Neurobiology of Emotion

1. NEUROBIOLOGY OF EMOTIONS
By
Dr Sunil Suthar Under guidance of
Prof. Dr. Pradeep
Sharma

2. DEFINITION OF EMOTION
• 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
colours the person’s perception of the world.
• Affect meaning short-lived emotion, is defined as
the patient’s present emotional responsiveness.

3. Brain and emotion
• Brain is involved in perceptions and evaluation of
situations that give rise to emotions. The core
parts involved are
 CEREBRAL CORTEX
 LIMBIC SYSTEM-mainly amygdala
 Brain Stem

5. The Limbic System Concept
Paul MacLean popularized term “limbic system”
• Evolution of limbic system allows animals to experience and
express emotions beyond stereotyped brain stem behaviors
Forming a ring around corpus callosum: Cingulate gyrus, medial surface
temporal lobe, hippocampus

6. The Limbic System Concept
• The Papez Circuit(1937)
– Papez circuit of the brain is one of the major pathways of the limbic
system and is chiefly involved in the cortical control of emotion

7. The Limbic System Concept
• The Papez Circuit
-Hippocampus: Hypothesized to mediate behavioral expression
of emotion
Rabies infection: Hyperemotional responses -cytological
changes in hippocampal neurons
- Anterior thalamus Lesions lead to spontaneous laughing,
crying.
- Subcallosal cingulate gyrus has been implicated as playing
an important role in major depression and has been the
target of deep brain Stimulation to treat that depression.

8. The Limbic System Concept
• Difficulties with the Single Emotion System Concept
– Diverse emotions
– Many structures involved in emotion
• No one-to-one relationship between structure and
function
– Limbic system: Utility of single, discrete emotion system
questionable

9. The Amygdala and Associated
Brain Circuits
• Anatomy of the Amygdala

10. Deep superior
colliculus
Startle
Fear Potentiation
The Amygdala and AssociateBrain Circuits

11. Auditory fear
conditioning
Information about the
CS is integrated with
information about the
US within the amygdala.

12. The Amygdala and Associated
Brain Circuits
• The Amygdala - Fear and Agression (evidence)
Bilateral amygdalectomy reduces fear and aggression in all animals
tested.
Anger, sadness, and disgust may also be affected.
S.M. case study(dec1994): Inability to recognize fear in facial
expressions(Urbach Wieth Disease).
Electrical stimulation of amygdala -> Increased vigilance or
attention.
Fearful faces produce greater amygdala activity than happy/neutral
faces.

13. The Amygdala and Aggression
– Predatory Aggression—Attacks
Against different species for food
Few vocalizations; Attack head or neck
No activity in sympathetic division of ANS
– Affective aggression-For show
Used for show, not kill for food
High levels of sympathetic activity
Makes vocalizations; Threatening posture
The Amygdala and Associated
Brain Circuits

14. KLUVER-BUCY SYNDROME(1939)
-Due to b/l destruction of amygdaloid body and inf
temporal cortex
- Decreased agression(tameness)
-Increase in sexual activity
-Compulsive tendency to place objects in mouth.
-Decreased emotionality
-Changes in eating behavior
-Visual agnosia
In Humans caused by
Herpes and other Encephalitis
Cerebral trauma
Alzheimers and other Dementias
Niemann-Pick disease and CVA
The Amygdala and Associated
Brain Circuits

15. – Surgery to Reduce Human Aggression
Amygdalectomy results in -
• Reduced aggressive asocial behavior
• Increased ability to concentrate
• Decreased hyperactivity
Psychosurgery – last resort
The Amygdala and Associated
Brain Circuits

16. The Amygdala and Associated
Brain Circuits
In Schizophrenic patient –
Exposure to scary face – amygdala not activated.
Exposure to neutral face – inappropriate hyperactivation of
amygdala.
Schizophrenic patient often have impairements in ability to identify and
interpret emotional stimuli. The neurobiological explanation for this may be
inefficient information processing with in Ventral system.
 Consistently in fMRI and PET studies, with emotionally valenced pictures,
faces, and odors, patients showed diminished activation in limbic and paralimbic
regions, especially the amygdala.
• Aggressive symptoms- orbitofrontal cortex and amygdala

17. HYPOTHALAMUS
• The Hypothalamus and Aggression (evidence)-
 Removal of cerebral hemispheres but not
hypothalamus -> sham rage
 This Behavior reversed with small lesions in
hypothalamus.

18. HYPOTHALAMUS
• The Hypothalamus and Aggression (Cont’d)
– Flynn, 1960s
Elicited affective aggression by
stimulation medial hypothalamus
Predatory aggression elicited by
stimulating lateral hypothalamus

19. PREFRONTAL CORTEX
 Emotional symptoms such as happiness and sadness are regulated by prefrontal
cortex and amygdala.
 Left prefrontal cortex appears to lift the mood.
 Activation of the right prefrontal cortex causes depression.
 Lesion to the right prefrontal area may produce laughter, euphoria, and moria or
witzelsucht, a tendency to joke and make puns.
 In treating depression, rTMS therapy targets the area left dorsolateral prefrontal
cortex (DLPFC). The DLPFC is readily accessible to the magnetic field and is highly
interconnected with limbic structures, which plays a dominant role in mood
modulation and major depression.

