The Limbic System

Midsagittal view of the brain showing the limbic system

The Limbic System

Functional anatomic system of interconnected cortical and subcortical structures
between the hypothalamus and cortex

Role in memory, learning and social interaction Paul Broca: limbic means border; border between hypothalamus and cerebral cortex

The Limbic System

Limbic lobe
Subcallosal gyrus Cingulate gyrus Isthmus of the cingulate gyrus Parahippocampal gyrus Uncus Hippocampal formation

 Originally, the limbic lobe was assigned was assigned a purely olfactory function It has been established that only a minor part of the limbic lobe has an olfactory function The rest of the limbic lobe, which forms part of the limbic system, plays a role in emotional behavior and memory

The Limbic System

Limbic system
Limbic lobe PLUS all the subcortical and cortical

structures related to it
Nucleus accumbens Nuclei of hypothalamus (related to mammillary body) Amygdaloid complex Substantia innominata Anterior and dorsomedial thalamus Habenular nuclei Ventral tegmental area Periaqueductal gray Prefrontal cortex

Limbic System
1. Emotional behavior 2. Memory 3. Integration of homeostatic responses such as those related to preservation of the species, securing food, and the fight or flight response 4. Sexual behavior 5. Motivation - The underlying mechanism for these different

The Limbic System

Main efferent fiber bundles of the limbic system
Fornix
Hippocampus and subiculum

Stria terminalis and Ventral amygdalofugal pathway

Amygdaloid complex

Mammillothalamic tract
Medial mammillary nucleus

Cytoarchitectural Definitions of The Limbic Cortex

Most cortices : neocortex with 6 layers
Primary sensory, motor and association cortices

Allocortex: < 6 layers

Most structures of limbic system

Paleocortex/paleopallidum/periallocortex : 3 to 5 layers
Parahippocampal gyrus (entorhinal cortex), Uncus (piriform cortex), Lateral olfactory stria (gyrus)

Archicortex /archipallidum/allocortex: 3 layers

hippocampus and dentate

Cytoarchitectural Definitions of The Limbic Cortex

Transition from one cortex to another
Funnel input from association areas of neocortex into allocortex Temporal pole, parts of insula, portions of parahippocampus, cingulate gyri

Papez Circuit
Emotion mediated through hypothalamus is controlled and modulated by fibers from fornix Cortical control of emotional activity originate from cingulate and hippocampus Circuit ends in the cingulate gyrus

Hippocampus fornix mammillary bodies anterior thalamic nucleus cingulate gyrus hippocampus
Areas of cerebral cortex recruited through connections of the cingulate gyrus Reciprocal connections with premotor, prefrontal areas, visual/auditory/somatosensory association cortices

 Areas of cerebral cortex recruited through connections of cingulate gyrus Reciprocalconnections with premotor, prefrontal areas, visual/auditory/somatosensory association cortices

Neural circuit for emotion proposed by James Papez and extended by Paul MacLean

The Circle of Willis

Blood Supply to the Limbic System

Internal CarotidArtery
Anterior choroidal artery
Hippocampal formation, parts of amygdaloid complex, stria terminalis

Anterior Cerebral Artery

Subcallosal area, rostral cingulate gyrus (branch) Pericallosal artery: most of cingulate gyrus

Anterior Communicating Artery

(+ branches from ACA): rostral hypothalamus

Blood Supply to the Limbic System

Middle Cerebral Artery
(+ branches from PCA): uncus

Posterior Cerebral Artery

(+ branches from Pcom): posterior hypothalamus Thalamoperforating artery: anterior nucleus of thalamus Temporal branches: parahippocampal gyrus

Hippocampal Development

Dorsal to the corpus callosum early in brain development Pulled down into the temporal lobe Forms by infolding of cortex, dentate & subiculum fuse

Hippocampal Development
Remnants of hippocampal formation remaining dorsal to corpus callosum
Medial and lateral longitudinal striae Indusium griseum (gray matter)

The Hippocampal Formation

Hippocampal Formation
1. Hippocampus- largest 2. Dentate gyrus: interval between the hippocampus & subiculum 3. Subiculum- in direct continuity with the hippocampus

Schematic diagram showing the components of hippocampal formation

DENTATE GYRUS toothed or beaded surface -- occupies the interval between the hippocampus and the subiculum part of the parahippocampus SUBICULUM PART OF THE PARAHIPPOCAMPUS direct continuation of the hippocampus

