This document provides an overview of the limbic system. It discusses the historical aspects of defining the limbic system. It then describes the key components of the limbic system including the amygdala, hippocampus, hypothalamus, and connections between these structures like the Papez circuit. Finally, it discusses some clinical implications of the limbic system, focusing on temporal lobe epilepsy which can arise from damage to limbic structures like the hippocampus and amygdala.

1. DR. BHARAT BHUSHAN
(DM-NEUROLOGY)
ASSOCIATE PROFESSOR
GOVERNMENT MEDICAL COLLEGE,KOTA

2. Contents
• Historical Aspects
• Introduction
• Components of Limbic System
• Papez Circuit
• Clinical Implications

3. Historical Aspects
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
1939 representation
of emotions in limbic
system
Paul Maclean 1952 Limbic System

4.  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.
INTRODUCTION

6. 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

7. COMPONENTS OF LIMBIC SYSTEM
Olfactory pathways
Anterior perforated substance
Pyriform lobe
Septal area
Amygdala
Limbic cortex
Hippocampal formation
Elements of diencephalon

8. Olfactory pathway
Olfactory epithelium
Olfactory nerve filaments
Olfactory bulb
Olfactory tract
Lateral Intermediate Medial
Blend with cortexOlfactory tubercalUncus

9. 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.

10. 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.

11. AMYGDALA

12. • 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

13. Amygdala Inputs
AMYGDALA
Corticomedial Nuclear
Group
Basolateral Nuclear
Group
Central Nucleus
Olfactory
System
Temporal Lobe
(associated with visual,
auditory, tactile senses)
Brainstem (viscerosensory relay
Nuclei: solitary nucleus
and parbrachial nucleus)
Ventral
Amygdalofugal
Fibers
Mediates behaviors
triggered by olfactory
stimuli
Mediates emotional
responses
Attaching emotional
significance to a
stimulus

14. Amygdala Outputs
AMYGDALA
Corticomedial Nuclear
Group
Basolateral Nuclear
Group
Central Nucleus
Ventral
Amygdalofugal
Fibers
Septal Nuclei
Hypothalamus
Limbic Association Cortex
Prefrontal Cortex
Hippocampal Formation
Dorsal motor n. Of X
Reticular formation
Hypothalamus
Nuclei of ANS
Ventral
Amygdalofugal
Fibers
Stria Terminalis
Learning
emotional
significance
Autonomic
responses
Regulation of
“appetitive
behaviours”;
i.e., Eating in
response to
smells

15. Amygdala stimulation produces emotional
behaviors through subcortical pathways

16. •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

17. • 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 Drinking
Fighting behavior
Mating and maternal care
Responses to physical or emotional stresses

18. 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.

19. 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.

20. 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.

21. 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

22. S shaped in coronal section.
 It has 3 distinct zones:
Dentate Gyrus
Hippocampus Proper
Subiculum
UPPER LIMB forms
hippocampus.
Two parts – Cornu Ammonis
Dentate Gyrus
MIDDLE LIMB connects cornu
ammonis with parahippcampal
gyrus – subiculam
LOWER LIMB – parahippocampal
gyrus

23. 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.

24. HIPPOCAMPUS (Ammon’s Horn)

25.  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).

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

27. Hippocampal Circuits
FornixFornix
(septal-hippocampal pathway) (Hippocampal commissure)
Afferents
Efferents
HIPPOCAMPUS
(Cortico-entorhinal projections)
ERC/Sub
(PHG)
Cortex
Septal nuclei
Mammillary Body
Contralateral
Hippocampus
1. & 2.

28. 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

29. 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.

30. Elements of Diencephalon
Habenular nucleus- Lies in habenular triangle at the root of
pineal body.
Mammilary Bodies
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.
Hypothalamus
The hypothalamus consists of only 4 cm3 of neural tissue, or
0.3% of the total brain.

31. Mammilary Bodies
• Located 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.

32. HYPOTHALAMUS

33. Hypothalamus
Lamina terminalis
Mamillary body
Hypothalamic sulcusSeptum pellucidum
Pellucidum
Choroid plexus
Aqueduct
Interventricular foramen
Relations of the Hypothalamus

34. 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
mamillary
body and
area above it)

35. Medial Zone
(Periventricular and
intermediate)
Lateral Zone
Pre optic region Preoptic nucleus
Supra optic region Paraventricular nucleus
Periventricular cell grps
Suprachiasmatic nucleus
Intermediate cell group
Suprachiasmatic
nucleus
Tuberal region Dorsomedial nucleus
Ventromedial nucleus
Arcuate/infundibular nu.
Premamillary nucleus
Lateral tuberal
nucleus
Mamillary or posterior
region
Posterior nucleus Tuberomamillary
nucleus
Mamillary body Mamillary nuclei
Hypothalamus and its Nuclei

36. Connections of the Hypothalamus

37. CONTROL OF HYPOPHYSIS CEREBRI BY HYPOTHALAMUS
Neurons in some hypothalamic nuclei produce
bioactive peptides discharged to neighborhood
capillaries (neurosecretion)
Control of neurohypophysis (posterior lobe)
-Vasopressin is secreted in supraoptic nuclei
-Oxytocin is secreted in paraventricular nucleus.
-

38. 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
their secretion.
Together known as
Hypoyhalamo-hypophyseal tract
Paraventicular nucleus
Hypophysis cerebri
Supraoptic
nucleusParaventriculo-
Hypophyseal tract
Supraoptico-hypophyseal
tract

39. Control of adenohypophysis by hypothalamus
Hypothalamus control adenohypophysis by producing number of releasing
factors.
Releasing factors travel through tubero-hypophyseal tract which receives
fibers
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.

40. 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.

41. Papez Circuit
(Medial Limbic Circuit)
Mammillary bodies
Other hypothalamic nuclei
Septal nuclei
Substantia innominata
(Basal nucleus of Meynert)
Hippocampal Formation
(hippocampus
and dentate gyrus)
Anterior Thalamic
nuclear group
Cortex of Cingulate Gyrus
Entorhinal Complex
(Parahippocampal Gyrus)
Neocortex
Fornix
Mammillothalamic
tract

42. 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.

43. Taxonomy of Long-term Memory Systems

44. LIMBIC SYSTEM - CLINICAL IMPLICATIONS

45. 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

46. 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 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.
 Absence seizures
 Spiritual religious experience

47. • Interictal Symptoms –
1. Personaltiy 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 – Halluciantions and paranoid delusions.
 Patient is usually warm and has appropriate affect in contrast to schizophrenia
3. Violence
4. Affective symptoms – Seen less than psychotic symptoms.
 Episodic
 High incidence of suicide in patients with epilepsy.

48. 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. Confusion
3. 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

49. 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.

50. 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.

51. • 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.

52. 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.

53. 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.

54. 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.

55. 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.

56. 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.

57. ADHD
 Disrupted connections between the amygdala and
orbitofrontalcortex 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

58. 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.

59. 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.

60. Henry Molaison
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
surgery.
Retained his short-term memory and
procedural memory as well.