Dopamine Measurement Using Engineered CNT-CQD-Polymer Coatings on Pt Microelectrodes.

This study aims to develop a microelectrode array-based neural probe that can record dopamine activity with high stability and sensitivity. To mimic the high stability of the gold standard method (carbon fiber electrodes), the microfabricated platinum microelectrode is coated with carbon-based nanomaterials. Carboxyl-functionalized multi-walled carbon nanotubes (COOH-MWCNTs) and carbon quantum dots (CQDs) were selected for this purpose, while a conductive polymer like poly (3-4-ethylene dioxythiophene) (PEDOT) or polypyrrole (PPy) serves as a stable interface between the platinum of the electrode and the carbon-based nanomaterials through a co-electrodeposition process. Based on our comparison between different conducting polymers and the addition of CQD, the CNT-CQD-PPy modified microelectrode outperforms its counterparts: CNT-CQD-PEDOT, CNT-PPy, CNT-PEDOT, and bare Pt microelectrode. The CNT-CQD-PPy modified microelectrode has a higher conductivity, stability, and sensitivity while achieving a remarkable limit of detection (LOD) of 35.20 ± 0.77 nM. Using fast-scan cyclic voltammetry (FSCV), these modified electrodes successfully measured dopamine's redox peaks while exhibiting consistent and reliable responses over extensive use. This electrode modification not only paves the way for real-time, precise dopamine sensing using microfabricated electrodes but also offers a novel electrochemical sensor for in vivo studies of neural network dynamics and neurological disorders.

Examining interrater agreement between self-report and proxy-report responses for the quality of life-aged care consumers (QOL-ACC) instrument.

BACKGROUND: Quality of life is an important quality indicator for health and aged care sectors. However, self-reporting of quality of life is not always possible given the relatively high prevalence of cognitive impairment amongst older people, hence proxy reporting is often utilised as the default option. Internationally, there is little evidence on the impact of proxy perspective on interrater agreement between self and proxy report. OBJECTIVES: To assess the impacts of (i) cognition level and (ii) proxy perspective on interrater agreement using a utility instrument, the Quality of Life-Aged Care Consumers (QOL-ACC). METHODS: A cross-sectional study was undertaken with aged care residents and family member proxies. Residents completed the self-report QOL-ACC, while proxies completed two proxy versions: proxy-proxy perspective (their own opinion), and proxy-person perspective (how they believe the resident would respond). Interrater agreement was assessed using quadratic weighted kappas for dimension-level data and concordance correlation coefficients and Bland-Altman plots for utility scores. RESULTS: Sixty-three residents (22, no cognitive impairment; 41, mild-to-moderate cognitive impairment) and proxies participated. In the full sample and in the mild-to-moderate impairment group, the mean self-reported QOL-ACC utility score was significantly higher than the means reported by proxies, regardless of perspective (p < 0.01). Agreement with self-reported QOL-ACC utility scores was higher when proxies adopted a proxy-person perspective. CONCLUSION: Regardless of cognition level and proxy perspective, proxies tend to rate quality of life lower than residents. Further research is needed to explore the impact of such divergences for quality assessment and economic evaluation in aged care.

Exploring older people's understanding of the QOL-ACC, a new preference-based quality-of-life measure, for quality assessment and economic evaluation in aged care: the impact of cognitive impairment and dementia.

BACKGROUND: Quality-of-life is an essential outcome for quality assessment and economic evaluation in health and social care. The-Quality-of-Life - Aged Care Consumers (QOL-ACC) is a new preference-based quality-of-life measure, psychometrically validated with older people in aged care. More evidence is needed to inform the self-report reliability of the QOL-ACC in older people with varying levels of cognitive impairment and dementia. METHODS: A think-aloud protocol was developed and applied with older residents. The Mini Mental State Examination (MMSE) was applied to assign participants to no cognitive impairment (NCI - MMSE score ≥ 27) and cognitive impairment (MMCI - MMSE score < 27) subgroups. Three independent raters utilised a Tourangeau survey response model-based framework to identify response issues. Data were compared across cognition subgroups and synthesized using a 'traffic light' grading to classify frequency and type of response issues. Gradings were utilised to assess self-report reliability according to different levels of cognitive impairment. RESULTS: Qualitative data from 44 participants (NCI = 20, MMCI = 24) were included for analysis. Response issues were more evident in the cognitive impairment subgroup than the no cognitive impairment subgroup. All participants who received a 'red' grade had an MMSE score of < 20 and 66% of 'amber' grades occurred in the cognitive impairment subgroup. CONCLUSIONS: The QOL-ACC is able to be completed reliably by older residents with an MMSE score > 17. Future research is needed to assess the generalisability of these findings to other preference-based quality of life instruments and for older people in other care settings including health systems.

