Limbic system - History, Components, Functional circuits and Psychiatric implications.

1. DR. BALAJI SAINATH. A
1ST YEAR PG
The Limbic System

2. 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.

3. History
 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).
 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.

4. Contd..
 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.

5. NEURAL CIRCUIT FOR EMOTION AS ORIGINALLY
PROPOSED BY JAMES PAPEZ

6. Contd..
 This concept was supported by
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.

7. Contd..
 Paul Maclean(1952) -- coined
the term limbic system to
describe broca’s lobe and
related subcortical nuclei as
the neural substitute for
emotion.

8. Concept of limbic system
 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.

9. Components 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 and cortical areas
 Other parts included are -- insula, entorhinal cortex,
nucleus accumbens

10. Drawing of the major anatomical structures of the
limbic system

12. 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.
)

13. 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
)

14. The Dentate gyrus
 Narrow notched band of gray
matter.
 Comprises of 3 layers - outer
acellular layer, middle granule
cell layer, inner polymorphic
layer.
 Lies between fimbria of the
hippocampus and the
parahippocampal gyrus
 Anteriorly– continued into the
uncus
 Posteriorly– continuous with
indusium griseum
)

15. The Hippocampus
 Curved elevation of gray matter.
 Extends throughout the entire legnth 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 & adjacent to
the polymorphic layer of hippocampus.
 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

16. The Subicular complex
 Includes presubiculum,
parasubiculum, and the
subiculam parts.
 The transition region
between the hippocampus
and parahippocampal
gyrus.
)

18. 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 posterior aspect.
 These nuclei form several distinct clusters: the basolateral
complex, the centromedial amygdaloid group, the olfactory
group.
 CB1 receptor immunoreactivity found in basolateral complex.
***
 Centromedial amygdala appears to be part of a larger
structure that is continuous through the sublenticular
substantia innominata with the bed nucleus of stria
terminalis (extended amygdala).

19. The Septal area
 Gray matter
structure located
immediately above
the anterior
commissure.

20. The hypothalamus, The Thalamus and
Cortical areas
 Is a crucial component of neural circuitry regulating not
only emotions, but also autonomic, endocrine, and some
somatic functions.
 Subdivided from anterior to posterior into 3 zones: the
supraoptic region, the infundibular region, and the
mamillary region.
 These 3 zones also are divided on each side into medial
and lateral areas by the fornix.
***
 The lateral and medial mamillary nuclei receive
hippocampal input through fornix and project to the
anterior nuclei of hypothlamus.

22. 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

23. The Uncus
 Formed by the amygdala and the rostral
hippocampus.
The Insula
 Medial cortical gyrus located between the amygdala
and the frontal lobe.
)

24. Connections of the limbic system
 The major structures of limbic system are
interconnected with each other and with other
components of nervous system in various ways.
 In general, 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

25. Functional circuit b/w hippocampal formation,
Thalamus, cerebral cortex and hypothalamus

26. Functional circuit b/w amygdala, hypothalamus
Prefrontal and temporal association cortices

27. Contd..
 Basolateral nuclei of amygdala directly and reciprocally
connected with the temporal, insular and prefrontal
cortices and shares bidirectional connections 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.

28. Contd..
 Both of these pathways reveal how the limbic system
is able to integrate the highly processed sensory and
cognitive information content of the cerebral cortical
circuit with the hypothalamic pathways that control
autonomic and endocrine systems.
 In addition,
 The limbic system also interacts with components of
the basal ganglia system.

29. Functional circuits b/w basal ganglia and
limbic system

30. Contd..
 The septal area reciprocally connected with the
hippocampus, the amygdala, and the hypothalamus
and projects to numerous structures in the
brainstem.
 Limbic system also receives inputs from the smell
receptors in the nose.

