic
emotions since imaging does not have the resolution necessary to conclude that the
similarity of activation in different states means similar neural mechanisms. Yet, I concur
with her conclusion that the foundation of support for the idea that basic emotions, as
conventionally conceived, have dedicated neural circuits is weak. This does not mean that
the mammalian brain lacks innate circuits that mediate fundamental phenomena relevant to
emotion. It simply means that emotions, as defined in the context of human basic emotions
theory, may not be the best way to conceive of the relevant innate circuits. Enter survival
circuits.
Survival Circuits
It has long been known that the body is a highly integrated system consisting of multiple
subsystems that work in concert to sustain life both on a moment to moment to basis and
over long time scales (Bernard, 1878–1879; Cannon, 1929; Lashley, 1938; Morgan, 1943;
Stellar, 1954; Selye, 1955; McEwen, 2009; Damasio, 1994, 1999; Pfaff, 1999; Schulkin,
2003). A major function of the brain is to coordinate the activity of these various body
systems. An important category of life-sustaining brain functions are those that are achieved
through behavioral interactions with the environment. As noted, these survival circuits
include, at a minimum, circuits involved in defense, maintenance of energy and nutritional
supplies, fluid balance, thermoregulation, and reproduction.
Survival circuits have their ultimate origins in primordial mechanisms that were present in
early life forms. This is suggested by the fact that extant single cell organisms, such as
bacteria, have the capacity to retract from harmful chemicals and to accept chemicals that
have nutritional value (Macnab and Koshland, 1972). With the evolution of multicellular,
and multisystem, eukaryotic organisms (Metazoa, or what we usually call animals),
fundamental survival capacities increase in complexity and sophistication, in large part due
to the presence of specialized sensory receptors and motor effectors, and a central nervous
system that can coordinate bodily functions and interactions with the environment
(Shepherd, 1988).
The brains of vertebrate organisms vary in size and complexity. Yet, in spite of these
differences, there is a highly conserved organizational plan that is characteristic of all
vertebrate brains (Nauta and Karten, 1970; Northcutt and Kass, 1995; Swanson, 2002;
Butler and Hodos, 2005; Striedter, 2005). This conservation is most often discussed in terms
of central sensory and motor systems. However, sensory motor systems do not exist in
isolation, and in fact evolved to negotiate interactions with the environment for the purpose
of sustaining life; for example, by maintaining energy and fluid supplies, regulating body
temperature, defending against harm, and enabling reproduction.
The survival circuits listed do not align well with human basic emotions. However, my goal
is not to align survival circuits with basic emotion categories. It is instead to break free from
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basic emotion categories based on human emotional feelings (introspectively labeled
subjective states) and instead let conserved circuits do the heavy lifting. For example, there
is no anger/aggression circuit in the present scheme. This might at first seem like a striking
omission. However, it is important to note that aggression is not a unitary state with a single
neural representation (Moyer, 1976; Chi and Flynn, 1971; Siegel and Edinger, 1981). The
distinct forms of aggression (consepcific, defensive, and predatory aggression) might be
more effectively segregated by the context in which the aggression occurs: defense circuitry
(aggression in an attempt to protect one’s self from harm); reproductive circuitry (aggression
related to competition for mates); feeding circuitry (predatory aggression towards prey
species). Similarly, a joy/pleasure/happiness kind of circuit is not listed and might seem like
a fatal flaw. However, behaviors used to index joy/pleasure/happiness are instead treated
products of specific circuits involved in energy and nutrition, fluid balance, procreation,
thermoregulation, etc. By focusing on the subjective state, joy/pleasure/happiness, emotion
theories tend to gloss over the underlying details of emotional processing for the sake of
converging on a single word that symbolizes diverse underlying states mediated by different
kinds of circuits.
Each survival circuit may itself need to be refined. For example, it is unlikely that there is a
single unified defense or reproductive circuit. The range of functions studied needs to be
expanded to more effectively characterize these. Some variations on defense are described
below, but still other refinements may be needed.
Another key difference between the survival circuit and basic emotions approaches is this.
Basic emotion circuits are meant as an explanation of the feelings for which each circuit is
said to be responsible. Survival circuits are not posited to have any direct relation (causal
role) in feelings. They indirectly influence feelings, as described later, but their function is to
negotiate behavioral interactions in situations in which challenges and opportunities exist,
not to create feelings.
Survival circuits help organisms survive and thrive by organizing brain functions. When
activated, specific kinds of responses rise in priority, other activities are inhibited, the brain
and body are aroused, attention is focused on relevant environmental and internal stimuli,
motivational systems are engaged, learning occurs and memories are formed (e.g. Morgan,
1943; Hebb, 1949; Bindra, 1969; Gallistel, 1980; Scherer, 1984, 2000; Maturana and Varela,
1987; LeDoux, 2002).
In sum, survival circuits are sensory-motor integrative devices that serve specific adaptive
purposes. They are tuned to detect information relevant to particular kinds of environmental
challenges and opportunities, and they use this information to control behavioral responses
and internal physiological adjustment that help bring closure to the situation. All complex
animals (invertebrates and vertebrates) have survival circuits. Core components of these
circuits are highly conserved in vertebrates. I focus on vertebrates, especially mammals in
this article, but consider the relation of invertebrate to vertebrate survival functions towards
the end.
Nature and Nurture in Survival Circuits
Survival circuits detect key trigger stimuli on the basis of innate programming or past
experience. By innate programming I mean genetically specified synaptic arrangements that
are established in early development. Innate evaluative networks make possible species-
wide stimulus-response connections that allow organisms to respond to specific stimulus
patterns in tried and true ways (i.e. with hard-wired/innate reactions) that have been honed
by natural selection.
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By experience I mean conditions under which associations are formed between novel stimuli
and biologically innately significant events, typically innate triggers. These experience-
dependent associations allow meaningless stimuli that occur in conjunction with significant
events to acquire the ability to activate the innate response patterns that are genetically wired
to innate trigger stimuli. The fact that the response patterns are innately wired and initially
expressed involuntarily does not mean that they are completely inflexible. Not only can they
be coupled to novel stimuli through experience and learning, they can be regulated in terms
of their time course and intensity, and perhaps in other ways.
Innate and experience-based evaluative mechanisms are, as noted, circuit-specific. Thus,
defense, nutritional, reproductive, thermoregulatory and other survival systems are wired to
detect unique innate triggers. By entering into associations with biologically significant
stimuli, novel sensory events become learned triggers that activate survival circuits. We will
consider innate and learned survival circuit triggers in the context of defense next. In the
field of emotion, these are described as unconditioned and conditioned fear stimuli.
Defense as an Example
The evidence for conservation across mammals of mechanisms underlying survival
functions such as defense (e.g. LeDoux, 1996, 2012; Phelps and LeDoux, 2005; Motta et al,
2009; Choi et al, 2005; Kalin et al, 2004; Amaral, 2003; Antoniadis et al, 2007) reproduction
(e.g. Pfaff, 1999; Oomura et al, 1988; Blaustein, 2008), thermoregulation (Nakamura and
Morrison, 2007), fluid balance (Johnson, 2007; Fitzsimons, 1979), and energy/nutritional
regulation (Elmquist et al, 2005; Morton et al 2006; Saper et al, 2002) is strong. Space does
not permit a detailed discussion of these circuits and their functions. Defense circuits in
mammals will be used as an initial illustration.
Defense against harm is a fundamental requirement of life. As noted above, even single cell
organisms can detect and respond to harmful environmental stimuli. In complex organisms
(invertebrates and vertebrates), threat detection involves processing of innate and learned
threats by the nervous system via transmission of information about the threat through
sensory systems to specialized defense circuits.
Unconditioned threat stimuli are species-specific. The most common threat triggers are
stimuli that signal other animals (predators and potentially harmful conspecifics), and these
will obviously be different for different species. Examples of innately wired stimuli for
rodents include predator odors (e.g. Motta et al, 2009; Pagani and Rosen, 2009; Blanchard et
al, 1990), as well as high frequency predator warning sounds emitted by conspecifics (e.g.
Litvin et al, 2007; Choi and Brown, 2003), high intensity auditory stimuli (e.g. Bordi and
LeDoux, 1992) and bright open spaces (Thompson and LeDoux, 1974; Gray, 1987; Walker
and Davis, 2002). In primates, the sight of snakes and spiders have an innate propensity to
trigger defense (Amaral, 2003; Ohman, 1986; Mineka and Ohman, 2002). In spite of being
genetically specified, innate stimulus processing is nevertheless subject to epigenetic
modulation by various factors inside and outside the organism during development, and
throughout life (Bendesky and Bargmann, 2011; Monsey et al, 2011; McEwen eta l, 2012;
Brown and Hariri, 2006; Casey et al, 2011; Zhang et al, 2004). Indeed, some aspects of
defense stimulus processing in primates, including humans, involves preferential rapid
learning to certain classes of innately “prepared” stimuli (Seligman,1971; Ohman, 1986;
Mineka and Ohman, 2002). Fearful and aggressive faces of conspecifics are also a potent
innate defense trigger in humans and other primates (Adolphs, 2008; Davis et al, 2011).
Recent studies have revealed in some detail the circuits that allow rodents to respond to
unconditioned threats, especially odors that signal predators or potentially dangerous
conspecifics (Dielenberg et al, 2001; Canteras, 2002; Petrovich et al, 2001; Markham et al,
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2004; Blanchard et al, 2003; Motta et al, 2009; Choi et al, 2005; Vyas et al, 2007; Pagani
and Rosen, 2009) (Figure 1). The odors are detected by the vermonasal olfactory system and
sent to the medial amygdala (MEA), which connects with the ventromedial hypothalamus
(VMH). Outputs of the latter reach the premammillary nucleus (PMH) of the hypothalamus,
which connects with dorsal periaqueductal gray (PAGd). But not all unconditioned threats
are signaled by odors. Unconditioned threats processed by other (non-olfactory) modalities
involve sensory transmission to the lateral amygdala (LA) and from there to the accessory
basal amygdala (ABA), which connects with the VMH-PM-PAGv circuitry (Motta et al,
2009). Different subnuclei of the MEA, PMH and PAGd are involved in processing
conspecific and predatory threats. Thus, in the case of both olfactory and non-olfactory
unconditioned threat signals, the PAGd and its outputs to motor control areas direct the
expression of behavioral responses that help promote successful resolution of the threatening
event. The PAG is also involved in detection of internal physiological signals that trigger
defensive behavior (Schimitel et al, 2011).
Biologically insignificant stimuli acquire status as threat signals results when they occur in
conjunction with biologically significant threats. This is called Pavlovian defense
conditioning, more commonly known as fear conditioning. Thus, a meaningless conditioned
stimulus (CS) acquires threat status after occurring in conjunction with an aversive
unconditioned stimulus (US). Most studies of Pavlovian defense conditioning involve the
use of electric shock as the biologically significant US, though other modalities have been
used as well. Typically, auditory, visual or olfactory stimuli as the insignificant CS. While a
strong US can induce learning to most kinds of sensory stimuli, associability is not
completely promiscuous — for example, taste stimuli associate more readily with gastric
discomfort than with electric shock (Garcia et al, 1968). Once the association is formed, the
CS itself has the ability to elicit innate defense responses.
The neural circuit by which a CS (auditory, visual, olfactory) elicits innate defense
responses, such as freezing behavior, involves transmission of sensory inputs to the LA,
intraamygdala connections (direct and indirect) linking the LA with the central nucleus of
the amygdala (CEA), and connections from the medial CEA (CEm) to the ventrolateral PAG
(PAGvl) (Johansen et al, 2011; LeDoux, 2000; Maren, 2001; Fanselow and Poulos, 2005;
Davis et al, 1997; Rosenkranz and Grace, 2002; Cousens and Otto, 1998; Pare et al, 2004;
Maren and Quirk, 2004; Quirk and Mueller, 2008). The indirect connections between LA
and CEA include the basal (BA), AB, and intercalated (ITC) nuclei (Pitkanen et al, 1997;
Pare et al, 2004). As with unconditioned threats, PAG outputs to motor control regions
direct behavioral responses to the threat. While damage to the PAGvl disrupts defensive
freezing behavior, lesions of the PAGdl enhance freezing (De Oca et al, 1998), suggesting
interactions between these regions. Whether the CEA and PAG might also be linked via the
VMH or other hypothalamic nuclei has not been carefully explored.
While most studies have focused on freezing, this behavior mainly occurs in confined spaces
where escape is not possible (Fanselow, 1994; Blanchard et al, 1990; de Oca et al, 2007;
Canteras et al, 2010). Little work has been done on the neural basis of defense responses
other than freezing that are elicited by a conditioned cues (but see de Oca and Fanselow,
2004).
An important goal for future work is to examine the relation of circuits involved in innate
and learned behavior. Electric shock simulates tissue damage produced by predator induced
wounds. However, it is difficult to trace the unconditioned stimulus pathways with this kind
of stimulus. Recent studies exploring interactions between circuits processing olfactory
conditioned and unconditioned stimuli is an important new direction (Pavesi et al, 2011).
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Another form of Pavlovian defense conditioning involves the association between a taste CS
and a nausea-inducing US. The circuits underlying so called conditioned taste aversion also
involve regions of the amygdala, such as CEA and the basoloateral complex (which includes
the LA, BA, and ABA nuclei), as well as areas of taste cortex (Lamprecht and Dudai, 2000).
However, the exact contribution of amygdala areas to learning and performance of the
learned avoidance response is less clear than for the standard defense conditioning
paradigms described above.
While much of the work on threat processing has been conducted in rodents, many of the
findings apply to other species. For example, the amygdala nuclei involved in responding to
conditioned threats in rodents appear to function similarly in rabbits (Kapp et al, 1992) and
non-human primates (Kalin et al, 2001, 2004; Antoniadis et al, 2007). Evidence also exists
for homologous amygdala circuitry in reptiles (Martinez-Garcia et al, 2002; Davies et al,
2002; Bruce and Neary, 1995) and birds (Cohen, 1974). In addition, functional imaging and
lesion results from humans (e.g. Phelps, 2006; Damasio 1994, 1999; LaBar and Cabeza,
2006; Whalen and Phelps, 2009; Buchel and Dolan, 2000; Mobbs et al, 2009; Schiller and
Delgado, 2010; Mobbs et al, 2009) show that the amygdala plays a key role in defense
conditioning, and thus suggest that, at least to a first approximation, similar circuits are
involved in humans as in other mammals. However, the level of detail that has been
achieved in humans pales in comparison to the animal work. Methods available for studying
humans are, and are likely to continue to be, limited to levels of anatomical resolution that
obscure circuit details.
Because animal research is thus essential for relating detailed structure to function in the
brain, it is extremely important that the phenomena of interest be conceptualized in a way
that is most conducive to understanding the relation of findings from animal research to the
human condition. Survival circuits provide such a conceptualization.
Interactions Between Survival Circuit Functions
Survival circuits interact to meet challenges and opportunities. Indeed, survival functions are
closely intertwined (e.g. Saper, 2006).
In the presence of a threat to survival or well-being, the brain’s resources are monopolized
by the task of coping with the threat. Other activities, such as eating, drinking, and sex, are
actively suppressed (Gray, 1987; Lima and Dill, 1990; Blanchard et al, 1990; Fanselow,
1994; Choi et al, 2005). However, increased behavioral activity of any kind (fighting,
fleeing, foraging for food or drink, sexual intercourse) expends energy, depleting metabolic
resources. At some point, the need to replenish energy rises in priority and override
defensive vigilance, which might otherwise keep the animal close to home. Foraging for
food or liquids often requires exposure to threats and a balance has to be struck between
seeking the needed resources and staying put. Metabolic activity during any active behavior
(whether fighting, feeding, foraging, fornicating) produces heat that has to be counteracted
by lowering body temperature. Thermoregulation is controlled directly by homeostatic
alterations that include increased sweating or panting, and by various behavioral means,
such as altering fluid intake or seeking shelter. We cannot consider all possible interactions
between survival circuits here. Thus, interactions between the energy/nutritional regulation
system and the defense system will be discussed in some detail for illustrative purposes.
Across mammalian species, circuits involving the arcuate, ventromeidal, dorsomedial, and
lateral hypothalamus, and regulated by leptin, ghrelin, glucose and insulin, control feeding
in relation to energy and nutritional demands (Elmquist et al, 2005; Morton et al 2006; Saper
et al, 2002; Saper, 2006). In satisfying nutritional/energy demands, behavioral responses are
guided by the sensory properties of potential food sources and by cues associated with food.
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For example, auditory or visual cues that occur in connection with food items can modulate
the energy/nutritional circuitry (e.g. Petrovich, 2011). Specifically, areas of the basolateral
amygdala (LA, BA, ABA) processes these learned cues associated with food and relay them
to the LH. Such cues, if sufficiently potent, can stimulate eating in animals that are sated.
