Limbic System

Presenter – Dr. Arpit KoolwalResident,

Department of PsychiatrySubharti Medical College,

Meerut

Contents

• Historical Aspects• Introduction• Components of Limbic System• Papez Circuit• Clinical Implications• Refrences

Historical AspectsThomas Willis 1664 Cerebri LimbusPaul Broca 1878 le grand lobe limbique James Papez 1937 Papez CircuitPaul Kluver & Heinrich Bucy First evidence of cortical1939 representation of emotions in limbic system Paul Maclean 1952 Limbic System

INTRODUCTION Functional anatomic system of interconnected cortical and

sub cortical structures.

Area of intimate processing between the hypothalamus and cortical information.

Plays a role in emotions, learning and autonomic regulation.

THE BROAD FUNCTIONAL DIVISIONS • Rostral limbic system: Amygdala, septum, orbitofrontal cortex,

anterior insula, and anterior cingulate. – Important for emotion

• Caudal limbic system: Hippocampus, posterior parahippocampal cortex and posterior cingulate.

– Important for memory and visual-spatial functions

COMPONENTS OF LIMBIC SYSTEM

Olfactory pathwaysAnterior perforated substancePyriform lobeSeptal area Amygdala Limbic cortex Hippocampal formation Elements of diencephalon

Olfactory pathwayOlfactory epithelium

Olfactory nerve filaments

Olfactory bulb

Olfactory tract

Lateral Intermediate Medial

Blend with cortexOlfactory tubercalUncus

Anterior perforated substance• Mass of gray matter on either side of optic chiasma• Perforated by central branch of MCA

Pyriform lobe• Sometimes also called as the Olfactory Cortex.• Uncus – Curved portion of anterior extremity of hippocampal gyrus• Principal region of awareness of olfaction• Fibers from lateral olfactory stria terminate in it• Limen insulae – Cortex of most medial part of insula• Entorhinal cortex- Anterior part of parahippcampal gyrus BA28• "Area Tempestas“ - Epileptogenic trigger zone, From this site chemical and

electrically evoked seizures can be triggered and is the site of action for the proconvulsant action of chemoconvulsants.

Septal Area • Location - Situated ventral to corpus callosum.• Parts - Paraterminal Gyrus & Septum Pellucidam.• Connections – 1. Receive olfactory fibre from medial olfactory stria. 2. Septal nuclei receive reciprocal connections from the Hippocampus via the fornix.• Functions – 1. Also called as the Medial Olfactory Area has no

relation to the sense of smell, but it is considered a pleasure zone in animals.

2. Septal nuclei play a role in reward and reinforcement along with the Nucleus Accumbens.

AMYGDALA

• Location - Two almond-shaped masses of neurons on either side of the thalamus at the lower end of the hippocampus.

• Nuclear components:1. Basolateral Nuclei2. Central Nuclei3. Corticomedial Nuclei

Amygdala Inputs

AMYGDALA

Corticomedial NuclearGroup

Basolateral NuclearGroup

Central Nucleus

OlfactorySystem

Temporal Lobe(associated with visual,auditory, tactile senses)

Brainstem (viscerosensory relayNuclei: solitary nucleus

and parbrachial nucleus)

VentralAmygdalofugal

Fibers

Mediates behaviors triggered by olfactory stimuli

Mediates emotional responses

Attaching emotional significance to a stimulus

Amygdala OutputsAMYGDALA

Corticomedial NuclearGroup

Basolateral NuclearGroup

Central Nucleus

VentralAmygdalofugal

Fibers

Septal NucleiHypothalamus

Limbic Association Cortex Prefrontal Cortex

Hippocampal Formation

Dorsal motor n. Of X Reticular formation

Hypothalamus Nuclei of ANS

VentralAmygdalofugal

Fibers

Stria Terminalis

Learning emotional significance

Autonomic responses

Regulation of “appetitive behaviours”; i.e., Eating in response to smells

Amygdala stimulation produces emotional behaviors through subcortical pathways

•Emotional Learning - Formation and storage of memories associated with emotional events.•Modulation of Memory Consolidation - Following any learning event, the long-term memory for the event is not formed instantaneously. Rather, information regarding the event is slowly assimilated into long-term storage over time, possibly via Long-term Potentiation.•Aggression - Animal studies have shown that stimulating the amygdala appears to increase both sexual and aggressive behavior. •Alcoholism and binge drinking - Alcoholism is associated with dampened activation in brain networks responsible for emotional processing, including the amygdala.

