NEUROANATOMY OF MENTAL AND NEUROBEHAVIOR DISORDERS

8/13/2019 NEUROANATOMY OF MENTAL AND NEUROBEHAVIOR DISORDERS

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Learning Objectives

1. Describe the structures involved in psychiatric andneurobehavioral disorders

2. Describe and diagram the basic morphology of thestructures comprising the limbic system

3. Describe and diagram the input-output relationshipsof 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 disordersassociated with dysfunctions of the limbic system


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OVERVIEW1. Anatomy of neurobehavior system

1. Overview of the human nervous system2. Anatomy of the brain

1. Cortex cerebri

2. Anatomy of the Limbic system

2. Physiology of neurobehavior system

1. Overview of the motor system1. Pyramidal system

2. Extrapyramidal system

2. Overview of the sensory system

3. Higher functions of the brain1. Intellectual functions of the brain

2. Learning

3. Memory

4. Emotion


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Structures Involved in Psychiatric and

Neurobehavioral Disorders1. Hippocampal formation2. Amygdala

3. Orbitofrontal cortex

4. Cingulate gyrus

5. Hypothalamus

6. Mammilary bodies7. Anterior thalamic nucleus

8. Medial dorsal thalamis nucleus

9. Ventral striatum

10. Frontal lobe

11. Rhinencephalon12. Mesencephalon1. Substantia Nigra

2. Ventral tegmental area (VTA)

3. Formatio reticularis

Limbic system


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OVERVIEW OF THE

FUNCTIONAL ANATOMY

OF THE BRAIN


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


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Spatial relationships between basal ganglia, thalamus, and

internal capsule as viewed from the left side.


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OVERVIEW OF THE

LIMBIC SYSTEM


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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


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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


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Limbic system

Hippocampal

formation

(archicortex,

three layers)

Limbic lobe,

(mesocortex, three

to five layers)

Neocortex,

(five to six layers)

Hippocampus

Dentate gyrus

Amygdala

Phylogenetically

oldest

Newest

Parahippocampal gyrus

Cingulate gyrus

Subcallosal gyrus

Primary motor cortex

Primary sensory cortexAssociation cortex


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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.


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Stuctures of the Limbic System

1. Hypothalamus

2. Amygdala

3. Septal area4. Hippocampal formation

5. Cingulate gyrus


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Fundamentals of Human Neuropsychology.

A. This medial view of the right hemisphere illustrates the principal structures of the

limbic system, including the cingulate cortex, the hippocampus, and theamygdala.

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.)


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Structure Connections

Dentate gyrusFrom entorhinal cortex (via perforant pathway and alvear pathway)

To hippocampus (via mossy fibers)

Hippocampus From 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 area From olfactory bulb, amygdala, fornix

To medial forebrain bundle, hypothalamus, habenula

Amygdala From primitive temporal cortex and sensory association cortex, opposite

amygdala (via anterior commissure)

To hypothalamus (direct amygdalofugal pathway), septal area, andhypothalamus (via stria terminalis)

Some Limbic System Connections

Clinical Neuroanatomy, Waxman,25thed.


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Medial aspect of the right hemispherium showing the corpus callosum.

CCg = Genu; CCb = Body; CCs = Splenium


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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.


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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.


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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.


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Diagram of the principal connections of the limbic system. Olfactory and

amygdaloid connections.


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Diagram of the principal connections of the limbic system. Hippocampal

system and great limbic lobe.


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Schematic llustration of the location of the limbic system between

the diencephalon and the neocortexClinical Neuroanatomy, Waxman,25thed.


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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.


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Schematic illustration (left oblique view) of the position of

hippocampal formation in the left hemisphere



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Le Grande Lobe Limbique as adapted from Brocasoriginal 1878 drawing of an

otters brain. Brocascallosal gyrus is now termed the cingulate gyrus.

Ref: Clinical Neuroanatomy.pdf


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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


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RHINENCEPHALON AND

OLFACTORY SYSTEM


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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 receptorsare

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.


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The olfactory nerve (lateral view)



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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) projectprecisely to a small number

of glomeruli within the

olfactory bulb.

Olf S


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Olfactory System,cont

The mitral cells of the olfactory bulb send their

axons posteriorly via the olfactory tracts(also

termed the medialand lateral olfactory stria) to

the olfactory projection area in the cortex. The lateral olfactory striais the projection bundle

of fibers that passes laterally along the floor of the

lateral fissure and enters the olfactory projection

areanear the uncus in the temporal lobe (the

pyriform, entorhinalcortex 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 striapasses medially

and up toward the subcallosal gyrus (the anterior

olfactory nucleus)which sends its axons back to

the olfactory bulbs on both sides, presumably aspart of a feedback circuit that modulates the

sensitivity of olfactory sensation.

Other olfactory fibers reach the anterior

perforated substance to serve olfactory reflex

reactions.