Feeding does not occur in a vacuum. As noted above, when threat levels rise, feeding is
suppressed (Gray, 1987; Lima and Dill, 1990; Blanchard et al, 1990; Fanselow, 1994). For
example, a tone previously paired with shock inhibits feeding (Petrovich, 2011) and food
motivated instrumental behavior (e.g. Cardinal et al, 2002). Connections from the
basolateral amygdala to the LH facilitate feeding by a CS associated with food, while the
suppression of feeding by an aversive CS involves outputs of the CEA. The exact target
remains to be determined but CEA connects with LH both directly and indirectly (Petrovich
et al, 1996; Pitkanen et al, 1997). While threat processing normally trumps feeding, at some
point the risk of encountering harm is balanced against the risk of starvation. A similar case
can be made for the suppression of other behaviors by threat processing. For example,
medial amygdala areas that process threat related odors suppress reproduction via
connections to VHM reproductive circuits (Choi et al, 2005).
The fact that the amygdala contributes to appetitive states (e.g. Rolls, 1999, 2005; Everitt et
al, 1999, 2003; Gallagher and Holland, 1994; Holland and Gallagher, 2004; Cardinal et al,
2002; Baxter and Murray, 2002; Moscarello et al, 2009) as well as defense (see above) does
not mean that the amygdala processes food and threat related cues in the same way.
Similarly, the fact that both appetitive and aversive stimuli activate the amgydala in fMRI
studies (e.g. Canli et al, 2002; Hamann et al, 2002; Lane et al, 1999) does not mean that
these stimuli are processed the same by the amygdala. Recent unit recording studies in
primates show that appetitive and aversive signals are processed by distinct neuronal
populations of cells in the lateral/basal amygdala (Paton et al, 2006; Belova et al, 2007;
Belova et al, 2008; Morrison and Salzman, 2010; Ono and Nishijo, 1992; Rolls, 1992, 1999,
2005). Molecular imaging techniques with cellular resolution show that similarities in
activation at the level of brain areas obscures differences at the microcircuit level (Lin et al,
2011).
Circuit Functions vs. Behavioral Responses
Because different groups of mammals faced different selective pressures, the behavioral
responses controlled by conserved survival circuits can differ. As ethologists have long
noted, many survival-related behaviors are expressed in species-specific ways (e.g.
Tinbergen, 1951; Lorenz, 1981; Manning, 1967).
Consider escape from a threat. We’ve seen evidence for conserved defense circuits across
mammals and even across vertebrates, but behavioral responses controlled by these circuits
can differ dramatically. For example, while most mammals flee on all fours, some use only
two legs (humans), others escape by flying (bats), and still others by swimming (whales,
seals and walrus). Similarly, sexual and feeding behavior, while largely conserved at the
neural system level, is also expressed behaviorally in diverse ways within mammals. For
example, although androgen activity in the hypothalamus is important in all male mammals,
the semen delivery process varies in males, in part because of different approaches required
given the configuration of the male and female body (e.g. Pfaff, 1999). This is perhaps most
dramatically illustrated by the lordosis posture of female rats. The male cannot insert his
penis into the vaginal cavity of a female unless she arches her back to adopt this posture,
which is regulated by the binding of estrogen during the fertile phase of her cycle (Pfaff,
1999; Blaustein, 2008). Further, some mammals use their snouts when eating and others
their snouts paws/hands, but the core circuits described above nevertheless regulate the
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various homeostatic and behavioral functions required to regulate energy and nutritional
supplies.
Thus, the responses used by survival circuits to achieve survival goals can be species-
specific even though the circuit is largely species-general (obviously, there must be some
differences in circuitry, at least in terms of motor output circuitry for different kinds of
behaviors, but the core circuit is conserved). By focusing on the evolved function of a circuit
(defense, reproduction, energy and nutrition maintenance, fluid balance, thermoregulation),
rather than on the actual responses controlled by the circuit, a species-independent set of
criteria emerge for defining brain systems that detect significant events and control
responses that help meet the challenges and opportunities posed by those events.
Information Processing By Survival Circuits: Computation of Stimulus
Significance
A key component of a survival circuits is a mechanism for computing circuit-specific
stimulus information. A defense circuit needs to be activated by stimuli related to predators,
potentially harmful conspecifcs, and other potential sources of harm, and not be triggered by
potential mates or food items. The goal of such computational networks is to determine
whether circuit-specific triggers are present in the current situation, and, if a trigger is
detected, to initiate hard-wired (innate) responses that are appropriate to the computed
evaluation. Such responses are automatically released (in the ethological sense — see
Tinbergen, 1951; Lorenz, 1981; Manning, 1967) by trigger stimuli.
The nature of behavioral responses released by survival circuit triggers should be briefly
discussed. Activation of a survival circuit elicits behavioral responses on the spot in some
cases (e.g. in the presence of defense triggers) but in other cases unless the goal object
(sexual partner, food, drink) is immediately present, the more general effect is the alteration
of information processing throughout the brain in such a way as to mobilize resources for
bringing the organism into proximity with suitable goal objects and thus dealing with the
opportunity or challenge signaled by the trigger. We will consider a number of different
consequences of survival circuit activation below. Here, we focus on information processing
related to trigger detection.
Above we briefly noted the species-specific nature of innate trigger stimuli. While the
original idea of the ethologists focused on complex Gestalt configural stimuli and pattern
recognition, simpler features are now emphasized. Thus, a rat can recognize a predator (cat,
fox) by specific chemical constituents of predator odors (Wallace and Rosen, 2000; Vyas et
al, 2007; Dielenberg et al, 2001; Markham et al, 2004; Blanchard et al, 2003), and does not
have to recognize the predator as a complex perceptual pattern. Moreover, humans can
recognize certain emotions by the eyes alone, and do not need to process the face as a whole
(e.g. Whalen et al, 2004), and evidence exists that this can be handled subcortically (Liddell
et al, 2005; Whalen, 1998; Morris et al, 1999; Tamietto et al, 2009; Luo et al, 2007). These
findings are consistent with the notion that that relatively simple sensory processing by
subcortical areas can provide the requisite inputs to structures such as the amygdala, by
passing or short-circuiting cortical areas (LeDoux, 1996). In contrast to innate trigger
stimuli, learned triggers are less restricted by species characteristics. Thus, many (though not
all, as noted above) stimuli can be associated with harm and become a trigger of defense
circuits later.
In the field of emotion, the term
automatic appraisal
is sometimes used when discussing how
significant stimuli elicit so-called emotional responses automatically (without deliberate
control), and is contrasted with
cognitive
or
reflective appraisal
, where processing that is
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deliberate, controlled and often conscious, determines stimulus meaning and predisposes
actions (e.g. Arnold, 1960; Bowlby, 1969; Frijda, 1986; Lazarus, 1991a, b; Leventhal and
Scherer, 1987; Lazarus and Folkman, 1984; Smith and Ellsworth, 1985; Scherer, 1988;
Scherer et al, 2001; Sander et al, 2005; Jarymowicz, 2009).
The stimulus significance evaluations by survival circuits are obviously more in line with
automatic, unconscious appraisal mechanisms. However, while stimulus evaluations by
survival circuits is clearly an example of automatic appraisal, one should not be too quick to
assume that what psychologists refer to as automatic appraisals in humans is identical to
survival circuit processing. The latter probably refers to a narrower set of phenomena than
the former, at least in humans, if not other species, though the range of phenomena in
question clearly overlap.
Multiple Roles of Innate and Learned Stimuli
So far we’ve seen that unconditioned and conditioned emotional stimuli can be thought of in
other terms, as unconditioned and conditioned survival circuit triggers. In addition, though,
they can also be described as incentives — stimuli that motivate instrumental behavior. The
same stimuli additionally function as reinforcers — stimuli that strengthen the probability
that an instrumental response will be learned and later performed. Motivation and
reinforcement are obviously closely aligned with the topic of emotion, though these are
often studied separately today. Let’s look more closely at how closely intertwined these
processes are to one another (Fig 2).
Consider a tone that is paired with food. This is a typical paradigm used to study positive
emotional states in animals. The tone in other words is an appetitive Pavlovian CS that
elicits innate approach behavior. However, it is also a survival circuit trigger, as it can
stimulate eating, even in satiated rats, by activating hypothalamic circuits involved in energy
management (Petrovich, 2011). The same CS will also function as a conditioned incentive
that can modulate instrumental behaviors (in contrast to the ability of a CS to elicit
Pavlovian innate responses (such as approach behaviors). Thus, a CS associated with food
will facilitate performance of an instrumental response that is also maintained by food (e.g.
bar-pressing for food) (Corbit and Balleine, 2005; Cardinal et al, 2002; Balleine and
Killcross, 2006). This is called Pavlovain-to-instrumental transfer since the value of the
Pavlovian CS is transferred to (alters performance of) the instrumental response. The degree
of transfer depends in part on the similarity of the US in the Pavlovian and instrumental
tasks. A tone CS can also be used to reinforce the learning of a new instrumental response
(e.g. Holland and Rescorla, 1975). Thus, a hungry rat will learn to press a bar simply to
receive the tone CS. In this case the tone is considered a reinforcer, a second-order or
conditioned reinforcer (a first order or primary reinforcer would be something like food
itself rather than a stimulus associated with food).
Similar relations hold for a tone paired with an aversive US, footshock. The tone CS elicits
innate freezing behavior (see above) and is thus often described as a conditioned emotional
stimulus (conditioned fear stimulus in this case). And just as an appetitive CS enhances bar
pressing for food, and aversive CS suppresses food-maintained bar pressing (Estes and
Skinner, 1941; Hammond, 1970; Cardinal et al, 2002; Balleine and Killcross, 2006).
However, an aversive CS will also facilitate performance of an aversively motivated
behavior (Hammond, 1970; Lazaro-Munoz et al, 2010). Further, just as rats wil l learn to
perform new instrumental responses for the sole reward of receiving an appetitive CS, they
will also learn new instrumental responses that are rewarded by the elimination of an
aversive CS (e.g. Cain and LeDoux, 2007).
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Although we’ve focused on multiple roles of CSs a similar argument can be made for USs.
These are simply stimuli that innately activate survival circuits, promote the performance of
consummatory responses (food is eaten, sex is consummated) in their presence, or that
support Pavlovain associative conditioning or instrumental conditioning.
If we choose, we can thus describe a variety of the effects of so-called “emotional” stimuli
without the use of the adjective “emotional.” These are innate or learned stimuli that activate
survival circuits and trigger the expression of the innate responses controlled by these
circuits, that modulate the performance of learned (previously reinforced) instrumental
behaviors, and that lead to the reinforcement of new instrumental behaviors (Table 1).
Motivation in the Survival Circuit Scheme
The bottom line of the preceding discussion is that emotion, motivation, and reinforcement
are closely intertwined processes. Let’s look a bit more closely at the interrelation between
these, focusing on motivation here, and reinforcement in the following section.
Emotion and motivation were traditionally treated as separate topics. Emotion was viewed
as a reaction (e.g. a fearful, angry, disgusted, joyful, or sad emotional reaction) to some
environmental situation, and motivation as a drive from within (e.g. hunger, thirst, or sexual
drive) (e.g. Hull, 1943; Stellar, 1954). In the late 1960s, the emergence of the concept of
incentives helped bring these together (Bindra, 1969; Trowill et al, 1969). Bindra (1969), for
example, argued that emotion, like motivation, is influenced by internal factors (e.g.
hormones) and motivation, like emotion, is impacted by external stimuli (incentives).
Motivation, as assessed behaviorally, involves approach towards desired outcomes and
avoidance of undesired outcomes (Tolman, 1932; McClelland et al, 1953; Schneirla 1959,
Elliot and Church, 1997; Cofer, 1972; Cofer and Appley, 1964; Miller, 1944; Trowill et al,
1969; Bindra, 1969; Davidson, 1993; Gray, 1982; Lang et al., 1990; Berridge, 2004;
Cardinal et al, 2002; Balleine and Dickinson, 1998; Holland and Gallagher, 2004; Gallagher
and Holland, 1994). So-called approach/avoidance motivation often occurs in two stages: an
anticipatory/exploratory/search for goal objects and the performance and consummatory
responses (innate responses controlled by surivial circuits) once goal objects are in reach
(Sherrington, 1906; Tinbergen, 1951; Cardinal et al, 2002; Berridge, 1999, 2007).
The anticipatory/exploratory/search phase is guided by incentives (Bindra, 1968; Trowill et
al, 1969; Balleine and Dickinson, 1998; Cardinal et al, 2002; Johnson et al, 2009; Petrovich
et al, 2002; Berridge, 1999, 2007, 2004; Rolls, 1999, 2005; Glimcher, 2003). Incentives, as
noted, are essentially innate or conditioned emotional stimuli; in other words, stimuli with
the potential to activate survival circuits.
One of the key discoveries that led to the rise of incentive views was that stimuli that lacked
the ability to satisfy needs and reduce drives (for example, the non-nutritive sugar substitute
saccharin) were nevertheless motivating (Sheffield and Roby, 1950, Cofer, 1972). A major
consequence was that the connection between motivation and specific functional circuits
(what we are calling survival circuits) began to be deemphasized. Motivation became a
somewhat generic process by which behavior was invigorated and guided towards goals by
incentives.
The nucleus accumbens emerged as a key focal point of this general motivational system
(Graybiel, 1976; Mogenson et al, 1980; Balleine and Killcross, 1994; Killcross and Robbins,
1993; Everitt et al, 1999; Cardinal et al, 2002; Ikemoto and Panksepp, 1999; Parkinson et al,
1999; Koob, 2009; Sesack and Grace, 2010; Berridge, 2007, 2009; Berridge and Robinson,
1998; Hyman et al, 2006; Nestler, 2004; Kelley, 2004). Behavioral invigoration or
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energization was said to be a function of dopamine release in the accumbens and incentive
processing by the accumbens was thought to guide behavior towards goals. Other areas
involved in incentive motivation, such as the obrbito-frontal cortex, are not considered here
(see Rolls, 1999, 2005).
A key question is whether motivation is a generic process or whether motivationally specific
processing by survival circuits might be significant as well. While there may indeed be
generic aspects of motivation (e.g. behavioral invigoration), evidence also supports
motivationally specific information processing as well. At the behavioral level, bar pressing
for food by a hungry obtain food is facilitated by a conditioned incentive that signals food, is
facilitated less by one that signals water, and is inhibited by one that signals shock (Corbit
and Balleine, 2005; Hammond, 1970), indicating that motivation is tied to specific survival
functions. Lateral hypothalamic circuits that control energy maintenace through feeding
modulate nucleus accumbens activity (Sears et al, 2010). The accumbens, once thought to be
mainly involved in processing appetitive stimuli is now know to contribute to the processing
of aversive incentives as well (Salamone, 1994; Schoenbaum and Setlow, 2003; Roitman et
al, 2005; Reynolds and Berridge, 2008). Within the accumbens information processing
segregated along motivational lines — aversive and appetitive stimuli are processed
separately at the cellular and molecular level (Roitman et al, 2005, 2008). While most work
is at the level of appetitive vs. aversive states, it would be important to determine whether
incentive related to different appetitive survival circuits (e.g. incentives related to food vs.
sex) are processed separately.
Once incentives have guided the organism to goal objects, innate consummatory responses,
which are specific to the particular survival circuit and function, are initiated. Their
termination essentially ends the survival (emotional) episode — food is eaten, liquid is
drunk, sex is consummated, safety is reached.
Before leaving the topic of motivation of instrumental goal-directed behavior it is important
to mention that such behaviors, when repeatedly performed in recurring situations, can
become habitual and divorced from the actual attainment of the goal. In such cases of
stimulus-response habit formation, the neural control switches from the ventral to the dorsal
striatum (Everitt and Robbins, 2005; Wickens et al, 2007; Packard and Knowlton, 2002).
Reinforcement and Survival Circuits
Reinforcement and motivation are closely related. Things that motivate are ofen reinforcing,
and vice versa. Like motivation, reinforcement was once linked to drive states (Hull, 1943),
but drifted towards generic mechanisms over the years. The discovery that behavior could
be reinforced by electrical stimulation of brain areas (Olds and Milner, 1954), and the
finding that electrical reinforcement could summate with different natural reinforcers
(Coons and White, 1977; Conover and Shizgal, 1994), were compatible with a generic
mechanism of reinforcement. Similarly, that addictive drugs and natural or electrical
reinforcers interact is also consistent with a generic mechanism (Wise, 2006). Further,
iunfluential mathematical models of reinforcement (e.g. Rescorla and Wagner, 1972; Sutton
and Barto, 1987) explained learning with singular learning rules. The modern paradigmatic
example of a generic reinforcement mechanism is the role of dopamine in the striatum as a
reward prediction error signal (Schultz, 1997).
Nevertheless, there have from time to time been calls for linking reinforcement more
directly to specific neurobiological systems. For example, Glickman and Schiff (1967)
poroposed that reinforcement is a facilitation of activity in neural systems that mediate
species-specific consummatory acts. In other words, they proposed a link between
reinforcement and motivationally-specific survival circuits. It is therefore of great interest
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that recent work on the role of dopamine as a reward prediction error signal is beginning to
recognize the importance of specific motivational states in modulating the effects of
dopamine as a reward prediction error signal (Schultz, 2006; Glimcher, 2011).
