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Neuroscience of apathy and anhedonia: a transdiagnostic approach

Abstract

Apathy and anhedonia are common syndromes of motivation that are associated with a wide range of brain disorders and have no established therapies. Research using animal models suggests that a useful framework for understanding motivated behaviour lies in effort-based decision making for reward. The neurobiological mechanisms underpinning such decisions have now begun to be determined in individuals with apathy or anhedonia, providing an important foundation for developing new treatments. The findings suggest that there might be some shared mechanisms between both syndromes. A transdiagnostic approach that cuts across traditional disease boundaries provides a potentially useful means for understanding these conditions.

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Fig. 1: Mechanisms underlying effort-based decision making to obtain rewards.
Fig. 2: Behavioural paradigms for assessing amotivation.
Fig. 3: Brain regions implicated in motivation, apathy and anhedonia.
Fig. 4: Optogenetic study of effort-based decision making in rodents.

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Acknowledgements

M.H. and J.P.R. are supported by awards from the Wellcome Trust. M.H. is also supported by the UK National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and the Wellcome Trust Centre for Integrative Neuroimaging, Oxford. J.P.R. is also supported by the Leverhulme Trust.

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Nature Reviews Neuroscience thanks J. Salamone and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Both authors researched data for the article, made substantial contributions to discussion of the content, wrote the manuscript and reviewed or edited the manuscript before submission.

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Correspondence to Masud Husain.

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Competing interests

M.H. has received an honorarium from Eli Lilly for speaking at their UK annual research symposium in 2017. J.P.R. is a consultant for Cambridge Cognition Ltd, Takeda and GE.

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Glossary

Motivation

A reason or reasons for acting or behaving in a particular way.

Negative symptoms

Thoughts, feelings or behaviours normally present that are absent or diminished.

DSM-IV field trials

Reports on the first attempts to apply the diagnostic criteria laid down in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition in real-world settings.

Avolition

Inability to perform self-directed, purposeful activities.

Abulia

Reduced spontaneous verbal, motor, cognitive and emotional behaviours.

Akinetic mutism

Loss of ability to self-initiate limb movement and speech.

Anergia

Loss of energy.

Fatigue

Weariness or diminished ability following mental or physical activity.

Appetitive

Approach or goal-seeking phase of behaviour.

Consummatory

Completion or consummation phase of behaviour.

Learning

Acquisition of information, in this case to alter future behaviour.

Fluency

The number of examples generated of a verbal category (for example, words beginning with the letter F) or a non-verbal category (for instance, different patterns on a dot array using four straight lines).

Pavlovian–instrumental transfer

(PIT). The influence of an irrelevant conditioned stimulus on ongoing instrumental behaviour.

Iowa Gambling task

A neuropsychological test of decision making for reward.

Reward responsiveness

The development of a bias towards a more frequently rewarded stimulus.

Overfitting

When a model becomes too complex (has too many parameters) and begins to describe random error in the data rather than the relationships between variables.

Inverse temperature parameter

A constant in the softmax decision rule. It affects the steepness of the function around the inflexion point, resulting in more consistent choices at higher values.

Incremental learning

Learning over trials.

Reward-prediction error

A computational quantity indicating the difference between expected and actual outcomes.

Primary reward

Rewarding stimuli that facilitate survival of an organism or its offspring, such as food, water and sex.

Behavioural activation therapy

A psychological therapy that focuses on activity scheduling to encourage patients to approach activities that they avoid and on analysing processes (for example, rumination) that serve as forms of avoidance.

Cognitive behavioural therapy

A psychological therapy that aims to assist a person to change their thinking and behaviour by practising effective strategies to decrease symptoms and distress.

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Husain, M., Roiser, J.P. Neuroscience of apathy and anhedonia: a transdiagnostic approach. Nat Rev Neurosci 19, 470–484 (2018). https://doi.org/10.1038/s41583-018-0029-9

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