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Anant Kumar Rathi
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.
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.
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.
Limbic system
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
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
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
Limbic system
Limbic system
Limbic system
Olfactory pathway
                    Olfactory epithelium


                Olfactory nerve filaments



                       Olfactory bulb


                       Olfactory tract


    Lateral            Intermediate              Medial



     Uncus           Olfactory tubercal     Blend with cortex
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
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
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
Limbic system
Limbic system
Amygdala stimulation produces emotional
 behaviors through subcortical pathways
• 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).
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
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.
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.
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.
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
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.
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
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
 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.
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
Pellucidum
    Septum pellucidum                                   Hypothalamic sulcus



                                                                              Choroid plexus




                                         Hypothalamus
     Interventricular foramen

                                                                               Aqueduct




Lamina terminalis
                                   Mamillary body
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)
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
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.
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)
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
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
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.

-
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
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
Limbic system
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
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
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)
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.
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
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
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)
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
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.
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.
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.
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
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




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Limbic system

  • 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