N400 Repetition Effect Research Articles

Cognitive Deficits and Associated ERP N400 Abnormalities in FXTAS With Parkinsonism

Objective: To examine cognitive deficits and associated brain activity in fragile X-associated tremor/ataxia syndrome (FXTAS) patients with parkinsonism (FXTp+), in relation to FXTAS patients without parkinsonism (FXTp-), and normal elderly controls (NC).Methods: Retrospective reviews were performed in 65 FXTAS patients who participated in the event-related brain potential (ERP) study and also had either a videotaped neurological examination or a neurological examination for extrapyramidal signs. Parkinsonism was defined as having bradykinesia with at least one of the following: rest tremor, postural instability, hypermyotonia, or rigidity. Eleven FXTp+ patients were identified and compared to 11 matched FXTp- and 11 NC. Main ERP measures included the N400 congruity effect, N400 repetition effect, and the late positive component (LPC) repetition effect.Results: When compared with FXTp- and NC, the FXTp+ group showed more severe deficits in executive function, cued-recall, recognition memory, along with a significantly reduced N400 repetition effect (thought to index semantic processing and verbal learning/memory) which was correlated with poorer verbal memory. Across all patients, FMR1 mRNA levels were inversely correlated with delayed recall on the California Verbal Learning Test (CVLT).Interpretation: The findings of more prominent executive dysfunction and verbal learning/memory deficits in FXTp+ than FXTp- are consistent with findings in Parkinson’s disease (PD), and may indicate that concomitant and/or synergistic pathogenetic mechanisms associated with PD play a role in FXTAS. These results have implications not only for understanding the cognitive impairments associated with the parkinsonism subtype of FXTAS, but also for the development of new interventions for these patients.

A Neurophysiological Study of Semantic Processing in Parkinson's Disease.

Cognitive-linguistic impairments in Parkinson's disease (PD) have been well documented; however, few studies have explored the neurophysiological underpinnings of semantic deficits in PD. This study investigated semantic function in PD using event-related potentials. Eighteen people with PD and 18 healthy controls performed a semantic judgement task on written word pairs that were either congruent or incongruent. The mean amplitude of the N400 for new incongruent word pairs was similar for both groups, however the onset latency was delayed in the PD group. Further analysis of the data revealed that both groups demonstrated attenuation of the N400 for repeated incongruent trials, as well as attenuation of the P600 component for repeated congruent trials. The presence of N400 congruity and N400 repetition effects in the PD group suggests that semantic processing is generally intact, but with a slower time course as evidenced by the delayed N400. Additional research will be required to determine whether N400 and P600 repetition effects are sensitive to further cognitive decline in PD. (JINS, 2017, 23, 78-89).

Bilingual memory representations in less fluent Chinese-English bilinguals: an event-related potential study.

The present study was designed to investigate bilingual memory representations in less fluent Chinese-English bilinguals and the effect of word familiarity on bilingual memory representations with a translation priming paradigm and the event-related potential (ERP) technique. Three factors (translation order, word familiarity, and repetition status) were manipulated in this study, and the major dependent variable was the magnitude of the N400 repetition effect, which is related to semantic expectation and is an important physiological index of language processing. The results confirmed the asymmetry in bilingual memory with stronger L2-LI links compared to L1-L2 links in less fluent Chinese-English bilinguals, and that word familiarity was an important factor in the memory representations of these less fluent bilinguals.

ERP abnormalities elicited by word repetition in fragile X-associated tremor/ataxia syndrome (FXTAS) and amnestic MCI

BackgroundFragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder caused by FMR1 gene premutations, typically associated with frontal-subcortical type cognitive impairments. High prevalence (~50%) of superimposed Alzheimer׳s pathology has been reported in FMR1 premutation carriers, and standardized neuropsychological tests have not yielded any robust discriminators between FXTAS and Alzheimer׳s disease (AD) dementia. The similarities/differences in memory processes between FXTAS and early AD remain underexplored. Methods32-channel event-related potentials (ERPs) were obtained from a semantic judgment task in which semantically congruous (50%) and incongruous pairs repeat pseudorandomly. The N400 and late positive component (LPC) of 25 FXTAS patients (Mage=71.2, MMSE=26.6) were compared to a matched group of 25 patients with MCI or early AD (1 mild AD dementia, 24 amnestic MCI, of whom 18 later converted to AD; Mage=73.4, MMSE=26.4), and 25 healthy elderly. ResultsBoth patient groups showed similar reductions in the N400 repetition effect and N400 congruity effect amplitudes, compared to controls, reflecting abnormal semantic priming and repetition priming. The MCI/AD group, however, had significantly smaller LPC word repetition effects and poorer learning and memory on the CVLT than FXTAS. The LPC and N400 repetition effects both correlated with verbal memory across all subjects, but only N400 correlated with memory in FXTAS. ConclusionFXTAS patients show relative sparing of the LPC repetition effect, and less disruption of explicit memory than prodromal/early AD. N400 abnormalities in FXTAS appear to account for much of their mild impairments in verbal learning and memory.

Memantine effects on verbal memory in fragile X-associated tremor/ataxia syndrome (FXTAS): a double-blind brain potential study.

Older FMR1 premutation carriers may develop fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder manifesting cognitive deficits that often subsequently progress to dementia. To date, there is no specific treatment available for FXTAS. Studies have demonstrated the premutation-associated overactivation of glutamatergic receptors in neurons. Memantine, a NMDA receptor antagonist approved for treatment of Alzheimer's disease, thus was tested in the first placebo-controlled, double-blind, randomized clinical trial in FXTAS. Prior event-related brain potential (ERP) studies in FXTAS found reduced N400 repetition effect, a glutamate-related electrophysiological marker of semantic priming, and verbal memory processes. This substudy of the randomized clinical trial of memantine in FXTAS sought to use the N400 repetition effect to evaluate effects of chronic memantine treatment on verbal memory. Subsequent recall and recognition memory tests for the experimental stimuli were administered to characterize verbal memory. Data from 41 patients who completed the 1-year memantine trial (21 on memantine) and also completed longitudinal ERP studies were analyzed. Results showed treatment-associated benefits on both cued-recall memory and N400 repetition effect amplitude. Importantly, improvement in cued recall was positively correlated with amplitude increase of the N400 repetition effect. The placebo group, in contrast, displayed a significant reduction of the N400 repetition effect after 1 year. These results suggest that memantine treatment may have beneficial effects on verbal memory in FXTAS. Additional studies of memantine, perhaps in combination with other therapeutic agents, appear warranted, as symptomatic treatments and neuroprotective treatments are both needed for this recently recognized neurodegenerative disorder.

PSPs and ERPs: Applying the dynamics of post-synaptic potentials to individual units in simulation of temporally extended Event-Related Potential reading data

The Parallel Distributed Processing (PDP) framework is built on neural-style computation, and is thus well-suited for simulating the neural implementation of cognition. However, relatively little cognitive modeling work has concerned neural measures, instead focusing on behavior. Here, we extend a PDP model of reading-related components in the Event-Related Potential (ERP) to simulation of the N400 repetition effect. We accomplish this by incorporating the dynamics of cortical post-synaptic potentials—the source of the ERP signal—into the model. Simulations demonstrate that application of these dynamics is critical for model elicitation of repetition effects in the time and frequency domains. We conclude that by advancing a neurocomputational understanding of repetition effects, we are able to posit an interpretation of their source that is both explicitly specified and mechanistically different from the well-accepted cognitive one.

