disorders of motivation

Question 1

what is motivation

Answer 1

the impetus that gives purpose or direction to behaviour

Question 2

what is volition

Answer 2

the faculty by which an individual decides upon and commits to a particular course of action especially when this occurs without direct external influence - active choice/response to events

Question 3

what are impulse control disorders

Answer 3

characterised by abnormal urges that interfere with normal life such as pathological gambling, punding and dopamine dysregulation disorder

Question 4

what is impulsivity

Answer 4

acting prematurely without forethought
observed as excessive action despite high cost

Question 5

what are the proposed mechanisms underlying impulsivity

Answer 5

reduced sensitivity to risk/uncertainty
steeper temporal discounting
reduced reflection
disinhibition
delay aversion
novelty preference

Question 6

what is apathy

Answer 6

diminished motivation in comparison to previous level of function not due to age or culture coupled with diminished goal-directed action, cognition or emotion not explained by physical/motor disabilities

Question 7

what are the proposed mechanisms of apathy

Answer 7

neuroeconomic approaches: increased effort cost; reduced reward sensitivity

stages of goal directed action: option generation, option selection, option initiation, learning

Question 8

why are so many different disorders associated with apathy

Answer 8

depression, schizophrenia, fronototemporal dementia, AD, PD, HD, stroke

diverse lesion sites and aetiology

Kos et al. (2016) argue that there is a final common pathway to apahty that can be reached via many different mechanisms
meta-analysis of areas associated with apathy argue that damage to any part of three functional circuits can result in apahty
two fronto-striatal circuits (reward and executive function) and the inferior parietal cortex

Le Heron et al., 2018
review of neurobiology of different conditions involved in apathy
consistent changes in frontostriatal circuits - dorsal ACC, medial PFC, VTA and ventral striatum
consistent finding that damage in the frontal and subcortical regions associated with DA transmission

Brown & Pluck 2000
apathy will help us model the cognitive processes underlying intentionality, volition and will
high prevalence of apathy or negative symptoms with pathology involving frontal cortex and subcortical structures
Alexander proposed network organisation into motor, cognitive and behavioural loops
apathy may result from the summation of cortical hypofunction of the various circuits
HPC input to ventral striatum disrupted in AD
VTA disrupted in PD
ACh in progressive supranuclear palsy (PSP)
NAc and amygdala in schizophrenia
but need to consider interactions with inputs from outside the loops
Motor: SNc → putamen → GPe/STN → GPi SNr→ vl/va thalamus → SMA
Cognitive: SNc → caudate → GPe/STN → GPi SNr→ vl/md thalamus → dlPFC
Affective: VTA → v striatum → GPe/STN → palladium → md thalamus → mOFC / cingulate (note key input from amygdala/ HPC)

PD (Baggio et al., 2015)
primary dopaminergic deficit, apathy seen every stage
resting state fMRI shows correlation of changes in BOLD signal between brain areas
reduced reciprocal connections between cortical areas (OFC, ACC, and striatum)

AD
70% report apathy (Mega et al., 1996)
Meta-analysis found reduced DA receptors (Pan et al., 2019)
PET showed reduced metabolism in OFC, ACC and ventral striatum (Holthoff et al., 2005)
atrophy of ACC, OFC correlates with disease associated apathy and frontotemporal dementia (Rosen et al., 2005)

Question 9

what is trait apathy

Answer 9

Bonelle et al., 2015
self-report apathy scores (Lille apathy rating scale)
task: decide to squeeze a gripper for reward
decision to act task: decide whether or not to squeeze gripper for reward
decreased willingness to exert effort for reward below a threshold with high behavioural apathy
indicates there are individual differences in the subjective valuation of reward and effort
fractional anisotrophy negatively correlstes with apathy score - integrity of the white matter bundle in the cingulum

may be associated with differences in brain systems underlying motivation to act or in action processing - the transformation of an intention to an action
decreased structural and functional connectivity between the ACC and SMA associated with increased behavioural apathy
inefficient communication between the ACC and SMA may lead to an increased physiological cost and greater effort sensitivity for action initiation in more apathetic people

Question 10

what is the relationship between motivation and mesolimbic dopamine

Answer 10

from behavioural experiments Kringelbach & Berridge 2012 have built up a biological model
they argue motivaiton is driven by dopaminergic inputs from the orbitofrontal and limbic system involved in weighing up the costs of actions
the reward signals from the orbitofrontal cortex and ventral striatum then work to counteract these costs

Question 11

what do tonic and phasic dopamine signal

Answer 11

disruption of NMDAR-dependent burst firing by dopamine neurons provides selective assessment of dopamine-dependent behaviour
phasic DA disruption impared the acquisition of conditioned behavioural responses and attenuated learning about cues that predict rewarding and aversive events

