anatomy, physiology of limbic system and its clinical implications

1. Anant Kumar Rathi

2. LEARNING OBJECTIVES
• Study the anatomy of limbic system.
• Describe the roles of limbic system.
• Discuss especially the roles of
– hippocampus
– amygdala
– hypothalamus
• Discuss the lesions of various parts of limbic
system, with neurophysiological basis and
effects.

3. LIMBIC SYSTEM
HISTORICAL ASPECTS OF LIMBIC SYSTEM
Thomas Willis 1664 Cerebri Limbus
Paul Broca 1878 - Grand Lobe Limbique=
limbic
James Papez 1937 Papez Circuit
Paul Maclean 1952 limbic system
Limbic: border
Refers to a ring of gray matter on the medial
aspect of the cerebral hemispheres.

4. LIMBIC SYSTEM
INTRODUCTION
 Functional anatomic system of interconnected cortical and
sub cortical structures.
 Area of intimate processing between the hypothalamus and
cortical information processing.
 Plays a role in emotions, learning and autonomic regulation.
 Named by Paul Broca: limbic means border and it names
structures forming a border between hypothalamus and
cerebral cortex.

6. LIMBIC SYSTEM
THE BROAD FUNCTIONAL DIVISIONS
• Rostral limbic system: Amygdala, septum, orbitofrontal
cortex, anterior insula, and anterior cingulate
– Important for emotion
• Caudal system: Hippocampus, posterior parahippocampal cortex
and posterior cingulate
– Important for memory and visual-spatial functions

7. limbic lobe V/S limbic system
Limbic system (Limbic lobe+
Limbic lobe (Cortical Nuclei +connection)
areas of the limbic • Nuclei:
system) – Amagdyla
• Parahippocampal – Septal nuclei
gyrus – Mammillary body
• Hippocampus – Anterial thalamus
• Orbitalfrontal. • Connection:
• Cingulate gyrus – Fornix
• Insula – Median forebrain bundle
– Stria terminalis
– Mamillothalamic tract

8. COMPONENTS OF LIMBIC SYSTEM
 Olfactory pathways
 Anterior perforated substance
 Pyriform lobe
 Septal area
 Amygdaloid body
 Limbic cortex
 Hippocampal formation
 Elements of diencephalon
 Bundles of axons connecting the above region

12. Olfactory pathway
Olfactory epithelium
Olfactory nerve filaments
Olfactory bulb
Olfactory tract
Lateral Intermediate Medial
Uncus Olfactory tubercal Blend with cortex

13. Anterior perforated substance
• Mass of gray matter on either side of optic chiasma
• Perforated by central branch of MCA
Pyriform lobe
• Uncus – Curved portion of anterior extremity of hippocampal
gyrus
• Principal region of awareness of olfaction
• Primary olfactory area
• 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

14. Septal area
• Situated ventral to corpus
callosum
• Includes paraterminal gyrus
& septum pellucidam
• Receive olfactory fibre from
medial olfactory stria
• Has recciprocal connections
with hippocampus though
fornix

15. Amygdala
• Almond shaped collection
of nuclei
• Lies above inferior horn
of lateral ventricle
• Embedded in uncus
• Window of limbic system:
wide afferent connections
with visual, auditory
association areas.
• Wide efferent
connections

18. Amygdala stimulation produces emotional
behaviors through subcortical pathways

19. • Involuntary movements
– (1) tonic movements, such as raising the head or
bending the body (2) circling movements (3)
occasionally clonic, rhythmical movements and (4)
different types of movements associated with
olfaction and eating, such as licking, chewing, and
swallowing.
• Fear and punishment
• Sexual effects :erection(copulatory
movements, ejaculation, ovulation, uterine
activity, and premature labor).

20. Functions of the Amygdala
• Behavioral awareness areas
• 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

21. LIMBIC LOBE
 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
the isthmus of the cingulate gyrus,
the parahippocampal gyrus
the subcallosal area.

22. CINGULATE GYRUS
 Situated dorsal to the corpus callosum
 Heavily interconnected with the
association areas of the cerebral cortex.
 Receives inputs from the anterior nucleus
of the thalamus and the
neocortex, somatosensory areas of the
cerebral cortex.
 It projects to the entorhinal cortex via the
cingulum.
 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.

