This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Extensive behavioral, neurophysiologic, and functional imaging data suggest that Amyotrophic Lateral Sclerosis (ALS) can be complicated by neuropsychologic dysfunction. Although a minority of ALS patients develop cognitive and compartmental impairments consistent with a fronto-temporal lobar dementia (FTLD), many others (at least one third) manifest cognitive dysfunction which, while less than that qualifying for dementia, is nonetheless clinically significant. Prior studies have attributed the majority of non-demented ALS-related cognitive impairment to executive dysfunction, presumably secondary to ALS-related prefrontal cortex involvement, though the precise functional neuroanatomy of this involvement remains unclear. ALS patients can also suffer from dysexecutive-related cognitive epiphenomena including memory deficits (e.g., secondary to impaired search strategies) and language impairment (e.g., secondary to impaired generative fluency). Further, clinical reports have long documented affective dysfunction, including increased prevalence of depression and emotional dysregulation (e.g., pseudo-bulbar affect) associated with ALS. However, actual emotional processing dysfunction in ALS patients has neither been well-characterized nor mechanistically studied. We wish to build-upon and extend these prior studies of neurobehavioral dysfunction in ALS by (1) better quantifying emotional processing dysfunction in ALS, (2) clarifying the functional neuroanatomy of ALS-related executive dysfunction, and (3) probing the extent to which executive dysfunction is independent or neurally modulated by aberrant emotional processing. We therefore propose applying a neuropsychological activation task, which combines emotional and executive probes, with fMRI to contemporaneously measure behavioral responses and neural activation patterns in ALS patients versus normal control subjects. Hypothesis: We hypothesize that ALS patients, relative to normal controls, will demonstrate (1) aberrant emotional responsivity (both behaviorally and neurally), (2) behavioral dyscontrol (e.g., as mediated by executive management on a go/no-go task), and (3) greater emotional interference with executive control operations (e.g., emotional stroop effect) as evidenced by prefrontal neural activation changes.
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