NEUROANATOMY OF MENTAL AND NEUROBEHAVIOR DISORDERSErial Bahar2012

Learning ObjectivesDescribe the structures involved in psychiatric and neurobehavioral disordersDescribe and diagram the basic morphology of the structures comprising the limbic systemDescribe and diagram the input-output relationships of limbic nucleiCharacterize the functions of limbic brain structures and their underlying mechanisms (where known)Develop an understanding of the structural and functional bases for clinical and behavioral disorders associated with dysfunctions of the limbic system

OVERVIEWAnatomy of neurobehavior systemOverview of the human nervous systemAnatomy of the brainCortex cerebriAnatomy of the Limbic systemPhysiology of neurobehavior systemOverview of the motor systemPyramidal systemExtrapyramidal systemOverview of the sensory systemHigher functions of the brainIntellectual functions of the brainLearningMemoryEmotion

Structures Involved in Psychiatric and Neurobehavioral DisordersHippocampal formationAmygdalaOrbitofrontal cortexCingulate gyrusHypothalamusMammilary bodiesAnterior thalamic nucleusMedial dorsal thalamis nucleusVentral striatumFrontal lobeRhinencephalonMesencephalonSubstantia NigraVentral tegmental area (VTA)Formatio reticularis Limbic system

OVERVIEW OF THE FUNCTIONAL ANATOMY OF THE BRAIN

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.

OVERVIEW OF THE LIMBIC SYSTEM

LIMBIC SYSTEMIs 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 homeostasisMotivated and goal-oriented behaviorsSurvival of the individualSurvival of the speciesLearning and memory

McLeans schema of the evolutionary development of a three-layered triune brain. Note the location of the limbic system in the middle tierBrain Circuitry and Signaling in Psychiatry

Limbic systemHippocampal formation(archicortex, three layers)Limbic lobe, (mesocortex, three to five layers)Neocortex, (five to six layers)Hippocampus Dentate gyrusAmygdalaPhylogeneticallyoldestNewestParahippocampal gyrusCingulate gyrusSubcallosal gyrusPrimary motor cortexPrimary sensory cortexAssociation cortex

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.

Stuctures of the Limbic SystemHypothalamusAmygdalaSeptal areaHippocampal formationCingulate gyrus

Some Limbic System ConnectionsClinical Neuroanatomy, Waxman,25th ed.

StructureConnectionsDentate gyrusFrom entorhinal cortex (via perforant pathway and alvear pathway) To hippocampus (via mossy fibers)HippocampusFrom dentate gyrus (via mossy fibers), septum (via fornix), limbic lobe (via cingulum) To mamillary bodies, anterior thalamus, septal area, and tuber cinereum (via fornix); subcallosal area (via longitudinal striae)Septal areaFrom olfactory bulb, amygdala, fornix To medial forebrain bundle, hypothalamus, habenulaAmygdalaFrom primitive temporal cortex and sensory association cortex, opposite amygdala (via anterior commissure) To hypothalamus (direct amygdalofugal pathway), septal area, and hypothalamus (via stria terminalis)

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 telencephalicfasciculus, 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.

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

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

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

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.

Schematic illustration (left oblique view) of the position of hippocampal formation in the left hemisphereClinical 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

Ref: Clinical Neuroanatomy.pdf

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.Papez circuit

Ref: Clinical Neuroanatomy.pdf

Ref: Clinical Neuroanatomy.pdf

Ref: Clinical Neuroanatomy.pdf

Ref: Clinical Neuroanatomy.pdf

Schematic showing some of the major limbic structures and pathways.

The limbic system receives inputs from sensory systems, including the cerebral cortex, and monoamine neuronal groups of the brainstem reticular formation. Primary outputs of the limbic system are directed to the hypothalamus. This arrangement allows the limbic system to alter the activity of the hypothalamus in response to sensory input. Because the hypothalamus provides the integrating mechanism for different forms of emotional behaviors as well as for other visceral and autonomic responses, 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.Information flow to and from the limbic system

RHINENCEPHALON AND OLFACTORY SYSTEM

Olfactory SystemOlfaction (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.

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

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,contThe 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.

