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Limbic system
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LIMBIC SYSTEM
PRESENTER : Dr.D. ARCHANAACHAIRPERSON : Dr. SIDDHARTH
History Paul Broca (1824-1880):
1878: “le grand lobe limbique”Refers to a ring of gray matter on the medial
aspect of the cerebral hemispheres.
James Papez (1883-1958):1930’s: defined a limbic system that might underlie the relationship between emotion and memory (Papez’ circuit).
JAMES PAPEZ (1883-1958)
PAUL BROCA (1824-1880)
NEUROANATOMY
Components Limbic cortex a) Cingulate Gyrusb) Parahippo campal Gyrus
Hippo campal formationa) Dentate Gyrusb) Hippo campusc) Subicular complex
Amygdala Septal area Hypothalamus
LIMBIC CORTEXCingulate gyrusParahippocampal gyrusCingulumHeavily connected to association corticesEntorhinal cortex – connections with hipocampus
Cingulate cortex• Located medial to corpus callosum• Has five layers of cells (distinct from neo-cortex)• Important influences on attention, response selection, &emotion; part of neural pathway for memory (LeBar &
Cabeza,2006; Lezak, 2004)• Detects error and conflict during information processingin conjunction with prefrontal cortex (Cohen et al., 2000)• Anterior cingulate receives projections from amygdala,whereas posterior cingulate receives projections fromhippocampus (Lezak, 2004)
SEPTAL AREAGray matter structure immediately above anterior commissureReciprocally connected with hippocampus , amygdala and
hypothalamusProjects to brain stem
HIPPOCAMPUS
HIPPOCAMPAL FORMATIONDentate gyrus HippocampusSubicular complexC shaped appearance 3 layered structures – outer molecular, intermediate
granular, inner polymorphic.Hippocampus – cytoarchitecture and connectivity – CA 1-
4.
• Three layers, including superficial molecular and deeppolymorphic layer• Intermediate striatum is granule cell layer in dentategyrus and pyramidal cell layer in hippocampusMolecular Layer: continuous over the dentate gyrus,hippocampus and entorhinal cortex.Pyramidal Layer : layer of axons and interneurons,
similar to layer 6 of the neocortex
Cont.Subicular complex – transition region between
hipocampus and parahippocampal gyrusMajor output pathway is fornixAlso serves as major input pathway from septal area and
amygdala
Amygdala
K. F. Burdach’s term
Amygdala Large nuclear group in temporal lobe. Afferents:
Olfactory tractSolitary nucleusParabrachial nucleusLimbic neocortex:
Cingulate gyrusParahippocampal gyrus
Regions of the Amygdala Large basolateral region:
Provides direct input to basal ganglia and motor system.
Small corticomedial group of nuclei:Related to olfactory cortex.
Medial and central nuclei:Connected to hypothalamus.
Hypothalamus Anatomy• Lines the walls of 3rd
ventricle, above the pituitary.
• Divided into medial and lateral regions by the fornix, bundles of fiber tracts that connect the hippocampus to the mamillary bodies.
HYPOTHALAMUS3 ZONES Supra optic , tuberal, and mammillary regionsMedial and lateral by fornix Supra optic region – SON, PVN, SCN, PRON.Tuberal region – ventromedial and arcuate nucleiMammillar region – posterior nucleus and mammillary
body
Hypothalamic Cell Group
Hypothalamic region Periventricular zone Medial zone Lateral zone
Anterior Preoptic Preoptic nucleus Medial preoptic nucleus
Lateral preoptic nucleus
Periventricular nucleus
Supraoptic Suprachiasmatic Anterior hypothalamic Lateral hypothalamic
Periventricular nuclei Paraventricular nucleus
Supraoptic nucleus
Middle Infundibular Arcuate Dorsomedial Lateral tubular
Ventromedial Lateral hypothalamic
Posterior Mamillary Mamillary Lateral hypothalamic
Posterior hypothalamic
NEUROPHYSIOLOGY
FUNCTIONSCingulate gyrus : autonomic function regulating heart rate
and blood pressure as well as cognitive , emotional and attentional processing
Parahippocampal gyrus : spatial memoryHippocampus : long term memoryAmygdala : anxiety, agression, fear conditioning,
emotional memory and social cognitions
Hypothlamus : regulates the autonomic nervous system via hormone production and release, secondarily affects and regulates blood pressure, heart rate, hunger , thirst, sexual arousal and circadian rhythm sleep/wake cycle
Mammilary body: memoryNucleus accumbens : reward, addiction
Functions “Emotional brain
Emotional and motivational aspects of behavior.
