Amygdala

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For other uses, see Amygdala (disambiguation).
Amygdala

Location of the amygdalae in the human brain

Subdivisions of the amygdala

Details
Identifiers
Latin corpus amygdaloideum
MeSH D000679
NeuroNames 237
NeuroLex ID birnlex_1241
TA98 A14.1.09.402
TA2 5549
FMA 61841
Anatomical terms of neuroanatomy
[edit on Wikidata]

Human brain in the coronal orientation. Amygdalae are shown in dark red.
The amygdala (/əˈmɪɡdələ/; plural: amygdalae /əˈmɪɡdəli, -laɪ/ or amygdalas; also corpus
amygdaloideum; Latin from Greek, ἀμυγδαλή, amygdalē, 'almond', 'tonsil'[1]) is one of two
almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's
cerebrum in complex vertebrates, including humans.[2] Shown to perform a primary role in the
processing of memory, decision making, and emotional responses (including fear, anxiety, and
aggression), the amygdalae are considered part of the limbic system.[3] The term "amygdala" was
first introduced by Karl Friedrich Burdach in 1822.[4]

Contents
• 1 Structure
• 1.1 Hemispheric specializations
• 2 Development and sex distinction
• 3 Function
• 3.1 Connections
• 3.2 Emotional learning
• 3.3 Reward
• 3.4 Memory modulation
• 4 Neuropsychological correlates of amygdala activity
• 4.1 Sexual orientation
• 4.2 Social interaction
• 4.3 Aggression
 • 4.4 Fear
• 4.5 Alcoholism and binge drinking
• 4.6 Anxiety
• 4.7 Posttraumatic stress disorder
• 4.8 Bipolar disorder
• 5 Additional images
• 6 See also
• 7 References
• 8 Further reading
• 9 External links

Structure

MRI coronal view of the right amygdala

Subdivisions of the mouse amygdala

The regions described as amygdala nuclei encompass several structures of the cerebrum with
distinct connectional and functional characteristics in humans and other animals.[5] Among these
nuclei are the basolateral complex, the cortical nucleus, the medial nucleus, the central nucleus, and
the intercalated cell clusters. The basolateral complex can be further subdivided into the lateral, the
basal, and the accessory basal nuclei.[3][6][7]
Anatomically, the amygdala,[8] and more particularly its central and medial nuclei,[9] have
sometimes been classified as a part of the basal ganglia.

Hemispheric specializations
In one study, electrical stimulations of the right amygdala induced negative emotions, especially
fear and sadness. In contrast, stimulation of the left amygdala was able to induce either pleasant
(happiness) or unpleasant (fear, anxiety, sadness) emotions.[10] Other evidence suggests that the
left amygdala plays a role in the brain's reward system.[11]
Each side holds a specific function in how we perceive and process emotion. The right and left
portions of the amygdala have independent memory systems, but work together to store, encode,
and interpret emotion.
The right hemisphere of the amygdala is associated with negative emotion.[12][13] It plays a role in
the expression of fear and in the processing of fear-inducing stimuli. Fear conditioning, which
occurs when a neutral stimulus acquires aversive properties, occurs within the right hemisphere.
When an individual is presented with a conditioned, aversive stimulus, it is processed within the
right amygdala, producing an unpleasant or fearful response. This emotional response conditions
the individual to avoid fear-inducing stimuli and more importantly, to assess threats in the
environment.
The right hemisphere is also linked to declarative memory, which consists of facts and information
from previously experienced events and must be consciously recalled. It also plays a significant role
in the retention of episodic memory. Episodic memory consists of the autobiographical aspects of
memory, permitting recall of emotional and sensory experience of an event. This type of memory
does not require conscious recall. The right amygdala plays a role in the association of time and
places with emotional properties.[14]

