Limbic system brain
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Transcript of Limbic system brain
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LIMBIC SYSTEM“visceral, vital, or emotional brain.”
DR PRAVEEN K TRIPATHI
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Scheme of presentation
HistoryAnatomy and organisationConnections and circuitsFunctionsDiseases and abnormalities
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History Concept of Limbic SystemBroca (1877) - ‘La Grand Lobe Limbique’
Papez (1937) - ‘Limbic Circuit’ - emotion
MacLean (1952) - ‘Limbic System’ - visceral brain
Nauta (1972) - ‘Septo-hypothalamo-mesencephalic continuum’
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PAUL BROCA (1824-1880)
JAMES PAPEZ (1883-1958)
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Paul D. MacLean (1913- )
Limbic System- term of Paul MacLean (1952)- Visceral Brain
HypothalamusNucleus accumbensamygdaloid nuclear complexorbitofrontal cortex
Some psychiatric implications onphysiological studies on fronto-temporal portions of limbic system(visceral brain). ElectroencephalogrClin Neurophysiol 4: 407-418, 1952
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Septo-(Preoptico)-Hypothalamo- Mesencephalic Continuum
Main Components of Limbic System
Septal Region Hypothalamus
LimbicMidbrain
Area Hippocampal
Formation
Limbic cortex
AmygdaloidNuclearComplex
SpinalCord
&BrainStem
Limbic System
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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.
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Heinrich Klüver Paul Clancy Bucy (1897-1979) (1904-1992)
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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.
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limbic lobe
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.
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Limbic lobe 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
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The Limbic System
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Components
Archicortex hippocampal formation and dentate gyrus
Paleocortex rostral parahippocampal gyrus and uncus
Juxtallocortex / mesocortex cingulate gyrus
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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
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Limbic system limbic lobe and all the cortical and subcortical
structures related to itSeptal nucleiAmygdalaHypothalamus (particularly the mamillary body)Thalamus (anterior and medial thalamic nuclei)Brain stem reticular formationEpithalamusNeocortical areas in the basal fronto-temporal regionOlfactory cortexVentral parts of the striatum
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Subcortical Structures 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.
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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.
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Hypothalamus highest subcortical center
body temperature Appetite water balance pituitary functions emotional content
most potent control of the autonomic nervous system
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Thalamusnociceptive pathwayshypothalamus reticular system cingulate, frontal association
cortex
Epithalamus habenular nuclei habenulopeduncular tract midbrain tegmentum and interpeduncular
nucleus.
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• Septal area
▪ septum pellucidum glia ,lined by ependyma
▪ septum verumvental to s. pellucidum
▪ Poorly developed in humans
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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
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Septal connectionsAmygdala stria terminalis ,ventral amygdalofugal
pathway
Hypothalamus medial forebrain bundl Midbrain (PAG and VTA )medial forebrain bundle Habenular nuclei stria medullaris thalami
Interpeduncular nucleus of the midbrain habenulointerpeduncular tract
Thalamic nuclei septothalamic tract
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Functions
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.
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AUTONOMIC EFFECTS Stimulation inhibitory effect
Cardiac deceleration reversible with atropine septal effects are mediated via the
cholinergic fibers of the vagus nerve.
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SEPTAL SYNDROME
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.
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Nucleus Accumbens
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.
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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
THE HIPPOCAMPUS
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The hippocampus (Ammon's horn)
Ammon the Egyptian Ram God Seahorse
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Ammon’s horn(Cornu Ammonis)
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Hippocampus Proper CA1 CA2 CA3 CA4 - Area Dentata Dentate Gyrus Subiculum Prosubiculum Subiculum Presubiculum Parasubiculum
Hippocampal Formation
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Hippocampus
Hippocampus of humans contains 1.2 million principal neurons on each side, a figure close to the number of pyramidal tract fibers
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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
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The HippocampusCA 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 ventricleB) Ependymal glia
C) Alvear layer
1. Polymorph Layer
2. Pyramidal Layer
3. Molecular Layer(pyramidal dendrite)
(pyramidal axon)
(pyramidal cell body)
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Hippocampus is divided in three parts Based on relation to brain stem Head : anterior edge of brain stemBody : adjacent to brain stemTail : ascending , curving behind brain stem
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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.
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Intrinsic ConnectionsClassic Trisynaptic Pathway1. 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
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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 --> DG4. 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 nuclei3. (septo-hippocampal path - thru fornix)
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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
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Entorhinal Cortex
.1 entorhinal cortex2. uncus 3. fornix4. dentate gyrus 5. hippocampal sulcus 6. collateral sulcus
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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
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Efferent Connections
FORNIX 1. Alveus 2. Fimbriae 3. Crus4.
Commissure5. Corpus 6. Column
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Efferent Connections
Fornix - from pyramidal neurons of hippocampus & subiculum
Postcommissural Fornix – main bundle toMammillary Body Anterior Thalamus Lateral Septal Nuclei
Hypothalamus Midbrain Tegmentum
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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 entorhinalcortex, which collects infofrom other association areasdentate gyrus hipp formation + subculumoutput to fornix andalso back to entorhinal cortex
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Summary of Hippocampal ConnectionsAfferent 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
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Efferent Connections
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
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Functions
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
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declarative (explicit) memoryfacts, words, and data that can be brought to mind and consciously inspected
plays a time-limited role (being needed only for recently acquired information)
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Episodic memory more severely disrupted than semantic memory
left hippocampus verbal memory right hippocampus nonverbal memory
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low threshold for epileptic activity spread of such epileptic activity to the
nonspecific thalamic system, and hence all over the cortex, is not usual
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Why Selective Vulnerability?