OLFACTORY RECEPTORMITRAL CELLTUFTED CELLPRIMARY OLFACTORY CORTEXSECONDARY OLFACTORY CORTEXTERTIARY OLFACTORY CORTEXPOSTEROLATERAL ORBITOFRONTAL CORTEXDORSOMEDIAL NUCLEUS(DMmc)AMYGDALAHYPOTHALAMUSPrepyriform pyriform cortexEntorhinal cortex (EC)Hippocampus (Hipp)Olfactory pathwayDiscriminationConscious perceptionuncinate fasciculus Stria terminalisEmotionBehavior ANS Endocrine response

Anosmia (loss of smell):Nasal infectionHead trauma that damages the cribrous plateOlfactory (or uncinate) hallucination:Might be a sign of temporal lobe tumorOlfactory System,Dysfunction

HIPPOCAMPAL FORMATION

Structures of the Hippocampal FormationHippocampus 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. 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.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 hippocampusClinical Neuroanatomy, Waxman,25th ed.

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

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.

Fibers that form the FORNIX

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 cortexFAC, Frontal association cortexPMC, premotor cortexAAC,auditory association cortexSAC,somatosensory association cortexSPL , superior parietal lobuleIPL, inferior parietal lobuleTAC, temporal association cortex,VAC, visual association cortex

BFC, basal frontal cortexOFC, orbitofrontal cortexFAC, Frontal association cortexPMC, premotor cortexCG, cingulate gyrusCC, corpus callosumPAC, parietal association cortexSAC,somatosensory association cortexTAC, temporal association cortex,VAC, visual association cortexA, amygdalaH, hippocampusE, entorhinal cortex

HIPPOCAMPAL AFFERENTSHIPPOCAMPAL EFFERENTSLgF, longitudinal fissurePCS, precentral sulcusCS, central sulcusLF, lateral fissureSTS, superior temporal sulcusMTS, middle temporal sulcusITS, inferior temporal sulcusCoS, collateral sulcus

HYPOTHALAMUS

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

AMYGDALAThe 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 :the semicircular stria terminalis to the septal area, preoptic areas and anterior hypothalamus. amygdalofugal pathway to the middle portion of the hypothalamus.

Nuclei of AmygdalaTwo distinct groups of neurons: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 smaller corticomedial nuclear group.The corticomedial nuclear group of the amygdala, located close to the olfactory cortex, is interconnected with it as well as the olfactory bulb. Connections also run, via the stria terminalis and amygdalofugal pathway, to and from the brain stem and hypothalamus.

the organization of the nuclei of the amygdala

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.

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

Dysfunction of the Limbic System

Klver-Bucy SyndromeOccurs 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.

Temporal Lobe EpilepsyThe temporal lobe (especially the hippocampus and amygdala) has a lower threshold for epileptic seizure activity than the other cortical areas. Seizures that originate in these regions, called psychomotor (complex partial) seizures, differ from the jacksonian seizures that originate in or near the motor cortex. Temporal lobe epilepsy may include abnormal sensations, especially bizarre olfactory sensations, sometimes called uncinate fits; repeated involuntary movements such as chewing, swallowing, and lip smacking; disorders of consciousness; memory loss; hallucinations; and disorders of recall and recognition.Etiology:tumor (eg, astrocytoma or oligodendroglioma) may be responsible, glial scar formation after trauma to the temporal poles may trigger seizures. 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 CORTEXLocated 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 CORTEXThe frontal lobe can be divided into three sections. The first, occupying the precentral gyrus, is the PRIMARY MOTOR CORTEX. Conscious movements are mediated in the primary motor cortex.the second, lying just anterior to it, is the PREMOTOR CORTEX. The planning of complex actions occurs in the premotor cortex. 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. 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.

Executive/Dorsolateral Prefrontal CortexThe dorsolateral prefrontal cortex receives innervation from both the parietal and the temporal association cortices. The dorsolateral prefrontal cortex is responsible for executive aspects of cognition. cognitive speed and flexibility, task sequencing, higher-order attention, working memory.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 CortexRegarded 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.

