LIMBIC SYSTEM

1. DR PRAVEEN KTRIPATHI

2.  History
 Anatomy and organisation
 Connections and circuits
 Functions
 Diseases and abnormalities

3.  Concept of Limbic System
 Broca (1877) - ‘La Grand Lobe Limbique’
 Papez (1937) - ‘Limbic Circuit’ - emotion
 MacLean (1952) - ‘Limbic System’ - visceral brain
 Nauta (1972) - ‘Septo-hypothalamo-mesencephalic
continuum’

4. PAUL BROCA
(1824-1880)
JAMES PAPEZ
(1883-1958)

5. Paul D. MacLean (1913- )
Limbic System
- term of Paul MacLean (1952)
- Visceral Brain
Hypothalamus
Nucleus accumbens
amygdaloid nuclear complex
orbitofrontal cortex
Some psychiatric implications on
physiological studies on fronto-
temporal portions of limbic system
(visceral brain). Electroencephalogr
Clin Neurophysiol 4: 407-418, 1952

6. Septo-(Preoptico)-Hypothalamo- Mesencephalic Continuum
Main Components of Limbic System
Septal
Region
Hypothalamus
Limbic
Midbrain
Area
Hippocampal
Formation
Limbic cortex
Amygdaloid
Nuclear
Complex
Spinal
Cord
&
Brain
Stem
Limbic System

7.  Scoville and Milner memory loss
following bilateral ATL
 Bilateral hippocampal ablation loss of recent
memory and anterograde amnesia
 The amygdala  German physician Burdach
in the early 19th century.

8. Heinrich Klüver Paul Clancy Bucy
(1897-1979) (1904-1992)

9.  Klüver and Bucy in 1939 hypersexuality
in monkeys after bilateral temporal lobectomy
 The human counterpart was described by
Terzian and Dalle Ore in 1955 and by
Marlowe in 1975.

10.  structures that form a limbus (ring or border) around the brain
stem.
 The limbic lobe is a synthetic lobe whose component parts are
derived from different lobes of the brain (frontal, parietal,
temporal)
 subcallosal gyrus
 cingulate gyrus
 isthmus
 parahippocampal gyrus
 uncus
The term limbic system refers to the limbic lobe and the
structures connected to it.

11.  crescent of tissue
that caps the lateral
end of the fissure,
bulges into the
medial wall and
floor of the
temporal horn and
then curves
medially above the
dentate gyrus

13.  Archicortex hippocampal formation and
dentate gyrus
 Paleocortex rostral parahippocampal
gyrus and uncus
 Juxtallocortex / mesocortex cingulate
gyrus

14.  Originally, the limbic lobe was assigned a
purely olfactory function.
 only a minor part of the limbic lobe has
olfactory function
 Rest of the limbic lobe plays a role in
emotional behavior and memory

15.  limbic lobe and all the cortical and subcortical
structures related to it
 Septal nuclei
 Amygdala
 Hypothalamus (particularly the mamillary body)
 Thalamus (anterior and medial thalamic nuclei)
 Brain stem reticular formation
 Epithalamus
 Neocortical areas in the basal fronto-temporal region
 Olfactory cortex
 Ventral parts of the striatum

17.  Reticular Formation of the Brain Stem and Spinal
Cord
 limbic nuclear groupings
(1) mesencephalic reticular formation hypothalamus,
thalamus, and septum
(2) the locus ceruleus of the upper pons and the raphe of
the midbrain ascending serotoninergic and
adrenergic systems onto the diencephalon and
telencephalon.

18. Interpeduncular Nucleus
 habenulopeduncular tract hypothalamus
and the midbrain limbic region
 Amygdaloidal information via the stria
terminalis to the septum and then from the
septum to the interpeduncular nucleus.

