Transcript Brain days-Part V-Limbic

kaan yücel m.d.,ph.d.
Outline
1. Introduction to the Limbic System
2. History of the Limbic System
3. Main Players of the Limbic System
4. Functional Anatomy of the Limbic System
5. Limbic System Dysfunction
5.1. Anatomy of major depressive disorder
5.2. Anatomy of some neuropsychiatric disorders
1.1. What does limbus mean?
1.1. What does limbus mean?
Limbo Lat.
Border
Edge
Circle
Ring
1.2. What is limbic system?
survival
YOUR MISSION IN LIFE?
Two main functions
Emotional processing
Motivation
The Anatomy of Behaviour
Medial Temporal Lobe
 Hippocampus
 Parahippocampal gyrus
 Amygdala
Emotion
Memory
The limbic system works to process our emotions and is
related to motivation and with its connections with the
cognitive parts of the brain helps us to “use our mind”
a.k.a. accomplish mental processes.
The limbic system structures are telencephalic & subcortical structures.
The complex network for the process of emotions and is also related
to memory and learning in addition to hippocampus, amygdala and
parahippocampus includes:
• Cingulate gyrus
• Hypothalamus
• Major areas in the prefrontal cortex
• Striatum
• Some thalamic nuclei
• Orbitofrontal cortex
• Septal area
• Some medial components of the midbrain (e.g. VTA)
• Habenula …
+ white matter tracts
H.M.
Henry Gustav Molaison
(1926 –2008)
Dr. William Beecher
Scoville
EPILEPSY
Treatment
Bilateral removal of
medial temporal lobe
hippocampus, amygdala
& parahippocampal
gyrus
Names
Phone numbers
SHORT- TERM MEMORY
Great Limbic Lobe
Le Grand Lobe Limbique
Pierre Paul Broca
Cingulate gyrus (L. cingulated=belt) &
parahippocampal gyrus
form a ring on the medial surface of the
mammalian brain.
James Papez
Papez Circuit
A list of structures in the brain and a closed
circuit related to emotions
Hippocampal formation (Subiculum) → fornix → mammillary bodies
Mammillary bodies → mammillothalamic tract → anterior thalamic nucleus
Anterior thalamic nucleus → genu of the internal capsule → cingulate gyrus
Cingulate gyrus → cingulum → parahippocampal gyrus
Parahippocampal gyrus → entorhinal cortex → perforant pathway → hippocampus.
Limbic System
added
 Amygdala
 Septum
 Pre-frontal cortex
to the Papez circuit
Paul D. MacLean
Klüver-Bucy Syndrome
bilateral removal of amygdala and hippocampal formation
What happens if we remove the medial temporal lobe of an animal, a monkey?
 Became docile;”good monkeys”.
 A tendency towards oral behaviour such as attempting to ingest inedible objects.
 Hypersexualized behaviour by mounting females of the same and different species.
 A compulsion to attend and react to every visual stimulus
 No fear.
 Change in dietary habits
1848 The patient Phineas Gage
1919 Pneumoencephalography was first introduced.
1936 First “frontal lobotomy” operation was performed on a
Kansas housewife.
1958 Nauta added midbrain structures in the limbic system, such
as habenula
1967 Freeman operated his last frontal lobotomy and after that
this operation was banned.
1974 Ingvar and Franzen first reported frontal lobe hypoperfusion
using Single Photon Emission Computed Tomography (SPECT)
in a series of chronic schizophrenic patients.
1974 Siemens Medical Solutions (then known as Siemens
Medical Engineering) presented the first commercially available
computed tomography system.
1975 Ventral striatum concept defined by Heimer
1977 Limbic striatum concept defined by Nauta and Domesick
1977 First MRI scan in history was accomplished.
1982 "Cortical atrophy in schizophrenia and mania: a
comparative CT study” published in Journal of Clinical Psychiatry
by Nasrallah and his colleagues.
1983 “Ventricular enlargement in child psychiatric patients: a
controlled study with planimetric measurements” published in
American Journal of Psychiatry by Reiss and his colleagues.
1988 The article of Robert Sapolsky from Stanford University
titled as “Glucocorticoid toxicity in the hippocampus: in vitro
demonstration” published in the journal Brain Research.
1992 “Anatomic basis of amygdaloid and hippocampal volume
measurement by magnetic resonance imaging” published in the
journal “Neurology” by Craig Watson and his colleagues.