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

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

PICTURES OF THE LIMBIC SYSTEM

From : Human Hippocampus

From : Human Hippocampus

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 cisternFrom : Human Hippocampus

From : Human Hippocampus

Intraventricular aspect of the hippocampus. (The temporal horn has been opened and the choroid plexuses removed.)hippocampal bodyhead and digitationes hippocampi (internal digitations)hippocampal tailfimbriacrus of fornixSubiculumsplenium of the corpus callosum;calcar aviscollateral trigonecollateral eminenceuncal recess of the temporal hornFrom : Human Hippocampus

From : Human Hippocampus

anterior paraolfactory sulcus (subcallosal sulcus)cingulate sulcussubparietal sulcus anterior calcarine sulcus; collateral sulcus rhinal sulcus. Limbic gyrus: subcallosal gyrus; posterior paraolfactory sulcus;cingulate gyrus; isthmus; parahippocampal gyrus, posterior part; 11, parahippocampal gyrus, anterior part (piriform lobe). entorhinal area; ambient gyrus; semilunar gyrus; prepiriform cortex. Intralimbic gyrus: prehippocampal rudiment; 16, paraterminal gyrus; indusium griseum. Hippocampus: gyrus dentatus; cornu Ammonis; gyri of Andreas Retzius; fimbria (displaced upwards, arrows); uncal apex; band of Giacomini; uncinate gyrus; anterior perforated substance; anterior commissure; fornix; corpus callosumFrom : Human Hippocampus

From : Human Hippocampus

anterior paraolfactory sulcus (subcallosal sulcus)cingulate sulcussubparietal sulcus anterior calcarine sulcus; collateral sulcus rhinal sulcus. Limbic gyrus: subcallosal gyrus; posterior paraolfactory sulcus;cingulate gyrus; isthmus; parahippocampal gyrus, posterior part; 11, parahippocampal gyrus, anterior part (piriform lobe). entorhinal area; ambient gyrus; semilunar gyrus; prepiriform cortex. Intralimbic gyrus: prehippocampal rudiment; 16, paraterminal gyrus; indusium griseum. Hippocampus: gyrus dentatus; cornu Ammonis; gyri of Andreas Retzius; fimbria (displaced upwards, arrows); uncal apex; band of Giacomini; uncinate gyrus; anterior perforated substance; anterior commissure; fornix; corpus callosumFrom : Human Hippocampus

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.

Afferents of Amygdala

Efferents of Amygdala

Nucleus accumbens (Nacc.)Reward centre VTAACCGPVA/VLPPMA/SMAMOTOR CORTEXPRESS LEVERSPONTANEOUS MOVE TO ATTEDED SIDEPREFRONTALCORTEXACGATTENTION,FREEZ,ARREST REACTIONDADAHerorinenicotineGlu

Neurocircuitry of reward: The mesolimbic dopaminergic pathway

http://journals.prous.com/journals/dof/20073205/html/df320429/images/fig01.jpg

* (cognitive) olfactory receptor neuron mitral cell tufted cell olfactory bulb primary olfactory fiber primary olfactory cortex gyrus ambiens,gyrus semilunaris (periamygdaloid coetex), corticomedial amygdala rostral entorhinal cortex Primary olfactory cortex secondary olfactory fiber secondary olfactory cortex entorhinal cortex (Brodmanns area 28) tertiary olfactory fiber tertiary olfactory cortex hippocampus hippocampus learning and memory Central processing olfactory cortex thalamus primary olfactory cortex uncinate fasciculus (discriminate) posterolateral orbitofrontal cortex conscious perception dorsomedial nucleus (DMmc : magnocellular portion) entorhinal cortex, amygdala DMmc hypothalamus (emotion and ANS and endocrine response)Afferents of amygdala 1. Direct olfactory inputs corticomedial amygdaloid nucleus amygdala. 2. Indirect olfactory inputs piriform cortex basolateral amygdaloid nucleus. 3. anterior commissure (posterior part). 4. indirect visceral information hypothalamus septal area. orbital, anterior temporal anterior cingulate cortices. audition, vision somatosensory sense. paparbrachial nucleus in rostral pons input solitary nucleus Olfactory system : Lateral olfactory stria

Basolateral nuclei receive sensory input (visual, gustatory, auditory and tactile); also projects to cortex for perception of emotionCorticomedial nuclei receive olfactory inputsCentral nuclei contain output neurons to hypothalamus and periaqueductal grey in brainstem for physiological responses

