Download Prefrontal Cortex

Prefrontal Cortex
Julianna Antonucci, Sydney Delfico,
Lorraine Garland, Danielle Renzi,
Ro-anna Thomas
Prefrontal Cortex
• https://www.youtube.com/watch?v=u76jBk59
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Structure
• anterior-most part of frontal lobe
• larger in humans
• Inputs from the amygdala and olfactory cortex
Medial dorsal nucleus PFC
• known as projection zone from medial dorsal
nucleus of the thalamus (or dorsomedial nucleus
of thalamus)
• interconnected with much of brain; cortical,
subcortical and brain stem sites
• brainstem arousal systems
Structure
Structure
• structure based on neurons arranged
in minicolumns with incoming and
outgoing connections distributed
across many brain regions
• in PFC minicolumns are
interconnected to each other
through horizontal ‘long range’
projections in L2/3
• Mini columns in dorsolateral
prefrontal cortex ‘bind’ perception
and executive selection of spatial
targets to guide goal-specific
behavior
Brodmann areas (maps of cortical areas)
of PFC includes
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8  Includes frontal eye fields
9 Dorsolateral prefrontal cortex
10 Anterior prefrontal cortex
11 Orbitofrontal area
44 Pars opercularis (part of the
inferior gyrus & part of Broca’s area)
• 45 Pars triangularis (part of the inferior frontal gyrus & part of Broca’s
area)
• 46 Dorsolateral prefrontal cortex
• 47 Pars orbitalis (part of the inferior frontal gyrus
Structure
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•
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95% of structure of brain formed by 5/6
PFC grows again right before puberty
Grey matter constantly changing throughout life, but peaks in early adolescence,
and a couple years later for boys
• Important because
grey matter contains
cell bodies and
connections between
cells (synapses)
• so important because
it deals with synaptic
pruning
Structure
• Synaptic pruning depends on environment child in
• Unused connections (unused grey matter) pruned away if
certain synapses aren’t used
• Pruning away synapses and wrapping myelin consolidates
learning
• “Use it or lose it principle”  pruning process begins at back
of brain; PFC remodeled last, so teens might rely more on
amygdala to make decisions and solve problems
“If a teen is doing; sports or academics, those are the
connections that will be hard wired. If they’re lying on the
couch or playing video games or MTV, those are the cells and
connections that are going to survive”
Sesame Street
• https://www.youtube.com/watch?v=9PnbKL3
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• 0:26-1:04
Function of the PFC
• Function- Executive Functioning
– Executive functions (also known as cognitive
control and supervisory attention system) is an umbrella
term for the management (regulation, control)
of cognitive processes.
• Functions include: Attention, memory and working
memory, reasoning, task flexibility, and problem
solving as well as planning and execution, judgment
and evaluation, reasoning and
"computation", comprehension and production
of language.
Function of the PFC
• Functions according to specific areas of the PFC
– The dorsolateral prefrontal cortex (DLPFC)involved in "on-line" processing of information
such as integrating different dimensions of
cognition and behavior.
– The anterior cingulate cortex (ACC)- involved in
emotional drives, experience and integration,
inhibition of inappropriate responses, decision
making and motivated behaviors.
Function of the PFC
• Functions according to specific areas of the
PFC:
– The orbitofrontal cortex (OFC)- involved
in impulse control, maintenance of set,
monitoring ongoing behavior and socially
appropriate behaviors, representing the
value of rewards based on sensory stimuli
and evaluating subjective emotional
experiences.
Development of Executive Functions
– The PFC is the last section of the brain to mature.
• Other brain areas are fully developed early in life, the
prefrontal cortex is not until the age of 25.
• The development of executive functions correspond
with the development of the PFC.
• Different abilities peak at different times (early or late
in childhood, adolescence, or adulthood.)
• Executive function abilities are shaped by physical
changes in the brain and by life experiences, in the
classroom and in the world at large.
Development of Executive Functions
– Executive functioning development corresponds with the
neurophysiological developments .
