1988 — 1993 |
Hillis, Argye |
U01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. U10Activity Code Description: To support clinical evaluation of various methods of therapy and/or prevention in specific disease areas. These represent cooperative programs between sponsoring institutions and participating principal investigators, and are usually conducted under established protocols. |
Central Vein Occlusion Study -- Coordination Center @ Scott and White Memorial Hospital
This application is for the Coordinating Center of a national collaborative randomized controlled clinical trial of photocoagulation treatment for central vein occlusion. The study will be conducted in nine clinical centers, with the Reading Center at the Bascom Palmer Eye Institute (University of Miami) and the Coordinating Center at Scott and White Hospital in Temple, Texas (Texas A&M University). Patients will be entered into four study groups: Nonperfused (Group N); Macular Edema (Group M); Perfused (Group P); and Indeterminant (Group I). Eyes in the first two groups will be randomly assigned to photocoagulation treatment and a control group. Patients in groups P and I will be followed for natural history and for possible later entry into the randomized study. Projected recruitment is 792 patients: 238 in in Group N; 396 in Group P and 158 in Group I. About half of these patients will also be in Group M. Patients will be recruited for the first three years of this five year study and all patients will be followed for three years or until termination of the study. The study is designed to provide information regarding whether or not photocoagulation is efficacious in preventing neovascularization and subsequent neovascular glaucoma in eyes with central vein occlusion and retinal ischemia and whether or not photocoagulation treatment is useful in preserving visual acuity in eyes with CVO and macular edema. Information collected at baseline and each follow-up visit will be forwarded to the Coordinating Center for processing and analysis. A data monitoring committee will review interim results of the study every six months.
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0.903 |
1989 — 1990 |
Hillis, Argye |
U01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. U10Activity Code Description: To support clinical evaluation of various methods of therapy and/or prevention in specific disease areas. These represent cooperative programs between sponsoring institutions and participating principal investigators, and are usually conducted under established protocols. |
Central Vein Occlusion Study @ Scott and White Memorial Hospital
This application is for the Coordinating Center of a national collaborative randomized controlled clinical trial of photocoagulation treatment for central vein occlusion. The study will be conducted in nine clinical centers, with the Reading Center at the Bascom Palmer Eye Institute (University of Miami) and the Coordinating Center at Scott and White Hospital in Temple, Texas (Texas A&M University). Patients will be entered into four study groups: Nonperfused (Group N); Macular Edema (Group M); Perfused (Group P); and Indeterminant (Group I). Eyes in the first two groups will be randomly assigned to photocoagulation treatment and a control group. Patients in groups P and I will be followed for natural history and for possible later entry into the randomized study. Projected recruitment is 792 patients: 238 in in Group N; 396 in Group P and 158 in Group I. About half of these patients will also be in Group M. Patients will be recruited for the first three years of this five year study and all patients will be followed for three years or until termination of the study. The study is designed to provide information regarding whether or not photocoagulation is efficacious in preventing neovascularization and subsequent neovascular glaucoma in eyes with central vein occlusion and retinal ischemia and whether or not photocoagulation treatment is useful in preserving visual acuity in eyes with CVO and macular edema. Information collected at baseline and each follow-up visit will be forwarded to the Coordinating Center for processing and analysis. A data monitoring committee will review interim results of the study every six months.
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0.903 |
1994 — 1995 |
Hillis, Argye |
U10Activity Code Description: To support clinical evaluation of various methods of therapy and/or prevention in specific disease areas. These represent cooperative programs between sponsoring institutions and participating principal investigators, and are usually conducted under established protocols. |
Central Vein Occlusion @ Scott and White Memorial Hospital
This application is for the Coordinating Center of a national collaborative randomized controlled clinical trial of photocoagulation treatment for central vein occlusion. The study will be conducted in nine clinical centers, with the Reading Center at the Bascom Palmer Eye Institute (University of Miami) and the Coordinating Center at Scott and White Hospital in Temple, Texas (Texas A&M University). Patients will be entered into four study groups: Nonperfused (Group N); Macular Edema (Group M); Perfused (Group P); and Indeterminant (Group I). Eyes in the first two groups will be randomly assigned to photocoagulation treatment and a control group. Patients in groups P and I will be followed for natural history and for possible later entry into the randomized study. Projected recruitment is 792 patients: 238 in in Group N; 396 in Group P and 158 in Group I. About half of these patients will also be in Group M. Patients will be recruited for the first three years of this five year study and all patients will be followed for three years or until termination of the study. The study is designed to provide information regarding whether or not photocoagulation is efficacious in preventing neovascularization and subsequent neovascular glaucoma in eyes with central vein occlusion and retinal ischemia and whether or not photocoagulation treatment is useful in preserving visual acuity in eyes with CVO and macular edema. Information collected at baseline and each follow-up visit will be forwarded to the Coordinating Center for processing and analysis. A data monitoring committee will review interim results of the study every six months.
