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Learning Objectives
1. Describe the structures involved in psychiatric and neurobehavioral disorders 2. Describe and diagram the basic morphology of the structures comprising the limbic system 3. Describe and diagram the input-output relationships of limbic nuclei 4. Characterize the functions of limbic brain structures and their underlying mechanisms (where known) 5. Develop an understanding of the structural and functional bases for clinical and behavioral disorders associated with dysfunctions of the limbic system
OVERVIEW
1. Anatomy of neurobehavior system
1. Overview of the human nervous system 2. Anatomy of the brain
1. 2. Cortex cerebri Anatomy of the Limbic system
4.
Emotion
Limbic system
Areas of the human cerebral cortex defined by Brodmann in his 1909 publication
Spatial relationships between basal ganglia, thalamus, and internal capsule as viewed from the left side.
LIMBIC SYSTEM
Is a system that concerns with specific motivated or goal-oriented behaviors, directly aimed at the maintenance of homeostasis and at the survival of the individual and of the species (Nieuwenhuys, 1996) The limbic system receives input from many parts of the cortex and contains multimodal association areas where various aspects of sensory experience come together to form a single experience. The hippocampus, within the limbic system, plays crucial roles in spatial problem solving and in memory. Functions: Maintenance of homeostasis Motivated and goal-oriented behaviors Survival of the individual Survival of the species Learning and memory
McLeans schema of the evolutionary development of a three-layered triune brain. Note the location of the limbic system in the middle tier
Brain Circuitry and Signaling in Psychiatry
Phylogenetically oldest
Limbic system
Limbic lobe, (mesocortex, three to five layers)
Newest
Diagram of the structure of the cerebral cortex. A: Golgi neuronal stain. B: Nissl cellular stain. C: Weigart myelin stain. D: Neuronal connections. Roman and Arabic numerals indicate the layers of the isocortex (neocortex); 4, external line of Baillarger (line of Gennari in the occipital lobe); 5b, internal line of Baillarger.
A. This medial view of the right hemisphere illustrates the principal structures of the limbic system, including the cingulate cortex, the hippocampus, and the amygdala. B. A model of the human limbic system and its major structures. Note: As proposed by Papez, the limbic system forms a circuit in which the hypothalamus (mammillary bodies) connect to the hippocampus through the cingulate gyrus, and the hippocampus connects to the hypothalamus through the fornix. (After Hamilton, 1976.)
Fundamentals of Human Neuropsychology.
Medial aspect of the right hemispherium showing the corpus callosum. CCg = Genu; CCb = Body; CCs = Splenium
Schematic drawing of the major anatomical structures of the limbic system. Note: The cingulated and parahippocampal gyri form the limbic lobe, a rim of tissue located along the junction of the diencephalons and the cerebral hemispheres. n, nucleus.
Upper cortex and white matter tracts of the brain removed, revealing the close relationship of the limbic system (hippocampus and fornix) and striatum in the center of the brain.
Schema depicting dorsal view of connections of the amygdala: 14 = olfactory structures, 5 = anterior commissure, 6 = olfactory tubercle, 7 = limen insulae, 8 = diagonal band of Broca, 9 = inferior thalamic peduncle, 10 = medial telencephalic fasciculus, 11 = ventral amygdalofugal pathway, 1217 = amygdaloid nuclei, 18 = lateral hypothalamic area, 1920 = nucleus and stria medullaris, 21 = stria terminalis, 22 = habenular commissure, 23 = septal nuclei.
Diagram of the principal connections of the limbic system. Olfactory and amygdaloid connections. Clinical Neuroanatomy, Waxman,25 ed.
th
Diagram of the principal connections of the limbic system. Hippocampal system and great limbic lobe.
Clinical Neuroanatomy, Waxman,25th ed
Schematic llustration of the location of the limbic system between the diencephalon and the neocortex
Clinical Neuroanatomy, Waxman,25th ed
This limbic lobe consists of a ring of cortex outside the corpus callosum, largely made up of the subcallosal and cingulate gyri as well as the parahippocampal gyrus.
Clinical Neuroanatomy, Waxman,25th ed
Schematic illustration (left oblique view) of the position of hippocampal formation in the left hemisphere
Clinical Neuroanatomy, Waxman,25th ed
Le Grande Lobe Limbique as adapted from Brocas original 1878 drawing of an otters brain. Brocas callosal gyrus is now termed the cingulate gyrus.
Ref: Clinical Neuroanatomy.pdf
Papez circuit
HIPPOCAMPAL FIBERS project to the MAMMILLARY BODIES, which, in turn, project through the MAMMILLOTHALAMIC TRACT to the ANTERIOR NUCLEUS. The anterior thalamic nucleus then projects to the CINGULATE GYRUS, and the axons of the cingulate gyrus then project back to the HIPPOCAMPAL FORMATION.
