Reduced sensitivity of the N400 and late positive component to semantic congruity and word repetition in left temporal lobe epilepsy.

We studied 14 patients with well-characterized refractory temporal lobe epilepsy (TLE), 7 with right temporal lobe epilepsy (RTE) and 7 with left temporal lobe epilepsy (LTE), on a word repetition ERP experiment. Much prior literature supports the view that patients with left TLE are more likely to develop verbal memory deficits, often attributable to left hippocampal sclerosis. Our main objectives were to test if abnormalities of the N400 or Late Positive Component (LPC, P600) were associated with a left temporal seizure focus, or left temporal lobe dysfunction. A minimum of 19 channels of EEG/EOG data were collected while subjects performed a semantic categorization task. Auditory category statements were followed by a visual target word, which were 50% "congruous" (category exemplars) and 50% "incongruous" (non-category exemplars) with the preceding semantic context. These auditory-visual pairings were repeated pseudo-randomly at time intervals ranging from approximately 10-140 seconds later. The ERP data were submitted to repeated-measures ANOVAs, which showed the RTE group had generally normal effects of word repetition on the LPC and the N400. Also, the N400 component was larger to incongruous than congruous new words, as is normally the case. In contrast, the LTE group did not have statistically significant effects of either word repetition or congruity on their ERPs (N400 or LPC), suggesting that this ERP semantic categorization paradigm is sensitive to left temporal lobe dysfunction. Further studies are ongoing to determine if these ERP abnormalities predict hippocampal sclerosis on histopathology, or outcome after anterior temporal lobectomy.

Spared access to idiomatic and literal meanings: a single-case approach.

The current study examines how patients with aphasia access the meanings of idioms during spoken sentence comprehension. In our experiment, we had 4 subjects whose native language is German: 2 left-hemisphere damaged patients (Wernicke's and global aphasia); 1 right-hemisphere damaged patient; and 1 age-matched healthy speaker. Ambiguous two-element German noun compounds carrying an idiomatic as well as a literal meaning served as target words. While listening to contextually biasing sentences containing the target words, the subjects performed a lexical decision task at the offset of each compound. All the subjects, including the aphasic patients, accessed the compounds' literal and idiomatic meanings simultaneously despite the existence of contextually biasing sentences. The data are discussed by taking account of the findings of recent studies of lexical semantic processing in aphasia.

Clinical applications of cognitive event-related potentials in Alzheimer's disease.

This article has reviewed several abnormalities in the cognitive ERPs of AD patients. These abnormalities are prominent from latencies of approximately 200 msec and later. In contrast, sensory-dependent evoked potentials, such as N100, are generally normal in AD. This finding is as one familiar with the neuropathology of AD would predict. Predilection sites in early AD include the medial temporal lobe, other limbic areas, and multimodal association cortices with sparing of primary sensory areas. Unimodal association cortex is involved in AD, but not as heavily as multimodal cortex. Particular advantages of studying a given ERP paradigm or component depend largely on the specific application or hypothesis being tested. A P300 paradigm can be useful in detecting a disorder of attention or in quantifying the effects of drugs that improve attention, such as the cholinesterase inhibitors. For the early diagnosis of AD or other memory disorders, a word-repetition paradigm with an explicit recognition task or one that fosters associative learning would be recommended. This article has discussed potential use of N400 in tracking disease progression. ERPs provide a flexible and powerful technique, with superb temporal resolution, which can be used as a probe into subtle "subclinical" abnormalities of cognitive processes. Despite being applied to AD for about 25 years since the early P300 studies, the full potential of ERPs in helping diagnose and treat AD patients has yet to be realized. In this era of rapidly evolving brain-imaging techniques, electrophysiologic data are important in advancing understanding of cognition. Brain-mapping techniques that can inform where and when key cognitive processes occur are finally emerging. A final example of potential clinical application of cognitive ERPs is in the development of rational combinational treatment of cognitive enhancing drugs. Along these lines, P300 investigations in epilepsy proved helpful in ranking the cognitive side effects of anticonvulsant drugs. Drug studies that use 2 x 2 combinational designs, which compare the effects of drug A, drug B, with A + B, are currently prohibitively expensive for full-scale clinical trials in AD. It is likely that precise ERP measures could hasten drug development in several ways. Smaller samples could be used, at lower cost, to test the cognitive effects of each specific drug combination. Optimal doses of combinational therapy perhaps could be identified by repeated within-subject ERP measures. Longitudinal changes in the ERP hold promise as a marker of individual responsivity to a particular agent, which could have diagnostic utility (eg, testing response to cholinergic or dopaminergic therapy). This horizon and many others remain wide open for well-planned explorations.