21. Autonomic nervous system

22. Autonomic nervous system controls physiological arousal
Sympathetic
division (arousing)
Parasympathetic
division (calming)
Pupils dilate EYES Pupils contract
Decreases SALVATION Increases
Perspires SKIN Dries
Increases RESPERATION Decreases
Accelerates HEART Slows
Inhibits DIGESTION Activates
Secrete stress
Hormones
(EMERGENCY
REACTION)
ADRENAL
GLANDS
Decrease secretion
of stress hormones
(RELAXATION RESPONSE)

23. • Vagus nerve stimulation (VNS) for treatment-resistant depressions-
Little is understood about exactly how vagal nerve stimulation modulates
mood but proposed mechanisms include alteration of norepinephrine release by
projections of solitary tract to the locus coeruleus, elevated levels of
inhibitory GABA related to vagal stimulation and inhibition of aberrant cortical
activity by reticular system activation.
Autonomic nervous system controls physiological arousal

24. AUTONOMIC&ENDOCRINE RESPONSES TO EMOTION
 Limbic stimulation causes changes in respiration & blood pressure
 Hypothalamic autonomic responses are triggered by a complex phenomenon mediated
by the cortical and limbic structures.
 The fear and rage responses mediated by the limbic system cause stimulation of
various parts of the hypothalamus, especially the lateral areas and produce diffuse
sympathethic Discharge.
 The physical symptoms of panic attacks can be reproduced by Carbon dioxide,
Yohimbine, and Caffeine and Epinephrine administration.
 The massive sympathetic discharge during stress is called the flight or fight response“.
Stress via cortical and limbic connections causes release of corticotropin-releasing
hormone (CRH) from the paraventricular nuclei of the hypothalamus. CRH release
mediates endocrine and immune response

25. 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.
 Hippocampus is critical for long-term,declarative memory storage
 Propranolol impairs memory for emotionally provocative story but not for
emotionally neutral story.

26. Chemical Neurotransmitters involved
in Emotions
• Monoamine neurotansmitters – Norepinephrine,
Serotonine, Dopamine.
• Aminoacid transmitters – GABA, Glutamate.
• Peptide neurotransmitters – CRH, Neuropeptide Y,
Substance P, Opioid.

27. Serotonergic System
• Neurotransmitter Serotonin
– Serotonergic raphe neurons
project to the hypothalamus
and limbic structures via the
medial forebrain bundle
– Serotonin turn-over
aggression in rodents
– Drug PCPA blocks serotonin
synthesis aggression

28. Serotonergic System
 5HT 1A receptor knock out mice show a marked elevation of anxiety and fear
behaviour.
 Postsynaptic 5HT 1A receptor gene expression is under tonic inhibition by adrenal
steroids.
 Downregulation of 5HT 1A receptor in response to chronic stress.
 Upregulation of 5HT 2A receptor during chronic stress
.
 Chronic administration 5HT 1A receptor partial agonist and 5HT 2A receptor antagonist
exert anxiolytic effect.
 5HT 1A receptor agonist and 5HT 2A receptor antagonist decrease rodent aggression.
 Drugs such as Risperidone actually have more antagonist effect at 5HT 2A receptors
than D2 receptors.
 Depressed patient have reduced concentration of serotonine metabolite 5-HIAA in CSF.

29. Noradrenergic System
 Norepinephrine (NE) released primarily from locus coeruleus(LC) which
located in pons.
 Exposure to acute stress/fear results in increase in NE in LC,
hypothalamus, hippocampus, amygadala, and cerebral cortex.
 Repeated exposure to stress/chronic stress- decreased release of NE in LC.
(learned helplessness)
 Patients with PTSD and panic disorder show evidence of increased NE
activity.
 Mice lacking Alpha-2 adrenergic receptors have hightened autonomic
activation and concomitant anxiety behaviour.

30. Corticotropin relasing hormone (CRH) system
 Central nucleus of amygdala contains CRH.
 Axons of central nucleus cells target locus coeruleus neurons (which have
CRH receptors and contain NE).
 In animal administration of CRH in cerebral ventricles effectively induces
anxiety responses, including hypervigilance, enhancement of the freezing
posture, and decreased exploration in unfamiliar situations.

31. γ-Amino Butyric Acid and the Benzodiazepine System- Role of
GABA and benzodiazepine receptors in anxiety is well documented in animal
studies.
Several studies of panic disorder patients have shown reduced GABA-A and
benzodiazepine binding, using PET and SPECT imaging, in areas such as the cortex,
hippocampus, and insula when compared to controls.
Dopaminergic System- Inhibition in nucleus accumbens dopamine activity
results in abnormalities in motivation and reward mechanisms.
Glutamate system- NMDA receptors are prominently involved in the
conditioning of fear learning.
Blockade of the NMDA receptor with antagonists such as APV can block fear
acquisitions, and some studies show that it may even block expression.
.

32. Neuropeptide Y- NPY has anxiolytic effects.
NPY has been shown to be involved in fear consolidation, with
preclinical studies showing that the administration of NPY impairs the
retention of traumatic memories and reduces anxiety during stressful
tasks
 Recently it has been observed that the neuropeptide cholecystokinin
(CCK) is involved in panic disorders.(antagonists of CCK-B receptor have
anxiolytic effect).

33. Concluding Remarks
• Neural Pathways
 Experience, expression of emotion involves widespread activity in the
nervous system from cortex to ANS as well as: limbic structures,
hypothalamus, amygdala
 Structures involved in emotions have other functions, including
learning and memory

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