lecture 2- noradrenaline, acetylcholine and alertness

Question 1

the brain stem and thalamus

Answer 1

• basic behavioural functions: sleep/wake cycle, reflexive response to sensory input

Question 2

ascending reticular activating system (ARAS)

Answer 2

• axons of ARAS project from brain stem to higher cortical regions (incl via thalamus)
• source of major excitatory neurotransmitters: noradrenaline (NA) and acetylcholine (ACh)
• regulates general levels of cortical arousal, alertness and consciousness
• Eysenck (1967) suggested a link between ARAS and extraversion: extraverts have low ‘resting’ ARAS activity (so they seek out more stimulation); introverts have high ‘resting’ ARAS activity (so they avoid overstimulation)

Question 3

anterior and posterior attention systems

Answer 3

• two attention systems in the cortex
• anterior (frontal) system= ‘top down’ (cognitive), voluntary, controlled, task-or goal driven attention, ‘executive functions’
• posterior (parietal) system= ‘bottom up’ (sensory), involuntary, automatic, stimulus driven attention, ‘orienting reflex’

Question 3

rough definition of alertness

Answer 3

• generalised readiness to process stimuli and respond. measured by subjective feelings or simple psychomotor tasks

Question 4

rough definition of attention

Answer 4

• enhanced processing of specific/selected stimuli. measured by behavioural performance - eg RT/accuracy

Question 5

rough definition of arousal

Answer 5

• physiological activation in autonomic nervous system (eg skin conductance) or central nervous system (using EEG, fMRI, ect); sleep/wake cycle

Question 6

what is Vigilance (or continous performance) tasks and what can be measured

Answer 6

• respond only to pre-specified target stimulus/sequence (eg “only respond to X” only respond if same letter is presented twice in succession”.)
• targets are rare (eg. 5% of trials); presentation is rapid
• requires sustained attention (=vigilance) and is more cognitively demanding than simple RT task (eg additional demands on working memory and response inhibition); involves anterior system

measures: average RT to targets, errors of omission (missed targets) and errors of commission (false alarm; responding to non-targets)

Question 7

how is one way alertness and attention measured?

Answer 7

simple detection / reaction time tasks

eg “press when you see the X”
- mean RT depends on average alertness during task (tonic alertness)

eg “press when you see the X; the dot will warn you that its about to appear”
- mean RT depends on temporary increase in alertness following warning cues (phasic alertness)

Question 8

psychopharmacology of alertness

Answer 8

• drugs that increase alertness/ arousal are called stimulants- examples include caffeine, nicotine, amphetamines and methylphenidate (Ritalin)
• these drugs mimic or enhance the effects of noradrenaline and /or acetylcholine in the brain- ie they are noradrenergic or cholinergic agonists
• drugs that reduce alertness/ arousal are sedatives- examples include GABA agonists , noradrenergic beta-blockers & cholinergic antagonists

Question 9

Noradrenaline

Answer 9

• noradrenaline comes from cells whos cell bodies are located in a particular part of the brain stem
• neurons in the locus coeruleus (LC, ‘blue spot’) in the brain stem are main sources of NA
• they project to many different ‘higher’ brain areas (incl. via thalamus)
• these projections allow LC to modulate general levels of brain arousal and alertness

Question 10

what does increased activity in the LC cause

Answer 10

increase activity in the LC (therefore, increased release of NA causes stress, anxiety and panic attacks

Question 11

drugs that increase NA-ergic activity

Answer 11

• these have psychostimulant (alertness-increasing) and anxiogenic (anxiety producing) effects
• amphetamines

Question 12

what are amphetamines and what do they do?

