Papers

It has been proposed that abnormalities in probabilistic prediction and dynamic belief updating explain multiple features of schizophrenia. Here, we used EEG to ask whether these abnormalities can account for the well-established reduction in semantic priming observed in schizophrenia under non-automatic conditions. We isolated predictive contributions to the neural semantic priming effect by manipulating the prime’s predictive validity and minimizing retroactive semantic matching mechanisms. We additionally examined the link between prediction and learning using a Bayesian model that probed dynamic belief updating as participants adapted to the increase in predictive validity. We found that patients were less likely than healthy controls to use the prime to predictively facilitate semantic processing on the target, resulting in a reduced N400 effect. Moreover, the trial-by-trial output of our Bayesian computational model explained between-group differences in trial-by-trial N400 amplitudes as participants transitioned from conditions of lower to higher predictive validity. These findings suggest that, compared to healthy controls, people with schizophrenia are less able to mobilize predictive mechanisms to facilitate processing at the earliest stages of accessing the meanings of incoming words. This deficit may be linked to a failure to adapt to changes in the broader environment. This reciprocal relationship between impairments in probabilistic prediction and Bayesian learning/adaptation may drive a vicious cycle that maintains cognitive disturbances in schizophrenia.

It has been hypothesized that schizophrenia is characterized by overly broad automatic activity within lexico-semantic networks. We used two complementary neuroimaging techniques, Magnetoencephalography (MEG) and functional Magnetic Resonance Imaging (fMRI), in combination with a highly automatic indirect semantic priming paradigm, to spatiotemporally localize this abnormality in the brain. Eighteen people with schizophrenia and 20 demographically-matched control participants viewed target words (“bell”) preceded by directly related (“church”), indirectly related (“priest”), or unrelated (“pants”) prime words in MEG and fMRI sessions. To minimize top-down processing, the prime was masked, the target appeared only 140ms after prime onset, and participants simply monitored for words within a particular semantic category that appeared in filler trials. Both techniques revealed a significantly larger automatic indirect priming effect in people with schizophrenia than in control participants. MEG temporally localized this enhanced effect to the N400 time window (300-500ms) — the critical stage of accessing meaning from words. fMRI spatially localized the effect to the left temporal fusiform cortex, which plays a role in mapping of orthographic word-form on to meaning. There was no evidence of an enhanced automatic direct semantic priming effect in the schizophrenia group. These findings provide converging neural evidence for abnormally broad highly automatic lexico-semantic activity in schizophrenia. We argue that, rather than arising from an unconstrained spread of automatic activation across semantic memory, this broader automatic lexico-semantic activity stems from looser connections between the form and meaning of words.

When semantic information is activated by a context prior to new bottom-up input (i.e. when a word is predicted), semantic processing of that incoming word is typically facilitated, attenuating the amplitude of the N400 event related potential (ERP) – a direct neural measure of semantic processing. N400 modulation is observed even when the context is a single semantically related “prime” word. This so-called “N400 semantic priming effect” is sensitive to the probability of encountering a related prime-target pair within an experimental block, suggesting that participants may be adapting the strength of their predictions to the predictive validity of their broader experimental environment. We formalize this adaptation using a Bayesian learning model that estimates and updates the probability of encountering a related versus an unrelated prime-target pair on each successive trial. We found that our model’s trial-by-trial estimates of target word probability accounted for significant variance in the amplitude of the N400 evoked by target words. These findings suggest that Bayesian principles contribute to how comprehenders adapt their semantic predictions to the statistical structure of their broader environment, with implications for the functional significance of the N400 component and the predictive nature of language processing.