Olfactory System
Olfaction (the sense of smell) is one of the oldest senses from a phylogenetic point of view. The olfactory system constitutes an important input to the limbic system. The olfactory receptors are specialized neurons located in the olfactory mucous membrane, a portion of the nasal mucosa. The axons of the olfactory receptors travel to the olfactory bulb.
Olfactory System,cont. Within the olfactory bulb, the olfactory receptor axons terminate in specialized synaptic arrangements (termed glomeruli) on the dendrites of mitral cells. Olfactory neurons expressing a specific odorant receptor (and thus responsive to a specific odorant stimulus) project precisely to a small number of glomeruli within the olfactory bulb.
Olfactory System,cont
The mitral cells of the olfactory bulb send their axons posteriorly via the olfactory tracts (also termed the medial and lateral olfactory stria) to the olfactory projection area in the cortex. The lateral olfactory stria is the projection bundle of fibers that passes laterally along the floor of the lateral fissure and enters the olfactory projection area near the uncus in the temporal lobe (the pyriform, entorhinal cortex and parts of the amygdala.) The pyriform cortex projects, in turn, via the thalamus to the frontal lobe, where conscious discrimination of odors presumably occurs. The small medial olfactory stria passes medially and up toward the subcallosal gyrus (the anterior olfactory nucleus) which sends its axons back to the olfactory bulbs on both sides, presumably as part of a feedback circuit that modulates the sensitivity of olfactory sensation. Other olfactory fibers reach the anterior perforated substance to serve olfactory reflex reactions.
HIPPOCAMPAL FORMATION
2. Dentate gyrus :
is a thin, scalloped strip of cortex that lies on the upper surface of the parahippocampal gyrus. serves as an input station for the hippocampal formation. receives inputs from many cortical regions that are relayed to it via the entorhinal cortex. The cells of the dentate gyrus project to the hippocampus.
3. Subiculum
Schematic illustration of the major connections to, within, and from the hippocampal formation. Dentate granule cells (DG) project to pyramidal neurons in the hippocampus. CA1 through CA4 are sectors of the hippocampus
Clinical Neuroanatomy, Waxman,25th ed
Schematic illustration of pathways between the hippocampal formation and the diencephalon. Notice the presence of a loop (Papez circuit), including the parahippocampal gyrus, hippocampus, mamillary bodies, anterior thalamus, and cingulate gyrus. Notice also that the neocortex feeds into this loop
Clinical Neuroanatomy, Waxman,25th ed
Hippocampal formation in relation to other limbic structures. A, amygdala; AC, anterior commissure; AN, anterior nucleus of the thalamus; B-F, basofrontal region; CC, corpus callosum (b, body; g, genu; s, splenium); CG, cingulate gyrus; E-RC, entorhinal cortex; F, fornix; Fm, fimbria; HF, hippocampal formation; IG, indusium griseum; MB, mammillary bodies; MTT, mammillothalamic tract; S, septal area; T, thalamus.
Diagram illustrates the histological appearance of the cell layers within the hippocampus and loci of the hippocampal fields, dentate gyrus, and subicular cortex. CA1-CA4 denote the four sectors of the hippocampus
Semischematic diagram illustrates: (1) inputs from the entorhinal region, which include the perforant and alvear pathways; (2) internal circuitry, which includes the connections of the mossy fibers and Schaffer collaterals; and (3) efferent projections of the hippocampal formation through the fimbria-fornix system of fibers.
Major projection targets of the hippocampal formation. The primary output is through the fornix to diencephalon (i.e., medial hypothalamus, mammillary bodies, and anterior thalamic nucleus) via the postcommissural fornix and to the septal area via the precommissural fornix. Other connections shown include efferent fibers that synapse in entorhinal cortex, which, in turn, project to amygdala and cingulate gyrus
OFC, orbitofrontal cortex FAC, Frontal association cortex PMC, premotor cortex AAC,auditory association cortex SAC,somatosensory association cortex SPL , superior parietal lobule IPL, inferior parietal lobule TAC, temporal association cortex, VAC, visual association cortex
BFC, basal frontal cortex OFC, orbitofrontal cortex FAC, Frontal association cortex PMC, premotor cortex CG, cingulate gyrus CC, corpus callosum PAC, parietal association cortex SAC,somatosensory association cortex TAC, temporal association cortex, VAC, visual association cortex A, amygdala H, hippocampus E, entorhinal cortex
LgF, longitudinal fissure PCS, precentral sulcus CS, central sulcus LF, lateral fissure STS, superior temporal sulcus MTS, middle temporal sulcus ITS, inferior temporal sulcus CoS, collateral sulcus
HIPPOCAMPAL AFFERENTS
HIPPOCAMPAL EFFERENTS
HYPOTHALAMUS
A. The approximate boundaries of the anterior, middle, and posterior divisions of the Hypothalamus B. The medial and lateral zones of the hypothalamus(shaded). Hypothalamic cells adjacent to the third ventricle is paraventricular zone.
