Artificial intelligence-based classification of echocardiographic views.

Aims: Augmenting echocardiography with artificial intelligence would allow for automated assessment of routine parameters and identification of disease patterns not easily recognized otherwise. View classification is an essential first step before deep learning can be applied to the echocardiogram. Methods and results: We trained two- and three-dimensional convolutional neural networks (CNNs) using transthoracic echocardiographic (TTE) studies obtained from 909 patients to classify nine view categories (10 269 videos). Transthoracic echocardiographic studies from 229 patients were used in internal validation (2582 videos). Convolutional neural networks were tested on 100 patients with comprehensive TTE studies (where the two examples chosen by CNNs as most likely to represent a view were evaluated) and 408 patients with five view categories obtained via point-of-care ultrasound (POCUS). The overall accuracy of the two-dimensional CNN was 96.8%, and the averaged area under the curve (AUC) was 0.997 on the comprehensive TTE testing set; these numbers were 98.4% and 0.998, respectively, on the POCUS set. For the three-dimensional CNN, the accuracy and AUC were 96.3% and 0.998 for full TTE studies and 95.0% and 0.996 on POCUS videos, respectively. The positive predictive value, which defined correctly identified predicted views, was higher with two-dimensional rather than three-dimensional networks, exceeding 93% in apical, short-axis aortic valve, and parasternal long-axis left ventricle views. Conclusion: An automated view classifier utilizing CNNs was able to classify cardiac views obtained using TTE and POCUS with high accuracy. The view classifier will facilitate the application of deep learning to echocardiography.

The reading-attention relationship: Variations in working memory network activity during single word decoding in children with and without dyslexia.

This study utilized a neuroimaging task to assess working memory (WM) network recruitment during single word reading. Associations between WM and reading comprehension skills are well documented. Several converging models suggest WM may also contribute to foundational reading skills, but few studies have assessed this contribution directly. Two groups of children (77 developmental dyslexia (DD), 22 controls) completed a functional magnetic resonance imaging (fMRI) task to identify activation of a priori defined regions of the WM network. fMRI trials consisted of familiar word, pseudoword, and false font stimuli within a 1-back oddball task to assess how activation in the WM network differs in response to stimuli that can respectively be processed using word recognition, phonological decoding, or non-word strategies. Results showed children with DD recruited WM regions bilaterally in response to all stimulus types, whereas control children recruited left-lateralized WM regions during the pseudoword condition only. Group-level comparisons revealed activation differences in the defined WM network regions for false font and familiar word, but not pseudoword conditions. This effect was driven by increased activity in participants with DD in right hemisphere frontal, parietal, and motor regions despite poorer task performance. Findings suggest the WM network may contribute to inefficient decoding and word recognition strategies in children with DD.

Properties of white matter tract diffusivity in children with developmental dyslexia and comorbid attention deficit/hyperactivity disorder.

BACKGROUND: Developmental dyslexia (DD) and attention deficit/hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders. Individuals with DD or ADHD have both been shown to have deficits in white matter tracts associated with reading and attentional control networks. However, white matter diffusivity in individuals comorbid with both DD and ADHD (DD + ADHD) has not been specifically explored. METHODS: Participants were 3rd and 4th graders (age range = 7 to 11 years; SD = 0.69) from three diagnostic groups ((DD (n = 40), DD + ADHD (n = 22), and typical developing (TD) (n = 20)). Behavioral measures of reading and attention alongside measures of white matter diffusivity were collected for all participants. RESULTS: DD + ADHD and TD groups differed in mean fractional anisotropy (FA) for the left and right Superior Longitudinal Fasciculus (SLF)-Parietal Terminations and SLF-Temporal Terminations. Mean FA for the DD group across these SLF tracts fell between the lower DD + ADHD and higher TD averages. No differences in mean diffusivity nor significant brain-behavior relations were found. CONCLUSIONS: Findings suggest that WM diffusivity in the SLF increases along a continuum across DD + ADHD, DD, and TD.

Within-individual BOLD signal variability in the N-back task and its associations with vigilance and working memory.

