The control of voluntary movement changes markedly with age. A critical component of motor control is the integration of sensory information with predictions of the consequences of action, arising from internal models of movement. This leads to sensorimotor attenuation—a reduction in the perceived intensity of sensations from self-generated compared with external actions. Here we show that sensorimotor attenuation occurs in 98% of adults in a population-based cohort (n=325; 18–88 years; the Cambridge Centre for Ageing and Neuroscience). Importantly, attenuation increases with age, in proportion to reduced sensory sensitivity. This effect is associated with differences in the structure and functional connectivity of the pre-supplementary motor area (pre-SMA), assessed with magnetic resonance imaging. The results suggest that ageing alters the balance between the sensorium and predictive models, mediated by the pre-SMA and its connectivity in frontostriatal circuits. This shift may contribute to the motor and cognitive changes observed with age.

‘Intentional binding’ describes the perceived temporal attraction between a voluntary action and its sensory consequence. Binding has been used in health and disease as an indirect measure of awareness of action or agency, that is, the sense that one controls one’s own actions. It has been proposed that binding results from cue integration, in which a voluntary action provides information about the timing of its consequences or vice versa. The perception of the timing of either event is then a weighted average, determined according to the reliability of each of these two cues. Here we tested the contribution of cue integration to the perception of action and its sensory effect in binding, that is, action and tone binding, by manipulating the sensory reliability of the outcome tone. As predicted, when tone reliability was reduced, action binding was diminished and tone binding was increased. However, further analyses showed that cue integration accounted for changes in action binding, but not tone binding. These findings establish a role for cue integration in action binding and support the growing evidence suggesting that action and tone binding are, at least in part, driven by distinct mechanisms.

The volitional impairments of alien limb and apraxia are a defining feature of the corticobasal syndrome, but a limited understanding of their neurocognitive aetiology has hampered progress towards effective treatments. Here we combined several key methods to investigate the mechanism of impairments in voluntary action in corticobasal syndrome. We used a quantitative measure of awareness of action that is based on well-defined processes of motor control; structural and functional anatomical information; and evaluation against the clinical volitional disorders of corticobasal syndrome. In patients and healthy adults we measured ‘intentional binding’, the perceived temporal attraction between voluntary actions and their sensory effects. Patients showed increased binding of the perceived time of actions towards their effects. This increase correlated with the severity of alien limb and apraxia, which we suggest share a core deficit in motor control processes, through reduced precision in voluntary action signals. Structural neuroimaging analyses showed the behavioural variability in patients was related to changes in grey matter volume in pre-supplementary motor area, and changes in its underlying white matter tracts to prefrontal cortex. Moreover, changes in functional connectivity at rest between the pre-supplementary motor area and prefrontal cortex were proportional to changes in binding. These behavioural, structural and functional results converge to reveal the frontal network for altered awareness and control of voluntary action in corticobasal syndrome, and provide candidate markers to evaluate new therapies.

Cognitive decline is a common feature of Parkinson’s disease, and many of these cognitive deficits fail to respond to dopaminergic therapy. Therefore, targeting other neuromodulatory systems represents an important therapeutic strategy. Among these, the locus coeruleus-noradrenaline system has been extensively implicated in response inhibition deficits. Restoring noradrenaline levels using the noradrenergic reuptake inhibitor atomoxetine can improve response inhibition in some patients with Parkinson’s disease, but there is considerable heterogeneity in treatment response. Accurately predicting the patients who would benefit from therapies targeting this neurotransmitter system remains a critical goal, in order to design the necessary clinical trials with stratified patient selection to establish the therapeutic potential of atomoxetine. Here, we test the hypothesis that integrity of the noradrenergic locus coeruleus explains the variation in improvement of response inhibition following atomoxetine. In a double-blind placebo-controlled randomised crossover design, 19 people with Parkinson’s disease completed an acute psychopharmacological challenge with 40 mg of oral atomoxetine or placebo. A stop-signal task was used to measure response inhibition, with stop-signal reaction times obtained through hierarchical Bayesian estimation of an ex-Gaussian race model. Twenty-six control subjects completed the same task without undergoing the drug manipulation. In a separate session, patients and controls underwent ultra-high field 7 T imaging of the locus coeruleus using a neuromelanin-sensitive magnetisation transfer sequence. The principal result was that atomoxetine improved stop-signal reaction times in those patients with lower locus coeruleus integrity. This was in the context of a general impairment in response inhibition, as patients on placebo had longer stop-signal reaction times compared to controls. We also found that the caudal portion of the locus coeruleus showed the largest neuromelanin signal decrease in the patients compared to controls. Our results highlight a link between the integrity of the noradrenergic locus coeruleus and response inhibition in Parkinson’s disease patients. Furthermore, they demonstrate the importance of baseline noradrenergic state in determining the response to atomoxetine. We suggest that locus coeruleus neuromelanin imaging offers a marker of noradrenergic capacity that could be used to stratify patients in trials of noradrenergic therapy and to ultimately inform personalised treatment approaches.