The expression of reinforcement as a change in the probability that an instrumental response
will be performed may well occur via a generic system in which the reinforcer strengthens
the response (e.g. via contributions of dopamine in the striatum to reward prediction errors).
But, in addition, survival circuit-specific motivational information is likely to contribute at a
fundamental level, providing the stimulus with the motivational value that allows it to
ultimately engage the more generic mechanisms that strengthen instrumental responses and
that motivate their performance.
Reinforcement principles have been used by some authors to classify emotional states (e.g.
Gray, 1982; Rolls, 1999, 2005; Cardinal et al, 2002; Hammond, 1970; Mowrer, 1960). In
these models various emotions defined in terms of the presentation or removal of
reinforcers. Mowrer (1960), for example, proposed a theory in which fear, hope, relief, and
disappointment were explained in these terms. Later authors have attempted to account for
more conventional emotions (fear, sadness, anger, pleasure, etc) as products of the
presentation or removal of reinforcement. This approach suffers from some of the same
problems as basic emotions theory in that it focuses on common language words related to
human feelings as the way to identify emotion mechanisms in the brain. Perhaps
reinforcement, like motivation, might be fruitfully linked to emotional phenomena through
the survival circuit conception.
Survival Circuits and Arousal
Survival circuits are engaged in situations in which challenges and/or opportunities exist, in
other words what we commonly call emotional or motivated situations. So far we have
focused on two major consequence of survival circuit activation. One is the elicitation of
specific kinds of hard-wired behavioral reactions. The second is an increase in the
probability that instrumental goal-directed actions relevant to the opportunity or challenge
will be learned (reinforced) and performed (motivated) — or, if the situation has been
experienced by the individual repeatedly in the past, stimulus-response habits may substitute
for incentive guided instrumental goal-directed action.
A third consequence of survival circuit activation is “generalized arousal” (Moruzzi and
Magoun, 1949; Lindsley, 1951; Schober et al, 2011; Lang, 1994; Pfaff et al, 2008). As
originally conceived, generalized arousal was a function of the brainstem reticular activating
system (Moruzzi and Magoun, 1949; Lindsley, 1951). Later, the undifferentiated reticular
activating system concept gave way to the notion that distinct populations of chemically-
specific neurons that underlie sleep-wake cycles and the degree of arousal, attention and
vigilance while awake (Jouvet, 1969, 1999; Steriade, 1995, 2004; Jacobs et al, 1990; Jones,
2003; Aston-Jones, 2005; Monti and Jantos, 2008; Sarter et al, 2005; Arnsten and Li, 2005;
Robbins, 2005; Nieuwenhuys, 1985; Nishino, 2011). Specifically, neurons that synthesize
and release biogenic amines (norepinephrine, dopamine, serotoinin, or acetylcholine) and
peptides (e.g. orexins) are believed to make significant contributions to brain arousal. While
these transmitters are released in widespread areas of the brain, their effects are especially
profound on neurons that are actively engaged in information processing (Aston-Jones et al,
1991; Foote et al, 1983, 1991; Aston-Jones and Bloom, 1981). That is, they modulate rather
than initiate neural activity, regulating neuronal excitability and neurotransmission
(Schildkraut and Kety, 1967; Hasselmo, 1995; Lopez and Brown, 1992). Also contributing
to generalized arousal are peripheral systems that release hormones into the circulation (e.g.
cortisol released from the adrenal cortex, adrenergic hormones, epinephrine and nor-
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epinephrine, from the adrenal medulla; and others) (Axelrod and Reisine, 1984; McEwen,
2009; Sapolsky et al, 1986). Cortisol crosses the blood brain barrier and binds to receptors in
a variety of areas, while adrenergic hormones affect the CNS indirectly (McGaugh, 2000).
The modulatory effects of central modulators are relatively rapid, whereas the effects of
peripheral hormones are considerably slower, allowing the prolongation of the survival state
for extended periods of time.
Generalized arousal has played a key role in a number of theories of emotion over the years
(e.g. Duffy, 1941; Lindsley, 1951; Schachter and Singer, 1962; Schachter, 1975; Schildkraut
and Kety, 1967; Mandler, 1975; Lang, 1994; Robbins, 1997) and is also important in
contemporary dimensional theories of emotion (Russell, 1980, 2003; Russell and Barrett,
1999) and some neural models of emotion (e.g. Whalen, 1998; Davis and Whalen, 2001;
Gallagher and Holland, 1994; Kapp et al, 1994; Lang and Davis, 2006). However, it is
important to ask how generalized arousal is triggered in emotional situations, and how the
arousal, once present, affects further processing. Again, the defense circuit is useful for
illustrative purposes.
The detection of a threat by defense circuits of the amygdala leads to the activation of
central neuromodulatory and peripheral hormonal systems (see Gray, 1993; LeDoux, 1992,
1995; Davis, 1992; Rodrigues et al, 2009;). Thus, central amygdala outputs target dendritic
areas of norpeiphrine, dopamine, serotonin, and acetylcholine containing neurons and cause
these to release their chemical products in widespread brain areas (e.g. Reyes et al, 2011;
Gray, 1993; Weinberger, 1995; Kapp et al, 1994). Central amygdala outputs also target
neurons that activate the sympathetic division of the autonomic nervous system, which
releases adrenergic hormones from the adrenal medulla, and the hypothalamic-pituitary-
adrenal axis, which releases cortisol from the adrenal cortex (Gray, 1993; Talarovicova et al,
2007; Loewy, 1991; Reis and LeDoux, 1987). Threats thus not only elicit specific defense
responses but also initiate generalized arousal in the brain and body. Body feedback has
played an important role in emotion theory for more than a century (James, 1884; Lange,
1885/1922; Schachter and Singer, 1962; Tomkins, 1962; Adelmann and Zajonc, 1989; Buck,
1980; Damasio, 1994, 1999).
One consequence of this pattern of connectivity is that central and peripheral arousal signals
facilitate processing in the survival circuit that triggered the activation of arousal. This
establishes a loop in which continued activation of the survival circuit by external stimuli
produces continued activation of the modulator release, which in turn facilitates the ability
of external stimuli to continue to drive the survival circuit. Indeed, modulators facilitate
activity in sensory processing areas (e.g. Hurley et al, 2004), which should enhance attention
to external stimuli present during survival circuit activation. Modulators also facilitate
processing areas involved in retrieving forming, and storing memories (McGaugh, 2003;
Roozendaal et al, 2009). All of these effects are recapitulated in motivational circuits once
the initial reaction begins to give way to goal-directed instrumental actions. For example,
dopamine contributes to the invigoration or activation of behavior during the exploratory
search phase of a motivated state (Berridge 2004; Berridge and Robinson, 1998; Robbins
and Everitt, 2007). Norepinephrine, serotoin, acetylcholine, orexins and other modulators
also contribute. While arousal is often discussed in terms of generic (generalized)
mechanisms, the possibility that some aspects of arousal might be survival circuit specific
should also be explored (Pfaff et al, 2008; Schober et al, 2011).
Global Organismic States
Survival circuit activation leads to the triggering of arousal responses in the CNS, and to the
potential expression of innate behaviors (depending on the circumstances), as well as
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expression of autonomic nervous system and hormonal responses in the body. Behavioral,
autonomic, and endocrine responses feedback to the brain and also contribute to arousal. In
addition, motivational systems are activated, potentially leading to goal-directed behaviors
(Figure 3). The overall result of survival circuit-specific activity, motivational activity, and
generalized arousal is the establishment of a state in which brain resources are coordinated
and monopolized for the purpose of enhancing the organism’s ability to cope with a
challenge and/or benefit from opportunities. The organism becomes especially attentive to
and sensitive to stimuli relevant to the survival function, memories relevant to the survival
function are retrieved, and previously learned instrumental responses relevant to the survival
function are potentiated. New learning occurs and new explict memories (via the
hippocampus and related cortical areas) and implicit memories (memories stored in the
survival circuit) are formed. Such states will be referred to here as global organismic states.
The fact that these states are global does not mean that they completely lack specificity.
They include survival circuit-specific components, as well as general motivational
components that control instrumental behavior and components that control non-specific or
generalized arousal within the brain and body.
The notion that emotional and motivated states have profound effects on the brain, recruiting
widespread areas into the service of the immediate situation, monopolizing and/or
synchronizing brain resources, has been proposed previously (Gallistel, 1980; Maturana and
Varela, 1987; Scherer, 2000; LeDoux, 2002, 2008). Particularly relevant is the “central
motive state” hypothesis (Morgan, 1943; Hebb, 1949; Bindra, 1969). Yet, the exact nature
of global organismic states is poorly understood. In part this is likely attributable to the lack
of techniques for assessing neural activity across widespread areas of the brain at a
sufficiently detailed level of resolution. Measurement of BOLD activity in the brains of
humans or animals with fMRI allows whole brain analysis of functional activity, but lacks
spatial resolution at the level of cells and circuits. Use of molecular markers, such as the
expression of immeditate early gene activity, in relation to behavior holds promise.
Particularly important would be the development of techniques that could provide
widespread assessment of changes in body physiology and brain activation and related to
survival circuit processing, general-purpose motivational processing, and generalized
arousal.
In point of fact, we may need a new kind of neuroscience to come to grips with whole brain
states that reflect the activity and inactivity of multiple interacting brain systems. The field
has been extremely good at studying individual brain systems but has not done as well in
understanding more global functions. If we are to ever truly relate notions of self and
personality to the brain, we will need these kinds of approaches (LeDoux, 2002).
Transcending Neuroanatomical Homology: Survival Throughout the Animal
World
Invertebrates do not have the same conserved circuits that vertebrates have. However, they
face many of the same problems of survival that vertebrates do: they must defend against
danger, satisfy energy and nutritional needs, maintain fluid balance and body temperature,
and reproduce. As in vertebrates, specific circuits are associated with such functions, though
different invertebrates have different nervous systems and different circuits.
The fact invertebrate nervous systems are diverse and differ from the canonical vertebrate
nervous system does not mean the invertebrates are irrelevant to understanding survival
functions (and thus so-called emotional behavior) in vertebrates. Much progress is being
made in understanding innate behaviors related to survival functions such as defense,
reproduction and arousal in invertebrates such as
Drosophila
(Wang et al, 2011; Lebetsky et
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al, 2009; Dickson, 2008) and C. elegans (McGrath et al, 2009; Pirri and Alkema, 2012;
Garrity et al, 2010). In these creatures, as in mammals and other vertebrates, G-protein
coupled receptors and their regulators play key roles in modulating neuronal excitability and
synaptic strength, and in setting the threshold for behavioral responses to incentives
associated with specific motivational/emotional states (Bendesky and Bargmann, 2011).
Biogenic amines and their G-protein coupled receptors also play a key role in arousal and
behavioral decision-making in
Drosophila
(Lebetsky et al, 2009) and C. elegans (Bendesky
et al, 2011) as in vertebrates (see above). Indeed, it would not be too far fetched to suggest
that biogenic amines and their G-protein coupled receptors create global organismic that
coordinate the activity multiple subsystems within the nervous system in invertebrates as
well as vertebrates.
Much has been also been learned about the cellular, molecular and genetic mechanisms
underlying survival based learning in invertebrates. For example, such as
Aplysia californica
many of the neurotransmitters (e.g. glutamate), neuromodulators (e.g. serotonin, dopamine),
intracellular signals (e.g. protein kinase A, map kinase), transcription factors (e.g. cyclic
AMP response element binding protein) involved in defense conditioning
Aplysia
(e.g.
Hawkins et al, 2006; Kandel, 2001; Carew and Sutton, 2001; Glanzman, 2010; Mozzachiodi
and Byrne, 2010) have been implicated in defense conditioning in the mammalian amygdala
(see Johansen et al, 2011). Further, studies in
Drosophila
have implicated some of the same
intracellular signals and transcription factors in defense based learning (Dudai, 1988; Yovell
et al, 1992; Yin and Tully, 1996; Margulies et al, 2005).
Similarities at the cellular and molecular level, and presumably at the level of genes that
encode these processes, across diverse groups of animals is impressive evidence for
conserved principles of organization underlying survival functions. However, an important
question is whether there might be more fundamental circuit principles that are instantiated
at the microcircuit level in nervous systems that are superficially distinct. If so, the key to
understanding the relation of survival functions across invertebrates and vertebrates is likely
to involve conserved principles of organization at the microcircuit level rather similarity of
anatomical structures or molecules (David Anderson, personal communication). Very
interesting examples are emerging from studies of olfactory processing, for which analogies
in behaviorally-relevant peripheral odor-encoding and central representation occur using
similar organizational principles in anatomically distinct (non-homologous) structures in
Drosophila
and rodents (see Bargmann, 2006; Sosulski et al, 2011; Wang et al, 2011).
Survival functions instantiated in specific neural circuits likely reflect conserved neural
principles. We should at least be amenable to the possibility that defense, reproduction, and
other survival functions in humans, may be related to survival functions in invertebrates.
This notion is not likely to be surprising to card carrying comparative neurobiologist, but
might meet more resistance from researchers who study humans since survival functions
account for some fundamental emotional functions in humans, and in humans emotions are
often equated with or closely tied to feelings. But the thrust of what has been said here is
that survival functions should not be treated as qualitatively differently in humans and other
mammals, in mammals and other vertebrates, in vertebrates and invetebrates. As noted
earlier, a case can even be made that solutions to fundamental problems of survival are in
the final analysis derived form solutions to these problems present primordial single cell
organisms.
Survival Circuits and Human Feelings: What Is An Emotional State?
When the term “emotional state” is used, the user typically has the notion of “feeling” in
mind. This article is an attempt to redefine the nature of such states, at least the components
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of such states that are shared across mammalian species (and likely across vertebrates, and
to some extent in invertebrates as well). Nevertheless, the history of emotion research and
theory is for the most part the history of trying to understand what feelings are and how they
come about. It is thus important to comment on the nature of feelings and their relation to
survival circuits.
One might be tempted to conclude that global organismic states, or at least the central
representation of such sates, constitute neural correlates of feelings. Global organismic states
make major contributions to conscious feelings but the two are not the same. Global
organismic states are part of the raw material from which certain classes of feelings are
constructed (those feelings associated with survival circuit activation). But they could, and
likely do, exist, independent of feelings, at least in relation to what humans call feelings. My
proposal is that these kinds of feelings (those associated with survival circuit activation)
occur in humans when consciousness (a) detects that a survival circuit is active or witnesses
the existence of a global organismic state initiated by the activation of a survival circuit in
the presence of particular kind of challenge or opportunity and (b) appraises and labels this
state. These are not the only kinds of feelings that can occur in humans. Other kinds include
feelings associated with higher order or social emotions (guilt, shame, envy, pride) or
sensory feelings (a pleasant touch or an annoying itch).
What about other animals? To the extent that non-human organisms have consciousness and
cognition, capacities that allow the observation, appraisal, and categorization of survival
circuit activity or global organismic states, they can have feelings when survical circuit
activity or global organismic states occur. To the extent that the mechanisms of
consciousness and cognition differ in different animals (with humans included as an animal),
and to the extent that the mechanisms underlying survival circuit or global organismic states
themselves differ, feelings will be different. This leaves open the possibility that conscious
feelings can be present in other mammals, other vertebrates, or even in invertebrates. But
rather than engaging in idle speculation about this, criteria can be offered that can help
address the question. Specifically, if we can understand what underlies conscious feelings in
humans, we can then search for whether those mechanisms are present, and to what extent
they are present, in other animals.
This, you probably noticed, is a different approach from the one advocated earlier for
survival circuits. We now ask whether processes in humans are present in other animals. But
just as the survival circuit question should be asked about whether mechanisms in other
animals are present in humans, the question of whether mechanisms shown to be present in
humans are present in other animals seems only addressable in the other direction. We can
never know whether another animal has conscious emotional feelings, but we might be able
to determine whether the mechanisms that make of consciousness and feelings possible in
humans also present in other animals.
The fact is that the brain mechanisms that underlie conscious emotional feelings in humans
are still poorly understood. However, this should not stand in the way of understanding
survival functions and the states that occur in the brain when the circuits mediating survival
functions are activated. There is much work to be done even if we don’t have viable
solutions to the problems of conscious feelings.
Research on feelings is complicated because feelings cannot be measured directly. We rely
on the outward expression of emotional responses, or on verbal declarations by the person
experiencing the feeling, as ways of assessing what that person is feeling. This is true both
when scientists do research on emotions, and when people judge emotions in their social
interactions with one another.
