This document provides an overview of the neurobiology of emotions. It discusses the history of theories of emotion, key brain structures involved in emotion regulation like the limbic system and its components, and functional circuits in the brain that mediate emotional responses. Specific neurotransmitter systems and how hormones like cortisol are involved in emotions like depression are also summarized. The limbic system, including structures like the amygdala, hippocampus and hypothalamus play important roles in emotional processing and expression. Circuits like the Papez circuit are involved in emotional memory and learning.

1. NEUROBIOLOGY OF EMOTIONS
Chaired by
Dr.Ramachandrankutty & Dr. Pratheesh
Presented by
Dr. Sherlyn E. Mammen

2. Overview
Emotion: definition & history
Theories of emotions
Neuro-anatomical structures
Limbic system: structure and functions
Functional circuits of emotions
Other systems in emotion regulation
Symptoms and circuits in depression
Symptoms and circuits in mania
Conclusion

3. HISTORY
ARISTOTLE: People are thinking animals
ROUSSEAU: Emotions are what makes
people special and gives us a reason for
living
HIPPOCRATES: Brain is the site of emotions
Emotion : Latin word EMOVERE = To stir up
or get agitated

4. PHINEAS GAGE (Sept 13,1848)

5. Definitions
• Emotion is a stirred-up state caused by
physiological changes occurring as a response
to some event and which tends to maintain or
abolish the causative event
Mood is a pervasive and sustained emotion
that colors the person’s perception of the world
Affect meaning short-lived emotion, is defined
as the patient’s present emotional
responsiveness

6. OVERVIEW OF EMOTION
2 COMPONENTS
MENTAL
PHYSICAL
EMOTION INVOLVES
COGNITION
AFFECT
CONATION
PHYSICAL CHANGES: HYPERTENSION,
TACHYCARDIA, SWEATING

7. BASIC EMOTIONS
BY EKMAN
HAPPINESS
SADNESS
FEAR
ANGER
SURPRISE
DISGUST
THESE COMBINE TO YIELD OTHER
COMPLEX EMOTIONS

8. Theories of emotion
• James-Lang theory
• Cannon-Bard theory
• Schachter-Singer theory
• Current Theory

9. James lange theory
• An emotional event
causes response in ANS
• This response is detected
by CNS to produce an
emotional experience
• Different emotional stimuli
produces different bodily
response and lead to
different emotions

10. Cannon-Bard Theory
• Emotional stimuli
simultaneously produce
a response in the ANS
and in the cerebral
cortex
• The emotional
experience is the
combination of these
two systems

11. Schachter-Singer theory
• Cognitive arousal theory
• A two-stage theory stating that for an emotion
to occur, there must be (1) physiological
arousal and (2) an explanation for the arousal
• Emotions are produced when autonomic
arousal is noticed by the person. He/She tries
to come up with an explanation for the arousal
and depending on the explanation, label their
emotion.

13. Current Theory
• No single neural system produces emotions
• Different emotions may depend on different
neural circuits, but many of these circuits
converge in the same parts of the brain
• Emotion results from the interplay between:
The amygdala, hypothalamus,
brain stem & ANS

14. BRAIN STRUCTURES THAT MEDIATE
EMOTIONS
Brain is involved in perceptions and evaluation of
situations that give rise to emotions
PFC & ACC
Hypothalamus
Limbic system
• Brainstem

15. VARIATIONS IN HEMISPHERE
DOMINANCE IN EMOTIONS
• L : dominant for positive emotions
• R : dominant for negative emotions
• R : dominant for emotional expression
• L : dominant for language
• R : dominant for emotion related cues like
facial expression, body posture and prosody

16. Prefrontal Cortex
Represents goals and appropriate responses to
obtain these goals
Left sided PFC activation increases goal directed
activities
Right sided PFC activation causes avoidance
behavior
Lesion to the right PFC: laughter, euphoria, and
moria or witzelsucht, a tendency to joke and
make puns
 In treating depression, rTMS therapy targets the
left DLPFC

17. Automatic & voluntary control of
emotions
• Voluntary control
lateral prefrontal cortical
system, DL & VL PFC
• Automatic control
medial PFC ( OFC, ACC,
DM PFC)

