DR. BHARAT BHUSHAN
GOVERNMENT MEDICAL COLLEGE,KOTA
• Historical Aspects
• Components of Limbic System
• Papez Circuit
• Clinical Implications
Thomas Willis 1664 Cerebri Limbus
Paul Broca 1878 le grand lobe limbique
James Papez 1937 Papez Circuit
Paul Kluver & Heinrich Bucy First evidence of cortical
of emotions in limbic
Paul Maclean 1952 Limbic System
Functional anatomic system of interconnected cortical and
sub cortical structures.
Area of intimate processing between the hypothalamus and
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
Anterior perforated substance
Elements of diencephalon
Anterior perforated substance
• Mass of gray matter on either side of optic chiasma
• Perforated by central branch of MCA
• Sometimes also called as the Olfactory Cortex.
• Uncus – Curved portion of anterior extremity of hippocampal
• 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.
• Location - Situated ventral to corpus callosum.
• Parts - Paraterminal Gyrus & Septum Pellucidam.
• Connections – 1. Receive olfactory fibre from medial olfactory
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.
• Location - Two almond-shaped masses of
neurons on either side of the thalamus at the
lower end of the hippocampus.
• Nuclear components:
1. Basolateral Nuclei
2. Central Nuclei
3. Corticomedial Nuclei
(associated with visual,
auditory, tactile senses)
Brainstem (viscerosensory relay
Nuclei: solitary nucleus
and parbrachial nucleus)
triggered by olfactory
significance to a
Limbic Association Cortex
Dorsal motor n. Of X
Nuclei of ANS
i.e., Eating in
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-
•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
• Relate environmental stimuli to coordinated behavioral
autonomic and endocrine responses seen in species-
• Responses include:
Feeding and Drinking
Mating and maternal care
Responses to physical or emotional stresses
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,
Location - Dorsal to the corpus callosum
Connections – 1. Heavily interconnected with the association areas of the cerebral
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.
Located - In the medial
Includes - 1. Perirhinal Cortex
Function - Important role in
memory encoding and
ERC funnels highly processed
cortical information to the
hippocampal formation and
serves as its major output
A subcortical banana-shaped
structure composed of allocortex
Location - In the temporal lobe
as the floor of the inferior horn
of the lateral ventricle.
The 3 components
S shaped in coronal section.
It has 3 distinct zones:
UPPER LIMB forms
Two parts – Cornu Ammonis
MIDDLE LIMB connects cornu
ammonis with parahippcampal
gyrus – subiculam
LOWER LIMB – parahippocampal
Lies between Fimbria of hippocampus & Parahippocampal
Toothed / beaded surface
Consists of three layers of neurons:
Granular - Most prominent, contains granule cells,
principal excitatory neurons of dentate gyrus.
Major Input- Perforant pathway from layer II & III of the
The Perforant Pathway - Medial Perforant path
Lateral Perforant path
It was in this pathway that long term potentiation was first
Function- Formation of memories
Play a role in depression.
In cross section resembles “sea horse”.
Is the inferomedial structure of the
Stretches in a ‘C’ shape formation over
the corpus callosum.
Divided into several zones of
pyramidal cells on the basis of the
CA1 – CA 4 fields
The most sensitive area in the brain for
Ischemic events in hippocampus is CA1
• Subiculum is the transitional zone between the six-layered
entorhinal cortex and the three-layered hippocampus.
• Components: Pre subiculum
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
Elements of Diencephalon
Habenular nucleus- Lies in habenular triangle at the root of
Anterior thalamic nucleus
Afferent from – Mamillary body
Efferent to – Cingulate gyrus
Thought to play a role in the modulation of alertness and
are involved in learning and episodic memory.
The hypothalamus consists of only 4 cm3 of neural tissue, or
0.3% of the total brain.
• Located at the ends of the
anterior arches of the fornix.
• Acts as a relay for impulses
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.
Hypothalamic sulcusSeptum pellucidum
Relations of the Hypothalamus
The hypothalamus also divide anteroposteriorly into four regions
-Lie above optic chiasma
area above it)
Pre optic region Preoptic nucleus
Supra optic region Paraventricular nucleus
Periventricular cell grps
Intermediate cell group
Tuberal region Dorsomedial nucleus
Mamillary or posterior
Posterior nucleus Tuberomamillary
Mamillary body Mamillary nuclei
Hypothalamus and its Nuclei
CONTROL OF HYPOPHYSIS CEREBRI BY HYPOTHALAMUS
Neurons in some hypothalamic nuclei produce
bioactive peptides discharged to neighborhood
Control of neurohypophysis (posterior lobe)
-Vasopressin is secreted in supraoptic nuclei
-Oxytocin is secreted in paraventricular nucleus.
Axons of paraventriculo-hypophyseal tract
join axons arising from supra-optic nucleus
to form supraoptico-hypophyseal tract.
The axons of supraoptico-hypophyseal tract pass
down into neurohypophysis where they branch
and end in relation to capillaries and release
Together known as
Control of adenohypophysis by hypothalamus
Hypothalamus control adenohypophysis by producing number of releasing
Releasing factors travel through tubero-hypophyseal tract which receives
from 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.
• 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.
(Medial Limbic Circuit)
Other hypothalamic nuclei
(Basal nucleus of Meynert)
and dentate gyrus)
Cortex of Cingulate Gyrus
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
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 gliosis
2. Dispersion of granule cell layer in dentate gyrus
Signs and Symptoms
• Pre-ictal symptoms –
1. Autonomic sensations – Fullness of stomach
Changes in respiration
2. Cognitive sensations – Deja vu, Jamais vu, forced thinking, dreamy states
3. Affective States – Fear, Depression, Elation
4. 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.
Spiritual religious experience
• Interictal Symptoms –
1. Personaltiy changes –
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 – Halluciantions and paranoid delusions.
Patient is usually warm and has appropriate affect in contrast to schizophrenia
4. Affective symptoms – Seen less than psychotic symptoms.
High incidence of suicide in patients with epilepsy.
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.
1. Severe impairment of short-term memory (cardinal sign)
3. Psychiatric symptoms (changes in behavior & mood –
irritability, depressive , sleep disturbances),
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
Neurodegenerative changes in
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
Cortex also degenerates early, leads
to retrograde amnesia and
Neurobehavioural syndrome associated with bilateral lesions in the
medial temporal lobe , particularly amygdala.
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
Inappropriate Sexual Behavior (Hyper sexuality
Visual Agnosia/ "psychic blindness" (inability to visually recognize
A combination of 3 or more symptoms is typically suggestive of the
• 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
• After the damage to amygdala, visual stimuli can no
longer be paired with affective responses.
Amnestic syndrome, caused by thiamine
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.
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.
•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
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
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
May be the result of a failure of the anterior cingulate and
hippocampus to modulate the activity of the amygdala
A fear circuitry, involving the amygdala, prefrontal and
anterior cingulate has been described (bottoms-up
• 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.
Disrupted connections between the amygdala and
orbitofrontalcortex may contribute to behavioral disinhibition
seen in individuals with ADHD.
Neuro-imaging has implicated the cortical-striatal-thalamic
PET imaging shows increased glucose metabolism in the
It is postulated that orbitofrontal – thalamic hyperactivity
gives rise to obsessive thoughts
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.
• 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
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
5. Amygdalotomy –
Target Site - Amygdala
It was developed as a treatment for aggression in 1961.
Popularly 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 TLE
Bilateral 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
Retained his short-term memory and
procedural memory as well.