The role of systematicity in early referent selection.

Previous studies showed that word learning is affected by children's existing knowledge. For instance, knowledge of semantic category aids word learning, whereas a dense phonological neighbourhood impedes learning of similar-sounding words. Here, we examined to what extent children associate similar-sounding words (e.g., rat and cat) with objects of the same semantic category (e.g., both are animals), that is, to what extent children assume meaning overlap given form overlap between two words. We tested this by first presenting children (N = 93, Mage = 22.4 months) with novel word-object associations. Then, we examined the extent to which children assume that a similar sounding novel label, that is, a phonological neighbour, refers to a similar looking object, that is, a likely semantic neighbour, as opposed to a dissimilar looking object. Were children to preferentially fixate the similar-looking novel object, it would suggest that systematic word form-meaning relations aid referent selection in young children. While we did not find any evidence for such word form-meaning systematicity, we demonstrated that children showed robust learning for the trained novel word-object associations, and were able to discriminate between similar-sounding labels and also similar-looking objects. Thus, we argue that unlike iconicity which appears early in vocabulary development, we find no evidence for systematicity in early referent selection.

Unravelling the Self-Report Versus Proxy-Report Conundrum for Older Aged Care Residents: Findings from a Mixed-Methods Study.

OBJECTIVES: No guidance currently exists as to the cognition threshold beyond which self-reported quality of life for older people with cognitive impairment and dementia is unreliable. METHODS: Older aged care residents (≥ 65 years) were randomly assigned to complete the EQ-5D-5L in computer-based (eye movements were tracked) or hard copy (participants were encouraged to 'think aloud') format. Cognition was assessed using the Mini-Mental State Examination (MMSE). Think aloud and eye tracking data were analysed by two raters, blinded to MMSE scores. At the participant level, predefined criteria were used to assign traffic light grades (green, amber, red). These grades indicate the extent to which extracted data elements provided evidence of self-report reliability. The MMSE-defined cognition threshold was determined following review of the distributions of assigned traffic light grades. RESULTS: Eighty-one residents participated and provided complete data (38 eye tracking, 43 think aloud). In the think aloud cohort, all participants with an MMSE score ≤ 23 (n = 10) received an amber or red grade, while 64% of participants with an MMSE score ≥ 24 (21 of 33) received green grades. In the eye tracking cohort, 68% of participants with an MMSE score ≥ 24 (15 of 22) received green grades. Of the 16 eye tracking participants with an MMSE score ≤ 23, 14 (88%) received an amber or red grade. CONCLUSIONS: Most older residents with an MMSE score ≥ 24 have sufficient cognitive capacity to self-complete the EQ-5D-5L. More research is needed to better understand self-completion reliability for other quality-of-life instruments in cognitively impaired populations.

Feasibility of self-reported health related quality of life assessment with older people in residential care: insights from the application of eye tracking technology.

PURPOSE: Increasingly there are calls to routinely assess the health-related quality of life (HRQoL) of older people receiving aged care services, however the high prevalence of dementia and cognitive impairment remains a challenge to implementation. Eye-tracking technology facilitates detailed assessment of engagement and comprehension of visual stimuli, and may be useful in flagging individuals and populations who cannot reliably self-complete HRQoL instruments. The aim of this study was to apply eye-tracking technology to provide insights into self-reporting of HRQoL among older people in residential care with and without cognitive impairment. METHODS: Residents (n = 41), recruited based on one of three cognition subgroups (no, mild, or moderate cognitive impairment), completed the EQ-5D-5L on a computer with eye tracking technology embedded. Number and length of fixations (i.e., eye gaze in seconds) for key components of the EQ-5D-5L descriptive system were calculated. RESULTS: For all dimensions, participants with no cognitive impairment fixated for longer on the Area of Interest (AOI) for the response option they finally chose, relative to those with mild or moderate cognitive impairment. Participants with cognitive impairment followed similar fixation patterns to those without. There was some evidence that participants with cognitive impairment took longer to complete and spent relatively less time attending to the relevant AOIs, but these differences did not reach statistical significance generally. CONCLUSIONS: This exploratory study applying eye tracking technology provides novel insights and evidence of the feasibility of self-reported HRQoL assessments in older people in aged care settings where cognitive impairment and dementia are highly prevalent.