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When not wearing a scientific hat, most of us apply introspectively based concepts to other
animals. When a deer freezes to the sound of a shotgun we say it is afraid, and when a kitten
purrs or a dog wags its tail, we say it is happy. In other words, we use words that refer to
human subjective feelings to describe our interpretation of what is going on in the animal’s
mind when it acts in way that has some similarity to the way we act when we have those
feelings. Some authors also claim that similarity of behavior is strongly suggestive of
similarity at the level of subjective experience (Panksepp, 1998, 2005) or more generally
that humans know what an animal feels from observing their behavior (Bekoff, 2007;
Masson and McCarthy, 1996). But it’s hard to justify anthropomorphic speculation in
science. Panksepp has attempted this (Panksepp, 1982; 1998, 2000; 2005), but few scientists
are convinced that this is the way to go, as there is no way to objectively verify what another
organism experiences.
So what’s the difference, if any, between attributing feelings to other people and to other
animals? There is a strong rationalization for assuming all humans have subjective mental
states, such as feelings, that are similar in kind. In the absence of genetic mutations of the
nervous system or acquired brain damage, each human possesses the same basic kind of
brain, a brain with the same basic neural systems, as every other human. As a result we
expect that other people have the same kinds of basic brain functions, and corresponding
mental capacities, that we have, and we can assume with some confidence that other people
experience the same kinds of feelings we do when we they behave the way we behave when
we have those feelings (unless they are being intentionally deceitful). We can therefore
fairly comfortably apply our introspections about our own feelings to the mental states of
other people on the basis of their behavior.
We should not, however, be so comfortable in talking about the mental states of other
species because their brains differ from ours. A key question, of course, is whether their
brains differ from ours in ways that matter. In other words, do the brain areas responsible for
states of consciousness, such as feelings, differ in humans and other animals?
There is considerable support for the idea that states of consciousness are made possible, at
least in part, through the representation of experience in a cognitive workspace involving
neocortical areas, including prefrontal (especially dorso-lateral prefrontal) and parietal
cortical areas (Crick and Koch, 1990, 2004, Dehaene and Changeux, 2004, Baars, 2005;
Frith and Dolan, 1996; Frith et al, 1999; Frith, 2008; Shallice, 1988; Shallice et al, 2008;
Goldman-Rakic, xxx). To the extent that feelings are states of consciousness about
emotional situations, they should be represented in these cognitive workspace circuits
(LeDoux, 1996, 2002, 2008).
The idea proposed here is that conscious feelings result when global organismic states are
represented in the cognitive workspace. The basic ingredients of the global organismic state
would include information about the stimulus and other aspects of the social and physical
environment, the survival circuit the stimulus activates, CNS arousal initiated by the
survival circuit, feedback from survival responses that are expressed in the body, and long-
term memories (episodic and semantic) about the stimulus and about the resulting state (Fig
4). Thus, in the presence of a survival circuit trigger (a.k.a. an emotional stimulus) the
various ingredients would be integrated, and the resulting state categorized by matching the
state with long-term memory stores. When this occurs, a conscious feeling of the global
organismic state begins to exist. Such a state, having been categorized on the basis of
memories of similar states, could be dimensional in nature (just based on arousal and
valence) or could take on specific qualities (could be more like what one felt when
previously in danger than when frustrated or when enjoying a tasty meal). Labeling of the
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state with emotion words adds additional specificity to the experience, creating specific
feelings (fear, pleasure, disgust, etc).
Dorsolateral prefrontal cortex, a key component of the cognitive workspace, is lacking in
most other mammals, and is less developed in non-human primates than in humans (Reep,
1984; Braak, 1980; Preuss, 1995; Wise, 2008). In humans, granular prefrontal cortex also
has unique cellular features (Semendeferi et al, 2011). Given that feelings are a category of
conscious experience, the usual mechanisms of conscious experience should be at work
when we have emotional experiences (LeDoux, 1996, 2002; 2008). And given that some of
the neural mechanisms involved in conscious representations may be different in humans
and other animals, we should be cautious in assuming that the subjectively experienced
phenomena that humans label as feelings are experienced by other animals when they
engage in behaviors that have some similarity to human emotional behavior. In short, if the
circuits that give rise to conscious representations are different in two species, we cannot use
behavioral similarity to argue for similarity of conscious feelings functionally. These
observations add neurobiological substance to the point famously argued by the philosopher
Thomas Nagel. He proposed that only a bat can experience the world like a bat, and only a
human can experience the world like a human (Nagel, 1974). We should resist the
inclination to apply our introspections to other species.
Also, given that humans are the only organisms with natural language, and language allows
a unique mode of information processing in the human brain, we need to be very cautious
when we make assumptions about non-human behavior regarding processes that language
affects. While the idea that language affects thought and conscious experience (Whorf,
1956) was out of favor for a while, it has reemerged as an important principle in recent times
(Lakoff, 1987; Lucy, 1997). One way that language is important is that it allows the
semantic categorization of experience, including emotional experience. For example, there
are more than 30 words in English for gradations of fear (fear, panic, anxiety, worry,
trepidation, consternation, etc) (Marks, 1987). The human brain may be able to categorize
emotional states in broad strokes without language but it is unlikely that specific emotions
(fear, anger, sadness, joy) could come about without words. Accordingly, lacking language
and emotion words, an animal brain cannot partition emotional experience in this way. In
short, the language of emotion likely contributes to the experiences one has in emotional
situations (Schachter, 1975; Johnson-Laird and Oatley, 1989; Scherer, 1984; Reisenzein,
1995). Indeed, different cultures and their languages express emotions differently (Kitayama
and Markus, 1994; Wierzbicka, 1994; Averill, 1980). The dimensional theory of emotion
views emotion words as markers in a multidimensional semantic space of feelings (Russell,
1980; Russell and Barrett, 1999). The dimensional theory is incompatible with a basic
emotions view, since the latter argues that feelings associated with basic emotions are due to
hard-wired circuits, but is compatible with the survival circuit view, which posits indirect
and non-obligatory, as opposed to casual, links between survival circuits and feelings.
But the impact of language goes far beyond simple semantics and labeling. We use syntactic
processes to evaluate the logical truth of propositional statements. While not all human
thought involves propositional statements and logic, syntactic processing provides the
human brain and mind with unique features and advantages. Through syntax, the human
mind can simulate who will do what to whom in a social situation instantaneously rather
than having to learn by trial and error.
So what then might a bat or a rat experience without the kind of cerebral hardware that is
characteristic of the human brain? Some have proposed that in addition to full blown
feelings that humans talk about, more basic, less differentiated feelings (crude states of
positive or negative valence, or maybe even somewhat finer categories based on memory of
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feelings from the past in similar situations) may exist in other animals. Such states have
been called core affects (Panksepp, 1998, 2005; Damasio. 1994, 1999; Barrett et al, 2007;
Russell, 2003). While we cannot ask other animals about their feelings, studies of humans
can begin to unravel how such states are experienced. Similarity of the structure of these
circuits in animals might then provide insight into their function in other animals (Panksepp,
1998, 2005), provided that we do a good job of clarifying the function of the circuits in
question (see survival circuit discussion above).
Consciousness and feelings are topics that are best studied in humans. Research on the
neural basis of feelings in humans is in its infancy (Panksepp, 1998; 2005; Damasio, 2003;
Damasio et al, 2000; Ochsner et al, 2002; Barrett et al, 2007; Rudrauf et al, 2009; Critchley
et al, 2004; Pollatos et al, 2007). We will never know what an animal feels. But if we can
find neural correlates of conscious feelings in humans (and distinguish them from correlates
of unconscious emotional computations in survival circuits), and show that similar correlates
exists in homologous brain regions in animals, then some basis for
speculating
about animal
feelings and their nature would exist. While such speculations would be empirically based,
they would nevertheless remain speculations.
Future Directions of Research
There are many topics that need further exploration in the study of emotional phenomena in
the brain. The following list is meant to point out a few of the many examples, and is not
meant to be exhaustive.
1. The circuits underlying defense in rodents is fairly well characterized and provides
a good starting point for further advancement. An important first step is elucidation
of the exact relation between innate and learned defense circuits. Paradigms should
be devised that directly compare circuits that are activated by innate and learned
cues of the same sensory modality and that elicit similar behavioral defense
responses (freezing, escape, attack, etc). Comparisons should proceed in stepwise
fashion within a species, with variation in the stimulus and response modalities
(though mundane, systematic studies are important).
2. More information is also needed regarding the manner in which external stimuli
function as defense triggers, incentives, and reinforcers within defense circuits.
Tasks should be developed that can be readily applied across species, but at the
same time easily tailored to species-specific factors. Further exploration of whether
there are different circuits for defense in different contexts would also be useful.
3. How do innate and learned stimuli trigger, motivate and reinforce behaviors in non-
defense survival circuits? What are the evaluative mechanisms that process such
stimuli within specific survival circuits (e.g. energy/nutrition, fluid balance,
reproduction, etc)? While incentives and reinforcers have been studied extensively
in the context of generic appetitive processes, also of interest is the relation of such
stimuli to the specific survival circuit on which they depend.
4. Can survival circuits be further differentiated? For example, to what extent do
different forms of defense utilize different circuits? Beyond classifications based on
the sensory modality that detects threats and whether the threat is learned or
unlearned, are there different circuits for threats related to conspecifics, predators,
injested substances, territory, etc. Similar questions arises for each survival circuit
category.
5. When a given brain area is involved in multiple survival functions, an effort should
be made to determine the extent to which underlying cellular mechanisms might
make distinct contributions. For example, the LA and BA and nucleus accumbens
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have been implicated in defensive and appetitive behaviors. As noted above, single
unit recordings suggest some independence of responses to aversive and appetitive
stimuli in these areas. However, questions remain. Do amygdala or accumbens
cells simply encode positive and negative valence or are they tied to more specific
survival functions? This is readily explored by examining cellular responses to
incentive stimuli related different forms of appetitive motivation. For example, do
the cells that respond to incentives related to food, drink and reproduction overlap
or are they survival-function specific? Single unit recordings are often restricted to
one or a small number of brain areas. New molecular imaging techniques are
beginning to allow such differences to be explored at the cellular level across the
whole brain. A recent study by Lin et al (2011) showing distinct populations of
cells in the ventromedial hypothalamus that contribute to mating and intruder attack
is a prime example. Genetic tools can also be used to provide more detailed
information about connectivity, including connectivity at the level of brain areas
but also between specific cell types. Such approaches have begun to be used but
systematic studies are needed.
6. It is generally assumed that circuits underlying defense, energy, fluid balance,
reproduction, thermoregulation, and other survival functions interact, but this has
been not been studied to any significant degree. This is a particularly important
topic that is best pursued by methods that allow evaluation of concurrent activity in
the multiple brain areas, such as fMRI in humans and fMRI and molecular imaging
in animals. Studies comparing activity patterns across the whole brain in response
processing signals related to various survival circuit functions could provide very
important information, especially if animal and human projects use related
behavioral paradigms. If homologies are found at the level of brain areas between
humans and other mammals, molecular imaging can be used in animal studies to
search for unique microcircuits that differentiate between functions and the cellular
and synaptic level.
7. Techniques are needed to assess physiological activity at the cellular level across
the whole brain and throughout the body (global organismic states) in the presence
of biological significant stimuli (triggers of survival circuit activity or motivating
incentives,) and during the performance of innate or learned survival responses as
well as goal directed responses. It will be especially useful to develop analytic tools
that will be able to separate contributions that are survival circuit specific from
more general purpose mechanisms, such as non-specific arousal, and generic
aspects of reinforcement and instrumental behavior control.
8. More comparative work is needed to elucidate similarities and differences in
survival functions and circuits between various groups of vertebrates. Particularly
pressing are studies of non-mammalian vertebrates.
9. What is the relation of survival functions in invertebrates to vertebrates? Are there
conserved molecules or genes, or conserved computational principles, that underlie
anatomically distinct kinds of circuits but that perform similar survival functions in
vertebrates and invertebrates?
10. Explorations of the mechanisms underlying conscious emotional feelings in
humans should be pursued more vigorously, including full-blown conscious
feelings (feelings of fear, joy, sadness, shame, embarrassment) and coarser
conditions (pleasant or unpleasant feelings). This information is important because
feelings are such a defining feature of human mental life. But in addition with such
information it will then be possible to ask if the required mechanisms of a given
kind of conscious state are present in other animals. Even if the mechanisms are
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present, the results would not allow the conclusion that other animals have feelings
that are homologous with human feelings. However, such a result would at least
provide a basis for saying whether there is a physical possibility for such states in
other animals.
Conclusion
The survival circuit concept provides a conceptualization of an important set of phenomena
that are often studied under the rubric of emotion — those phenomena that reflect circuits
and functions that are conserved across mammals. Included are circuits responsible for
defense, energy/nutrition management, fluid balance, thermoregulation, and procreation,
among others. With this approach, key phenomena relevant to the topic of emotion can be
accounted for without assuming that the phenomena in question are fundamentally the same
or even similar to the phenomena people refer to when they use emotion words to
characterize subjective emotional feelings (like feeling afraid, angry, or sad). This approach
shifts the focus away from questions about whether emotions that humans consciously
experience (feel) are also present in other mammals, and towards questions about the extent
to which circuits and corresponding functions that are relevant to the field of emotion and
that are present in other mammals are also present in humans. By reassembling ideas about
emotion, motivation, reinforcement, and arousal in the context of survival circuits,
hypotheses emerge about how organisms negotiate behavioral interactions with the
environment in process of dealing with challenges and opportunities in daily life.
References
Adelmann PK, Zajonc RB. Facial efference and the experience of emotion. Annu Rev Psychol. 1989;
40:249–280. [PubMed: 2648977]
Adolphs R. Fear, faces, and the human amygdala. Curr Opin Neurobiol. 2008; 18:166–172. [PubMed:
18655833]
Amaral DG. The amygdala, social behavior, and danger detection. Ann N Y Acad Sci. 2003;
1000:337–347. [PubMed: 14766647]
Antoniadis EA, Winslow JT, Davis M, Amaral DG. Role of the primate amygdala in fear-potentiated
startle: effects of chronic lesions in the rhesus monkey. J Neurosci. 2007; 27:7386–7396. [PubMed:
17626199]
Arnold, MB. Emotion and Personality. New York: Columbia University Press; 1960.
Arnsten AF, Li BM. Neurobiology of executive functions: catecholamine influences on prefrontal
cortical functions. Biol Psychiatry. 2005; 57:1377–1384. [PubMed: 15950011]
Aston-Jones G. Brain structures and receptors involved in alertness. Sleep Med. 2005; 6(Suppl 1):S3–
7. [PubMed: 16140243]
Aston-Jones G, Bloom FE. Norepinephrine-containing locus coeruleus neurons in behaving rats
exhibit pronounced responses to non-noxious environmental stimuli. J Neurosci. 1981; 1:887–900.
[PubMed: 7346593]
Aston-Jones G, Shipley MT, Chouvet G, Ennis M, van Bockstaele E, Pieribone V, Shiekhattar R,
Akaoka H, Drolet G, Astier B, Charlety P, Valentino RJ, Williams JT. Afferent regulation of locus
coeruleus neurons: Anatomy, physiology, and pharmacology. Progress in Brain Research. 1991;
88:47–75. [PubMed: 1687622]
Averill, J. Emotion and anxiety: Sociocultural, biological, and psychological determinants. In: Rorty,
AO., editor. Explaining emotions. Berkeley: University of California Press; 1980.
Axelrod J, Reisine TD. Stress hormones: their interaction and regulation. Science. 1984; 224:452–459.
[PubMed: 6143403]
Baars BJ. Global workspace theory of consciousness: toward a cognitive neuroscience of human
experience. Prog Brain Res. 2005; 150:45–53. [PubMed: 16186014]
LeDoux Page 23
Neuron
. Author manuscript; available in PMC 2013 April 15.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Balleine B, Killcross S. Effects of ibotenic acid lesions of teh nucleus accumbens on instrumental
action. Behavioral Brain Research. 1994; 65:181–193.
Balleine BW, Dickinson A. Goal-directed instrumental action: contingency and incentive learning and
their cortical substrates. Neuropharmacology. 1998; 37:407–419. [PubMed: 9704982]
Balleine BW, Killcross S. Parallel incentive processing: an integrated view of amygdala function.
Trends Neurosci. 2006; 29:272–279. [PubMed: 16545468]
Bargmann CI. Comparative chemosensation from receptors to ecology. Nature. 2006; 444:295–301.
[PubMed: 17108953]
Barrett LF. Are Emotions Natural Kinds? Perspectives on Psychological Science. 2006a; 1:28–58.
Barrett LF. Solving the emotion paradox: categorization and the experience of emotion. Pers Soc
Psychol Rev. 2006b; 10:20–46. [PubMed: 16430327]
Barrett LF, Lindquist KA, Bliss-Moreau E, Duncan S, Gendron M, Mize J, Brennan L. Of Mice and
Men: Natural Kinds of Emotions in the Mammalian Brain? A Response to Panksepp and Izard.
