Bruce Crosson - US grants

The purpose of this study is to test the hypothesis that the left anterior temporal cortex participates in object naming but not in action naming. It is also hypothesized that nouns are organized in a category-specific manner in the brain, and that natural objects are processed by the left anterior temporal cortex while artifactual objects are processed primarily by other parts of the brain.

DESCRIPTION (Adapted from the Investigator's Abstract): Language disturbance is common in persons with brain injury and disease. The development of effective treatments for such language disturbances requires an understanding of the neurological bases of language and related functions. Intention is preparation to respond and is important for all activities, including those involving language. The literature suggests that different neural systems are engaged when intentional processes involve retrieval of information from internal knowledge stores versus when intentional processes involve simple responses to external stimuli, such as repetition. Further, the nature of information used to generate language may affect which systems are engaged to accomplish the task. The current proposal plans to explore the role and location of the medial frontal cortex involved in the intentional aspects of language expression using functional magnetic resonance imaging (fMRI). It is hypothesized that the medial frontal cortex involved in intentional language activities requiring retrieval from internal knowledge stores will be located in the dominant medial frontal gyrus, just anterior to supplementary motor area (SMA) and within the sulcus directly inferior to this cortex. This cortex is more connected to prefrontal cortex involved in action planning than SMA, which is more directly connected to motor structures. Further, this cortex is distinguishable from the limbic cortex of anterior cingulate gyrus. For repetition which involves replicating external information, it is hypothesized that SMA is involved because repetition simply requires producing the correct motor activities and sequences to replicate the stimulus. Finally, it is hypothesized that medial frontal cortex is involved in generation of language responses only when words are generated and not when meaningless syllables are generated. Eventually, the tasks and procedures involved in this study can be used to study intentional activity in patients with language impairment because of brain injury or disease.

Growing evidence indicates that deficits in attention (defined as selection of one external source of information for further processing) and intention (defined as preparation to respond, including choosing one course of action as opposed to others) accompany aphasia. These deficits may exacerbate language symptoms such as naming difficulty in some instances, and language functions may improve when attention/intention manipulations are applied. Specifically, when some premorbidly right-handed patients with aphasia after left-hemisphere lesion are required to attend to stimuli in their left hemispace or gesture with their left hands, they are better able to formulate and/or understand language. In such cases, it seems likely that attending to stimuli in hemispace contralateral to the intact hemisphere or initiating an action with the hand contralateral to the intact hemisphere, engages intact attention or intention mechanisms, respectively, in that hemisphere which then compensate for dysfunctional mechanisms in the damaged hemisphere. The purpose of this subproject is to develop and apply aphasia treatments designed to recruit attention or intention mechanisms in the intact hemisphere and to engage them in language processing. Treatments will target naming; patients who have chronic difficulty in naming will be studied. In addition to assessing the effectiveness of treatments for individual patients, fMRI will be used to explore whether the effects are accomplished by shifting attention and intention demands to the mechanisms in the non-dominant hemisphere. Broader "functional" aspects of language will also be assessed.

