Erial Bahar 2011

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

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

2. Physiology of neurobehavior system
1. Overview of the motor system
1. 2. Pyramidal system Extrapyramidal system

2. Overview of the sensory system 3. Higher functions of the brain
1. 2. 3. Intellectual functions of the brain Learning Memory



Structures Involved in Psychiatric and Neurobehavioral Disorders
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Hippocampal formation Amygdala Orbitofrontal cortex Cingulate gyrus Hypothalamus Mammilary bodies Anterior thalamic nucleus Medial dorsal thalamis nucleus Ventral striatum Frontal lobe Rhinencephalon Mesencephalon
1. 2. 3. Substantia Nigra Ventral tegmental area (VTA) Formatio reticularis

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.


directly aimed at the maintenance of homeostasis and at the survival of the individual and of the species (Nieuwenhuys. plays crucial roles in spatial problem solving and in memory. • The hippocampus.LIMBIC SYSTEM • Is a system that concerns with specific motivated or goal-oriented behaviors. 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. within the limbic system. • Functions: – Maintenance of homeostasis – Motivated and goal-oriented behaviors – Survival of the individual – Survival of the species – Learning and memory .

McLean’s 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 .

three layers) Hippocampus Dentate gyrus Amygdala Phylogenetically oldest Limbic system Limbic lobe. (mesocortex. three to five layers) Parahippocampal gyrus Cingulate gyrus Subcallosal gyrus Neocortex. (five to six layers) Primary motor cortex Primary sensory cortex Association cortex Newest .Hippocampal formation (archicortex.

internal line of Baillarger. external line of Baillarger (line of Gennari in the occipital lobe). . 5b. 4. A: Golgi neuronal stain. D: Neuronal connections. C: Weigart myelin stain. Roman and Arabic numerals indicate the layers of the isocortex (neocortex).Diagram of the structure of the cerebral cortex. B: Nissl cellular stain.

3. 4. 5. 2. Hypothalamus Amygdala Septal area Hippocampal formation Cingulate gyrus .Stuctures of the Limbic System 1.

(After Hamilton.) Fundamentals of Human Neuropsychology. . and the hippocampus connects to the hypothalamus through the fornix. and the amygdala. 1976. This medial view of the right hemisphere illustrates the principal structures of the limbic system. Note: As proposed by Papez. A model of the human limbic system and its major structures. the limbic system forms a circuit in which the hypothalamus (mammillary bodies) connect to the hippocampus through the cingulate gyrus. B.A. the hippocampus. including the cingulate cortex.

limbic lobe (via cingulum) To mamillary bodies.25th ed . and tuber cinereum (via fornix). habenula From primitive temporal cortex and sensory association cortex. septal area. opposite amygdala (via anterior commissure) To hypothalamus (direct amygdalofugal pathway). .Some Limbic System Connections Structure Dentate gyrus Hippocampus Connections From entorhinal cortex (via perforant pathway and alvear pathway) To hippocampus (via mossy fibers) From dentate gyrus (via mossy fibers). fornix To medial forebrain bundle. Waxman. anterior thalamus. amygdala. hypothalamus. septum (via fornix). and hypothalamus (via stria terminalis) Septal area Amygdala Clinical Neuroanatomy. septal area. subcallosal area (via longitudinal striae) From olfactory bulb.

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: 1–4 = 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, 12–17 = amygdaloid nuclei, 18 = lateral hypothalamic area, 19–20 = nucleus and stria medullaris, 21 = stria terminalis, 22 = habenular commissure, 23 = septal nuclei.

Waxman. Clinical Neuroanatomy. Olfactory and amygdaloid connections.Diagram of the principal connections of the limbic system.25 ed. th .

. Waxman. Hippocampal system and great limbic lobe.Diagram of the principal connections of the limbic system.25th ed . Clinical Neuroanatomy.

.25th ed . Waxman.Schematic llustration of the location of the limbic system between the diencephalon and the neocortex Clinical Neuroanatomy.

Waxman. largely made up of the subcallosal and cingulate gyri as well as the parahippocampal gyrus.This limbic lobe consists of a ring of cortex outside the corpus callosum. Clinical Neuroanatomy.25th ed . .

