NEUROPSYCHIATRIC IMPLICATIONS OF LIMBIC SYSTEM

Jayita Biswas
PGT,Department of Psychiatry
RGKMCH
OVERVIEW

● Anatomy of Limbic system

● Physiology of Limbic system
● Neuropsychiatric implications of the limbic
system
● Neuromodulation of the limbic system
● SUMMARY
 ANATOMY OF THE LIMBIC SYSTEM
There is no universal agreement on the total list of
structures.Nevertheless the commonly listed
structures are
1)LIMBIC CORTEX
a)Cingulate gyrus
b)Parahippocampal gyrus
2)HIPPOCAMPAL FORMATION
a)Dentate gyrus
b)Hippocampus
c)Subicular complex
3)AMYGDALA
4)SEPTAL AREA
5)HYPOTHALAMUS AND RELATED CORTICAL
AND THALAMIC AREA.
 Cingulate gyrus
● C shaped stretch of cortex
Divided into
subcallosal,anterior,middle,posterior
and retroplenial cingulate cortex
● Parahippocampal gyrus is posterio
Inferior continuation of cingulate
gyrus
● Include Entorhinal cortex that carry
information to hippocampal
formation
● Function-spatial memory
● Parahippocampal asymmetry seen
in schizophrenia
 HIPPOCAMPAL FORMATION

● Located in the floor of

temporal horn of lateral
ventricle
● Extends from amygdala to
splenium of corpus
callosum
● Related to Entorhinal
cortex via perforant
pathway
HIPPOCAMPUS

● Dentate gyrus has 3 layers-outer

acellular molecular layer,middle
granule layer &inner polymorphic
● Based on cytoarchitecture and
connectivity-CA1 ,CA2,CA3
● Subicular complex has 3
components-
presubiculum,parasubiculum
&subiculum and serve as transition
between hippocampus and
parahippocampal gyrus
AMYGDALA

● Basolateral complex,Central amygdaloid group and

olfactory group
● Basolateral complex is largest and directly and reciprocally
connected with temporal,insular,prefrontal cortices
● Central has 2 subdivision(central part and lateral portion of
bed nucleus of stria terminalis)and is reciprocally
connected with brain stem and lateral hypothalamus
HYPOTHALAMUS
● Divided into 3 zones
● Supraoptic region
● Tuberal region
● Mammillary region
● 3 zones are divided into
Medial and lateral area
By fornix
Regulate emotion,autonomic,
Endocrine and somatic function
 NUCLEUS ACCUMBENS

● Situated rostral to preoptic area of hypothalamus

● Nucleus accumbens &Olfactory tubercle form ventral
striatum,important component of basal ganglia
● Dopaminergic neuron of mesolimbic pathway project
GABAergic medium spiny neuron of nucleus accumbens
and olfactory tubercle.
● Significant role in cognitive processing of
motivation,reward,aversion and reinforcement learning
FUNCTIONAL CIRCUITS AND NEUROPHYSIOLOGY OF LIMBIC
SYSTEM
PAPEZ CIRCUIT AND MODIFIED PAPEZ CIRCUIT
● “The hypothalamus, the anterior thalamic nucleus, the cingulate gyrus,
the hippocampus and their interconnections, constitute a harmonious
mechanism which may elaborate the functions of central emotion as well
as participate in the emotional expression.” James Papez(1937)
● Maclean modified the circuit to include not only hippocampus but
also amygdala and septum involved in the functions of memory as
well as emotions
● Role in episodic memory and damage is seen in
Alzheimer’s,Parkinson’s and Korsakoff psychosis
FUNCTIONS OF LIMBIC SYSTEM
SLEEP CYCLE
APPETITE AND EATING BEHAVIOUR

● Amygdala-emotional modulation of food intake

● Lateral nucleus of hypothalamus-centre for control of
feeding
● Ventromedial nucleus-satiety centre
FIGHT OR FLIGHT
MEMORY ● Hippocampus
learning and
formation of new
memories
● Amygdala-
emotional learning
and memory
● Hippocampus
consolidates the
new memories
MOTIVATION /REWARD CIRCUIT
SEXUAL BEHAVIOUR
LIMBIC SYSTEM- CLINICAL IMPLICATION
EPILEPSY
● Caused by HIPPOCAMPAL
sclerosis with additional
involvement of the amygdala
and parahippocampal
gyrus(MESIAL TEMPORAL
SCLEROSIS)
● MTS is not limited to the
medial temporal lobe but
instead represent a limbic
system disorder
LIMBIC ENCEPHALITIS

