Lisa S. Aziz-Zadeh - US grants

DESCRIPTION (provided by applicant): Prosody, the melody and intonation of speech, is an extremely important and usually undervalued component of human communication. A significant component of human social interactions depends on prosody. The aim of the present project is to explore the application of recent approaches and concepts in human brain mapping to the study of perception and production of prosody. The initial goal of the research is to determine the degree to which perception and production of prosody rely on shared neural systems. This will be determined by an fMRI study of regions of overlap in the inferior frontal gyrus (IFG) during the perception and production of a meaningless phrase in different prosodic intonations. A second goal is to determine individual differences in this shared circuitry for perception and production. Here, we ask: Why are some people better than others at picking up subtle intonations in speech? Are such people more empathetic to the emotions of other people? Are they better at simulating another's prosodic input onto their own motor representations? To explore these questions, subjects will complete behavioral measures in prosody production, perception, and/or empathy. Scores on these measures will be correlated with brain activity in the region of the IFG previously identified as active in that individual for both prosody perception and production. Elucidating the neural basis of prosody will make an important contribution to the neurobiology of non-verbal communication, and by extension, of social communication. Furthermore, this research will improve the understanding of the communication deficits which result from brain injury, as well as the understanding of core deficits of socially isolating neurological and psychiatric disorders (such as stroke, traumatic head injury, autism). PUBLIC HEALTH RELEVANCE: One of the primary mechanisms of communication and social interaction is the exchange of prosodic information. Understanding the neural basis of prosody will make an important contribution to elucidating the neurobiology of non-verbal communication, and by extension, of social communication. Also, this is important for better understanding core deficits of socially isolating psychiatric and neurological disorders, such as autism and traumatic head injury.

DESCRIPTION (provided by applicant): The putative human mirror neuron system (MNS) is defined as motor brain regions that respond both when we perform an action, and when we observe similar actions being performed by others. Thus, the motor system may be engaged without overt movement. Rehabilitation of motor function after stroke is often challenging due to poor to absent voluntary movement ability. Methods in stroke rehabilitation that engage the MNS, for example, action observation, may help to rebuild motor function despite impairments by using covert practice as an alternative or complement to voluntary practice during physical therapy. The first component of the proposed study will identify the MNS in participants with stroke and damage to the primary motor or premotor cortex by measuring brain activity during action observation and execution in fMRI. The PIs aim to better understand how stroke and motor deficits affect the MNS, and to assess for common patterns of adaptive functional reorganization of the MNS after stroke. The second component of the proposed study will compare the whole brain response between observation of actions that use the counterpart to the paretic and the non-paretic limb. In the healthy brain, action observation is processed primarily by the MNS to support action understanding and imitation. After stroke, some observed actions may be difficult or impossible for the observer to perform due to motor impairments, and thus may engage a more deliberative processing supported by other multimodal cognitive brain regions commonly referred to as the "mentalizing system." The PIs aim to test the hypotheses that (1) observing actions that use the counterpart to the non-paretic limb engages the MNS;whereas (2) observing actions that use the counterpart to the paretic limb engages the MNS plus the mentalizing system. The PIs aim to better understand the cooperative roles of the MNS and the mentalizing system for imitation and social cognition after stroke. The overall aim of this research program is to inform the development of methods that engage the MNS to promote recovery from stroke, and to identify which patients might benefit most from therapy involving action observation. PUBLIC HEALTH RELEVANCE: The mirror neuron system (MNS) - motor brain regions that respond when we perform an action and when we observe similar actions being performed by others - may be engaged to promote motor recovery after stroke in patients with limited voluntary movement ability. By studying how the brain perceives actions after stroke, we will better understand how to use methods that engage the MNS for stroke rehabilitation, for example, action observation. By asking how the brain perceives actions that use the counterpart to the paretic limb, we will better understand the role of the MNS and the mentalizing system for action perception, imitation, and social cognition.

