LIMBIC SYSTEMDR. YASHASREE POUDWAL

K.J.SOMAIYA HOSPITAL

INTRODUCTION

Limbic- border

Refers to a ring of grey matter on the medial aspect of the cerebral hemispheres

Entire neuronal circuitry that controls emotional behavior and motivational drive

Network of structures associated with emotions, basic survival and sociosexual behavioral patterns, motivation and learning

HISTORY

Paul Pierre Broca in 1878 described The Great Limbic lobe or ‘le grand lobe limbique’

In 1937 James Papez wrote a paper called ‘proposed mechanism of emotion’ which elaborated the putative role in emotion.

In 1952 Paul Mclean coined the term “limbic system’. Also proposed the ‘Triune brain theory’

PAUL BROCA

COMPONENTS Limbic lobe Cingulate gyrus Parahippocampal gyrus Hippocampal formation Dentate gyrus Hippocampus Subicular complex Amygdala Septal area Hypothalmus Mamillary body Ant. Nucleus of thalamus

LIMBIC LOBE Situated on inferomedial aspect of cerebral

hemispheres

2 concentric gyri surrounding the corpus callosum

Outer larger gyrus ‘limbic gyrus- consists of isthmus of cingulate gyrus, parahippocampal gyrus (continuous-cingulum) and subcallosal area.

Inner smaller ‘intralimbic gyrus’

Enthorhinal complex(ERC) which funnels highly processed cortical information to hippocampal formation. Major output pathway

Cerebral association area for control of behavior

Two way communication and association linkage between the neocortex and lower limbic structures

Essentially all behavioural patterns can be elicited by specific portions of the limbic cortex

Ablation of some limbic cortical areas can cause persistent changes in an animal’s behavior

HIPPOCAMPAL FORMATION

Hippocampus and its adjacent temporal and parietal lobe structures, all together called the hippocampal formation

Has numerous but mainly indirect connections with many portions of the cerebral cortex, amygdala, hypothalamus, septum and the mammillary bodies

Hyper-excitable- prolonged discharges with slight stimulus

Involved with sensations

Associated with long term memory

DENTATE GYRUS 3 layered- outer acellular molecular, granular

middle and inner polymorphic layer

Thought to contribute to formation of new episodic memories, spontaneous exploration of novel environments.

One of few sites in brain known to have high rates of neurogenesis.

HIPPOCAMPUS

Sea horse in Greek

Trilaminate

On basis of different cytoarchitecture and connectivity has 4 fields: CA1,CA2, CA3, CA4

The thin layer of fibers adjacent to the polymorphic layer of the hippocampus is known as the alveus. These fibers coalesce to form the fimbria.

SUBICULAR COMPLEX

Most inferior component

Lies between the entorhinal cortex and CA1 subfield of the hippocampus

Believed to play a role in human epilepsy

Also implicated in working memory and drug addiction

Suggested that dorsal subiculum is involved in spatial relations and ventral cubiculum regulates the HPA axis

AMYGDALA

Almond shaped structure deep within temporal lobe

Lies at the ant. End of the hippocampal formation and ant. Tip of inferior horn of the lateral ventricle

Structurally diverse. Consists of 13 nuclei

Window of the limbic system: wide aff and eff connections with visual and auditory association areas

FUNCTIONS OF AMYGDALA

Behavioral awareness area

Project into the limbic system one's current status in relation to both surroundings and thoughts

Make the person’s behavioral response appropriate for each occasion

Relate environmental stimuli to coordinated behavioral autonomic and endocrine responses in species preservation-

REGIONS OF THE AMYGDALA

Large basolateral region: provides direct input to basal ganglia and motor system

Small corticomedial group of nuclei: related to olfactory cortex especially in lower animals

Medial and central nuclei: connected to hypothalamus

Other amygdaloidal nuclei

Extended amygdala ( centromedial amygdala, sublenticular sustantia innominata and bed nucleus of stria terminalis

SEPTAL AREA

Grey matter structure immediately above the anterior commissure

Extensive reciprocal connections with the hippocampus via fornix

HYPOTHALAMUS

Lies at the center of the limbic system

Confluence of many neural pathways

Subdivided from ant to post into 3 zones- supraoptic, tuberal region and the mammillary region.

governs the involuntary internal responses of various body systems in preparation for appropriate action to accompany a particular emotional state.

MAMILLARY BODIES

act as a relay for impulses coming from the amygdalae and hippocampi via the mamillo-thalamic tract to the thalamus

This circuit, from amygdalae to mammillary bodies, and then on to the thalamus, is part of the larger 'Papez circuit'.