Abbreviations:
A, AC, AcN, CN, CP, Fc, Fcrus, Inf, MB, OC, ON, OT, P, Pit, S, SN, SubT, T, amygdala; anterior commissure; accumbens nucleus; caudate nucleus; cerebral peduncles; columns of the fornix; crus of fornix; infundibulum; mammillary body; optic chiasm; optic nerve; optic tract; putamen; pituitary gland; septal nuclei; substantia nigra; subthalamus; thalamus.
HYPOTHALAMICPITUITARY CONNECTIONS.
The posterior portion of the pituitary (neurohypophysis) is innervated by hypothalamic neurons that transport the hypothalamic hormones (oxytocin and vasopressin) down their axons to be released into capillary beds of the posterior pituitary from where they enter the general circulation. By contrast, the capillary beds of the anterior pituitary (adenohypophysis) are supplied with hypothalamic hormones (either releasing or inhibitory factors) via a blood portal system from capillary beds in the hypothalamus itself. Once released into the adenohypophysis, these hypothalamic hormones then stimulate pituitary cells to synthesize and secrete their own (pituitary) hormones, which then are released into the bloodstream. Note: Some hypothalamic hormones inhibit the production/secretion of pituitary hormones.
SEPTAL AREA
Topographically organized projections from the hippocampal formation to the septal area (left side) and topographically arranged efferent projections from the diagonal band of Broca to the hippocampal formation (right side).
Diagram illustrates other projections from the septal area to the medial hypothalamus, mammillary bodies, medial thalamus, prefrontal cortex, and anterior cingulate gyrus.
AMYGDALA
AMYGDALA
The amygdala (amygdaloid nuclear complex) is a gray matter mass that lies in the medial temporal pole between the uncus and the parahippocampal gyrus. It is situated just anterior to the tip of the anterior horn of the lateral ventricle. Its fiber connections include :
1. the semicircular stria terminalis to the septal area, preoptic areas and anterior hypothalamus. 2. amygdalofugal pathway to the middle portion of the hypothalamus.
Nuclei of Amygdala
Two distinct groups of neurons: 1. the large basolateral nuclear group.
receives higher-order sensory information from association areas in the frontal, temporal, and insular cortex. Axons run back from the amygdala to the association regions of the cortex. also connected, via the stria terminalis and the amygdalofugal pathway, to the ventral striatum and the thalamus.
The major efferent projections of the amygdala. One principal output includes the stria terminalis, which projects to the bed nucleus of the stria terminalis and to the rostro-caudal extent of the medial hypothalamus. Fibers from the bed nucleus also supply similar regions of the hypothalamus. Another important output to the hypothalamus and midbrain PAG uses the ventral amygdalofugal pathway. Other fibers pass rostrally from the amygdala to the prefrontal cortex.
Klver-Bucy Syndrome
Occurs in patients with bilateral temporal lobe lesions. The major characteristics of this syndrome are
hyperorality (a tendency to explore objects by placing them in the mouth together with the indiscriminate eating or chewing of objects and all kinds of food); hypersexuality, sometimes described as a lack of sexual inhibition; psychic blindness, or visual agnosia, in which objects are no longer recognized; presumably results from damage to the amydala. personality changes, usually with abnormal passivity or docility.
Although anticonvulsant drugs are often given to control the seizures, they may be ineffective. In these cases, neurosurgical removal of the seizure focus in the temporal lobe may provide excellent seizure control.
PREFRONTAL CORTEX
PREFRONTAL CORTEX
Located in front of the motor cortex. This is one of the anatomic structures that distinguishes humans from other mammal. Comprises 29% of the total cortex. Dysfunction in the PFC is implicated as a possible source of pathology in many psychiatric disorders depression, schizophrenia, anxiety, and attention deficit hyperactivity disorder (ADHD) as well as anger and violence.
FRONTAL CORTEX
The frontal lobe can be divided into three sections. 1. The first, occupying the precentral gyrus, is the PRIMARY MOTOR CORTEX. Conscious movements are mediated in the primary motor cortex. 2. the second, lying just anterior to it, is the PREMOTOR CORTEX. The planning of complex actions occurs in the premotor cortex. 3. The third area, is the PREFRONTAL CORTEX. The prefrontal cortex is the portion of the frontal cortex lying anterior to the premotor and primary motor cortices.