The Hippocampus
3 layers Molecular
Axons and dendrites

Pyramidal
Cells are principal neurons Axons are only outflow tract, forming alveus and fimbria (fuse to become fornix)

Stratum oriens/ Polymorphic layer

Intrinsic neurons basket cells; GABAergic Glial elements Axons of pyramidal cells

Dentate Gyrus
3 layers
Molecular- continuous with the hippocampus Granular
Small densely packed granule cells Axon forms the mossy fiber system which links the dentate gyrus and the hippocampus

Polymorphic Pyramidal and basket cells Unlike the hippocampus, the output of the dentate gyrus does not leave the hippocampal formation

Hippocampus: Subiculum
Transitional area 3 layers
Molecular Pyramidal
Axons contribute to output of hippocampal formation

Polymorphic

Parts
Prosubiculum Subiculum proper Presubiculum parasubiculum

The Hippocampus
4 fields
Cornu Ammonis (CA) 1/ Sommers sector/ vulnerable sector
Largest; between hippocampus and subiculum Pyramidal neurons sensitive to anoxia and ischemia TLE trigger

Cornu Ammonis (CA) 2 Cornu Ammonis (CA) 3 Cornu Ammonis (CA) 4/ Bratz sector
Between hippocampus and dentate Medium vulnerability to hypoxia

Parahippocampal Gyrus
Major input to hippocampus Gateway between cerebral cortex and hippocampus
2 routes Perforant Pathway
Main input Travels through subicular area

Alvear Pathway
Via ventricular surface, where alveus is formed

Entorhinal Area (Brodmanns Area 28) of the parahippocampal gyrus

The entorhinal area serves as an important gateway between the cerebral cortex and the hippocamus Information from many cortical areas (limbic, modalitysensory specific, & multimodal association cortices) in the frontal, temporal, parietal, and occipital lobes conveying visual, auditory, and somatosensory information converges on the enterohinal cortex & the posterior parahiccocampal gyrus The enterohinal cortex is the most heavily damaged in Alheizers disease & is the site of early onset of the disease.

Hippocampal Circuit
Limbic association areas Entorhinal cortex

Fimbria

Dentate Granule Cells Alveus

Mossy fibers (granule cell axons) CA3 pyramidal cells

CA1 pyramidal cells

Outflow of Hippocampus
Cells of Subiculum and Pyramidal cells of hippocampus
Axons enter alveus

Glutaminergic Traverse extent of fornix, some enter hippocampal decussation

Anterior to splenium of Corpus Callosum

Outflow of Hippocampus
Fornix divides at level of anterior commissure
Postcommissural
Fibers from subiculum
Medial mammillary nucleus (majority) Anterior nucleus of the dorsal thalamus Ventromedial nucleus of hypothalamus

Precommissural
Fibers from hippocampus
Septal nuclei Medial areas of frontal cortex Preoptic and anterior nuclei of hypothalamus Nucleus accumbens

Schema of Fornix

Hippocampal Afferents & Efferents

 A temporary depository for long term memory. Ultimately, transfers the learned information to the other areas, the cerebral
cortex. The key components of the medial temporal lobe important for memory storage can be
seen in the medial (left) and ventral (right) surface of the cerebral hemisphere

The Hippocampus

The Hippocampus
Functions as a waystation for the long term memory or a facilitation system that is essential for the storage of memory elsewhere in the brain.

The Anatomical Organization of the hippocampal formation

Perforant pathway Parahippocampal cortex Unimodal and polymodal Association areas (frontal, temporal, and parietal lobes) Entorhinal Cortex Perirhinal cortex

Dentate gyrus
Mossy Fiber pathway Schaffer collateral pathway Hippocampus CA1

Hippocampus CA3

Subiculum

The input and output pathways of the hippocampal formation

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SUPERIOR DISSECTION OF THE HIPPOCAMPUS AND AND FORNIX

HIPPOCAMPUS

Efferent Pathway
ENTORHINAL AREA LIMBIC SENSORY SPECIFIC and MULTIMODAL ASSOCIATION CORTICES
POSTCOMISSURAL FORNIX **major component