Perspect Psychol Sci. 2007; 2:297–311. [PubMed: 19079552]
Baxter MG, Murray EA. The amygdala and reward. Nat Rev Neurosci. 2002; 3:563–573. [PubMed:
12094212]
Bekoff, M. The Emotional Lives of Animals: A leading scientist explores animal joy, sorrow, and
empathy - and why they matter. Novato, CA: New World Library; 2007.
Belova MA, Paton JJ, Salzman CD. Moment-to-moment tracking of state value in the amygdala. J
Neurosci. 2008; 28:10023–10030. [PubMed: 18829960]
Belova MA, Paton JJ, Morrison SE, Salzman CD. Expectation modulates neural responses to pleasant
and aversive stimuli in primate amygdala. Neuron. 2007; 55:970–984. [PubMed: 17880899]
Bendesky A, Bargmann CI. Genetic contributions to behavioural diversity at the gene-environment
interface. Nat Rev Genet. 2011; 12:809–820. [PubMed: 22064512]
Bendesky A, Tsunozaki M, Rockman MV, Kruglyak L, Bargmann CI. Catecholamine receptor
polymorphisms affect decision-making in C. elegans. Nature. 2011; 472:313–318. [PubMed:
21412235]
Bernard, C. Lecons sur les phenomenes de la vie communs aux animaus et aux vegetaux. Paris:
Bailliere; 1878–1879.
Berridge, KC. Pleasure, pain, desire, and dread: hidden core processes of emotion. In: Kahnemann, D.;
Diener, E.; Schwarz, N., editors. Well-Being. New York: Russell Sage Foundation; 1999.
Berridge KC. Motivation concepts in behavioral neuroscience. Physiol Behav. 2004; 81:179–209.
[PubMed: 15159167]
Berridge KC. The debate over dopamine’s role in reward: the case for incentive salience.
Psychopharmacology (Berl). 2007; 191:391–431. [PubMed: 17072591]
Berridge KC. ‘Liking’ and ‘wanting’ food rewards: brain substrates and roles in eating disorders.
Physiol Behav. 2009; 97:537–550. [PubMed: 19336238]
Berridge KC, Robinson TE. What is the role of dopamine in reward: hedonic impact, reward learning,
or incentive salience? Brain Res Brain Res Rev. 1998; 28:309–369. [PubMed: 9858756]
Bindra D. Neuropsychological interpretation of the effects of drive and incentive-motivation on
general activity and instrumental behavior. Psychol Rev. 1968; 75:1–22.
Bindra D. A unfied interpretation of emotion and motivation. Ann N Y Acad Sci. 1969; 159:1071–
1083. [PubMed: 5260290]
Blanchard CD, Blanchard RJ. Innate and conditioned reactions to threat in rats with amygdaloid
lesions. Journal of Comparative Physiological Psychology. 1972; 81:281–290.
Blanchard DC, Blanchard RJ, Rodgers RJ. Pharmacological and neural control of anti-predator
defense in the rat. Aggressive Behavior. 1990; 16:165–175.
Blanchard DC, Li CI, Hubbard D, Markham CM, Yang M, Takahashi LK, Blanchard RJ. Dorsal
premammillary nucleus differentially modulates defensive behaviors induced by different threat
stimuli in rats. Neurosci Lett. 2003; 345:145–148. [PubMed: 12842277]
Blaustein JD. Neuroendocrine regulation of feminine sexual behavior: lessons from rodent models and
thoughts about humans. Annu Rev Psychol. 2008; 59:93–118. [PubMed: 17678443]
LeDoux Page 24
Neuron
. Author manuscript; available in PMC 2013 April 15.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Bolles RC, Fanselow MS. A perceptual-defensive-recuperative model of fear and pain. Behavioral and
Brain Sciences. 1980; 3:291–323.
Bordi F, LeDoux J. Sensory tuning beyond the sensory system: an initial analysis of auditory response
properties of neurons in the lateral amygdaloid nucleus and overlying areas of the striatum. J
Neurosci. 1992; 12:2493–2503. [PubMed: 1613543]
Bowlby, J. Attachment. Vol. 1. New York: Basic Books; 1969. Attachment and Loss.
Braak E. On the structure of IIIab-pyramidal cells in the human isocortex. A Golgi and electron
microscopical study with special emphasis on the proximal axon segment. J Hirnforsch. 1980;
21:437–442. [PubMed: 7451942]
Brown SM, Hariri AR. Neuroimaging studies of serotonin gene polymorphisms: exploring the
interplay of genes, brain, and behavior. Cogn Affect Behav Neurosci. 2006; 6:44–52. [PubMed:
16869228]
Bruce LL, Neary TJ. The limbic system of tetrapods: a comparative analysis of cortical and amygdalar
populations. Brain Behav Evol. 1995; 46:224–234. [PubMed: 8564465]
Buchel C, Dolan RJ. Classical fear conditioning in functional neuroimaging. Curr Opin Neurobiol.
2000; 10:219–223. [PubMed: 10753800]
Buck R. Nonverbal behavior and the theory of emotion: the facial feedback hypothesis. J Pers Soc
Psychol. 1980; 38:811–824. [PubMed: 7381683]
Butler, AB.; Hodos, W. Comparative Vertebrate Neuroanatomy: Evolution and Adaptation. 2.
Hoboken: John Wiley & Sons, Inc; 2005.
Cain CK, LeDoux JE. Escape from fear: a detailed behavioral analysis of two atypical responses
reinforced by CS termination. J Exp Psychol Anim Behav Process. 2007; 33:451–463. [PubMed:
17924792]
Canli T, Sivers H, Whitfield SL, Gotlib IH, Gabrieli JD. Amygdala response to happy faces as a
function of extraversion. Science. 2002; 296:2191. [PubMed: 12077407]
Cannon WB. The James-Lange theory of emotions: a critical examination and an alternative theory.
Am J Psychol. 1927; 39:106–124.
Cannon, WB. Bodily changes in pain, hunger, fear, and rage. New York: Appleton; 1929.
Cannon WB. Again the James-Lange and the thalamic theories of emotion. Psychol Rev. 1931;
38:281–295.
Canteras NS. The medial hypothalamic defensive system: hodological organization and functional
implications. Pharmacol Biochem Behav. 2002; 71:481–491. [PubMed: 11830182]
Canteras NS, Resstel LB, Bertoglio LJ, de Carobrez AP, Guimaraes FS. Neuroanatomy of anxiety.
Curr Top Behav Neurosci. 2010; 2:77–96. [PubMed: 21309107]
Cardinal RN, Parkinson JA, Hall J, Everitt BJ. Emotion and motivation: the role of the amygdala,
ventral striatum, and prefrontal cortex. Neurosci Biobehav Rev. 2002; 26:321–352. [PubMed:
12034134]
Carew TJ, Sutton MA. Molecular stepping stones in memory consolidation. Nat Neurosci. 2001;
4:769–771. [PubMed: 11477415]
Casey BJ, Ruberry EJ, Libby V, Glatt CE, Hare T, Soliman F, Duhoux S, Frielingsdorf H, Tottenham
N. Transitional and translational studies of risk for anxiety. Depress Anxiety. 2011; 28:18–28.
[PubMed: 21225849]
Chi CC, Flynn JP. Neural pathways associated with hypothalamically elicited attach behavior in cats.
Science. 1971; 171:703–706. [PubMed: 5099720]
Choi GB, Dong HW, Murphy AJ, Valenzuela DM, Yancopoulos GD, Swanson LW, Anderson DJ.
Lhx6 delineates a pathway mediating innate reproductive behaviors from the amygdala to the
hypothalamus. Neuron. 2005; 46:647–660. [PubMed: 15944132]
Choi JS, Brown TH. Central amygdala lesions block ultrasonic vocalization and freezing as
conditional but not unconditional responses. J Neurosci. 2003; 23:8713–8721. [PubMed:
14507971]
Cofer, C.; Appley, M. Motivation, Theory and Research. New York: John Wiley & Sons, Inc; 1964.
LeDoux Page 25
Neuron
. Author manuscript; available in PMC 2013 April 15.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Cohen, DH. The neural pathways and informational flow mediating a conditioned autonomic response.
In: Di Cara, LV., editor. Limbic and Autonomic Nervous System Research. New York: Plenum
Press; 1974. p. 223-275.
Conover KL, Shizgal P. Differential effects of postingestive feedback on the reward value of sucrose
and lateral hypothalamic stimulation in rats. Behav Neurosci. 1994; 108:559–572. [PubMed:
7917050]
Coons EE, White HA. Tonic properties of orosensation and the modulation of intracranial self-
stimulation: the CNS weighting of external and internal factors governing reward. Ann NY Acad
Sci. 1977; 290:158–179. [PubMed: 276290]
Corbit LH, Balleine BW. Double dissociation of basolateral and central amygdala lesions on the
general and outcome-specific forms of pavlovian-instrumental transfer. J Neurosci. 2005; 25:962–
970. [PubMed: 15673677]
Cousens G, Otto T. Both pre- and posttraining excitotoxic lesions of the basolateral amygdala abolish
the expression of olfactory and contextual fear conditioning. Behav Neurosci. 1998; 112:1092–
1103. [PubMed: 9829787]
Crick F, Koch C. Toward a neurobiological theory of consciousness. Neurosciences. 1990; 2:263–275.
Crick, FC.; Koch, C. A Framework for Consciousness. In: Gazzaniga, MS., editor. The Cognitive
Neurosciences. 3. Cambridge: MIT Press; 2004. p. 1133-1143.
Critchley HD, Wiens S, Rotshtein P, Ohman A, Dolan RJ. Neural systems supporting interoceptive
awareness. Nat Neurosci. 2004; 7:189–195. [PubMed: 14730305]
Damasio, A. Descarte’s error: Emotion, reason, and the human brain. New York: Gosset/Putnam;
1994.
Damasio A. Feelings of emotion and the self. Ann N Y Acad Sci. 2003; 1001:253–261. [PubMed:
14625365]
Damasio, AR. The feeling of what happens: Body and emotion in the making of consciousness. New
York: Harcourt Brace; 1999.
Damasio AR, Grabowski TJ, Bechara A, Damasio H, Ponto LL, Parvizi J, Hichwa RD. Subcortical
and cortical brain activity during the feeling of self- generated emotions. Nat Neurosci. 2000;
3:1049–1056. [PubMed: 11017179]
Darwin, C. The expression of the emotions in man and animals. London: Fontana Press; 1872.
Davidson RJ. Cerebral asymmetry and emotion: Conceptual and methodological conundrums.
Cognition and Emotion. 1993; 7:115–138.
Davies DC, Martinez-Garcia F, Lanuza E, Novejarque A. Striato-amygdaloid transition area lesions
reduce the duration of tonic immobility in the lizard Podarcis hispanica. Brain Res Bull. 2002;
57:537–541. [PubMed: 11923024]
Davis FC, Somerville LH, Ruberry EJ, Berry AB, Shin LM, Whalen PJ. A tale of two negatives:
differential memory modulation by threat-related facial expressions. Emotion. 2011; 11:647–655.
[PubMed: 21668114]
Davis, M. The role of the amygdala in conditioned fear. In: Aggleton, JP., editor. The Amygdala:
Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction. NY: Wiley-Liss, Inc;
1992. p. 255-306.
Davis M, Whalen PJ. The amygdala: vigilance and emotion. Mol Psychiatry. 2001; 6:13–34. [PubMed:
11244481]
Davis M, Walker DL, Lee Y. Amygdala and bed nucleus of the stria terminalis: differential roles in
fear and anxiety measured with the acoustic startle reflex. Philosophical Transactions of the Royal
Society of London Series B: Biological Sciences. 1997; 352:1675–1687.
de Oca BM, Fanselow MS. Amygdala and periaqueductal gray lesions only partially attenuate
unconditional defensive responses in rats exposed to a cat. Integr Physiol Behav Sci. 2004;
39:318–333. [PubMed: 16295774]
de Oca BM, Minor TR, Fanselow MS. Brief flight to a familiar enclosure in response to a conditional
stimulus in rats. J Gen Psychol. 2007; 134:153–172. [PubMed: 17503692]
De Oca BM, DeCola JP, Maren S, Fanselow MS. Distinct regions of the periaqueductal gray are
involved in the acquisition and expression of defensive responses. J Neurosci. 1998; 18:3426–
3432. [PubMed: 9547249]
LeDoux Page 26
Neuron
. Author manuscript; available in PMC 2013 April 15.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Dehaene, S.; Changeux, J-P. Neural Mechanisms for Access to Consciousness. In: Gazzaniga, MS.,
editor. The Cognitive Neurosciences. 3. Cambridge: MIT Press; 2004. p. 1145-1157.
Dickson BJ. Wired for sex: the neurobiology of Drosophila mating decisions. Science. 2008; 322:904–
909. [PubMed: 18988843]
Dielenberg RA, Hunt GE, McGregor IS. “When a rat smells a cat”: the distribution of Fos
immunoreactivity in rat brain following exposure to a predatory odor. Neuroscience. 2001;
104:1085–1097. [PubMed: 11457592]
Dixon BA. Animal Emotion. Ethics and the Environment. 2001; 6:22–30.
Dudai Y. Neurogenetic dissection of learning and short-term memory in Drosophila. Annu Rev
Neurosci. 1988; 11:537–563. [PubMed: 3129981]
Duffy E. Emotion: an example of the need for reorientation in psychology. Psychol Rev. 1934;
41:184–198.
Duffy E. An explanation of “emotional” phemomena without the use of the concept “emotion”.
Journal of General Psychology. 1941; 25:283–293.
Ekman, P. Universals and Cultural Differences in Facial Expressions of Emotions. In: Cole, J., editor.
Nebraska Symposium on Motivation. Lincoln, Nebraska: University of Nebraska Press; 1972. p.
207-283.
Ekman, P. Biological and cultural contributions to body and facial movement in the expression of
emotions. In: Rorty, AO., editor. Explaining Emotions. Berkeley: University of California Press;
1980.
Ekman, P. Expression and nature of emotion. In: Scherer, K.; Ekman, P., editors. Approaches to
Emotion. Hillsdale, NJ: Earlbaum; 1984. p. 319-343.
Ekman P. An argument for basic emotions. Cognition and Emotion. 1992; 6:169–200.
Ekman, P. Basic Emotions. In: Dalgleish, T.; Power, M., editors. Handbook of Cognition and Emotion.
Chichester: John Wiley and Sons, Co; 1999a. p. 45-60.
Ekman, P. Annotated update of Charles Darwin’s “The Expression of the Emotions in Man and
Animals”. New York: Harpercollins; 1999b.
Ekman, P.; Davidson, R. The nature of emotion: fundamental questions. New York: Oxford University
Press; 1994.
Elliot A, Church M. A hierarchical model of approach motivation and avoidance achievement
motivation. Journal of Personality and Social Psychology. 1997; 72:218–232.
Ellsworth PC. William James and emotion: is a century of fame worth a century of misunderstanding?
Psychol Rev. 1994; 101:222–229. [PubMed: 8022957]
Elmquist JK, Coppari R, Balthasar N, Ichinose M, Lowell BB. Identifying hypothalamic pathways
controlling food intake, body weight, and glucose homeostasis. J Comp Neurol. 2005; 493:63–71.
[PubMed: 16254991]
Estes WK, Skinner BF. Some quantitative properties of anxiety. Journal of Experimental Psychology.
1941; 29:390–400.
Everitt BJ, Robbins TW. Neural systems of reinforcement for drug addiction: from actions to habits to
compulsion. Nat Neurosci. 2005; 8:1481–1489. [PubMed: 16251991]
Everitt BJ, Cardinal RN, Parkinson JA, Robbins TW. Appetitive behavior: impact of amygdala-
dependent mechanisms of emotional learning. Ann N Y Acad Sci. 2003; 985:233–250. [PubMed:
12724162]
Everitt BJ, Parkinson JA, Olmstead MC, Arroyo M, Robledo P, Robbins TW. Associative processes in
addiction and reward. The role of amygdala- ventral striatal subsystems. Ann N Y Acad Sci.
1999; 877:412–438. [PubMed: 10415662]
Fanselow MS. Neural organization of the defensive behavior system responsible for fear. Psychonomic
Bulletin and Review. 1994; 1:429–438.
Fanselow MS, Poulos AM. The neuroscience of mammalian associative learning. Annu Rev Psychol.
2005; 56:207–234. [PubMed: 15709934]
Ferris CF, Stolberg T, Kulkarni P, Murugavel M, Blanchard R, Blanchard DC, Febo M, Brevard M,
Simon NG. Imaging the neural circuitry and chemical control of aggressive motivation. BMC
Neurosci. 2008; 9:111. [PubMed: 19014547]
LeDoux Page 27
Neuron
. Author manuscript; available in PMC 2013 April 15.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Fitzsimons JT. The physiology of thirst and sodium appetite. Monogr Physiol Soc. 1979:1–572.
[PubMed: 400173]
Flynn, JP. The neural basis of aggression in cats. In: Glass, DG., editor. Biology and Behavior:
Neurophysiology and Emotion. New York: Rockefeller University Press and Russell Sage
Foundation; 1967. p. 40-60.