1. 2. 3. the executive prefrontal cortex, occupying the dorsal and lateral aspects of the prefrontal cortex; the paralimbic prefrontal cortex, occupying the orbital and medial aspects of the prefrontal cortex; the anterior cingulate area.
The dorsolateral prefrontal cortex projects to the premotor cortex lying just posterior to it, suggesting its role in the transformation of sensory information into preparation for movement.
Paralimbic/Orbitofrontal Cortex
Regarded as an extension of the limbic system. It is involved in complex aspects of human behavior, such as regulation of IMPULSES, MOOD, AND PERSONALITY. The orbitofrontal cortex receives innervation from the mediodorsal nucleus of the thalamus, which in turn receives input from almost all other cortical structures. The orbitofrontal cortex has reciprocal connections to the amygdala both through the ventral amygdalofugal tract and through the stria terminalis. These pathways provide the orbitofrontal cortex with access to all information necessary to respond to the environment with respect to the motivational and cognitive state of the individual.
An acetylcholinesterase-rich matrix.
rich in D2 receptors with close connections to the substantia nigra. whereas the matrix is a major component of the extrapyramidal motor system.
1. hippocampus; 2. parahippocampal gyrus; 3. fusiform gyrus; 4. inferior temporal gyrus; 5. middle temporal gyrus; 6. superior temporal gyrus; 7. lateral fissure; 8. postcentral gyrus; 9. central sulcus; 10. precentral gyrus; 11. superior frontal gyrus; 12. cingulate gyrus; 13. corpus callosum; 14. lateral ventricle; 14. caudate nucleus; 15. thalamus; 16. putamen; 17. temporal (inferior) horn of the lateral ventricle; 18. red nucleus; 19. substantia nigra; 20. pons; 21. tentorium cerebelli; 22. ambient cistern
1. hippocampal body 2. head and digitationes hippocampi (internal digitations) 3. hippocampal tail 4. fimbria 5. crus of fornix 6. Subiculum 7. splenium of the corpus callosum; 8. calcar avis 9. collateral trigone 10. collateral eminence 11. uncal recess of the temporal horn
1. anterior paraolfactory sulcus (subcallosal sulcus) 2. cingulate sulcus 3. subparietal sulcus 4. anterior calcarine sulcus; 5. collateral sulcus 6. rhinal sulcus. Limbic gyrus: 7. subcallosal gyrus; 8. posterior paraolfactory sulcus; 9. cingulate gyrus; 10. isthmus; 11. parahippocampal gyrus, posterior part; 11, parahippocampal gyrus, anterior part (piriform lobe). 12. entorhinal area; 13. ambient gyrus; 14. semilunar gyrus; 15. prepiriform cortex. Intralimbic gyrus: 16. prehippocampal rudiment; 16, paraterminal gyrus; 17. indusium griseum. Hippocampus: 18. gyrus dentatus; 19. cornu Ammonis; 20. gyri of Andreas Retzius; 21. fimbria (displaced upwards, arrows); 22. uncal apex; 23. band of Giacomini; 24. uncinate gyrus; 25. anterior perforated substance; 26. anterior commissure; 27. fornix; 28. corpus callosum
From : Human Hippocampus
1. anterior paraolfactory sulcus (subcallosal sulcus) 2. cingulate sulcus 3. subparietal sulcus 4. anterior calcarine sulcus; 5. collateral sulcus 6. rhinal sulcus. Limbic gyrus: 7. subcallosal gyrus; 8. posterior paraolfactory sulcus; 9. cingulate gyrus; 10. isthmus; 11. parahippocampal gyrus, posterior part; 11, parahippocampal gyrus, anterior part (piriform lobe). 12. entorhinal area; 13. ambient gyrus; 14. semilunar gyrus; 15. prepiriform cortex. Intralimbic gyrus: 16. prehippocampal rudiment; 16, paraterminal gyrus; 17. indusium griseum. Hippocampus: 18. gyrus dentatus; 19. cornu Ammonis; 20. gyri of Andreas Retzius; 21. fimbria (displaced upwards, arrows); 22. uncal apex; 23. band of Giacomini; 24. uncinate gyrus; 25. anterior perforated substance; 26. anterior commissure; 27. fornix; 28. corpus callosum
From : Human Hippocampus
Schematic view of frontal-subcortical-thalamic circuits, shown at the level of the pallidum and thalamus. The extrapyramidal motor circuit involves the globus pallidus interna (GPi) and ventral lateral nucleus of the thalamus (VLo) and connects to the supplementary motor cortex. The related circuit of the ventral striatum involves the ventral pallidum (VP) and mediodorsal nucleus of the thalamus (MD) and connects to the prefrontal cortex. IC = internal capsule; III = third ventricle; R = reticular nucleus of the thalamus; GPe = globus pallidus externa.