FORNIX

SUBICULUM

PRECOMISSURAL FORNIX

MAMILLARY BODY
SEPTAL NUCLEI
MEDIAL FRONTAL CORTEX HYPOTHALAMUS

ANTERIOR NUCLEUS OF THALAMUS

VENTRAL STRIATUM

Axons of pyramidal neurons in the subiculum and hippocampus which gather at the ventricular surface of the hippocampus as ALVEUS FIMBRIAE (flattened ribbon of white matter)

CRUS OF THE FORNIX (under the splenium of the corpus callosum)

BODY OF THE FORNIX (attached to the inferior surface of the septum pellucidum) ANTERIOR COLUMNS (flattened ribbon of white matter) MAMILLARY BODIES 75% ANTERIOR NUCLEUS OF THE THALAMUS REST

The Amygdaloid Complex

Amygdala almonds; located at the tip of the temporal lobe beneath the cortex of the uncus and rostral to the hippocampus and inferior horn of the lateral ventricle

Amygdaloid Nuclei
2 Main Groups
Corticomedial-central group :related to olfaction Basolateral group : Connections with cortical structures

The Amygdaloid Complex: Afferents

Basolateral cell group
Dorsal thalamus Prefrontal cortex Cingulate and parahippocampal gyri Temporal lobe Insular cortex Subiculum Supply somatosensory, visual and visceral information

The Amygdaloid Complex: Afferents

Corticomedial-central cell group
Hypothalamus (VM, lateral) Dorsal thalamus (DM, medial) Brainstem nuclei related to visceral functions (parabrachial nuclei, solitary nucleus, periaqueductal gray) Olfactory input

The Amygdaloid Complex: Efferents

Stria terminalis
From corticomedial nuclei Between caudate and dorsal thalamus Associated with bed nucleus of the stria terminalis Connects to hypothalamus, nucleus accumbens, septal nuclei, rostral caudate nucleus, putamen
Ventral amygdalofugal

pathway

Major efferent bundle From basolateral group and central nucleus hypothalamus, septal nuclei substantia innominata Diffuse cholinergic projection to cortex cortical activation Prefrontal/frontal, cingulate, insular & inferior temporal cortices

2 main output pathways from the amygdala:

STRIA TERMINALIS Arises predominantly from the corticomedial group Supplies the septal nuclei Anterior,preoptic, ventromedial nuclei of the hypothalamus
VENTRAL AMYGDALOFUGAL originates from the basolateral and central amygdalar nuclei Projects to thalamus (DM nucleus) Prefrontal, entorhinal area, cingulate Nucleus basalis, septal area, hypothalamus

Schematic diagram of the major efferent connections of the amygdala

The Amygdaloid Complex: Efferents

Stria medullaris thalami
Hippocampus and amygdala

Septal nuclei

Habenular nuclei Habenulointerpeduncular tract Midbrain: Interpeduncular nuclei, ventral tegmental area, periaqueductal gray

Septal Nuclei
Found adjacent to septum pellucidum Afferent pathways
Hippocampus Amygdaloid complex VTA of midbrain Hypothalamus

Septal Nuclei
Efferent pathways
Septohippocampal fibers (via fornix) hypothalamus Habenular nuclei Medial thalamic nuclei (stria medullaris thalami) VTA
Via medial forebrain bundle
Conveys inputs to hypothalamus then septal area Major conduit through which septal nuclei and portions of hypothalamus communicate with brainstem Dopamine containing fibers = pleasure

Nucleus Accumbens
Inputs
Amygdaloid complex (via ventral amygdalofugal pathway and stria terminalis) Hippocampal formation (through precommissural fornix) Bed nucleus of stria terminalis VTA (via medial forebrain bundle)

Outputs
Hypothalamus Brainstem nuclei Globus pallidus

Functions of the Limbic System

Aversion and gratification centers
Hippocampus and amygdala: aversion predominant Nucleus accumbens: gratification predominant Role in addiction

Modulation of
Aggressive behavior Certain forms of learning and memory

Aggression and Rage

Experimental studies in animals
Activation of the part of the hippocampal formation closest to the amygdala facilitates predatory attack behavior Activation of the HF near the septal formation suppresses the aggression

In humans, published reports linking lesions, tumors, and epileptogenic activity of the hippocampal formation with aggressive reactions ( varied; hostility and explosive acts of physical violence)

MEMORY
Explicit
Knowing that
Conscious retrieval of information Supports the learning and retention of facts and the conscious recollection of prior events