Abnormal semantic processing in females with fragile X‐associated tremor/ataxia syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder, affects fragile X (FMR1) gene premutation carriers in late life. Studies have shown cognitive impairments in FXTAS including executive dysfunction, working memory and visuospatial deficits. However, less is known about cognition in females with FXTAS. Thus, we examined semantic processing and verbal memory in female FXTAS patients with event-related potentials (ERPs) and neuropsychological testing. Sixty-one females (34 FXTAS, Mage = 62.7; 27 controls, Mage = 60.4) were studied with 32-channel ERPs during a category judgment task in which semantically congruous (50%) and incongruous items were repeated approximately 10-140 seconds later. N400 and P600 amplitude data were submitted to analysis of covariance. Neuropsychological testing demonstrated lower performance in verbal learning and executive function in females with FXTAS. Event-related potential analyses showed a significant reduction of the N400 congruity effect (incongruous - congruous) in the FXTAS group. The N400 congruity effect reduction in females with FXTAS was mainly due to increased N400 amplitude to congruous new words. No significant abnormalities of the N400 repetition effect or the P600 repetition effect were found, indicating preserved implicit memory and verbal memory, respectively, in females with FXTAS. The decreased N400 congruity effect suggests abnormal semantic expectancy and/or semantic network disorganization in female FXTAS patients. The enhanced N400 amplitude to congruous new words may reflect decreased cognitive flexibility among FXTAS women, making access to less typical category exemplar words more difficult.

Won't get fooled again: An event-related potential study of task and repetition effects on the semantic processing of items without semantics

A growing body of evidence suggests that semantic access is obligatory. Several studies have demonstrated that brain activity associated with semantic processing, measured in the N400 component of the event-related brain potential (ERP), is elicited even by meaningless, orthographically illegal strings, suggesting that semantic access is not gated by lexicality. However, the downstream consequences of that activity vary by item type, exemplified by the typical finding that N400 activity is reduced by repetition for words and pronounceable nonwords but not for illegal strings. We propose that this lack of repetition effect for illegal strings is caused not by lack of contact with semantics, but by the unrefined nature of that contact under conditions in which illegal strings can be readily categorised as task-irrelevant. To test this, we collected ERPs from participants performing a modified Lexical Decision Task, in which the presence of orthographically illegal acronyms rendered meaningless illegal strings more difficult lures than normal. Confirming our hypothesis, under these conditions illegal strings elicited robust N400 repetition effects, quantitatively and qualitatively similar to those elicited by words, pseudowords, and acronyms.

The N400-concreteness effect reflects the retrieval of semantic information during the preparation of meaningful actions

The present ERP study investigated when and how action semantics, i.e. the conceptual knowledge that we acquired over the course of our lives, is activated during the preparation of object-directed actions. Subjects were required to grasp one of two objects and were implicitly instructed to either perform a meaningful action (e.g. moving a cup towards the mouth) or a meaningless action with the object (e.g. moving a cup towards the eye). A larger anterior N400 was found for the preparation of meaningful compared to meaningless actions, likely reflecting the retrieval of action semantic information in case a meaningful action was required with the object. The distribution and the latency of the anterior N400-effect were strongly related to standard N400-repetition effects, thereby further corroborating the semantic nature of the effect. In sum, the present study provides new insight in the neural and temporal dynamics underlying semantics for action.

Abnormal N400 word repetition effects in fragile X-associated tremor/ataxia syndrome

