Transcript Synaptic receptors, neurotransmitters and brain modulators

Function of limbic system and
the cerebral cortex
Prof. Romana Šlamberová, MD PhD
Department of Normal, Pathological and
Clinical Physiology
Limbic system
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from Latin limbus, means
"border" or "belt„
Main parts:
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Hippocampus
Amygdala
anterior thalamic nuclei
limbic cortex
Function:
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Emotion
Behavior
Long-term memory
Olfaction
History
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in 1878 - French physician Paul Broca first
called this part of the brain „le grand lobe
limbique“
in 1937 - American physician James Papez
described his anatomical model of emotion, the
Papez circuit.
in 1952 - American physician Paul D. MacLean
expanded these ideas to include additional
structures in a more dispersed "limbic system"
Limbic system - basic parts
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Amygdala - emotions (reward, fear, social functions)
Hippocampus – cognition (long-term memories, map
navigation, spatial memory)
Parahippocampal gyrus – cognition (spatial memory)
Cingulate gyrus - autonomic functions (heart rate, blood
pressure) and cognition (attentional processing)
Fornix - carries signals from the hippocampus to the
mammillary bodies and septal nuclei
Hypothalamus - autonomic functions (hormones, blood
pressure, heart rate, hunger, thirst, sexual arousal,
sleep/wake cycle)
Thalamus - The "relay station" to the cerebral cortex
Limbic system – additional
parts
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Mammillary body - cognition (formation of
memory)
Pituitary gland – regulating homeostasis
(hormones)
Dentate gyrus – cognition (new memories) and
emotions (happiness)
Entorhinal cortex and piriform cortex - sensation
(smell input in the olfactory system)
Olfactory bulb - sensation (olfactory sensory input)
Nucleus accumbens - reward, pleasure, and
addiction
Orbitofrontal cortex - decision making
Papez circuit
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the major pathways
of the limbic system involved in the
cortical control of
emotion
plays a role in
storing memory
Papez discovered the
circuit after injecting
rabies virus into a
cat's hippocampus
and monitoring its
progression through
the brain.
Amygdala (1)
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from Greek = Almond
primary role in the processing
and memory of emotional
reactions
related to many psychological
disorders (social phobia,
autism, bipolar disorder)
Nuclei:
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basolateral complex (lateral,
basal, accessory basal nuclei)
centromedial nucleus
cortical nucleus
Amygdala (2)
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Connections to:
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hypothalamus - important activation of the sympathetic
nervous system
thalamic reticular nucleus - increased reflexes
nuclei of the trigeminal nerve and facial nerve - facial
expressions of fear
ventral tegmental area, locus coeruleus, and laterodorsal
tegmental nucleus - activation of DA, NE and E
Inputs from:
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from the olfactory bulb and olfactory cortex to the cortical
nucleus - sense of smell and pheromone-processing.
from the sensory systems to the lateral amygdalae
Emotions
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Emotions can be differentiated:
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Feelings are best understood as a subjective
representation of emotions
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Moods are diffuse affective states that generally
last for much longer durations than feelings and
are also usually less intense than feelings
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Affect is an encompassing term, used to describe
the topics of emotion, feelings, and moods
together
A distinction can be made between emotional episodes
and emotional dispositions.
Emotions can be measured by multidimensional scaling.
The emotional experiences are divided into two
dimensions known as:
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valences (how negative or positive the experience
was)
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arousal (extent of reaction to stimuli)
Bipolar disorder
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Bipolar affective disorder, manic-depressive disorder, or
manic depression) is a mental illness typically classified as a
mood disorder
Characterized by episodes of an elevated or agitated mood
known as mania, usually alternating with episodes of depression
About 3% of people, a proportion consistent for both men and
women and across racial and ethnic groups
Causes - both genetic and environmental risk factors are
believed to play a role
Treatment:
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Psychotherapy
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Medication
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lithium, effective in treating acute manic episodes,
preventing relapses, reduces the risk of suicide
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anticonvulsants (carbamazepin, sodium valproate,
lamotrigine)
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Antipsychotic medications – only for short-term
treatment of bipolar manic episodes
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Benzodiazepines may be used in addition to other
medications until mood stabilizing become effective
Emotions and memory
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Emotion can have a powerful impact
on memory.