• Processing capacity of the frontal lobes and other
interconnected regions increase in size= emergence of core
executive functions. Thus, for every developmental stage in
human development, the functions are constantly developing.
• Functions do not fully mature during the early childhood,
preadolescence, and adolescence stages so children will
continue to make mistakes related to these emerging abilities,
not because they lack the abilities but because they do not
understand when and how to use these abilities. Naturally,
they older they get, the more they are able to understand how
and when to use these abilities.
Developmental Stages (cont’d)
– Preadolescence
• Children exhibit certain growth spurts in
executive functions, experience a growth in
verbal working memory, goal-directed behavior
(with a potential spurt around 12 years of age);
response inhibition and selective attention; and
strategic planning and organizational skills.
• Ages 8 to 10 years- cognitive flexibility starts
to match that of adults.
Development of Executive Functions
– Adolescence
• Brain systems become better integrated= more effective and
efficient use and improvement of executive functions.
• Planning and goal-directed behavior experiences ongoing
growth.
• Attention control, with a potential spurt at 15, along with
working memory continues to develop.
– Adulthood
• Major change= constant myelination if neurons in the PFC.
• Ages 20-29: executive functions are a their peaks.
– These skills begin to decline with working memory and
spatial span being the areas where decline is most
readily noted. Cognitive flexibility, however, starts
declining around age 70.
Phineas gage
• https://www.youtube.com/watch?v=WGl5SU
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• Stop at 55 seconds
Damage to the Prefrontal Cortex
The Case of Phineas Gage
• First reported case of Traumatic Brain Injury (TBI) to Prefrontal Cortex
• Led to personality changes “no longer Gage”
• Cognitive, intellectual, and language skills intact
• Ability to reason, particularly within a social context, seriously impaired
• No autopsy, but skull exhumed and accident reconstructed using modern
neuroimaging techniques to estimate place of injury as Ventromedial PFC
Damage to the Prefrontal Cortex
• Fascinating constellations of deficits
found in other patients with damage from:
– TBI: Injuries from violent blow to the head,
sports, falling down stairs,
car crash etc.
– Stroke: Interruption of blood flow
to the brain
– Tumors: Cancerous or noncancerous
mass of abnormal cells in the brain
Damage to the Prefrontal Cortex
In the left prefrontal cortex:
A: MRI of acute stroke
B: Coronal slice of stroke
In the right prefrontal cortex:
C. MRI of tumor
D: Axial slice of tumor
Damage often extends into multiple areas and there are
substantial overlapping and interactive functions
across these regions
Assessing Damage to the Prefrontal Cortex
• Non-invasive technologies - fMRI, CT, PET, EEG, MRI etc.
– Assess structural damage
– Measure brain activity correlated to cognition, behavior or emotion
during task performance
• Neuropsychological tests sensitive to consequences of localized
brain damage
• Two areas studied in depth
– Orbitofrontal-Ventromedial
– Dorsolateral
Damage to Orbitofrontal/Ventromedial PFC
• Inhibitory control and decision making deficits
– More risky, maladaptive decisions
– Problems learning and relearning stimulusreward/punishment associations
– Trouble updating behavior based on these associations
in order to reach goals.