Schematic illustration (left oblique view) of the position of hippocampal formation in the left hemisphere Clinical Neuroanatomy.25th ed . . Waxman.

Broca’s “callosal gyrus” is now termed the cingulate gyrus.“Le Grande Lobe Limbique” as adapted from Broca’s original 1878 drawing of an otter’s brain. Ref: Clinical Neuroanatomy.pdf .

which. .Papez circuit HIPPOCAMPAL FIBERS project to the MAMMILLARY BODIES. 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. in turn.

Ref: Clinical Neuroanatomy.pdf .

Ref: Clinical Neuroanatomy.pdf .

.Schematic showing some of the major limbic structures and pathways.

Information flow to and from the limbic system  The limbic system receives inputs from sensory systems.  Because the hypothalamus provides the integrating mechanism for different forms of emotional behaviors as well as for other visceral and autonomic responses. and monoamine neuronal groups of the brainstem reticular formation. the limbic system serves as a key modulating region of these processes by virtue of its inputs into the hypothalamus.  Inputs to the limbic system from monoamine pathways can provide the substrates underlying mood changes. including the cerebral cortex. . This arrangement allows the limbic system to alter the activity of the hypothalamus in response to sensory input.  Primary outputs of the limbic system are directed to the hypothalamus.


• The olfactory system constitutes an important input to the limbic system. • The olfactory receptors are specialized neurons located in the olfactory mucous membrane.Olfactory System • Olfaction (the sense of smell) is one of the oldest senses from a phylogenetic point of view. a portion of the nasal mucosa. • The axons of the olfactory receptors travel to the olfactory bulb. .

25th ed .The olfactory nerve (lateral view) Clinical Neuroanatomy. . Waxman.

cont. • Within the olfactory bulb. • 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. the olfactory receptor axons terminate in specialized synaptic arrangements (termed glomeruli) on the dendrites of mitral cells. .

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.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.Olfactory System. entorhinal cortex and parts of the amygdala.) The pyriform cortex projects. in turn. where conscious discrimination of odors presumably occurs. presumably as part of a feedback circuit that modulates the sensitivity of olfactory sensation. 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. • • • . Other olfactory fibers reach the anterior perforated substance to serve olfactory reflex reactions. via the thalamus to the frontal lobe.

Anosmia (loss of smell): 1. Head trauma that damages the cribrous plate 2.Dysfunction 1. Might be a sign of temporal lobe tumor .Olfactory System. Nasal infection 2. Olfactory (or uncinate) hallucination: 1.


Subiculum . 2. receives inputs from many cortical regions that are relayed to it via the entorhinal cortex. Hippocampus proper (also called Ammon's horn) : – extends the length of the floor of the inferior horn of the lateral ventricle – continuous with the fornix below the splenium of the corpus callosum. scalloped strip of cortex that lies on the upper surface of the parahippocampal gyrus. Dentate gyrus : – – – is a thin. – 3.Structures of the Hippocampal Formation 1. serves as an input station for the hippocampal formation. The cells of the dentate gyrus project to the hippocampus.

CA1 through CA4 are sectors of the hippocampus Clinical Neuroanatomy.Schematic illustration of the major connections to. and from the hippocampal formation. within. Dentate granule cells (DG) project to pyramidal neurons in the hippocampus. Waxman.25th ed . .

Schematic illustration of pathways between the hippocampal formation and the diencephalon. Notice the presence of a loop (Papez circuit). and cingulate gyrus. Waxman. mamillary bodies. . Notice also that the neocortex feeds into this loop Clinical Neuroanatomy. hippocampus.25th ed . including the parahippocampal gyrus. anterior thalamus.

Hippocampal formation in relation to other limbic structures. MB. . basofrontal region. mammillary bodies. S. anterior commissure. amygdala. CG. F. s. genu. AC. anterior nucleus of the thalamus. T. hippocampal formation. fornix. mammillothalamic tract. AN. HF. entorhinal cortex. Fm. corpus callosum (b. thalamus. indusium griseum. body. MTT. cingulate gyrus. A. splenium). IG. CC. g. E-RC. B-F. fimbria. septal area.

Fibers that form the FORNIX .

Diagram illustrates the histological appearance of the cell layers within the hippocampus and loci of the hippocampal fields. and subicular cortex. CA1-CA4 denote the four sectors of the hippocampus . dentate gyrus.