Development and sex distinction

See also: Neuroscience of sex differences
The amygdala is one of the best-understood brain regions with regard to differences between the
sexes. The amygdala is larger in males than females in children aged 7 to 11,[15] adult humans,[16]
and adult rats.[17]
There is considerable growth within the first few years of structural development in both male and
female amygdalae.[18] Within this early period, female limbic structures grow at a more rapid pace
than the male ones. Amongst female subjects, the amygdala reaches its full growth potential
approximately 1.5 years before the peak of male development. The structural development of the
male amygdala occurs over a longer period than in women. Despite the early development of
female amygdalae, they reach their growth potential sooner than males, whose amygdalae continue
to develop. The larger relative size of the male amygdala may be attributed to this extended
developmental period.
Hormonal factors may also contribute to sex-specific developmental differences. The amygdala is
rich in androgen receptors – nuclear receptors that bind to testosterone. Androgen receptors play a
role in the DNA binding that regulates gene expression. Though testosterone is present within the
female hormonal systems, women have lower levels of testosterone than men. The abundance of
testosterone in the male hormonal system may contribute to development. In addition, the grey
matter volume on the amygdala is predicted by testosterone levels, which may also contribute to the
increased mass of the male amygdala.
There are observable developmental differences between the right and left amygdala. The left
amygdala reaches its developmental peak approximately 1.5–2 years prior to the right amygdala.
Despite the early growth of the left amygdala, the right increases in volume for a longer period of
time. The right amygdala is associated with response to fearful stimuli as well as face recognition. It
is inferred that the early development of the left amygdala functions to provide infants the ability to
detect danger.[18] In childhood, the amygdala is found to react differently to same-sex versus
opposite-sex individuals. This reactivity decreases until a person enters adolescence, where it
increases dramatically at puberty.[19]
Other functional and structural differences between male and female amygdalae have been
observed. Subjects' amygdala activation was observed when watching a horror film and subliminal
stimuli. The results of the study showed a different lateralization of the amygdala in men and
women. Enhanced memory for the film was related to enhanced activity of the left, but not the right,
amygdala in women, whereas it was related to enhanced activity of the right, but not the left,
amygdala in men.[20] Similarly, a study of decision-making ability in patients with unilateral
amygdala damage suggested that men with right (but not left) amygdala damage were more likely
to be impaired in decision-making ability, while women with left (but not right) amygdala damage
were more likely to be impaired in decision-making ability.[21][22] One study found evidence that
on average, women tend to retain stronger memories for emotional events than men.[23]

Function
Connections
A simple view of the information processing through the amygdala follows as: the amygdala sends
projections to the hypothalamus, the dorsomedial thalamus, the thalamic reticular nucleus, the
nuclei of the trigeminal nerve and the facial nerve, the ventral tegmental area, the locus coeruleus,
and the laterodorsal tegmental nucleus.[6] The basolateral amygdala projects to the nucleus
accumbens, including the medial shell. [24][25]

Coronal section of brain through intermediate mass of third ventricle. Amygdala is shown in purple.
The medial nucleus is involved in the sense of smell and pheromone-processing. It receives input
from the olfactory bulb and olfactory cortex.[26] The lateral amygdalae, which send impulses to the
rest of the basolateral complexes and to the centromedial nuclei, receive input from the sensory
systems. The centromedial nuclei are the main outputs for the basolateral complexes, and are
involved in emotional arousal in rats and cats.[6][7][27]