1994 “Functional magnetic resonance imaging at 1.5 T: activation
pattern in schizophrenic patients receiving neuroleptic
medication.” published in the journal ”Magnetic Resonance
Imaging” by Wenz and his colleagues.
the most famous two guys of
the limbic system
hippocampus & amygdala
3.1. Hippocampal formation/Hippocampus
Temporal horn
of lateral
ventricle
HC
TERMINOLOGY
HIPPOCAMPAL
FORMATION
VS.
HIPPOCAMPUS
1. Hippocampus (proper)
Cornu Ammonis (CA) CA1-CA4
2. Dentate gyrus
3. Subicular complex
Fornix [Arch]
The road/white matter tract from the hippocampus
Precommissural fibers 25%
Septal area
Postcommmissural fibers originate from the subicular complex
Mamillary bodies
Fornix
3.2. Amygdaloid complex/Amygdala
Two main pathways emerging from the amygdala
Stria terminalis
terminate in the septal area, the medial preoptic area of the hypothalamus, and
the bed nucleus of stria terminalis
Ventral amygdalahypothalamic tract (Ventral amygdalofugal pathway)
main projection pathway from the amygdala to the hypothalamus
3.3. Parahippocampal gyrus
3.4. Cingulate gyrus
3.4.1. Anterior cingulate cortex (ACC)
1=BA25 (subcallosal gyrus)
2=BA24sg (SGPFC)
3=BA32 (paracingulate gyrus)
3.4.2. Posterior cingulate cortex (PCC)
Right Cingulate Cortex
Subgenual prefrontal cortex
(SGPFC)
Rostral ACC
Caudal ACC
PCC
Röthlisberger M, Riecher-Rössler A, Aston J,
Fusar-Poli P, Radü EW, Borgwardt S. Cingulate
volume abnormalities in emerging psychosis. Curr
Pharm Des. 2012;18:495-504.
3.5. Limbic structures in the Prefrontal cortex (PFC)
3.5. Limbic structures in the Prefrontal cortex (PFC)
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DLPFC, dorsolateral prefrontal cortex
VLPFC, ventrolateral prefrontal cortex
FP, frontopolar cortex
OFC, orbitofrontal cortex
DMPFC dorsomedial prefrontal cortex
VMPFC, ventromedial prefrontal cortex
3.6. Hypothalamus
Glaser R, Kiecolt-Glaser JK. Stress-induced
immune dysfunction: implications for
healthNat Rev Immunol. 2005 Mar;5(3):243-51.
3.7. Thalamus
Limbic thalamic nuclei
 Anterior thalamic nuclei
 Mediodorsal thalamic nuclei
3. 8. Striatum
4 major nuclei
(1) corpus striatum
Caudate nucleus
Putamen
Ventral striatum –nuc.accumbens
(2) globus pallidus
internal and external segments
(3) substantia nigra
pars compacta
pars reticulata
(4) subthalamic nucleus
3.1.9. Basal forebrain nuclei
1. Septal nuclei (medial and lateral)
2. Nucleus of the diagonal band of Broca
3. Basal nucleus of Meynert (a group of neurons in the substantia
innominata of the basal forebrain)
4. Bed nucleus of stria terminalis (BNST)
5. Medial ventral pallidum
3.10. Structures related to the limbic system in the
brainstem
Ventral tegmental area (VTA) midbrain
dopamine
Periaqueductal gray matter (PAG) midbrain
Locus coeruleus pons
noradrenaline
Dorsal raphe nuclei brainstem
serotonin
Reticular formation brainstem
VENTRAL TEGMENTAL AREA (VTA)
modulates the processing of memory via dopamingergic
fibers that terminate in cortical areas related to the limbic
system
5 dopaminergic pathways
1. Mesostriatal pathway
Origin: Substantia nigra (and also some from VTA)
to the anteromedial and ventral neostriatum
2. Mesolimbic pathway
Origin: VTA (and also some from substantia nigra)
to the nuc.accumbens, amygdala, ACC, entorhinal cortex,
hippocampus
3. Mesocortical pathway
Origin: VTA (and also some from substantia nigra)
to the neocortex (sensory, motor, and association cortices,
such as prefrontal, temporal and insular cortices)
4. Mesodiencephalic pathway
Origin: VTA and Substantia nigra
to the several thalamic and hypothalamic nuclei.