Semischematic diagram illustrates: (1) inputs from the entorhinal region. and (3) efferent projections of the hippocampal formation through the fimbria-fornix system of fibers. . which include the perforant and alvear pathways. which includes the connections of the mossy fibers and Schaffer collaterals. (2) internal circuitry.

. which. in turn. mammillary bodies. Other connections shown include efferent fibers that synapse in entorhinal cortex.e. The primary output is through the fornix to diencephalon (i. and anterior thalamic nucleus) via the postcommissural fornix and to the septal area via the precommissural fornix.Major projection targets of the hippocampal formation. medial hypothalamus. project to amygdala and cingulate gyrus .

inferior parietal lobule TAC.auditory association cortex SAC.OFC. superior parietal lobule IPL. temporal association cortex. visual association cortex . premotor cortex AAC. VAC. Frontal association cortex PMC.somatosensory association cortex SPL . orbitofrontal cortex FAC.

somatosensory association cortex TAC. cingulate gyrus CC. orbitofrontal cortex FAC. hippocampus E. parietal association cortex SAC. premotor cortex CG. basal frontal cortex OFC. temporal association cortex. amygdala H. entorhinal cortex .BFC. corpus callosum PAC. VAC. Frontal association cortex PMC. visual association cortex A.

precentral sulcus CS. inferior temporal sulcus CoS.LgF. superior temporal sulcus MTS. central sulcus LF. middle temporal sulcus ITS. longitudinal fissure PCS. collateral sulcus HIPPOCAMPAL AFFERENTS HIPPOCAMPAL EFFERENTS . lateral fissure STS.


T. thalamus. substantia nigra. and posterior divisions of the Hypothalamus B. . The approximate boundaries of the anterior. optic chiasm. Hypothalamic cells adjacent to the third ventricle is paraventricular zone. Abbreviations: A. SubT. anterior commissure. MB. CP. caudate nucleus. pituitary gland. crus of fornix. amygdala. putamen. optic tract. Fcrus. accumbens nucleus. Inf. P. subthalamus. Pit. infundibulum. AC. cerebral peduncles. S. SN. columns of the fornix. OC. septal nuclei.A. AcN. middle. ON. optic nerve. The medial and lateral zones of the hypothalamus(shaded). Fc. CN. OT. mammillary body.

these hypothalamic hormones then stimulate pituitary cells to synthesize and secrete their own (pituitary) hormones. Note: Some hypothalamic hormones inhibit the production/secretion of pituitary hormones. By contrast. which then are released into the bloodstream. Once released into the adenohypophysis. 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.HYPOTHALAMIC–PITUITARY CONNECTIONS. 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. .


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). .

. medial thalamus. prefrontal cortex. and anterior cingulate gyrus.Diagram illustrates other projections from the septal area to the medial hypothalamus. mammillary bodies.


preoptic areas and anterior hypothalamus. . • It is situated just anterior to the tip of the anterior horn of the lateral ventricle. amygdalofugal pathway to the middle portion of the hypothalamus. • Its fiber connections include : 1. the semicircular stria terminalis to the septal area. 2.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.

to and from the brain stem and hypothalamus. located close to the olfactory cortex. also connected. is interconnected with it as well as the olfactory bulb. Axons run back from the amygdala to the association regions of the cortex. the smaller corticomedial nuclear group. temporal. to the ventral striatum and the thalamus. the large basolateral nuclear group. . • Connections also run. • The corticomedial nuclear group of the amygdala. 2. and insular cortex. via the stria terminalis and amygdalofugal pathway. • • • receives higher-order sensory information from association areas in the frontal. via the stria terminalis and the amygdalofugal pathway.Nuclei of Amygdala • Two distinct groups of neurons: 1.

the organization of the nuclei of the amygdala .