How do older adults receiving aged care services understand and respond to the EQ-5D-5L? A think-aloud study in residential care.

PURPOSE: The EQ-5D-5L is a preference-based instrument for measuring and valuing health-related quality of life (HRQoL). The EQ-5D-5L has been used extensively in economic evaluation, including in aged care. However, older adults' understanding of the EQ-5D-5L has not been comprehensively investigated to date. This research aimed to assess older adults' understanding of the EQ-5D-5L using a think-aloud protocol with two cognition groups: no cognitive impairment and mild/moderate cognitive impairment. METHODS: Participants' cognition was assessed using the Standardised Mini-Mental State Examination (SMMSE). Face-to face interviews were conducted with concurrent and retrospective think-aloud encouraged through verbal probing. Audio recordings were transcribed, and qualitative analysis, informed by the Tourangeau four-stage Response Model (comprehension, retrieval, decision process, response process) was conducted in NVivo. RESULTS: In total, 46 older adults (age 65 +) were recruited from 10 residential care facilities across South Australia (n = 25 no cognitive impairment, n = 21 mild/moderate cognitive impairment). Comprehension, retrieval, judgement and response mapping issues were common across all cognition levels and EQ-5D-5L dimensions. The two dimensions resulting in the most response issues were usual activities and personal care. CONCLUSION: Older adults may bring a different understanding to the EQ-5D-5L descriptive system than that expected given testing with general population samples. Dimension descriptors that are more relevant to this population may facilitate responses that better align with the underlying EQ-5D-5L concept model.

A 512-Ch Dual-Mode Microchip for Simultaneous Measurements of Electrophysiological and Neurochemical Activities.

In the study of the brain, large and high-density microelectrode arrays have been widely used to study the behavior of neurotransmission. CMOS technology has facilitated these devices by enabling the integration of high-performance amplifiers directly on-chip. Usually, these large arrays measure only the voltage spikes resulting from action potentials traveling along firing neuronal cells. However, at synapses, communication between neurons occurs by the release of neurotransmitters, which cannot be measured on typical CMOS electrophysiology devices. Development of electrochemical amplifiers has resulted in the measurement of neurotransmitter exocytosis down to the level of a single vesicle. To effectively monitor the complete picture of neurotransmission, measurement of both action potentials and neurotransmitter activity is needed. Current efforts have not resulted in a device that is capable of the simultaneous measurement of action potential and neurotransmitter release at the same spatiotemporal resolution needed for a comprehensive study of neurotransmission. In this paper, we present a true dual-mode CMOS device that fully integrates 256-ch electrophysiology amplifiers and 256-ch electrochemical amplifiers, along with an on-chip 512 electrode microelectrode array capable of simultaneous measurement from all 512 channels.

The P600 as a continuous index of integration effort.

The integration of word meaning into an unfolding utterance representation is a core operation of incremental language comprehension. There is considerable debate, however, as to which component of the ERP signal-the N400 or the P600-directly reflects integrative processes, with far reaching consequences for the temporal organization and architecture of the comprehension system. Multi-stream models maintaining the N400 as integration crucially rely on the presence of a semantically attractive plausible alternative interpretation to account for the absence of an N400 effect in response to certain semantic anomalies, as reported in previous studies. The single-stream Retrieval-Integration account posits the P600 as an index of integration, further predicting that its amplitude varies continuously with integrative effort. Here, we directly test these competing hypotheses using a context manipulation design in which a semantically attractive alternative is either available or not, and target word plausibility is varied across three levels. An initial self-paced reading study revealed graded reading times for plausibility, suggesting differential integration effort. A subsequent ERP study showed no N400 differences across conditions, and that P600 amplitude is graded for plausibility. These findings are inconsistent with the interpretation of the N400 as an index of integration, as no N400 effect emerged even in the absence of a semantically attractive alternative. By contrast, the link between plausibility, reading times, and P600 amplitude supports the view that the P600 is a continuous index of integration effort. More generally, our results support a single-stream architecture and eschew the need for multi-stream accounts.