19. Hypothalamus
 highest subcortical center
 body temperature
 Appetite
 water balance
 pituitary functions
 emotional content
 most potent control of the autonomic
nervous system

20.  Thalamus
nociceptive
pathways
hypothalamus
reticular system cingulate, frontal association cortex
 Epithalamus
 habenular nuclei  habenulopeduncular tract
midbrain tegmentum and interpeduncular nucleus.

21. • Septal area
▪ septum pellucidum  glia ,lined by ependyma
▪ septum verumvental to s. pellucidum
▪ Poorly developed in humans

22.  The hippocampal-septal relationship is
topographically organized
 specific areas of the hippocampus project on
specific regions of the septum
 CA1 medial septal region
 CA3 and CA4 lateral septal region
 medial septal region to CA3 and CA4

23.  Amygdala stria terminalis ,ventral amygdalofugal pathway
 Hypothalamus medial forebrain bundl

 Midbrain (PAG andVTA )medial forebrain bundle
 Habenular nuclei  stria medullaris thalami
 Interpeduncular nucleus of the midbrain
habenulointerpeduncular tract
 Thalamic nuclei septothalamic tract

25.  ACTIVITY
 high initial state of activity in response to a novel
situation which rapidly declines almost to
immobility.
 LEARNING
 tend to learn tasks quickly and perform them
effectively once they have been learned.
 REWARD
 Stimulation pleasure or rewarding effects.

26.  AUTONOMIC EFFECTS
 Stimulation inhibitory effect
 Cardiac deceleration  reversible with
atropine
 septal effects are mediated via the cholinergic
fibers of the vagus nerve.

27.  Destruction of the septal nuclei behavioral
overreaction to most environmental stimuli.
 changes occur in sexual and reproductive behavior,
feeding, drinking, and the rage reaction
 ACh euphoria and sexual orgasm
 Septal recording during sexual intercourse spike and
wave activity
 septal damage  increased sexual activity in humans.

28.  below the caudate
 amygdala ventral amygdalofugal pathway
 basal ganglia major link between the limbic and
basal nuclei
 high content of acetylcholine
 Alzheimer’s disease  significant loss of cholinergic
neurons in this nucleus.

29.  crescent of tissue that caps the lateral end of
the fissure, bulges into the medial wall and
floor of the temporal horn and then curves
medially above the dentate gyrus

30. The hippocampus (Ammon's horn)
Ammon the Egyptian Ram God
Seahorse

31. Ammon’s horn
(Cornu Ammonis)

32. Hippocampus Proper
CA1
CA2
CA3
CA4 - Area
Dentata
Dentate Gyrus
Subiculum
Prosubiculum
Subiculum
Presubiculum
Parasubiculum
Hippocampal Formation

33.  Hippocampus of humans contains 1.2 million
principal neurons on each side, a figure close
to the number of pyramidal tract fibers

34. Archicortex - 3 layers
Hippocampus Proper
Molecular Layer
Pyramidal Layer
Polymorphic Layer
Dentate Gyrus
Molecular Layer
Granular Layer
Polymorphic Layer
Subiculum
Transitional type between hippocampal archicortex and entorhinal
paleocortex
Hippocampal Formation - Archicortex

35. The Hippocampus
CA fields
A) Lateral Ventricle, B) ependymal glia (ventricular surface), C) Alvear Layer, (pyramidal axons)
3 layers of hippocampus (archicortex):
1. Polymorph Layer (pyramidal axons & basket cells (-))
2. Hippocampal pyramidal layer (pyramidal cell bodies)
3. Molecular Layer (pyramidal dendrites)
A) Lateral ventricle
B) Ependymal glia
C) Alvear layer
1. Polymorph Layer
2. Pyramidal Layer
3. Molecular Layer(pyramidal dendrite)
(pyramidal axon)
(pyramidal cell body)

36. Hippocampus is divided in three parts
Based on relation to brain stem
Head : anterior edge of brain stem
Body : adjacent to brain stem
Tail : ascending , curving behind brain stem

37. Hippocampal Head
The hippocampal head is the voluminous anteror part of the
arc of the hippocapus.
It includes an intraventricular part and an extraventricular
part.