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0.903 |
1999 — 2001 |
Hillis, Argye E. |
K23Activity Code Description: To provide support for the career development of investigators who have made a commitment of focus their research endeavors on patient-oriented research. This mechanism provides support for a 3 year minimum up to 5 year period of supervised study and research for clinically trained professionals who have the potential to develop into productive, clinical investigators. |
Neural Basis of Anomia and Neglect in Hyperacute Stroke @ Johns Hopkins University
DESCRIPTION (adapted from the applicant's abstract): The proposed study utilizes the investigator's experience in speech-language pathology and cognitive neuropsychology as well as her training in clinical neurology to identify brain- behavior relationships in hyperacute stroke (within 24 hours of onset), that is, before the opportunity for brain reorganization. The investigation will focus on the characterization and localization of naming disorders and hemispatial neglect. Cognitive testing in the hyperacute period, at 3 days and at 3 months will evaluate the mental representations and processes underlying naming and spatial attention. Areas of hypometabolism, hypoperfusion, and actual infarct associated with specific impairments in these cognitive domains will be identified with magnetic resonance imaging techniques of Perfusion Imaging (MRPI) and Diffusion Weighted Imaging (DWI) and with follow-up conventional MRI. The correlations between acute functional impairments of specific cognitive representations and physiologic or structural lesions will be used to predict the size and site of infarcted or hypoperfused neural tissue from cognitive impairments in hyperacute stroke, and will thus be useful in treatment decisions and prognosis.
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0.958 |
2002 — 2006 |
Hillis, Argye E. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neural Basis of Lexical Deficits in Hyperacute Stroke @ Johns Hopkins University
DESCRIPTION (provided by applicant): The question of how and where language is represented in the brain has been an area of intense investigation for more than a century. The various methodologies that have addressed this question each have their own limitations, and the various methodologies have yielded divergent answers. However, some conclusions have been robust across investigations: (1) a given language task (say, naming a picture) requires a number of distinct processes or levels of mental representation; (2) there is some specialization across cortical regions, such that each distinct level of processing may take place in separate brain regions; thus, a whole network of regions might subserve the task; (3) these structure/function relationships are fairly similar across most individuals, but can change in response to brain damage. Yet, there are many unanswered questions. What are the precise areas that are either necessary or sufficient for any given language process? How fine-grained are the structure/function relationships with respect to language in the brain? That is, for any given level of representation, such as a lexical (word form) representation, are there distinct regions for different types of words (e.g., nouns versus verbs) and/or for different output modalities (e.g., spoken versus written) for the same word? The goal of this project is to address these questions with a novel approach utilizing MR perfusion weighted imaging (PWI) and diffusion weighted imaging (DWI), along with testing of language processing at the same time, in subjects <24 hours post onset of stroke. The major hypothesis is that PWI and DWI with concurrent language testing can reveal areas of neural dysfunction, with or without structural damage, associated with disruption of each level of representation underlying lexical tasks such as naming, reading, or spelling a word. The imaging and language tests together are expected to show that there are distinct areas of cortex that are essential for the processing of phonological representations (or spoken word forms) versus orthographic representations (or written word forms), and that the regions are specific to a particular grammatical word class (e.g., nouns versus verbs). It is also predicted that still other regions are crucial for representing the meanings of various types of words, or for more peripheral components of speech or written output for all types of words. It is also hypothesized that repeat DWI, PWI, and language tests at 3 days post-onset will reveal mechanisms of early recovery of lexical functions in acute stroke.