The most vivid autobiographical
memories tend to be of emotional
events.
The activity of emotionally enhanced
memory retention can be linked to
human evolution.
The process of learning became
genetically embedded in humans and all
animal species in what is known as flight
or fight instinct.
Emotionally arousing stimuli can lead to
retrograde amnesia for preceding events
and anterograde amnesia for
subsequent events.
Hippocampus
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From Greek - hippos =
horse, kampos = sea
monster)
part of the telencephalon
(forebrain)
located inside the medial
temporal lobe of the cerebral
cortex
The strongest connections of
the hippocampus are with the
entorhinal cortex (EC).
History
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In 1564 - the anatomist Giulio Cesare Aranzi - first used the
term hippocampus (connected with the sense of smell)
Around 1900 - the Russian neurophysiologist Vladimir
Bekhterev - the role of the hippocampus in memory
the 1950s - HM (patient) (Henry Gustav Molaison (1926–
2008) - memory-impaired patient
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In 1953 – William Scoville (surgeon at Hartford Hospital) removed twothirds of his hippocampus, parahippocampal gyrus, and amygdala
(for diagnosed focal epilepsy in medial temporal lobes)
After the surgery - severe anterograde amnesia (he could not commit
new events to long-term memory).
His ability to form long-term procedural memories was intact - he could
learn new motor skills, despite not being able to remember learning
them.
Function
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storing and processing spatial information
(London's taxi drivers – larger hippocampus)
important role in the formation of new memories
about experienced events (episodic or
autobiographical memory)
Damage to the hippocampus
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profound difficulties in forming new memories (anterograde
amnesia)
also affects access to memories prior to the damage
(retrograde amnesia)
Damage to the hippocampus does not affect the
ability to learn new skills (playing a musical
instrument)
LTP – Long-term potentiation
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long-lasting improvement in
communication between two
neurons that results from
stimulating them simultaneously
one of the major cellular
mechanisms that underlies
learning and memory
LTP was first observed by Terje
Lømo in 1966 in the Oslo, Norway
who studied the hippocampus of
rabits for short-term memory.
 electrical stimulation to a fiber
of the perforant pathway
caused an excitatory
postsynaptic potential (EPSP)
in a cell of the dentate gyrus
Basic hippocampal circuit
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The alveus - most superficial
layer - contains axons from
pyramidal neurons
Stratum oriens - cell bodies
of inhibitory basket cells
Stratum pyramidale - cell
bodies of the pyramidal
neurons
Stratum lucidum - mossy
fibers from DG granule cells
Stratum lacunosum Schaffer collateral fibers and
perforant path
Stratum moleculare –
synaps between perforant
path fibers and dendrites of
pyramidal cells
The hippocampal sulcus or
fissure - cell-free region that
separates CA1 from DG
Parahippocampal gyrus
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a grey matter
cortical region of
the brain that
surrounds the
hippocampus
important role in
memory encoding
and retrieval
The anterior part
of the gyrus
includes the
perirhinal and
entorhinal cortices.
Memory disorders
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Amnesia - loss of memory
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Hyperthymesia - condition of possessing an extremely detailed autobiographical
memory
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reason is not known
Alzheimer's disease - the most common form of dementia
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caused by brain damage, disease, or psychological trauma
two main types of amnesia: retrograde amnesia and anterograde amnesia
Cause – genetic in 1-5%
Cholinergic hypothesis - reduced synthesis of the neurotransmitter acetylcholine
Amyloid hypothesis - extracellular beta-amyloid (Aβ) deposits
Tau hypothesis - tau protein abnormalities initiate the disease cascade
Korsakoff's syndrome - a neurological disorder caused by a lack of thiamine
(vitamin B1) in the brain
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Cause - chronic alcohol abuse and/or severe malnutrition
Symptoms – retrograde and anterograde amnesia, confabulation, apathy
The Hypothalamus (1)
A division of the diencephalon
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It sub serves 3 major systems:
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AUTONOMIC NERVOUS SYSTEM
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ENDOCRINE SYSTEM
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LIMBIC SYSTEM
11 important nuclei:
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MEDIAL PREOPTIC NUCLEUS
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Regulates the release of gonadotropic hormones from the Adenohypophysis
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SUPRACHIASMIC NUCLEUS
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Receives input directly form the retina.