25. Anterior cingulate cortex
VENTRAL PART: connects
PFC with limbic system
Contains N. Accumbens of
the reward system
DORSAL PART: emotional
processing and
appropriate responses to
stimuli

26. HYPOTHALAMUS
Part of Diencephalon which lies below the
thalamus
Forms the floor and lower parts of the lateral
walls of the 3rd ventricle
Mainly acts through 3 systems
ANS ,endocrine system and the limbic
system

27. BOUNDARIES
 Anteriory:
lamina terminalis ( extends from
the optic chiasma to the
ant.commissure)
 Posteriorly: subthalamus
 Inferiorly:
structures in the floor of the 3rd
ventricle.ie, tuber cinereum,
infundibulam and mammillary bodies
 Superiorly: thalamus
 Lateral boundary: internal capsule
 Medially bounded by the cavity of
3rd ventricle

28. Antero_posteriorly divided
into
 PREOPTIC region_ area
adjoining the lamina
terminalis
 SUPRAOPTIC region
__above the optic
chiasma
 TUBERAL region
includes the tuber
cinereum,infundibulam
and area around it
 MAMMILLARY region_
includes the mammillary
bodies and area around
it
Subdivisions of hypothalamus

30. AFFERENT CONNECTIONS OF
HYPOTHALAMUS

31. EFFERENT CONNECTIONS

32. Limbic system history
 Paul Pierre Broca in 1878 described
The Great Limbic lobe or ‘le grand
lobe limbique’
In 1937 James Papez wrote a paper
called ‘proposed mechanism of
emotion’ which elaborated it’s
putative role in emotion
In 1952 Paul Mclean coined the term
“limbic system”

33. Evolution of limbic system allows animals to
experience and express emotions beyond
stereotyped brain stem behaviors
The cortical and subcortical structures
forming a ring around the brainstem

34. LIMBIC SYSTEM
COMPONENTS
Limbic Cortex
Cingulate gyrus
Parahippocampal gyrus
Hippocampal Formation
Dentate gyrus
Hippocampus
Subicular complex
Amygdala
Septal area
Hypothalmus
Mamillary body
Ant. Nucleus of thalamus

40. LIMBIC LOBE
 2 concentric gyri surrounding
the corpus callosum
 Outer larger gyrus ‘limbic
gyrus- consists of isthmus of
cingulate gyrus,
parahippocampal gyrus and
subcallosal area
 Inner smaller ‘intralimbic
gyrus’
 Enthorhinal complex(ERC)
which funnels highly
processed cortical
information to hippocampal
formation. Major output
pathway

41. Cerebral association area for control of behavior
Two way communication and association linkage
between the neocortex and lower limbic
structures
Essentially all behavioural patterns can be
elicited by specific portions of the limbic cortex
Ablation of some limbic cortical areas can cause
persistent changes in an animal’s behavior
Limbic lobe

42. HIPPOCAMPAL FORMATION
Hippocampus, dentate gyrus,
subiculum and entorhinal cortex
makes the hippocampal formation
Associated with long term memory

44. Fibers from the entorhinal
area, dentate gyrus,
ammon’s horn and subiculum
The three primary pathways
are the perforant pathway,
mossyfibers and Schaffer
collaterals
The alvear pathway, has
been questioned, from the
entorhinal area to ammon’s
horn
INTERNAL CIRCUITS

45. HIPPOCAMPUS
 Sea horse in Greek
4 fields: CA1,CA2, CA3, CA4
The thin layer of fibers adjacent
to the polymorphic layer of the
hippocampus is known as the
alveus
These fibers coalesce to form
the fimbria.

