Upload
aryanarayanan06
View
219
Download
2
Embed Size (px)
Citation preview
NEUROBIOLOGY OF EMOTIONSChaired by Dr.Ramachandrankutty & Dr. PratheeshPresented by Dr. Sherlyn E. Mammen
Overview Emotion: definition & historyTheories of emotionsNeuro-anatomical structuresLimbic system: structure and functionsFunctional circuits of emotionsOther systems in emotion regulationSymptoms and circuits in depressionSymptoms and circuits in maniaConclusion
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
PHINEAS GAGE (Sept 13,1848)
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
OVERVIEW OF EMOTION2 COMPONENTSMENTALPHYSICAL
EMOTION INVOLVESCOGNITIONAFFECTCONATIONPHYSICAL CHANGES: HYPERTENSION,
TACHYCARDIA, SWEATING
BASIC EMOTIONSBY EKMANHAPPINESSSADNESSFEARANGERSURPRISEDISGUSTTHESE COMBINE TO YIELD OTHER
COMPLEX EMOTIONS
Theories of emotion• James-Lang theory
• Cannon-Bard theory
• Schachter-Singer theory
• Current Theory
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
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
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.
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
BRAIN STRUCTURES THAT MEDIATE EMOTIONSBrain is involved in perceptions and evaluation of
situations that give rise to emotions
PFC & ACC
Hypothalamus
Limbic system
• Brainstem
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
Prefrontal CortexRepresents 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
Automatic & voluntary control of emotions
• Voluntary control lateral prefrontal
cortical system, DL & VL PFC
• Automatic control medial PFC ( OFC, ACC,
DM PFC)
Anterior cingulate cortexVENTRAL PART: connects
PFC with limbic system Contains N. Accumbens
of the reward system
DORSAL PART: emotional processing and appropriate responses to stimuli
HYPOTHALAMUSPart 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
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
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
AFFERENT CONNECTIONS OF HYPOTHALAMUS
EFFERENT CONNECTIONS
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”
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
LIMBIC SYSTEMCOMPONENTSLimbic CortexCingulate gyrus Parahippocampal gyrusHippocampal Formation Dentate gyrus Hippocampus Subicular complex AmygdalaSeptal area Hypothalmus Mamillary body Ant. Nucleus of thalamus
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
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
HIPPOCAMPAL FORMATION
Hippocampus, dentate gyrus, subiculum and entorhinal cortex makes the hippocampal formation
Associated with long term memory
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
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.
Hippocampus Learning & memory
Emotional or contextual learning
Fear conditioning
Inhibitory regulation of HPA axis activity
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
SUBICULAR COMPLEXMost 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
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
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
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
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
MAMMILLARY BODIESAct 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.
ANTERIOR THALAMIC NUCLEUSCollection 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
FUNCTIONAL CIRCUITS OF EMOTION
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
He proposed that emotional expression is organized in the hippocampusexperienced 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
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
Cerebral cortex and limbic system
Basal ganglia and limbic system
Amygdala, hypothalamus and cortex
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.
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
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
Neurotransmitters in emotions
Monoamine neurotansmitters – Norepinephrine, Serotonine, Dopamine
Aminoacid transmitters – GABA, Glutamate
Peptide neurotransmitters – CRH, Neuropeptide Y, Substance P, Opioids
SEROTONIN DOPAMINE
NOR ADRENALINE
ACETYLCHOLINE
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
GLUTAMATE
• Excess glutamate- neurotoxic effects
• Drugs antagonizing NMDA receptors (ketamine) may have antidepressant effects
• Abnormalities in G-protein signalling/ second messenger system dysregulation
NEUROPEPTIDESOpioids :• 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.
Endocrine systems
• HPA activity
• Thyroid axis activity
• Growth hormone
• Prolactin
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.
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
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
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
IMMUNOLOGICAL HYPOTHESIS
BDNF HYPOTHESIS
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
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
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
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
CIRCUITS IN DEPRESSION
CIRCUITS IN MANIA
PET SCAN IMAGES
OVERVIEW OF NEUROBIOLOGY OF EMOTIONS
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