39. Intrinsic Connections
ClassicTrisynaptic Pathway
1. Entorhinal cortex (perforant
path)
 dentate gyrus granular cell
2. Granular cell axon (mossy fiber)
CA3 pyramidal cell
3. Pyramidal cell (Schaffer
collateral)
CA1 pyramidal cell
 subiculum  entorhinal cortex

40. The Hippocampus Dentate Complex
(HC-DG)
Afferent Pathways
Pyramidal cell
(CA1,2)
PHG (ERC, Sub)
1. Perforant Pathway: PHG (ERC) --> DG
Also ….
2. Alvear Pathway: PHG --> CA1
3. Septo-hippocampal path (via fornix): Septal nuclei --> DG
4. Hippocampal commissure (connects bilateral hippocampi)
Dentate gyrus
(granule cells)
(mossy fibers)
Pyramidal cell
(CA3)
(schaffer collaterals)
1. (perforant path)
(Also note: this efferent path
closes the HC circuit loop!)
2. (alvear path)
Septal nuclei
3. (septo-hippocampal
path - thru fornix)

41. Afferent Connections
From Entorhinal Cortex
Alveolar Path
from medial part of EC
to CA1 and Subiculum
Perforant Path
from lateral part of EC
to CA1, CA2, CA3 and
Dentate Gyrus

42. Entorhinal Cortex
.1 entorhinal cortex
2. uncus
3. fornix
4. dentate gyrus
5. hippocampal
sulcus
6. collateral sulcus

43. Afferent Connections
EC & Hippocampal Afferents
Surrounding Neocortex
from association areas
- temporal, frontal lobe
Limbic System
from hypothalamus,
amygdala, septal area,
anterior thalamic nuclei,
and midbrain limbic area

44. Efferent Connections
FORNIX
1. Alveus
2. Fimbriae
3. Crus
4. Commissure
5. Corpus
6. Column

45. Efferent Connections
Fornix
- from pyramidal neurons of hippocampus &
subiculum
Postcommissural Fornix – main bundle
to Mammillary Body
Anterior Thalamus
Lateral Septal Nuclei
Hypothalamus
Midbrain Tegmentum

46. Hippocampal Formation:
Circuitry.
A.Components and structure –
a banana-shaped structure with its
components (dentate, hipp,
subiculum) folded upon one
another like a “jelly roll”.
Inputs are from entorhinal
cortex, which collects info
from other association areas
dentate gyrus
hipp formation + subculum
output to fornix and
also back to entorhinal cortex

47. Summary of Hippocampal Connections
 Entorhinal Cortex
Alveolar Path
from medial part of EC to CA1 and Subiculum
Perforant Path
from lateral part of EC
to CA1, CA2, CA3 and
Dentate Gyrus
 Dentate Gyrus
Mossy fiber - CA3
Schaefer fiber (CA3-CA1)
 Others
Hypothalamus, Septal Nuclei, Substantia Innominata
Midbrain Limbic Area

48.  fornix
 from Pyramidal Neurons of hippocampus & subiculum
 Precommissural Fornix
 Nucleus Accumbens Septi
 Anterior Hypothalamic Area
 Medial Surface of Frontal Lobe
 Anterior Olfactory Nucleus
 Postcommissural Fornix
 to Mammillary Body
 Anterior Thalamus
 Hypothalamus
 Bed Nucleus of Stria Terminalis

49.  attention and alertness
 Stimulation of the hippocampus in animals
 glancing and searching movements
 bewilderment and anxiety
 Unilateral ablation of the hippocampus in humans
does not affect memory to a significant degree

50.  declarative (explicit) memoryfacts, words, and
data that can be brought to mind and consciously
inspected
 plays a time-limited role (being needed only for
recently acquired information)

51.  Episodic memory more severely disrupted than
semantic memory
 left hippocampus verbal memory
 right hippocampus  nonverbal memory

52.  low threshold for epileptic activity
 spread of such epileptic activity to the nonspecific
thalamic system, and hence all over the cortex, is
not usual

53.  CA1 NMDA receptors.
 dentate hilus ,CA3 sector kainate receptors
 Activation by glutamate entry of calcium ions into
the pyramidal neurons
 The pyramidal neurons of these sectors contain very
little calcium-buffering protein
 repeated activation of these pyramidal neurons
could result in cell death.

