ANATOMY OF THE MENTAL AND NEUROBEHAVIOR DISORDER

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

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

INTRODUCTIONThe human brain is the organ that is the basis of what persons sense, do, feel, and think; or put in more formal terms, our sensory, behavioral, affective, and cognitive experiences and attributes. It is the organ that perceives and affects the environment and integrates past and present.By processing external stimuli into neuronal impulses, sensory systems create an internal representation of the external world. A separate map is formed for each sensory modality. Motor systems enable persons to manipulate their environment and to influence others' behavior through communication. In the brain, sensory input, representing the external world, is integrated with internal drivers, memories, and emotional stimuli in association units, which in turn drive the actions of motor units. Although psychiatry is primarily concerned with the brain's association function, an appreciation of the sensory and motor systems' information processing is essential for sorting logical thought from the distortions introduced by psychopathology.

Primary sensory cortexPrimary motor cortexAssociation cortexSensory systemLower Motor neuron

OVERVIEW OF THE FUNCTIONAL ANATOMY OF THE BRAIN

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

Areas of the human cerebral cortex defined by Brodmann in his 1909 publication

The six layers of the neocortex, from the pial surface above layer 1 to the white matter below layer 6.

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.

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)Functions:Maintenance of homeostasisMotivated and goal-oriented behaviorsSurvival of the individualSurvival of the speciesLearning and memory

Stuctures of the Limbic SystemHypothalamusAmygdalaSeptal areaHippocampal formationCingulate gyrus

The limbic structures. The right hemisphere, as viewed from the medial aspect. The regions and cell groups indicated in red are usually included in the term limbic system.

The hippocampal formation, fornix, mammillary nucleus, and the amygdala. Left: Viewed obliquely from behind. Right: Viewed from above.

Schematic illustration of the location of the limbic system between the diencephalon and the neocortical hemispheres

Schematic illustration of the concentric main components of the limbic sytem.

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.

Schematic illustration (left oblique view) of the position of the hippocampal formation within the left hemisphere

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

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

HIPPOCAMPAL FORMATION

Structures constitute the Hippocampal FormationSubiculumDentate gyrus Hippocampus proper

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

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

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

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.

The amygdala. Frontal section through the left hemisphere . Some of the amygdaloid nuclei are marked. The amygdala and the cerebral cortex of the temporal lobe are closely connected.

Afferent connections of the amygdala

Efferent connections of the amygdala

The amygdala and conditioned fear. The neural substrate of the responses elicited by a conditioned stimulus (sound) associated with an electric foot shock. The connections of the amygdala with the sensory association areas are necessary for discriminative aspects of stimulus analysis, while connections with the hippocampus mediate contextual conditioning.

Main connections of the cingulate gyrus. The cingulate gyrus has connections with cortical association areas and with limbic structures and may act as a mediator between them.