When a look is enough: Neurophysiological correlates of referential speaker gaze in situated comprehension.

Behavioral studies have shown that speaker gaze to objects in a co-present scene can influence listeners' expectations about how the utterance will unfold. These findings have recently been supported by ERP studies that linked the underlying mechanisms of the integration of speaker gaze with an utterance meaning representation to multiple ERP components. This leads to the question, however, as to whether speaker gaze should be considered part of the communicative signal itself, such that the referential information conveyed by gaze can help listeners not only form expectations but also to confirm referential expectations induced by the prior linguistic context. In the current study, we investigated this question by conducting an ERP experiment (N=24, Age:[19,31]), in which referential expectations were established by linguistic context together with several depicted objects in the scene. Those expectations then could be confirmed by subsequent speaker gaze that preceded the referential expression. Participants were presented with a centrally positioned face performing gaze actions aligned to utterances comparing two out of three displayed objects, with the task to judge whether the sentence was true given the provided scene. We manipulated the gaze cue to be either Present (toward the subsequently named object) or Absent preceding contextually Expected or Unexpected referring nouns. The results provided strong evidence for gaze as being treated as an integral part of the communicative signal: While in the absence of gaze, effects of phonological verification (PMN), word meaning retrieval (N400) and sentence meaning integration/evaluation (P600) were found on the unexpected noun, in the presence of gaze effects of retrieval (N400) and integration/evaluation (P300) were solely found in response to the pre-referent gaze cue when it was directed toward the unexpected referent with attenuated effects on the following referring noun.

Modulation of myeloid and T cells in vivo by Bruton's tyrosine kinase inhibitor ibrutinib in patients with metastatic pancreatic ductal adenocarcinoma.

BACKGROUND: In preclinical studies of pancreatic ductal adenocarcinoma (PDAC), ibrutinib improved the antitumor efficacy of the standard of care chemotherapy. This led to a phase 1b clinical trial to determine the safety, tolerability, and immunologic effects of ibrutinib treatment in patients with advanced PDAC. METHODS: Previously untreated patients with PDAC were enrolled in a phase 1b clinical trial (ClinicalTrials.gov) to determine the safety, toxicity, and maximal tolerated dose of ibrutinib when administered with the standard regimen of gemcitabine and nab-paclitaxel. To study the immune response to ibrutinib alone, the trial included an immune response arm where patients were administered with ibrutinib daily for a week followed by ibrutinib combined with gemcitabine and nab-paclitaxel. Endoscopic ultrasonography-guided primary PDAC tumor biopsies and blood were collected before and after ibrutinib monotherapy. Changes in abundance and functional state of immune cells in the blood was evaluated by mass cytometry by time of flight and statistical scaffold analysis, while that in the local tumor microenvironment (TME) were assessed by multiplex immunohistochemistry. Changes in B-cell receptor and T-cell receptor repertoire were assessed by sequencing and analysis of clonality. RESULTS: In the blood, ibrutinib monotherapy significantly increased the frequencies of activated inducible T cell costimulator+(ICOS+) CD4+ T cells and monocytes. Within the TME, ibrutinib monotherapy led to a trend in decreased B-cell abundance but increased interleukin-10+ B-cell frequency. Monotherapy also led to a trend in increased mature CD208+dendritic cell density, increased late effector (programmed cell death protein 1 (PD-1-) eomesodermin (EOMES+)) CD8+ T-cell frequency, with a concomitantly decreased dysfunctional (PD-1+ EOMES+) CD8+ T-cell frequency. When ibrutinib was combined with chemotherapy, most of these immune changes were not observed. Patients with partial clinical responses had more diverse T and B cell receptor repertoires prior to therapy initiation. CONCLUSION: Ibrutinib monotherapy skewed the immune landscape both in the circulation and TME towards activated T cells, monocytes and DCs. These effects were not observed when combining ibrutinib with standard of care chemotherapy. Future studies may focus on other therapeutic combinations that augment the immunomodulatory effects of ibrutinib in solid tumors. TRIAL REGISTRATION NUMBER: NCT02562898.

