limbic system and its clinical importance.pptx

limbic system

1. LIMBIC SYSTEM-IT’S CLINICAL IMPLICATION PRESENTER – Dr. Shaitan Singh Jat SR Neurology MODERATORS – Dr. Trilochan Shrivastava Sir Dr. Rahul Gupta Sir

2. Contents Historical Aspects Introduction Components of Limbic System Papez Circuit Clinical Implications

3. Historical Aspects Paul Broca 1878 le grand lobe limbique James Papez 1937 Papez Circuit Paul Kluver & Heinrich Bucy First evidence of cortical 1939 representation of emotions in limbic system Paul Maclean 1952 Limbic System

4. Functional anatomic system of interconnected cortical and sub cortical structures. Area of intimate processing between the hypothalamus and cortical information. Plays a role in emotions, learning and autonomic regulation. INTRODUCTION

5. THE BROAD FUNCTIONAL DIVISIONS • Rostral limbic system : Amygdala, septum, orbitofrontal cortex, anterior insula, and anterior cingulate. – Important for emotion • Caudal limbic system : Hippocampus, posterior parahippocampal cortex and posterior cingulate. – Important for memory and visual-spatial functions

6. Limbic lobe Cingulate gyrus Para hippocampal Gyrus Hippocampal formation Dentate Gyrus Hippocampus proper Subiculum Amygdala Septal area Hypothalamus Others - cortex and insula, uncus, stria terminalis Components of limbic system

7. The amygdala Located in medial temporal lobe Just anterior to the hippocampal formation It is fused with the tip of the tail of the caudate nucleus Stria terminalis emerges from its post aspect

8. Amygdala Inputs AMYGDALA Corticomedial Nuclear Group Basolateral Nuclear Group Central Nucleus Olfactory System Temporal Lobe (associated with visual, auditory, tactile senses) Brainstem ( viscerosensory relay Nuclei: solitary nucleus and parbrachial nucleus) Ventral Amygdalofugal Fibers Mediates behaviors triggered by olfactory stimuli Mediates emotional responses Attaching emotional significance to a stimulus

9. Amygdala Outputs AMYGDALA Corticomedial Nuclear Group Basolateral Nuclear Group Central Nucleus Ventral Amygdalofugal Fibers Septal Nuclei Hypothalamus Limbic Association Cortex Prefrontal Cortex Hippocampal Formation Dorsal motor n. Of X Reticular formation Hypothalamus Nuclei of ANS Ventral Amygdalofugal Fibers Stria Terminalis Learning emotional significance Autonomic responses Regulation of “appetitive behaviours ”; i.e. , Eating in response to smells

10. Emotional Learning - Formation and storage of memories associated with emotional events. Modulation of Memory Consolidation - Following any learning event, the long-term memory for the event is not formed instantaneously. Rather, information regarding the event is slowly assimilated into long-term storage over time, possibly via Long-term Potentiation. Aggression - Animal studies have shown that stimulating the amygdala appears to increase both sexual and aggressive behaviour.  Alcoholism and binge drinking - Alcoholism is associated with dampened activation in brain networks responsible for emotional processing, including the amygdala. Functions of the Amygdala

11. 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 Continue..

12. Limbic Cortex 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 Isthmus of the cingulate gyrus, Parahippocampal gyrus Subcallosal area.

13. CINGULATE GYRUS Location - Dorsal to the corpus callosum Connections – 1. Heavily interconnected with the association areas of the cerebral cortex. 2. Receives inputs from the anterior nucleus of the thalamus and the neocortex, somatosensory areas of the cerebral cortex. 3. It projects to the entorhinal cortex via the cingulum. Functions - 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.

14. PARAHIPPOCAMPAL GYRUS Located - In the medial temporal lobe. Includes - 1. Perirhinal Cortex 2.Entorhinal Cortex Function - Important role in memory encoding and retrieval. ERC funnels highly processed cortical information to the hippocampal formation and serves as its major output pathway.

