1. The Limbic System
PRESENTER:
DR. MD. OSMAN ALI

2. Scheme of presentation
 Introduction
 Anatomy
 Physiology
 Applied aspects

3. Case of Arthur Shawcross

4. What is limbic system?
 It includes structures
forming a border
between
hypothalamus and
cerebral cortex.
 It is simply functional
anatomic system of
interconnected
cortical and
subcortical structures.

5. Parts of limbic system
Parts mostly listed are
 Limbic cortex—the cingulate and the
parahippocampal gyri

The hippocampal formation– the dentate gyrus, the
hippocampus, the subicular complex.

The amygdala

The septal area

The hypothalamus, the related thalamic(ant) and
cortical areas
Other parts included are--- insula, entorhinal
cortex, nucleus accumbens
No unanimity exists on brain structures that constitute
the LS


6. History of concept of the limbic system 1
 Paul Broca– coined the term limbic(Le
Grand Lobe Limbique)-- to include
curved rim of cortex including
cingulate and parahippocampal gyrus
which was different from the rest of the
cerebral mantle(appeared
paler)(Broca’s cortex/lobe).
This cortex later shown to be
composed of only three layers–
labelled allocortex to distinguish it
from the six layered eucortex that
make up most of the cerebral mantle

7. History of concept of the limbic
system 2
 James Papez(1937)– postulated
these cortical regions(the
cingulate gyrus and the
parahippocampal gyrus ) are
linked to
hippocampus, mamillary body
and anterior thalamus in circuit
that mediated emotional
behaviour(Papez circuit)
 Emotions tend to go round and
round in this circuit

8. History of concept of the LS 3
 Heinrich Kluver and Paul
Bucy(1939)—by removing
temporal lobes in monkeys they
found that amygdala of temporal
lobe has role in taming and other
basic instincts–
fighting, fleeing, feeding and sex
 Kluver Bucy syndrome

9. History of concept of the LS 4
 Paul Maclean(1952)--- coined
the term limbic system to
describe broca’s lobe and
related subcortical nuclei as
the neural substitute for
emotion

10. History of concept of limbic system 5
 Originally term limbic system encompassed only
Broca’s cortex and Papez’s circuitry and later
amygdala is included
 Further, the functions of amygdala and
hippocampal system proved to have more to do
with attention and formation of specific memories
than with emotions

11. The Cingulate gyrus
 Located dorsal to corpus callosum
 Includes several cortical regions
that are heavily interconnected
with) the association areas of the
cerebral cortex
 Posteriorly, it becomes
continuous (via cingulate bundle
of fibres in the white matter) with
the parahippocapal gyrus.

12. The Parahippocampal gyrus
 Located in medial
temporal lobe
 Lies between the
)hippocampal
fissure and
the collateral sulcus
 Continuous with the
hippocampus along with
the medial edge of the
temporal lobe

13. The Dentate gyrus
 Narrow notched band of gray
matter
 Lies between fimbria of the
hippocampus and the
parahippocampal gyrus
)
 Anteriorly– contunued into the
uncus
 Posteriorly– continuous with
indusium griseum

14. The hippocampus
 Curved elevation of gray matter
 Extends throughout the entire lenghth of the floor
of the inferior horn of the lateral ventricle
 Expanded anterior end --- pes hippocampus
 Terminates posteriorly– beneath the splenium of
corpus callosum
 Alveus– thin layer of white matter beneath the
convex ventricular surface
 Fimbria– bundle formed by nerve fibres originated
in hippocampus--- becomes continuous with the
crus of fornix – passes anteriorly and inferiorly--coloumn of fornix pass through hypothalamus into
the mamillary bodies

15. The Subicular complex
 Includes pre, para, and the
subicular parts
 The transition region
)
between the hippocampus
and parahippocampal
gyrus

16. 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
 It– is a group of nuclei larger
basolater, smaller centromedial
 Centromedial amygdala appears to be part of
a larger structure that is continuous through
the sublenticular innominate with bed
nucleus of stria terminalis(extended
amygdala)

17. The septal area
 Gray matter
structure located
immediately above
the anterior
commissure

18. The insula
 Medial cortical gyrus located
between the amygdala and the
frontal lobe
)

19. The uncus
 Formed by the amygdala and the
rostral hippocampus

20. The entorhinal cortex
 Located in the anterior part of the parahippocampal
gyrus, on medial surface of temporal lobe
 Transition zone between hippocampus and temporal
neocortex