Functions of the Amygdala

• Project into the limbic system one’s current status in relation to both surroundings and thoughts.

• Make the person behavioral response appropriate for each occasion.

• Relate environmental stimuli to coordinated behavioral autonomic and endocrine responses seen in species-preservation.

• Responses include:Feeding and DrinkingFighting behaviorMating and maternal careResponses to physical or emotional stresses

Limbic Cortex Situated at the inferomedial aspect of the cerebral hemispheres.

Consists of two concentric gyri surrounding the corpus callosum.

Broca proposed - the larger outer gyrus -" limbic gyrus" smaller inner one "the intralimbic gyrus".

The limbic gyrus (limbic lobe) consists Isthmus of the cingulate gyrus, Parahippocampal gyrus Subcallosal area.

CINGULATE GYRUS

Location - Dorsal to the corpus callosum

Connections – 1. Heavily interconnected with the association areas of the cerebral cortex. 2. Receives inputs from the anterior nucleus of the thalamus and the

neocortex, somatosensory areas of the cerebral cortex. 3. It projects to the entorhinal cortex via the cingulum.

Functions - Involved with emotion formation and processing, learning, and memory, central role in attention, feelings of safety and security have also been attributed to this part of the brain.

PARAHIPPOCAMPAL GYRUS

Located - In the medial temporal lobe.

Includes - 1. Perirhinal Cortex 2.Entorhinal Cortex Function - Important role in

memory encoding and retrieval.

ERC funnels highly processed cortical information to the hippocampal formation and serves as its major output pathway.

A subcortical banana-shaped structure composed of allocortex structure.

Location - In the temporal lobe as the floor of the inferior horn of the lateral ventricle.

The 3 components

Hippocampal Formation

S shaped in coronal section.

It has 3 distinct zones: Dentate Gyrus Hippocampus Proper SubiculumUPPER LIMB forms hippocampus. Two parts – Cornu Ammonis Dentate GyrusMIDDLE LIMB connects cornu ammonis with parahippcampal gyrus – subiculamLOWER LIMB – parahippocampal gyrus

DENTATE GYRUS Lies between Fimbria of hippocampus & Parahippocampal

gyrus. Toothed / beaded surface Consists of three layers of neurons: Molecular Granular - Most prominent, contains granule cells, principal excitatory neurons of dentate gyrus. Polymorphic Major Input- Perforant pathway from layer II & III of the Entorhinal Cortex

The Perforant Pathway - Medial Perforant path Lateral Perforant path

It was in this pathway that long term potentiation was first discovered. Function- Formation of memories Play a role in depression.

HIPPOCAMPUS (Ammon’s Horn)

In cross section resembles “sea horse”.

Is the inferomedial structure of the parahippocampal formation.

Stretches in a ‘C’ shape formation over the corpus callosum.

Divided into several zones of pyramidal cells on the basis of the fiber connections:

CA1 – CA 4 fields

Trilaminate structure Molecular Pyramidal Polymorphic

The most sensitive area in the brain for Ischemic events in hippocampus is CA1 (Sommer’s Sector).

SUBICULAR COMPLEX• Subiculum is the transitional zone between the six-layered entorhinal cortex and the three-layered hippocampus.• Components: Pre subiculum Para subiculum Subiculum

Hippocampal Circuits

Fornix

bran

ch

(Postcomm

isuralBranch)

Fornix

(Pre

com

miss

ural)

(septal-hippocampal pathway) (Hippocampal commissure)

(Perforant & alvear path)

AfferentsEfferents

HIPPOCAMPUS(Cortico-entorhinal projections)

ERC/Sub(PHG)

Cortex

Septal nuclei

Mammillary Body

ContralateralHippocampus

1. & 2.

The Hippocampus Dentate Complex(HC-DG)

Afferent Pathways

Pyramidal cell(CA1,2)

PHG (ERC, Sub)Dentate gyrus (granule cells)

mossy fibers

Pyramidal cell(CA3)

schaffer collaterals

perforant path

alvear path

Septal nuclei septo-hippocampal path - thru fornix

Functions of the Hippocampus

1. Declarative Memory – Facts and events.2. Spatial Memory - The hippocampus contains

place cells that encode spatial memory (where have I been?)