5. Mesorhombencephalic pathway
Origin: VTA- Substantia nigra
to the superior collicilus, reticular formation,PAG, and spinal
cord
Movement, cognition, emotion, and positive
reinforcement are influenced by mesostriatal,
mesocortical, and mesolimbic dopamine systems.
There is nigral degeneration attending Parkinson's
disease and Parkinson’s disease is related to deficit in
the nigrastriatal (mesostriatal) pathway and lower tone
of dopamine as a result.
PERIACQUEDUCTAL GRAY MATTER (PAG)
o Anatomic & functional interface
between forebrain &lower brainstem
o A major role in integrated behavioral responses to
internal (e.g., pain) or external (e.g., threat) stressors
o A critical component of “emotional motor system.”
PERIACQUEDUCTAL GRAY MATTER (PAG)
o Involvement in affective and motivational processes
o Suggested that PAG is a core region involved in human
emotion.
o A role in emotional coping strategies.
o Receives prefrontal and hypothalamic afferents.
3.11.1. Habenula
• A pair of small nuclei located above the thalamus at its posterior end
• Rostral to the posterior commissure
• Habenular commissure runs between them
3.11.1. Habenula
medial habenular nucleus (MHb)
lateral habenular nucleus (LHb)
involved in motivational control
of behavior
wide range of behaviors
including
• Olfaction
• Ingestion
• Mating
• Endocrine and reward
function
• Pain and analgesia
3.11.1. Habenula
Stria medullaris thalami
Connects hypothalamus and other limbic system structures with
habenula
Dorsomedial surface of the thalamus
Limbic system influences the brainstem reticular formation.
Habenulointerpeduncular tract (fasciculus retroflexus)
From habenula to the interpedincular nucleus which is located
between the cerebral peduncles in the midbrain.
Dorsal diencephalic conduction (DDC) system
Limbic forebrain –midbrain /hindbrain connection
The other is Medial Forebrain Bundle
3 components
Habenula
Stria medullaris
Fasciculus retroflexus
• Cognitive processes, in particular relating to spatial learning
and attention
• Circadian rhythms
• Involvement of the LHb in defence responses to stressful
stimuli
Dorsal diencephalic conduction (DDC) system
DDC circuitry is implicated in various psychological conditions
depression
anxiety
schizophrenia
neuropathological responses to addictive drugs
Dorsal diencephalic conduction (DDC) system
 LHb, serves as a convergence point for limbic and basal
ganglia circuits.
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 Given the broad involvement across numerous functions and
behaviors, the region seems to have a basic but vital role as an
evaluator, and acts as a major point of convergence where
external stimuli is received, evaluated, and redirected for
motivation of appropriate behavioral response.
3.11.2. Medial Forebrain Bundle
In addition to the dorsal
diencephalon conduction
system/circuit, there is the medial
forebrain bundle carrying
information from the limbic
forebrain to the midbrain.
 As you might guess, (VTA,
dopamine) we are talking
about the reward and pleasure.
Actually the street drugs like
MFB runs from medial regions of
cocaine stimulate MFB.
the mesencephalon to forebrain
regions, especially the ventral
striatal nuclei (e.g., nucleus
accumbens) and medial frontal
cortices.
3.12. Insula
o A cortical structure with extensive connections to many
areas of the cortex and limbic system.
o Integrates external sensory input with the limbic system
and
o Integral to the awareness of the body’s internal state
(interoception). SELF
o Processing emotional and sensory stimuli
Anterior insula
Extensive and reciprocal
connections to limbic areas, higherorder visual areas, olfactory areas
and to the posterior insula
Processing the emotional component of interoceptive
awareness , the anticipation and evaluation of emotional
stimuli, and self-awareness.
Involved in extending self-awareness to other ‘selves’
through action.
EMPATHY
Posterior insula
Reciprocal connections from
higher-order visual areas, auditory
processing areas, somatosensory
areas and to the anterior insula.
Directly experienced, multimodal sensory processing;
particularly somatosensory processing
1) Topographical-functional organization
2) Functions of the structures within the circuits of the limbic
system
4. 1. Hippocampus and amygdala: Emotions & Memory
Right hippocampus Left hippocampus
Spatial memory
Verbal memory
Anterior hippocampus
rostral hypothalamus and amygdala
HPA-axis control
Stress
Posterior hippocampus
spatial memory
Multiple functions of the hippocampus
Learning and memory
Mood regulation - Affect - Emotional
Behavior
Regulation of HPA axis
Pain
Erectile function
Attention
When you meet someone you know
at the street
Hippocampus......