Emotional learning
Main article: Emotion and memory
In complex vertebrates, including humans, the amygdalae perform primary roles in the formation
and storage of memories associated with emotional events. Research indicates that, during fear
conditioning, sensory stimuli reach the basolateral complexes of the amygdalae, particularly the
lateral nuclei, where they form associations with memories of the stimuli. The association between
stimuli and the aversive events they predict may be mediated by long-term potentiation,[28][29] a
sustained enhancement of signaling between affected neurons.[30] There have been studies that
show that damage to the amygdala can interfere with memory that is strengthened by emotion. One
study examined a patient with bilateral degeneration of the amygdala. He was told a violent story
accompanied by matching pictures and was observed based on how much he could recall from the
story. The patient had less recollection of the story than patients with functional amygdala, showing
that the amygdala has a strong connection with emotional learning.[31]
Emotional memories are thought to be stored in synapses throughout the brain. Fear memories, for
example, are considered to be stored in the neuronal connections from the lateral nuclei to the
central nucleus of the amygdalae and the bed nuclei of the stria terminalis (part of the extended
amygdala). These connections are not the sole site of fear memories given that the nuclei of the
amygdala receive and send information to other brain regions that are important for memory such as
the hippocampus. Some sensory neurons project their axon terminals to the central nucleus.[32] The
central nuclei are involved in the genesis of many fear responses such as defensive behavior
(freezing or escape responses), autonomic nervous system responses (changes in blood pressure and
heart rate/tachycardia), neuroendocrine responses (stress-hormone release), etc. Damage to the
amygdalae impairs both the acquisition and expression of Pavlovian fear conditioning, a form of
classical conditioning of emotional responses.[30] Accumulating evidence has suggested that
multiple neuromodulators acting in the amygdala regulates the formation of emotional memories.
[33][34][35]
The amygdalae are also involved in appetitive (positive) conditioning. It seems that distinct neurons
respond to positive and negative stimuli, but there is no clustering of these distinct neurons into
clear anatomical nuclei.[36][37] However, lesions of the central nucleus in the amygdala have been
shown to reduce appetitive learning in rats. Lesions of the basolateral regions do not exhibit the
same effect.[38] Research like this indicates that different nuclei within the amygdala have different
functions in appetitive conditioning.[39][40] Nevertheless, researchers found an example of
appetitive emotional learning showing an important role for the basolateral amygdala: The naïve
female mice are innately attracted to non-volatile pheromones contained in male-soiled bedding, but
not by the male-derived volatiles, become attractive if associated with non-volatile attractive
pheromones, which act as unconditioned stimulus in a case of Pavlovian associative learning.[41] In
the vomeronasal, olfactory and emotional systems, Fos (gene family) proteins show that non-
volatile pheromones stimulate the vomeronasal system, whereas air-borne volatiles activate only the
olfactory system. Thus, the acquired preference for male-derived volatiles reveals an olfactory-
vomeronasal associative learning. Moreover, the reward system is differentially activated by the
primary pheromones and secondarily attractive odorants. Exploring the primary attractive
pheromone activates the basolateral amygdala and the shell of nucleus accumbens but neither the
ventral tegmental area nor the orbitofrontal cortex. In contrast, exploring the secondarily attractive
male-derived odorants involves activation of a circuit that includes the basolateral amygdala,
prefrontal cortex and ventral tegmental area. Therefore, the basolateral amygdala stands out as the
key center for vomeronasal-olfactory associative learning.[42]

Reward
Glutamatergic neurons in the basolateral amygdala send projections to the nucleus accumbens shell
and core. Activation of these projections drive motivational salience. The ability of these
projections to drive incentive salience is dependent upon dopamine receptor D1.[24][25]

Memory modulation
The amygdala is also involved in the modulation of memory consolidation. Following any learning
event, the long-term memory for the event is not formed instantaneously. Rather, information
regarding the event is slowly assimilated into long-term (potentially lifelong) storage over time,
possibly via long-term potentiation. Recent studies suggest that the amygdala regulates memory
consolidation in other brain regions. Also, fear conditioning, a type of memory that is impaired
following amygdala damage, is mediated in part by long-term potentiation.[28][29]
During the consolidation period, the memory can be modulated. In particular, it appears that
emotional arousal following the learning event influences the strength of the subsequent memory
for that event. Greater emotional arousal following a learning event enhances a person's retention of
that event. Experiments have shown that administration of stress hormones to mice immediately
after they learn something enhances their retention when they are tested two days later.[43]
The amygdala, especially the basolateral nuclei, are involved in mediating the effects of emotional
arousal on the strength of the memory for the event, as shown by many laboratories including that
of James McGaugh. These laboratories have trained animals on a variety of learning tasks and
found that drugs injected into the amygdala after training affect the animals' subsequent retention of
the task. These tasks include basic classical conditioning tasks such as inhibitory avoidance, where
a rat learns to associate a mild footshock with a particular compartment of an apparatus, and more
complex tasks such as spatial or cued water maze, where a rat learns to swim to a platform to escape
the water. If a drug that activates the amygdalae is injected into the amygdalae, the animals had
better memory for the training in the task.[44] If a drug that inactivates the amygdalae is injected,
the animals had impaired memory for the task.
In rats, DNA damage was found to increase in the amygdala immediately after exposure to stress.
[45] Stress was induced by 30 minutes of restraint or by forced swimming. By seven days after
exposure to these stresses, increased DNA damage was no longer detectable in the amygdala,
probably because of DNA repair.[45]
Buddhist monks who do compassion meditation have been shown to modulate their amygdala,
along with their temporoparietal junction and insula, during their practice.[46] In an fMRI study,
more intensive insula activity was found in expert meditators than in novices.[47] Increased activity
in the amygdala following compassion-oriented meditation may contribute to social connectedness.
[48]
Amygdala activity at the time of encoding information correlates with retention for that
information. However, this correlation depends on the relative "emotionalness" of the information.
More emotionally arousing information increases amygdalar activity, and that activity correlates
with retention. Amygdala neurons show various types of oscillation during emotional arousal, such
as theta activity. These synchronized neuronal events could promote synaptic plasticity (which is
involved in memory retention) by increasing interactions between neocortical storage sites and
temporal lobe structures involved in declarative memory.[49]