Damage to Orbitofrontal/Ventromedial PFC
• Emotional and social control issues
– Lack of affect or poorly modulated
emotional reactions
– Disinhibited or socially inappropriate
behavior with social conventions
ignored
– Defective social and moral reasoning
Damage to Orbitofrontal/Ventromedial PFC
• Theory of mind
– Impaired insight and difficulty in inferring the
mental states of others
– Failure to use emotions to guide decisions leading to
poor social decision making
– Impaired recognition of emotional expressions
– Inability to adjust initial judgments after receiving
more information
Damage to Dorsolateral PFC
• Working memory issues
– Online maintenance of recent memories
– Inability to rearrange, transform, or track the relative status
of stimuli within working memory
• Attention issues
– Increased distractibility
– Decreased responses to visual and auditory stimuli
• Executive Function deficits
– Planning, anticipation and problem solving
– Goal neglect and diminished motivation
– Difficulty with delaying gratification
Damage to Dorsolateral PFC
• Rule learning and task switching problems
Perseveration with
Wisconsin Card
Sorting test
• Declarative memory deficits
– Source memory especially for places, and famous faces
– Monitoring and control of memory processes, both at the
time of encoding and at the time of retrieval
Recovery of Function Following Damage to
PFC
• Reorganization
– Intact portions may compensate for damaged area but prognosis for full
recovery is poor
• Compensatory cognitive retraining to learn new skill
– Operant conditioning – response-cost procedure for disinhibiting issues
– Portable electronic memory devices
• Direct intervention to regain old skills such as attention, working
memory, or goal-directed behavior
– Computer based programs
– Goal management techniques
– Mindfulness training
ADHD
• ADHD is a common
neuropsychiatric disorder
that affects attention,
impulsiveness, and
hyperactivity
• Exact origin of ADHD is
unknown, but ADHD has
been described as
neurobehavioral,
neuropsychiatric and
neurodevelopmental
disorder
Facts about ADHD
• ADHD appears more often in males (3:1)
• These behavioral issues appear before the age
of 7
• Over the course of development ADHD puts
those at risk for many issues in school and
socially
Impairment with ADHD
• Attention networks and inhibitory control
networks
• Inappropriate neurotransmitters levels may
also impair function in the prefrontal cortex
• Any slight change in levels of norepinephrine
and dopamine can have lasting effects on the
prefrontal cortex causing symptoms associated
with ADHD
What Causes ADHD?
• There is no definite cause of ADHD but
scientists believe it may be a combination of
risk factors
– Genes
– Environmental factors
– Brain injuries
– Sugar
– Food additives
Three Subtypes of ADHD
• Predominantly
hyperactiveimpulsive
• Predominantly
inattentive
• Combined
hyperactiveimpulsive and
inattentive
Symptoms of ADHD
• Inattention
– Easily distracted, can’t focus, trouble with turning in
homework, losing things, day dream, issues following
instructions
• Impulsivity
– Very impatient, inappropriate comments, interrupt
others
• Hyperactivity
– Fidget, nonstop talking, touching everything in sight,
constantly in motion
Treatments of ADHD
• Medications are used
– Most common is a “stimulant”
– Many different types some are short-acting or
long-acting
• Ritalin, Focalin, Adderall
– Decreased appetite and sleep problems most
common
– Less common tics and flat personality
Future Research on ADHD
• Over time, research has shown that ADHD is not just
a behavior disorder but a developmental impairment
of the brain’s executive functions- the self-managing
systems
• Motivation and emotional regulation are major issues
for those with ADHD but are not included in criteria
• Need to look at overlapping disorders, to treat
properly
• Diagnosing females with ADHD must be separate
from diagnosing males.
Schizophrenia
• https://www.youtube.com/watch?v=SN1GCoV
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• 3:00-4:15
Schizophrenia and the
Prefrontal Cortex: Symptoms
• Schizophrenia is a mental disorder associated with abnormal social
behavior and delusions
• Two classifications of symptoms: Positive and Negative
• Positive Symptoms- Extra feelings and behaviors not normally
present
– Delusions and hallucinations(most commonly auditory)
– Disordered thought and speech
• Negative Symptoms- A lack of feelings and behaviors usually
present
– Flat or inappropriate expression and emotion
– Speech Difficulty
– Lack of pleasure, motivation, and desire for relationships
• Symptoms typically being in early adulthood and reduces life
expectancy by about 25 years
Schizophrenia and the
Prefrontal Cortex: Possible Causes
• Not a definite cause, but both environmental and genetic factors offer
possible associations
• Environmental factors:
– Drug use- alcohol, amphetamine, cocaine, alcohol
– Prenatal Stressors: illness, stress, malnutrition of mother, or being born in the spring or
winter all correlated
– Social Isolation or social stress
• Genetics and Schizophrenia:
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Search for a gene that explains excess dopamine in cerebral cortex
Those with a family member with schizophrenia have a 20-40% of also being diagnosed
Exact gene not known
Observed to be associated with NOTCH4, histone protein loci, zinc finger protein 804A,
COMT gene
– COMT (Catecho-o-methytransferase) siblings and this gene
– Genetics lead into the research surrounding cognitive effects and mechanisms of
schizophrenia
– Research surrounding gene affecting prefrontal cortex functioning
Schizophrenia and Cognition:
The Role of the Prefrontal Cortex
• Schizophrenia has been associated with cognitive deficits in
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–
–
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working memory
long term memory
Attention
Executive functioning
• Treatments
– Antipsychotic Drugs
– Cognitive-Behavioral Therapy
– Social Skills Training
– There is no cure
How is schizophrenia associated with these cognitive deficits? What
is being done to better understand the relationship between
cognitive effects to help refine treatments?