Context
Amygdala.....
Emotions
Emotional Memory
Fear
Amygdala
4.2. Reward-Punishment System
 Reward is a central component for driving incentive based learning,
appropriate responses to stimuli, and the development of goaldirected behaviors.
T he reward circuit comprises several cortical and subcortical regions
forming a complex network that mediates different aspects of
incentive-based learning, leading to control circuits.
Emotions have been defined as a group of interrelated superior
cerebral functions, resulting from states of reward and punishment.
Behavioural rewarding conditions reinforce certain reactions
in a quest to experience a favourable result, which brings
satisfaction, comfort, or wellbeing.
Main neurotransmitter: Dopamine
Released @ VTA in midbrain
Serotonin modulates dopamine release.
Glutaminergic inputs from PFC, hippocamps and amygdala to VTA and
nucleus accumbens influence the mesocortical dopamine system.
Medial forebain bundle: An important tract between VTA and forebrain
ACC
attention, emotional processing and self monitoring
OFC
behavioral inhibition, signaling of expected outcomes and
reward/punishment sensitivity.
Understanding the roles of key brain areas in reward requires
analysis of network interactions between subareas of the
amygdala, nucleus accumbens, prefrontal cortex, ventral
tegmental area and other structures involved in reward and
motivation.
The projections descending from the PFC to nucleus
accumbens, amygdala and other limbic brain regions have
regulatory control over reward-seeking behavior.
Here we have four main cores in the reward-punishment
systems.
1) VTA in the midbrain
2) Basal ganglia
3) Prefrontal cortex
4) Hippocampus and amygdala
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Reward circuit embedded within
Cortico-basal ganglia circuit
central component for developing and monitoring motivated behaviors
ACC, OFC, ventral striatum, ventral pallidum, midbrain
+ dorsal prefrontal cortex, amygdala, hippocampus, thalamus, and
lateral habenular nucleus, and specific brainstem structures such as
the pedunculopontine nucleus, and the raphe nucleus
key components in regulating the reward circuit
Ventral striatum receives its main cortical input from OFC and ACC,
(1) Fibers from
and a massive dopaminergic input from the midbrain
. different prefrontal
areas converge within
subregions of the striatum.
(2) Through the organization of
striato-nigro-striatal projections,
the VS can influence the dorsal
striatum.
(3) The cortico-thalamic projection
carries information from rewardrelated regions, through
cognitive, and motor controls.
4.3. Memory & Learning: Anatomy
Learning acquisition of new information
Memory keeping it
Long-term memory
•Declerative memory
Medial temporal lobe
•Non-declerative (procedural memory)
Striatum
4.3.3. Anatomy of working memory
 The network of cortical and subcortical areas typically includes
posterior brain regions (eg, visual association areas) that are linked
with prefrontal regions to form a circuit.
 Particularly, the dorsolateral prefrontal cortex (DLPFC) is involved
with working memory.
4.3.4. PFC & memory
Whereas the medial temporal lobe has traditionally been
associated with the encoding, storage and retrieval of long-term
memories, the prefrontal cortex has been linked with cognitive
control processes such as selection, engagement, monitoring
and inhibition.
4.4. Anatomy of
cognition & emotion
Two circuits & Crossing roads
cognition means thinking and emotion means feeling
TWO MAIN CIRCUITS IN THE BRAIN
COGNITIVE CIRCUIT EMOTION CIRCUIT
DORSAL CIRCUIT
VENTRAL CIRCUIT
The cognitive networks inhibit the ventral circuit.
Dorsal (cognitive) circuit
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Hippocampus
Dorsolateral prefrontal cortex (DLPFC)
Dorsal regions of the anterior cingulate cortex (ACC)
Parietal cortex
Posterior insular region
Modulates selective attention, planning and effortful regulation of
affective state.
Ventral (limbic) circuit structures:
o Amygdala
o Insula (Particularly, anterior insula)
o Ventral striatum
o Ventral regions of the anterior cingulate cortex (ACC)
o Orbitofrontal cortex (OFC) and medial PFC
We can also add “hippocampus” in the limbic circuit.
It is possible that the altered emotional regulation
or cognition found in all of these syndromes
involves aberrant function of these circuits, but
perhaps with different patterns on a molecular
level.