15. A subcortical banana-shaped structure composed of allocortex structure. Location - In the temporal lobe as the floor of the inferior horn of the lateral ventricle. The 3 components Hippocampal Formation

16. S shaped in coronal section. It has 3 distinct zones: Dentate Gyrus Hippocampus Proper Subiculum UPPER LIMB forms hippocampus. Two parts – Cornu Ammonis Dentate Gyrus MIDDLE LIMB connects cornu ammonis with parahippcampal gyrus – subiculum LOWER LIMB – parahippocampal gyrus

17. DENTATE GYRUS Lies between 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 Major Input- Perforant pathway from layer II & III of the Entorhinal Cortex The Perforant Pathway - Medial Perforant path Lateral Perforant path It was in this pathway that long term potentiation was first discovered. Function- Formation of memories Play a role in depression.

18. In cross section resembles “sea horse”. Is the inferomedial structure of the parahippocampal formation. Stretches in a ‘C’ shape formation over the corpus callosum. Divided into several zones of pyramidal cells on the basis of the fiber connections: CA1 – CA 4 fields Trilaminate structure Molecular Pyramidal Polymorphic The most sensitive area in the brain for Ischemic events in hippocampus is CA1 (Sommer’s Sector). HIPPOCAMPUS

19. SUBICULAR COMPLEX Subiculum is the transitional zone between the six-layered entorhinal cortex and the three-layered hippocampus. Components: Pre subiculum Para subiculum Subiculum

20. Hippocampal Circuits F o r n i x branch ( Postcommisural Branch) F o r n i x ( Precommissural ) ( septal-hippocampal pathway) (Hippocampal commissure) ( Perforant & alvear path) Afferents Efferents HIPPOCAMPUS (Cortico-entorhinal projections) ERC/Sub (PHG) Cortex Septal nuclei Mammillary Body Contralateral Hippocampus 1. & 2.

21. The Hippocampus Dentate Complex (HC-DG) Afferent Pathways Pyramidal cell (CA1,2) PHG (ERC, Sub) Dentate gyrus (granule cells) mossy fibers Pyramidal cell (CA3) schaffer collaterals perforant path alvear path Septal nuclei septo - hippocampal path - thru fornix

22. Functions of the Hippocampus Declarative Memory – Facts and events. Spatial Memory - The hippocampus contains place cells that encode spatial memory Recalling of place, and of the routes required to navigate them requires hippocampal activation.

23. Septal Area Location - Situated ventral to corpus callosum. Parts - Paraterminal Gyrus & Septum Pellucidum. Connections – 1. Receive olfactory fiber from medial olfactory stria. 2. Septal nuclei receive reciprocal connections from the Hippocampus via the fornix. Functions – 1. Also called as the Medial Olfactory Area has no relation to the sense of smell, but it is considered a pleasure zone in animals. 2. Septal nuclei play a role in reward and reinforcement along with the Nucleus Accumbens .

24. Elements of Diencephalon Habenular nucleus- Lies in habenular triangle at the root of pineal body. Mammillary Bodies Anterior thalamic nucleus Afferent from – Mammillary body Efferent to – Cingulate gyrus Thought to play a role in the modulation of alertness and are involved in learning and episodic memory. Hypothalamus

25. Mammillary Bodies Located at the ends of the anterior arches of the fornix. Acts as a relay for impulses coming from the amygdala and hippocampi, via the  mamillo -thalamic tract to the thalamus. This circuit, from amygdalae to mammillary bodies, and then on to the thalamus, is part of the larger ' Papez circuit'. Fuctions – 1. Episodic Memory 2. Adding the element of smell to the memories.

26. Hypothalamus Lamina terminalis Mamillary body Hypothalamic sulcus Septum pellucidum Pellucidum Choroid plexus Aqueduct Interventricular foramen HYPOTHALAMUS

27. The hypothalamus also divide anteroposteriorly into three regions Supraoptic ( chiasmatic ) -Lie above optic chiasma Tuberal ( infundibulotuberal ) -includes infundibulum tubercinereum Mamillary (posterior) -consists of mamillary body and area above it)

28. Functions Hormonal Release – Through its control of the anterior and posterior pituitary. Hormonal and Behavioural Circadian Rhythms Control of food intake - Extreme lateral part of the ventromedial nucleus of the hypothalamus is responsible for the control of food intake. Fear processing - The medial zone of hypothalamus is part of a circuitry that controls motivated behaviours, like defensive behaviours.

