Beyond the “urge to move”: objective measures for the study of agency in the post-Libet era

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

Neurotransmitter deficits from frontotemporal lobar degeneration.

Frontotemporal lobar degeneration causes a spectrum of complex degenerative disorders including frontotemporal dementia, progressive supranuclear palsy and corticobasal syndrome, each of which is associated with changes in the principal neurotransmitter systems. We review the evidence for these neurochemical changes and propose that they contribute to symptomatology of frontotemporal lobar degeneration, over and above neuronal loss and atrophy. Despite the development of disease-modifying therapies, aiming to slow neuropathological progression, it remains important to advance symptomatic treatments to reduce the disease burden and improve patients' and carers' quality of life. We propose that targeting the selective deficiencies in neurotransmitter systems, including dopamine, noradrenaline, serotonin, acetylcholine, glutamate and gamma-aminobutyric acid is an important strategy towards this goal. We summarize the current evidence-base for pharmacological treatments and suggest strategies to improve the development of new, effective pharmacological treatments

Dopaminergic modulation of positive expectations for goal-directed action: evidence from Parkinson's disease.

Parkinson's disease (PD) impairs the control of movement and cognition, including the planning of action and its consequences. This provides the opportunity to study the dopaminergic influences on the perception and awareness of action. Here we examined the perception of the outcome of a goal-directed action made by medicated patients with PD. A visuomotor task probed the integration of sensorimotor signals with the positive expectations of outcomes (Self priors), which in healthy adults bias perception toward success in proportion to trait optimism. We tested the hypotheses that (i) the priors on the perception of the consequences of one's own actions differ between patients and age- and sex-matched controls, and (ii) that these priors are modulated by the levodopa dose equivalent (LDEs) in patients. There was no overall difference between patients and controls in the perceptual priors used. However, the precision of patient priors was inversely related to their LDE. Patients with high LDE showed more accurate priors, representing predictions that were closer to the true distribution of performance. Such accuracy has previously been demonstrated when observing the actions of others, suggesting abnormal awareness of action in these patients. These results confirm a link between dopamine and the positive expectation of the outcome of one's own actions, and may have implications for the management of PD.This work was funded by the Wellcome Trust [103838], Medical Research Council (MC-A060-5PQ30), and the James S McDonnell Foundation 21st Science Initiative award on Understanding Human Cognition; NW was funded by a Gates Cambridge Scholarship and the Raymond and Beverley Sackler Foundation.This is the final version of the article. It first appeared from Frontiers via http://dx.doi.org/10.3389/fpsyg.2015.0151

Progressive supranuclear palsy: diagnosis and management.

Treating patients with progressive supranuclear palsy (PSP) is both effective and rewarding. This review aims to share our experience in the proactive management of PSP, considering the patient, the family and the medical context in which the illness unfolds. There are many opportunities to assist your patients, ameliorate their symptoms, reduce their risks and harm, and guide them through the complex medical, social and legal minefield that characterises life with chronic neurological illness. We summarise the challenges of early diagnosis, consider PSP mimics and the role of investigations in excluding these, and discuss the available pharmacological and non-pharmacological treatment strategies to tackle the common and challenging symptoms of PSP. The best treatment will be patient centred and as part of a multidisciplinary team

Separation of Parallel Encoded Complex-Valued Slices (SPECS) From A Single Complex-Valued Aliased Coil Image

Purpose Achieving a reduction in scan time with minimal inter-slice signal leakage is one of the significant obstacles in parallel MR imaging. In fMRI, multiband-imaging techniques accelerate data acquisition by simultaneously magnetizing the spatial frequency spectrum of multiple slices. The SPECS model eliminates the consequential inter-slice signal leakage from the slice unaliasing, while maintaining an optimal reduction in scan time and activation statistics in fMRI studies. Materials and Methods When the combined k-space array is inverse Fourier reconstructed, the resulting aliased image is separated into the un-aliased slices through a least squares estimator. Without the additional spatial information from a phased array of receiver coils, slice separation in SPECS is accomplished with acquired aliased images in shifted FOV aliasing pattern, and a bootstrapping approach of incorporating reference calibration images in an orthogonal Hadamard pattern. Result The aliased slices are effectively separated with minimal expense to the spatial and temporal resolution. Functional activation is observed in the motor cortex, as the number of aliased slices is increased, in a bilateral finger tapping fMRI experiment. Conclusion The SPECS model incorporates calibration reference images together with coefficients of orthogonal polynomials into an un-aliasing estimator to achieve separated images, with virtually no residual artifacts and functional activation detection in separated images

Neuroinflammation in Lewy body dementia.