54.  75% of the complex partial seizures arise in the temporal lobe;
the remainder arise in the frontal lobe
 Seizures might arise in the temporal neocortex, majority arise
in the mesial temporal structures, particularly the hippocampus
 The hippocampus has a low threshold for seizure discharge;
consequently, stimulation of any region that supplies
hippocampal afferents or stimulation of the hippocampus itself
might produce seizures
 Hippocampal stimulation respiratory and cardiovascular
changes, as well as automatisms (stereotyped movements)
involving the face, limb, and trunk

55.  critical age during infancy and early childhood for
the acquisition of the pathology
 There might be an age-related remodeling of
intrinsic hippocampal connections

56.  anterior thalamic nuclei
 contralateral and ipsilateral cingulate cortex
 temporal lobe via the cingulum bundle
 corpus striatum and most of the subcortical limbic
nuclei.

57.  The cingulate
cortex is
continuous
with the
parahippocamp
al gyrus at the
isthmus behind
the splenium of
the corpus
callosum.

58.  Stimulation respiratory, vascular, and visceral
changes, but changes less than hypothalamic
stimulation.
 Interruption of the cingulum bundle, which lies deep
to the cingulate cortex and the parahippocampal
gyrus, has been proposed as a less devastating way
to produce the effects of prefrontal lobotomy
without a major reduction in intellectual capacity

59. Amygdala
K. F. Burdach’s
term

60.  tip of the temporal lobe beneath the cortex of
the uncus and rostral to the hippocampus and
the inferior horn of the lateral ventricle.

62.  Corticomedial - central : small ,phylogenetically
older
 connections with the phylogenetically older
regions -olfactory bulb, hypothalamus, and brain
stem
 Basolateral : larger , phylogenetically recent
 connections with the cerebral cortex
 intimately and reciprocally connected with the
prefrontal cortex via the uncinate fasciculus

63. Cerebral cortex
Olfactory system
Thalamus
Brainstem reticular formation
Hypothalamus
AMYGDALA
Stria
terminalis
Ventral Amygdalofugal
fibers

64. 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

65. AMYGDALA
Corticomedial Nuclear
Group
Basolateral Nuclear
Group
Central Nucleus
Ventral
Amygdalofugal
Fibers
Septal Nuclei
Hypothalamus
Dorsal Medial Thalamic Nucleus
Nucleus Accumbens
Hypothalamus
Nuclei of
ANS
Ventral
Amygdalofugal
Fibers
Stria Terminalis

66. Connections of the Amygdala

67. Extended Amygdala
Connections
Afferents from
Intra-amygdaloid association
fibers from basolateral
amygdaloid nucleus,
whic recieves wealth of
modality-specific and
multimodal sensory input
from the cerebral cortex.
Efferents to
Hypothalamus and
Brain Stem
Extended Amygdala
- bridging cell groups directly
interconnects amygdaloid
and bed nucleus of stria
terminalis (BST)
which refered to as
Extended amygdala.

68.  Acetylcholine
 gamma-aminobutyric acid (GABA)
 noradrenaline
 serotonin
 dopamine
 substance P
 enkephalin.

69.  exteroceptive afferents :olfactory, somatosensory,
auditory, and visual) for integration with interoceptive
stimuli from a variety of autonomic areas
(1) prefrontal, temporal, occipital, and insular
corticeshighly processed somatosensory, auditory,
and visual sensory information from modality-specific
and multimodal association areas as well as visceral
information
(2) the thalamus (dorsomedial nucleus)
(3) the olfactory cortex
(4) cholinergic input from the nucleus basalis of Meynert

70.  Mostly terminate in nuclei that regulate
endocrine and autonomic function, and others
are directed to the neocortex

71.  The two amygdala communicate with each other
through the stria terminalis and the anterior
commissure
 Nuclear groups within each amygdaloid nuclear
complex communicate with each other via short
fiber systems

72.  AUTONOMIC EFFECTS
 heart rate, respiration, BP, and gastric motility
 Stimulation  Both increase and decrease
depending on the.