Phillips et al. 2003
MPFC (medial prefrontal cortex) and related limbic and
striato-pallido-thalamic structures organize emotional
expression.
4.4. 1. Cerebellum & vermis
The cerebellum is a great modulator of neurologic
function, and that whatever it does to motor control, it
also does the same thing to other kinds of behaviors.
4.4. 1. Cerebellum & vermis
For many years, functions related only to movement, gait,
posture, and balance were attributed to the cerebellum.
However, some studies have suggested a possible
involvement of the cerebellum in cognition, emotion
processing and behavior.
4.4. 1. Cerebellum & vermis
4.4. 1. Cerebellum & vermis
Vermis or posterior vermis
Limbic cerebellum
Anterior
4.4.1. Loops through the basal ganglia
Functional anatomy of basal ganglia
5 LOOPS THROUGH THE BASAL GANGLIA
1. LIMBIC CIRCUIT
Anterior part of ACC- Ventral striatum (nuc.accumbens)
behavior control and adaptation of behaviours after making a
mistake. The damage of this circuit results in emotional
disorders especially deep apathy and lack of spontaneity.
Lowered mood is accompanied by weakening of affect and
motor adynamy. It was shown that the anterior cingulate loop
is responsible for correcting behavior following a mistake.
4.4.1. Loops through the basal ganglia
Functional anatomy of basal ganglia
5 LOOPS THROUGH THE BASAL GANGLIA
2. PREFRONTAL (ASSOCIATIVE LOOP)
Between DLPFC- head of nuc.caudatus
choice of aims, planning, programming of the sequence of mental
actions and behaviours, switching between sentences (the ability to
change attitude flexibly), verbal and spatial working memory,
selfcontrol and metacognition (self-consciousness)
4.4.1. Loops through the basal ganglia
Functional anatomy of basal ganglia
3. LATERAL OFC LOOP
Between lateral OFC aand head of nuc.caudatus
initiating social behaviours motivated by an award and in
inhibiting behaviours, which can trigger punishment.
Incorrect functioning of this circuit may result in
disinhibition of behaviours, personality changes, lack of
control and emotional liability, as well as irritability and
gaiety. The damage of this loop can cause perseverations,
which make it difficult to process information from external
environment and adaptation of behaviours to a particular
situation.
Orbito-frontal circuit
socially adjusted behaviour and hampering not socially accepted one
important for the estimation of the risk of the behavior chosen
4.5. White Matter Tracts of the Limbic System
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Alveus, fimbria and fornix
Perforant pathway
Cingulum
Septohippocampal tract
Ventral amygdalohypothalamic tract
Mammillothalamic tract (mammillary fasciculus)
Mammillointerpeduncular tract
Mammillotegmental tract
Stria terminalis
Stria medullaris (thalami)
Anterior commissure
Diagonal band of Broca
Habenulointerpeduncular tract
4.5. Default Network

Must have a total of 5 symptoms for at least 2 weeks.
One of the symptoms must be depressed mood or loss
of interest.
1. Depressed mood.
2. Markedly diminished interest or pleasure in all or
almost all activities.
3. Significant (>5% body weight) weight loss or gain, or
increase or decrease in appetite.
4. Insomnia or hypersomnia.
5. Psychomotor agitation or retardation.
6. Fatigue or loss of energy.
7. Feelings of worthlessness or inappropriate guilt.
8. Diminished concentration or indecisiveness.
9. Recurrent thoughts of death or suicide.
Response to stress
Response to stress is about “fight” or “flight”.
In any case, you need some energy to run or have the battle
(or go back to sleep- you wake up early and study- or study all
night).
Response to stress
The sympathetic-adrenomedullary (SAM) system
implicated in releasing adrenaline which facilitates the
flight/fight response and the HPA axis are regulated by
“limbic brain circuits that involve the amygdala,
hippocampus and orbital/medial prefrontal cortex.
Depressed brain
brain networks that normally regulate the evaluative,
expressive and experiential aspects of emotional behavior
in the pathophysiology of mood disorder
Limbic-cortical-striatal-pallidal-thalamic
circuits
(LCSPT)
formed by connections between
o Orbital and medial prefrontal cortex (OMPFC)
o Amygdala
o Hippocampus
o Striatum
o Thalamic nuclei
o Ventral pallidum
Depressed brain
o The most prominent volumetric abnormality reported to date
has been a reduction in gray matter in the left anterior cingulate
cortex (ACC) ventral to the corpus callosum genu (i.e.,
‘‘subgenual’’).
o Reductions in the size of genu and splenium of corpus callosum
also have been observed in patients with MDD.