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0.958 |
2004 — 2007 |
Hillis, Argye E. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neural Basis of Unilateral Spatial Neglect @ Johns Hopkins University
DESCRIPTION (provided by applicant): Accumulating evidence from single cell recording studies in primates indicates that neurons encode spatial information in a variety of reference frames, which may be transformed to a single, common viewer (eye-) centered representation in posterior parietal cortex used for planning movements. Functional imaging studies also indicate that posterior parietal cortex is crucial for localization of objects in space (essential for planning saccades or reaching) in humans, whereas temporal cortex is crucial for object and word recognition. Lesions studies in both monkeys and humans indicate that spatial representations with different reference frames can occasionally be separately disrupted by brain damage, variously impairing action or perception on the side contralateral to the brain lesion (causing different forms of unilateral spatial neglect, or USN). However, the cortical organization of such spatial representations is fundamentally different in primates vs. humans, as indicated by the fact that lesions in either hemisphere cause comparable USN in monkeys, whereas right cortical lesions cause more common, severe, and persistent USN in humans. Conflicting results regarding the neural correlates of various types of USN in humans have been reported, which may be due to limitations of chronic lesion-deficit correlation studies. The goal of this project is to identify the nature and the neural basis of different types of USN with a novel approach utilizing MR perfusion weighted imaging (PWl) and diffusion weighted imaging (DWl), along with testing of USN at the same time, in subjects <24 hours post onset of stroke, and at three days after onset. This method complements functional imaging studies and avoids many of the pitfalls of chronic lesion-deficit studies. PWI shows regions of hypoperfused, dysfunctional tissue, while DWl reveals densely ischemic or infarcted tissue, in acute stroke. The major hypothesis is that PWl and DWl with concurrent USN testing can reveal areas of neural dysfunction, with or without structural damage, associated with USN in different reference frames or in different tasks, before substantial reorganization. It is further hypothesized that restoration of tissue function in a given region (by restoring regional blood flow) will result in resolution of specific types of USN. Results are expected to reveal distinct areas of cortex crucial for computing spatial representations with different reference frames, and to reveal mechanisms of USN in tasks with different purposes.
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0.958 |
2004 — 2006 |
Hillis, Argye |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Reperfusion Therapy in Stroke Candidates Using Mr Perfusion &Diffusion Imaging @ Hugo W. Moser Res Inst Kennedy Krieger |
0.909 |
2007 — 2016 |
Hillis, Argye E. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neural Bases of Language and Cognitive Deficits in Acute Stroke and Recovery @ Johns Hopkins University
DESCRIPTION (provided by applicant): In the previous funding period we identified areas of the brain essential for distinct cognitive processes underlying lexical tasks, by identifying areas of tissue dysfunction associated with specific lexical deficits immediately after left hemisphere ischemic stroke in 317 patients. We used MRI scans, including diffusion weighted imaging and perfusion weighted imaging, to identify dysfunctional tissue and language tests to identify deficits in lexical processing within 24 hours of stroke onset. We also determined which deficits recovered in association with tissue recovery in specific regions by Day 3-5. We found new evidence that lexical tasks such as naming, reading, and spelling depend on overlapping networks of brain regions, but that distinct cognitive processes underlying these tasks depend differentially on one or more of the neural regions in this network. In this competitive continuation we propose to use this methodology to investigate the neural regions critical for a number of language and cognitive processes that all have been hypothesized to rely on Broca's area, or have been reported to be impaired in patients with Broca's aphasia, or both. We will test specific hypotheses about cognitive processes that depend on Broca's area (based on functional imaging and chronic lesion studies), and hypotheses about cognitive/linguistic deficits underlying Broca's aphasia (generated from psycholinguistic and neuropsychological studies). We aim to determine what cognitive functions underlying language are specifically associated with acute damage/dysfunction of Broca's area and/or chronic damage to Broca's area. In addition, we aim to determine whether or not impairments of these functions are associated with the clinical diagnosis of Broca's aphasia, or components of this clinical syndrome, in the acute or chronic stage. This research is expected to clarify the role of Broca's area in language and cognitive processing, and to clarify the relationship between deficits in cognitive functions attributed to Broca's area and the language characteristics of Broca's aphasia (e.g. agrammatic speech, apraxia of speech, and asyntactic comprehension). We expect the results to contribute to the understanding of the neural and cognitive mechanisms underlying sentence comprehension and production. The results will also have clinical impact by aiding in functional prognosis in acute stroke and in identifying appropriate candidates for intervention to restore blood flow in patients with language deficits due to acute stroke.