Rorschach test blot 03

Research using Rorschach test blot 03 finds that the number of unique responses to this random
figure links to larger sized amygdalae. The researchers note, "Since previous reports have indicated
that unique responses were observed at higher frequency in the artistic population than in the
nonartistic normal population, this positive correlation suggests that amygdalar enlargement in the
normal population might be related to creative mental activity."[50]

Neuropsychological correlates of amygdala activity

Early research on primates provided explanations as to the functions of the amygdala, as well as a
basis for further research. As early as 1888, rhesus monkeys with a lesioned temporal cortex
(including the amygdala) were observed to have significant social and emotional deficits.[51]
Heinrich Klüver and Paul Bucy later expanded upon this same observation by showing that large
lesions to the anterior temporal lobe produced noticeable changes, including overreaction to all
objects, hypoemotionality, loss of fear, hypersexuality, and hyperorality, a condition in which
inappropriate objects are placed in the mouth. Some monkeys also displayed an inability to
recognize familiar objects and would approach animate and inanimate objects indiscriminately,
exhibiting a loss of fear towards the experimenters. This behavioral disorder was later named
Klüver-Bucy syndrome accordingly,[52] and later research proved it was specifically due to
amygdala lesions. Monkey mothers who had amygdala damage showed a reduction in maternal
behaviors towards their infants, often physically abusing or neglecting them.[53] In 1981,
researchers found that selective radio frequency lesions of the whole amygdala caused Klüver-Bucy
syndrome.[54]
With advances in neuroimaging technology such as MRI, neuroscientists have made significant
findings concerning the amygdala in the human brain. A variety of data shows the amygdala has a
substantial role in mental states, and is related to many psychological disorders. Some studies have
shown children with anxiety disorders tend to have a smaller left amygdala. In the majority of the
cases, there was an association between an increase in the size of the left amygdala with the use of
SSRIs (antidepressant medication) or psychotherapy. The left amygdala has been linked to social
anxiety, obsessive and compulsive disorders, and post traumatic stress, as well as more broadly to
separation and general anxiety.[55] In a 2003 study, subjects with borderline personality disorder
showed significantly greater left amygdala activity than normal control subjects. Some borderline
patients even had difficulties classifying neutral faces or saw them as threatening.[56] Individuals
with psychopathy show reduced autonomic responses to instructed fear cues than otherwise healthy
individuals.[57] In 2006, researchers observed hyperactivity in the amygdala when patients were
shown threatening faces or confronted with frightening situations. Patients with severe social
phobia showed a correlation with increased response in the amygdala.[58] Similarly, depressed
patients showed exaggerated left amygdala activity when interpreting emotions for all faces, and
especially for fearful faces. This hyperactivity was normalized when patients were administered
antidepressant medication.[59] By contrast, the amygdala has been observed to respond differently
in people with bipolar disorder. A 2003 study found that adult and adolescent bipolar patients
tended to have considerably smaller amygdala volumes and somewhat smaller hippocampal
volumes.[60] Many studies have focused on the connections between the amygdala and autism.[61]
Studies in 2004 and 2006 showed that normal subjects exposed to images of frightened faces or
faces of people from another race will show increased activity of the amygdala, even if that
exposure is subliminal.[62][63] However, the amygdala is not necessary for the processing of fear-
related stimuli, since persons in whom it is bilaterally damaged show rapid reactions to fearful
faces, even in the absence of a functional amygdala.[64]