Provides emotional component to learning process:
Especially the amygdala. Associated with memory
Especially the hippocampus. Associated with pain/pleasure, rage
FUNCTIONAL CIRCUITS
Connections of Hippocampal Formation
1. Intrinsic Connectionsclassic trisynaptic pathway
2. Afferent Connections perforant and alveolar path
3. Efferent Connections fornix
Intrinsic Connections
Classic Trisynaptic Pathway1. Entorhinal cortex (perforant path) dentate gyrus granular cell
2. Granular cell axon (mossy fiber) CA3 pyramidal cell
3. Pyramidal cell (Schaffer
collateral) CA1 pyramidal cell
subiculum entorhinal cortex
Hippocampal formation cont..Intrinsic neural circuit of HF
ERC
Dentate Gyrus
CA3
CA1
Subicular Complex
Afferent Connections
From Entorhinal Cortex
Alveolar Path from medial part of EC to CA1 and Subiculum
Perforant Path from lateral part of EC to CA1, CA2, CA3 and Dentate Gyrus
Efferent Connections
Fornix - from pyramidal neurons of hippocampus & subiculum - 1.2 million fibers in humans
Postcommissural Fornix – main bundle to Mammillary Body Anterior Thalamus Lateral Septal Nuclei
Hypothalamus Midbrain Tegmentum
Circuits Of Hippocampal Formation and Anterior Thalamus
Association Cortices [orbital/Temporal]
Cingulate Cortex
Ento Rhinal Cortex
Hippo Campal Formation
Hypothalamus and Septal Area
Brain Stem and Spinal Cord
Anterior Thalamus
Fornix
MTT
alveolar path
perforant path
Entorhinal Cortex(Area 28)
HippocampalFormation
MammillaryBody
CingulateGyrus
AnteriorThalamic Nuclei
mammillothalamic tract
fornix
cingulum
thalamocortical radiation
Papez Circuit
Functions of the Amygdala Relate environmental stimuli to coordinated behavioral
autonomic and endocrine responses seen in species-preservation.
Responses include:Feeding and drinkingAgnostic (fighting) behaviorMating and maternal careResponses to physical or emotional stresses.
Circuits Of AmygdalaPrefrontal and
Temporal Association Cortices
AmygdalaMedial Dorsal
Thalamus
Hypothalamus and Septal Area
Brain Stem and Spinal Cord
V
SV
S=Stria Terminalis
V=Ventral Amygdalo Fugal Pathway
Circuits Of AmygdalaPrefrontal and Association Cortex
Hippocampus and Amygdala
Medial Dorsel Thalamus
Ventral Pallidum Ventral Striatum
Baso Lateral circuitDorsomedial N of
ThalamusOFC
Amygdala Anterior Temporal Cortex
V
V = Ventral Amygdalo Fugal Pathway
Hypothalamus: Integrative Functions
• The hypothalamus helps regulate five basic physiological needs:1) Controls blood pressure and electrolyte (drinking and salt
appetite).2) Regulates body temperature through influence both of the
autonomic nervous system and of brain circuits directing motivated behavior (e.g. behavior that seeks a warmer or cooler environment).
3) Regulates energy metabolism through influence on feeding, digestion, and metabolic rate.
4) Regulates reproduction through hormonal control of mating, pregnancy and lactation.