● Inflammatory process involving hippocampus,amygdala and

other region of limbic system
● Cardinal sign-severe impairment of short term memory
● Change in behaviour,mood
● Paraneoplastic LE-severe form most commonly associated
with small cell lung carcinoma
 DEMENTIA

● Marked atrophy in Dentate gyrus and

hippocampus
● In Alzheimer’s disease,senile plaques
and neurofibrillary tangles are
dispersed throughout the cerebral
cortex and basal ganglia but
hippocampus and amygdala are often
severely involved
● Entorhinal cortex and performant
pathway-first area affected in
Alzheimer’s disease
SCHIZOPHRENIA
● Reduced Limbic volume especially HIPPOCAMPAL formation
● Involvement of Papez circuit-decreased size of hippocampus and
reduced number of GABAergic cells in the cingulate and anterior
thalamus with resultant glutamatergic excitotoxicity
● Basolateral circuit also mediates the social cognition deficits in
schizophrenia
● Mesolimbic pathway is also responsible for the positive symptoms
of schizophrenia
SCHIZOPHRENIA BRAIN HEALTHY BRAIN
AFFECTIVE DISORDERS

● Decreased prefrontal and anterior cingulate activity

● Variation in volume of frontal lobe,basal
ganglia,amygdala,hippocampus
● Dysfunction of anterior limbic network is suggested in
bipolar disorder
● Subgenual anterior cingulate gyrus-implicated in major
depression
OCD

● Low level of glutamate activity in anterior cingulate cortex in

contrast to many other brain regions that are thought to have
excessive glutamate activity in OCD
● It has been postulated that orbitofrontal thalamic hyperactivity
give rise to obsessive thoughts
● PET show increased glucose metabolism in orbital gyri
● Deep brain stimulation of sub thalamic nucleus
ANXIETY DISORDER
● Failure of the anterior cingulate and
hippocampus to modulate the activity of the
amygdala (Top down regulation)
● A fear circuit,involving amygdala, prefrontal and
anterior cingulate has been described(Bottom
up regulation)
KLUVER BUCY SYNDROME
● Bilateral destruction of the amygdaloid body and inferior
temporal cortex
● Visual
agnosia,placidity,hyperphagia,hypermetamorphosis,
● Hyperorality,hypersexuality
● Caused by many conditions including cerebral
trauma,infections including herpes and other encephalitic
syndromes,Alzheimer’s and other dementia,Niemann
Pick disease and cerebrovascular disease
 AUTISM
● Basolateral circuit integral for social cognition
disrupted in autism spectrum disorder
● Amygdala and Hippocampus enlarged in
autism
● Altered neurons and connection in temporal
lobe
● Smaller number of purkinje cells in cerebellum
● Alteration in structure and activity of cerebral
cortex
ADHD

● Behavioural disinhibition-disturbed connections between

amygdala and orbitofrontal cortex
● Enlarged hippocampus
KORSAKOFF’S PSYCHOSIS

● Mammillary
bodies,dorsomedial
nucleus of thalamus
and hypothalamus
affected
● Recent memory
characteristically
disturbed than remote
memory
● Immediate recall
usually reserved
LIMBIC NEUROMODULATION
ADDICTION

● Nucleus accumbens
and cingulate gyrus
and the other nuclei
in the Limbic reward
network may be
potential target for
Neuromodulation for
drug addiction
Post traumatic stress disorder (PTSD)
● AMYGD
ALA
targeted
for DBS
MEMORY
● Anterior nucleus of thalamus -Target of DBS in the treatment
of intractable epilepsy

● The Entorhinal area,HIPPOCAMPUS and fornix are potential

DBS targets for dementia
 SUMMARY
● Limbic system plays an integral role in understanding human
behaviour and its aberration
● 5Fs-feeding( satiety and hunger) ,Forgetting (memory),Fight
or Flight (emotional response)Family(sexual reproduction)
● Highly processed sensory and cognitive information
integrated with emotions and autonomic and endocrine
system is controlled
● Understanding of the neuronal circuitry may play a vital role in
the treatment of various associated neuropsychiatric disorders