Sexual orientation
Recent studies have suggested possible correlations between brain structure, including differences
in hemispheric ratios and connection patterns in the amygdala, and sexual orientation. Homosexual
men tend to exhibit more feminine patterns in the amygdala than heterosexual males do, just as
homosexual females tend to show more masculine patterns in the amygdala than heterosexual
women do. It was observed that amygdala connections were more widespread from the left
amygdala in homosexual males, as is also found in heterosexual females. Amygdala connections
were more widespread from the right amygdala in homosexual females, as in heterosexual males.
[65][66]

Social interaction
Amygdala volume correlates positively with both the size (the number of contacts a person has) and
the complexity (the number of different groups to which a person belongs) of social networks.[67]
[68] Individuals with larger amygdalae had larger and more complex social networks. The
amygdala is responsible for facial recognition and allows others to respond appropriately to
different emotional expressions.[69] They were also better able to make accurate social judgments
about other persons' faces.[70] The amygdala's role in the analysis of social situations stems
specifically from its ability to identify and process changes in facial features. It does not, however,
process the direction of the gaze of the person being perceived.[71][72]
The amygdala is also thought to be a determinant of the level of a person's emotional intelligence. It
is particularly hypothesized that larger amygdalae allow for greater emotional intelligence, enabling
greater societal integration and cooperation with others.[73]
The amygdala processes reactions to violations concerning personal space. These reactions are
absent in persons in whom the amygdala is damaged bilaterally.[74] Furthermore, the amygdala is
found to be activated in fMRI when people observe that others are physically close to them, such as
when a person being scanned knows that an experimenter is standing immediately next to the
scanner, versus standing at a distance.[74][75]

Aggression
Animal studies have shown that stimulating the amygdala appears to increase both sexual and
aggressive behavior. Likewise, studies using brain lesions have shown that harm to the amygdala
may produce the opposite effect. Thus, it appears that this part of the brain may play a role in the
display and modulation of aggression.[76]

Fear
There are cases of human patients with focal bilateral amygdala lesions due to the rare genetic
condition Urbach-Wiethe disease.[77][78] Such patients fail to exhibit fear-related behaviors,
leading one, S.M., to be dubbed the "woman with no fear". This finding reinforces the conclusion
that the amygdala "plays a pivotal role in triggering a state of fear".[77]

Alcoholism and binge drinking

The amygdala appears to play a role in binge drinking, being damaged by repeated episodes of
intoxication and withdrawal.[79] [80]Protein kinase C-epsilon in the amygdala is important for
regulating behavioral responses to morphine, ethanol, and controlling anxiety-like behavior. The
protein is involved in controlling the function of other proteins and plays a role in development of
the ability to consume a large amount of ethanol.[81][82] The duration of chronic alcohol
consumption and abstinence may affect dynamic brain network adaptations. [80] When excessive
drinking occurs, the amygdala is affected through behavioral changes and reduces the brain's
plasticity. Brain plasticity is how our brain grows and develops; it is also how our neurons can make
connections with other neurons. This ultimately increases our neural pathways allowing us to
increase our knowledge of the world around us. When our brain plasticity decreases, it makes it
difficult for neurons to make connections to other neurons. Often when binge drinking, or
alcoholism occurs, our amygdala is affected and leads to behavior damage. These behavioral
damages can be lack of control, inability to conduct oneself in a mature manner, aggressive
behavior, loss of conduct, anxiety, depression, personality disorders, excessive drug intake, bi-polar
disorder, confusion, higher tolerance levels, irritability, and inappropriate sexual behaviors with
others and self. [83]