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.
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Seizure Activity
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
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Why Not All Pathological Processes Produce Seizures?
critical age during infancy and early childhood for the acquisition of the pathology
There might be an age-related remodeling of intrinsic hippocampal connections
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Cingulate Cortex
anterior thalamic nuclei contralateral and ipsilateral cingulate
cortex temporal lobe via the cingulum bundle corpus striatum and most of the
subcortical limbic nuclei.
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The cingulate cortex is continuous with the parahippocampal gyrus at the isthmus behind the splenium of the corpus callosum.
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Cingulate Cortex
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
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Amygdala
K. F. Burdach’s term
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The amygdalar nuclei (Gk :“almonds”)
tip of the temporal lobe beneath the cortex of the uncus and rostral to the hippocampus and the inferior horn of the lateral ventricle.
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Nuclei
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
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Amygdala ConnectionsCerebral cortex
Olfactory systemThalamus
Brainstem reticular formationHypothalamus
AMYGDALA
Striaterminalis
Ventral Amygdalofugalfibers
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Amygdala Inputs
AMYGDALACorticomedial Nuclear
GroupBasolateral Nuclear
GroupCentral Nucleus
OlfactorySystem
Temporal Lobe(associated with visual,auditory, tactile senses)
Brainstem (viscerosensory relayNuclei: solitary nucleus
and parbrachial nucleus)
VentralAmygdalofugal
Fibers
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Amygdala Outputs
AMYGDALACorticomedial Nuclear
GroupBasolateral Nuclear
GroupCentral Nucleus
VentralAmygdalofugal
Fibers
Septal NucleiHypothalamus
Dorsal Medial Thalamic NucleusNucleus Accumbens
Hypothalamus
Nuclei ofANS
VentralAmygdalofugal
Fibers
Stria Terminalis
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Connections of the Amygdala
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Extended Amygdala
ConnectionsAfferents 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.
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Neurotransmitters
Acetylcholine gamma-aminobutyric acid (GABA) noradrenaline serotonin dopamine substance P enkephalin.
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Afferent Pathways
exteroceptive afferents :olfactory, somatosensory, auditory, and visual) for integration with interoceptive stimuli from a variety of autonomic areas
(1) prefrontal, temporal, occipital, and insular corticeshighly 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
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Efferent Pathways
Mostly terminate in nuclei that regulate endocrine and autonomic function, and others are directed to the neocortex
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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
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Functions AUTONOMIC EFFECTS
heart rate, respiration, BP, and gastric motility
Stimulation Both increase and decrease depending on the.
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ORIENTING RESPONSEStimulation 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.
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EMOTIONAL BEHAVIOR AND FOOD INTAKE
corticomedial nuclear group Lesionaphagia, decreased emotional
tone, fear, sadness, and aggression Stimulation defensive and aggressive
reaction basolateral nuclear group
Lesionhyperphagia, happiness, and pleasure reactions.
Stimulation fear and flight.
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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
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FACIAL EXPRESSION
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 expressionsfor negatively valenced emotions (fear, anger, and
sadness).
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AROUSAL RESPONSE
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
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SEXUAL ACTIVITY
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.
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MOTOR ACTIVITY
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
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CLINICAL ASPECT
low threshold for electrical discharges focus of seizures.
kindlingCPS : oral and licking movements
with a loss of conscious activity
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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
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Basal Forebrain Area
structures deep to the anterior perforating substance
Olfactory Tubercle Substantia Innominata Basal Nucleus of Meynert
Ventral Pallidum - non cholinergic portions of the substantia innominata - part of limbic basal ganglia
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Limbic Basal Ganglia
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
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Limbic System and Basal Nuclei
Medial and lateral temporal lobeHippocampus
AmygdalaEntorhinal cortex (24)
Ventral Striatum(nucleus accumbens)
Caudate Nucleus(head)
Anterior Cingulate GyrusOrbitofrontal Areas (10, 11)
Ventral PallidumMedial Globus Pallidus
Pars Reticularis(Substantia nigra)
Ventral Anterior NucleusDorsomedial Nucleus
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Papez Circuit (Emotions)Mammillary bodies
Other hypothalamic nucleiSeptal nuclei
Substantia innominata(Basal nucleus of Meynert)
Hippocampal Formation(hippocampus
and dentate gyrus)Anterior Thalamic
nuclear group
Cortex of Cingulate GyrusParahippocampal Gyrus
Neocortex
Fornix Mammillothalamictract
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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.
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Taxonomy of Long-term Memory Systems
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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.
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Overview of Limbic Motor Systems
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TRANSIENT GLOBAL AMNESIA
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
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KLÜVER-BUCY SYNDROME
amygdala, hippocampal formation, and adjacent neural structures.Visual agnosia or psychic blindnessHyperoralityHypersexuality Lack of emotional response, blunted
affect, and apathy.Increased appetiteMemory deficit.
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SCHIZOPHRENIA
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
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ALZHEIMER'S DISEASE
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.
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Limbic encephalitis
InfectiousNon infectious
Paraneoplastic Non PLE ; VGKC Ab LE
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HERPES SIMPLEX ENCEPHALITIS severe focal necrotizing process with a
predilection for the limbic system
intranuclear viral inclusions (Cowdry type A inclusions) and inflammation within limbic structures
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Wenicke’s –Korsakkof’s syndrome 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
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AMYGDALO-HIPPOCAMPECTOMY
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 by Yasargil. More restrictive and greater risk of injury to M1 portion of MCA within sylvian fissure
Complications: vascular injury is the most significant risk.
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Cingulotomy for Intractable Psychiatric Illness
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
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References 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
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