In a group of healthy adults (N = 48), this study evaluated how fMRI Blood Oxygen Level-Dependent (BOLD) signal variability differed across letter n-back task load and quantified the extent to which BOLD signal variability was associated with in-scanner accuracy and reaction time as well as out-of-scanner measures of vigilance and working memory (WM). Within-individual BOLD signal variability in regions of interest (ROIs, identified as peak coordinates in an attention/vigilance and WM network using Neurosynth) was differentially modulated across vigilance and WM trials. Within-individual BOLD signal variability was significantly greater across the majority of the ROIs in the working memory trials (2- and 3-back trials) compared to 0-back trials. Notably, this increased variability across the network was accompanied by significantly less variability in the left cingulate gyrus and left inferior temporal lobe during the working memory trials. Significantly fewer differences in within-individual BOLD signal variability were identified for vigilance trials (0- and 1-back trials) compared to crosshair. We hypothesized that increased BOLD signal variability would be associated with n-back task performance and with out-of-scanner measures of vigilance (Digit Span Forward) and WM (Auditory Consonant Trigrams and Digit Span Backward). These results were non-significant after correcting for multiple comparisons. Furthermore, using multivariate analyses (partial least squares regression; PLS-R), within-individual BOLD signal variability in regions associated with a WM-vigilance network did not significantly predict out-of-scanner test performance after appropriate cross validation, yet provided a promising trend for WM trials; greater within-individual BOLD signal variability during WM n-back trials was associated with decreased performance on all included neuropsychological measures, which provides partial support for previous findings. This study demonstrates that patterns of variability differ based on task load in the scanner and illustrates an intriguing association between within-individual BOLD signal variability and out-of-scanner behavioral performance that may be better explored in future studies with a larger sample size.

Sex-specific associations between traumatic experiences and resting-state functional connectivity in the Philadelphia Neurodevelopmental Cohort.

BACKGROUND: Traumatic experiences during childhood or adolescence are a significant risk factor for multiple psychiatric disorders and adversely affect multiple cognitive functions. Resting-state functional magnetic resonance imaging has been used to investigate the effects of traumatic experiences on functional connectivity, but the impact of sex differences has not been well documented. This study investigated sex-specific associations between resting-state functional connectivity (rsFC) and traumatic experiences in typically developing youth. METHODS: The sample comprised 1395 participants, aged 8-21 years, from the Philadelphia Neurodevelopmental Cohort. Traumatic experiences were assessed based on the structured psychiatric evaluation. Sex, the number of traumatic events, and their interaction were regressed onto voxel-wise intrinsic connectivity distribution parameter values derived from resting-state functional magnetic resonance imaging. Brain regions that passed cluster correction were used as seeds to define resting-state networks. RESULTS: After quality control, the final sample had 914 participants with mean (SD) age 14.6 (3.3) years; 529 (57.8%) females; 437 (47.8%) experienced at least one kind of traumatic event. Four discrete anatomical clusters showed decreased functional connectivity as the number of traumatic events increased. The resting-state networks defined by using these four clusters as seeds corresponded with the somatomotor network. Sex-specific associations were identified in another three clusters for which males showed increased connectivity, and females showed decreased connectivity as the number of traumatic events increased. The resting-state networks defined by the three sex-specific clusters corresponded with the default mode network (DMN). CONCLUSIONS: In youth without psychiatric diagnoses, traumatic experiences are associated with an alteration of rsFC in brain regions corresponding with the somatomotor network. Associations differ in direction between males and females in brain regions corresponding with the DMN, suggesting sex-specific responses to early exposure to trauma.

Is that a pibu or a pibo? Children with reading and language deficits show difficulties in learning and overnight consolidation of phonologically similar pseudowords.

Word learning is critical for the development of reading and language comprehension skills. Although previous studies have indicated that word learning is compromised in children with reading disability (RD) or developmental language disorder (DLD), it is less clear how word learning difficulties manifest in children with comorbid RD and DLD. Furthermore, it is unclear whether word learning deficits in RD or DLD include difficulties with offline consolidation of newly learned words. In the current study, we employed an artificial lexicon learning paradigm with an overnight design to investigate how typically developing (TD) children (N = 25), children with only RD (N = 93), and children with both RD and DLD (N = 34) learned and remembered a set of phonologically similar pseudowords. Results showed that compared to TD children, children with RD exhibited: (i) slower growth in discrimination accuracy for cohort item pairs sharing an onset (e.g. pibu-pibo), but not for rhyming item pairs (e.g. pibu-dibu); and (ii) lower discrimination accuracy for both cohort and rhyme item pairs on Day 2, even when accounting for differences in Day 1 learning. Moreover, children with comorbid RD and DLD showed learning and retention deficits that extended to unrelated item pairs that were phonologically dissimilar (e.g. pibu-tupa), suggestive of broader impairments compared to children with only RD. These findings provide insights into the specific learning deficits underlying RD and DLD and motivate future research concerning how children use phonological similarity to guide the organization of new word knowledge.

