1. Neurochemistry of executive functions
Saeed Basirian Jahromi
Aalto university
February 2016

2. What are executive functions?
A range of higher-order cognitive functions that enable organized and goal- directed behavior.
Includes:
Planning
Execution of plans (motor system)
Flexibility (sensitivity to feedback)
Selective attention
Working memory
Emotions
Decision making
Problem solving and reasoning

3. Role of the prefrontal cortex
A heterogeneous area
Central hub
Reciprocal connections to other areas
Historical example: Phineas Gage (19th century)
Extensive damage to frontal lobe due to accident
Personality change
*Images from Wikipedia

4. Constituents of executive functions
Setting and keeping goals across different timescales
Ability to sequence sub goals
Inhibition of competing/interfering impulses
Measured by reaction time in neuropsychological tests
Deficiency in ADHD patients
Flexibility to feedback
Motor system
Hierarchy of increasingly complex motor sequences
Responsible for motor imagery and planning
Complex network of prefrontal cortex, basal ganglia, and thalamus responsible for choosing between alternative actions and inhibiting competing plans

5. Constituents of executive functions (cntd.)
Selective attention and working memory
Selecting and manipulating task-relevant information
Dorsolateral prefrontal cortex and posterior parietal cortex
Hierarchy of memory schemas in the ventromedial prefrontal cortex
Emotions and mood
*Image from thebrain.mcgill.ca

6. Relevant neuropsychological tests
Stroop color-word task
Word fluency test
Wisconsin card sorting test

7. Diffuse modulatory systems of the brain
Regulate vast assemblies of post-synaptic neurons
Properties:
A small number of neurons at the core of each system
Arise from the central core of the brain (mostly brain stem)
Each neuron can influence many others
They release neurotransmitters in the extra-cellular fluid
4 major systems: norepinephrine, serotonin, acetylcholine, dopamine

8. Diffuse modulatory systems of the brain (cntd.)
Noradrenergic system
Locus Coeruleus in Pons
Innervates almost everywhere!
Involved in regulation of attention, arousal, sleep-wake cycles, learning and memory, anxiety and pain, mood, and brain metabolism
Best activated by new, unexpected, nonpainful stimuli
Participates in general arousal of the brain in interesting events
Increases brain responsiveness
*Images hereafter from Mark F. Bear et al., Neuroscience: exploring the brain

9. Diffuse modulatory systems of the brain (cntd.)
Serotonergic system
Mostly clustered in the 9 Raphe nuclei (in brain stem)
Those more rostral innervate in the same way as locus ceoruleus
Also most active when animal is aroused
This and noradrenergic systems part of the ascending reticular activating system
Also involved in regulating:
sleep-wake cycles, mood, and certain types of emotions

10. Diffuse modulatory systems of the brain (cntd.)
Cholinergic system:
Basal forebrain complex
Several related nuclei medial and ventral to the basal ganglia
Also regulates general brain excitability during arousal, and sleep-wake cycles
Has a special role in learning and memory
Possible role in Alzheimer’s
Pontomesensephalotegmental complex:
Acts mainly on dorsal thalamus
Regulates excitability of sensory relay nuclei

11. Diffuse modulatory systems of the brain (cntd.)
Dopaminergic system
Substantia nigra
Projects to striatum (in basal ganglia)
Facilitates the initiation of movement
Implicated in Parkinson’s disease
Ventral tegmental area
Projects to the frontal cortex and the limbic system
Involved in the reward system

12. Effect of dopamine in basal ganglia
Low dopamine level
Reduced ability to initiate actions and shift cognitive sets Parkinson’s disease
High dopamine level
Inability to prevent inadvertent shifts in sets Schizophrenia

13. Other neurotransmitters
Blocking NMDA glutamate receptors decreased WCST performance
Benzodiazepines enhancing GABA receptors Increased inhibition (sedation)
Alcohol (ethanol) enhancing GABA receptors

14. Key points
Executive functions are a range of higher-order cognitive functions that enable organized and goal-directed behavior.
The prefrontal cortex acts as the central hub for executive functions.
The 4 diffuse modulatory neurotransmitter systems have an impact on executive functions.
Dopamine especially greatly affects the ability to initiate actions and shift cognitive sets.

15. References
Introduction to cognitive neuroscience, Iiro P. Jääskeläinen
Neuroscience: exploring the brain, Mark F. Bear et al., 2015
Neural bases of set-shifting deficits in Parkinson’s disease, O. Monchi et al., The journal of neuroscience, 2004

16. Questions?