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)