The temporal dynamics of first and second language processing: ERPs to spoken words in Mandarin-English bilinguals.

The dynamics of bilingual spoken word recognition remain poorly characterized, especially for individuals who speak two languages that are highly dissimilar in their phonological and morphological structure. The present study compared first language (L1) and second language (L2) spoken word processing within a group of adult Mandarin-English bilinguals (N = 34; ages 18-25). Event-related potentials (ERPs) were recorded while participants completed the same cross-modal matching task separately in their L1 Mandarin and L2 English. This task consisted of deciding whether spoken words matched pictures of items. Pictures and spoken words either matched (e.g., Mandarin: TANG2-tang2; English: BELL-bell), or differed in word-initial phonemes (e.g., Mandarin: TANG2-lang2; English: BELL-shell), word-final phonemes (e.g., Mandarin: TANG2-tao2; English: BELL-bed), or whole words (e.g., Mandarin: TANG2-xia1: English: BELL-ham). Each mismatch type was associated with a pattern of modulation of the Phonological Mapping Negativity, the N400, and the Late N400 that was distinct from those of the other mismatch types yet similar between the two languages. This was interpreted as evidence of incremental processing with similar temporal dynamics in both languages. These findings support models of spoken word recognition in bilingual individuals that adopt an interactive-activation framework for both L1 and L2 processing.

Effect of READ1 on latent profiles of reading disorder and comorbid attention and language impairment subtypes.

Recent studies of co-occurring reading disorder (RD) and attention deficit/hyperactivity disorder (ADHD), and co-occurring RD and language impairment (LI), support a core disability plus co-occurrence model focused on language and attention. Genetic factors have been associated with poor reading performance. However, little is known about whether different genetic variants independently contribute to RD co-occurrence subtypes. We aimed to identify subgroups of struggling readers using a latent profile analysis (LPA) in a sample of 1,432 Hispanic American and African American youth. RD classes were then tested for association with variants of READ1, a regulatory element within the candidate RD risk gene, DCDC2. Six groups were identified in the LPA using RD designation as a known-class variable. The three RD classes identified groups of subjects with neurocognitive profiles representing RD+ADHD, specific phonological deficit RD, and RD+LI. Genetic associations across RD subtypes were investigated against functional groupings of READ1. The RU1-1 group of READ1 alleles was associated with RD cases that were marked by deficits in both processing speed and attention (RD+ADHD). The DCDC2 microdeletion that encompasses READ1 was associated with RD cases showing a phonological deficit RD profile. These findings provide evidence for differential genetic contribution to RD subtypes, and that previously implicated genetic variants for RD may share an underlying genetic architecture across population groups for reading disorder.

Examining individual differences in reading and attentional control networks utilizing an oddball fMRI task.

The aim of the current study was to develop an fMRI task capable of characterizing individual differences in reading and attentional domains. Forty-nine students with a range of reading and attentional control abilities completed an event-related fMRI oddball task consisting of printed word and false font stimuli. Reading network activation was assessed by contrasting printed words with false font stimuli. Left inferior frontal gyrus and superior/middle temporal gyrus showed a main effect of stimulus type. The magnitude of the difference in activation between words and false font was correlated with word reading for both regions and reading fluency for superior/middle temporal gyrus. Regions including bilateral middle cingulate, insula and right inferior frontal gyrus showed a main effect of trial type. The difference in activation between oddball and standard trials in the right superior/middle temporal gyrus and left cerebellum was correlated with attentional control measures. Results indicate the task tapped both reading and attentional control resources. Understanding the contribution of the neural networks supporting each of these domains may provide insight into the shared neural deficits underlying the co-morbidity between developmental dyslexia and attention deficit hyperactivity disorder.

Common neural basis of motor sequence learning and word recognition and its relation with individual differences in reading skill.

To investigate the neural basis of a common statistical learning mechanism involved in motor sequence learning and decoding, we recorded same participants' brain activation in a serial reaction time (SRT) and word reading task using functional magnetic resonance imaging. In the SRT, a manual response was made depending on the location of a visual cue, and the order of the locations was either fixed or random. In the word reading task, visual words were passively presented. Compared to less skilled readers, more skilled readers showed greater differences in activation in the inferior frontal gyrus pars triangularis (IFGpTr) and the insula between the ordered and random condition in the SRT task and greater activation in those regions in the word reading task. It suggests that extraction of statistically predictable patterns in the IFGpTr and insula contributes to both motor sequence learning and orthographic learning, and therefore predicts individual differences in decoding skill.