Depressed brain
Dysregulation
Activity
Ventral prefrontal areas; ventrolateral prefrontal
cortex (vlPFC), in subgenual anterior cingulate
cortex (sgACC) and in the amygdala
Activity
DLPFC, dorsomedial PFC
History of abuse in childhood
a significant factor in depression and suicidal diathesis
Hippocampal volume loss
Decrease in ACC volume
with increase in amygdala
volume in suicidal
patients with MDD
5.2.1. Anorexia Nervosa (AN)
 Common in adolescent girls
 Affects 0.3% to 0.7% of the
population
 Symptoms on eating
behavior and body image
distortions
5.2.1. Anorexia Nervosa (AN)
Disturbances of limbic and cognitive neural circuits -perhaps
related to altered serotonin and dopamine metabolismImpaired balance between the ventral (limbic) circuit and
dorsal (cognitive) circuit
5.2.1. Anorexia Nervosa (AN)
 ACC; processing the conflict between available behaviors and
outcomes e.g., “shall I eat this cake and satisfy my hunger now or
shall I not eat this cake and stay thin?”
 OFC; adjusts reward valuation based on the current body state of
the individual.
 DPLFC switches between competing behavioral programs based
on the error signal it receives from the ACC.
 Insula; interoceptive dysfunction
 Striatum; altered reward modulation
5.2.2. Obsessive Compulsive Disorder (OCD)
Characterized by intrusive anxiety-provoking
thoughts (obsessions) and subsequent repetitive
time-consuming ritualistic behaviours
(compulsions)
Imbalance between the dorsal and ventral frontal–
striatal circuits in the symptoms and cognitive
deficits.
Ventral frontal–striatal impairment contributes to the inability to
inhibit cognitions and behaviours.
Dorsal frontal–striatal failure contributes to impaired executive
performance and enhanced error monitoring processes,
corresponding to the patients' frequent feeling that ‘something is
wrong’.
5.2.2. Obsessive Compulsive Disorder (OCD)
 Cortico-basal ganglia-thalamo-cortical loops; deficits observed in the
orbitofrontal cortex (OFC), PFC, anterior cingulate cortex (ACC),
thalamus, and caudate nucleus
 Orbitofrontal-striatal-thalamic circuits; associated with implicit
processing deficit and intrusive symptoms.
 Other structures with abnormalities in OCD: insula, amygdala and
the white matter tract; cingulum
5.2.3. Posttraumatic Stress Disorder (PTSD)
Developed by some individuals after exposure to emotionally severe
traumatic events such as childhood abuse, war traumas, and natural
accidents, among others.
 A circuit of brain regions, including the hippocampus, prefrontal
cortex (including anterior cingulate), and amygdala, in the
symptoms of PTSD.
 During emotion regulation, an increase in vmPFC activity is
associated with a decrease in amygdala activity as well as a
decrease in the experience of negative affect. The relation between
vmPFC and amygdala in emotion regulation is suggested to be
abnormal in patients with PTSD as well as in MDD.
 Insula is also found abnormal in PSTD.
5.2.4. Social Phobia
Fear of social or performance situations when the person
feels they are under scrutiny by others and fears that
they will do something embarrassing or humiliating.
Right DLPFC & left parietal cortex
Greater activation in these areas may be related to planning affective
responses and to awareness of body position.
A neural circuit involving the striatum, thalamus, amygdala and cortical
structures may provide a framework for integrating much of the
current knowledge on the neurobiology of social phobia.
5.2.5. Autism spectrum disorders (ASD)
Characterized by deficits in social interaction,
communication, and stereotyped or repetitive behaviors
Increased total brain volume
Most popular structures investigated in ASD:
cerebellum (vermis) & amygdala
Also deficits in
 Hippocampus
 Striatum.
 Fusiform face area (FFA)
 Cingulate cortex
 Thalamus
 Insula
 Corpus callosum
 Brainstem
 Default network
5.2.6. Pathological Gambling (PG)
Inappropriate, persistent, and maladaptive gaming behavior
 VTA- OFC
 Dysfunction in the cortico-striatal networks from the
prefrontal cortex to midbrain
 Dysfunction in the DLPFC and ventral striatal networks