Foote SL, Bloom FE, Aston-Jones G. Nucleus locus ceruleus: new evidence of anatomical and
physiological specificity. Physiol Rev. 1983; 63:844–914. [PubMed: 6308694]
Foote SL, Berridge CW, Adams LM, Pineda JA. Electrophysiological evidence for the involvement of
the locus coeruleus in alerting, orienting, and attending. Prog Brain Res. 1991; 88:521–532.
[PubMed: 1813932]
Frijda, N. The Emotions. Cambridge: Cambridge University Press; 1986.
Frith C, Dolan R. The role of the prefrontal cortex in higher cognitive functions. Brain Res Cogn Brain
Res. 1996; 5:175–181. [PubMed: 9049084]
Frith C, Perry R, Lumer E. The neural correlates of conscious experience: an experimental framework.
Trends in Cognitive Sciences. 1999; 3:105–114. [PubMed: 10322462]
Frith, CD. The social functions of consciousness. In: Weiskrantz, L.; Davies, M., editors. Frontiers of
Consciousness: Chichele lectures. Oxford: Oxford University Press; 2008. p. 225-244.
Fusar-Poli P, Placentino A, Carletti F, Landi P, Allen P, Surguladze S, Benedetti F, Abbamonte M,
Gasparotti R, Barale F, Perez J, McGuire P, Politi P. Functional atlas of emotional faces
processing: a voxel-based meta-analysis of 105 functional magnetic resonance imaging studies. J
Psychiatry Neurosci. 2009; 34:418–432. [PubMed: 19949718]
Gallagher M, Holland PC. The amygdala complex: multiple roles in associative learning and attention.
Proc Natl Acad Sci U S A. 1994; 91:11771–11776. [PubMed: 7991534]
Gallistel, R. The organization of action: A new synthesis. Hillsdale, NJ: Erlbaum; 19800.
Garcia J, McGowan BK, Ervin FR, Koelling RA. Cues: their relative effectiveness as a function of the
reinforcer. Science. 1968; 160:794–795. [PubMed: 5646420]
Garrity PA, Goodman MB, Samuel AD, Sengupta P. Running hot and cold: behavioral strategies,
neural circuits, and the molecular machinery for thermotaxis in C. elegans and Drosophila. Genes
Dev. 2010; 24:2365–2382. [PubMed: 21041406]
Glanzman DL. Common mechanisms of synaptic plasticity in vertebrates and invertebrates. Curr Biol.
2010; 20:R31–36. [PubMed: 20152143]
Glickman SE, Schiff BB. A biological theory of reinforcement. Psychol Rev. 1967; 74:81–109.
[PubMed: 5342347]
Glimcher, PW. Decisions, Uncertainty, and the Brain: The science of neuroeconomics. Cambridge:
MIT Press; 2003.
Glimcher PW. Understanding dopamine and reinforcement learning: the dopamine reward prediction
error hypothesis. Proc Natl Acad Sci U S A. 2011; 108(Suppl 3):15647–15654. [PubMed:
21389268]
Gray, JA. The Neuropsychology of Anxiety. New York: Oxford University Press; 1982.
Gray, JA. The Psychology of Fear and Stress. New York: Cambridge University Press; 1987.
Gray TS. Amygdaloid CRF pathways. Role in autonomic, neuroendocrine, and behavioral responses to
stress. Annal NY Academy of Science. 1993; 697:53–60.
Graybiel, A. Input-output anatomy of the basal ganglia. Toronto, Canada: Lecture at the Society for
Neuroscience; 1976.
Griffiths, PE. What Emotions Really Are: The problem of psychological categories. Chicago:
University of Chicago Press; 1997.
Griffiths, PE. Is emotion a natural kind?. In: Solomon, RC., editor. Thinking about feeling:
Contemporary philosophers on emotions. Oxford: Oxford University Press; 2004. p. 233-249.
Hamann SB, Ely TD, Hoffman JM, Kilts CD. Ecstasy and agony: activation of the human amygdala in
positive and negative emotion. Psychol Sci. 2002; 13:135–141. [PubMed: 11933997]
Hammond, LJ. Conditional emotional states. In: Black, P., editor. Physiological Correlates of Emotion.
New York: Academic Press; 1970.
LeDoux Page 28
Neuron
. Author manuscript; available in PMC 2013 April 15.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Hasselmo ME. Neuromodulation and cortical function: modeling the physiological basis of behavior.
Behav Brain Res. 1995; 67:1–27. [PubMed: 7748496]
Hawkins RD, Kandel ER, Bailey CH. Molecular mechanisms of memory storage in Aplysia. Biol Bull.
2006; 210:174–191. [PubMed: 16801493]
Hebb, DO. The Organization of Behavior. New York: John Wiley and Sons; 1949.
Hess, WR. Functional organization of the diencephalon. New York: Grune and Stratton; 1954.
Holland PC, Rescorla RA. Second-order conditioning with food unconditioned stimulus. J Comp
Physiol Psychol. 1975; 88:459–467. [PubMed: 1120816]
Holland PC, Gallagher M. Amygdala-frontal interactions and reward expectancy. Curr Opin
Neurobiol. 2004; 14:148–155. [PubMed: 15082318]
Hull, CL. Principles of behavior. New York: Appleton-Century-Crofts; 1943.
Hurley LM, Devilbiss DM, Waterhouse BD. A matter of focus: monoaminergic modulation of
stimulus coding in mammalian sensory networks. Curr Opin Neurobiol. 2004; 14:488–495.
[PubMed: 15321070]
Hyman SE, Malenka RC, Nestler EJ. Neural mechanisms of addiction: the role of reward-related
learning and memory. Annu Rev Neurosci. 2006; 29:565–598. [PubMed: 16776597]
Ikemoto S, Panksepp J. The role of nucleus accumbens dopamine in motivated behavior: a unifying
interpretation with special reference to reward-seeking. Brain Res Brain Res Rev. 1999; 31:6–41.
[PubMed: 10611493]
Izard CE. Basic emotions, relations among emotions, and emotion-cognition relations. Psychological
Review. 1992; 99:561–565. [PubMed: 1502277]
Izard CE. Basic emotions, natural kinds, emotion schemas, and a new paradigm. Perspectives on
Psychological Science. 2007; 2:260–280.
Jacobs BL, Wilkinson LO, Fornal CA. The role of brain serotonin. A neurophysiologic perspective.
Neuropsychopharmacology. 1990; 3:473–479. [PubMed: 2078280]
James W. What is an emotion? Mind. 1884; 9:188–205.
Jarymowicz, M. Emotions as evaluative processes from primary affects to appraisals based on
deliberative thinking. In: Blachnio, A.; Przepiorka, A., editors. Closer to emotions. Lublin:
Wydawnictwo KUL; 2009. p. 55-72.
Johansen JP, Cain CK, Ostroff LE, LeDoux JE. Molecular mechanisms of fear learning and memory.
Cell. 2011; 147:509–524. [PubMed: 22036561]
Johnson-Laird PN, Oatley K. The language of emotions: An analysis of a semantic field. Cognition
and Emotion. 1989; 3:81–123.
Johnson AK. The sensory psychobiology of thirst and salt appetite. Med Sci Sports Exerc. 2007;
39:1388–1400. [PubMed: 17762373]
Johnson AW, Gallagher M, Holland PC. The basolateral amygdala is critical to the expression of
pavlovian and instrumental outcome-specific reinforcer devaluation effects. J Neurosci. 2009;
29:696–704. [PubMed: 19158296]
Jones BE. Arousal systems. Front Biosci. 2003; 8:s438–451. [PubMed: 12700104]
Jouvet M. Biogenic amines and the states of sleep. Science. 1969; 163:32–41. [PubMed: 4303225]
Jouvet M. Sleep and serotonin: an unfinished story. Neuropsychopharmacology. 1999; 21:24S–27S.
[PubMed: 10432485]
Kagan, J. What is emotion? history, measures, and meanings. New Haven: Yale University Press;
2007.
Kalin NH, Shelton SE, Davidson RJ. The role of the central nucleus of the amygdala in mediating fear
and anxiety in the primate. J Neurosci. 2004; 24:5506–5515. [PubMed: 15201323]
Kalin NH, Shelton SE, Davidson RJ, Kelley AE. The primate amygdala mediates acute fear but not the
behavioral and physiological components of anxious temperament. J Neurosci. 2001; 21:2067–
2074. [PubMed: 11245690]
Kandel ER. The molecular biology of memory storage: a dialog between genes and synapses. Biosci
Rep. 2001; 21:565–611. [PubMed: 12168768]
Kapp BS, Supple WF Jr, Whalen PJ. Effects of electrical stimulation of the amygdaloid central nucleus
on neocortical arousal in the rabbit. Behav Neurosci. 1994; 108:81–93. [PubMed: 8192853]
LeDoux Page 29
Neuron
. Author manuscript; available in PMC 2013 April 15.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Kapp, BS.; Whalen, PJ.; Supple, WF.; Pascoe, JP. Amygdaloid contributions to conditioned arousal
and sensory information processing. In: Aggleton, JP., editor. The Amygdala: Neurobiological
Aspects of Emotion, Memory, and Mental Dysfunction. New York: Wiley-Liss; 1992. p.
229-254.
Kelley AE. Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-
related learning. Neurosci Biobehav Rev. 2004; 27:765–776. [PubMed: 15019426]
Killcross AS, Robbins TW. Differential effects of intra-accumbens and systemic amphetamine on
latent inhibition using an on-baseline, within-subject conditioned suppression paradigm.
Psychopharmacology (Berl). 1993; 110:479–489. [PubMed: 7870920]
Kitayama, S.; Markus, HR., editors. Emotion and culture: Empirical studies of mutual influence.
Washington, DC: American Psychological Association; 1994.
Koob GF. Brain stress systems in the amygdala and addiction. Brain Res. 2009; 1293:61–75.
[PubMed: 19332030]
LaBar KS, Cabeza R. Cognitive neuroscience of emotional memory. Nat Rev Neurosci. 2006; 7:54–
64. [PubMed: 16371950]
Lakoff, G. Women, Fire, and Dangerous Things: What Categories Reveal about the mind. Chicago:
The University of Chicago Press; 1987.
Lamprecht, R.; Dudai, Y. The amygdala in conditioned taste aversion: it’s there, but where?. In:
Aggleton, J., editor. The Amygdala. Oxford: Oxford U. Press; 2000.
Lane RD, Chua PM, Dolan RJ. Common effects of emotional valence, arousal and attention on neural
activation during visual processing of pictures. Neuropsychologia. 1999; 37:989–997. [PubMed:
10468363]
Lang PJ. The varieties of emotional experience: a meditation on James-Lange theory. Psychol Rev.
1994; 101:211–221. [PubMed: 8022956]
Lang PJ, Davis M. Emotion, motivation, and the brain: reflex foundations in animal and human
research. Prog Brain Res. 2006; 156:3–29. [PubMed: 17015072]
Lang PJ, Bradley MM, Cuthbert BN. Emotion, Attention, and the Startle Reflex. Psychological
Review. 1990; 97:377–395. [PubMed: 2200076]
Lange, CG. The emotions. In: Dunlap, E., editor. The Emotions. Baltimore: Williams and Wilkins;
1885/1922.
Lashley KS. Experimental analysis of instinctive behavior. Psychol Rev. 1938; 45:445–471.
Lazaro-Munoz G, LeDoux JE, Cain CK. Sidman instrumental avoidance initially depends on lateral
and Basal amygdala and is constrained by central amygdala-mediated Pavlovian processes. Biol
Psychiatry. 2010; 67:1120–1127. [PubMed: 20110085]
Lazarus RS. A cognitivist’s reply to Zajonc on emotion and cognition. American Psychologist. 1981;
36:222–223.
Lazarus RS. Cognition and Motivation in Emotion. American Psychologist. 1991a; 46:352–367.
[PubMed: 2048794]
Lazarus, RS. Emotion and Adaptation. New York: Oxford University Press; 1991b.
Lazarus, RS.; Folkman, S. Stress, Appraisal and Coping. New York: Springer; 1984.
Lebestky T, Chang JS, Dankert H, Zelnik L, Kim YC, Han KA, Wolf FW, Perona P, Anderson DJ.
Two different forms of arousal in Drosophila are oppositely regulated by the dopamine D1
receptor ortholog DopR via distinct neural circuits. Neuron. 2009; 64:522–536. [PubMed:
19945394]
LeDoux, JE. Emotion and the Amygdala. In: Aggleton, JP., editor. The Amygdala: Neurobiological
Aspects of Emotion, Memory, and Mental Dysfunction. New York: Wiley-Liss, Inc; 1992. p.
339-351.
LeDoux, JE. Seting “Stress” into Motion. In: Friedman, MJ.; Charney, DS.; Deutch, AY., editors.
Neurobiological and Clinical Consequences of Stress: from Normal Adaptation to PTSD. New
York: Raven Press; 1995. p. 125-134.
LeDoux, JE. The Emotional Brain. New York: Simon and Schuster; 1996.
LeDoux JE. Emotion circuits in the brain. Annu Rev Neurosci. 2000; 23:155–184. [PubMed:
10845062]
LeDoux Page 30
Neuron
. Author manuscript; available in PMC 2013 April 15.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
LeDoux, JE. Synaptic Self: How our brains become who we are. New York: Viking; 2002.
LeDoux, JE. Emotional colouration of consciousness: how feelings come about. In: Weiskrantz, L.;
Davies, M., editors. Frontiers of Consciousness: Chichele Lectures. Oxford: Oxford University
Press; 2008. p. 69-130.
LeDoux JE. Evolution of human emotion A view through fear. Prog Brain Res. 2012; 195:431–442.
[PubMed: 22230640]
Leventhal H, Scherer K. The relationship of emotion to cognition: a functional approach to a semantic
controversy. Cognition and Emotion. 1987; 1:3–28.
Liddell BJ, Brown KJ, Kemp AH, Barton MJ, Das P, Peduto A, Gordon E, Williams LM. A direct
brainstem-amygdala-cortical ‘alarm’ system for subliminal signals of fear. Neuroimage. 2005;
24:235–243. [PubMed: 15588615]
Lima SL, Dill LM. Behavioral decision made under the risk of predation: a review and prospectus.
Can J Zool. 1990; 68:619–640.
Lin D, Boyle MP, Dollar P, Lee H, Lein ES, Perona P, Anderson DJ. Functional identification of an
aggression locus in the mouse hypothalamus. Nature. 2011; 470:221–226. [PubMed: 21307935]
Lindsley, DB. Emotions. In: Stevens, SS., editor. Handbook of Experimental Psychology. New York:
Wiley; 1951. p. 473-516.
Litvin Y, Blanchard DC, Blanchard RJ. Rat 22kHz ultrasonic vocalizations as alarm cries. Behav
Brain Res. 2007; 182:166–172. [PubMed: 17173984]
Loewy AD. Forebrain nuclei involved in autonomic control. Prog Brain Res. 1991; 87:253–268.
[PubMed: 1866449]
Lopez HS, Brown AM. Neuromodulation. Curr Opin Neurobiol. 1992; 2:317–322. [PubMed:
1643413]
Lorenz, KZ. The Foundations of Ethology: The principal ideas and discoveries in animal behavior.
New York: Simon and Schuster; 1981.
Lucy JA. Linguistic Relativity. Annu Rev Anthropol. 1997; 26:291–312.
Luo Q, Holroyd T, Jones M, Hendler T, Blair J. Neural dynamics for facial threat processing as
revealed by gamma band synchronization using MEG. Neuroimage. 2007; 34:839–847.
[PubMed: 17095252]
Lyons, W. Emotion. Cambridge: Cambridge University Press; 1980.
MacLean PD. Psychosomatic disease and the “visceral brain”: recent developments bearing on the
Papez theory of emotion. Psychosomatic Medicine. 1949; 11:338–353. [PubMed: 15410445]
MacLean PD. Some psychiatric implications of physiological studies on frontotemporal portion of
limbic system (visceral brain). Electroencephalography and Clinical Neurophysiology. 1952;
4:407–418. [PubMed: 12998590]
Macnab RM, Koshland DE Jr. The gradient-sensing mechanism in bacterial chemotaxis. Proc Natl
Acad Sci U S A. 1972; 69:2509–2512. [PubMed: 4560688]
Mandler, G. Mind and Emotion. New York: Wiley; 1975.
Manning, A. An introduction to animal behaviour. Reading, MA: Addison-Wesley; 1967.
Maren S. Neurobiology of Pavlovian fear conditioning. Annu Rev Neurosci. 2001; 24:897–931.
[PubMed: 11520922]
Maren S, Quirk GJ. Neuronal signalling of fear memory. Nat Rev Neurosci. 2004; 5:844–852.