Fragile X-associated tremor/ataxia syndrome, a neurodegenerative disorder associated with premutation alleles (55-200 CGG repeats) of the FMR1 gene, affects many carriers in late-life. Patients with fragile X-associated tremor/ataxia syndrome typically have cerebellar ataxia, intranuclear inclusions in neurons and astrocytes, as well as cognitive impairment. Dementia can also be present with cognitive deficits that are as severe as in Alzheimer's disease, however frontosubcortical type impairment is more pronounced in fragile X-associated tremor/ataxia syndrome. We sought to characterize the P600 and N400 word repetition effects in patients with fragile X-associated tremor/ataxia syndrome, using an event-related potential word repetition paradigm with demonstrated sensitivity to very early Alzheimer's disease. We hypothesized that the fragile X-associated tremor/ataxia syndrome-affected participants with poor declarative verbal memory would have pronounced abnormalities in the P600 repetition effect. In the event-related potential experiment, subjects performed a category decision task whilst an electroencephalogram was recorded. Auditory category statements were each followed by an associated visual target word (50% 'congruous' category exemplars, 50% 'incongruous' nouns). Two-thirds of the stimuli (category statement-target word pairs) were repeated, either at short-lag (approximately 10-40 s) or long-lag (approximately 100-140 s). The N400 and P600 amplitude data were submitted to split-plot analyses of variance. These analyses of variance showed a highly significant reduction of the N400 repetition effect (F = 22.5, P < 0.001), but not of the P600 repetition effect, in mild fragile X-associated tremor/ataxia syndrome (n = 32, mean age = 68.7, mean Mini-Mental State Examination score = 26.8). Patients with fragile X-associated tremor/ataxia syndrome had significantly smaller late positive amplitude (550-800 ms post-stimulus onset) to congruous words (P = 0.04 for group effect). Reduced P600 repetition effect amplitude was associated with poorer recall within fragile X-associated tremor/ataxia syndrome patients (r = 0.66) and across all subjects (r = 0.52). Larger P600 amplitude to new congruous words also correlated significantly with higher free recall scores (r = 0.37, P < 0.01) across all subjects. We found a correlation between the amplitude of late positivity and CGG repeat length in those with fragile X-associated tremor/ataxia syndrome (r = 0.47, P = 0.006). Higher levels of FMR1 mRNA were associated with smaller N400s to incongruous words and larger positive amplitudes (between 300 and 500 ms) to congruous words. In conclusion, event-related potential word repetition effects appear sensitive to the cognitive dysfunction present in patients with mild fragile X-associated tremor/ataxia syndrome. Their more severe reduction in N400 repetition effect, than P600, is in contrast to the reverse pattern reported in amnestic mild cognitive impairment and incipient Alzheimer's disease (Olichney et al., 2008).

Language representation and processing in fluent bilinguals: Electrophysiological evidence for asymmetric mapping in bilingual memory

The purpose of this investigation was to test the assumption of asymmetric mapping between words and concepts in bilingual memory as proposed by the Revised Hierarchical Model (RHM, Kroll & Stewart, 1994). Twenty four Spanish–English bilinguals (experiment 1) and twenty English–Spanish bilinguals (experiment 2) were presented with pairs of words, one in English and one in Spanish, and asked to indicate whether or not the words had the same meaning. In half the trials the Spanish word preceded the English, and in the other half the English word preceded the Spanish. In each condition half of the words had the same meaning, and the experiment included both concrete and abstract word trials. Event-related potentials (ERPs) were used to examine lexical-semantic activation during word translation. As predicted, a direction-dependent translation asymmetry was observed in the magnitude of the N400 repetition effect. Specifically, the N400 effect was larger during backward translation (L2–L1) than during forward translation (L1–L2) in both groups of bilinguals. Results are considered in the context of different models of bilingual memory.

N400 repetition effect in unidentifiable Chinese characters: evidence for automatic process

A new matter of debate is whether N400 is exclusively sensitive to automatic or postlexical processes. Recent studies showing N400 modulation by masked primes support an automatic process account. However, these studies cannot directly prove an automatic process. Event-related brain potentials to blurred targets were recorded to substantiate N400 repetition (priming) effects as an index of pure automatic process during a matching task with Chinese characters. Highly blurred target characters, which were unidentifiable, as well as identifiable target characters were shown to elicit greater N400 when repeated, with N400 peak latency being longer for slightly blurred targets than for highly blurred targets. These results provide evidence that N400 is modulated directly by automatic processes rather than by postlexical processes.

Greater N400 repetition effect indicates development of recognition memory in primary-school children

Greater N400 repetition effect indicates development of recognition memory in primary-school children

Patients with MCI and N400 or P600 abnormalities are at very high risk for conversion to dementia