They, along with the anterior and dorsomedial nuclei in the thalamus, are involved with the processing of memory

They are believed to add the element of smell to memories.

ANTERIOR THALAMIC NUCLEUS

Collection of nuclei at rostral end of the dorsal thalamus

Receive afferents from mammillary bodies and subiculum

Project to the cingulate gyrus

Play a role in modulation of alertness, learning and memory

FUNCTIONAL CIRCUITARY

PAPEZ CIRCUIT

James Papez’s delineation of a circuit unraveled the basis of cortical control of emotion.

Recent studies show that it has a more significant role in memory functions than in emotions

Papez circuit was later modified by American neuroscientist and physician Paul D. MacLean

The Papez circuit involves various structures of the brain. It begins and ends with the hippocampus

linked the hippocampus with the cingulate cortex, via the mammillary bodies and anterior thalamus.

He proposed that emotional expression is organized in the hippocampus, experienced in the cingulate gyrus and expressed via the mammillary bodies.

The hypothalamus was considered to be the site where hippocampal processes gain access to the autonomic outflow that controls the peripheral expression of emotional states.

The Papez circuit is now widely accepted to be involved with cognitive processes.

PAPEZ CIRCUIT

HIPPOCAMPAL AFFERENTS

Major input into the hippocampal formation arises from neurons in layers II and III of the entorhinal cortex.

In addition, some septal and hypothalamic formation reach the hippocampal formation via the fornix

Few fibers also arrive from contralateral hippocampal formation via the hippocampal commissure

Connections of hippocampal formation

INTERNAL CIRCUITS

Intrinsic connections of the hippocampus involve fibers from the entorhinal area, dentate gyrus, ammon’s horn and subiculum.

The three primary pathways of this area are called the perforant pathway, mossyfibers and Schaffer collaterals.

Existence of a fourth pathway, the alvear pathway, has been questioned, from the entorhinal area to ammon’s horn

Perforant path where glutamateric fibers from the entorhinal area perforate the subiculum and reach the dentate gyrus.

The glutamatergic mossy fibers then extend from the dentate gyrus to CA3 (pyramidal layer)

Many axons of CA3, however, give off the Schaffer collaterals that reach the dendrites of CA1.

CA1 is considered the main output of the hippocampus with fibers extending to the alveus, fimbria and then fornix.

A supplementary linkage with the subiculum also is believed to be present

INTERNAL CIRCUIT

CIRCUITS OF AMYGDALA

Serves to integrate information processing between prefrontal/ temporal association cortices and the hypothalamus.

The amgdala has two major outputs

Dorsal route- via stria terminalis projects to the septal area and hypothalamus

Ventral route- via ventral amygdalofugal pathway.

AMYGDALO-SEPTAL PATHWAY

AMYGDALA BASAL GANGLIA CIRCUIT

FUNCTIONS OF THE LIMBIC SYSTEM

OLFACTION:

limbic structures are closely related to the olfactory cortex and have a role in the processing of olfactory sensation

Amygdala is involved in the emotional response to smell while the entorhinal cortex is concerned with olfactory memories

APPETITE AND EATING BEHAVIOUR:

Amygdala plays a role in food choice and emotional modulation of food intake.

SLEEP AND DREAMS:

PET and MRI have shown that the limbic system is the most active brain areas during the process of dreaming.

Probably interweaves unconscious primal emotions with conscious cognitive thoughts

The suprachiasmatic nucleus of the hypothalamus generates the circadian cycle. Controls sleep-wake cycle.

EMOTIONAL RESPONSES:

FEAR: fear responses are produced by the stimulation of the hypothalamus and amygala. Amygdala is also involved in fear learning.

RAGE AND PLACIDITY: Rage reponses to minor stimuli are observed after removal of the neocortex. Destruction of the the ventromedial hypothalamic nuclei and septal nuclei also induces rage.

AUTONOMIC AND ENDOCRINE RESPONSES TO EMOTION:

Limbic stimulation causes changes in respiration and blood pressure.

The stimulation of the cingulate gyrus and hypothalamus can elicit autonomic responses

The fear and rage responses mediated by the limbic system cause stimulation of various parts of the hypothalamus, especially the lateral areas and produce diffuse sympathetic discharge. The massive sympathetic discharge during stress is called the —fight or fright response“.

Stress via cortical and limbic connections causes release of corticotropin-releasing hormone (CRH) from the paraventricular nuclei of the hypothalamus.

