Vikram S. Chib - US grants

DESCRIPTION (provided by applicant): Everyday tasks, such as handling and manipulating objects, may pose difficult challenges for survivors of stroke. The way in which our brain controls arm movements is likely to be shaped by our experience of interactions with objects and their mechanical and dynamic properties. Objects that we handle can be divided into two broad classes: rigid objects, such as a hammer, and objects with internal dynamics, such as a cup of water. Free reaching and interactions with rigid objects have been studied extensively, while interactions with objects with internal dynamics have not been adequately explored. Experiments presented in this proposal will focus on understanding how movements of the arm are controlled and coordinated when manipulating objects with internal dynamics. Aspects from modern control theory will be used to design and classify dynamic systems with which subjects interact. The experiments presented are centered on the hypothesis that healthy subjects learn to control objects with internal dynamics by developing an internal representation of their dynamics. Further, it is hypothesized that the ability to form an internal representation of these systems is contingent upon intrinsic object properties such as its controllability and observability.

[unreadable] DESCRIPTION (provided by applicant): Everyday tasks, such as handling and manipulating objects, may pose difficult challenges for survivors of stroke. The way in which our brain controls arm movements is likely to be shaped by our experience of interactions with objects and their mechanical and dynamic properties. During reaching movements information about surfaces and obstacles is implicitly incorporated into our actions. Much research has been performed to understand how humans acquire haptic information through touch. There has also been a great deal of work performed to understand how we generate reaching movements. While each of these topics in and of itself is important to understand how we interact with our environment, it is evident that true understanding of environmental interaction involves the simultaneous incorporation of the neural processes involved in haptic interaction as well as reaching movement. However, very little work has been performed to understand how movement is effected by haptic sense. This proposal will examine the neural processes involved during reaching movements in contact with fixtures. My goal is to bring haptic research and motor control research into a unified conceptual framework. I hypothesize that haptic interactions with surfaces can be described by the nervous system's combination of two distinct motor primitives: a position control primitive and a force control primitive. This proposal will present experiments and computational modeling to establish if these primitives do in fact exist in the nervous system, and if these primitives may be trained to enhance haptic perception. [unreadable] [unreadable] [unreadable]

How effortful a task feels is an integral aspect of human decision-making that shapes motivation. If a task feels very effortful we may be unwilling to perform the work required, whereas if a task feels less effortful we may be more likely to persevere. Despite the importance of these perceptions for decision-making, the behavioral and neural mechanisms of subjective effort valuation are not well understood. Furthermore, the National Institutes of Mental Health (NIMH) Research Domain Criteria (RDoC) has identified ?Effort Valuation / Willingness to Work? as a key subconstruct for understanding deficits in motivated performance in mental disorders. The goal of this proposal is to understand the mechanisms of subjective valuation of physical and cognitive effort, and the common and distinct systems that underlie these representations. To this end, we will use a combination of experiments in healthy human participants, computational modeling of behavior, and functional magnetic resonance imaging (fMRI). In Aim 1 we will identify common and distinct physical and cognitive effort valuation mechanisms. We will computationally model participants' subjective valuation of physical and cognitive effort to test if there are similarities in subjective preferences for these different types of effort. We will use model-based fMRI to examine the common and distinct brain regions that encode the subjective valuation of physical and cognitive effort, and the network of brain regions that incorporate such preferences to motivate effortful engagement. In Aim 2 we will investigate the behavioral and neural mechanisms by which physical and cognitive fatigue effect effort valuation. We will fatigue participants with sustained physical or cognitive exertion and examine how being in a fatigued state influences subjective valuation of physical and cognitive effort; and associated signals in the brain's valuation network. In Aim 3 we will explore how motivational state modulates decisions to exert physical and cognitive effort. We will pair choices for physical and cognitive effort with motivational cues (i.e., cues that formerly predicted reward) in order to modulate participants' motivational state. This manipulation will allow us to behaviorally and neurally dissociate motivation from effort valuation in order to understand how these processes interact to give rise to motivated physical and cognitive engagement. In sum, our proposed studies will have a broad impact on the field of decision-making by dissecting the behavioral and neural mechanisms responsible for physical and cognitive effort valuation. In the long term, these studies may reveal novel behavioral and neural markers to aid in the study, classification, and treatment of amotivation.

PROJECT SUMMARY A major hurdle to compliance with rehabilitation therapies is poor effort on the part of patients, caused by fatigue and feelings of insurmountable effort. If a physical exercise feels very effortful one may be unwilling to exert the effort required, whereas if an exercise feels less effortful one may be more likely to persevere. Despite the ubiquity of effort-based judgments, and their disruption in a variety of neurological conditions, the mechanisms responsible for the subjective valuation of physical effort have received limited investigation. The central hypothesis of this proposal is that an individual's subjective valuation of effort is reflected in her inherent excitability of motor cortex, and that this metric is sensitive to disease state. We will perform experiments in healthy human participants; and a group of participants with multiple sclerosis (MS). We have developed a novel effort-based choice paradigm that allows us to obtain a precise objective measure of an individual's subjective valuation of effort. We will use this approach, in combination with computational modeling, functional magnetic resonance imaging (fMRI), and noninvasive brain stimulation, to investigate the mechanisms responsible for the subjective valuation of effort. In Aim 1 we will study how motor physiology influences subjective effort valuation in healthy participants. We will use transcranial magnetic stimulation (TMS) to non invasively probe the physiological properties of participants' motor cortex; and we will have the same participants make decisions about effort while they are scanned with fMRI, and use this data to computationally model their subjective valuation of effort and associated brain activity. These experiments will allow us to test the relationships between an individual's representations of effort value and motor physiology. In Aim 2 we will identify the mechanisms of subjective effort valuation in patients with MS. We will use TMS and fMRI to investigate the neural and behavioral representations of effort value in MS. These experiments will shed light on the neural circuits that are disrupted in individuals with MS, suffering from feelings of fatigue. Our studies will have a broad impact on the fields of decision-making and motor control by dissecting the fundamental mechanisms responsible for physical effort valuation. This work will provide an understanding of the neural mechanisms underlying disrupted feelings of effort in MS, and may eventually reveal neurobehavioral markers and neuromodulatory interventions to aid in the prediction and treatment of rehabilitation non-compliance.