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0.958 |
2009 — 2013 |
Hillis, Argye E. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neural Bases of Empathy and Prosody @ Johns Hopkins University
DESCRIPTION (provided by applicant): In the previous funding period this project focused on identifying areas of the brain essential for spatial attention in distinct reference frames and modalities, by identifying areas of tissue dysfunction associated with specific spatial attention deficits immediately after right or left hemisphere ischemic stroke in 661 patients. MRI scans, including diffusion weighted imaging and perfusion weighted imaging, were used to identify dysfunctional tissue, along with cognitive tests to identify specific types of hemispatial neglect within 24 hours of stroke onset. Repeat MRI and cognitive testing determined which deficits recovered in association with tissue recovery in specific regions by Day 3- 5. This work has shed some light on mechanisms of spatial attention and their neural correlates, as well as the cognitive impairments that underlie various types of hemispatial neglect. In the course of this work, the investigators noted the frequency and importance of other deficits that are frequently associated neglect -- such as loss of empathy and emotional expression -- particularly in individuals with right hemisphere stroke. These deficits have an enormous impact on the dignity of the individuals and on their relationships with spouses and other caregivers. Along with hemispatial neglect, they are among the most common and disabling consequences of right hemisphere stroke. In the next funding cycle, the project will use the same innovative methodology to identify and characterize the nature and neural correlates of two potentially related impairments that frequently co-occur with neglect: (1) loss of empathy and (2) affective aprosodia (impairment in one or more aspects of understanding and producing language with appropriate intonation, rate, pauses, and stress to convey emotion), and their association with hemispatial neglect, loss of sympathy, and other negative behavioral changes perceived by caregivers. The effects of age, brain volume, stroke volume, and metabolic factors, as well as location of dysfunctional tissue on the degree of impairment will be determined. Patients will be studied longitudinally through 6 months, to determine the factors, such as improved regional blood flow, that contribute to recovery. PUBLIC HEALTH RELEVANCE: This research will contribute to the understanding of the neural and cognitive mechanisms underlying the ability to recognize and respond to emotions of others and to the ability to understand and express emotions through tone of voice, by studying stroke patients in whom these abilities are often impaired. A better understanding of these impairments and how they recover is essential, because of the impact of these deficits on the interpersonal relationships of stroke survivors. The results will also have clinical impact by aiding in functional prognosis in acute stroke, and in identifying appropriate candidates for intervention to restore blood flow in patients with such deficits due to acute stroke.
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0.958 |
2009 — 2014 |
Hillis, Argye E. |
R25Activity Code Description: For support to develop and/or implement a program as it relates to a category in one or more of the areas of education, information, training, technical assistance, coordination, or evaluation. |
Ninds Research Education Programs For Residents and Fellows in Neurology and Neur @ Johns Hopkins University
SUMMARY Residency in an academic neurology program is the ideal setting for a young physician to develop into a clinician-scientist in the neurosciences. Senior faculty in every subspecialty are available to assist residents in starting a basic science, clinical, or translational research program, to help them start a successful clinical practice, to provide a model in balancing the research and clinical work, and to mentor them in publishing and obtaining research funding. However, funds for both research and clinical training are tight, and there previously had been no financial support for time devoted to research training during residency. This R25 mechanism will fill this need for outstanding residents who will be the future leaders in neurology research. However, there is also a need for developing future mentors, who will be exceptional role models and mentors for the increasingly diverse resident applicants in the coming years. Our goal is provide the highest level of education in research skills, research ethics, data analysis and reporting, and career development for clinician-scientists, who will be successful in obtaining funding for their mentored (and later, independent) productive research. Another goal is for our senior mentors, who are clinician scientists with extensive experience in training young physician investigators, to mentor more junior mentors with successful research programs who will be able to carry out our primary goal in future years. Our junior mentors are a racially and ethnically diverse group of men and women who will be exceptional role models for the diverse set of current and future residents and fellows in this program. To meet these goals, each resident who participates in this program will be paired with both a senior mentor and junior research mentor, who will assist the resident in obtaining necessary skills for his or her project and help guide the resident through all steps of a successful research project in the laboratory of one of the mentors and/or their close colleagues with productive, funded research. We will track success of each resident with respect to awards of funding for mentored research (K08 or K23 awards), independent research grants, and publications, for a minimum of 10 years after residency.