Extending the NegEx lexicon for multiple languages.

We translated an existing English negation lexicon (NegEx) to Swedish, French, and German and compared the lexicon on corpora from each language. We observed Zipf's law for all languages, i.e., a few phrases occur a large number of times, and a large number of phrases occur fewer times. Negation triggers "no" and "not" were common for all languages; however, other triggers varied considerably. The lexicon is available in OWL and RDF format and can be extended to other languages. We discuss the challenges in translating negation triggers to other languages and issues in representing multilingual lexical knowledge.

fMRI congruous word repetition effects reflect memory variability in normal elderly.

Neural circuits mediating repetition effect for semantically congruous words on functional MRI were investigated in seventeen normal elderly (mean age=70). Participants determined if written words were semantically congruent (50% probability) with spoken statements. Subsequent cued-recall revealed robust explicit memory only for congruous items (83% versus 8% for incongruous). Event-related BOLD responses to New>Old congruous words were found in the left>right cingulate and fusiform gyri, left parahippocampal cortex, middle and inferior frontal gyri (IFG). A group with above-median subsequent recall had markedly more widespread BOLD responses than a Low-Recall subgroup, with larger responses in the left medial temporal lobe (LMTL), IFG, and bilateral cingulate gyri. The magnitude of LMTL activation (New-Old) correlated with subsequent cued-recall, while the spatial extent of LMTL activation (New>Old) correlated with recall and recognition. Both magnitude and spatial extent of left fusiform activation correlated with subsequent recall/recognition. A neural circuit of left-hemisphere brain regions, many identified as P600 generators by invasive electrophysiological studies, was activated by New>Old congruous words, likely mediating successful verbal encoding.

fMRI responses to words repeated in a congruous semantic context are abnormal in mild Alzheimer's disease.

BACKGROUND: We adapted an event-related brain potential word repetition paradigm, sensitive to early Alzheimer's disease (AD), for functional MRI (fMRI). We hypothesized that AD would be associated with reduced differential response to New/Old congruous words. METHODS: Fifteen mild AD patients (mean age=72.9) and 15 normal elderly underwent 1.5T fMRI during a semantic category decision task. RESULTS: We found robust between-groups differences in BOLD response to congruous words. In controls, the New>Old contrast demonstrated larger responses in much of the left-hemisphere (including putative P600 generators: parahippocampal, cingulate, fusiform, perirhinal, middle temporal (MTG) and inferior frontal gyri (IFG)); the Old>New contrast showed modest activation, mainly in right parietal and prefrontal cortex. By contrast, there were relatively few regions of significant New>Old responses in AD patients, mainly in the right-hemisphere, and their Old>New contrast did not demonstrate a right-hemisphere predominance. Across subjects, the spatial extent of New>Old responses in left medial temporal lobe (MTL) correlated with subsequent recall and recognition (r's>or=0.60). In controls, the magnitude of New-Old response in left MTL, fusiform, IFG, MTG, superior temporal and cingulate gyrus correlated with subsequent cued recall and/or recognition (0.51Old responses to congruous words in normal elderly). This network appears dysfunctional in mild AD patients, as reflected in decreased word repetition effects particularly in left association cortex, paralimbic and MTL structures.