31. Functions of the limbic system
 Olfaction – entorhinal cortex
 Appetite and eating behaviours
 Amygdala – food choice & modulation of food intake
 Lateral nucleus – feeding
 Ventromedial nucleus – satitey
 Sleep and dreams
 Suprachiasmatic nucleus – circadian rhythm/ sleep-wake
cycle
 Ventrolateral preoptic nucleus (VLPO) – sleep switch/
promoting (REM) sleep

32. Contd..
 Emotional responces
 Fear – amygdala
 Rage – neocortex, ventromedial nucleus, septal
nucleus
 Placidity – B/L amygdala
 Autonomic and endocrine responces to emotion –
cingulate gyrus & hypothalamus
 Sexual behaviour – medial preoptic area of
hypothalamus (MPOA) & medial amygdala (MeA)
 Addiction and motivation – amygdala & nucleus
accumbens

33. Contd..
 Memory
 Emotional memory – amygdala , prefrontal cortex,
medial temporal lobe
 Longterm declarative memory – hippocampus
 Social cognition – cingulate gyrus & amygdala

34. LS Vs Adrenal gland
 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

35. The LS (amygdala) in Emotions
 In generel, amygdala assign emotional significance
to sensory experiences.
 LS directs the hypothalamus to express the motor
and endocrine components of emotional states.
 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 repetition as
they become familiar (habituation).

36. Contd..
 The amygdala was shown to be important to
processing these experiences.
 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.

37. The LS (hippocampus) in Memory
 Hippocampus is concerned
with recent memory
converting it to long term
memory– memory of the
remote past events before
the lesion developed is
unaffected.
 In damage to
hippocampus– the memory
of what is happening to the
patient personally fails to
become familiar.

38. Contd..
 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.

39. The LS (hippocampus) in Motivation and
Attidude
 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.

40. The LS in Sexual behavior
 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.

41. The LS in Violence behavior
 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 responses.
 Aggressive behavior 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.

42. Case of Arthur Shawcross
Was an American serial killer, also known as the Genesee
River Killer in Rochester, New York.
Psychiatrists had assessed Shawcross as a "schizoid psychopath".
Shawcross pleaded not guilty by reason of insanity.
Prosecution psychiatrist Dr. Park Dietz said Shawcross had antisocial
personality disorder.

43. The LS in positive mental health
(anterior cingulate and insula)
 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.
 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.

44. Contd..
 Anterior cingulate fMRI images light up when a lover
gazes at pictures of a partner’s face or when a new
mother hear her infant’s cry.
 Insula helps to bring visceral feelings into consciousness.
 The pain in one’s heart or grief , the warmth in one’s
heart or love, and the tightness in one’s gut from fear all
make their way into consciousness through the insula.
 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.

45. 1 . SCHIZOPHRENIA
2. BPAD
3. ANXIETY & OCD
4. AUTISM
5. ALZHIEMERS
6. LIMBIC ENCEPHALOPATHY
7 . WERNICKE & KORSAKOFF
8. EPILEPSY
9. KLOVER BUCY SYNDROME
10.PSYCHOSURGERY
Clinical implications

46. Schizophrenia
 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.

47. Contd..
 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.

48. BPAD
 Evidence of hyperactivity and hyperfunction of some
limbic and para limbic areas - including amygdala
and ventral striatum as well as in the cerebellum.
 Evidence of limbic hyperactivity is consistent with
the lack of modulation and overswings in both manic
and depressive behaviours.
 Amygdala is small in children and large in adults
when compared to controls in BPAD.
 The number of hospitalizations for mania was
directly associated with increased size of the
amygdala.

49. 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.

50.  Disproportionate impairment in specific aspects of
social cognition.
 Limbic structures involved - cingulate gyrus and
amygdala which mediate cognitive and affective
processing.
 The basolateral circuit integral for social cognition is
disrupted in autism spectrum disorders.
Autism

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

52. 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.

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

54. Epilepsy in hippocampal sclerosis
 Hippocampal cell loss can be considered as a cause
and consequence of repeated seizures.
 Hippocampal sclerosis seen in 47—70% of all TLE.

55. 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.

56. 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 - indscriminately seek
partnership with male, female animals.

57. 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.

58. THANK YOU