73.  ORIENTING RESPONSE
 Stimulation enhances the orienting response to
novel events.
 Animals with amygdalar lesions manifest reduced
responsiveness to novel events in the visual
environment
 Their responsiveness, however, is improved if they
are rewarded for the response.

74.  corticomedial nuclear group
 Lesionaphagia, decreased emotional tone, fear,
sadness, and aggression
 Stimulation defensive and aggressive reaction
 basolateral nuclear group
 Lesionhyperphagia, happiness, and pleasure
reactions.
 Stimulation  fear and flight.

75.  attack behavior
 Amygdalar stimulation gradual buildup and
gradual subsidence upon the onset and cessation
of stimulation.
 Hypothalamic stimulation begins and subsides
almost immediately after the onset and cessation
of the stimulus.
 prior septal stimulation prevents aggressive
behavior of both amygdala and hypothalamus
stimulation

76.  link the perception of the face to the retrieval of
knowledge about its emotional and social meaning.
 Bilateral amygdalar lesions alteration in social behavior
and social cognition, especially as related to the
recognition of social cues from faces,impaired recognition
of facial expressions
 Functional imaging studies activation of the amygdala
during presentation of emotional facial expressions
 for negatively valenced emotions (fear, anger, and
sadness).

77.  Stimulation of the basolateral nuclear group of the
amygdala arousal response that is similar to but
independent of that of ARAS.
 Stimulation of the corticomedial nuclear group of
the amygdala, by contrast, produces the reverse
effect (a decrease in arousal and sleep).
 The net total effect of the amygdala, however, is
facilitatory

78.  contains the highest density of receptors for sex
hormones
 Stimulation erection, ejaculation, copulatory
movements, and ovulation
 Bilateral lesions of the amygdala produce
hypersexuality and perverted sexual behavior.

79.  Stimulation CMN group complex rhythmic
movements related to eating, such as chewing,
smacking of the lips, licking, and swallowing
 Electric stimulation of the amygdala elicits
defensive or fear-related behavior
 The amygdaloid projections to the hypothalamus
via the ventral amygdalofugal pathway seem to be
essential for fear-related behavior

80.  low threshold for electrical discharges
focus of seizures.
 kindling
 CPS : oral and licking movements with a loss
of conscious activity

81.  Stimulation of the amygdala during brain
surgery autonomic and emotional reactions
,feeling of fear and anxiety, déjà vu
 Destruction of both amygdalas  relieve
intractable epilepsy and treat violent behavior.
 Such patients usually become complacent
and sedate and show significant changes in
emotional behavior

82. structures deep to the anterior perforating substance
 OlfactoryTubercle
 Substantia Innominata
 Basal Nucleus of Meynert
 Ventral Pallidum
 - non cholinergic portions of the substantia innominata
 - part of limbic basal ganglia

83.  Ventral Striatum
 Afferents
hippocampal formation
amygdaloid body
cingulate gyrus
ventral tegmental area
dorsal raphe nuclei
 Efferents
mediodorsal (MD) thalamus
substantia nigra
subthalamic nucleus
amygdaloid nucleus
lateral habenular nucleus

84. Medial and lateral temporal lobe
Hippocampus
Amygdala
Entorhinal cortex (24)
Ventral Striatum
(nucleus accumbens)
Caudate Nucleus
(head)
Anterior Cingulate Gyrus
Orbitofrontal Areas (10, 11)
Ventral Pallidum
Medial Globus Pallidus
Pars Reticularis
(Substantia nigra)
Ventral Anterior Nucleus
Dorsomedial Nucleus

86. 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 GyrusParahippocampal Gyrus
Neocortex
Fornix
Mammillothalamic
tract

87. Memory
• Short-term memory
– The information is accessed via temporary
links or associations formed in the
hippocampus.
• Long-term memory
– The links in the hippocampus are replaced
by more permanent connections within the
cerebral cortex itself.
• Both types of memories involve the
storage of information in the cerebral
cortex.

