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Limbic system and psychiatric disorders

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limbic system anatomy and functions and its importance in psychiatry and neurology

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Limbic system and psychiatric disorders

  1. 1. By : Dr. Karrar husain Moderator: Dr. Piyush P Singh
  2. 2.  The term "limbic"  Latin word limbus, for "border" or "edge“.  Paul Broca coined the term based on its physical location in the brain, sandwiched between two functionally different components.
  3. 3.  Paul Broca first called this part of the brain "le grand lobe limbique" in 1878,  but most of its putative role in emotion was developed only in 1937 when  the American physician James Papez described his anatomical model of emotion, the Papez circuit.
  4. 4.  James Papez published a journal article(1937) in which he outlined a "new" circuit to account for emotion.  He hypothesized that the hippocampus, the cingulate gyrus, the hypothalamus, the anterior thalamic nuclei,  and the interconnections among these structures constituted a mechanism which elaborate the functions of emotions
  5. 5.  Papez believed that the experience of emotion was determined by activity in  the cingulate cortex and, less directly, other cortical areas.  Emotional expression was thought to be governed by the hypothalamus.
  6. 6. NEURAL CIRCUIT FOR EMOTION AS ORIGINALLY PROPOSED BY JAMES PAPEZ
  7. 7.  Paul D. MacLean (May 1, 1913 – December 26, 2007) proposed triune brain theory.  MacLean's proposed that the human brain was in reality three brains in one:  the reptilian complex,  the limbic system,  and the neocortex.
  8. 8.  The Reptilian Brain : Core brainstem  homeostasis and survival.  The Paleomammalian Brain : the limbic system  Social and emotional attachment and motivated behaviours.  The Neomammalian Brain : neocortex and neocerebellum  skilled movements, logic thinking, languages and higher brain functions.
  9. 9.  There is no universal agreement on the total list of structures that should be included in limbic system.  All the authors include limbic cortex (cingulate and parahippocampal gyri), the hippocampal formation ,the amygdala, and the septal area.  Most include the hypothalamus, part of midbrain reticular formation and the olfactory areas.  Beyond that boundry get fuzzy; some authors include thalamic and neocortical regions
  10. 10. Hippocampus: Learning and Memory
  11. 11. Hippocampus: Learning and Memory Amygdala: Emotions and Aggression
  12. 12. Hippocampus: Learning and Memory Amygdala: Emotions and Aggression Hypothalamus: Hunger, Thirst Temperature Control
  13. 13. Hippocampus: Learning and Memory Amygdala: Emotions and Aggression Hypothalamus: Hunger, Thirst Temperature Control Thalamus: Relay Center for Sensory Information
  14. 14. Hippocampus: Learning and Memory Amygdala: Emotions and Aggression Hypothalamus: Hunger, Thirst Temperature Control Thalamus: Relay Center for Sensory Information
  15. 15. Drawing of the major anatomical structures of the limbic system
  16. 16.  limbic cortex  the cingulate gyrus and the parahippocampal gyrus.  The cingulate gyrus, located dorsal to the corpus callosum,  includes several cortical regions that are heavily interconnected with the association areas of the cerebral cortex.
  17. 17.  posteriorly, it becomes continuous with the parahippocampal gyrus, located in the medial temporal lobe.  Entorhinal cortex funnels highly processed cortical information to the hippocampal formation,  and also is a major output pathway from the hippocampal formation.
  18. 18.  Located in the floor of the temporal horn of the lateral ventricle  Three distinct zones—the dentate gyrus,  the hippocampus,  and the subicular complex.  These zones are composed of adjacent strips of cortical tissue, and fold over each other mediolaterally in a spiral fashion, giving rise to a C-shaped appearance
  19. 19.  Dentate gyrus  3 layers:  outer  acellular molecular layer  a middle layer  granule cells, extend their dendritic trees into the molecular and form the mossy fiber projection to the hippocampus;  and an inner polymorphic layer.
  20. 20.  Hippocampus is also a trilaminate structure  composed of molecular and polymorphic layers and a middle layer of pyramidal neurons.  hippocampus is divided into three distinct fields  CA3, CA2, and CA, on the basis of cytoarchitecture.
  21. 21.  subicular complex  3 components  the presubiculum,  the parasubiculum,  and the subiculum  It serve as transition regions between the hippocampus and the parahippocampal gyrus.
  22. 22. Drawing of a cross-sectional view of the hippocampal formation
  23. 23.  major input to the hippocampal formation arises layers II and III of the entorhinal cortex  that project to the dentate gyrus,  where they synapse on the dendrites of granule cells.