Recalling of place, and of the routes required to navigate them requires hippocampal activation.

Elements of DiencephalonHabenular nucleus- Lies in habenular triangle at the root of pineal

body.Mammilary BodiesAnterior thalamic nucleusAfferent from – Mamillary bodyEfferent to – Cingulate gyrusThought to play a role in the modulation of alertness and are

involved in learning and episodic memory.Hypothalamus The hypothalamus consists of only 4 cm3 of neural tissue, or 0.3% of

the total brain.

Mammilary Bodies• Location - At the ends of the

anterior arches of the fornix.• Acts as a relay for impulses

coming from the amygdalae and hippocampi, via the mamillo-thalamic tract to the thalamus.

• This circuit, from amygdalae to mammillary bodies, and then on to the thalamus, is part of the larger 'Papez circuit'.

• Fuctions – 1. Episodic Memory 2. Adding the element

of smell to the memories.

HYPOTHALAMUS

Hypothalamus

Lamina terminalisMamillary body

Hypothalamic sulcusSeptum pellucidum

Pellucidum

Choroid plexus

Aqueduct

Interventricular foramen

Relations of the Hypothalamus

The hypothalamus also divide anteroposteriorly into four regions

Preoptic-Adjoins lamina terminalis

Supraoptic(chiasmatic)-Lie above optic chiasma

Tuberal (infundibulotuberal)-includes infundibulum tubercinereum

Mamillary(posterior)-consists of mamillarybody andarea above it)

Medial Zone(Periventricular and intermediate)

Lateral Zone

Pre optic region Preoptic nucleus

Supra optic region Paraventricular nucleusPeriventricular cell grpsSuprachiasmatic nucleusIntermediate cell group

Suprachiasmatic nucleus

Tuberal region Dorsomedial nucleusVentromedial nucleusArcuate/infundibular nu.Premamillary nucleus

Lateral tuberal nucleus

Mamillary or posterior region

Posterior nucleus Tuberomamillarynucleus

Mamillary body Mamillary nuclei

Hypothalamus and its Nuclei

Connections of the Hypothalamus

CONTROL OF HYPOPHYSIS CEREBRI BY HYPOTHALAMUS

Neurons in some hypothalamic nuclei producebioactive peptides discharged to neighborhoodcapillaries (neurosecretion)

Control of neurohypophysis (posterior lobe)

-Vasopressin is secreted in supraoptic nuclei

-Oxytocin is secreted in paraventricular nucleus.

-

Axons of paraventriculo-hypophyseal tractjoin axons arising from supra-optic nucleusto form supraoptico-hypophyseal tract.

The axons of supraoptico-hypophyseal tract passdown into neurohypophysis where they branchand end in relation to capillaries and releasetheir secretion.

Together known as Hypoyhalamo-hypophyseal tract

Paraventicular nucleus

Hypophysis cerebri

Supraoptic nucleusParaventriculo-

Hypophyseal tract

Supraoptico-hypophysealtract

Control of adenohypophysis by hypothalamus

Hypothalamus control adenohypophysis by producing number of releasing factors.

Releasing factors travel through tubero-hypophyseal tract which receives fibersfrom various nuclei.

Release the factors into the capillaries

The capillaries carry the factors into the pars anterior of hypophysis cerebri through hypothalamo-hypophseal portal system.

Functions• Hormonal Release – Through its control of the anterior and

posterior pituitary.• Hormonal and Behavioural Circadian Rhythms• Control of food intake - Extreme lateral part of

the ventromedial nucleus of the hypothalamus is responsible for the control of food intake. Stimulation of this area causes increased food intake. Bilateral lesion of this area causes complete cessation of food intake.

• Fear processing - The medial zone of hypothalamus is part of a circuitry that controls motivated behaviors, like defensive behaviors.