21. The hypothalamus, the thalamus and
cortical areas
 The lateral and medial mamillary
nuclei receive hippocampal input
through fornix and project to the
anterior nuclei of hypothlamus

28. Histology of the limbic system 1
 Cortical structure of parahippocampal gyrus is
six layered. As the cortex is traced into the
hippocampus,there is gradual trasnition from a
six to a three layered arrangement
 The hippocampus has-- outer molecular, middle
pyramidal and inner polymorphic layer. It is
divided into three distinct fields– CA1, CA2 and
CA3 (CA=Cornu Ammonis)
--Molecular layer-- consist of nerve fibres and
scattered small neurons
--Pyramidal layer-- consist of many large
pyramid shaped neurons
---Polymorphic layer-- is similar to the
polymorphic layer of the cortex seen else where

29. Histology of limbic system 2
 The dentate gyrus comprises three layers– outer acellular
molecular, middle granular and inner polymorphic layer.
Pyramidal layer is replaced by the granular layer
---Granular layer is composed of densely arranged
rounded or oval neurons that give rise to axons that
terminate upon the dendrites of the pyramidal cells in
hippocampus
 Basolateral nuclei of amygdala– have connectivity and
some other anatomical characteristics similar to cortical
region

30. Histology of limbic system 3
 John Allman and Giacomo
Rizzolatti identified the limbic
spindle cells and mirror cells the
undergrid prosocial mentation
 Spindle cells(Von Economo)–20
times more in humans than apes--concentrated in ant cingulate
gyrus, prefrontal cortex, the insula-- central to governance of social
emotion and moral judgement

31. Histology of limbic system 4
 Mirror cells– more developed in
humans than in primates--reside in insula, ant cingualte—
 - mediate empathy– the
experience of feeling the
emotions of another

32. Connections of the limbic system 1
 The major structures of limbic system are
interconnected with each other and with other
components of nervous system in various ways.
 In generel, it is area of intimate processing between
hypothalamus and cortical information processing
 The connecting pathways of limbic system are– the
alveus, the fimbriae, the fornix, the mamillothalamic
tract, and the stria terminalis

33. Connections of limbic system 2
 Entorhinal cortex funnesl highly processed cortical
information to the hippocampal formation and dentate
gyrus
 The layers of dentate gyrus connected each other and
finally project to the hippocampus
 The fields CA3 and CA1 of hippocampus are connected
each other and finally project to subicular complex

34. Connections of limbic system 3
 Basolateral nuclei of amygdala directly and reciprocally
connected with the temporal, insular and prefrontal
cortices---- n shares bidirectional connctions with the
medial dorsal thalamic nuclei
 Medial amygdaloid nucleus has reciprocal connections
with endocrine portion of hypothalamus
 Lateral part of extended amygdala connected with
brainstem and lateral hypothalamus and receives cortical
limbic region and the basolateral amygdaloid complex

35. Connections of the LS 4
 The septal area reciprocally connected with the
hippocampus, the amygdala, and the hypothalamus and
projects to numerous structures in the brainstem
 Posterior nuclei of hypothalamus shares reciprocal
connections with extended amygdala
 LS also interacts with components of the basal ganglial
system. Thus functions of basal ganglia extens beyond the
regulation of motor activities
 Limbic system recieves inputs from the smell receptors in the
nose

36. Functions of the limbic system 1
 The Ls is involved in behaviour required for self-
preservation and the preservation of species
 control over instinctual behaviour regulated by
hypothalamus and brainstem
 Critical in emotions such as fear
 Plays a role is sexual behaviour
 Has special role in memory

37. Functions of limbic system(ant, post
cingulate) 2
 Ant cingulate -- for integrating affective and motor
behaviour– stimulation of the anterior cingulate
triggers autonomic nervous system
 Excessive stimulation leads to amplification of
emotions and motor responses and may lead to
anxiety, tics, impulsivity, and OCD. Inhibition leads
to akinetic mutism
 Post cingulate is important for visual spatial and
memory functions

38. Functions of limbic system(amygdala vs
adrenal gland)3
 Anatomy and physiology of the adrenal gland are
reflected in the anatomy and physiology of the
amygdala circuit and hippocampal circuit
 Adrenaline secreted by the adrenal core is processed
by the amygdala system
 Cortisone secreted by adrenal cortex is processed by
the hippocampal formation

39. Functions of limbic system (functional
divisions) 4
 Rostral limbic system—
amygdala, septum, orbitofrontal cortex, anterior
insula, and anterior cingulate --important for
emotions
 Caudal system– hippocampus, posterior
parahippocampal cortex and posterior cingulate -important for memory and visual spatial functions

