William M. Perlstein - US grants

DESCRIPTION: (Adapted from applicant's abstract) This resubmission of an application (K01 MH01857-01) for an MRSDA outlines a program of training and research in the cognitive neuroscience of emotion in healthy and: anxiety-disordered subjects. The candidate is a new Assistant Professor with previous training in clinical-cognitive neuroscience. His recent work has focused on working memory and prefrontal cortex functioning in severe psychopathology. This proposal seeks to build on this work and develop the candidate's research skills in the areas of affective information processing, autonomic and somatic psychophysiology, and hemodynamic and electroencenphalographic human brain imaging methods. The candidate will be mentored in the design and conduct of a set of related studies using standardized affective stimuli in a cognitive task that simultaneously engages prefrontal cortex and functionally-connected emotion-critical brain regions. The overall purpose of this research is to develop a new experimental approach-based on psychophysiological recording of bodily activity, and complementary measures of brain activity-to study the interaction between high-level cortex and deeper brain structures that mediate normal and abnormal emotional experience and its physiological expression. To achieve these goals, the candidate will pursue career development activities which build upon his existing skills and enhance his expertise in: (a) The design, conduct, and analysis of high-density electroencephalographic and functional MRI studies; (b) developing conceptual and practical skills to integrate these brain imaging methods; (c) developing skills necessary for assessment and empirical measurement of anxiety disorder symptomatology; and (d) extending a knowledge base of functional neuroanatomy and circuitry based on animal models to inform this research approach. The following specific aims are addressed: (a) Develop a probe of prefrontal cortical and emotion-critical deep cortical and subcortical structures; (b) employ imaging methods to track probe effects on affect-working memory interactions in the brain; and (c) apply probe and imaging methods to clinically fear-disordered patients to test hypotheses concerning regional brain interactions and their dysfunction. The preceptor, Dr. Peter Lang, will provide mentorship in cooperation with expert consultants to ensure a coherent and intellectually rigorous framework for career development and research conduct. This training, which can not be accomplished under any other funding mechanism, will enable the candidate to combine, in the most informative ways possible, clinical and cognitive psychology, electrocortical and hemodynamic measures of brain activity, and anxiety disorder symptom assessment. Completion of this award would place the candidate in the position to continue programmatic research along these lines and provide a unique contribution to the cognitive neuroscience study of emotion and its disorders.

[unreadable] DESCRIPTION (provided by applicant): Closed head injury (CHI) is a significant public health issue in the US and is associated with impairments in cognitive functioning, particularly in the domain of "executive" control. The primary aim of this exploratory grant is to examine the componential nature and neural bases of cognitive control dysfunction in CHI. The specific aims are to: 1) Identify the most critical components of cognitive control dysfunction across the continuum of CHI severity; 2) identify the neural bases of this dysfunction; and 3) determine relationships among cognitive control dysfunction, its neural bases, and manifest symptomatology in CHI. The specific hypotheses motivating the proposed research are that: 1) Patients with acute CHI exhibit severity dependent impairments in at least one of several components of cognitive control (i.e., implementation of cognitive control, detecting processing conflicts, performance monitoring); 2) regions of the frontal cortex mediate this impairment; and 3) aspects of these impairments and associated neural dysfunction are related to patient symptomatic experience. Study methods will examine adult mild, moderate and severe acute CHI patients while performing a novel cognitive task designed to temporally dissociate components of cognitive control in combination with measures of task-related neural activity. High-density event-related potentials will be used to dissociate strategic processes supporting the implementation of cognitive control, and evaluative processes supporting the detection of processing conflicts and performance monitoring. Functional magnetic resonance imaging will be used to identify the neural systems supporting these processes in healthy individuals, and those exhibiting dysfunction in patients with CHI. Self- and other-reported measures of symptom experience will provide information in the domains of cognitive, behavioral and affective expression, which will then be examined for relationships with measures of cognitive control and task-related brain activity. Accomplishing the aims outlined in this proposal will provide the foundation for future longitudinal studies to examine the temporal course of cognitive recovery, the mechanisms of successful intervention, and the design and evaluation of behavioral and pharmacological intervention strategies. [unreadable] [unreadable]