SEXUAL BEHAVIOUR:

The medial preoptic area of the hypothalamus is a key structure in the central control of male sexual behavior. Chemosensory efferents from the main and accessory olfactory systems project to the medial amygdala (MeA)

REWARD AND PUNISHMENT:

electrical stimulation of certain limbic area pleased or satisfies the animal or cause terror, pain, fear, defense, escape reactions

Reward centers: along the course of the medial forebrain bundle and lateral and ventromedial nuclei of the hypothalamus

Punishment centers: central gray area surrounding the aqueduct of sylvius in the mesencephalon and extending upward into the periventricular zones of the hypothalmus and thalamus

MEMORY:

Emotional memory: Amygdala is involved in consolidation and retrieval of emotional memories. also involved in the acquisition, extinction and recovery of fears to cues and contexts. Hippocampus is critical for long-term, declarative memory storage.

Medial temporal lobe memory system: include the hippocampus and adjacent cortex, the parahippocampal regions (PHG) . This memory system is involved in the storage of new memories

Diencephalic memory system: consists of the hypothalamus, mammillary body and the dorsomedial nucleus of thalamus. This circuit is important for the storage of recent memory; a dysfunction of this circuit results in Korsakoff’s syndrome.

SOCIAL COGNITION:

refers to thought processes involved in understanding and dealing with other people.

Social cognition involves regions that mediate face perception, emotional processing; theory of mind (TOM); self-reference and working memory.

Together, the functioning of these regions would support the complex behaviors necessary for social interactions.

Limbic structures involved are the cingulate gyrus and amygdala

CLINICAL IMPLICATIONS

TEMPORAL LOBE EPILEPSY:

Most common epilepsy in adults and is most often caused by hippocampal sclerosis. Seizures that occur in these areas are called psychomotor seizures.

Temporal lobe epilepsy may include: abnormal sensations (uncinate fits), repeated involuntary movements, memory loss, hallucinations and disorders of recall and recognition

Although anticonvulsant drugs are often given to control the seizures they maybe ineffective. In these cases neurosurgical removal of the focus may provide excellent seizure control

LIMBIC ENCEPHALITIS:

Paraneoplastic syndrome reported in carcinoma of the lung, breast etc. Mechanism is unknown but manifests as encephalitis. Afflicted patients develop sub acute onset of memory loss, dementia, involuntary movements and ataxia.

DEMENTIA:

Degenerative changes in the limbic system likely have a role in the genesis if neurodegenerative diseases esp. Pick’s disease and Alzheimer’s disease. Marked atrophy is found most notably the dentate gyrus and hippocampus.

ANXIETY DISORDERS:

Maybe result of a failure of the ant. Cingulate and hippocampus to modulate the amygdala.

SCHIZOPHRENIA:

Studies have shown reduced limbic volumes. There is involvement of papez circuit. The other circuit involved is the basolateral circuit which mediates the social cognition deficits in schizophrenia.

AFFECTIVE DISORDERS:

decreased prefrontal and anterior cingulate activity in affective disorders.

ADHD:

The enlarged hippocampus in children and adolescents with ADHD may represent a compensatory response to the presence of disturbances in the perception of time, temporal processing and stimulus-seeking associated with ADHD.

AUTISM:

Autism and Asperger’s syndrome involve the disproportionate impairment in specific aspects of social cognition. Limbic structures involved include the cingulate gyrus and amygdala, which mediate cognitive and affective processing.

KLUVER-BUCY SYNDROME:

Kluver-Bucy syndrome results due to a bilateral destruction of the amygdaloid body and inferior temporal cortex.

Major characteristics of this syndrome include: hyperorality, hyper sexuality, psychic blindness, personality changes, usually with the development of abnormal passivity or docility.

Combination of at least 3 or more of the symptoms suggest the syndrome

This disorder may be caused by many conditions including cerebral trauma; infections, Alzheimer’s disease and other dementias; Niemann-Pick disease and cerebrovascular disease

The psychic blindness observed presumably results from damage to the amygdalae, which usually functions as a site of transfer of information between sensory association cortex and the hypothalamus

After damage, visual stimuli can no longer be paired with affective responses

Treatment:1) carbamazepine- potent inhibitor of amygdaloid kindling. Useful agent for eliminating some of the the symptoms. 2) leuprolides- decrease sexual behavior 3)antipsychotics like haloperidol to reduce behavioral abnormalities

KORSAKOFF PSYCHOSIS:

Caused by damage to mammillary bodies, dorsomedial nucleus of thalamus

Due to thiamine deficiency in chronic alcoholics

Associated with impairment of recent and remote memory. (recent> remote)

Immediate recall is usually preserved.

Confabulation maybe present and marked

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