40. The functions of limbic
system(neurotransmitters) 5
 Neurotransmitter system in limbic system include–
dopamine, serotonin, noradrenergic, and cholinergic
systems

41. The LS (amygdala) in emotions 1
 In generel, amygdala assign emotional significance
to sensory experiences
 Ls directs the hypothalamus to express the motor
and endocrine components of emotional states

42. The LS (amygdala) in emotions 2
 Emotional experiences and expressions per se are
accompanied and even initiated by body responses
(change in heart and respiratory rate and blood
pressure). The responses waned with repitition as
they become familiar(habituation)
 The amygdala was shown to be important to
processing these experiences.(selective activation of
amygdala=framing effect)

43. The LS(amygdala) in emotions 3
 The body responses help a person to attain via the
amygdala, a certain kind of memory and that
emotions is due to a challenge to the pattern of that
memory, not the body responses themselves
 Fear is not an expression of an experience per se, but
of a memory based anticipation of pain that may be
realistic and imagined

44. The LS (hippocampus) in memory 1
 Hippocampus is concerned
with recent memory
converting it to long term
memory– memory of the
remote past events before the
lesion developed is unaffected.
 Anterograde amnesia is
present
 Hippocampal circuit places
bounds, boundaries on
experience and behaviour

45. The LS (hippocamppus) in memory 2
 The hippocampus is important to an organism’s ability to
reset an internal co-ordinate system. This process is critical to
navigation and episodic memory
 While the amygdala is processing what is novel during
habituation, the hippocampus is processing the context within
which habituation is happening: the hippocampus is
processing what is already familiar
 The co-ordinates are constructed by attending to what is
not, at the moment, the focus of navigating our world. Eg: to
walk through a door we must process the walls so as not to
bump into them

46. The LS (hippocampus) in memory 3
 In damage to hippocampus– the memory of what is
happening to the patient personally fails to become
familiar

47. The LS(hippocampus) in motivation and
attidude 1
 The hippocampal circuit brings together emotion
and motivation
---The emotion—the processing of familiarty
---The Motivation– the processing of readiness to
engage the world in practical manner
 Attitudes (emotions plus motivation) are
dispositional states that embody the experience of
the individual

48. The LS(hippocampus) in motivation and
attitude 2
 Freud’s project for a scientific psychology developed
a theory of motivation based on memory rather than
on drive. Freud noted that motivation are the
prospective aspects of memories
 Papez simply stated that the circuit could account for
attitudes without saying how

49. The LS in sexual behaviour
 Directly involved in elements of sexual functioning
 Stimulation of various sites of the limbic system have elicited penile
erection.
 Hippocampus– genital tumescence, regulation of release of
gonadotropins.
 Amagdala– in oral and then in genital benaviour
 Olfactory sense is strongly involved in both feeding and mating
 Those areas activated by emotions of fear and anxiety are notably
quiescent when the woman experience an orgasm

50. The LS in violence behaviour
 The fear is processed in amygdala – stimulation of it elicits
defensive and aggressive responses
 Other parts involved are– hypothalamus and septal area
 The prefrontal cortex allows humans to exercise some control
over their resposes
 Aggressive behaviour have been noted individual with damage
to the medial temporal lobe and with developing brain tumor
in the limbic system
 Frontal lobe injury commonest type in infancy and early
childhood have lifelong consequences
 Case of serial killer Arthur Shawcross

51. The LS in positive mental health(ant
cingulate and insula) 1
 Both the limbic anterior cingulate and insula appears
to be active in the positive emotions of humor, trust
and empathy
 The prosocial biological activity of the anterior
cingulate cortex and insula was highest in
individiuals with highest level of social awareness--the biological differences for positive mental health

52. The LS(ant cingulate gyrus) in positive
mental health 2
 Anterior cingulate gyrus links valence and memory
to create attachment
 Along with the hippocampus, the anterior cingulate
is the brain region most responsible for making the
past meaningful
 Anterior cingulate fMRI images light up when a lover
gazes at a pictures of a partner’s face or when a new
mother hear her infant’s cry

53. The LD(insula) in positive mental health 3
 Helps to bring visceral feelings into consciousness
 The pain in one’s heart of grief , the warmth in one’s
heart of love, and the tightness in one’s gut from fear
all make their way into consciousness through the
insula

