The medial frontal-prefrontal network for altered awareness and control of action in corticobasal syndrome

Abstract

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.

Anticipating conflict: Neural correlates of a Bayesian belief and its motor consequence

“…Notably, because pre-SMA activity anticipates the motor outcome, this finding is in accord with the proposition that pre-SMA activity is driven by the engagement of attentional or working memory resources and not by stimulus-driven processes typical of reactive control (Criaud and Boulinguez, 2013). More broadly, the finding is consistent with numerous studies supporting a role of pre-SMA in response selection (Krieghoff et al, 2009; Mueller et al, 2007; Rae et al, 2014) and awareness of voluntary action (Ritterband-Rosenbaum et al, 2014; Wolpe et al, 2014). …”

The acute brain response to levodopa heralds dyskinesias in Parkinson disease

“…Moreover, the L‐dopa–induced increase in No‐Go activity in preSMA, but not in putamen, predicted individual severity of dyskinesias. Interestingly, activation of preSMA has been linked to internally generated movements and the intention to act,35 including the generation of involuntary actions 37. The connectivity of this region to motor regions is abnormal in PD38 and modulated by dopamine 39.…”

Alien Hand Syndrome

“…The pre-SMA has many cortical and subcortical connections important for volitional movement [44]. It connects to the dorsolateral prefrontal cortex, with increased functional connectivity during conscious intention; the basal ganglia to influence behavior according to desired goals; the insular cortex associated with the sense of self-agency; and possibly the premotor-posterior parietal network linked to the experience of conscious intent to act [59][60][61][62].…”

“…Wolpe et al investigated the mechanism by which voluntary actions are impaired in AHS [61]. Healthy controls and CBS patients were compared for Bintentional binding.T his marker of awareness of voluntary action measures the perception of timing of an action and its sensory effect.…”