Anxiety
There may also be a link between the amygdala and anxiety.[84] In particular, there is a higher
prevalence of females that are affected by anxiety disorders. In an experiment, degu pups were
removed from their mother but allowed to hear her call. In response, the males produced increased
serotonin receptors in the amygdala but females lost them. This led to the males being less affected
by the stressful situation.
The clusters of the amygdala are activated when an individual expresses feelings of fear or
aggression. This occurs because the amygdala is the primary structure of the brain responsible for
fight or flight response. Anxiety and panic attacks can occur when the amygdala senses
environmental stressors that stimulate fight or flight response. The amygdala is directly associated
with conditioned fear. Conditioned fear is the framework used to explain the behavior produced
when an originally neutral stimulus is consistently paired with a stimulus that evokes fear. The
amygdala represents a core fear system in the human body, which is involved in the expression of
conditioned fear. Fear is measured by changes in autonomic activity including increased heart rate,
increased blood pressure, as well as in simple reflexes such as flinching or blinking.
The central nucleus of the amygdala has direct correlations to the hypothalamus and brainstem –
areas directly related to fear and anxiety. This connection is evident from studies of animals that
have undergone amygdalae removal. Such studies suggest that animals lacking an amygdala have
less fear expression and indulge in non-species-like behavior. Many projection areas of the
amygdala are critically involved in specific signs that are used to measure fear and anxiety.
Mammals have very similar ways of processing and responding to danger. Scientists have observed
similar areas in the brain – specifically in the amygdala – lighting up or becoming more active when
a mammal is threatened or beginning to experience anxiety. Similar parts of the brain are activated
when rodents and when humans observe a dangerous situation, the amygdala playing a crucial role
in this assessment. By observing the amygdalae's functions, it can determined why one rodent may
be much more anxious than another. There is a direct relationship between the activation of the
amygdala and the level of anxiety the subject feels.
Feelings of anxiety start with a catalyst – an environmental stimulus that provokes stress. This can
include various smells, sights, and internal sensations that result in anxiety. The amygdala reacts to
this stimuli by preparing to either stand and fight or to turn and run. This response is triggered by
the release of adrenaline into the bloodstream. Consequently, blood sugar rises, becoming
immediately available to the muscles for quick energy. Shaking may occur in an attempt to return
blood to the rest of the body. Apart from initiation of stress, long-term changes in amygdala neurons
may also increase anxiety after long-term or traumatic stress, led by the action of stress-related
hormones within the amygdala.[85] On the flip side, blocking the action of stress hormones in the
amygdala reduces anxiety.[86] A better understanding of the amygdala and its various functions
may lead to a new way of treating clinical anxiety.[87]

Posttraumatic stress disorder

There seems to be a connection with the amygdalae and how the brain processes posttraumatic
stress disorder. Multiple studies have found that the amygdalae may be responsible for the
emotional reactions of PTSD patients. One study in particular found that when PTSD patients are
shown pictures of faces with fearful expressions, their amygdalae tended to have a higher activation
than someone without PTSD.[88]

Bipolar disorder
Amygdala dysfunction during face emotion processing is well-documented in bipolar disorder.
Individuals with bipolar disorder showed greater amygdala activity (especially the
amygdala/medial-prefrontal-cortex circuit).[89][90]
Additional images

Frontal and side view of amygdala

Amygdala along with other subcortical regions, in glass brain.

Dorsal view of the amygdala in an average human brain

Frontal view of the amygdala in an average human brain

•
 Left lateral view of the amygdala in an average human brain

Amygdala highlighted in green on coronal T1 MRI images

Amygdala highlighted in green on sagittal T1 MRI images

Amygdala highlighted in green on transversal T1 MRI images

See also
• Accessory olfactory cortical areas
• Amygdala hijack
• BELBIC
• Intercalated cells of the amygdala
• List of regions in the human brain
• Triune brain
• Amygdalotomy
• Amygdalohippocampectomy
• S.M. (patient)

Left lateral view of the amygdala in an average human brain

 •

Amygdala highlighted in green on coronal T1 MRI images

Amygdala highlighted in green on sagittal T1 MRI images

Amygdala highlighted in green on transversal T1 MRI images

See also
• Accessory olfactory cortical areas
• Amygdala hijack
• BELBIC
• Intercalated cells of the amygdala
• List of regions in the human brain
• Triune brain
• Amygdalotomy
• Amygdalohippocampectomy
• S.M. (patient)

References