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1. Anosmia (loss of smell):

1. Nasal infection

2. Head trauma that damages the cribrous plate

2. Olfactory (or uncinate) hallucination:

1. Might be a sign of temporal lobe tumor

Olfactory System,Dysfunction


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HIPPOCAMPAL

FORMATION

Structures of the Hippocampal Formation


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Structures of the Hippocampal Formation

1. 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.

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


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Schematic illustration of the major connections to, within, and from the

hippocampal formation. Dentate granule cells (DG) project to pyramidal neurons

in the hippocampus. CA1through CA4are sectors of the hippocampus



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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


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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.

Fib th t f th FORNIX


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Fibers that form the FORNIX


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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


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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.


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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


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OFC, orbitofrontal cortex

FAC, Frontal association cortex

PMC, premotor cortex

AAC,auditory association cortex

SAC,somatosensory association cortex

SPL , superior parietal lobuleIPL, inferior parietal lobule

TAC, temporal association cortex,

VAC, visual association cortex


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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 cortexTAC, temporal association cortex,

VAC, visual association cortex

A, amygdala

H, hippocampus

E, entorhinal cortex


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HIPPOCAMPAL AFFERENTS HIPPOCAMPAL EFFERENTS

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


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HYPOTHALAMUS

A. The approximate boundaries of the


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pp

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, 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.

HYPOTHALAMIC

PITUITARY CONNECTIONS.


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The posterior portion of the pituitary

(neurohypophysis) is innervated by

hypothalamic neurons that transport the

hypothalamic hormones (oxytocin and

vasopressin) down their axons to bereleased 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 (eitherreleasing 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.


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SEPTAL AREA


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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).


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AMYGDALA

AMYGDALA


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AMYGDALA

The amygdala (amygdaloid

nuclear complex) is a gray

matter mass that lies in themedial temporal pole

between the uncus and the

parahippocampal gyrus.

It is situated just anterior tothe tip of the anterior horn of

the lateral ventricle.

Its fiber connections include :

1. the semicircular stria terminalistothe septal area, preoptic areas and

anterior hypothalamus.

2. amygdalofugal pathwayto the

middle portion of the

hypothalamus.

Nuclei of Amygdala


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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 amygdalofugalpathway, to the ventral striatum and the thalamus.

2. 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.


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the organization of the nuclei of the amygdala


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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.

Dysfunction of the Limbic System


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Stimulation alters somatic motor responses, leading

to bizarre eating and drinking habits, changes insexual 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 alsoprofoundly affect memory.

Dysfunction of the Limbic System

Klver-Bucy Syndrome


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y y

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 tothe amydala.

personality changes,usually with abnormal passivity or

docility.

Temporal Lobe Epilepsy


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Temporal Lobe Epilepsy

The 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.


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PREFRONTAL CORTEX

PREFRONTAL CORTEX


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PREFRONTAL CORTEX

Located in front of the motor cortex. This is one of

the anatomic structures that distinguishes humansfrom other mammal.

Comprises 29% of the total cortex.

Dysfunction in the PFC is implicated as a possiblesource of pathology in many psychiatric disorders

depression, schizophrenia, anxiety, and attention

deficit hyperactivity disorder (ADHD) as well as anger

and violence.

FRONTAL CORTEX


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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 theprimary 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. the executive prefrontal cortex, occupying the dorsal and lateralaspects of the prefrontal cortex;

2. the paralimbic prefrontal cortex, occupying the orbital and medial

aspects of the prefrontal cortex;

3. the anterior cingulate area.

Executive/Dorsolateral Prefrontal Cortex


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Executive/Dorsolateral Prefrontal Cortex

The 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 thetransformation of sensory information into preparation for

movement.

Paralimbic/Orbitofrontal Cortex


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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 themotivational and cognitive state of the individual.

Anterior Cingulate Gyrus


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Anterior Cingulate Gyrus

The 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 Striatum


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Basal Ganglia and Ventral Striatum

The striatum consists of the caudate and the putamen.

The more dorsal components of the striatum are associated with theextrapyramidal 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.


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PICTURES OF THE LIMBIC SYSTEM


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From : Human Hippocampus


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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



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Intraventricular aspect of

the hippocampus.(The temporal horn has been opened

and the choroid plexuses removed.)

1. hippocampal body2. head and digitationes

hippocampi (internal

digitations)

3. hippocampal tail

4. fimbria

5. crus of fornix

6. Subiculum7. splenium of the corpus

callosum;

8. calcar avis

9. collateral trigone

10. collateral eminence

11. uncal recess of thetemporal horn


1. anterior paraolfactory sulcus(subcallosal sulcus)

2. cingulate sulcus

3 b i t l l


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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 callosumFrom : Human Hippocampus

1. anterior paraolfactory sulcus(subcallosal sulcus)

2. cingulate sulcus

3 b i t l l


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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 callosumFrom : Human Hippocampus


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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.


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NEUROANATOMY OF MENTAL AND NEUROBEHAVIOR DISORDERS

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