  24. 24.  The mossy fiber axons of the granule cells then provide a projection to CA3  Axon from CA3 project to the CA1 field of the hippocampus.  This region, in turn, projects to the subicular complex,  which provides output to the entorhinal cortex, completing the circuit.
  25. 25. Drawing showing intrinsic connectivity of hippocampal formation
  26. 26.  Group of nuclei  Located in the medial temporal lobe just anterior to the hippocampal formation  These nuclei form several distinct clusters:  the basolateral complex,  the centromedial amygdaloid group,  and the olfactory group, includes the cortical amygdaloid nuclei.
  27. 27.  Basolateral complex  largest group,  its connectivity and anatomical characteristics are more similar to cortical regions than to the remaining amygdaloid nuclei.  the basolateral nuclei are directly and reciprocally connected with the temporal, insular, and prefrontal cortices.
  28. 28.  like cortical regions, the basolateral complex shares bidirectional connections with the medial dorsal thalamic nucleus  and receives projections from the midline and intralaminar thalamic nuclei.  Neurons are pyramidal like and use excitatory neurotransmitter.
  29. 29.  the centromedial amygdala  two major subdivisions.  The central subdivision  central amygdaloid nucleus +lateral portion of the bed nucleus of the stria terminalis.  reciprocally connected with brainstem viscerosensory and visceromotor regions and with the lateral hypothalamus.  Also receives afferents from cortical limbic regions and the basolateral amygdaloid complex.
  30. 30.  the medial subdivision  composed of the medial amygdaloid nucleus  reciprocally connected with the medial or endocrine portions of the hypothalamus
  31. 31.  gray matter structure  above the anterior commissure.  The septal nuclei are reciprocally connected with the hippocampus,  the amygdala,  and the hypothalamus and project to a number of structures in the brainstem.
  32. 32.  lies at the center of the limbic system  subdivided into three zones:  the supraoptic region,  the tuberal region  and the mammillary region.  The three zones are divided on each side into medial and lateral areas by the fornix.
  33. 33. Drawing of the nuclei in the medial hypothalamus
  34. 34.  The major structures of the limbic system are interconnected with each other and with other components of the nervous system  sensory information from the cingulate, the orbital and temporal cortices, and the amygdala is transmitted to the entorhinal cortex of the parahippocampal gyrus and then to the hippocampal formation.
  35. 35.  After traversing the intrinsic circuitry of the hippocampal formation, information is projected through the fornix either to the anterior thalamus, which, in turn, projects to the limbic cortex, or to the septal area and the hypothalamus.  These latter two regions provide feedback to the hippocampal formation through the fornix.  In addition, the mammillary bodies of the hypothalamus project to the anterior thalamus.  Finally, the hypothalamus and the septal area project to the brainstem and the spinal cord
  36. 36. Functional circuit b/w hippocampul formation, Thalamus,cerebral cortex and hypothalamus
  37. 37.  Sensory information, primarily from the association regions of the prefrontal and temporal cortices, projects to the amygdala.  Output from the amygdala is conducted through two main pathways .  A dorsal route, the stria terminalis, project primarily to the septal area and the hypothalamus..
  38. 38.  The second major output route, the ventral amygdalofugal pathway, terminate in the septal area, the hypothalamus, and the medial dorsal thalamic nucleus.  The medial dorsal nucleus, in turn, projects heavily to prefrontal and some temporal cortical regions
  39. 39. Functional circuit b/w amygdala,hypothalamus Prefrontal and temporal ass. cortices
  40. 40.  Both of these pathways reveal how the limbic system is able to integrate the highly processed sensory and cognitive information content of the cerebral cortical circuitry with the hypothalamic pathways that control autonomic and endocrine systems
  41. 41.  the ventral amygdalofugal pathway also projects to the nucleus accumbens (ventral striatum),  the area where the head of the caudate nucleus fuses with the putamen.  This region sends efferents to the ventral palladium, an extension of the globus pallidus.  This area, in turn, projects to the medial dorsal thalamic nucleus.
  42. 42. Functional circuits b/w basal ganglia and limbic system
  43. 43.  The limbic structures are closely related to the olfactory cortex.  Amygdala is involved in the emotional response to smell  entorhinal cortex, is concerned with olfactory memories
  44. 44. Olfactory role of limbic system
  45. 45.  Amygdala plays a role in food choice and emotional modulation of food intake.  The lateral nucleus of the hypothalamus is the center for control of feeding  whereas the ventromedial nucleus functions as the satiety center.
  46. 46.  PET and fMRI have shown that the limbic system is one of the most active brain areas during dreaming.  The limbic system probably interweaves unconscious primal emotions with our conscious cognitive thoughts and perceptions  and thereby ties together emotions and memory during REM sleep to form the content of dreams.