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Plays a role in regulating circadian rhythm
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ANTERIOR NUCLEUS
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Important in temperature regulation
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Stimulates PNS
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It’s destruction results in hyperthermia
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PARAVENTRICULAR NUCLEUS
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Synthesizes ADH- and thus regulates water balance
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Releases oxytocin
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Projects directly to autonomic nuclei of brain stem and all spinal cord levels
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The Hypothalamus (2)
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SUPRAOPTIC NUCLEUS
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DORSOMEDIAL NUCLEUS
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Contains neurons that produce factors that stimulate or inhibit action of hypothalamus
Contains neurons that produce Dopamine
MAMILLARY NUCLEUS
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Induces eating
ARCUATE (INFUNDIBULAR) NUCLEUS
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Is the satiety center- this means that once it is stimulates, it inhibits the urge to eat
LATERAL HYPOTHALAMIC NUCLEUS
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When stimulated in animals, causes savage behavior!
VENTROMEDIAL NUCLEUS
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Synthesizes ADH- and thus regulates water balance
Releases oxytocin
Lesions (in Wernicke’s Encephalopathy patients) are associated with thiamine deficiency
and alcoholicism
POSTERIOR HYPOTHALAMIC NUCLEUS
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Plays a role in thermoregulation
Lesion results in poikilothermia
Hypothalamic nuclei
Function of the hypothalamus
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AUTONOMIC
 Stimulation of the ANTERIOR HYPOTHALAMUS: excitatory effect on
parasympathetic system
 Stimulation of POSTERIOR HYPOTHALAMUS: excitatory effect of
sympathetic system
THERMOREGULATION
 Stimulation of ANTERIOR HYPOTHALAMUS: regulates and maintains
temperature
 Stimulation of POSTERIOR HYPOTHAMUS: produces and conserves
heat
WATER BALANCE
 Paraventricular (Supraoptic) nuclei synthesize ADH and control kidney
water excretion
FOOD INTAKE
 Stimulation of VENTROMEDIAL NUCLEUS inhibits the urge to eat
 Stimulation of LATERAL HYPOTHALAMIC NUCLEUS induces the
urge to eat
Cerebral cortex
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In humans - 2–4 mm (0.08–0.16 inches) thick
neocortex (isocortex) - phylogenetically most recent part of the cerebral
cortex (older part = hippocampus – archicortex)
Layers from outside (pial surface) to inside (white matter):
 molecular layer I - apical dendrites, horizontally-oriented axons, glial
cells
 external granular layer II - small pyramidal neurons and stellate
neurons
 external pyramidal layer III - small and medium-size pyramidal
neurons, non-pyramidal neurons with vertically-oriented intracortical
axons (main cortico-cortico efferents)
 internal granular layer IV - stellate and pyramidal neurons (main
thalamo-cortical afferents)
 internal pyramidal layer V - large pyramidal neurons (Betz cells
in the primary motor cortex)
 multiform layer VI - small spindle-like pyramidal and multiform
neurons (efferents to thalamus)
Sensory areas
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Primary sensory areas - receive sensory inputs
from the thalamus
In general, the two hemispheres receive information
from the contralateral side of the body.
Topographic maps - the organization of sensory maps
in the cortex correspond with the sensing organs
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the primary visual cortex - retinotopic map
the primary auditory cortex - tonotopic map
the primary somatosensory cortex - somatotopic map
(homunculus)
Visual cortex
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Located and around the calcarine fissure in
the occipital lobe.
Anatomically - Brodmann area BA 17
6 layers - Layer 4, which receives most visual
input from the lateral geniculate nucleus
Primary visual cortex – V1 (visual
orientations, spatial frequencies and colors)
Extrastriate visual cortical areas – V2,
V3, V4, V5 – BA 18, 19 (attention, working
memory, and reward expectation)
Function:
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The dorsal stream ("Where Pathway"
or “How Pathway“) - motion, object
locations, control of the eyes and arms
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The ventral stream (“What Pathway“) - The dorsal stream (green) and ventral
form recognition and object
stream (purple) are shown. They
representation, storage of long-term
originate from primary visual cortex.
memory.