[unreadable] DESCRIPTION (provided by applicant): A new treatment manipulating intention substrates for language production in "nonfluent" aphasia patients was developed. The intention component involves initiating word-finding trials with a complex left-hand movement. In a preliminary study, the rate of change in naming accuracy was faster for this treatment than for a similar treatment without the intention component. However, the assumption that the treatment evokes a shift of language production functions from the left to the right frontal lobe has been tested only in a small number of patients (N = 5) whose lateralization was variable before treatment, and appropriate stringent control procedures to verify that the shift in lateralization was due to the intention component were not used. The proposed study will address the hypothesized shift in lateralization in a larger sample of "nonfluent" aphasia patients and with an appropriate control group. In a parallel group design, 13 patients will receive the intention treatment and 13 patients will receive a control treatment that is identical to the intention except that the intention component is absent. All subjects will participate in functional magnetic resonance imaging (fMRI) scans of word-finding before and after treatment to measure changes in lateralization of lateral frontal and pre-SMA activity. Only patients with a substantial degree of left frontal activity on the pre-treatment scan will participate. The long-term objective is to determine if the intention treatment produces the hypothesized rightward shift in lateral frontal and pre-SMA activity. There are three specific aims: (1) to determine if repetitive initiation of word production with a complex left-hand movement leads to increased right- hemisphere lateralization of pre-SMA and lateral frontal activity and if these changes can be attributed to the intention component of treatment, (2) to determine whether activity in posterior perisylvian cortices that is entrained to right frontal activity shows a greater increase in right-hemisphere lateralization for the intention than for the control group from pre- to post-treatment fMRI, and (3) to determine whether onset of hemodynamic responses (HDRs) in right motor/premotor cortex becomes more closely associated with the temporal onset of participants' spoken responses across treatment for the intention vs the control treatment. The proposed study has the following potential benefits: First, if successful, the treatment can provide a new treatment vehicle for increasing language function and reducing suffering in patients with "nonfluent" aphasia. Second, the treatment can produce a paradigm shift in the development of aphasia treatment by emphasizing mechanisms for producing desirable changes in the brain mechanisms for language production and by verifying the target changes with fMRI. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Almost all Alzheimer's disease (AD) patients eventually develop anomia. Recent literature indicates that such word-finding problems are not monolithic. Lexical and semantic deficits can exist independently in AD patients, and both can impair word finding. The long-term goal of this R21 application is to develop a model of regional brain activity and atrophy that explains different patterns of picture-naming deficit in AD. Sixteen AD patients with lexical deficits, 16 AD patients with semantic deficits, and 16 normal controls will perform a picture naming task during functional MRI (fMRI), and activity from each group will be compared to activity from each other group in voxelwise t-test images. Main hypotheses are: (1) Patients with lexical deficits will demonstrate decreased activity relative to normal controls in left perisylvian regions that support lexical functions. (2) Patients with semantic deficits will show decreased activity relative to normal controls in both left inferior temporal cortex supporting semantic functions and left perisylvian cortex supporting lexical functions. Activity decrease in perisylvian cortex is expected not because of underlying neuropathology, but because this cortex is not adequately stimulated by semantic input from inferior temporal cortex. In post hoc analyses, activity in frontal cortex also will be examined to determine if the AD groups demonstrate compensatory activity increases in different frontal regions. Further, functional activity in the left inferior temporal and posterior perisylvian cortices will be correlated with measures of semantic and lexical deficits to determine if this activity correlates with these two impairments, respectively. In addition, structural images from the different groups will be compared using voxel-based morphometry (VBM) to assess regional differences in gray matter atrophy. It is expected that AD patients with lexical deficits will show the greatest atrophic changes relative to controls in left perisylvian cortex, and AD patients with semantic deficits will show the greatest atrophic changes relative to controls in left inferior temporal cortex. Finally, correlation images between fMRI signal intensities from picture naming and VBM intensities from anatomic images will be generated. It is expected that fMRI activity decreases in the left inferior temporal cortex during naming will correlate with degree of atrophy in this region in a combined analysis of all subject groups;however, according to the proposed model, fMRI activity decreases in the left perisylvian cortex will correlate with atrophy in that region only for the lexical deficit group and not for a combined analysis of all subjects. Once these different patterns of deficit are understood, interventions for each pattern can be developed to extend the duration of functional communication during the course of the disease. Maintenance of functional communication further into the disease will improve quality of life for patients and families and will prolong independence, thereby delayin institutionalization and decreasing costs. PUBLIC HEALTH RELEVANCE: The long-term goal of the proposed research is to develop a model of regional brain activity and atrophy that explains different patterns of picture-naming deficit in Alzheimer's disease. Once these different patterns of deficit are understood, different interventions for each pattern can be developed to extend the duration of functional communication during the course of the disease. Maintenance of functional communication further into the disease process will improve quality of life for patients and their families and will prolong their independence, thereby reducing the need for institutionalization and decreasing health care costs.