Question 12

what is goal-directed action

Answer 12

behaviour driven by the expectation of achieving a desired outcome
requires causal knowledge of the potential consequences of action to flexibly pursue a current goal

Question 13

what is the evidence for impaired option generation in apathy

Answer 13

Radakovic et al., 2017
amyotrophic lateral sclerosis cohort
verbal fluency and random number generation
write or orate as many words beginning with a particular letter in a minute then say or write a number every second
significant difference in performance between ALS patients on verbal fluency but not random number generation
could reflect an executive impairment in WM confounded by this task
number generation task is very simple, may be that as the complexity of options increases patients become impaired
ultimately it is difficult to observe how options are generated
- initially equal weights so random - but with learning different actions/choices will be associated with specific outcomes
DA hypothesised to reflect precision in these estimates

Question 14

what is the evidence for reduced desire for information in impulsivity

Answer 14

Djamshidian et al., 2012
PD patients, ICD patients and matched controls
presented with two cups of beads, each reported to have a differnet proportion of blue and green beads
each trial one bead was drawn and participants were asked if they would like to sample another bead or guess which cup the beads were being drawn from
the number of beads participants sample before making their decision indicates how much information they need before choosing an action
PD, ICD patients and substance abusers desire less information than controls before making a choice
indicating that the threshold for information needed to decide to act
- reduced concern for consequences of wrong choices such as loss of potential reward
e.g higher tolerance for risk (Rao et al., 2008)
fMRI of PD patients with ICDs using balloon analogue risk task
BOLD - PD without ICD activate mesolimbic pathway
ICD patients show diminsed BOLD activity in right ventral striatum

(Kringelbach & Berridge, 2012)
motivation driven by DAergic signals from VTA to ventral striatum
reward signals from orbitofrontal cortex and ventral striatum counteract costs from cingulate / limbic system

aberman & salamone 1999 - depleting mesolimbic DA in rats decreases the amount of lever presses rats would make to receive reward - persistence with work to get reward

ventral striatal dopamine overdose hypothesis
e.g unaffected in PD so overdose on DA agonist
disrupted in AD so apathy
support by Le Heron et al., 2018 review

higher uncertainty tolerance
DA hypohthesised to reflect precision of estimates
increased DA may mean there is greater confidence that an action will lead to a desired outcome

habitual vs goal directed action

Question 15

what is the evidence for impaired optimal selection (based on attribution and discrimination of relative value) in apathy

Answer 15

optimal selection of a course of action involves assigning relative value (magnitude x likelihood of reward) each option
Rochat et al., 2013
stroke patients
cued reinforcement reaction time task
participants presented with a cue indicating the likelihood that a response will be rewarded before judging the odd-one out
patients with more severe apathy (controlling for mood and lesion size) did not increase the speed of response for high probability rewards
reward insensitivity associated with the ventral putamen, globus pallidus, dorsal thalamus, insula and PFC
reduced motivational affect of reward
perhaps because of impaired assignment of relative value

Le Heron et al., 2018
PD patients
had to decide whether they were willing to exert variable amounts of physical effort for variable rewards
apathetic PD patients were less willing to accept lower offers when accompanied by high levels of effort
willing to exert high levels of effort but only when the offered rewards were considerably higher than necessary for acceptance in controls
so sensitivity to reward

Saleh et al., 2021
drift diffusion model
apathetic patients with small vessel cerebrovascular disease accepted fewer offers on a decision making task involving accepting or rejecting monetary rewards in return for exerting different levels of physical effort

Question 16

what is the evidence for failure to factor in potential cost in relative value in impulsivity

Answer 16

risk is the variance in possible outcomes

cools et al., 2003
PD ON patients
decision making gambling task
variable ratio of red and blue boxes out of ten
yellow token hidden inside one
participants had to pick the colour box the token was hidden behind
rate confidence correct by placing a bet
to indicate bet participants had to stop a slowly increasing or decreasing number corresponding to the proportion of points they would win
measured the frequency with which participants selected the more probable colour and how much they bet
rational decision making - proportion of choices with most likely outcome
but abnormal betting strategy
placed larger bets in descending condition and smaller bets in ascending condition
impulsivity in placing bets more quickly - delay aversion or motor impulsivity
bet corresponds to confidence - seems random

externally generated action - affordances
PD is specifically an impairment in internally generated action

Delay aversion associated with ADHD (Sonuga-Barke, 2002) due to abnormal reward mechanisms associated with limbic striatal-circuitry (nucleus accumbens and vPFC)
Attention and inhibitory control
Treated with methylphenidate which blocks DA reuptake
Contradicts traditional DA overdose as treatment with DA reduces impulsivity

patients with first-episode schizophrenia take longer to select a box and more frequently choose the less favourable response than controls
higher bets in descending condition but not quicker to place bets in ascending condition
mimics results of patients with OFC lesions