Worldwide distribution of the DCDC2 READ1 regulatory element and its relationship with phoneme variation across languages.

DCDC2 is a gene strongly associated with components of the phonological processing system in animal models and in multiple independent studies of populations and languages. We propose that it may also influence population-level variation in language component usage. To test this hypothesis, we investigated the evolution and worldwide distribution of the READ1 regulatory element within DCDC2, and compared its distribution with variation in different language properties. The mutational history of READ1 was estimated by examining primate and archaic hominin sequences. This identified duplication and expansion events, which created a large number of polymorphic alleles based on internal repeat units (RU1 and RU2). Association of READ1 alleles was studied with respect to the numbers of consonants and vowels for languages in 43 human populations distributed across five continents. Using population-based approaches with multivariate ANCOVA and linear mixed effects analyses, we found that the RU1-1 allele group of READ1 is significantly associated with the number of consonants within languages independent of genetic relatedness, geographic proximity, and language family. We propose that allelic variation in READ1 helped create a subtle cognitive bias that was amplified by cultural transmission, and ultimately shaped consonant use by different populations over time.

Individual Differences in Reading Skill Are Related to Trial-by-Trial Neural Activation Variability in the Reading Network.

Recent work has suggested that variability in levels of neural activation may be related to behavioral and cognitive performance across a number of domains and may offer information that is not captured by more traditional measures that use the average level of brain activation. We examined the relationship between reading skill in school-aged children and neural activation variability during a functional MRI reading task after taking into account average levels of activity. The reading task involved matching printed and spoken words to pictures of items. Single trial activation estimates were used to calculate the mean and standard deviation of children's responses to print and speech stimuli; multiple regression analyses evaluated the relationship between reading skill and trial-by-trial activation variability. The reliability of observed findings from the discovery sample (n = 44; ages 8-11; 18 female) was then confirmed in an independent sample of children (n = 32; ages 8-11; 14 female). Across the two samples, reading skill was positively related to trial-by-trial variability in the activation response to print in the left inferior frontal gyrus pars triangularis. This relationship held even when accounting for mean levels of activation. This finding suggests that intrasubject variability in trial-by-trial fMRI activation responses to printed words accounts for individual differences in human reading ability that are not fully captured by traditional mean levels of brain activity. Furthermore, this positive relationship between trial-by-trial activation variability and reading skill may provide evidence that neural variability plays a beneficial role during early reading development.SIGNIFICANCE STATEMENT Recent work has suggested that neural activation variability, or moment-to-moment changes in the engagement of brain regions, is related to individual differences in behavioral and cognitive performance across multiple domains. However, differences in neural activation variability have not yet been evaluated in relation to reading skill. In the current study, we analyzed data from two independent groups of children who performed an fMRI task involving reading and listening to words. Across both samples, reading skill was positively related to trial-by-trial variability in activation to print stimuli in the left inferior frontal gyrus pars triangularis, even when accounting for the more conventional measure of mean levels of brain activity. This finding suggests that neural variability could be beneficial in developing readers.

Neural representations for newly learned words are modulated by overnight consolidation, reading skill, and age.

Word learning depends not only on efficient online binding of phonological, orthographic and lexical information, but also on consolidation of new word representations into permanent lexical memory. Work on word learning under a variety of contexts indicates that reading and language skill impact facility of word learning in both print and speech. In addition, recent research finds that individuals with language impairments show deficits in both initial word form learning and in maintaining newly learned representations over time, implicating mechanisms associated with maintenance that may be driven by deficits in overnight consolidation. Although several recent studies have explored the neural bases of overnight consolidation of newly learned words, no extant work has examined individual differences in overnight consolidation at the neural level. The current study addresses this gap in the literature by investigating how individual differences in reading and language skills modulate patterns of neural activation associated with newly learned words following a period of overnight consolidation. Specifically, a community sample of adolescents and young adults with significant variability in reading and oral language (vocabulary) ability were trained on two spoken artificial lexicons, one in the evening on the day before fMRI scanning and one in the morning just prior to scanning. Comparisons of activation between words that were trained and consolidated vs. those that were trained but not consolidated revealed increased cortical activation in a number of language associated and memory associated regions. In addition, individual differences in age, reading skill and vocabulary modulated learning rate in our artificial lexicon learning task and the size of the cortical consolidation effect in the precuneus/posterior cingulate, such that older readers and more skilled readers had larger cortical consolidation effects in this learning-critical region. These findings suggest that age (even into late adolescence) and reading and language skills are important individual differences that affect overnight consolidation of newly learned words. These findings have significant implications for understanding reading and language disorders and should inform pedagogical models.