Input: sensory system : Olfactory (lateral olfactory stria), taste (Nucleus solitarius), and auditory (temporal cortex). Sensory, prefrontal & cingulate cortex.Motor system : ventral striatum

Efferents of amygdala 1. Stria terminalis fasciculus temporal lobe caudate nucleus thalamostriate (terminal) vein. caudate nucleus thalamus interventricular foramen. Fibers septal area hypothalamus. medial forebrain bundle brain stem. stria medullaris thalami habenula. anterior commissure amygdala . 2. Ventral amygdalofugal pathway fibers lenticular nucleus base brain septal area, hypothalamus, anterior olfactory nucleus, anterior perforated substance, prepyriform cortex, orbital anterior cingulate cortices. fiber dorsal dorsomedial thalamic nucleus. amygdalar efferents entorhinal cortex anterior temporal cortex.

N.ANS : CN X , solitary n. parabrachial n = control cardiovascular and visceral functionDM thalamus =affective tone Hypothal (Lat. Hypothalamic and lat. Preoptic area) =feeding centerSeptum fiber diagnalband of brocaVentral striatum : Nacc+olfatory tubercle fiber Amyg addiction and rewardDorsal striatum (caudate and putamen)Connect to striatum for motor activities integrator to appropriate with emotion and motivation

Output:1. Stria terminalis (CM > hypothalamus, septal area),2. Ventral amygdalofugal tract (BL > hypothalamus, PAG)3. Diagonal Band of Broca (septal area)4. Direct: Cortical/ hippocampus/ DM thalamus/ striatum/ brainstem.Only meager projections back from hippocampus, thalamus & hypothalamus.

(Pleassure, hedonic, reinforcement

Accumbens septi telencephalic structure preoptic area lateral septum septum coronal section accumbens ventromedial striatum anterior commissure ventral striatum limbic structure limbic striatum paleostriatum dorsolateral striatum neocortex neostriatum amygdala archistriatum Dopamine Dopamine accumbens lateral interpeduncular nucleus (posterior perforated substance) mesencephalon ventral tegmental area septum. accumbens ventral tegmental area mesolimbic dopaminergic system ventral tegmental area MFB lateral hypothalamus accumbens amygdala, lateral hypothalamus, bed nucleus of stria terminalis hippocampus ventral tegmental area dopamine accumbens motivation reinforcement motivation reinforcer primary(natural) reinforcer secondary(conditioned) reinforcer reinforcer amygdala amygdala reinforcer motivation reinforcer positive reiforcer negative reinforcer reinforcer abnormal reinforcer heroine, nicotine, amphetamine cocain ventral tegmental area accumbens dopamine accumbens (addiction)

The accepted view of reward is that when an activity increases dopamine (DA) transmission in the nucleus accumbens, the rise in DA is translated into a motivational activity of the animal such that the behaviour is repeated. With few exceptions, addictive drugs are those that enhance neural firing and /or neurotransmitter release from dopaminergic neurons located in the ventral tegmental area whose projections innervate the nucleus accumbens (Gardner 2005, Wise, 1996, Wise and Bozarth, 1984), prefrontal cortex and amygdale

Accumbens septi telencephalic structure preoptic area lateral septum septum coronal section accumbens ventromedial striatum anterior commissure ventral striatum limbic structure limbic striatum paleostriatum dorsolateral striatum neocortex neostriatum amygdala archistriatum Dopamine Dopamine accumbens lateral interpeduncular nucleus (posterior perforated substance) mesencephalon ventral tegmental area septum. accumbens ventral tegmental area mesolimbic dopaminergic system ventral tegmental area MFB lateral hypothalamus accumbens amygdala, lateral hypothalamus, bed nucleus of stria terminalis hippocampus ventral tegmental area dopamine accumbens motivation reinforcement motivation reinforcer primary(natural) reinforcer secondary(conditioned) reinforcer reinforcer amygdala amygdala reinforcer motivation reinforcer positive reiforcer negative reinforcer reinforcer abnormal reinforcer heroine, nicotine, amphetamine cocain ventral tegmental area accumbens dopamine accumbens (addiction)