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0.958 |
2014 — 2021 |
Hillis, Argye E. |
R25Activity Code Description: For support to develop and/or implement a program as it relates to a category in one or more of the areas of education, information, training, technical assistance, coordination, or evaluation. |
Research Education Program For Residents and Fellows in Neurology @ Johns Hopkins University
DESCRIPTION (provided by applicant): This Research Education Program is designed to provide teaching in the science of investigation, in addition to protected time, structure, resources, mentoring, and research skills training to diverse and outstanding neurology residents who will become the next generation of leaders in clinical neuroscience research. Some unique aspects of our programs are (1) that we are able to provide nine months of 80% protected time for research education and research participation during residency; and (2) that we pair each participant with both a Senior Mentor and a Junior Mentor who are closely engaged in the participant's research and training. The Hopkins environment is highly collaborative across disciplines and provides superb research education resources, through the Clinical and Translational Science Award, the Bloomberg School of Public Health, The Brain Sciences Institute, Neuro-ICE (Institute of Cellular Engineering), the Kirby Functional Imaging Center, The Mind Brain Institute, and many other interdisciplinary programs. This program is also designed to develop a diverse group of talented and inspirational mentors who will continue to serve role models and effective coaches, enabling residents and fellows to become independent clinician scientists with a passion for discovery in the mechanisms of neurological disease, improving diagnosis and treatment of neurological disease, and facilitating recovery of neurological function. We accomplish this aim through mentoring of Junior Mentors by Senior Mentors, with structured feedback and evaluations. To date this grant has supported 10 exceptional residents, who all remain actively engaged in research. Three have faculty positions in medical schools, and two of these have applied for K23 funding (pending review). The others remain in residency or fellowship training. The program has also been exceptionally successful in recruiting participants and Junior Mentors from minorities that are traditionally under-represented in science. We have also been very successful in including women both as mentors and mentees.
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0.958 |
2017 — 2021 |
Hillis, Argye E. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Recovery of Affective Prosody After Stroke @ Johns Hopkins University
Research on stroke outcomes has focused almost exclusively on recovery of very basic functions, such as feeding oneself, bathing, walking, and speaking. However, impairments in social function, including impaired recognition and expression of emotions, are also common consequences of stroke. Diminished affective prosody (understanding and conveying emotion through vocal intonation, rate, pauses, and stress), is a particularly common impairment after right hemisphere stroke, and can be misinterpreted as loss of empathy, apathy, or depression (problems that can also be important consequences of stroke, but require different management). Appropriate expression and recognition of prosody is also critical for effective social interaction. Despite the impact of diminished affective prosody on quality of life and function in society, these disorders are understudied, and there are few evidence-based treatments for these disorders. To design effective and efficient interventions that will improve quality of life and facilitate full participation in society, and to plan treatment trials to evaluate the interventions, we first need to lay the groundwork. We need to identify the perceptual, cognitive, and motor deficits that can disrupt affective prosody; characterize the natural history of recovery and variables that influence recovery of these deficits; and identify the neural networks that support these functions and their recovery. Identifying the networks that support these processes will allow us to select interventions that will help recruit these networks to augment behavioral therapy. In this project we will integrate: 1) detailed longitudinal analysis of the impaired perceptual, cognitive, and motor processes underlying prosody in each patient at four time points over the first year after stroke, and (2) detailed longitudinal analysis of the structural and functional lesions (e.g., in right ventral and dorsal streams) and functional connectivity between critical regions in each patient at the same four time points over the first year after stroke, and (3) analyses of variables (such as timing and doses of antidepressants) and co-morbidities (such as depression) that influence recovery. By integrating these methods, we will have a better understanding of the natural recovery trajectories and the neural basis of both the impairments and their recovery. Combining these datasets will allow us to test specific hypotheses about the perceptual, cognitive, and motor processes and their neural mechanisms underlying affective prosody and about recovery of these process after disruption due to focal lesions. Furthermore, by building linear mixed effect models to identify the potential impact of independent variables on outcomes, we will be able to prognosticate and identify variables that modify prognosis. These three sets of data will also provide a foundation for designing treatments that combine behavioral therapy with medications or neurally-targeted interventions such as transcranial direct current stimulation. Integration of these datasets will also provide evidence to guide who needs treatment, when to treat, and where in the brain to treat these functions.