A molecular-genetic and imaging-genetic approach to specific comprehension difficulties in children.

Children with poor reading comprehension despite typical word reading skills were examined using neuropsychological, genetic, and neuroimaging data collected from the Genes, Reading and Dyslexia Study of 1432 Hispanic American and African American children. This unexpected poor comprehension was associated with profound deficits in vocabulary, when compared to children with comprehension skills consistent with their word reading. Those with specific comprehension difficulties were also more likely to have RU2Short alleles of READ1 regulatory variants of DCDC2, strongly associated with reading and language difficulties. Subjects with RU2Short alleles showed stronger resting state functional connectivity between the right insula/inferior frontal gyrus and the right supramarginal gyrus, even after controlling for potentially confounding variables including genetic ancestry and socioeconomic status. This multi-disciplinary approach advances the current understanding of specific reading comprehension difficulties, and suggests the need for interventions that are more appropriately tailored to the specific comprehension deficits of this group of children.

Do you hear 'feather' when listening to 'rain'? Lexical tone activation during unconscious translation: Evidence from Mandarin-English bilinguals.

Although lexical tone is a highly prevalent phonetic cue in human languages, its role in bilingual spoken word recognition is not well understood. The present study investigates whether and how adult bilinguals, who use pitch contours to disambiguate lexical items in one language but not the other, access a tonal L1 when exclusively processing a non-tonal L2. Using the visual world paradigm, we show that Mandarin-English listeners automatically activated Mandarin translation equivalents of English target words such as 'rain' (Mandarin 'yu3'), and consequently were distracted by competitors whose segments and tones overlapped with the translations of English target words ('feather', also 'yu3' in Mandarin). Importantly, listeners were not distracted by competitors that overlapped with the translations of target words in all segments but not tone ('fish'; Mandarin 'yu2'), nor were they distracted by competitors that overlapped with the translations of target words in rime and tone ('wheat', Mandarin 'gu3'). These novel results demonstrate implicit access to L1 lexical representations through automatic/unconscious translation, as a result of cross-language top-down and/or lateral influence, and highlight the critical role of lexical tone activation in bilingual lexical access.

Dynamic spatial organization of the occipito-temporal word form area for second language processing.

Despite the left occipito-temporal region having shown consistent activation in visual word form processing across numerous studies in different languages, the mechanisms by which word forms of second languages are processed in this region remain unclear. To examine this more closely, 16 Chinese-English and 14 English-Chinese late bilinguals were recruited to perform lexical decision tasks to visually presented words in both their native and second languages (L1 and L2) during functional magnetic resonance imaging scanning. Here we demonstrate that visual word form processing for L1 versus L2 engaged different spatial areas of the left occipito-temporal region. Namely, the spatial organization of the visual word form processing in the left occipito-temporal region is more medial and posterior for L2 than L1 processing in Chinese-English bilinguals, whereas activation is more lateral and anterior for L2 in English-Chinese bilinguals. In addition, for Chinese-English bilinguals, more lateral recruitment of the occipito-temporal region was correlated with higher L2 proficiency, suggesting higher L2 proficiency is associated with greater involvement of L1-preferred mechanisms. For English-Chinese bilinguals, higher L2 proficiency was correlated with more lateral and anterior activation of the occipito-temporal region, suggesting higher L2 proficiency is associated with greater involvement of L2-preferred mechanisms. Taken together, our results indicate that L1 and L2 recruit spatially different areas of the occipito-temporal region in visual word processing when the two scripts belong to different writing systems, and that the spatial organization of this region for L2 visual word processing is dynamically modulated by L2 proficiency. Specifically, proficiency in L2 in Chinese-English is associated with assimilation to the native language mechanisms, whereas L2 in English-Chinese is associated with accommodation to second language mechanisms.

Encoding lexical tones in jTRACE: a simulation of monosyllabic spoken word recognition in Mandarin Chinese.

