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12 Apathy in neurological disease
  1. Sanjay Manohar1,2
  1. 1MRC Clinician Scientist, University of Oxford
  2. 2An Honorary Consultant Neurologist at the John Radcliffe Hospital

Abstract

Sanjay examines how reward motivates us, using eye movements and pupillometry. His work focuses on mechanisms of reward processing, and their disruption in focal brain damage and Parkinson’s disease.

Motivation is commonly disrupted in neurological and psychiatric disorders leading to clinical apathy. A traditional view is that motivation directs behaviour towards goals. According to this view, apathetic patients fail to select behaviours apposite to their goals. But clinically, these patients describe something more specific: a subjective inability to generate effortful action.

An alternative view focuses not on action selection, but on initiation and energisation. This view characterises motivation as driving true performance enhancement. Improving performance is costly, and motivation enables us to pay these costs. Apathy amounts to an inability to overcome costs, such as physical energy or mental concentration.

I studied the energisation of action using saccades – simple fast eye movements generated by well-understood circuits in the midbrain. When high rewards are at stake, saccades are earlier, more precise, and more energetic, indicating a higher signal-to-noise ratio in generating movements. Midbrain dopamine depletion in Parkinson’s disease makes eye movements insensitive to reward. Damage to the globus pallidus may also reduce reward sensitivity of eye movements, and responds to dopaminergic therapy. Rewards can even drive improvements when we are unable to influence the outcome, indicating their primitive inflexible nature. Energisation of action may therefore be controlled at a primitive brainstem level by reward expectation.

How might rewards influence such low-level mechanisms? One possibility is through autonomic arousal. Pupils dilate when incentives are expected, but this dilatation is attenuated in Parkinson’s disease. Pupil reactivity is restored with medication, and correlates with clinical apathy.

These effects in the eyes also generalise to voluntary motor systems, as measured by willingness to exert manual effort in order to obtain rewards. Apathetic individuals needed higher incentives to engage in effort, and this correlated with structural and functional connectivity between preSMA and cingulate cortex. Patients with PD showed a similar behaviour pattern that was reversed with dopaminergic drugs.

I conclude that human motivation, viewed in terms of energisation of behaviour, appears to operate at multiple levels in the brain, involving brainstem arousal mechanisms, basal ganglia dopamine, and motor cortex connectivity.

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