46. Hippocampus
Learning & memory
Emotional or contextual learning
Fear conditioning
Inhibitory regulation of HPA axis activity

47. DENTATE GYRUS
3 layered- outer acellular
molecular, granular middle
and inner polymorphic layer
Formation of new episodic
memories, spontaneous
exploration of novel
environments
High rates of neurogenesis

48. SUBICULAR COMPLEX
Most inferior component
Lies between the entorhinal cortex and CA1 subfield of the
hippocampus
Believed to play a role in human epilepsy
Also implicated in working memory and drug addiction
Suggested that dorsal subiculum is involved in spatial
relations and ventral subiculum regulates the HPA axis

49. AMYGDALA
 Almond shaped structure
deep within temporal lobe
Lies at the ant. end of the
hippocampal formation and
ant. Tip of inferior horn of
the lateral ventricle
Consists of 14 nuclei
Window of the limbic system

51. Functions of amygdala
 Behavioral awareness
Project into the limbic system one's current
status in relation to both surroundings and
thoughts
Make the person’s behavioral response
appropriate for each occasion

52. Bilateral amygdalectomy reduces fear and
aggression in all animals
Electrical stimulation of amygdala: increased
vigilance or attention
Fearful faces produce greater amygdala
activity than happy faces

53. Case S.M

S.M., is a female patient first described in 1994

Had exclusive and complete bilateral amygdala
destruction since late childhood as a consequence of
an extremely rare genetic condition known as Urbach–
Wiethe disease

She has little to no capacity to experience fear in her
life, "woman with no fear"

S.M. has been studied extensively in scientific
research, and has helped researchers to elucidate the
function of the amygdala

54. MAMMILLARY BODIES
Act as a relay for impulses
coming from the amygdalae
and hippocampi via the
mamillo-thalamic tract to
the thalamus
They are involved with the
processing of memory &
add the element of smell to
memories.

56. ANTERIOR THALAMIC NUCLEUS
Collection of nuclei at rostral end of the
dorsal thalamus
 Receive afferents from mammillary bodies
and subiculum
Project to the cingulate gyrus
Play a role in modulation of alertness,
learning and memory

58. FUNCTIONAL CIRCUITS OF EMOTION

59. PAPEZ CIRCUIT
 James Papez’s delineation of a circuit
unravelled the basis of cortical control of
emotion
Recent studies show that it has a more
significant role in memory functions than in
emotions
Papez circuit was later modified by American
neuroscientist and physician Paul D

60. He proposed that emotional expression is
organized in the hippocampus
experienced in the cingulate gyrus and
expressed via the mammillary bodies
The hypothalamus was considered to be the
site where hippocampal processes gain
access to the autonomic outflow that controls
the peripheral expression of emotional states

61. The original circuit proposed by Papez is shown by thick lines and
more recent connections as proposed by Paul D Mac Lean are shown
by thin lines

62. Cerebral cortex and limbic system

63. Basal ganglia and limbic system

64. Amygdala, hypothalamus and
cortex

65. EMOTIONAL RESPONSES
 FEAR: fear responses are produced by the
stimulation of the hypothalamus and amygala.
Amygdala is also involved in fear learning.
Amygdala destruction abolishes fear and its
autonomic and endocrine responses.
RAGE AND PLACIDITY: Rage reponses to minor
stimuli are observed after removal of the
neocortex. Destruction of the the ventromedial
hypothalamic nuclei and septal nuclei also
induces rage.

66. AUTONOMIC AND ENDOCRINE
RESPONSES TO EMOTION
The stimulation of the cingulate gyrus and
hypothalamus can elicit autonomic responses
The fear and rage responses mediated by the limbic
system cause stimulation of various parts of the
hypothalamus, produce diffuse sympathetic
discharge; fight or fright response
Stress via cortical and limbic connections causes
release of CRH from the paraventricular nuclei of
the hypothalamus

67. Emotional memory
• Emotion has powerful influence on learning and
memory
• Amygdala, in conjunction with prefrontal cortex
&medial temporal lobe, is involved in
consolidation and retrieval of emotional
memories
• Amygdala, prefrontal cortex and hippocampus
are also involved in the acquisition, extinction
and recovery of fears to cues and contexts

69. Neurotransmitters in emotions
Monoamine neurotansmitters –
Norepinephrine, Serotonine, Dopamine
Aminoacid transmitters – GABA, Glutamate
Peptide neurotransmitters – CRH,
Neuropeptide Y, Substance P, Opioids