Other fibers pass rostrally from the amygdala to the prefrontal cortex. Fibers from the bed nucleus also supply similar regions of the hypothalamus. One principal output includes the stria terminalis. Another important output to the hypothalamus and midbrain PAG uses the ventral amygdalofugal pathway.The major efferent projections of the amygdala. . which projects to the bed nucleus of the stria terminalis and to the rostro-caudal extent of the medial hypothalamus.

leading to bizarre eating and drinking habits.Dysfunction of the Limbic System • Stimulation alters somatic motor responses. • Damage to some areas of the limbic system may also profoundly affect memory. changes in sexual and grooming behavior. • There can be changes in autonomic responses. altering cardiovascular or gastrointestinal function. and defensive postures of attack and rage. with shifts from passive to aggressive behavior. . and in personality.

usually with abnormal passivity or docility. – psychic blindness. presumably results from damage to the amydala. in which objects are no longer recognized. – personality changes. . • 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). sometimes described as a lack of sexual inhibition. or visual agnosia. – hypersexuality.Klüver-Bucy Syndrome • Occurs in patients with bilateral temporal lobe lesions.

sometimes called uncinate fits.Temporal Lobe Epilepsy • The temporal lobe (especially the hippocampus and amygdala) has a lower threshold for epileptic seizure activity than the other cortical areas. astrocytoma or oligodendroglioma) may be responsible. disorders of consciousness. swallowing. – glial scar formation after trauma to the temporal poles may trigger seizures. neurosurgical removal of the seizure focus in the temporal lobe may provide excellent seizure control. and lip smacking. • Seizures that originate in these regions. • Temporal lobe epilepsy may include abnormal sensations. hallucinations. called psychomotor (complex partial) seizures. • Etiology: – tumor (eg. especially bizarre olfactory sensations. . differ from the jacksonian seizures that originate in or near the motor cortex. they may be ineffective. In these cases. repeated involuntary movements such as chewing. memory loss. and disorders of recall and recognition. • Although anticonvulsant drugs are often given to control the seizures.


PREFRONTAL CORTEX • Located in front of the motor cortex. . anxiety. and attention deficit hyperactivity disorder (ADHD) as well as anger and violence. • Comprises 29% of the total cortex. schizophrenia. This is one of the anatomic structures that distinguishes humans from other mammal. • Dysfunction in the PFC is implicated as a possible source of pathology in many psychiatric disorders depression.

lying just anterior to it. is the PREFRONTAL CORTEX. 2. the anterior cingulate area. the executive prefrontal cortex. 3. The prefrontal cortex is the portion of the frontal cortex lying anterior to the premotor and primary motor cortices. The third area. is the PRIMARY MOTOR CORTEX. is the PREMOTOR CORTEX. occupying the dorsal and lateral aspects of the prefrontal cortex. 1. 2. the second. The first. . 1.FRONTAL CORTEX The frontal lobe can be divided into three sections. occupying the orbital and medial aspects of the prefrontal cortex. occupying the precentral gyrus. 3. the paralimbic prefrontal cortex. The planning of complex actions occurs in the premotor cortex. Conscious movements are mediated in the primary motor cortex.

task sequencing. • The dorsolateral prefrontal cortex projects to the premotor cortex lying just posterior to it. .Executive/Dorsolateral Prefrontal Cortex • The dorsolateral prefrontal cortex receives innervation from both the parietal and the temporal association cortices. – – – – cognitive speed and flexibility. • The dorsolateral prefrontal cortex is responsible for executive aspects of cognition. suggesting its role in the transformation of sensory information into preparation for movement. working memory. higher-order attention.

• The orbitofrontal cortex receives innervation from the mediodorsal nucleus of the thalamus. which in turn receives input from almost all other cortical structures. 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. • The orbitofrontal cortex has reciprocal connections to the amygdala both through the ventral amygdalofugal tract and through the stria terminalis. such as regulation of IMPULSES.Paralimbic/Orbitofrontal Cortex • Regarded as an extension of the limbic system. . • It is involved in complex aspects of human behavior. AND PERSONALITY. MOOD.

motivation.Anterior Cingulate Gyrus • The cingulate gyrus spans the medial surface of the brain from the prefrontal cortex to the parieto-occipital junction. drive. • The anterior cingulate is involved in attention. and sensory processing. – Akinetic mutism in which the person is alert but has tremendous inertia. with little spontaneous movement or speech. • Providing a bridge between the systems performing emotional. – Obsessive compulsive disorder . • Dysfunction causes: – Apathy. cognitive. and initiation of speech. memory. motor.

