Category: Abstract (Page 3 of 3)

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

November 5, 2015 / jbcosca

Clin Electroencephalogr, 33(3):111-8.

Abstract

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.

Abnormal verbal event related potentials in mild cognitive impairment and incipient Alzheimer’s disease

November 5, 2015 / jbcosca

J Neurol Neurosurg Psychiatry, 73(4):377‐84.

BACKGROUND: It has been reported that patients with amnesia have a reduced effect of word repetition upon the late positive component of the event related potential (ERP), which peaks at around 600 ms after word onset. OBJECTIVE: To study a word repetition ERP paradigm in subjects with mild cognitive impairment. SUBJECTS: 14 patients with mild cognitive impairment (mean mini‐mental state examination score = 27); 14 normal elderly controls. METHODS: Auditory category statements were each followed by a single visual target word (50% “congruous” category exemplars, 50% “incongruous”) while ERPs were recorded. N400 (an ERP component elicited by semantically “incongruous” words) and LPC amplitude data were submitted to analysis of variance. RESULTS: The latency of the N400 was slower in mild cognitive impairment. In normal controls, the ERPs to “congruous” targets showed a late positive component to new words, which was greatly diminished with repetition. This repetition effect in normal subjects started before 300 ms at right frontal sites, and peaked at approximately 600 ms post‐stimulus over posterior sites. In contrast, the group with mild cognitive impairment had a reduced repetition effect (p < 0.02), which started around 500 ms, with a more central distribution. Further comparisons within the cognitive impairment group showed no appreciable congruous word repetition effect among seven individuals who subsequently converted to probable Alzheimer’s disease. The congruous word repetition effect in the group with mild cognitive impairment was almost entirely accounted for by the non‐converters. The amplitude of the congruous late positive component word repetition effect was significantly correlated (0.38 < or = r < or = 0.73) with several verbal memory measures. CONCLUSIONS: The congruous word repetition ERP effect appears sensitive to the memory impairment in mild cognitive impairment and could have value in predicting incipient Alzheimer’s disease.

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

October 13, 2015 / jbcosca

Abstract

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.

Anosmia is very common in the Lewy body variant of Alzheimer’s disease

October 13, 2015 / jbcosca

Abstract

BACKGROUND: Olfactory abnormalities are reported in Alzheimer’s disease and Parkinson’s disease. Anosmia appears to be common in dementia with Lewy bodies but not in pure Alzheimer’s disease. OBJECTIVE: To determine whether anosmia improves discrimination between the Lewy body variant (LBV) of Alzheimer’s disease and “pure” Alzheimer’s disease. METHODS: 106 cases of necropsy confirmed pure Alzheimer’s disease (n = 89) or LBV (n = 17) were reviewed. All had received butanol odour threshold testing. Anosmia was defined as a score < or = 1.0 on a 0-9 point scale. Logistic regression analysis was used to model potential predictors (for example, parkinsonism, smoking, hallucinations) of neuropathological diagnosis and anosmia. RESULTS: LBV cases had an increased prevalence of anosmia (65%) compared with Alzheimer’s disease (23%; odds ratio (OR) = 6.3, p = 0.00045), or normal elderly people (6.7%). Within the dementia cases, the negative predictive value (92%) and specificity (78%) of anosmia were both good; sensitivity for detecting LBV was 65%, but the positive predictive value (PPV) was only 35%. Logistic regression models showed anosmia (OR = 5.4, p = 0.005) and visual hallucinations (OR = 7.3, p = 0.007) were strong independent predictors of Lewy body pathology. When anosmia was added as a core feature to consensus diagnostic criteria for probable Lewy body dementia, five additional cases of LBV were detected (29% increased sensitivity), but with four additional false positives (1% increased discrimination, 4% decreased specificity, 33% decreased PPV). CONCLUSIONS: Anosmia is very common in LBV. Adding anosmia as a core feature improved sensitivity for detecting LBV, but did not improve discrimination between Alzheimer’s disease and LBV owing to a concomitant increase in false positives.

Absent event-related potential (ERP) word repetition effects in mild Alzheimer’s disease

October 13, 2015 / jbcosca

Abstract

OBJECTIVE: We hypothesized that an ERP word repetition paradigm, which reliably elicits and modulates the P600 and N400 components, would be particularly sensitive to the memory deficits and altered synaptic plasticity in mild Alzheimer’s disease (AD). The P600 (a late positive component, or ‘LPC’), and the N400, are sensitive indices of memory encoding and semantic processing, respectively. METHODS: We studied 11 patients with mild AD (mean MMSE=22.9) and 11 elderly (mean age=77.1) normal controls (NC) on a paradigm in which semantically ‘congruous’ category statement/exemplar pairs (50%) and ‘incongruous’ category statement/non-exemplar pairs (50%) repeat at 10-140 s intervals. A minimum of 19 channels ERP data were recorded and submitted to split-plot ANOVAs. RESULTS: Normal ERP data showed: (1) a significant word repetition effect for congruous words, with a wide-spread late positivity between approximately 300 and 800 ms post-stimulus (P600) that is larger for New than Old words; (2) a significant N400 repetition effect for incongruous words, with a right posterior negativity that is reduced for Old relative to New words. By contrast, neither of these word repetition effects was reliably present in the mild AD group. Good group discrimination was achieved by requiring that both these repetition effects were > or = the 10th percentile, with 100% sensitivity and 82% specificity. CONCLUSIONS: We found significant abnormalities of the N400 and P600 in mild AD, with both potentials showing markedly reduced sensitivity to word repetition. SIGNIFICANCE: The absence of normal N400 and LPC/P600 word repetition effects suggests impaired functioning of their neural generators, several of which are located in medial temporal lobe predilection sites (e.g. anterior fusiform, parahippocampal gyrus, hippocampus) for AD/tau pathology.

From amnesia to dementia: ERP studies of memory and language

October 13, 2015 / jbcosca

Abstract

Cognitive event-related potential (ERP) studies of memory and language impairments in amnesia and Alzheimer’s disease (AD) are reviewed. Well-circumscribed lesions of the medial temporal lobe (MTL) or diencephalon causing an amnestic syndrome, an inability to encode and retrieve episodic memories beyond the brief duration of working memory, appear to produce altered plasticity of the late positive P600 component, but usually spare P300 and N400 components. The neuropathology of AD affects MTL and extends to neocortical association areas, causing deficits of episodic and semantic memory. In AD dementia, the P300, N400, and P600 all commonly show abnormalities. ERP studies of individuals with mild cognitive impairment may reveal neurophysiological changes prior to the emergence of clinical deficits, which could advance the early detection and diagnosis of AD.