Amphetamine abusers and healthy volunteers with acutely depleted tryptophan show slower deliberation times and choose the least likely outcome but are not more impulsive (Rodgers et al., 1999)

Question 17

what is the evidence that impulsivity may lead to an increased reliance on the habit system

Answer 17

Theories of habitual vs goal-directed action
dual-route for optimising behaviour
one distributed reciprocal neural network underlying goal-directed action - motivation, sustenance and learning of action

instrumental learning paradigms indicate that conditioning can occur through either goal-directed learning of stimulus-response outcome associations and habit based learning of stimuli/context response relationships (Dickenson, 1985)
neuroimaging supports these as being mediated by two distinct systems: prefrontal cortex and dorsomedial striatum (GD) and dorsolateral striatum (HB) - Balleine & Dickinson 1998

Hogarth et al., 2012
explains absence of consideration for an action’s consequences
separated student smokers into those who smoked every day or less (corresponds to likelihood of perseveration and reaching dependency)
Barratt’s impulsivity scale
concurrent choice training of two instrumental responses associated with either chocolate or water reward on half of trials
selective satiety and extinction
devaluation effect diminished in those high on the BIS
greater reliance on cues to drive action and greater reliance on habit

Question 18

what is the evidence for impaired action preparation and initiation in apathy and impulsivity

Answer 18

Obeso et al., 2011
PD patients tested on stop-signal and stroop
impaired inhibition of prepotent responses

Adam et al., 2013
elderly people and apathetic patients with basal ganglia lesions
traffic light task
elderly and apathetic patients did not anticipate
restored on DA medication

apathy increases with age in healthy communit dwelling individuals particularly over 65+ (Brodaty et al., 2010)
associated with reduced grey matter volume in right ACC
and increases with cognitive impairment

Question 19

what factors can increase the risk of developing an ICD

Answer 19

PD patients who are younger, smokers or have family histories of gambling are more likely to develop an ICD (Voon et al., 2011)

polymorphisms in VMAT, DAT and D2 receptor associated with increased impulsivity

lower D2/D3 receptor binding ON medication in patients with pathological gambling (Steeves et al., 2009)

Motivation and neurochemical state changes will have different effects on individuals with different baseline motivational system states (Cools & Robin)
Patients with ICDs have higher scores on measures of depression, state and trait anxiety and obsessive-compulsive symptoms
Complex interactions between existing traits and disorder induced states that can either decrease or increase goal-directed action

Question 20

what do animal models tell us about the role of dopamine in behaviour

Answer 20

salamone et al., 1994
lesioned ventral striatal dopamine
increased fixed-ratio of lever press to food delivery
reduced lever pressing with increasing fixed ratio compared to controls
increased effort sensitivity such that value of reward is not enough for behaviour
but could be explained by general motor fatigue

Walton et al., 2002
medial frontal lesions in rats
T maze manipulated choice of low/high reward for low/high effort
medial frontal lesion rats show preference for low effort fork

Question 21

what is the ventral striatal dopamine overdose hypothesis

Answer 21

efficient dopamine-mediated function follows an inverted U-shape
hyperactive DA results in disordered impulsivity and hypodopaminergic state results in apathy

in PD there is nigrostriatal depletion but ventral striatum is intact DAergic treatment restores nigrostriatal depletion but overdoses ventral striatal DA system hypothesised to be a goal-directed evaluation system

in contrast AD atrophy of HPC deafferents the ventral striatum –> apathy

but treatment of ADHD with DA reuptake inhibitors reduces impulsivity

Improvement in apathy following D2 agonist in 57% of AD patients (Drayton et al., 2004)

there is little evidence for a dose-dependent relationship

relies on apathy and impulsivity as existing at opposite ends of one spectrum
there are PD patients who display both apathy and impulsivity
these disorders have multiple dimensions corresponding to different stages in processing and extending beyond action - cognition and emotion
some mechanisms may be dopamine-dependent but a full account of disorders of motivation needs to include all the mechanisms that can contribute to impairment
e.g serotonin, acetylcholine and noradrenaline

Question 22

what is the evidence for the involvement of different neurotransmitters in apathy and impulsivity

Answer 22

acetylcholinesterase reduces apathy in PD (Devos et al., 2017)
but the same effects are not seen with AD (Sephrey et al., 2017)

selective lesions of the rat NAc induces persistent impulsive choice on delayed reinforcement task (Cardinal et al., 2001)
5-HT depletion following lesions on the ascending serotonergic projections in the rat increased impulsive behaviour on a 5 choice reaction time test (Harrison et al., 1997) and delayed reward procedure (Mobini et al., 2000)

although this may be due to the removal of an inhibitory influence on DAergic transmission

5-HT receptor stimulation inhibits the activity of mesolimbic DAergic neurons and reduces release in frontal cortex and NAc (Millan et al., 2002)

DRN 5-HT neurons may also be affected in PD