Limbic.system

DR. BALAJI SAINATH. A1S T YEAR PG

The Limbic System

What is limbic system?It includes structures

forming a border between hypothalamus and cerebral cortex.

It is simply functional

anatomic system of interconnected cortical and subcortical structures.

History

Paul Broca– coined the term limbic(Le Grand Lobe Limbique) to include curved rim of cortex including cingulate and parahippocampal gyrus which was different from the rest of the cerebral mantle(appeared paler).

This cortex later shown to be composed of only three layers– labelled allocortex to distinguish it from the six layered eucortex that make up most of the cerebral mantle.

Contd..

James Papez(1937)– postulated these cortical regions(the cingulate gyrus and the parahippocampal gyrus ) are linked to hippocampus, mamillary body and anterior thalamus in circuit that mediated emotional behaviour(Papez circuit).

Emotions tend to go round and round in this circuit.

NEURAL CIRCUIT FOR EMOTION AS ORIGINALLY PROPOSED BY JAMES PAPEZ

Contd..

This concept was supported by Heinrich Kluver and Paul Bucy(1939)—by removing temporal lobes in monkeys they found that amygdala of temporal lobe has role in taming and other basic instincts– fighting, fleeing, feeding and sex.

Contd..

Paul Maclean(1952) -- coined the term limbic system to describe broca’s lobe and related subcortical nuclei as the neural substitute for emotion.

Concept of limbic system

Originally term limbic system encompassed only Broca’s cortex and Papez’s circuitry and later amygdala is included.

Further, the functions of amygdala and hippocampal system proved to have more to do with attention and formation of specific memories than with emotions.

Components of limbic system

Parts mostly listed are,

Limbic cortex - the cingulate and the parahippocampal gyri

The hippocampal formation - the dentate gyrus, the hippocampus, the subicular complex.

The amygdalaThe septal areaThe hypothalamus, the related thalamic and

cortical areasOther parts included are -- insula, entorhinal

cortex, nucleus accumbens

Drawing of the major anatomical structures of the limbic system

The Cingulate gyrus

Located dorsal to corpus callosum

Includes several cortical regions that are heavily interconnected with the association areas of the cerebral cortex

Posteriorly, it becomes continuous (via cingulate bundle of fibres in the white matter) with the parahippocapal gyrus.

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The Parahippocampal gyrus

Located in medial temporal lobe

Lies between the

hippocampal fissure and the collateral sulcus

Continuous with the hippocampus along with the medial edge of the temporal lobe

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The Dentate gyrus

Narrow notched band of gray matter.

Comprises of 3 layers - outer acellular layer, middle granule cell layer, inner polymorphic layer.

Lies between fimbria of the hippocampus and the parahippocampal gyrus

Anteriorly– continued into the uncus

Posteriorly– continuous with indusium griseum

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The Hippocampus

Curved elevation of gray matter. Extends throughout the entire legnth of the

floor of the inferior horn of the lateral ventricle.

Expanded anterior end - Pes hippocampus Terminates posteriorly– beneath the

splenium of corpus callosum Alveus– thin layer of white matter beneath

the convex ventricular surface & adjacent to the polymorphic layer of hippocampus.

Fimbria– bundle formed by nerve fibres originated in hippocampus becomes continuous with the crus of fornix passes anteriorly and inferiorly coloumn of fornix pass through hypothalamus into the mamillary bodies

The Subicular complex

Includes presubiculum, parasubiculum, and the subiculam parts.

The transition region between the hippocampus and parahippocampal gyrus.

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The Amygdala

Located in medial temporal lobe.Just anterior to the hippocampal formation.It is fused with the tip of the tail of the caudate nucleus.Stria terminalis emerges from its posterior aspect.These nuclei form several distinct clusters: the basolateral

complex, the centromedial amygdaloid group, the olfactory group.

CB1 receptor immunoreactivity found in basolateral complex.***Centromedial amygdala appears to be part of a larger

structure that is continuous through the sublenticular substantia innominata with the bed nucleus of stria terminalis (extended amygdala).

The Septal area

Gray matter structure located immediately above the anterior commissure.

The hypothalamus, The Thalamus and Cortical areas

Is a crucial component of neural circuitry regulating not only emotions, but also autonomic, endocrine, and some somatic functions.

Subdivided from anterior to posterior into 3 zones: the supraoptic region, the infundibular region, and the mamillary region.

These 3 zones also are divided on each side into medial and lateral areas by the fornix.

***The lateral and medial mamillary nuclei receive

hippocampal input through fornix and project to the anterior nuclei of hypothlamus.

The Entorhinal cortex

Located in the anterior part of the parahippocampal gyrus, on medial surface of temporal lobe

Transition zone between hippocampus and temporal neocortex

The UncusFormed by the amygdala and the rostral

hippocampus.

The InsulaMedial cortical gyrus located between the

amygdala and the frontal lobe.

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Connections of the limbic system

The major structures of limbic system are interconnected with each other and with other components of nervous system in various ways.

In general, it is area of intimate processing

between hypothalamus and cortical information processing.