Auditory cortex
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Anatomically – BA 41, 42
Inputs from the medial
geniculate nucleus of the
thalamus.
Function:
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Primary auditory cortex - in
the superior temporal lobe sensation of basic characteristics
of sound (pitch and rhythm)
Additional areas - in the
frontal and parietal lobes processing of acoustic signals
(distinguished between speech,
music, noise)
Association auditory
cortex
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Broca's area (pars opercularis and pars triangularis
of the inferior frontal gyrus) BA 44, 45
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Wernicke's area (where the temporal lobe meets
the parietal lobe) posterior part of BA 22
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responsible for speech production
Broca’s (motor) aphasia – understands, but problems
with fluent speaking
responsible for understanding
Wernicke’s (receptive, sensory) aphasia – can speak,
but does not understand
In the left hemisphere (in most people specialized for
language skills)
Somatosensory cortex
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The postcentral gyrus - the sense of touch
Primary somatosensory cortex - BA 3, 1 and 2
Secondary somatosensory cortex – BA 5, 7
Lesions:
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Agraphesthesia - disorder of directional cutaneous kinesthesia (writing
on skin)
Astereognosia (tactile agnosia) - impaired ability to recognize or identify
objects by touch alone
Loss of vibration, proprioception, fine touch
Hemineglect - ignoring the contralesional side of their body (no shaving,
no make-up)
It could also reduce nociception, thermoception and crude touch (but
these are more in insular cortex and cingulate gyrus).
Somatosensory homunculus
Motor areas
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The primary motor cortex
(M1) - the posterior portion of
the frontal lobe.
Precentral gyrus = BA 4
M1 contains large neurons
known as Betz cells (pyramidal
cells in layer V) - long axons to
alpha motoneurons in the
spinal cord.
Involved in:
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planning actions (basal ganglia)
refining movements
(cerebellum)
Motor homunculus
Motor tracts
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The corticospinal tract
originates from pyramidal cells
in layer V of the cerebral
cortex.
About half of its fibres arise
from the primary motor cortex.
Other contributions come from:
 supplementary motor area
 premotor cortex
 somatosensory cortex
 parietal lobe
 cingulate gyrus
Supplementary motor area
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BA 6 - on the medial face of the hemisphere,
just in front of primary motor cortex
(premotor cortex)
Function:
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planning of motor actions
bimanual control
In contrast to M1 - actions that are under internal
control (performance of a sequence of
movements from memory)
involved in retrieving the sequence of movements
Frontal lobe
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Reaches full maturity around age 25
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increased myelin in the frontal lobe white matter of young adults
compared to that of teens
A typical onset of schizophrenia in early adult years correlates with
poorly myelinated (inefficient) connections between cells in the forebrain.
The frontal lobe contains most of the dopamine-sensitive
neurons in the cerebral cortex.
Functions (involved in higher mental functions):
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to recognize future consequences resulting from current actions
to choose between good and bad actions
override and suppress unacceptable social responses
determine similarities and differences between things or events
Psychosurgery
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In the early 20th century - Portuguese
neurologist Egas Moniz developed a medical
treatment for mental illness
Damage of the pathways connecting the
frontal lobe and the limbic system
Frontal lobotomy successfully reduced
distress, but suppressed emotions, volition
and personality.
Damage of the frontal lobes
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Impaired mental flexibility and spontaneity, but
IQ is not reduced.
Talking may increase or decrease dramatically.
Increase of risk taking behavior.
Socialization can diminish or increase.
Orbital frontal lobe damage can result in perverse
sexual habits.
Diminished creativity and problem solving skills.
Frequent distractions.
Prefrontal cortex
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the anterior part of the frontal lobes
defined by the presence of an internal granular layer IV (in
contrast to the agranular premotor cortex)
Parts:
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orbitofrontal (OFC) and ventromedial areas (vm-PFC)
dorsolateral prefrontal cortex (dl-PFC)
anterior and ventral cingulate cortex
ventrolateral cortex (vl-PFC)
medial prefrontal cortex (m-PFC)
anterior prefrontal cortex (a-PFC).
Function:
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planning complex cognitive behaviors
personality expression
decision making
moderating correct social behavior
Prefrontal cortex