54. The LS in positive mental
health(hippocampus and amygdala) 4
 fMRI studies of kundalini yoga practitioners
demonstrates-- the meditation activates the activity
of the hippocampus and right lateral amygdala which
in turn leads to parasympathetic stimulation and
sensation of deep peacefulness

55. The LS in positive mental health(frontal
lobe) 5
 Frontal lobe connectivity to the limbic system
underscores its executive function which includes the
ability to delay gratification, comprehend symbolic
language, and most important, to establish temporal
sequencing
 Frontal lobes through their connection to the
amygdala, hippocampus and other limbic structures
encode emotional learning quite distinct from both
conventional conditioning and declarative memory

56. The LS in schizophrenia 1
 Because of its role in controlling emotions, the LS has
been hypothesized to be involved in pathophysiology of
schizophrenia
 Limbic activation is diminished
 Abnormally increased limbic activation time(threat
related fascial emotions of anger and fear)
 Antipsychotics block limbic receptors to dopamine as
well as receptors of the extrapyramidal system

57. The LS in schizophrenia 2
 Neuropathology findings—decrease
in size of regions including the
amygdala the hippocampus and
parahippocmapal gyrus
 Hippocampus is not only
smaller, but is functionally
abnormal as indicated by
disturbances in glutamate
transmission
 Disorganisaion of neurons within
the hippocampus has also been
reported

58. The LS in BPAD
 Hyperactivity and hyperfunction of some limbic and
para limbic areas---including amygdala and ventrial
striation as well as in the cerebellum

59. The LS is anxiety and OCD
 In addition to receiving noradrenergic and
serotonergic innervation the LS contains highest
concentration of GABA A receptors
 Increased activity of the septohippocampal
pathway—leads to anxiety
 Cingulate gyrus has been particulary implicated in
pathophysiology of OCD

60. The LS in dementia
Involved in
 Alzheimers disease
 Limbic encephalitis
 Wernick/Korsakoff
 Anoxic encephalopathy
 HSV encephalitis
 Post traumatic amnesia
 Strokes involving PCA or thalamoperforators
 ACOM aneursyms

61. The LS in Alzhiemers
 Gross– medial temporal lobe atrophy and
hippocampal atrophy most common
 Plaques and tangles most frequently present in
hippocampal and entorhinal cortex

62. Limbic encephalopathy
 Usually due to metastatic ca of lung
 Marked disturbance of memory for recent events
 Affective disturbance– severe anxiety and depression
 Pathology– combination of degeneration and
inflammation on the medial temporal lobe structures—
the hippocampus, uncus, amygdaloid nucleus, dentate
gyrus, insular and posterior orbital cortex
 Where memory failure is predominat feature the
possibity of limbic encephalopathy should be considered

63. The LS in Wernicke and Korsakoff
 Caused by B1 deficiency
 Changes involve periventricular areas: medial
thalamus, hypothalamus, mamillary
bodies, PAG, reticular formation
 Lesions show petechial hemorrhages, edema, myelin
loss, and reactive gliosis. Neurons generally
preserved.

64. The LS in epilepsy n hippocampal
sclerosis
 Hippocampal cell loss can be considered a cause and
consequence of repeated seizures
 Hippocampal sclerosis—seen in 47—70% of all TLE

65. Limbic epilepsy
 Limbic epilepsy can originate in the
amygdala, hippocampus, entorhinal cortex, cingulate
or orbital frontal cortex
 Pts classically describe fear, déjà vu, jamais
vu, elementary and complex visual
hallucinations, illusions, forced thinking, or
emotional distress.

66. Kluver Bucy syndrome
 Bilateral removal of temporal lobe– amygdala, para
amygdala area
 Features– no evidence of fear or anger, unable to
appreciate object visually, increased
appetite, increased sexual activity- indscriminatly
seek partnership with male, female animals

67. Herpes simplex encephalitis

68. The LS in psychosurgery
 Stereotactic operations on the amygdaloid nuclei:
decreased emotional excitability
 OCD: cingulotomy, anterior cingulotomy, and limbic
leucotomy may be effective
 Pain: cingulotomy
 Epilepsy:TLE
 Tourette: disconnection of the anterior cingulate from
the thalamus results in improvement of symptoms

69. References
 Kaplan and saddock’s comprehensinve textbook of
psychiatry 9th ed (2009), lippincott w&w
 Lishman, organic psychiatry
 Snell’s clinical neuroanatomy for medical students
 Ganong’s review of physiology,Lange
 Internet

70. Thank you