5) Directs responses to stress by influencing blood flow to specific tissues, and by stimulating the secretion of adrenal stress hormones.
Hypothalamus: Inputs and OutputsNeural Output Hormonal
Output
Neural Input Controls the autonomic nervous system (e.g. emotion)
Controls release of oxytocin for milk lactaction
Hormonal Input Used for drives and motivated behavior
Controls release of vasopressin for fluid regulation
Hypothalamic area/nucleus
Effects of Stimulation Effects of Lesion
Supra optic area Release of ADH DI
Paraventricular Release of oxytocin
Pre optic sweating, heat loss,cutaneous vasodilatn
hyperthermia
Suprachiasmatic medial hypothalamic area
Secretion of hypo physiotropic hormones
Various endocrine deficiency
Ventro medial nucleus Cessation of eating,placidity
Voracious eating,obesity,aggression
Lateral hypothalamic area Voracious eating Wt loss
Posterior HT area Cutaneosvasoconstriction, rage,piloerection
Loss of thermo regulation
Axons of olfactory neurons
Olfactory Receptors
OlfactoryBulb(mitral & tufted)
Piriform Cortex(Primary olfactory cortex)
Entorhinal Cortex
Amygdala
Olfaction
Amygdala lesions lack of food choice (appetite)
Amygdala emotional modulation of food intake
Hypothalamus
Lateral nucleus -feeding centre
VM nucleus satiety- centre
Appetite and Feeding
Behavioral changes of maintenance of self (appetites)
PET and fMRI Limbic activity (REM)
Limbic system interweaves unconscious primal emotions
with our conscious cognitive thoughts
Tie together emotions and memory (REM)
SCN circadian rhythm
VLPOSleep Switch
Sleep
Stimulation of hypothalamus and amygdala
Amygdalar destruction abolishes fear and its autonomic and
endocrine responses
Amygdala fear learning
Viewing fearful faces activate the left amygdala
Fear
• Rage Removal of the neocortex
Destruction of the VMHN and septal nuclei
Stimulation of an area extending through lateral hypothalamus
to the central grey area of the midbrain
B/L amygdala destruction Placidity
Rage & Placidity
Complex Phenomenon
• Lateral Hypothalamus Sympathetic discharge
• CA release
Mass sympathetic discharge in animals exposed to stress
the flight or fright response
StressCortical and limbic connections CRH (PVN)
CRH release Endocrine and immune responses
Autonomic Endocrine Response
Autonomic Endocrine Response
B/L lesions piriform cortex intensification of sexual behaviour
B/L amygdaloid lesions hypersexualityStimulation of MFB and neighboring hypothalamic areas -
penile erection with emotional behaviour (animals)Anterior hypothalamic lesions abolishes behavioural heat
(female sheep) Medial preoptic area of HT – key for male sexual behaviour
Sexual Behaviour
The pathway of motivated behaviour in addiction
PFC-Amygdala-Nac-VP-MDT
Amygdala Cue induced Relapse
Cues, stress, and a single dose of drug excitatory NT
(hippocampus, amygdala) project to the VTA and nucleus
accumbens
Addiction
Amygdala (PFC & MTL) Consolidation and retrieval of
emotional memories
Amygdala & hippocampus (PFC) Acquisition, extinction,
& recovery of fears to cues and contexts
Emotional Memory
• Social cognition refers to thought processes involved in understanding and dealing with other people
oCingulate gyrus and amygdala
oBasolateral circuit
Social Cognition
Clinical implicationsEPILEPSY temporal lobe epilepsy most common type in adults most often caused by hippocampal sclerosis hippocampal sclerosis in addition with involvement
of amygdala and parahippocampal gyrus – mesial temporal sclerosis(MTS)
MTS is not limited to medial temporal lobe, but represents a limbic system disorder
LIMBIC ENCEPHALITIS is a para-neoplastic syndrome mechanism of the disease not known manifests as encephalitis involving hippocampus,
amygdala, cingulate gyrus, insula, orbital-frontal cortex afflicted patients develop sub acute onset of memory loss,
dementia, involuntary movements and ataxia
DEMENTIA degenerative changes in limbic system likely have a
role in genesis of pick’s disease and Alzheimer’s diseaseMarked atrophy found in dentate gyrus and hippocampus in Alzheimer’s disease senile plaques and neurofibrillary
tangles dispersed through out cerebral cortex and basal ganglia, but hippocampus and amygdala are often severely involved
Korsakoff’s syndromeIt is caused by damage to mamillary bodies,dorso medial
nucleus of thalamus &HTIt is associated with chronic prominent impairment of
recent and remote memoryRecent memory is characteristically more disturbed than
remote memoryConfabulation may be marked
ANXIETY DISORDERS may be a failure of anterior cingulate and
hippocampus to modulate the activity of amygdala (top- down regulation)
SCHIZOPHRENIA reduced limbic volume Papez circuit probably involved distortion of the cortical neuronal organization of layer
2 of ERC. decreased size of hippocampus and reduced number of
GABAergic cells in the cingulate and anterior thalamus with resultant glutamatergic excitotoxicity.