We sought cognitive event-related potential (ERP) biomarkers of disease progression and subsequent conversion to dementia in mild cognitive impairment (MCI). Two ERP components, the P600 and N400, are sensitive to abnormal episodic/declarative memory and semantic processing. When congruous category-exemplars are repeated, smaller P600s (relative to initial presentation) are normally elicited. Repetitions of semantically incongruous words yield smaller N400 amplitude. In mild Alzheimer disease (AD), abnormalities of both the N400 and P600 repetition effects are present, suggesting a widespread failure of synaptic plasticity. Patients with amnestic MCI (n = 32) were longitudinally studied annually with an ERP paradigm in which semantically congruous (50%) and incongruous target words are repeated 10 to 140 seconds after initial presentation. ERP data were analyzed to contrast MCI-to-AD converters (within 3 years) vs nonconverters, using split-plot analyses of variance. A statistically significant P600 congruous word repetition effect was found only in the nonconverter group (F = 9.9, p = 0.005 vs MCI converters). This effect correlated with verbal memory measures. Repetition of incongruous words produced a significant N400 amplitude attenuation (across right-hemisphere sites) in nonconverters, but not in converters. Patients with MCI with abnormal/reduced N400 or P600 word repetition effects had an 87 to 88% likelihood of dementia within 3 years while those with normal/spared N400 and P600 repetition effects had only an 11 to 27% likelihood. Abnormalities of the P600 or N400 in mild cognitive impairment are associated with an increased risk of subsequent conversion to Alzheimer disease (AD). These event-related potential components may offer useful biomarkers for the detection and staging of very early AD.

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

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 ∼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 ≥ 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.

Recognition Memory for High- and Low-Frequency Words in Adult Normal and Dyslexic Readers: An Event-Related Brain Potential Study

Differences in word processing between adult developmental dyslexic (n = 12) and normal readers (n = 12) were studied using event-related brain potentials recorded while subjects performed a recognition memory task. During the first part of the experiment, words were presented consecutively, and within this phase one third of the words were repeated. Subjects had to indicate whether a given word had previously been seen or not. After a delay of 1 hr, a second phase was administered. Here, another list containing 33% old words (presented in Phase 1) and 66% new words was shown and an old/new decision was required. In both categories, half of the words presented in either phase were of high normative frequency, and the other half were of low-frequency in the German language. Recognition performance was superior in normal readers for both high- and low-frequency words. In Phase 1, a fronto-centrally distributed N400 repetition effect discriminated between correctly identified old and new words (new words more negative). This effect was present for dyslexic as well as normal readers and for high- and low-frequency words. Between 450 and 800 ms, a ‘P600 old/new effect’ emerged (ERPs evoked by old words were more positive than those for new words). This effect was larger for low-frequency words. In Phase 2, an old/new effect was obtained for normal readers only. These findings are discussed in relation to current concepts of dyslexia and of semantic processing.

Word repetition in amnesia. Electrophysiological measures of impaired and spared memory.

Amnesic patients often show improved performance when stimuli are repeated, even in the absence of conscious memory for those stimuli. Although these performance changes are typically attributed to perceptual or motor systems, in some cases they may be related to basic language processing. We examined two neurophysiological measures that vary with word repetition in 12 amnesic patients and 12 control subjects: (i) a late positive component of the event-related potential (ERP) linked to conscious memory and (ii) the N400 component that varies with language comprehension. In each trial, the subject heard a category name, then viewed a word, and then decided whether the word was semantically congruous or incongruous (e.g. 'yes' for 'baby animal: cub'; 'no' for 'water sport: kitchen'). Recall and recognition testing at the end of the experiment showed that control subjects had better memory for congruous than for incongruous words, as did the amnesic patients, who performed less well overall. In contrast, amnesic patients were unimpaired on the category decisions required in each trial and, like the control subjects, showed a large N400 for incongruous relative to congruous words. Similarly, when incongruous trials were repeated after 0-13 intervening trials, N400s were reduced in both groups. When congruous trials were repeated, a late positive repetition effect was observed, but only in the control group. Furthermore, the amplitude of the late positive repetition effect was highly correlated with later word recall in both patients and controls. In the patients, the correlation was also observed with memory scores from standardized neuropsychological tests. These data are consistent with a proposed link between the late positive repetition effect and conscious memory. On the other hand, the N400 repetition effect was not correlated with episodic memory abilities, but instead indexed an aspect of memory that was intact in the amnesic patients. The preserved N400 repetition effect is an example of preserved memory in amnesia that does not easily fit into the categories of low-level perceptual processing or of motor learning. Instead, the sensitivity of the N400 to both semantic context and repetition may reflect a short-term memory process that serves language comprehension in realtime.