Are Australians willing to pay more tax to support wage increases for aged care workers? Findings from a national survey.

OBJECTIVE: To explore the perceptions of the Australian public regarding Australia's aged care workforce, including their willingness to pay more tax to fund better pay and conditions for aged care workers. METHODS: An online survey was developed and administered to a representative sample of Australian adults (aged ≥18 years) by age group, gender and Australian state. Survey respondents completed a series of attitudinal statements to elicit their perceptions of the value of Australia's aged care workforce and were asked to indicate their willingness to pay additional tax to fund better pay and conditions for aged care workers. Those who gave a positive response were then asked to indicate what percentage of additional tax per year they would be willing to pay to ensure better pay and conditions for aged care workers. RESULTS: A total of 2033 adult respondents completed the survey. A majority (78%) of respondents either 'agreed' or 'strongly agreed' that aged care workers should be paid more. Approximately half of the respondents (50.57%) expressed a willingness to pay more tax to ensure better pay and conditions for aged care workers. The mean willingness to pay was 1.31% additional tax overall, and mean percentage additional tax values were relatively consistent across key socio-demographic indicators. CONCLUSIONS: A majority of the Australian public are in favour of improving the wages and employment conditions of aged care workers. However, only one in two Australians is willing to pay more tax to ensure better pay and conditions for aged care workers.

Why are neurosurgeons sued? A single-center, half-decade review.

Purpose:The burden of medicolegal claims in neurosurgery is increasing in the UK. Trepidation associated with malpractice claims has the potential to negatively impact surgical practice and patient safety. What are the causes of these claims and can we address them? The aim of this study was to identify the incidence and total burden of litigation claims related to neurosurgery in a London tertiary center.Methods:We retrospectively reviewed all consecutive cases of claims in neurosurgery that were reported to NHSR between March 2013 and April 2018 by St George's Hospital legal department. This was an extension of previous study by Mukherjee et al., who studied the medicolegal claims in our institution in the preceding 9-year period (2004-2013).Results:There were 18 litigation claims against neurosurgery. Claims were reviewed for clinical event, cause, likelihood of pay-out and legal outcome. Eleven claims were settled in court and seven were settled without court proceeding. All claims were spinal cases, 56% emergency admissions. Causes included faulty surgical technique (39%), delayed treatment (33%), delayed diagnosis/misdiagnosis (17%), and lack of information (11%) with a likelihood of financial success of 43%, 67%, 33%, and 100%, respectively. The highest median pay-outs were for lack of information (£2.8 million) and faulty surgical technique (£1 million). When compared to the preceding 9-year period, there a modest reduction in claims per year, despite an increase in workload. Distribution of litigation causes remained similar but overall financial burden was higher.Conclusion:Spinal surgery has the highest malpractice claim risk in neurosurgical practice. Our review shows that faulty surgical technique is the leading cause of neurosurgical claims. Claims against lack of information, although less frequent, resulted in the highest median pay-out. This study reinforces previously published data that good surgical technique and thorough process of informed consent may reduce litigation in neurosurgery.

Rational Redundancy in Referring Expressions: Evidence from Event-related Potentials.

In referential communication, Grice's Maxim of Quantity is thought to imply that utterances conveying unnecessary information should incur comprehension difficulties. There is, however, considerable evidence that speakers frequently encode redundant information in their referring expressions, raising the question as to whether such overspecifications hinder listeners' processing. Evidence from previous work is inconclusive, and mostly comes from offline studies. In this article, we present two event-related potential (ERP) experiments, investigating the real-time comprehension of referring expressions that contain redundant adjectives in complex visual contexts. Our findings provide support for both Gricean and bounded-rational accounts. We argue that these seemingly incompatible results can be reconciled if common ground is taken into account. We propose a bounded-rational account of overspecification, according to which even redundant words can be beneficial to comprehension to the extent that they facilitate the reduction of listeners' uncertainty regarding the target referent.