  47. 47.  The suprachiasmatic nucleus of hypothalamus is the circadian rhythm generator controlling the sleep-wake cycle.  The ventrolateral preoptic nucleus (VLPO) of the hypothalamus sends projections to the histaminergic tuberomamillary nucleus (TMN),  the serotonergic dorsal and median raphe nucleus  and the noradenergic locus coeruleus.
  48. 48.  It also sends axons to the cholinergic basal forebrain,  the pedunculo pontine thalamic nucleus (PPT)  and lateral dorsal thalamic nucleus (LDT).  The VLPO projections to these areas are inhibitory.  The VLPO via its inhibition of the major arousal mechanisms, functions as a 'sleep switch', promoting sleep
  49. 49.  The VLPO by its disinhibition of the PPT-LDT also promotes REM sleep.  The lateral hypothalamic area (LHA) contains orexinergic neurons that promote wakefulness.  The orexinergic neurons inhibit the sleep-promoting VLPO and the REM sleep-promoting neurons in the PPT-LDT.
  50. 50.  FEAR  Fear responses are produced by the stimulation of the hypothalamus and amygdala.  Amygdala destruction abolishes fear and its autonomic and endocrine responses.  Amygdala is also involved in fear learning  Imaging studies have shown that viewing fearful faces activates the left amygdala.
  51. 51. Rage and placidity  The destruction of the ventromedial hypothalamic nuclei and septal nuclei in animals may induce rage.  Bilateral destruction of the amygdala results in placidity.  However, when the ventromedian nucleus is destroyed after the destruction of the amygdala, the placidity generated is converted to rage.
  52. 52. Autonomic and endocrine responses to emotion  Limbic stimulation causes changes in respiration and blood pressure.  The stimulation of the cingulate gyrus and hypothalamus can elicit autonomic responses.  Hypothalamic autonomic responses are mediated by the cortical and limbic structures processing drives and emotions.
  53. 53.  The fear and rage responses mediated by the limbic system cause stimulation the hypothalamus, especially lateral areas and produce diffuse sympathetic discharge.  The massive sympathetic discharge during stress is called the "flight or fright response".
  54. 54.  Stress via cortical and limbic connections causes release of corticotropin-releasing hormone (CRH) from the paraventricular nuclei of the hypothalamus.  CRH release mediates endocrine and immune responses
  55. 55. Limbic system and autonomic and endocrine responses
  56. 56.  medial preoptic area of the hypothalamus is the central control of male sexual behavior.  Chemosensory efferents olfactory systems project to the medial amygdala (MeA).  MeA sends innervations (through the stria terminalis) to the medial preoptic area (MPOA).  MPOA and MeA receive genitosensory input from the spinal cord through the central tegmental field (CTF).
  57. 57.  The MPOA sends efferents to the paraventricular nucleus of the hypothalamus (PVN), the ventral tegmental area, the nucleus paragigantocellularis and other autonomic and somatomotor areas
  58. 58. Neural Circuit of Male Sexual Behavior CTF: Central Tegmental Field,MeA: Medial Amygdala, BNST: Bed Nucleus of Stria Terminalis, VTA: Ventral Tegmental Area, MPOA: Medial Preoptic Area
  59. 59.  The parvocellular part of the paraventricular nucleus (PVN) of the hypothalamus send direct oxytocinergic and vasopressinergic projections to the lumbosacral cord.  Activation of oxytocinergic neurons in the PVN by dopamine and its agonists-excitatory amino acids (N-methyl-D-aspartic acid)  or oxytocin itself or by electrical stimulation leads to penile erection.
  60. 60.  The inhibition of these neurons by GABA and its agonists or by opioid peptides and opiate-like drugs, inhibits this sexual response.  The activation of these neurons is secondary to the activation of nitric oxide synthase (NOS), which produces nitric oxide.
  61. 61.  glutamatergic inputs to the MPOA from the medial amygdala (MeA) and bed nucleus of the stria terminalis (BNST),  mediate the female-stimulated increase in dopamine, which in turn, enhances copulatory ability.  Extracellular glutamate in the MPOA increases during copulation,  especially during ejaculation and increased glutamate facilitates copulation and genital reflexes.
  62. 62.  The reward circuitry underlying addictive behavior includes amygdala and nucleus accumbens.  The amygdala plays a central role in cue-induced relapse.  Relapse associated with cues, stress and a single dose of a drug of abuse results in release of excitatory neurotransmitters in brain areas like hippocampus and amygdala.