Answer 12

• amphetamines are synthetic drugs, derived from ephedrine or pseudoephedrine (found in the Ephedra plant)
• amphetamines increase release and block reuptake of noradrenaline (and dopamine)

Question 13

amphetamines- acute effects

Answer 13

subjective effects- feelings of alertness and energy; increased anxiety at higher doses

task performance
- low dose: improved performance in simple psychomotor and vigilance tasks
- high dose: impaired task performance; increased distractability

Question 14

inverted -U relationship between arousal and task performance (Yerkes- Dodson, 1908)

Answer 14

• underaroasal (fatigue, boredom) and over-arousal (anxiety, stress, excitement) can both impair performance
• therefore, increasing arousal with a psychostimulant can improve performance (if arousal low) or impair performance (if arousal high)
• this effect may be due to arousal narrowing the attentional focus, which can be too narrow for optimal performance (esp. with complex tasks)

Question 15

drugs that reduce NA-ergic activity and example

Answer 15

• these have sedative (alertness reducing) anxiolytic (anxiety reducing) effects
• noradrenergic beta-blockers some of the receptors on the post synaptic cell for noradrenaline are celled beta receptors and if they are blocked with an antagonist, noradrenaline can no longer bind preventing it from having its effect resulting in reduced anxiety
• eg propranolol; mainly used clinically for effects on blood pressure and heart are B-receptor antagonists

Question 16

acetylcholine (ACh)?

Answer 16

• cholinergic neurons release acetylcholine (ACh)
• cholinergic neurons project from bsal forebrain nuclei throughout entire cortex.
• activation of these systems is associated with alertness, attention, learning and memory
• cholinergic nuclei in the midbrain (upper brain stem) project to thalamus and regulate arousal and sleep/wake cycle

Question 17

drugs that increase cholinergic activity

Answer 17

• cholinesterase inhibitors are used in the treatment of Alzheimer’s disease. (ACh cells in basal forebrain are lost in AD; cholinesterase inhibitors increase ACh availability
• acetylcholine is broken down into two parts by an enzyme called acetylcholinesterase. if prevented, its not disabled or deactivated its still being acetylcholine and still the right shape to fit like a key in a lock and activate the receptors
• cholinergic receptor agonists (eg nicotine) mimic effects of ACh at their receptors increasing subjective alertness

Question 18

drugs that reduce cholinergic activity

Answer 18

• cholinergic receptor antagonists block effects of ACh at receptors, therefore reduce subjective alertness
• these drugs cause general cognitive impairment (‘delirium’) similar to Alzheimer’s disease
• an example of a cholinergic antagonist is a scopolamine which is found in various toxic plants (eg deadly nightshade family)
• scopolamine can be got from that and will antagonize the cholinergic system giving general cognitive impairment

Question 19

Wesnes et al, 1988 (human psychopharmacology 3, 27-41)

Answer 19

• 0.6mg sub-cutaneous scopolamine (v. placebo) reduced subjective alertness, increased errors and slower RTs vigilance task, impaired memory for word list (all p <.001), in healthy participants

Question 20

adhd

Answer 20

• attention deficit hyperactivity disorder
• adhd is estimated to affect about 5% of the population
• it is more common (or at least more frequently detected) in males than females
• its characteristics are first present in childhood; these persist significantly into adulthood in about 50% of cases
• key characteristics: inattention/ or hyperactivity
• also includes forgetfulness, impulsivity and destructibility

Question 21

adhd medications

Answer 21

adhd is often treated with a psychostimulant drug
- amphetamine (adderall)
- methylphenidate (Ritalin)

• these drugs increase levels of both noradrenaline and dopamine in the brain
• some newer drug treatments more selectively target noradrenaline levels (eg atomoxetine, a noradrenaline reuptake inhibitor)

Question 22

zeiner et al. (1999) response to methylphenidate in boys with ADHD

Answer 22

• 36 boys diagnosed with ADHD, aged 7-11 years
• double blind, placebo-controlled, crossover (within-subjects) design
• three weeks of daily drug/placebo treatment
• one week ‘washout’ period between treatments
• assessments were made in final week of each treatment

Question 23

results of Zeiner

Answer 23

• ## vigilance was improved, fewer errors in a task where the boys what they heard

Question 24

Why would a stimulant drug reduce hyperactivity?

Answer 24

• If ADHD involves abnormally low levels of intrinsic arousal (fitting
  with, e.g., low vigilance scores), hyperactivity might be aimed at
  increasing arousal to more optimal levels.
• Increasing arousal with a psychostimulant drug instead could then
  reduce the need for hyperactivity, as well as improve cognitive
  functioning.