Assessing the relative importance of key quality of life dimensions for people with and without a disability: an empirical ranking comparison study.

BACKGROUND: In economic evaluation, the quality of life of people with a disability has traditionally been assessed using preference-based instruments designed to measure and value quality of life. To provide robust measurement of the effectiveness of programs designed to improve the quality of life of people living with a disability, preference-based measures need to be sufficiently sensitive to detect incremental changes in the quality of life dimensions that are most important to people who have a disability. This study sought to explore whether there was a difference in the ranked order of importance of quality of life dimensions between people with a disability and people without a disability. METHODS: An online survey was developed and administered Australia wide. The first sample (n = 410) comprised adults (aged ≥ 18 years) with a disability (n = 208) and family carers of person/s with a disability who were asked to respond on behalf of the person with a disability (n = 202). The second sample included adults without disability (n = 443). Respondents were asked to rank the importance of 12 quality of life dimensions extracted from the content of established preference-based quality of life measures (EQ-5D, AQoL and ASCOT). RESULTS: People with a disability placed relatively higher importance on broader quality of life dimensions (e.g. Control, Independence, Self-care) relative to health status focused dimensions (e.g. Vision, Hearing, Physical mobility). This distinction was less differentiable for those 'without a disability'. The biggest differences in ranked importance of dimensions were in: Vision ('with disability' = 10th, 'without disability' = 4th), Self-care ('with disability' = 3rd, 'without disability' = 7th) and Mental well-being ('with disability' = 6th, 'without disability' = 2nd). CONCLUSIONS: The relative importance of quality of life dimensions for people with a disability differs to people without a disability. Quality of life is a key outcome for economic evaluation and for assessing the impact of disability care policy and practice in Australia and internationally. It is important that the effectiveness of interventions is measured and valued in ways which are fully reflective of the quality of life preferences of people with a disability.

Retrieval (N400) and integration (P600) in expectation-based comprehension.

Expectation-based theories of language processing, such as Surprisal theory, are supported by evidence of anticipation effects in both behavioural and neurophysiological measures. Online measures of language processing, however, are known to be influenced by factors such as lexical association that are distinct from-but often confounded with-expectancy. An open question therefore is whether a specific locus of expectancy related effects can be established in neural and behavioral processing correlates. We address this question in an event-related potential experiment and a self-paced reading experiment that independently cross expectancy and lexical association in a context manipulation design. We find that event-related potentials reveal that the N400 is sensitive to both expectancy and lexical association, while the P600 is modulated only by expectancy. Reading times, in turn, reveal effects of both association and expectancy in the first spillover region, followed by effects of expectancy alone in the second spillover region. These findings are consistent with the Retrieval-Integration account of language comprehension, according to which lexical retrieval (N400) is facilitated for words that are both expected and associated, whereas integration difficulty (P600) will be greater for unexpected words alone. Further, an exploratory analysis suggests that the P600 is not merely sensitive to expectancy violations, but rather, that there is a continuous relation. Taken together, these results suggest that the P600, like reading times, may reflect a meaning-centric notion of Surprisal in language comprehension.

When components collide: Spatiotemporal overlap of the N400 and P600 in language comprehension.

The problem of spatiotemporal overlap between event-related potential (ERP) components is generally acknowledged in language research. However, its implications for the interpretation of experimental results are often overlooked. In a previous experiment on the functional interpretation of the N400 and P600, it was argued that a P600 effect to implausible words was largely obscured - in one of two implausible conditions - by an overlapping N400 effect of semantic association. In the present ERP study, we show that the P600 effect of implausibility is uncovered when the critical condition is tested against a proper baseline condition which elicits a similar N400 amplitude, while it is obscured when tested against a baseline condition producing an N400 effect. Our findings reveal that component overlap can result in the apparent absence or presence of an effect in the surface signal and should therefore be carefully considered when interpreting ERP patterns. Importantly, we show that, by factoring in the effects of spatiotemporal overlap between the N400 and P600 on the surface signal, which we reveal using rERP analysis, apparent inconsistencies in previous findings are easily reconciled, enabling us to draw unambiguous conclusions about the functional interpretation of the N400 and P600 components. Overall, our results provide compelling evidence that the N400 reflects lexical retrieval processes, while the P600 indexes compositional integration of word meaning into the unfolding utterance interpretation.