basolateral circuit which mediates social cognition deficit in schizophrenia
AFFECTIVE DISORDERS dysfunction of anterior limbic network suggested in bipolar disorder, but its role in
depression is unclear
ADHD enlarged hippocampus in children and adolescents may
be a compensatory response to the disturbances in perception of time, temporal processing, and stimulus seeking associated with ADHD
disrupted connections between amygdala and orbitofrontal cortex may contribute to behavioral disinhibition seen in ADHD
AUTISM limbic structures involved include cingulate gyrus and
amygdala which mediate cognitive and affective processing.
the basolateral circuit for social cognition – disrupted.
Kluver-Bucy Syndrome Results from bilateral destruction of amygdala. Characteristics:
Increase in sexual activity.Compulsive tendency to place objects in mouth.Decreased emotionality.Changes in eating behavior.Visual agnosia.
Heinrich Klüver Paul Clancy Bucy (1897-1979) (1904-1992)
Pathologies (lesions) Voracious appetite Increased (perverse) sexual activity Docility:
Loss of normal fear/anger response Memory loss:
Damage to hippocampus portion:Cells undergoing calcium-induced changes
associated with memory
Klüver-Bucy syndrome in cats: Mating behavioral changes
conclusionLS plays a pivotal role in behavior The intricate functional neuroanatomy of LS with its
diverse circuit may explain some of its manifestations of neuro psychiatric disorders
relentless research has identified the role of amygdala and significance Of HT in various neuro vegetative functions suggest the integral role of limbic system in understanding human behavior and its aberrations.
THANK U
Connections of the Amygdala
Autism
Dysfunction ofamygdala
MercuryRising
Klüver-Bucy syndrome
Monkey or cats with bilateral damage of temporal lobes including amygdala and hippocampal formation
Fail to display normal fear of anxiety (docility) - attempt to pick up snakes and lighted matches
Regression to oral stage - put almost anything into mouth
Marked increase in both the amount and diversity of sexual activity
Evolution and Limbic System
- Triune Concept of MacLean
Protoreptilian Brain (R Complex) ---- Instinct
Paleomammalian Brain --- Limbic System ---- Emotion
Neomammalian Brain --- Neocortex --- Analytical, Reasoning
Ammon’s horn(Cornu Ammonis)
Karen Anne Carpenter(1950-1983)
AnorexiaNervosa
Silent Attack
- little emotional expression
- evoked by electric stimulation of perifornical nuc. of hypothalamus
“The cat moves swiftlyand with little sign ofemotion to bite therat’s neck and kill it”(Siegel & Brutus, 1990)
Sham Rage
- an affective attack expression
- evoked by radio stimulation of medial hypothalamus
“Because the cat does notdirect its attack toward anytarget, we regard this as just a fragment of a normalattack” (Delgado, 1981)