The connecting pathways of limbic system are– the alveus, the fimbriae, the fornix, the mamillothalamic tract, and the stria terminalis

Functional circuit b/w hippocampal formation,

Thalamus, cerebral cortex and hypothalamus

Functional circuit b/w amygdala, hypothalamus

Prefrontal and temporal association cortices

Contd..

Basolateral nuclei of amygdala directly and reciprocally connected with the temporal, insular and prefrontal cortices and shares bidirectional connections with the medial dorsal thalamic nuclei.

Medial amygdaloid nucleus has reciprocal connections with endocrine portion of hypothalamus.

Lateral part of extended amygdala connected with brainstem and lateral hypothalamus and receives cortical limbic region and the basolateral amygdaloid complex.

Contd..

Both of these pathways reveal how the limbic system is able to integrate the highly processed sensory and cognitive information content of the cerebral cortical circuit with the hypothalamic pathways that control autonomic and endocrine systems.

In addition,The limbic system also interacts with

components of the basal ganglia system.

Functional circuits b/w basal ganglia and limbic system

Contd..

The septal area reciprocally connected with the hippocampus, the amygdala, and the hypothalamus and projects to numerous structures in the brainstem.

Limbic system also receives inputs from the smell receptors in the nose.

Functions of the limbic system

Olfaction – entorhinal cortexAppetite and eating behaviours Amygdala – food choice & modulation of food

intake Lateral nucleus – feeding Ventromedial nucleus – satiteySleep and dreams Suprachiasmatic nucleus – circadian rhythm/

sleep-wake cycle Ventrolateral preoptic nucleus (VLPO) – sleep

switch/ promoting (REM) sleep

Contd..

Emotional responces Fear – amygdala Rage – neocortex, ventromedial nucleus, septal

nucleus Placidity – B/L amygdalaAutonomic and endocrine responces to emotion –

cingulate gyrus & hypothalamusSexual behaviour – medial preoptic area of

hypothalamus (MPOA) & medial amygdala (MeA)Addiction and motivation – amygdala & nucleus

accumbens

Contd..

Memory Emotional memory – amygdala , prefrontal

cortex, medial temporal lobe Longterm declarative memory –

hippocampusSocial cognition – cingulate gyrus &

amygdala

LS Vs Adrenal gland

Anatomy and physiology of the adrenal gland are reflected in the anatomy and physiology of the amygdala circuit and hippocampal circuit

Adrenaline secreted by the adrenal core is processed by the amygdala system

Cortisone secreted by adrenal cortex is

processed by the hippocampal formation

The LS (amygdala) in Emotions

In generel, amygdala assign emotional significance to sensory experiences.

LS directs the hypothalamus to express the motor and endocrine components of emotional states.

Emotional experiences and expressions per se are accompanied and even initiated by body responses (change in heart and respiratory rate and blood pressure). The responses waned with repetition as they become familiar (habituation).

Contd..

The amygdala was shown to be important to processing these experiences.

The body responses help a person to attain via the amygdala, a certain kind of memory and that emotions is due to a challenge to the pattern of that memory, not the body responses themselves.

Fear is not an expression of an experience per se, but of a memory based anticipation of pain that may be realistic and imagined.

The LS (hippocampus) in Memory

Hippocampus is concerned with recent memory converting it to long term memory– memory of the remote past events before the lesion developed is unaffected.

In damage to hippocampus– the memory of what is happening to the patient personally fails to become familiar.

Contd..

The hippocampus is important to an organism’s ability to reset an internal co-ordinate system. This process is critical to navigation and episodic memory.

While the amygdala is processing what is novel during habituation, the hippocampus is processing the context within which habituation is happening, the hippocampus is processing what is already familiar.

The co-ordinates are constructed by attending to what is not, at the moment, the focus of navigating our world. Eg: to walk through a door we must process the walls so as not to bump into them.

The LS (hippocampus) in Motivation and Attidude

The hippocampal circuit brings together emotion and motivation,

The emotion—the processing of familiarty The motivation– the processing of

readiness to engage the world in practical manner

Attitudes (emotions plus motivation) are dispositional states that embody the experience of the individual.

The LS in Sexual behavior

Directly involved in elements of sexual functioning.Stimulation of various sites of the limbic system

have elicited penile erection.Hippocampus– genital tumescence, regulation of

release of gonadotropins.Amagdala– in oral and then in genital benaviour.Olfactory sense is strongly involved in both feeding

and mating.Those areas activated by emotions of fear and

anxiety are notably quiescent when the woman experience an orgasm.

The LS in Violence behavior

The fear is processed in amygdala – stimulation of it elicits defensive and aggressive responses.

Other parts involved are– hypothalamus and septal area.

The prefrontal cortex allows humans to exercise some control over their responses.

Aggressive behavior have been noted individual with damage to the medial temporal lobe and with developing brain tumor in the limbic system.

Frontal lobe injury commonest type in infancy and early childhood have lifelong consequences.