72. SEROTONIN DOPAMINE

73. NOR ADRENALINE

75. ACETYLCHOLINE

76. GABA
• GABA have inhibitory effect on ascending
monoamine pathways
• Reductions in GABA observed in plasma, CSF
and brain areas in depression
• GABA receptors up regulated by
antidepressants
• Some GABAergic medications have weak
antidepressant effects

77. GLUTAMATE
• Excess glutamate- neurotoxic effects
• Drugs antagonizing NMDA receptors
(ketamine) may have antidepressant effects
• Abnormalities in G-protein signalling/ second
messenger system dysregulation

78. NEUROPEPTIDES
Opioids :
• Placebo controlled studies – No significant
antidepressant efficacy
• Continued interest in use of opioid
antagonists in Rx of refractory depression
Neuropeptide Y
• Dec CSF level in major depression
• Neg correlation b/w levels of NPY and rating
of anxiety in depressed pts.
• NPY levels in cortex increased by imipramine
& ECT.

79. Endocrine systems
• HPA activity
• Thyroid axis
activity
• Growth hormone
• Prolactin

80. HPA AXIS
1. Pts with MDD have cortisol in plasma, CSF & urine
2. Pts with MDD show resistance to normal suppression of
cortisol and corticotropin secretion by dexamethasone
3. Depressed pts have CSF CRH
4. Adrenal gland hypertrophy and increased sensitivity to
CRH may be a reversible state marker of depression.

81. Dexamethasone suppression test
• Detects resistance to glucocorticoid mediated
feedback
• Diagnostic marker of MDD
• 1mg of dexa at 11pm, blood drawn at 4pm &
11pm next day
• High plasma cortisol level(5gm/dl) assoc with
MDD
• Degree of nonsuppression correlated with
severity of depression

82. HPA axis
• Increased activity in the HPA axis in depression
is viewed as the “most venerable finding in all of
biological psychiatry” (Nemeroff , 1998)
• CRH is hypersecreted in depression (Nemeroff,
1992, 1998)
• HPA normalization precedes clinical recovery
and return to abnormal HPA precedes clinical
relapse – suggest that HPA dysregulation is not a
result of depression

83. Thyroid axis activity
• Depression : low levels of circulating thyroid
hormone, elevated basal TSH level, increased
TSH response to TRH, elevated anti- thyroid
antibody levels
• 20 to 30% of depressed patients have blunted
TSH response to TRH challenge • Blunted TSH
response is evidence of an increased risk of
relapse
• Blunted TSH response to TRH does not
normalize with effective treatment

85. IMMUNOLOGICAL HYPOTHESIS

86. BDNF HYPOTHESIS

87. NEURONAL PLASTICITY
• Brain mechanisms for adaptation to stress
plays fundamental role in the
pathophysiology of mood disorders
• Antidepressants & mood stabilizers act by
targeting these processes
• In mammalian hippocampus neuronal
arborization & formation of new neurons are
decreased by stress & increased by 5HT
and NE

88. 2nd
messenger system hypothesis
• Altered platelet phosphatidyl inositol
• Abnormal intracellular calcium metabolism
Electrolyte abnormalities
• Intracellular sodium is increased in mania &
depression and normalizes with recovery
• Decreased sodium pump in RBCs & increased
intracellular calcium in WBC and platelets

89. Kindling effect
• Like seizures, mood episodes can occur without
obvious triggers, and have fairly abrupt
beginnings and endings
• Initial stress---mood episodes----episodes beget
episodes—frequency increases/ worsens

90. Sleep changes
• Impaired sleep continuity and duration
• Decreased stage 3 and 4 sleep
• Decreased REM latency
• Increased proportion of REM sleep in
the early part of the night
• Decreased REM latency may persist &
indicate a vulnerability to relapse

91. CIRCUITS IN DEPRESSION

99. CIRCUITS IN MANIA

106. PET SCAN IMAGES

107. OVERVIEW OF NEUROBIOLOGY OF
EMOTIONS

108. REFERENCES
• Kaplan and Saddock’s Comprehensive text book of
psychiatry 9th
edition
• Stephen M. Stahl’s Essential psychopharmacology 4th
edition
• Shorter oxford text book of psychiatry 6th
edition
• Allan Tassman’s Psychiatry 4th
edition