[PubMed: 15496862]
Margulies C, Tully T, Dubnau J. Deconstructing memory in Drosophila. Curr Biol. 2005; 15:R700–
713. [PubMed: 16139203]
Markham CM, Blanchard DC, Canteras NS, Cuyno CD, Blanchard RJ. Modulation of predatory odor
processing following lesions to the dorsal premammillary nucleus. Neurosci Lett. 2004; 372:22–
26. [PubMed: 15531081]
Marks, I. Fears, Phobias, and Rituals: Panic, Anxiety and Their Disorders. New York: Oxford
University Press; 1987.
Martinez-Garcia F, Martinez-Marcos A, Lanuza E. The pallial amygdala of amniote vertebrates:
evolution of the concept, evolution of the structure. Brain Res Bull. 2002; 57:463–469. [PubMed:
11923011]
LeDoux Page 31
Neuron
. Author manuscript; available in PMC 2013 April 15.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Masson, JM.; McCarthy, S. When elephants weep: The emotional lives of animals. New York:
Delacorte; 1996.
Maturana, H.; Varela, F. The tree of knowledge: The biological roots of human understanding. Boston:
New Science Library; 1987.
McClelland, D.; Atkinson, J.; Clark, R.; Lowell, E. The achievement motive. New York: Irvington
Publishers; 1953.
McEwen BS. The brain is the central organ of stress and adaptation. Neuroimage. 2009; 47:911–913.
[PubMed: 19501171]
McEwen BS, Eiland L, Hunter RG, Miller MM. Stress and anxiety: structural plasticity and epigenetic
regulation as a consequence of stress. Neuropharmacology. 2012; 62:3–12. [PubMed: 21807003]
McGaugh JL. Memory--a century of consolidation. Science. 2000; 287:248–251. [PubMed: 10634773]
McGaugh, JL. Memory and Emotion: The making of lasting memories. London: The Orion Publishing
Group; 2003.
McGrath PT, Rockman MV, Zimmer M, Jang H, Macosko EZ, Kruglyak L, Bargmann CI.
Quantitative mapping of a digenic behavioral trait implicates globin variation in C. elegans
sensory behaviors. Neuron. 2009; 61:692–699. [PubMed: 19285466]
McNaughton, N. Biology and emotion. Cambridge: Cambridge University Press; 1989.
Miller, N. Experimental studies of conflict. In: Endler, NS.; Hunt, JM., editors. Personality and the
Behavioral Disorders. New York: Ronald Press; 1944. p. 431-465.
Mineka S, Ohman A. Phobias and preparedness: the selective, automatic, and encapsulated nature of
fear. Biol Psychiatry. 2002; 52:927–937. [PubMed: 12437934]
Mobbs D, Marchant JL, Hassabis D, Seymour B, Tan G, Gray M, Petrovic P, Dolan RJ, Frith CD.
From threat to fear: the neural organization of defensive fear systems in humans. J Neurosci.
2009; 29:12236–12243. [PubMed: 19793982]
Mogenson GJ, Jones DL, Yim CY. From motivation to action: functional interface between the limbic
system and the motor system. Prog Neurobiol. 1980; 14:69–97. [PubMed: 6999537]
Monsey MS, Ota KT, Akingbade IF, Hong ES, Schafe GE. Epigenetic alterations are critical for fear
memory consolidation and synaptic plasticity in the lateral amygdala. PLoS One. 2011;
6:e19958. [PubMed: 21625500]
Monti JM, Jantos H. The roles of dopamine and serotonin, and of their receptors, in regulating sleep
and waking. Prog Brain Res. 2008; 172:625–646. [PubMed: 18772053]
Morgan, CT. Physiological Psychology. New York: McGraw-Hill; 1943.
Morris JS, Ohman A, Dolan RJ. A subcortical pathway to the right amygdala mediating “unseen” fear.
Proceedings of the National Academy of Sciences, USA. 1999; 96:1680–1685.
Morrison SE, Salzman CD. Re-valuing the amygdala. Curr Opin Neurobiol. 2010; 20:221–230.
[PubMed: 20299204]
Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW. Central nervous system control of
food intake and body weight. Nature. 2006; 443:289–295. [PubMed: 16988703]
Moruzzi G, Magoun HW. Brain Stem Reticular Formation and Activation of the EEG.
Electroencephalography and Clinical Neurophysiology. 1949; 1:455–473. [PubMed: 18421835]
Moscarello JM, Ben-Shahar O, Ettenberg A. Effects of food deprivation on goal-directed behavior,
spontaneous locomotion, and c-Fos immunoreactivity in the amygdala. Behav Brain Res. 2009;
197:9–15. [PubMed: 18706934]
Motta SC, Goto M, Gouveia FV, Baldo MV, Canteras NS, Swanson LW. Dissecting the brain’s fear
system reveals the hypothalamus is critical for responding in subordinate conspecific intruders.
Proc Natl Acad Sci U S A. 2009; 106:4870–4875. [PubMed: 19273843]
Mowrer, OH. Learning theory and behavior. New York: Wiley; 1960.
Moyer, KE. The psychobiology of aggression. New York: Harper & Row; 1976.
Mozzachiodi R, Byrne JH. More than synaptic plasticity: role of nonsynaptic plasticity in learning and
memory. Trends Neurosci. 2010; 33:17–26. [PubMed: 19889466]
Nagel T. What is it like to be a bat? Philosophical Review. 1974; 83:4435–4450.
LeDoux Page 32
Neuron
. Author manuscript; available in PMC 2013 April 15.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Nakamura K, Morrison SF. Central efferent pathways mediating skin cooling-evoked sympathetic
thermogenesis in brown adipose tissue. Am J Physiol Regul Integr Comp Physiol. 2007;
292:R127–136. [PubMed: 16931649]
Nauta, WJH.; Karten, HJ. A general profile of the vertebrate brain, with sidelights on the ancestry of
cerebral cortex. In: Schmitt, FO., editor. The Neurosciences: Second Study Program. New York:
The Rockefeller University Press; 1970. p. 7-26.
Nesse R. Evolutionary explanations of emotions. Human Nature. 1990; 1:261–289.
Nestler EJ. Molecular mechanisms of drug addiction. Neuropharmacology. 2004; 47(Suppl 1):24–32.
[PubMed: 15464123]
Nieuwenhuys, R. Chemoarchitecture of the Brain. Berlin: Springer-Verlag; 1985.
Nishino S. Hypothalamus, hypocretins/orexin, and vigilance control. Handb Clin Neurol. 2011;
99:765–782. [PubMed: 21056227]
Northcutt RG, Kaas JH. The emergence and evolution of mammalian neocortex. Trends in
Neurosciences. 1995; 18:373–379. [PubMed: 7482801]
Ochsner KN, Gross JJ. The cognitive control of emotion. Trends Cogn Sci. 2005; 9:242–249.
[PubMed: 15866151]
Ochsner KN, Bunge SA, Gross JJ, Gabrieli JD. Rethinking feelings: an FMRI study of the cognitive
regulation of emotion. J Cogn Neurosci. 2002; 14:1215–1229. [PubMed: 12495527]
Ohman A. Of snakes and faces: an evolutionary perspective on the psychology of fear. Scand J
Psychol. 2009; 50:543–552. [PubMed: 19930253]
Öhman A. Face the beast and fear the face: animal and social fears as prototypes for evolutionary
analyses of emotion. Psychophysiology. 1986; 23:123–145. [PubMed: 3704069]
Olds, J. Drives and Reinforcement. New York: Raven; 1977.
Olds J, Milner P. Positive reinforcement produced by electrical stimulation of septal and other regions
of the brain. J Comp Physiol Psychol. 1954; 47:419–427. [PubMed: 13233369]
Ono, T.; Nishijo, H. Neurophysiological Basis of the Kluver-Bucy Syndrome: Responses of Monkey
Amygdaloid Neurons to Biologically Significant Objects. In: Aggleton, JP., editor. The
Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction. New York:
Wiley-Liss, Inc; 1992. p. 167-190.
Oomura Y, Aou S, Koyama Y, Fujita I, Yoshimatsu H. Central control of sexual behavior. Brain Res
Bull. 1988; 20:863–870. [PubMed: 3409059]
Ortony A, Turner TJ. What’s basic about basic emotions? Psychological Review. 1990; 97:315–331.
[PubMed: 1669960]
Packard MG, Knowlton BJ. Learning and memory functions of the Basal Ganglia. Annu Rev
Neurosci. 2002; 25:563–593. [PubMed: 12052921]
Pagani JH, Rosen JB. The medial hypothalamic defensive circuit and 2,5-dihydro-2,4,5-
trimethylthiazoline (TMT) induced fear: comparison of electrolytic and neurotoxic lesions. Brain
Res. 2009; 1286:133–146. [PubMed: 19559688]
Panksepp J. Toward a general psychobiological theory of emotions. Behavioral and Brain Sciences.
1982; 5:407–467.
Panksepp, J. Affective Neuroscience. New York: Oxford U. Press; 1998.
Panksepp, J. Emotions as natural kinds within the mammalian brain. In: Lewis, M.; Haviland-Jones,
JM., editors. Handbook of Emotions. 2. New York: The Guilford Press; 2000. p. 137-156.
Panksepp J. Affective consciousness: Core emotional feelings in animals and humans. Conscious
Cogn. 2005; 14:30–80. [PubMed: 15766890]
Pare D, Quirk GJ, LeDoux JE. New vistas on amygdala networks in conditioned fear. J Neurophysiol.
2004; 92:1–9. [PubMed: 15212433]
Parkinson JA, Olmstead MC, Burns LH, Robbins TW, Everitt BJ. Dissociation in effects of lesions of
the nucleus accumbens core and shell on appetitive pavlovian approach behavior and the
potentiation of conditioned reinforcement and locomotor activity by D-amphetamine. J Neurosci.
1999; 19:2401–2411. [PubMed: 10066290]
LeDoux Page 33
Neuron
. Author manuscript; available in PMC 2013 April 15.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Paton JJ, Belova MA, Morrison SE, Salzman CD. The primate amygdala represents the positive and
negative value of visual stimuli during learning. Nature. 2006; 439:865–870. [PubMed:
16482160]
Pavesi E, Canteras NS, Carobrez AP. Acquisition of Pavlovian fear conditioning using beta-
adrenoceptor activation of the dorsal premammillary nucleus as an unconditioned stimulus to
mimic live predator-threat exposure. Neuropsychopharmacology. 2011; 36:926–939. [PubMed:
21209611]
Petrovich GD. Learning and the motivation to eat: forebrain circuitry. Physiol Behav. 2011; 104:582–
589. [PubMed: 21549730]
Petrovich GD, Risold PY, Swanson LW. Organization of projections from the basomedial nucleus of
the amygdala: a PHAL study in the rat. J Comp Neurol. 1996; 374:387–420. [PubMed: 8906507]
Petrovich GD, Canteras NS, Swanson LW. Combinatorial amygdalar inputs to hippocampal domains
and hypothalamic behavior systems. Brain Res Brain Res Rev. 2001; 38:247–289. [PubMed:
11750934]
Petrovich GD, Setlow B, Holland PC, Gallagher M. Amygdalo-hypothalamic circuit allows learned
cues to override satiety and promote eating. J Neurosci. 2002; 22:8748–8753. [PubMed:
12351750]
Pfaff D, Ribeiro A, Matthews J, Kow LM. Concepts and mechanisms of generalized central nervous
system arousal. Ann N Y Acad Sci. 2008; 1129:11–25. [PubMed: 18591465]
Pfaff, DW. Drive: neurobiological and molecular mechanisms of sexual motivation. Cambridge, MA:
MIT Press; 1999.
Phelps EA. Emotion and cognition: insights from studies of the human amygdala. Annu Rev Psychol.
2006; 57:27–53. [PubMed: 16318588]
Phelps EA, LeDoux JE. Contributions of the amygdala to emotion processing: from animal models to
human behavior. Neuron. 2005; 48:175–187. [PubMed: 16242399]
Pinker, S. How the Mind Works. New York: Norton; 1997.
Pirri JK, Alkema MJ. The neuroethology of C. elegans escape. Curr Opin Neurobiol. 2012
Pitkänen A, Savander V, LeDoux JE. Organization of intra-amygdaloid circuitries in the rat: an
emerging framework for understanding functions of the amygdala. Trends Neurosci. 1997;
20:517–523. [PubMed: 9364666]
Pollatos O, Gramann K, Schandry R. Neural systems connecting interoceptive awareness and feelings.
Hum Brain Mapp. 2007; 28:9–18. [PubMed: 16729289]
Preuss TM. Do rats have prefrontal cortex? The Rose-Woolsey-Akert program reconsidered. Journal
of Cognitive Neuroscience. 1995; 7:1–24.
Prinz, J. Which emotions are basic?. In: Cruise, P.; Evans, D., editors. Emotion, Evolution and
Rationality. Oxford: Oxford University Press; 2004. p. 69-87.
Quirk GJ, Mueller D. Neural mechanisms of extinction learning and retrieval.
Neuropsychopharmacology. 2008; 33:56–72. [PubMed: 17882236]
Reep R. Relationship between prefrontal and limbic cortex: a comparative anatomical review. Brain,
Behavior and Evolution. 1984; 25:5–80.
Reis DJ, LeDoux JE. Some central neural mechanisms governing resting and behaviorally coupled
control of blood pressure. Circulation. 1987; 76:2–19.
Reisenzein R. On Oatley and Johnson-Laird’s Theory of emotion and hierarchical structures in the
affective lexicon. Cognition and Emotion. 1995; 9:383–416.
Rescorla, RA.; Wagner, AR. A theory of Pavlovian conditioning: Variations in the effectiveness of
reinforcement and nonreinforcement. In: Black, AA.; Prokasy, WF., editors. Classical
Conditioning II: Current Research and Theory. New York: Appleton-Centry-Crofts; 1972. p.
64-99.
Reyes BA, Carvalho AF, Vakharia K, Van Bockstaele EJ. Amygdalar peptidergic circuits regulating
noradrenergic locus coeruleus neurons: linking limbic and arousal centers. Exp Neurol. 2011;
230:96–105. [PubMed: 21515261]
Reynolds SM, Berridge KC. Emotional environments retune the valence of appetitive versus fearful
functions in nucleus accumbens. Nat Neurosci. 2008; 11:423–425. [PubMed: 18344996]
LeDoux Page 34
Neuron
. Author manuscript; available in PMC 2013 April 15.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Robbins TW. Arousal systems and attentional processes. Biol Psychol. 1997; 45:57–71. [PubMed:
9083644]
Robbins TW. Chemistry of the mind: neurochemical modulation of prefrontal cortical function. J
Comp Neurol. 2005; 493:140–146. [PubMed: 16254988]
Robbins TW, Everitt BJ. A role for mesencephalic dopamine in activation: commentary on Berridge
(2006). Psychopharmacology (Berl). 2007; 191:433–437. [PubMed: 16977476]
Rodrigues SM, LeDoux JE, Sapolsky RM. The influence of stress hormones on fear circuitry. Annu
Rev Neurosci. 2009; 32:289–313. [PubMed: 19400714]
Roitman MF, Wheeler RA, Carelli RM. Nucleus accumbens neurons are innately tuned for rewarding
and aversive taste stimuli, encode their predictors, and are linked to motor output. Neuron. 2005;
45:587–597. [PubMed: 15721244]
Roitman MF, Wheeler RA, Wightman RM, Carelli RM. Real-time chemical responses in the nucleus
accumbens differentiate rewarding and aversive stimuli. Nat Neurosci. 2008; 11:1376–1377.
[PubMed: 18978779]
Rolls, ET. Neurophysiology and Functions of the Primate Amygdala. In: Aggleton, JP., editor. The
Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction. New York:
Wiley-Liss, Inc; 1992. p. 143-165.
Rolls, ET. The Brain and Emotion. Oxford: Oxford University Press; 1999.
Rolls, ET. Emotion Explained. New York: Oxford University Press; 2005.
Roozendaal B, McEwen BS, Chattarji S. Stress, memory and the amygdala. Nat Rev Neurosci. 2009;
10:423–433. [PubMed: 19469026]
Rorty, AO. Explaining emotions. In: Rorty, AO., editor. Explaining emotions. Berkeley: University of
California Press; 1980.
Rosenkranz JA, Grace AA. Dopamine-mediated modulation of odour-evoked amygdala potentials
during pavlovian conditioning. Nature. 2002; 417:282–287. [PubMed: 12015602]
Rudrauf D, Lachaux JP, Damasio A, Baillet S, Hugueville L, Martinerie J, Damasio H, Renault B.
Enter feelings: somatosensory responses following early stages of visual induction of emotion.
Int J Psychophysiol. 2009; 72:13–23. [PubMed: 18938199]
Russell JA. A Circumplex Model of Affect. J Pers Soc Psychol. 1980; 39:1161–1178.
Russell, JA. Natural language concepts of emotion. In: Hogan, R.; Jones, WH.; Stewart, AJ.; Healy,
JM.; Ozer, DJ., editors. Perspectives in Personality. London: Jessica Kingsley; 1991.