Papez Circuit (Medial Limbic Circuit)

Mammillary bodiesOther hypothalamic nuclei

Septal nucleiSubstantia innominata

(Basal nucleus of Meynert)

Hippocampal Formation(hippocampus

and dentate gyrus)Anterior Thalamic

nuclear group

Cortex of Cingulate GyrusEntorhinal Complex(Parahippocampal Gyrus)

Neocortex

Fornix Mammillothalamictract

Functions

1. Emotion – Initially believed that the Papez circuit was involved in emotions. But no further evidence of involvement in emotions.

2. Memory – Especially Episodic and Spatial memory.

LIMBIC SYSTEM - CLINICAL IMPLICATIONS

TEMPORAL LOBE EPILEPSY• Form of focal epilepsy, characterized by recurrent epileptic seizures arising from one

or both temporal lobes• Two main types 1. Mesial temporal lobe epilepsy (MTLE) – Arises from Hippocampus,

Parahippocampal gyrus and Amygdala.2. Lateral temporal lobe epilepsy (LTLE) • Mesial temporal sclerosis – Cause of 47-70% of all TLE• Pathological abnormalities:-1. Specific pattern of hippocampal neuron cell loss - Severe neuronal loss in CA1, May

spread to involve CA3 and CA4, CA2 and dentate are only mildly involved Associated with hippocampal atrophy and gliosis2. Dispersion of granule cell layer in dentate gyrus

Signs and Symptoms• Pre-ictal symptoms – 1. Autonomic sensations – Fullness of stomach Blushing Changes in respiration 2. Cognitive sensations – Deja vu, Jamais vu, forced thinking, dreamy states3. Affective States – Fear, Depression, Elation4. Automatisms – Lip smacking, rubbing, chewing

• Ictal Symptoms – Recuurent seizures usually simple partial but can be complex partial also.

Duration – 1-2 minutes Sensory hallucinations – visual auditory, olfactory (m.c.) and gustatory. Absence seizures Spiritual religious experience

• Interictal Symptoms – 1. Personality changes – Hyposexuality Emotional intensity Perseverative approach to interactions (viscosity) References to personal destiny and philosophical themes (left TLE) Excessive emotionality (right TLE)2. Psychotic symptoms – Interictal are more common than intraictal psychosis. 10% of all complex partial epilepsy patients develop psychotic symptoms. Classically they appear in those who have had epilepsy for a long time and

developed personality changes. Most characteristic symptoms – Hallucinations and paranoid delusions. Patient is usually warm and has appropriate affect in contrast to schizophrenia3. Violence4. Affective symptoms – Seen less than psychotic symptoms. Episodic High incidence of suicide in patients with epilepsy.

LIMBIC ENCEPHALITIS Limbic encephalitis is a form of encephalitis.

An inflammatory process involving the hippocampi, amygdala and less frequently frontobasal and insular regions of the limbic system and other parts of the brain.

Clinical features:-1. Severe impairment of short-term memory (cardinal sign)2. Confusion3. Psychiatric symptoms (changes in behavior & mood – irritability, depressive , sleep disturbances),4. Seizures

60% of the time, limbic encephalitis is paraneoplastic in origin. Paraneoplastic limbic encephalitis (PLE) is a particularly severe form of limbic

encephalitis caused by neoplasms most commonly associated with small cell lung carcinoma. Whereas the majority of encephalities are viral in nature, PLE is often associated with cancer

ALZHEIMERS’ DISEASE

Neurodegenerative changes in limbic system.

Amyloid proteins build up and form amyloid plaques (outside cells).

Neurofibrilllary tangles (inside cells), leads to neuronal death.

Hippocampus is one of first areas to degenerate, leads to anterograde amnesia.

Cortex also degenerates early, leads to retrograde amnesia and dementia.

KLUVER-BUCY SYNDROME Neurobehavioural syndrome associated with bilateral lesions in the

medial temporal lobe , particularly amygdala.

Clinical features Facial Blunting (may not respond appropriately to stimuli) Hyperphagia (extreme weight gain without a strictly monitored diet) Hyperorality (marked tendency to examine all objects orally) Hypermetamorphosis (an irresistible impulse to attend & react to visual

stimuli) Inappropriate Sexual Behavior (Hyper sexuality Visual Agnosia/ "psychic blindness" (inability to visually recognize

objects) A combination of 3 or more symptoms is typically suggestive of the

diagnosis.

• The visual agnosia in KB syndrome presumably results from damage to the amygdalae, which normally functions as a site of transfer of information between sensory association cortex and the Hypothalamus.

