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: borderRefers to a ring of gray matter on the medial aspect of the cerebral hemispheres.
LIMBIC SYSTEMINTRODUCTION 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 SYSTEMTHE 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
Anterior perforated substance• Mass of gray matter on either side of optic chiasma• Perforated by central branch of MCAPyriform 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
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 COMPLEXSubuculum is the transitional zone between the six-layered entorhinal cortex and the three-layered hippocampusthree 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
The hypothalamus also divide anteroposteriorly into four regionsPreoptic 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 nucleusMamillary or posterior Posterior nucleus Tuberomamillaryregion nucleusMamillary body Mamillary nuclei
Connections of the hypothalamusHypothalamus is concerned withvisceral functionConnected to various parts oflimbic system, reticularformation, autonomic centers inbrainstem and spinal cord.It also releases secretions into theblood stream and into CSF.
Afferent connections NeocortexThe hypothalamus receives visceral(including taste) through spinal cord and Thalamus Limbic systembrainstem.Afferents from nucleus of tractussolitarius to hypothalamus carry taste Hypothalamussensation.Somatic afferents reach through Visual inputcollaterals of major ascending tractAfferents from olfactory pathway andlimbic system. Ascending(anterior perforated substance, septal Somatosensory Visceral centers pathway In brainstem &nuclei, amygdaloid Spinal cord.complex, hippocampus, pyriform cortex)
Cortico-hypothalamic fibresHypothalamus receive fibers from the cortex of the frontal lobeMany fibers relay in the thalamus (medial dorsal and midlinenuclei 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 nucleiThalamus -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 hypothalamusNeurons in some hypothalamic nuclei producebioactive peptides discharged to neighborhoodcapillaries (neurosecretion)Control of neurohypophysis (posterior lobe)-Vasopressin is secreted in supraoptic nuclei-Oxytocin is secreted in paraventricular nucleus.-
Control of hypophysis cerebri by hypothalamusAxons of paraventriculo-hypophyseal tractjoin axons arising from supra-optic nucleus Paraventicular nucleusto form supraoptico-hypophyseal tract.The axons of supraoptico-hypophyseal tract passdown into neurohypophysis where they branchand end in relation to capillaries and releasetheir secretion. Supraoptic Paraventriculo- nucleus Hypophyseal tractTogether known asHypoyhalamo-hypophyseal tract Supraoptico-hypophyseal tract Hypophysis cerebri
Control of adenohypophysis by hypothalamusHypothalamus control adenohypophysis by Paraventricular nucleusProducing number of releasing factors.Releasing factors travel through tubero-hypophyseal tract which receives fibers Limbic systemfrom various nuclei. Supra-Release the factors into the capillaries Tubero- chiasmatic infundib nucleus ularThe capillaries carry the factors into the tractpars anterior of hypophysis cerebri throughhypothalamo-hypophseal portal system. Fibres from Hypophysis cerebri brainstem
FUNCTIONAL CIRCUTARYOF LIMBIC SYSTEMPAPEZ 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 cats 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 SYSTEM - CLINICAL IMPLICATIONSTEMPORAL LOBE EPILEPSYForm of focal epilepsy, a chronic neurological condition, Characterized by Recurrent epileptic seizures arising from one or both temporal lobesTwo main types Mesial temporal lobe epilepsy (MTLE) Lateral temporal lobe epilepsy (LTLE)Mesial temporal sclerosis –47-70% of all TLESevere neuronal loss in CA1, May spread to involve CA3 and CA4,CA2 and dentate are only mildly involvedPathological abnormalities:- Specific pattern of hippocampal neuron cell loss (m/c) Associated with hippocampal atrophy and gliosis Dispersion of granule cell layer in dentate gyrusPts 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 amygdalaClinical 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 DISORDERREDUCTIONS IN VOLUME OF THE Frontal lobes Basal ganglia Amygdala HippocampusFunctional 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 ADHDOCD 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 Thank You