  63. 63.  The pathway of motivated behavior involves the prefrontal cortex, the ventral tegmental area (VTA), the amygdala especially the basolateral amygdala and extended amygdala, the nucleus accumbens core and the ventral pallidum.  This pathway is involved in the motivation to take drugs of abuse (drug-seeking) and the compulsive nature of drug-taking
  64. 64.  Emotional memory  Emotion has powerful influence on learning and memory.  Amygdala, prefrontal cortex and medial temporal lobe, is involved in consolidation and retrieval of emotional memories.  Amygdala, prefrontal cortex and hippocampus are also involved in the acquisition, extinction and recovery of fears to cues and contexts.  Hippocampus is critical for long-term, declarative memory storage
  65. 65.  Medial temporal lobe memory system  include the hippocampus and adjacent cortex,  the parahippocampal regions (PHG) and the entorhinal and perirhinal regions.  involved in the storage of new memories.
  66. 66.  Diencephalic memory system  consists of the hypothalamus, mammillary body and the dorsomedial nucleus of thalamus.  important for the storage of recent memory;  a dysfunction of this circuit results in Korsakoff's syndrome.
  67. 67.  Social cognition  thought processes involved in understanding and dealing with other people.  Limbic structures involved are the cingulate gyrus and amygdala.
  68. 68.  Degenerative changes in the limbic system likely have a role in neurodegenerative diseases,  particularly Pick's disease and Alzheimer's disease.  Marked atrophy is found in the limbic system, most notably the dentate gyrus and hippocampus.
  69. 69.  In Alzheimer's disease, senile plaques and neurofibrillary tangles are dispersed throughout the cerebral cortex and basal ganglia,  but the hippocampus and amygdala are often severely involved
  70. 70.  may be the result of a failure of the anterior cingulate and hippocampus to modulate the activity of the amygdala.  A fear circuitry, involving the amygdala, prefrontal and anterior cingulate has been described.
  71. 71.  Studies have shown reduced limbic volumes.  The Papez circuit is probably involved in schizophrenia.  distortion of cortical neurons of layer II of the ERC,  decreased size of hippocampus
  72. 72.  reduced number of GABAergic cells in the cingulate and anterior thalamus  with glutamatergic excitotoxicity.  The other circuit involved is the basolateral circuit which mediates the social cognition deficits in schizophrenia
  73. 73.  Studies have shown variation in the volumes of the frontal lobes, basal ganglia, amygdala and hippocampus.  Functional studies have revealed decreased prefrontal and anterior cingulate activity.  Recently, researchers have posited that affective and cognitive symptomatology represents dysfunction within a network-the anterior limbic network,
  74. 74.  which includes prefrontal regions and subcortical structures such as the thalamus, striatum and the amygdala.  The dysfunction of this system (anterior limbic network) is suggested in bipolar disorder, but its role in depression is unclear.
  75. 75.  The enlarged hippocampus represent a compensatory response to the presence of disturbances in the perception of time,  temporal processing  and stimulus-seeking associated with ADHD.  Disrupted connections between the amygdala and orbitofrontal cortex may contribute to behavioral disinhibition.
  76. 76.  bilateral destruction of the amygdaloid body and inferior temporal cortex.  characterized by visual agnosia,  placidity,  hypermetamorphosis,  hyperorality  and hypersexuality.
  77. 77.  caused by cerebral trauma;  infections including herpes and other encephalitides;  Alzheimer's disease and other dementias;  Niemann-Pick disease and cerebrovascular disease
  78. 78.  damage to mammillary bodies, dorsomedial nucleus of thalamus and hypothalamus (diencephalic memory circuit).  chronic prominent impairment of recent and remote memory (recent > remote)  Immediate recall is usually preserved.  Confabulation may be marked but is not invariably present
  79. 79.  disproportionate impairment in specific aspects of social cognition.  Limbic structures involved  cingulate gyrus and amygdala, which mediate cognitive and affective processing.  The basolateral circuit integral for social cognition is disrupted in autism spectrum disorders.
  80. 80.  Temporal lobe epilepsy is the most common epilepsy in adults  and is most often caused by hippocampal sclerosis.  Hippocampal sclerosis with involvement of amygdala and parahippocampal gyrus  mesial temporal sclerosis (MTS).  The frequency and widespread distribution of cerebral abnormalities suggest that MTS is not limited to the medial temporal lobe but instead, represents a limbic system disorder.
  81. 81.  a paraneoplastic syndrome reported with carcinoma of the lung, breast and some other primaries.  manifests as encephalitis that primarily involves the hippocampus, amygdala, cingulate gyrus, insula and orbital- frontal cortex.  Afflicted patients develop subacute onset of memory loss, dementia, involuntary movements and ataxia.
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