Russell JA. Core affect and the psychological construction of emotion. Psychol Rev. 2003; 110:145–
172. [PubMed: 12529060]
Russell JA, Barrett LF. Core affect, prototypical emotional episodes, and other things called emotion:
dissecting the elephant. J Pers Soc Psychol. 1999; 76:805–819. [PubMed: 10353204]
Salamone JD. The involvement of nucleus accumbens dopamine in appetitive and aversive motivation.
Behav Brain Res. 1994; 61:117–133. [PubMed: 8037860]
Sander D, Grandjean D, Scherer KR. A systems approach to appraisal mechanisms in emotion. Neural
Netw. 2005; 18:317–352. [PubMed: 15936172]
Saper CB. Staying awake for dinner: hypothalamic integration of sleep, feeding, and circadian
rhythms. Prog Brain Res. 2006; 153:243–252. [PubMed: 16876579]
Saper CB, Chou TC, Elmquist JK. The need to feed: homeostatic and hedonic control of eating.
Neuron. 2002; 36:199–211. [PubMed: 12383777]
Sapolsky RM, Krey LC, McEwen BS. The neuroendocrinology of stress and aging: The glucocorticoid
cascade hypothesis. Endocrine Reviews. 1986; 7:284–301. [PubMed: 3527687]
Sarter M, Hasselmo ME, Bruno JP, Givens B. Unraveling the attentional functions of cortical
cholinergic inputs: interactions between signal-driven and cognitive modulation of signal
detection. Brain Res Brain Res Rev. 2005; 48:98–111. [PubMed: 15708630]
Scarantino A. Core affect and natural affective kinds. Philosophy of Science. 2009; 76:940–957.
Schachter, S. Cognition and centralist-peripheralist controversies in motivation and emotion. In:
Gazzaniga, MS.; Blakemore, CB., editors. Handbook of Psychobiology. New York: Academic
Press; 1975. p. 529-564.
LeDoux Page 35
Neuron
. Author manuscript; available in PMC 2013 April 15.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Schachter S, Singer JE. Cognitive, social, and physiological determinants of emotional state. Psychol
Rev. 1962; 69:379–399. [PubMed: 14497895]
Scherer, K. Emotions as episodes of subsystem synchronization driven by nonlinear appraisal
processes. In: Lewis, M.; Granic, I., editors. Emotion, development, and self-organization:
Dynamic systems approaches to emotional development. New York: Cambridge University
Press; 2000. p. 70-99.
Scherer KR. Emotion as a multicomponent process: A model and some cross-cultural data. Review of
Personality and Social Psychology. 1984; 5:37–63.
Scherer, KR. Criteria for emotion-antecedent appraisal: A review. In: Hamilton, V.; Bower, GH.;
Frijda, NH., editors. Cognitive Perspectives on Emotion and Motivation. Norwell, MA: Kluwer
Academic Publishers; 1988. p. 89-126.
Scherer, KR.; Schorr, A.; Johnstone, T., editors. Appraisal processes in emotion: Theory, Methods,
Research. London: London University Press; 2001.
Schildkraut JJ, Kety SS. Biogenic amines and emotion. Science. 1967; 156:21–37. [PubMed:
5335690]
Schiller D, Delgado MR. Overlapping neural systems mediating extinction, reversal and regulation of
fear. Trends Cogn Sci. 2010; 14:268–276. [PubMed: 20493762]
Schimitel FG, de Almeida GM, Pitol DN, Armini RS, Tufik S, Schenberg LC. Evidence of a
suffocation alarm system within the periaqueductal gray matter of the rat. Neuroscience. 2011
Schneirla, TC. An evolutionary theory of biphasic processes underlying approach and withdrawal. In:
Jones, MR., editor. Nebraska Symposium on Motivation. University of Nebraska Press; 1959. p.
1-42.
Schober J, Weil Z, Pfaff D. How generalized CNS arousal strengthens sexual arousal (and vice versa).
Horm Behav. 2011; 59:689–695. [PubMed: 20950622]
Schoenbaum G, Setlow B. Lesions of nucleus accumbens disrupt learning about aversive outcomes. J
Neurosci. 2003; 23:9833–9841. [PubMed: 14586012]
Schulkin, J. Rethinking homeostasis: Allostatic regulation in physiology and pathophysiology.
Cambridge: MIT Press; 2003.
Schultz W. Dopamine neurons and their role in reward mechanisms. Curr Opin Neurobiol. 1997;
7:191–197. [PubMed: 9142754]
Schultz W. Behavioral theories and the neurophysiology of reward. Annu Rev Psychol. 2006; 57:87–
115. [PubMed: 16318590]
Sears RM, Liu RJ, Narayanan NS, Sharf R, Yeckel MF, Laubach M, Aghajanian GK, DiLeone RJ.
Regulation of nucleus accumbens activity by the hypothalamic neuropeptide melanin-
concentrating hormone. J Neurosci. 2010; 30:8263–8273. [PubMed: 20554878]
Seligman MEP. Phobias and Preparedness. Behavior therapy. 1971; 2:307–320.
Selye H. Stress and disease. Science. 1955; 122:625–631. [PubMed: 13255902]
Semendeferi K, Teffer K, Buxhoeveden DP, Park MS, Bludau S, Amunts K, Travis K, Buckwalter J.
Spatial organization of neurons in the frontal pole sets humans apart from great apes. Cereb
Cortex. 2011; 21:1485–1497. [PubMed: 21098620]
Sesack SR, Grace AA. Cortico-Basal Ganglia reward network: microcircuitry.
Neuropsychopharmacology. 2010; 35:27–47. [PubMed: 19675534]
Seymour B, Dolan R. Emotion, decision making, and the amygdala. Neuron. 2008; 58:662–671.
[PubMed: 18549779]
Shallice, T. Information processing models of consiousness. In: Marcel, A.; Bisiach, E., editors.
Consciousness in contemporary science. Oxford: Oxford U. Press; 1988. p. 305-333.
Shallice T, Stuss DT, Alexander MP, Picton TW, Derkzen D. The multiple dimensions of sustained
attention. Cortex. 2008; 44:794–805. [PubMed: 18489960]
Sheffield FD, Roby TB. Reward value of a non-nutritive sweet taste. Journal of Comparative
Physiology and Psychology. 1950; 43:471–481.
Shepherd, G. Neurobiology. 2. New York: Oxford; 1988.
Sherrington, CS. The Integrative Action of the Nervous System. New Haven: Yale U. Press; 1906.
LeDoux Page 36
Neuron
. Author manuscript; available in PMC 2013 April 15.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Siegel, A.; Edinger, H. Neural control of aggression and rage behavior. In: Morgane, PJ.; Panksepp, J.,
editors. Handbook of the Hypothalamus, Vol. 3, Behavioral Studies of the Hypothalamus. New
York: Marcel Dekker; 1981. p. 203-240.
Skinner, BF. The behavior of organisms: An experimental analysis. New York: Appleton-Century-
Crofts; 1938.
Smith CA, Ellsworth PC. Patterns of cognitive appraisal in emotion. Journal of Personality and Social
Psychology. 1985; 56:339–353. [PubMed: 2926633]
Sosulski DL, Bloom ML, Cutforth T, Axel R, Datta SR. Distinct representations of olfactory
information in different cortical centres. Nature. 2011; 472:213–216. [PubMed: 21451525]
Stellar E. The physiology of motivation. Psychol Rev. 1954; 61:5–22. [PubMed: 13134413]
Steriade M. Brain activation, then (1949) and now: coherent fast rhythms in corticothalamic networks.
Arch Ital Biol. 1995; 134:5–20. [PubMed: 8919189]
Steriade M. Acetylcholine systems and rhythmic activities during the waking--sleep cycle. Prog Brain
Res. 2004; 145:179–196. [PubMed: 14650916]
Striedter, GF. Principles of Brain Evolution. Sunderland: Sinauer Associates; 2005.
Sutton, RS.; Barto, AG. A temporal-difference model of classical conditioning. Proceedings of the
Ninth Annual Conference of the Cognitive Science Society; 1987. p. 355-378.
Swanson LW. Cerebral hemisphere regulation of motivated behavior. Brain Res. 2000; 886:113–164.
[PubMed: 11119693]
Swanson, LW. Brain Architecture: Understanding the Basic Plan. Oxford: Oxford University Press;
2002.
Talarovicova A, Krskova L, Kiss A. Some assessments of the amygdala role in suprahypothalamic
neuroendocrine regulation: a minireview. Endocr Regul. 2007; 41:155–162. [PubMed:
18257652]
Tamietto M, Castelli L, Vighetti S, Perozzo P, Geminiani G, Weiskrantz L, de Gelder B. Unseen facial
and bodily expressions trigger fast emotional reactions. Proc Natl Acad Sci U S A. 2009;
106:17661–17666. [PubMed: 19805044]
Thompson R, LeDoux JE. Common brain regions essential for the expression of learned and
instinctive visual habits in the albino rat. Bull Psychon Soc. 1974; 4:78–80.
Tinbergen, N. The Study of Instinct. New York: Oxford University Press; 1951.
Tolman, EC. Purposive behavior. New York: Appleton-Century-Crofts; 1932.
Tomkins, SS. Affect, Imagery, Consciousness. New York: Springer; 1962.
Tooby J, Cosmides L. The past explains the present: Emotional adaptations and the structure of
ancestral environments. Ethological Sociobiology. 1990; 11:375–424.
Trowill JA, Panksepp J, Gandelman R. An incentive model of rewarding brain stimulation. Psychol
Rev. 1969; 76:264–281. [PubMed: 4893202]
von Holst E, von Saint-Paul U. Electrically controlled behavior. Sci Am. 1962; 206:50–59. [PubMed:
13908550]
Vyas A, Kim SK, Giacomini N, Boothroyd JC, Sapolsky RM. Behavioral changes induced by
Toxoplasma infection of rodents are highly specific to aversion of cat odors. Proc Natl Acad Sci
U S A. 2007; 104:6442–6447. [PubMed: 17404235]
Walker DL, Davis M. Light-enhanced startle: further pharmacological and behavioral characterization.
Psychopharmacology (Berl). 2002; 159:304–310. [PubMed: 11862363]
Wallace KJ, Rosen JB. Predator odor as an unconditioned fear stimulus in rats: elicitation of freezing
by trimethylthiazoline, a component of fox feces. Behav Neurosci. 2000; 114:912–922.
[PubMed: 11085605]
Wang L, Han X, Mehren J, Hiroi M, Billeter JC, Miyamoto T, Amrein H, Levine JD, Anderson DJ.
Hierarchical chemosensory regulation of male-male social interactions in Drosophila. Nat
Neurosci. 2011; 14:757–762. [PubMed: 21516101]
Weinberger, NM. Retuning the brain by fear conditioning. In: Gazzaniga, MS., editor. The Cognitive
Neurosciences. Cambridge, MA: The MIT Press; 1995. p. 1071-1090.
Whalen PJ. Fear, vigilance and ambiguity: initial neuroimaging studies of the human amygdala
[manuscript]. 1998
LeDoux Page 37
Neuron
. Author manuscript; available in PMC 2013 April 15.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Whalen, PJ.; Phelps, EA. The human amygdala. New York: Guilford Press; 2009.
Whalen PJ, Kagan J, Cook RG, Davis FC, Kim H, Polis S, McLaren DG, Somerville LH, McLean AA,
Maxwell JS, Johnstone T. Human amygdala responsivity to masked fearful eye whites. Science.
2004; 306:2061. [PubMed: 15604401]
Whorf, BL. Language, thought, and reality. Cambridge: Technology Press of MIT; 1956.
Wickens JR, Horvitz JC, Costa RM, Killcross S. Dopaminergic mechanisms in actions and habits. J
Neurosci. 2007; 27:8181–8183. [PubMed: 17670964]
Wierzbicka, A. Emotion, language, and cultural scripts. In: Kitayama, S.; Markus, HR., editors.
Emotion and Culture: Empirical studies of mutual influence. Washington, DC: American
Psychological Association; 1994. p. 133-196.
Wise RA. Role of brain dopamine in food reward and reinforcement. Philos Trans R Soc Lond B Biol
Sci. 2006; 361:1149–1158. [PubMed: 16874930]
Wise SP. Forward frontal fields: phylogeny and fundamental function. Trends Neurosci. 2008;
31:599–608. [PubMed: 18835649]
Yin JC, Tully T. CREB and the formation of long-term memory. Curr Opin Neurobiol. 1996; 6:264–
268. [PubMed: 8725970]
Yovell Y, Kandel ER, Dudai Y, Abrams TW. A quantitative study of the Ca2+/calmodulin sensitivity
of adenylyl cyclase in Aplysia, Drosophila, and rat. J Neurochem. 1992; 59:1736–1744.
[PubMed: 1402918]
Zachar P. The classification of emotion and scientific realism. J Theor Philosoph Psychol. 2006;
26:120–138.
Zajonc R. Feeling and thinking: preferences need no inferences. American Psychologist. 1980;
35:151–175.
Zhang TY, Parent C, Weaver I, Meaney MJ. Maternal programming of individual differences in
defensive responses in the rat. Ann N Y Acad Sci. 2004; 1032:85–103. [PubMed: 15677397]
LeDoux Page 38
Neuron
. Author manuscript; available in PMC 2013 April 15.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Figure 1. Circuits Underlying Defense Reactions Elicited by Unconditioned (Unlearned) and
Conditioned (Learned) Threats
Abbreviations: ABA, accessory basal amygdala; BA, basal amygdala; CEA, central
amygdala; LA, lateral amygdala; LH, lateral hypothalamus; MEA, medial amygdala; NAcc,
nucleus accumbens; VMH, ventromedial hypothalamus; PAGd, dorsal periaqueductal gray
region; PAGv, venral periaqueductal gray region; PMH, premammilary nucleus of the
hypothalamus.
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Figure 2. Multiple Roles for a Conditioned Stimulus
A CS functions as a survival circuit trigger (by activating a specific survival circuit related
to the US that was used during conditioning), and as a conditioned incentive and a
conditioned reinforcer (by way of connections from the survival circuit to motivational and
reinforcement systems). Other routes by which a CS might influence motivational and
reinforcement circuitry are not shown.
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Figure 3. Consequences of Survival Circuit Activation
When a survival circuit trigger activates a survival circuit, a number of consequences follow.
(1) Innate behavioral responses are potentially activated, as well as autonomic nervous
system (ANS) responses and hormonal responses. These each generate feedback to the
brain. (2) Neuromodulator systems are activated and begin to regulate excitability and
neurotransmission throughout the brain. (3) Goal directed instrumental behavior is initiated
by the motivation system. (4) Sensory, cognitive, and explicit memory systems are also
affected, leading to enhanced attention to relevant stimuli and the formation of new explicit
memories (memories formed by the hippocampus and related cortical areas) and implicit
memories (memories formed within the survival circuit).
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Figure 4.
Ingredients of Feelings in a Cognitive Workspace. An emotional feeling is hypothesized to
be a representation of a global organismic state initiated by an external stimulus. The
representation includes sensory information about the stimulus and the social and physical
context, information about the survival circuit that is active, information about CNS arousal,
body feedback information, and mnemonic information about the stimulus situation and the
state itself. When such a global organismic state is categorized and labeled a conscious
feeling of a certain type (e.g. a feeling of fear, pleasure, disgust, etc) results. To the extent
that any of these components differ in human and non-human species, the nature of the
resulting state would differ as well.
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LeDoux Page 43
TABLE 1
Multiple Roles for so-called “Emotional” Stimuli
1. Survival Circuit Trigger Stimulus Activates a specific survival circuit
Innate (Unconditioned) trigger Elicits innate responses to stimuli without the need for prior exposure to the stimulus and mobilizes other brain resources to deal with the opportunity
or challenge presented by the innate trigger
Learned (Conditioned) trigger Potentially elicits innate responses to stimuli after being associated (via Pavlovian conditioning) with an innate trigger; more generally, mobilizes brain
resources to deal with the challenge or opportunity signaled by the learned trigger
2. Incentive Modulates instrumental goal-directed behavior to help meet the opportunity or challenge signaled by the stimulus that is triggering activation of a
specific survival circuit
Innate (unconditioned or primary) incentive Increases approach toward or avoidance of the stimulus in an effort to resolve the challenge or opportunity present
Learned (conditioned or secondary) incentive Invigorates and guides behavior toward situations where the challenge or opportunity present can be resolved
3. Reinforcer Supports the learning of Pavlovian or instrumental associations
Innate (unconditioned or primary) reinforce Induces the formation of associations with neutral stimuli that occur in its presence (through Pavlovian conditioning) and to the formation of
associations with responses that lead to the presentation (appetitive stimuli) or removal (aversive stimuli) of the stimulus (through instrumental
conditioning)
Learned (conditioned or second-order reinforce Induces formation of associations with other stimuli (through Pavlovian second-order conditioning) or with goal directed responses (through second-
order instrumental conditioning)
Neuron
. Author manuscript; available in PMC 2013 April 15.
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