MEMORY
Explicit
Knowing that
SHORT TERM MEMORY/ WORKING MEMORY memory of limited amount of information eg 7 digit phone number - decays in seconds if not refreshed continuously LONG TERM /REMOTE MEMORY memory that can be retrieved after delays EPISODIC (UNIQUE) memory of personally experienced facts and events SEMANTIC (GENERIC) memory of culturally and educationally acquired encyclopedic knowledge eg math, historical information etc

MEMORY
Implicit
Knowing how
Supports learning and retention of skills
Memory of experience-affected behaviors that are performed unconsciously

PROCEDURAL MEMORY repeated performance of motor act eg biking, enhances and automates future skill of the same act resistant to forgetting PRIMING short lived enhancement of perceptually based performance ff recent exposure to visually similar object

Anatomic Correlates of Memory

EPISODIC MEMORY
Mesial temporal cortex( hippocampus and parahippocampal gyrus) are critical for this type of memory Unable to acquire new explicit memory (anterograde amnesia) No new information is retained beyond the span of 40-60 sec Other brain structures implicated in episodic memory
Hippocampus-mamillary body-anterior and medial thalamic nuclei via the fornix and mamillothalamic tract Cortico-cortical connections from the anterior and posterior neocortices to the entorhinal cortex Basal forebrain cholinergic nuclei

Long Term Potentiation and Memory

Underlies memory consolidation
AMPA receptor Presynaptic neuron Na+ Postsynaptic neuron [Ca2+]

NMDA receptor

Mg2+

Glutamate

Calcium

Hippocampus and Memory

Consolidation of immediate and short term memory to long term memories Case of H.M.
Temporal lobe epilepsy underwent removal of both medial temporal lobes after the surgery, lost the capacity for consolidating short term memory to long term memory

May be seen also in patients after a hypoxic/anoxic event

Sommer sector involvement
May have epilepsy

Hippocampus and Memory

Alzheimers Disease
Subiculum and EC first affected by plaques and tangless

Hippocampus and Memory

Korsakoff syndrome
Thiamine deficiency Primarily affects mammillary bodies, DM nucleus of the thalamus, Columns of the fornix, hippocampal formation Dementia with confabulation

Wernicke-Korsakoff Syndrome
If with gaze palsies and ataxia

Kluver Bucy Syndrome

Bilateral temporal Lobe injuries involving amygdaloid complex Behavioral Dysfunction
Visual agnosia (+/- tactile and auditory agnosia) Hyperorality Hypermeetamorphosis Hypersexuality Docility Lack of emotional response, blunted affect Memory deficit

Temporal Lobe Seizures

Spread to adjacent TL or both TL Uncus involvement
Uncinate fits Olfactory or gustatory

Complex partial Seizure

Temporal categories of memory

Immediate memory
Recall of a memory trace after few seconds

Short-term memory
Ability to hold information in mind for periods of seconds to minutes once the present moment has passed

Working memory
Ability to hold things in mind long enough to carry out sequential actions

Long-term memory
Retention of information for days, weeks, years or even a lifetime

Clinical subdivisions of memory

Immediate memory Recent memory
Ability to learn new material and to retrieve that material after an interval of minutes, hours, or days

Remote memory
Recollection of facts and events that occurred years previously

The Major Temporal Categories of Human Memory

Immediate memory or sense of the Present (fractions of a second-seconds)

Short term memory (seconds-minutes))

Immediate memory or sense of the Present (fractions of a second-seconds)

Long term memory (days-years)

FORGETTING

Understanding Memory
Removal of the medial temporal lobes left him with a devastating memory deficit; but:
. normal short-term memory . perfectly good long-term memory for events . perfectly good command of language . IQ of bright-normal. His main defect was the ability to transfer new short-term memory into long-term memory

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Understanding Memory
Patients with bilateral medial temporal lobe lesions can perform tasks and other forms of simple reflexive learning, including habituation, sensitization, classical conditioning and operant conditioning.
. tasks that have 2 things in common
tasks tend to be reflexive rather than reflective they do not require conscious awareness or complex cognitive processes.

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Two forms of memory

Implicit memory ( non-declarative memory) a memory that is recalled unconsciously involved in training reflexive motor or perceptual skills rigid and tightly connected to the original stimulus

Explicit memory ( declarative memory) factual knowledge of people, places and things and what these facts mean recalled by a deliberate conscious effort highly flexible and involves the association of bits and pieces of information.