DESCRIPTION (provided by applicant): The putative human mirror neuron system (MNS) is defined as motor brain regions that respond both when we perform an action, and when we observe similar actions being performed by others. Thus, the motor system may be engaged without overt movement. Rehabilitation of motor function after stroke is often challenging due to poor to absent voluntary movement ability. Methods in stroke rehabilitation that engage the MNS, for example, action observation, may help to rebuild motor function despite impairments by using covert practice as an alternative or complement to voluntary practice during physical therapy. The first component of the proposed study will identify the MNS in participants with stroke and damage to the primary motor or premotor cortex by measuring brain activity during action observation and execution in fMRI. The PIs aim to better understand how stroke and motor deficits affect the MNS, and to assess for common patterns of adaptive functional reorganization of the MNS after stroke. The second component of the proposed study will compare the whole brain response between observation of actions that use the counterpart to the paretic and the non-paretic limb. In the healthy brain, action observation is processed primarily by the MNS to support action understanding and imitation. After stroke, some observed actions may be difficult or impossible for the observer to perform due to motor impairments, and thus may engage a more deliberative processing supported by other multimodal cognitive brain regions commonly referred to as the mentalizing system. The PIs aim to test the hypotheses that (1) observing actions that use the counterpart to the non-paretic limb engages the MNS; whereas (2) observing actions that use the counterpart to the paretic limb engages the MNS plus the mentalizing system. The PIs aim to better understand the cooperative roles of the MNS and the mentalizing system for imitation and social cognition after stroke. The overall aim of this research program is to inform the development of methods that engage the MNS to promote recovery from stroke, and to identify which patients might benefit most from therapy involving action observation.

DESCRIPTION (provided by applicant): While social communication deficits are considered the hallmark of Autism Spectrum Disorders (ASD), there is increasing evidence that sensorimotor deficits are also common in individuals with ASD diagnoses. A large body of research suggests that brain systems for execution and observation of actions are involved in higher social cognitive processes, including intention understanding and empathy, yet research has not yet clarified the extent to which motor deficits, such as imitation ability and motor planning, are central to ASD nor whether social and motor deficits are related neurobiologically in ASD. Understanding the neurobiological basis for ASD is crucial for developing effective therapies. However, researching the neurobiology of ASD is complicated by the heterogeneity of ASD; patients vary in symptomology- e.g., some individuals may show extensive impairment in motor functioning while others may not. Our study is designed to accommodate and understand the relationship between symptomalogical variation in ASD along the dimensions of both social and motor impairments. We aim to show how variations in social and motor symptoms in ASD relate to functioning in social and motor brain networks and functional connectivity between them. We propose to conduct functional MRI studies that compare 120 children on two continua of symptomology: (1) degree of social impairment (as measured by the SRS-2 and NEPSY-II), and (2) degree of motor impairment (as measured by the MABC-2 and Praxis Test). To ensure a range of impairment along these continua, children with ASD and children with Developmental Coordination Disorder (DCD, sometimes called dyspraxia) as well as typically developing (TD) children will participate in the study. The ASD group will range in motor impairment but should show high social impairment, while the DCD group will range in social impairment (generally lower than ASD) but high in motor impairment. Our fMRI tasks are likewise selected to range on a continuum from purely motor tasks to social processing tasks, beginning with motor (hand) execution and imitation tasks and progressing to tasks that incorporate increasing dimensions of social processing (e.g., non-emotional face imitation, emotional face imitation, intention understanding). By testing individuals who represent a continuum of social and motor deficits along a continuum of social and motor tasks we will be able to isolate and understand, in ASD, interactions between: (1) social and sensorimotor symptomologies; (2) activity in social and motor brain networks; and (3) functional connectivity between social and motor brain networks. This understanding will be crucial for developing individualized treatments for ASD. To our knowledge, no fMRI study has examined children with ASD across these multiple continua, nor directly compared them to children with DCD. In addition to contributing to our understanding of ASD, this study will better elucidate the neural mechanisms underlying DCD, which affects 6-13% of school-aged children.