Inhibitory control requires precise regulation of activity and connectivity within multiple brain networks. Previous studies have typically evaluated age-related changes in regional activity or changes in interregional interactions. Instead, we test the hypothesis that activity and connectivity make distinct, complementary contributions to performance across the life span and the maintenance of successful inhibitory control systems. A representative sample of healthy human adults in a large, population-based life span cohort performed an integrated Stop-Signal (SS)/No-Go task during functional magnetic resonance imaging (n = 119; age range, 18–88 years). Individual differences in inhibitory control were measured in terms of the SS reaction time (SSRT), using the blocked integration method. Linear models and independent components analysis revealed that individual differences in SSRT correlated with both activity and connectivity in a distributed inhibition network, comprising prefrontal, premotor, and motor regions. Importantly, this pattern was moderated by age, such that the association between inhibitory control and connectivity, but not activity, differed with age. Multivariate statistics and out-of-sample validation tests of multifactorial functional organization identified differential roles of activity and connectivity in determining an individual's SSRT across the life span. We propose that age-related differences in adaptive cognitive control are best characterized by the joint consideration of multifocal activity and connectivity within distributed brain networks. These insights may facilitate the development of new strategies to support cognitive ability in old age.SIGNIFICANCE STATEMENT The preservation of cognitive and motor control is crucial for maintaining well being across the life span. We show that such control is determined by both activity and connectivity within distributed brain networks. In a large, population-based cohort, we used a novel whole-brain multivariate approach to estimate the functional components of inhibitory control, in terms of their activity and connectivity. Both activity and connectivity in the inhibition network changed with age. But only the association between performance and connectivity, not activity, differed with age. The results suggest that adaptive control is best characterized by the joint consideration of multifocal activity and connectivity. These insights may facilitate the development of new strategies to maintain cognitive ability across the life span in health and disease.

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People perceive the consequences of their own actions differently to how they perceive other sensory events. A large body of psychology research has shown that people also consistently overrate their own performance relative to others, yet little is known about how these “illusions of superiority” are normally maintained. Here we examined the visual perception of the sensory consequences of self-generated and observed goal-directed actions. Across a series of visuomotor tasks, we found that the perception of the sensory consequences of one's own actions is more biased toward success relative to the perception of observed actions. Using Bayesian models, we show that this bias could be explained by priors that represent exaggerated predictions of success. The degree of exaggeration of priors was unaffected by learning, but was correlated with individual differences in trait optimism. In contrast, when observing these actions, priors represented more accurate predictions of the actual performance. The results suggest that the brain internally represents optimistic predictions for one's own actions. Such exaggerated predictions bind the sensory consequences of our own actions with our intended goal, explaining how it is that when acting we tend to see what we want to see.

The investigation of human volition is a longstanding endeavor from both philosophers and researchers. Yet because of the major challenges associated with capturing voluntary movements in an ecologically relevant state in the research environment, it is only in recent years that human agency has grown as a field of cognitive neuroscience. In particular, the seminal work of Libet et al. (1983) paved the way for a neuroscientific approach to agency. Over the past decade, new objective paradigms have been developed to study agency, drawing upon emerging concepts from cognitive and computational neuroscience. These include the chronometric approach of Libet’s study which is embedded in the “intentional binding” paradigm, optimal motor control theory and most recent insights from active inference theory. Here we review these principal methods and their application to the study of agency in health and the insights gained from their application to neurological and psychiatric disorders. We show that the neuropsychological paradigms that are based upon these new approaches have key advantages over traditional experimental designs. We propose that these advantages, coupled with advances in neuroimaging, create a powerful set of tools for understanding human agency and its neurobiological basis.