• After the damage to amygdala, visual stimuli can no longer be paired with affective responses.

KORSAKOFF’S SYNDROME Amnestic syndrome, caused by thiamine deficiency.

Associated with poor nutritional habits of people with chronic alcohol abuse, gastric carcinoma, haemodialysis etc.

Leads to damage to mammillary bodies and dorsomedial nucleus of thalamus.

Symptoms Amnesia, confabulation, attention deficit,

disorientation, and vision impairment, change in personality like - lack of initiatives, spontaneity, lack of interest or concern, executive function deficits.

Recent memory more affected than remote, Immediate recall is usually preserved.

Semantic Dementia

•Rare degenerative disorder that exhibits defects in all semantic memory functions, including naming, single word comprehension and impoverished general knowledge, with relative preservation of other components of speech, perceptual and nonverbal problem-solving skills, and episodic memory.•Damage to mammillary bodies, ventral anterior nucleus, and ventral lateral nucleus.

LIMBIC SYSTEM IN SCHIZOPHRENIA

Ventricular enlargement Reduced limbic volumes Decreased volume of hippocampus Decreased amygdala response during facial recognition tasks (fMRI) Decreased activity in dorsolateral prefrontal cortex (PET) Papez circuit is probably involved in schizophrenia. Distortion of cortical neuronal organization of layer II of the ERC Reduced number of GABAergic cells in the cingulate and anterior

thalamus with resultant glutamatergic excitotoxicity.

LIMBIC SYSTEM IN BIPOLAR DISORDER

REDUCTIONS IN VOLUME OF THE Frontal lobes Basal ganglia Amygdala Hippocampus

Functional studies have revealed decreased activity in the prefrontal cortex and anterior cingulate gyrus, which is the centre for integration of attentional and emotional output and helps effortful control of emotional arousal.

ANXIETY DISORDERS May be the result of a failure of the anterior cingulate and

hippocampus to modulate the activity of the amygdala (top-down regulation).

A fear circuitry, involving the amygdala, prefrontal and anterior cingulate has been described (bottoms-up regulation).

• The limbic system, which is involved in storing memories and creating emotions, is also thought to play a central role in processing all anxiety-related information.

• People with obsessive-compulsive disorder (OCD) often show increased activity in the basal nuclei, in particular the striatum and other frontal lobe areas of the forebrain.

ADHD Disrupted connections between the amygdala and orbitofrontal

cortex may contribute to behavioral disinhibition seen in individuals with ADHD.

OCD Neuro-imaging has implicated the cortical-striatal-thalamic circuit PET imaging shows increased glucose metabolism in the orbital

gyri It is postulated that orbitofrontal – thalamic hyperactivity gives

rise to obsessive thoughts

AUTISM Limbic structures involved include the cingulate gyrus and

amygdala, which mediate cognitive and affective processing. The basolateral circuit integral for social cognition is disrupted

in autism spectrum disorders.

Psychosurgery• All forms of psychosurgeries in use today target the limbic system –1. Anterior cingulotomy – Most commonly used psychosurgery in U.S. Target Site – Anterior Cingulate cortex Disconnects the thalamic and posterior frontal regions and damages the anterior

cingulate region.2. Anterior capsulotomy – Disconnects the orbitofrontal cortex and thalamic nuclei.3. Subcaudate tractotomy - Target Site- Lower medial quadrant of the frontal lobes. Disconnects limbic

system and supra-orbital part of the frontal lobe.4. Limbic leucotomy - Combination of subcaudate tractotomy and anterior

cingulotomy. 5. Amygdalotomy – Target Site - Amygdala It was developed as a treatment for aggression in 1961.

Henry MolaisonPopularly known as Patient H.M. H.M. suffered from temporal lobe epilepsy , which could not controlled with drug alone.So in 1953 – Surgery to control TLEBilateral removal of part of temporal lobes including hippocampus.Anterograde amnesia: inability to form new memories.Moderate retrograde amnesia which inhibited his ability to remember any events one to three years before his surgery. Retained his short-term memory and procedural memory as well.

References

• Kaplan And Sadock’s Comprehensive Texbook of Psychiatry

• Oxford Textbook of Psychiatry• Guyton – Textbook of Physiology