Transcript Neurochemistry of executive functions

Neurochemistry of
executive functions
Saeed Basirian Jahromi
Aalto university
February 2016
What are executive functions?
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A range of higher-order cognitive functions that enable organized and goaldirected behavior.
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Includes:
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Planning
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Execution of plans (motor system)
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Flexibility (sensitivity to feedback)
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Selective attention
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Working memory
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Emotions
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Decision making
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Problem solving and reasoning
Role of the prefrontal cortex
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A heterogeneous area
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Central hub
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Reciprocal connections to other areas
Historical example: Phineas Gage (19th century)
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Extensive damage to frontal lobe due to accident
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Personality change
*Images from Wikipedia
Constituents of executive functions
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Setting and keeping goals across different timescales
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Ability to sequence sub goals
Inhibition of competing/interfering impulses
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Measured by reaction time in neuropsychological tests
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Deficiency in ADHD patients
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Flexibility to feedback
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Motor system
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Hierarchy of increasingly complex motor sequences
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Responsible for motor imagery and planning
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Complex network of prefrontal cortex, basal ganglia, and thalamus responsible for
choosing between alternative actions and inhibiting competing plans
Constituents of executive functions
(cntd.)
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Selective attention and working memory
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Selecting and manipulating task-relevant information
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Dorsolateral prefrontal cortex and posterior parietal cortex
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Hierarchy of memory schemas in the ventromedial prefrontal cortex
Emotions and mood
*Image from thebrain.mcgill.ca
Relevant neuropsychological tests
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Stroop color-word task
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Word fluency test
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Wisconsin card sorting test
Diffuse modulatory systems of the brain
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Regulate vast assemblies of post-synaptic neurons
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Properties:
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A small number of neurons at the core of each system
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Arise from the central core of the brain (mostly brain stem)
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Each neuron can influence many others
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They release neurotransmitters in the extra-cellular fluid
4 major systems: norepinephrine, serotonin, acetylcholine, dopamine
Diffuse modulatory systems of the brain
(cntd.)
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Noradrenergic system
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Locus Coeruleus in Pons
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Innervates almost everywhere!
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Involved in regulation of attention, arousal, sleep-wake cycles, learning and
memory, anxiety and pain, mood, and brain metabolism
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Best activated by new, unexpected, nonpainful stimuli
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Participates in general arousal of the brain in interesting events
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Increases brain responsiveness
*Images hereafter from Mark F. Bear et al., Neuroscience: exploring the brain
Diffuse modulatory systems of the brain
(cntd.)
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Serotonergic system
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Mostly clustered in the 9 Raphe nuclei (in brain stem)
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Those more rostral innervate in the same way as locus ceoruleus
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Also most active when animal is aroused
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This and noradrenergic systems part of the ascending reticular activating system
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Also involved in regulating:
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sleep-wake cycles, mood, and certain types of emotions
Diffuse modulatory systems of the brain
(cntd.)
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Cholinergic system:
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Basal forebrain complex
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Several related nuclei medial and ventral to the basal ganglia
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Also regulates general brain excitability during arousal, and sleep-wake cycles
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Has a special role in learning and memory
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Possible role in Alzheimer’s
Pontomesensephalotegmental complex:
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Acts mainly on dorsal thalamus
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Regulates excitability of sensory relay nuclei
Diffuse modulatory systems of the brain
(cntd.)
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Dopaminergic system
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Substantia nigra
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Projects to striatum (in basal ganglia)
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Facilitates the initiation of movement
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Implicated in Parkinson’s disease
Ventral tegmental area
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Projects to the frontal cortex and the limbic system
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Involved in the reward system
Effect of dopamine in basal ganglia
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Low dopamine level
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Reduced ability to initiate actions and shift cognitive sets
disease
Parkinson’s
High dopamine level
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Inability to prevent inadvertent shifts in sets
Schizophrenia
Other neurotransmitters
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Blocking NMDA glutamate receptors
decreased WCST performance
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Benzodiazepines enhancing GABA receptors
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Alcohol (ethanol) enhancing GABA receptors
Increased inhibition (sedation)
Key points
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Executive functions are a range of higher-order cognitive functions that
enable organized and goal-directed behavior.
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The prefrontal cortex acts as the central hub for executive functions.
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The 4 diffuse modulatory neurotransmitter systems have an impact on
executive functions.
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Dopamine especially greatly affects the ability to initiate actions and shift
cognitive sets.
References
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Introduction to cognitive neuroscience, Iiro P. Jääskeläinen
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Neuroscience: exploring the brain, Mark F. Bear et al., 2015
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Neural bases of set-shifting deficits in Parkinson’s disease, O. Monchi et al.,
The journal of neuroscience, 2004
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www.wikipedia.org
Questions?