Specific Aims: The proposed Language-Related Potential experiments aim to characterize the electrophysiological correlates of memory impairment in amnesia, dementia and aging. We will use the Event-Related Potential (ERP) technique to investigate language and verbal memory processes along with behavioral measures of these processes. The specific brain potentials of interest are the N4OO, a late negative ERP which peaks at approximately 400 msec post-stimulus, and the late positive component (LPC) which follows. The N400 potential has been shown to be a measure of semantic processing with its amplitude having a strong inverse correlation with the probability of the eliciting word appearing in a given context. The LPC, akin to the P300 or """"""""P3b"""""""", has been related to both task difficulty and memory processes. We have designed an ERP word repetition paradigm which utilizes auditory context/visual target word pairs in a semantic categorization task and repeats these pairs at varying time intervals. This paradigm shows promise in providing electrophysiological measures of both implicit and explicit verbal memory processes. Our preliminary studies of amnesic patients suggest that the difference in the N400 to new versus repeated target words (i.e. the """"""""N400 repetition effect~) is equivalent to that seen in normal controls. In contrast, the amnesics show an abnormal reduced LPC repetition effect and the degree of this reduction correlates well with impairment of explicit memory. Specific hypotheses to be tested are: 1) Amnesic patients will have a reduced effect of word repetition upon the LPC, but not upon the N400, reflecting impairment of explicit, not implicit, memory processes. 2) A reduced LPC repetition effect will be a sensitive sign of memory impairment and may help distinguish non-demented individuals with age- associated memory impairment (AAMI) from normal elderly. 3) Patients with refractory depression will have a reduced LPC repetition effect when amnesic during the course of electroconvulsive therapy (ECT) but not prior to nor following ECT. 4) Among patients diagnosed as being """"""""at risk"""""""" for Alzheimer's disease, those with abnormal N400 potentials or LPC repetition effects will be more likely to develop dementia than those with normal ERPs. 5) The N400 potential and LPC repetition effects will differ between subjects with Alzheimer's disease, multi-infarct dementia and normal elderly controls. Research design: Case-control and longitudinal studies of ERPs with comparisons to relevant behavioral data. Methods: ERPs will be recorded from normal and memory-impaired subjects during a semantic categorization task. Repetition and congruity (degree of fit with a category) will be varied systematically in order to elicit and modulate N400 and LPC brain potentials. Comparisons of N400 and LPC characteristics will be made between and within subject groups and related to explicit memory abilities and other neuropsychological data.
| Armstrong, Richard A; Ellis, William; Hamilton, Ronald L et al. (2010) Neuropathological heterogeneity in frontotemporal lobar degeneration with TDP-43 proteinopathy: a quantitative study of 94 cases using principal components analysis. J Neural Transm (Vienna) 117:227-39 |