23. PARAHIPPOCAMPAL GYRUS
 Situated in the medial temporal lobe.
 Important role in memory encoding
and retrieval.
 The ERC funnels highly processed
cortical information to the
hippocampal formation and serves as
its major output pathway.

24. HIPPOCAMPAL FORMATION
 located in the temporal lobe as the floor
of the inferior horn of the lateral
ventricle.
 A curved and recurved sheet of cortex
folded into the medial surface of the
temporal lobe.
 S shaped in coronal section.
 It has 3 distinct zones:
dentate gyrus,
hippocampus proper ,
subiculum.
 Upper limb form hippocampus.
 Two parts – cornu ammonis &
dentate gyrus
 Middle limb connects cornu ammonis
with parahippcampal gyrus – subiculam
 Lower limb – parahippocampal gyrus

25. DENTATE GYRUS
 Lies b/w 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
 The major input- perforant pathway from layer II of the
entorhinal cortex
 The perforant pathway - medial perforant path
lateral perforant path
 Function- formation of memories
play a role in depression.

26. HIPPOCAMPUS
 In cross section resembles “sea horse”
 Is the inferomedial structure of the
parahippocampal formation.
 Hippocampus is divided into several
zones of pyramidal cells:
 CA1 – CA 4 fields
 Trilaminate structure
Molecular
Pyramidal
Polymorphic
 The most sensitive area in the brain for
Ischemic events in hippocampus is
CA1.
 Stretches in a ‘C’ shape formation over
the corpus callosum

27. SUBICULAR COMPLEX
Subuculum is the transitional zone between the six-layered
entorhinal cortex and the three-layered hippocampus
three components: pre subiculum,
para subiculum
subiculum

28.  Elements of diencephalon
• Hebenular nucleus- lies in hebenular triangle at the
root of pineal body
• Anterior thalamic nucleus
• Afferent from – mamillary body
• Efferent to – cingulate gyrus
• Hypothalamus
• The hypothalamus consists of only 4 cm3 of neural
tissue, or 0.3% of the total brain.

29. Hypothalamus
• Relations
 Anteriorly:
• Extends up to lamina terminalis
and merges with olfactory
Structures.
 Posteriorly :
• Merges with ventral thalamus
 Medial side:
• Forms the wall of the third
ventricle
 Laterally :
• Contact with the internal capsule
 Inferiorly:
• Related to the structures of the
third ventricle

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

31. The hypothalamus also divide anteroposteriorly into four regions
Preoptic Supraoptic(chiasmatic) Tuberal Mamillary
-Adjoins lamina -Lie above optic chiasma (infundibulotuberal) (posterior)
terminalis -includes infundibulum -consists of
tubercinereum mamillary
body and
area above it)

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

33. Connections of the hypothalamus
Hypothalamus is concerned with
visceral function
Connected to various parts of
limbic system, reticular
formation, autonomic centers in
brainstem and spinal cord.
It also releases secretions into the
blood stream and into CSF.

34. Afferent connections
Neocortex
The hypothalamus receives visceral
(including taste) through spinal cord and Thalamus Limbic system
brainstem.
Afferents from nucleus of tractus
solitarius to hypothalamus carry taste Hypothalamus
sensation.
Somatic afferents reach through Visual input
collaterals of major ascending tract
Afferents from olfactory pathway and
limbic system. Ascending
(anterior perforated substance, septal Somatosensory Visceral centers
pathway In brainstem &
nuclei, amygdaloid
Spinal cord.
complex, hippocampus, pyriform cortex)

35. Cortico-hypothalamic fibres
Hypothalamus receive fibers from the cortex of the frontal lobe
Many fibers relay in the thalamus (medial dorsal and midline
nuclei and reach hypothalamus through periventricular fibers
Efferent connections
The hypothalamus sends fibers to autonomic centers in
brain and spinal cord
In brainstem:-Nucleus of solitary tract
-Dorsal nucleus of vagus
-Nucleus ambiguous
-Para brachial nucleus

