The document discusses the limbic system's structure, functions, and clinical implications, highlighting its role in emotions, learning, and autonomic regulation. It covers historical developments, components like the amygdala and hippocampus, and conditions such as temporal lobe epilepsy and Alzheimer's disease. Additionally, it explores various syndromes and disorders related to the limbic system, including Kluver-Bucy syndrome and bipolar disorder.

1. LIMBIC SYSTEM-IT’S CLINICAL IMPLICATION
PRESENTER – Dr. Shaitan Singh Jat
SR Neurology
MODERATORS – Dr. Trilochan Shrivastava Sir
Dr. Rahul Gupta Sir

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

3. Historical Aspects
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

5. 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

6. 1. Limbic lobe
a) Cingulate gyrus
b) Para hippocampal Gyrus
2. Hippocampal formation
a) Dentate Gyrus
b) Hippocampus proper
c) Subiculum
3. Amygdala
4. Septal area
5. Hypothalamus
Others - cortex and insula, uncus, stria terminalis
Components of limbic system

7. The amygdala
• Located in medial temporal lobe
• Just anterior to the hippocampal
formation
• It is fused with the tip of the tail of
the caudate nucleus
• Stria terminalis emerges from its post
aspect

8. 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

9. 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

10. •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 behaviour.
•Alcoholism and binge drinking - Alcoholism is associated with
dampened activation in brain networks responsible for emotional
processing, including the amygdala.
Functions of the Amygdala

11. • 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
Continue..

12. Limbic Cortex
 Situated at the inferomedial aspect of thecerebral 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.

13. 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.

14. 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.

15. 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

16. 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 – subiculum
LOWER LIMB – parahippocampal
gyrus

17. 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.

18.  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).
HIPPOCAMPUS

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

20. Hippocampal Circuits
Fornix
b
r
a
n
c
h
(P
o
s
tc
o
m
m
is
u
r
a
l
B
r
a
n
c
h
)
Fornix
(
P
r
e
c
o
m
m
i
s
s
u
r
a
l
)
(septal-hippocampal pathway) (Hippocampal commissure)
(Perforant
&
alvear path)
Afferents
Efferents
HIPPOCAMPUS
(Cortico-entorhinal projections)
ERC/Sub
(PHG)
Cortex
Septal nuclei
Mammillary Body
Contralateral
Hippocampus
1. & 2.

21. 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

22. Functions of the Hippocampus
1. Declarative Memory – Facts and events.
2. Spatial Memory - The hippocampus contains
place cells that encode spatial memory
Recalling of place, and of the routes required
to navigate them requires hippocampal
activation.

23. Septal Area
• Location - Situated ventral to corpus callosum.
• Parts - Paraterminal Gyrus & Septum Pellucidum.
• Connections – 1. Receive olfactory fiber 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.

24. Elements of Diencephalon
Habenular nucleus- Lies in habenular triangle at the root
of pineal body.
Mammillary Bodies
Anterior thalamic nucleus
Afferent from – Mammillary body
Efferent to – Cingulate gyrus
Thought to play a role in the modulation of alertness and
are involved in learning and episodic memory.
Hypothalamus

25. Mammillary Bodies
• Located at the ends of the
anterior arches of the fornix.
• Acts as a relay for impulses
coming from
the amygdala 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.

26. Hypothalamus
Lamina terminalis
Mamillary body
Hypothalamic sulcus
Septum pellucidum
Pellucidum
Choroid plexus
Aqueduct
Interventricular foramen
HYPOTHALAMUS

27. The hypothalamus also divide anteroposteriorly into three regions
Supraoptic(chiasmatic)
-Lie above optic chiasma
Tuberal
(infundibulotuberal)
-includes infundibulum
tubercinereum
Mamillary
(posterior)
-consists of
mamillary
body and
area above it)

28. 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.
• Fear processing - The medial zone of hypothalamus is part of a
circuitry that controls motivated behaviours, like defensive
behaviours.

29. 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

30. 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.

31. LIMBIC SYSTEM - CLINICAL IMPLICATIONS

32. 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,
Para hippocampal 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

33. Signs and Symptoms
• Pre-ictal symptoms –
1. Autonomic sensations – Fullness of stomach
Blushing
Changes in respiration
2. Cognitive sensations – Deja vu, Jamais vu, dreamy states
3. Affective States – Fear, Depression, Elation
4. Automatisms – Lip smacking, rubbing, chewing
• Ictal Symptoms – Recurrent 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

34. • Interictal Symptoms –
1. Personality changes –
 Hyposexuality
 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.
3. Violence
4. Affective symptoms – Seen less than psychotic symptoms.
 Episodic
 High incidence of suicide in patients with epilepsy.

35. LIMBIC ENCEPHALITIS:
 Limbic encephalitis is a form of encephalitis.
 An inflammatory process involving the hippocampi, amygdala and less frequently fronto-
basal 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 behaviour & 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 encephalitis are viral in nature, PLE is often associated with cancer

36. ALZHEIMERS’ DISEASE
 Neurodegenerative changes in limbic
system.
 Amyloid proteins build up and form
amyloid plaques (outside cells).
 Neurofibrillary 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.

37. KLUVER-BUCY SYNDROME
Neurobehavioral 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 Behaviour (Hyper sexuality
 Visual Agnosia/ "psychic blindness" (inability to visually recognize
objects)
 A combination of 3 or more symptoms is typically suggestive of the
diagnosis.

38. • The visual agnosia in KB syndrome presumably
results from damage to the amygdala, 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.

39. 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, lack of interest
or concern, executive function deficits.
 Recent memory more affected than remote,
Immediate recall is usually preserved.

40. 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.

41. 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.

42. 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.

43. THANK
YOU