88. Taxonomy of Long-term Memory Systems

89. Memory
• Hippocampus
– Essential for acquiring new long-tern
memories, but not for maintaining them.
• Amygdala
– Formation and storage of memories
associated with emotional events.
– Involved in the modulation of memory
consolidation.

90. Overview of Limbic Motor Systems

91.  sudden memory loss of recent events, transient
inability to retain new information (anterograde
amnesia), retrograde amnesia of variable extension.
 Complete recovery within a few hours.
 epilepsy, migraine headache, and tumor.
 bilateral transient ischemia of medial temporal
structures
 spreading cortical depression in medial temporal
structures

92.  amygdala, hippocampal formation, and adjacent
neural structures.
 Visual agnosia or psychic blindness
 Hyperorality
 Hypersexuality
 Lack of emotional response, blunted affect, and
apathy.
 Increased appetite
 Memory deficit.

93.  disorganized thought processes, hallucinations,
delusions, and cognitive deficits.
 Vulnerability to schizophrenia is 60% genetic and 40%
environmental.
 Cytoarchitectural studies in schizophrenic brains point
to abnormal laminar organization in limbic structures
that are suggestive of abnormal neuronal migration
during brain development

94.  atrophic gyri and widened sulci most prominent in
the limbic cortex
 Association cortices are heavily affected,
primary sensory cortices are minimally affected and
the motor cortex is least affected.

95.  Infectious
 Non infectious
 Paraneoplastic
 Non PLE ;VGKC Ab LE

96.  severe focal necrotizing process with a predilection
for the limbic system
 intranuclear viral inclusions (Cowdry type A
inclusions) and inflammation within limbic
structures

97.  Thiamine deficiency mammilary body
 Infarcts of the medial or anterior thalamic areas
 mammillothalamic tract
 Tumors of the posterior hypothalamus.
 Lesions in the fornix .
 corpus callosum
 Lesions of the basal forebrain

98. Two basic approaches:
1. transcortical: image guidance is very helpful
 A. Niemeyer approach: 2-3 cm longitudinal cortical
incision through the middle temporal gyrus centered at
a point ≈ 4 cm posterior to the temporal tip
 B. approach through the anterior superior temporal
gyrus
2. transsylvian: approach advocated byYasargil. More
restrictive and greater risk of injury to M1 portion of
MCA within sylvian fissure
 Complications: vascular injury is the most significant
risk.

99.  The major psychiatric diagnostic groups that might
benefit from cingulotomy are
1. chronic anxiety states, including OCD, and
2. major affective disorder (i.e., major depression or
bipolar disorder).
 Oblique coronal MR images are obtained and
typically, target coordinates are calculated for a
point in the anterior cingulate gyrus 2 to 2.5 cm
posterior to the tip of the frontal horn, 7 mm from
the midline, and 2 to 3 mm above the corpus
callosum bilaterally

100.  Stephen G.Waxman, MD, PhD;
ClinicalNeuroanatomy,Twenty-Sixth Edition
 Snell, Richard S; Clinical Neuroanatomy, 7th Edition
 T. Scarabino,U. Salvolini ;Atlas of Morphology and Functional
Anatomy of the brain
 Stanley Jacobson, Elliott M Marcus; Neuroanatomy for the
Neuroscientist
 Charles R. Noback, Norman L. Strominger;The Human
Nervous System Structure and Function , sixth edition

101. THANKYOU