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0.958 |
2018 — 2021 |
Hillis, Argye E. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neural Bases of Recovery of Language in the First Year After Stroke @ Johns Hopkins University
Aphasia is among the most common and disabling consequences of stroke. Language rehabilitation is frequently effective, but recovery is often incomplete and slow. A few small studies have shown that medications, including cholinesterase inhibitors and selective serotonin reuptake inhibtors (SSRIs), can augment language rehabilitation to enhance aphasia recovery. These investigations have been based on strong theoretical grounds, as cholinesterase inhibitors and SSRIs increase the availability of neurotransmitters that are essential for neuroplasticity. But results have been inconsistent, with small effects. Aphasia treatment could be substantially advanced by a large randomized trial showing clinically significant benefit of specific medications, along with language intervention. However, clinical trials are premature because the most effective medications and the characteristics of individuals most likely to respond have not yet been identified. In previous funding cycles, we have shown that the volume and location of stroke, other medications that might block the effect of the tested medication, and the health of the uninfarcted tissue might strongly affect the response to treatment. Furthermore, it is essential to base the timing of intervention on empirical evidence regarding the time at which intervention has the greatest effect. We propose to obtain all of this essential information to design a rational randomized trial of medications (versus placebo), along with language therapy, that will have the greatest probability of identifying clinically important and reliable effects. We will obtain this new information in a prospective, longitudinal study of language recovery and multimodality brain imaging at four time points after stroke (Week 1, Month 3, Month 6, and Month 12). We will not attempt to manipulate medications, as there are insufficient data on their effects. Rather, medication use (prescribed at the discretion of the physician team) will be recorded at each visit, and confirmed through pharmacy records and pill counting. Our progress and record of enrolling large numbers of participants show that we will have sufficient power to find any significant effects. The structural and resting state fMRI studies will help us understand the mechanisms of recovery (or decline) after stroke. We hypothesize that beneficial medications will enhance connectivity between critical nodes in the language network, while medications with a negative effect (by blocking neurotransmitters or their receptors) will be associated with decrease in connectivity between these nodes. The brain imaging and behavioral data together will also help us achieve another important goal, aligned with the mission of NIDCD, to improve prognosis for aphasia recovery at an individual level. Identifying lesion and brain characteristics, medications, demographics, and number of rehabilitation sessions that independently contribute to aphasia recovery will allow us to better predict who is likely to achieve the greatest recovery and under what conditions, as well as provide the critical basis for a well- designed, multicenter clinical trial that will likely have an important impact on aphasia rehabilitation.
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0.958 |
2019 |
Hillis, Argye E. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
The Neural Basis of Impaired Affective Prosody in Alzheimer's Disease and Frontotemporal Degeneration @ Johns Hopkins University
PROJECT SUMMARY Many patients with Alzheimer?s Disease (AD) and Frontotemporal Degeneration (FTD) have impairments in social function, including impaired recognition and expression of emotions in speech. Diminished affective prosody (understanding and conveying emotion through vocal intonation, rate, pauses, and stress) often appears even in the early stages of disease. It is also a common impairment in patients with right hemisphere (RH) strokes. In the parent grant of this supplement, we seek to identify the perceptual, cognitive, and motor deficits that can disrupt affective prosody, and characterize the natural history of spontaneous recovery following a RH stroke. In this Administrative Supplement we extend our research to focus on affective prosody deficits in patients with AD and FTD. Affective prosody deficits can negatively impact social relationships and quality of life in patients with neurodegenerative diseases, and they often lead to more behavioral problems and increased conflict with caregivers. The main objective of this supplement is to identify the perceptual, cognitive, and motor deficits that disrupt affective prosody in AD and FTD, and to identify the neural networks that support these functions. Furthermore, evidence suggests patterns of deficits in expressive and receptive affective prosody differ between the different variants of AD and FTD. Therefore, we will compare patterns of deficits in the following five subtypes of AD and FTD. Two subtypes of AD: (1) typical AD, and (2) logopenic variant Primary Progressive Aphasia (lvPPA); three subtypes of FTD: (1) behavioral variant FTD (bvFTD), (2) nonfluent variant PPA (nfvPPA), and (3) semantic variant PPA (svPPA). PPA is a neurodegenerative syndrome where language impairments are the most prominent deficit in early stages of the disease. In Specific Aim 1 we will identify acoustic abnormalities and the deficit underlying these abnormalities in perception and expression of affective prosody that can be independently damaged by focal atrophy in each subtype. We will also examine the impact of these deficits on quality of life. Patients will be tested on a battery of cognitive and affective prosody tests, developed as part of the parent grant, to identify behavioral patterns of deficits. In Specific Aim 2 we will identify the neural streams necessary for the processes that subserve affective prosody. We will use structural MRI measures to investigate relationships between atrophy patterns and performance on the cognitive and affective prosody tasks. These data will provide robust preliminary data for the submission of a larger grant that will be designed to longitudinally follow patients to identify variation in the course of the disease, and will allow us to better predict to which variant early stage unclassifiable AD and FTD patients will evolve. Our research will also provide the basis for designing future behavioral and neuromodulatory treatments to slow the rate of decline in affective prosody.
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0.958 |