Research is prompted by the Dopamine Hypothesis of
Schizophrenia…
Gruber, Oliver, Antonella Santuccione, and Helmut Aach. "Figure 1. Example for Consequences of NMDA Receptor Hypofunction in Glutamatergic–
dopaminergic Circuits." Magnetic Resonance Imaging in Studying Schizophrenia, Negative Symptoms, and the Glutamate System. 2014 ed. N.p.: Fronteirs,
n.d. N. pag. April. Psychiatry.
The Dopamine Hypothesis of
Schizophrenia
• Attributes psychotic effects of schizophrenia to overactive
dopamine receptors
• Hypothesis formed on antipsychotic research: Antipsychotic
drugs used to treat schizophrenia have receptor antagonistic
effects
• Areas affected differ based on relationship to glutamate,
where glutamate is too low, dopamine is overactive
– Antipsychotics recept at 5-HT2C receptor, release dopamine in
several areas, including prefrontal cortex
– Other areas of release involved: mesolimbic, mesocortical,
Broca’s and Wernicke’s area
• Prefrontal Cortex has NMDAR(N-methyl-D-aspartate
receptors) that are associated with cognitive impairments,
• Contains most of the dopamine sensitive neurons
Finding the Link:
Schizophrenia and the Prefrontal
Cortex(Lindenberg et. al, 2002)
• National Institute of Mental Health research
• Findings: Psychotic symptoms could be caused by
reduced prefrontal cortex activation, which causes
excess dopamine in striate cortex
• Uses PET scan: Radioactive oxygen reveals where
blood flows and indicates which brain areas are
activated during working memory task, radioactive
precursor chemical of dopamine indicated
dopamine activity
• Schizophrenic patients showed lower performance
and reduced prefrontal activation
http://neuronbank.org/wiki/index.php/Chandelier_Neuron
Schizophrenia and the Prefrontal
Cortex: Where are we now?
• The finding of a connection indicated that Schizophrenia
could be due to a primary defect of the prefrontal cortex
• Schizophrenia in diagnosis is marked by a lack of links
between prefrontal cortex and areas in the cortex associated
with higher-order thinking
• Connection from prefrontal cortex to striate cortex is
inhibitory, an offered explanation indicates that an
anatomical change in the PFC in schizophrenia stops the
inhibition of dopamine release.
• New from Yale researchers Anticevic et. al, 2015, shows
that in onset, there is an initial spike in connection, followed
by a decline, current research into relationship between
interaction of excitatory and inhibitory connection
References
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Spinks, Sarah. "Adolescent Brains Are Works in Progress." PBS. PBS, 9 Mar. 2000. Web. 25 Apr. 2015.
"Your Teenager’s Developing Brain." Raising Children Network, with the Centre for Adolescent Health,
n.d. Web.
Opris, Loan. "Prefrontal Cortical Microcircuits Bind Perception to Executive Control." Nature.com. Nature
Publishing Group, 29 July 2013. Web. 27 Apr. 2015.
