Neurochemistry of executive functions Saeed Basirian Jahromi Aalto university February 2016

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

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

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

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

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

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

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

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

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

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

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

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

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.

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 www.wikipedia.org

Questions?