29. Papez Circuit (Medial Limbic Circuit) Mammillary bodies Other hypothalamic nuclei Septal nuclei Substantia innominata (Basal nucleus of Meynert ) Hippocampal Formation (hippocampus and dentate gyrus) Anterior Thalamic nuclear group Cortex of Cingulate Gyrus Entorhinal Complex ( Parahippocampal Gyrus ) Neocortex Fornix Mammillothalamic tract

30. Functions 1. Emotion – Initially believed that the Papez circuit was involved in emotions. But no further evidence of involvement in emotions. 2. Memory – Especially Episodic and Spatial memory.

31. LIMBIC SYSTEM - CLINICAL IMPLICATIONS

32. TEMPORAL LOBE EPILEPSY Form of focal epilepsy, characterized by recurrent epileptic seizures arising from one or both temporal lobes Two main types Mesial temporal lobe epilepsy (MTLE) – Arises from Hippocampus, Para hippocampal gyrus and Amygdala. Lateral temporal lobe epilepsy (LTLE) Mesial temporal sclerosis – Cause of 47-70% of all TLE Pathological abnormalities:- Specific pattern of hippocampal neuron cell loss - Severe neuronal loss in CA1, May spread to involve CA3 and CA4, CA2 and dentate are only mildly involved Associated with hippocampal atrophy and gliosis 2. Dispersion of granule cell layer in dentate gyrus

33. Signs and Symptoms Pre- ictal symptoms – 1. Autonomic sensations – Fullness of stomach Blushing Changes in respiration 2. Cognitive sensations – Deja vu, Jamais vu, dreamy states 3. Affective States – Fear, Depression, Elation 4. Automatisms – Lip smacking, rubbing, chewing Ictal Symptoms – Recurrent seizures usually simple partial but can be complex partial also. Duration – 1-2 minutes Sensory hallucinations – visual auditory, olfactory ( m.c .) and gustatory. Absence seizures

34. Interictal Symptoms – Personality changes – Hyposexuality Perseverative approach to interactions (viscosity) References to personal destiny and philosophical themes (left TLE) Excessive emotionality (right TLE) Psychotic symptoms – Interictal are more common than intraictal psychosis. 10% of all complex partial epilepsy patients develop psychotic symptoms. Classically they appear in those who have had epilepsy for a long time and developed personality changes. Most characteristic symptoms – Hallucinations and paranoid delusions. Violence Affective symptoms – Seen less than psychotic symptoms. Episodic High incidence of suicide in patients with epilepsy.

35. LIMBIC ENCEPHALITIS: Limbic encephalitis is a form of encephalitis. An inflammatory process involving the hippocampi, amygdala and less frequently fronto -basal and insular regions of the limbic system and other parts of the brain.  Clinical features:- 1. Severe impairment of short-term memory (cardinal sign) 2. Confusion 3. Psychiatric symptoms (changes in behaviour & mood – irritability, depressive , sleep disturbances), 4. 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 encephalitis are viral in nature, PLE is often associated with cancer

36. ALZHEIMERS’ DISEASE Neurodegenerative changes in limbic system. Amyloid proteins build up and form amyloid plaques (outside cells). Neurofibrillary 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.

37. KLUVER-BUCY SYNDROME Neurobehavioral 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) Hypermetamorphosi s (an irresistible impulse to attend & react to visual stimuli) Inappropriate Sexual Behaviour (Hyper sexuality Visual Agnosia/ "psychic blindness" ( inability to visually recognize objects) A combination of 3 or more symptoms is typically suggestive of the diagnosis.

38. The visual agnosia in KB syndrome presumably results from damage to the amygdala, which normally functions as a site of transfer of information between sensory association cortex and the Hypothalamus. After the damage to amygdala, visual stimuli can no longer be paired with affective responses.

39. 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, lack of interest or concern, executive function deficits. Recent memory more affected than remote, Immediate recall is usually preserved.

40. LIMBIC SYSTEM IN SCHIZOPHRENIA Ventricular enlargement Reduced limbic volumes Decreased volume of hippocampus Decreased amygdala response during facial recognition tasks ( fMRI ) Decreased activity in dorsolateral prefrontal cortex (PET) Papez circuit is probably involved in schizophrenia. Distortion of cortical neuronal organization of layer II of the ERC Reduced number of GABAergic cells in the cingulate and anterior thalamus with resultant glutamatergic excitotoxicity.

41. 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.

42. 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.

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