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Various Forms of Memory

Two forms of long term memory

Explicit (declarative)

Implicit (nondeclarative)

Facts

Events

Priming

Associative learning: Procedural (skills and habits) Classical and Operant conditioning

Nonassociative learning: Habituation and sensitization

Emotional response

Skeletal musculature

Medial temporal lobe

Neocortex

Striatum

Amygdala

Cerebellum

Reflex pathway

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Human Memory

(available to consciousness)

Declarative

(generally not available to consciousness)

Procedural

episodes

Daily

and their meanings

Words

and their meanings

Words

Motor Skills

Associations

Priming Cues

Puzzle Solving Skills

Qualitative categories of memory

Declarative memory (explicit)
Storage and retrieval of material that is available to the conscious mind and which therefore be encoded in symbols and expressed by language Memory for facts, events a. Episodic memory - explicit recollection of specific personal events b. Semantic memory general knowledge of facts & concepts not specified in time & space

Semantic Memory
Our experience of knowledge as a seamless orderly and crossreferenced data base is the product of integration of multiple representations in the brain at many distinct anatomical sites. There is no general semantic memory; semantic memory is not stored in a single region.

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Semantic Memory
Type of long-term memory that embraces knowledge of objects, facts and concepts, words and their meaning.
includes naming of objects, definition of spoken words and verbal fluency.

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EPISODIC MEMORY
Episodic (autobiographical) knowledge involves the prefrontal cortex.
the areas of the neocortex for long-term storage of episodic knowledge are the association areas of the frontal lobe. Source amnesia forgetting how information was acquired.

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Explicit knowledge involves four distinct processes:

1. Encoding the process by which newly learned information is attended to and processed when first encountered.
memory storage is stronger when one is well-motivated.

2. Consolidation those processes that alter the newly stored and still labile information so as to make it stable for long-term storage.
involves the expression of genes and synthesis of new proteins leading to structural changes that store memory stably over time.

3. Storage refers to the mechanisms and sites by which memory is retained over time.

4. Retrieval refers to those processes that permit the recall and use of the stored information.
. most effective in the presence of some cues.

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How is explicit memory recalled and brought to consciousness?

The initial encoding and ultimate recall of explicit knowledge are thought to require recruitment of stored information into a

special short-term memory store called

WORKING MEMORY.

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Components of working memory

1. Attention control system ( central executive) located in the prefrontal cortex. - regulates the information flow to two rehearsal systems that are thought to maintain memory for temporary use: the articulatory loop for language and the visuo-spatial sketch pad for visions and action.
Articulatory loop is a storage system with a rapidly decaying memory trace where memory for words and numbers can be maintained by subvocal speech. e.g. remembering a telephone number Visuo-spatial sketch pad represents both the visual properties and spatial location of objects to be remembered.

2.

3.

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IMPLICIT MEMORY
1. 2. Does not depend on conscious processes Does not require a conscious search for memory

3.
4.

Builds up slowly through repetition over many trials

expressed primarily in performance, not in words.
Examples. perceptual and motor skills learning of certain types of procedures and rules

5. Acquired through different forms of learning and involved different regions.

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Hippocampus and Memory

Alzheimers Disease
Amyloid plaques

Subiculum and EC first affected by plaques and tangles

Neurofibrillary tangles (NFT)

Hippocampus and Memory

Korsakoff syndrome
Thiamine deficiency Primarily affects mammillary bodies, DM nucleus of thalamus Columns of fornix, hippocampal formation Dementia with confabulation

Wernicke-Korsakoff syndrome
If with gaze palsies and ataxia

Cingulate Gyrus
Bilateral lesions of anterior part
Akinetic mutism Immobile, mute, unresponsive Not in coma Memory affected

Kluver Bucy Syndrome

Bilateral temporal lobe injuries involving amygdaloid complex Behavioral dysfunction
Visual agnosia (+/- tactile and auditory agnosia) Hyperorality Hypermetamorphosis Hyperphagia Hypersexuality Docility Lack of emotional response, blunted affect Memory deficit

Temporal Lobe Seizures

Spread to adjacent TL or both TL Uncus involvement
Uncinate fits olfactory or gustatory aura

Complex partial seizures