Despite its prevalence as one of the most highly influential models of spoken word recognition, the TRACE model has yet to be extended to consider tonal languages such as Mandarin Chinese. A key reason for this is that the model in its current state does not encode lexical tone. In this report, we present a modified version of the jTRACE model in which we borrowed on its existing architecture to code for Mandarin phonemes and tones. Units are coded in a way that is meant to capture the similarity in timing of access to vowel and tone information that has been observed in previous studies of Mandarin spoken word recognition. We validated the model by first simulating a recent experiment that had used the visual world paradigm to investigate how native Mandarin speakers process monosyllabic Mandarin words (Malins & Joanisse, 2010). We then subsequently simulated two psycholinguistic phenomena: (1) differences in the timing of resolution of tonal contrast pairs, and (2) the interaction between syllable frequency and tonal probability. In all cases, the model gave rise to results comparable to those of published data with human subjects, suggesting that it is a viable working model of spoken word recognition in Mandarin. It is our hope that this tool will be of use to practitioners studying the psycholinguistics of Mandarin Chinese and will help inspire similar models for other tonal languages, such as Cantonese and Thai.

Dough, tough, cough, rough: A "fast" fMRI localizer of component processes in reading.

In the current study, we present a novel fMRI protocol in which words, pseudowords, and other word-like stimuli are passively presented in a rapid, sequential fashion. In this "fast" localizer paradigm, items are presented in groups of four; within sets, words are related in orthographic, phonological, and/or semantic properties. We tested this protocol with a group of skilled adult readers (N=18). Analyses uncovered key regions of the reading network that were sensitive to different component processes at the group level; namely, left fusiform gyrus as well as the pars opercularis subregion of inferior frontal gyrus were sensitive to lexicality; several regions including left precentral gyrus and left supramarginal gyrus were sensitive to spelling-sound consistency; the pars triangularis subregion of inferior frontal gyrus was sensitive to semantic similarity. Additionally, in a number of key brain regions, activation in response to semantically similar words was related to individual differences in reading comprehension outside the scanner. Importantly, these findings are in line with previous investigations of the reading network, yet data were obtained using much less imaging time than comparable paradigms currently available, especially relative to the number of indices of component processes obtained. This feature, combined with the relatively simple nature of the task, renders it appropriate for groups of subjects with a wide range of reading abilities, including children with impairments.

Developmental differences in the influence of phonological similarity on spoken word processing in Mandarin Chinese.

The developmental trajectory of spoken word recognition has been well established in Indo-European languages, but to date remains poorly characterized in Mandarin Chinese. In this study, typically developing children (N=17; mean age 10; 5) and adults (N=17; mean age 24) performed a picture-word matching task in Mandarin while we recorded ERPs. Mismatches diverged from expectations in different components of the Mandarin syllable; namely, word-initial phonemes, word-final phonemes, and tone. By comparing responses to different mismatch types, we uncovered evidence suggesting that both children and adults process words incrementally. However, we also observed key developmental differences in how subjects treated onset and rime mismatches. This was taken as evidence for a stronger influence of top-down processing on spoken word recognition in adults compared to children. This work therefore offers an important developmental component to theories of Mandarin spoken word recognition.

The reliability of the N400 in single subjects: implications for patients with disorders of consciousness.

Functional neuroimaging assessments of residual cognitive capacities, including those that support language, can improve diagnostic and prognostic accuracy in patients with disorders of consciousness. Due to the portability and relative inexpensiveness of electroencephalography, the N400 event-related potential component has been proposed as a clinically valid means to identify preserved linguistic function in non-communicative patients. Across three experiments, we show that changes in both stimuli and task demands significantly influence the probability of detecting statistically significant N400 effects - that is, the difference in N400 amplitudes caused by the experimental manipulation. In terms of task demands, passively heard linguistic stimuli were significantly less likely to elicit N400 effects than task-relevant stimuli. Due to the inability of the majority of patients with disorders of consciousness to follow task commands, the insensitivity of passive listening would impede the identification of residual language abilities even when such abilities exist. In terms of stimuli, passively heard normatively associated word pairs produced the highest detection rate of N400 effects (50% of the participants), compared with semantically-similar word pairs (0%) and high-cloze sentences (17%). This result is consistent with a prediction error account of N400 magnitude, with highly predictable targets leading to smaller N400 waves, and therefore larger N400 effects. Overall, our data indicate that non-repeating normatively associated word pairs provide the highest probability of detecting single-subject N400s during passive listening, and may thereby provide a clinically viable means of assessing residual linguistic function. We also show that more liberal analyses may further increase the detection-rate, but at the potential cost of increased false alarms.