36. Efferent connections of Hypothalamus
Limbic system
Neocortex
-Hippocampus
-Septal nuclei
Thalamus -Amygdaloid complex
-From mamillary
body Hypothalamus
Neuroendocrine influence
Visceral center in of hypophysis cerebri
Brainstem
-nucleus tractus solitary tract
-Dorsal nucleus of vagus
-Nucleus Ambiguous
-Parabrachial nucleus
Spinal cord : Intermediolateral grey
column

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. Control of hypophysis cerebri by hypothalamus
Axons of paraventriculo-hypophyseal tract
join axons arising from supra-optic nucleus Paraventicular 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. Supraoptic
Paraventriculo- nucleus
Hypophyseal tract
Together known as
Hypoyhalamo-hypophyseal tract
Supraoptico-hypophyseal
tract
Hypophysis cerebri

39. Control of adenohypophysis by hypothalamus
Hypothalamus control adenohypophysis by
Paraventricular nucleus
Producing number of releasing factors.
Releasing factors travel through tubero-
hypophyseal tract which receives fibers Limbic system
from various nuclei.
Supra-
Release the factors into the capillaries Tubero-
chiasmatic
infundib nucleus
ular
The capillaries carry the factors into the tract
pars anterior of hypophysis cerebri through
hypothalamo-hypophseal portal system.
Fibres from Hypophysis cerebri
brainstem

41. FUNCTIONAL CIRCUTARYOF LIMBIC SYSTEM
PAPEZ CIRCUIT (NEURAL CIRCUIT
FOR EMOTIONS)
 James Papez, 1937
 Cortical control of emotions &
emotional expression
 Role in storing memory
 Papez discovered the circuit after
injecting rabies virus into a cat's
hippocampus and monitoring its
progression through the brain

42. FUNCTIONS OF THE LIMBICSYSTEM
 Olfaction
 Autonomic responses BP, Resp.
 Appetite and eating behavior
 Sleep and dreams
 Emotional responses
Fear
Rage and placidity
Autonomic and endocrine
responses
 Sexual behavior
 Addiction and motivation
 Memory
 Social cognition

43. LIMBIC CLINICAL SYNDROMES
Hypolimbic Hyperlimbic
Mania
Depression OCD
Apathy
Utilization Behaviour
Amnesia (Hippocampus)
Social disdecorum
Kluver-Bucy Syndrome (Amygdala)
Anxiety/Panic
Psychosis
Limbic Epilepsy
Limbic encephalitis
Rage (Hypothalamus & Amygdala)

44. LIMBIC SYSTEM - CLINICAL IMPLICATIONS
TEMPORAL LOBE EPILEPSY
Form of focal epilepsy, a chronic neurological condition, Characterized by Recurrent
epileptic seizures arising from one or both temporal lobes
Two main types
Mesial temporal lobe epilepsy (MTLE)
Lateral temporal lobe epilepsy (LTLE)
Mesial temporal sclerosis –
47-70% of all TLE
Severe neuronal loss in CA1, May spread to involve CA3 and CA4,
CA2 and dentate are only mildly involved
Pathological abnormalities:-
Specific pattern of hippocampal neuron cell loss (m/c)
Associated with hippocampal atrophy and gliosis
Dispersion of granule cell layer in dentate gyrus
Pts classically describe fear, déjà vu, jamaisvu, elementary and complex visual
hallucinations, illusions, forced thinking, emotional distress.

45. 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:-
severe impairment of short-term memory (cardinal sign),
confusion,
psychiatric symptoms (changes in behavior & mood –
irritability, depressive , sleep disturbances),
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

46. 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

47. 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) atypical sexual
behavior, mounting inanimate objects.
 Visual Agnosia/ "psychic blindness" (inability to visually recognize
objects)

48. 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

49. LIMBIC SYSTEM IN SCHIZOPHRENIA
 Ventricular enlargement
 Reduced limbic volumes
 Decreased size of hippocampus & thalamic
 Decreased amygdala response during facial recognition tasks (fMRI)
 Decreased activity in dorsolateral prefrontal cortex (PET)
 The Papez circuit is probably involved in schizophrenia.
 The distortion of cortical neuronal organization of layer II of the ERC
 Decreased size of hippocampus
 Reduced number of GABAergic cells in the cingulate and anterior
thalamus with resultant glutamatergic excitotoxicity.

50. 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.

51. 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.

52. 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

53. 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
Thank You