Neurobehavioral Correlates of Surprisal in Language Comprehension: A Neurocomputational Model.

Expectation-based theories of language comprehension, in particular Surprisal Theory, go a long way in accounting for the behavioral correlates of word-by-word processing difficulty, such as reading times. An open question, however, is in which component(s) of the Event-Related brain Potential (ERP) signal Surprisal is reflected, and how these electrophysiological correlates relate to behavioral processing indices. Here, we address this question by instantiating an explicit neurocomputational model of incremental, word-by-word language comprehension that produces estimates of the N400 and the P600-the two most salient ERP components for language processing-as well as estimates of "comprehension-centric" Surprisal for each word in a sentence. We derive model predictions for a recent experimental design that directly investigates "world-knowledge"-induced Surprisal. By relating these predictions to both empirical electrophysiological and behavioral results, we establish a close link between Surprisal, as indexed by reading times, and the P600 component of the ERP signal. The resultant model thus offers an integrated neurobehavioral account of processing difficulty in language comprehension.

Reevaluating pragmatic reasoning in language games.

The results of a highly influential study that tested the predictions of the Rational Speech Act (RSA) model suggest that (a) listeners use pragmatic reasoning in one-shot web-based referential communication games despite the artificial, highly constrained, and minimally interactive nature of the task, and (b) that RSA accurately captures this behavior. In this work, we reevaluate the contribution of the pragmatic reasoning formalized by RSA in explaining listener behavior by comparing RSA to a baseline literal listener model that is only driven by literal word meaning and the prior probability of referring to an object. Across three experiments we observe only modest evidence of pragmatic behavior in one-shot web-based language games, and only under very limited circumstances. We find that although RSA provides a strong fit to listener responses, it does not perform better than the baseline literal listener model. Our results suggest that while participants playing the role of the Speaker are informative in these one-shot web-based reference games, participants playing the role of the Listener only rarely take this Speaker behavior into account to reason about the intended referent. In addition, we show that RSA's fit is primarily due to a combination of non-pragmatic factors, perhaps the most surprising of which is that in the majority of conditions that are amenable to pragmatic reasoning, RSA (accurately) predicts that listeners will behave non-pragmatically. This leads us to conclude that RSA's strong overall correlation with human behavior in one-shot web-based language games does not reflect listener's pragmatic reasoning about informative speakers.

Splitting event-related potentials: Modeling latent components using regression-based waveform estimation.

Event-related potentials (ERPs) provide a multidimensional and real-time window into neurocognitive processing. The typical Waveform-based Component Structure (WCS) approach to ERPs assesses the modulation pattern of components-systematic, reoccurring voltage fluctuations reflecting specific computational operations-by looking at mean amplitude in predetermined time-windows. This WCS approach, however, often leads to inconsistent results within as well as across studies. It has been argued that at least some inconsistencies may be reconciled by considering spatiotemporal overlap between components; that is, components may overlap in both space and time, and given their additive nature, this means that the WCS may fail to accurately represent its underlying latent component structure (LCS). We employ regression-based ERP (rERP) estimation to extend traditional approaches with an additional layer of analysis, which enables the explicit modeling of the LCS underlying WCS. To demonstrate its utility, we incrementally derive an rERP analysis of a recent study on language comprehension with seemingly inconsistent WCS-derived results. Analysis of the resultant regression models allows one to derive an explanation for the WCS in terms of how relevant regression predictors combine in space and time, and crucially, how individual predictors may be mapped onto unique components in LCS, revealing how these spatiotemporally overlap in the WCS. We conclude that rERP estimation allows for investigating how scalp-recorded voltages derive from the spatiotemporal combination of experimentally manipulated factors. Moreover, when factors can be uniquely mapped onto components, rERPs may offer explanations for seemingly inconsistent ERP waveforms at the level of their underlying latent component structure.