Case of Arthur Shawcross

Was an American serial killer, also known as the Genesee River Killer in Rochester, New York.Psychiatrists had assessed Shawcross as a "schizoid psychopath".Shawcross pleaded not guilty by reason of insanity.Prosecution psychiatrist Dr. Park Dietz said Shawcross had antisocial personality disorder.

The LS in positive mental health (anterior cingulate and insula)

Both the limbic anterior cingulate and insula appears to be active in the positive emotions of humor, trust and empathy.

The prosocial biological activity of the anterior cingulate cortex and insula was highest in individiuals with highest level of social awareness the biological differences for positive mental health.

Anterior cingulate gyrus links valence and memory to create attachment.

Along with the hippocampus, the anterior cingulate is the brain region most responsible for making the past meaningful.

Contd..

Anterior cingulate fMRI images light up when a lover gazes at pictures of a partner’s face or when a new mother hear her infant’s cry.

Insula helps to bring visceral feelings into consciousness.The pain in one’s heart or grief , the warmth in one’s heart

or love, and the tightness in one’s gut from fear all make their way into consciousness through the insula.

fMRI studies of kundalini yoga practitioners demonstrates the meditation activates the activity of the hippocampus and right lateral amygdala which in turn leads to parasympathetic stimulation and sensation of deep peacefulness.

1. SCHIZOPHRENIA2. BPAD3. ANXIETY & OCD4. AUTISM5. ALZHIEMERS6. LIMBIC ENCEPHALOPATHY7. WERNICKE & KORSAKOFF8. EPILEPSY9. KLOVER BUCY SYNDROME10.PSYCHOSURGERY

Clinical implications

Schizophrenia

Because of its role in controlling emotions, the LS has been hypothesized to be involved in pathophysiology of schizophrenia.

Limbic activation is diminished.

Abnormally increased limbic activation time (threat related fascial emotions of anger and fear).

Antipsychotics block limbic receptors to dopamine as well as receptors of the extrapyramidal system.

Contd..

Neuropathology findings—decrease in size of regions including the amygdala, the hippocampus and parahippocmapal gyrus.

Hippocampus is not only smaller, but is functionally abnormal as indicated by disturbances in glutamate transmission.

Disorganisaion of neurons within the hippocampus has also been reported.

BPAD

Evidence of hyperactivity and hyperfunction of some limbic and para limbic areas - including amygdala and ventral striatum as well as in the cerebellum.

Evidence of limbic hyperactivity is consistent with the lack of modulation and overswings in both manic and depressive behaviours.

Amygdala is small in children and large in adults when compared to controls in BPAD.

The number of hospitalizations for mania was directly associated with increased size of the amygdala.

Anxiety and OCD

In addition to receiving noradrenergic and serotonergic innervation the LS contains highest concentration of GABA A receptors.

Increased activity of the septohippocampal pathway leads to anxiety.

Cingulate gyrus has been particulary implicated in pathophysiology of OCD.

Disproportionate impairment in specific aspects of social cognition.

Limbic structures involved - cingulate gyrus and amygdala which mediate cognitive and affective processing.

The basolateral circuit integral for social cognition is disrupted in autism spectrum disorders.

Autism

Alzhiemers disease

Gross– medial temporal lobe atrophy and hippocampal atrophy most common.

Plaques and tangles most frequently present in hippocampal and entorhinal cortex.

Limbic encephalopathy

Usually due to metastatic ca of lung.Marked disturbance of memory for recent events.Affective disturbance - severe anxiety and

depression.Pathology - combination of degeneration and

inflammation on the medial temporal lobe structures -the hippocampus, uncus, amygdaloid nucleus, dentate gyrus, insular and posterior orbital cortex.

Where memory failure is predominat feature the possibity of limbic encephalopathy should be considered.

Wernicke and Korsakoff

Caused by B1 deficiency.

Changes involve periventricular areas: medial thalamus, hypothalamus, mamillary bodies, reticular formation.

Lesions show petechial hemorrhages, edema, myelin loss, and reactive gliosis. Neurons generally preserved.

Epilepsy in hippocampal sclerosis

Hippocampal cell loss can be considered as a cause and consequence of repeated seizures.

Hippocampal sclerosis seen in 47—70% of all TLE.

Limbic epilepsy

Limbic epilepsy can originate in the amygdala, hippocampus, entorhinal cortex, cingulate or orbital frontal cortex.

Pts classically describe fear, déjà vu, jamais vu, elementary and complex visual hallucinations, illusions, forced thinking, or emotional distress.

Kluver Bucy syndrome

Bilateral removal of temporal lobe– amygdala, para amygdala area.

Features No evidence of fear or anger, unable to appreciate object visually, increased appetite, increased sexual activity - indscriminately seek partnership with male, female animals.

Psychosurgery

Stereotactic operations on the amygdaloid nuclei: decreased emotional excitability.

OCD: cingulotomy, anterior cingulotomy, and limbic leucotomy may be effective.

Pain: cingulotomy.

Epilepsy (TLE)

Tourette: disconnection of the anterior cingulate from the thalamus results in improvement of symptoms.

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