Blakemore, Sarah. "The Mysterious Workings of the Adolescent Brain." Sarah-Jayne Blakemore:. Ted
Talks, June 2012. Web. 27 Apr. 2015
"Prefrontal Cortex." Wikipedia. N.p., n.d. Web.
Barkley, R. A. (1997). Behavioral inhibition, sustained attention, and executive functions: Constructing a
unifying theory of ADHD. Psychological Bulletin, 121(1), 65-94. doi:10.1037/0033-2909.121.1.65
Nikkelen, S. C., Valkenburg, P. M., Huizinga, M., & Bushman, B. J. (2014). Media use and ADHD-related
behaviors in children and adolescents: A meta-analysis. Developmental Psychology, 50(9), 2228-2241.
doi:10.1037/a0037318
•
Attention Deficit Hyperactivity Disorder (ADHD). (n.d.). Retrieved April 22, 2015, from
http://www.nimh.nih.gov/health/topics/attention-deficit-hyperactivity-disorder-adhd/index.shtml
•
Researchers on ADHD Research. (n.d.). Retrieved April 21, 2015, from
http://www.chadd.org/Understanding-ADHD/Parents-Caregivers-of-Children-with-ADHD/Symptoms-andCauses/Researchers-on-ADHD-Research.aspx
References
• Damasio, H., Grabowski, T., Frank, R., Galaburda, A. M., &
Damasio, A. R. (2005). The Return of Phineas Gage: Clues about
the Brain from the Skull of a Famous Patient. In J. T. Cacioppo, G.
• G. Berntson, J. T. Cacioppo, & G. G. Berntson (Eds.), (Key reading
in social psychology, pp. 21-28). New York, NY, US: Psychology
Press.
• Szczepanski, S. M., & Knight, R. T. (2014). Insights into human
behavior from lesions to the prefrontal cortex. Neuron, 83(5), 100218. doi:http://dx.doi.org/10.1016/j.neuron.2014.08.011
• http://www.theguardian.com/commentisfree/2015/mar/17/missouriexecuting-cecil-clayton-missing-a-part-of-hisbrain?CMP=share_btn_link
• Executive functions. (n.d.). Retrieved April 25, 2015, from
http://en.wikipedia.org/wiki/Executive_functions
•
References
Anticevic, Alan, et al. "Early-Course Unmedicated Schizophrenia Patients Exhibit Elevated
Prefrontal Connectivity Associated with Longitudinal Change." The Journal of Neuroscience 35.1
(2015): 267-286.
•
"Dopamine Hypothesis of Schizophrenia." Wikipedia. Wikimedia Foundation, n.d. Web. 23 Apr.
2015.
•
Gruber, Oliver, Antonella Santuccione, and Helmut Aach. "Figure 1. Example for Consequences of NMDA Receptor Hypofunction in
Glutamatergic–dopaminergic Circuits." Magnetic Resonance Imaging in Studying Schizophrenia, Negative Symptoms, and the Glutamate
System. 2014 ed. N.p.: Fronteirs, n.d. N. pag. April. Psychiatry.
•
Hathaway, Bill. "Too Much of a Bad Thing: Schizophrenia Onset Linked to Elevated Neural Links."
Yale News. Yale University, 6 Jan. 2015.
•
Meyer-Lindenberg, Andreas, Robert S. Miletich, Philip D. Kohn, Giuseppe Esposito, Richard E.
Carson, Mario Quarantelli, Daniel R. Weinberger, and Karen Faith Berman. "Reduced Prefrontal
Activity Predicts Exaggerated Striatal Dopaminergic Function in Schizophrenia." Nature
Neuroscience 5.3 (2002): 267-71.
•
"NIH News Release-Gene Slows Frontal Lobes, Boosts Schizophrenia Risk" U.S National Library
of Medicine. U.S. National Library of Medicine, 29 May. 2001.
•
"Schizophrenia." Wikipedia. Wikimedia Foundation, n.d. Web. 23 Apr. 2015.