Neuroinflammation is increasingly recognized as a key factor in the pathogenesis of neurodegenerative conditions. However, it remains unclear whether it has a protective or damaging role. Studies of Alzheimer's disease and Parkinson's disease have provided much of the evidence for inflammatory pathology in neurodegeneration. Here we review the evidence for inflammation in dementia with Lewy bodies and Parkinson's disease dementia. Neuroinflammation has been confirmed in vivo using PET imaging, with microglial activation seen in Parkinson's disease dementia and recently in dementia with Lewy bodies. In Parkinson's disease and Parkinson's disease dementia, microglial activation suggests a chronic inflammatory process, although there is also evidence of its association with cognitive ability and neuronal function. Alpha-synuclein in various conformations has also been linked to activation of microglia, with a broad range of components of the innate and adaptive immune systems associated with this interaction. Evidence of neuroinflammation in Lewy body dementia is further supported by pathological and biomarker studies. Genetic and epidemiological studies support a role for inflammation in Parkinson's disease, but have yet to provide the same for Lewy body dementia. This review highlights the need to identify whether the nature and extent of microglial activation in Lewy body dementia can be linked to structural change, progression of domain specific cognitive symptoms and peripheral inflammation as a marker of central microglial pathology. Answers to these questions will enable the evaluation of immunotherapies as potential therapeutic options for prevention or treatment of dementia with Lewy bodies and Parkinson's disease dementia.This research was supported by the National Institute for Health Research (NIHR) Cambridge Dementia Biomedical Research Unit based at the Cambridge Biomedical Campus. James Rowe is supported by the Wellcome Trust.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.parkreldis.2015.10.00

Seeing what you want to see: priors for one's own actions represent exaggerated expectations of success.

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.We thank J. D. Carlin for his help with acquiring eye gaze data. This work was funded by the Wellcome Trust [088324], Medical Research Council and a Scholar Award from the James S. McDonnell Foundation 21st Century Science Initiative: understanding human cognition (to James B. Rowe) as well as the Human Frontier Science Program and the Royal Society Noreen Murray Professorship in Neurobiology (to Daniel M. Wolpert); Noham Wolpe was funded by a Gates Cambridge Scholarship and the Raymond and Beverley Sackler Foundation.This is the final version of the article. It first appeared from Frontiers via http://dx.doi.org/10.3389/fnbeh.2014.0023

Apathy is associated with reduced precision of prior beliefs about action outcomes.

Apathy is a debilitating syndrome that is associated with reduced goal-directed behavior. Although apathy is common and detrimental to prognosis in many neuropsychiatric diseases, its underlying mechanisms remain controversial. We propose a new model of apathy, in the context of Bayesian theories of brain function, whereby actions require predictions of their outcomes to be held with sufficient precision for "explaining away" differences in sensory inputs. In the active inference model, apathy results from reduced precision of prior beliefs about action outcomes. We tested this hypothesis using a visuomotor task in healthy adults (N = 47), with experimental manipulation of physical effort and financial reward. Bayesian modeling of performance and participants' perception of their performance was used to infer the precision of their priors. We confirmed that the perception of performance was biased toward the target, which was accounted for by relatively precise prior beliefs about action outcomes. These priors were consistently more precise than the corresponding performance distribution, and were scaled to effort and reward. Crucially, prior precision was negatively associated with trait apathy, suggesting that apathetic individuals had less precise prior beliefs about action outcomes. The results support a Bayesian account of apathy that could inform future studies of clinical populations. (PsycINFO Database Record (c) 2020 APA, all rights reserved)

Separating vascular and neuronal effects of age on fMRI BOLD signals.

Accurate identification of brain function is necessary to understand the neurobiology of cognitive ageing, and thereby promote well-being across the lifespan. A common tool used to investigate neurocognitive ageing is functional magnetic resonance imaging (fMRI). However, although fMRI data are often interpreted in terms of neuronal activity, the blood oxygenation level-dependent (BOLD) signal measured by fMRI includes contributions of both vascular and neuronal factors, which change differentially with age. While some studies investigate vascular ageing factors, the results of these studies are not well known within the field of neurocognitive ageing and therefore vascular confounds in neurocognitive fMRI studies are common. Despite over 10 000 BOLD-fMRI papers on ageing, fewer than 20 have applied techniques to correct for vascular effects. However, neurovascular ageing is not only a confound in fMRI, but an important feature in its own right, to be assessed alongside measures of neuronal ageing. We review current approaches to dissociate neuronal and vascular components of BOLD-fMRI of regional activity and functional connectivity. We highlight emerging evidence that vascular mechanisms in the brain do not simply control blood flow to support the metabolic needs of neurons, but form complex neurovascular interactions that influence neuronal function in health and disease. This article is part of the theme issue 'Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity'.This work is supported by the British Academy (PF160048), the Guarantors of Brain (G101149), the Wellcome Trust (103838), the Medical Research Council (SUAG/051 G101400; and SUAG/046 G101400), European Union’s Horizon 2020 (732592) and the Cambridge NIHR Biomedical Research Centre