• The more dorsal components of the striatum are associated with the extrapyramidal system and motor control. • The striatum is composed of – Striosomes : acetylcholinesterase-poor patches rich in opiate receptors. • The more ventral areas are involved in motivation. • At their ventralmost extent. • whereas the matrix is a major component of the extrapyramidal motor system. • have high levels of D1 receptors and prominent limbic input. • mostly involved in cognitive and behavioral processing.Basal Ganglia and Ventral Striatum • The striatum consists of the caudate and the putamen. and emotion. – An acetylcholinesterase-rich matrix. called the nucleus accumbens. . cognition. • rich in D2 receptors with close connections to the substantia nigra. the caudate and putamen appear to merge into a single structure.


From : Human Hippocampus .

parahippocampal gyrus. 3. putamen. cingulate gyrus. caudate nucleus. tentorium cerebelli. 8. 10. 16. superior frontal gyrus. 20. 7. 19. lateral ventricle. 9. 21. temporal (inferior) horn of the lateral ventricle. fusiform gyrus. 4. ambient cistern From : Human Hippocampus . 12. central sulcus. lateral fissure. thalamus. superior temporal gyrus. 13. precentral gyrus. red nucleus. middle temporal gyrus. pons. 17. 14. 11. postcentral gyrus. corpus callosum. inferior temporal gyrus. 18. 6. 22. 5.1. substantia nigra. 15. hippocampus. 14’. 2.

fimbria 5. crus of fornix 6. (The temporal horn has been opened and the choroid plexuses removed. 8. Subiculum 7. calcar avis 9. head and digitationes hippocampi (internal digitations) 3. hippocampal tail 4. collateral eminence 11.Intraventricular aspect of the hippocampus.) 1. hippocampal body 2. collateral trigone 10. uncal recess of the temporal horn From : Human Hippocampus . splenium of the corpus callosum.

fornix. Hippocampus: 18. subcallosal gyrus. prepiriform cortex. 14. gyrus dentatus. entorhinal area. fimbria (displaced upwards. 24. 19. arrows). 10. subparietal sulcus 4. 27. 12. uncal apex. ambient gyrus. anterior calcarine sulcus. cornu Ammonis. rhinal sulcus. anterior part (piriform lobe). posterior paraolfactory sulcus. Limbic gyrus: 7. 11. anterior perforated substance. collateral sulcus 6. anterior commissure. 26. 17. semilunar gyrus. 23. posterior part. 20. 25. 8. 28. 22. parahippocampal gyrus. 16’. 9. 21. 11’. cingulate gyrus. indusium griseum. prehippocampal rudiment. corpus callosum From : Human Hippocampus .1. uncinate gyrus. parahippocampal gyrus. 15. cingulate sulcus 3. 5. 13. gyri of Andreas Retzius. paraterminal gyrus. Intralimbic gyrus: 16. isthmus. band of Giacomini. anterior paraolfactory sulcus (subcallosal sulcus) 2.

25. corpus callosum From : Human Hippocampus . 12. entorhinal area. anterior perforated substance. 26. 20. uncinate gyrus. 19. fimbria (displaced upwards. 8. semilunar gyrus. cornu Ammonis. anterior commissure. 21. prepiriform cortex. 13. prehippocampal rudiment. indusium griseum. 16’. anterior part (piriform lobe). fornix. uncal apex. cingulate gyrus. 24. paraterminal gyrus. 15.1. parahippocampal gyrus. posterior paraolfactory sulcus. 11’. posterior part. gyrus dentatus. cingulate sulcus 3. 23. Intralimbic gyrus: 16. 28. ambient gyrus. subparietal sulcus 4. isthmus. gyri of Andreas Retzius. 9. 11. anterior paraolfactory sulcus (subcallosal sulcus) 2. band of Giacomini. 5. Limbic gyrus: 7. anterior calcarine sulcus. 22. Hippocampus: 18. collateral sulcus 6. arrows). rhinal sulcus. 14. 10. 17. 27. parahippocampal gyrus. subcallosal gyrus.

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. . IC = internal capsule. R = reticular nucleus of the thalamus.Schematic view of frontal-subcortical-thalamic circuits. shown at the level of the pallidum and thalamus. 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. III = third ventricle. GPe = globus pallidus externa.