A large literature in social neuroscience has associated the medial prefrontal cortex (mPFC) with the processing of self-related information. However, only recently have social neuroscience studies begun to consider the large behavioral literature showing a strong self-positivity bias, and these studies have mostly focused on its correlates during self-related judgments and decision making. We carried out a functional MRI (fMRI) study to ask whether the mPFC would show effects of the self-positivity bias in a paradigm that probed participants’ self-concept without any requirement of explicit self-judgment. We presented social vignettes that were either self-relevant or non-self-relevant with a neutral, positive, or negative outcome described in the second sentence. In previous work using event-related potentials, this paradigm has shown evidence of a self-positivity bias that influences early stages of semantically processing incoming stimuli. In the present fMRI study, we found evidence for this bias within the mPFC: an interaction between self-relevance and valence, with only positive scenarios showing a self vs other effect within the mPFC. We suggest that the mPFC may play a role in maintaining a positively-biased self-concept and discuss the implications of these findings for the social neuroscience of the self and the role of the mPFC.

Introduction: Lexico-semantic disturbances are considered central to schizophrenia. Clinically, their clearest manifestation is in language production. However, most studies probing their underlying mechanisms have used comprehension or categorization tasks. Here, we probed automatic semantic activity prior to language production in schizophrenia using event-related potentials (ERPs). Methods: 19 people with schizophrenia and 16 demographically-matched healthy controls named target pictures that were very quickly preceded by masked prime words. To probe automatic semantic activity prior to production, we measured the N400 ERP component evoked by these targets. To determine the origin of any automatic semantic abnormalities, we manipulated the type of relationship between prime and target such that they overlapped in (a) their semantic features (semantically related, e.g. “cake” preceding a <picture of a pie>, (b) their initial phonemes (phonemically related, e.g. “stomach” preceding a <picture of a starfish>), or (c) both their semantic features and their orthographic/phonological word form (identity related, e.g. “socks” preceding a <picture of socks>). For each of these three types of relationship, the same targets were paired with unrelated prime words (counterbalanced across lists). We contrasted ERPs and naming times to each type of related target with its corresponding unrelated target.  Results: People with schizophrenia showed abnormal N400 modulation prior to naming identity related (versus unrelated) targets: whereas healthy control participants produced a smaller amplitude N400 to identity related than unrelated targets, patients showed the opposite pattern, producing a larger N400 to identity related than unrelated targets. This abnormality was specific to the identity related targets. Just like healthy control participants, people with schizophrenia produced a smaller N400 to semantically related than to unrelated targets, and showed no difference in the N400 evoked by phonemically related and unrelated targets. There were no differences between the two groups in the pattern of naming times across conditions. Conclusion: People with schizophrenia can show abnormal neural activity associated with automatic semantic processing prior to language production. The specificity of this abnormality to the identity related targets suggests that that, rather than arising from abnormalities of either semantic features or lexical form alone, it may stem from disruptions of mappings (connections) between the meanings of words and their form.

Background: Schizophrenia is characterized by abnormalities in referential communication, which may be linked to more general deficits in proactive cognitive control. We used event-related potentials (ERPs) to probe the timing and nature of the neural mechanisms engaged as people with schizophrenia linked pronouns to their preceding referents during word-by-word sentence comprehension.Methods: We measured ERPs to pronouns in two-clause sentences from 16 people with schizophrenia and 20 demographically-matched control participants. Our design crossed the number of potential referents (1-referent, 2-referent) with whether the pronoun matched the gender of its preceding referent(s) (matching, mismatching). This gave rise to four conditions: (1) 1-referent matching (“…Edward took courses in accounting but he…”), (2) 2-referent matching (“…Edward and Phillip took courses but he…”), (3) 1-referent mismatching (“…Edward took courses in accounting but she…”), and (4) 2-referent mismatching (“…Edward and Phillip took courses but she…”).Results: Consistent with previous findings, healthy controls produced a larger left anteriorly-distributed negativity between 400-600ms to 2-referent matching than to 1-referent matching pronouns (the “Nref effect”). In contrast, people with schizophrenia produced a larger centro-posterior positivity effect between 600-800ms. Both patient and control groups produced a larger positivity between 400-800ms to mismatching than to matching pronouns.Conclusions: These findings suggest that proactive mechanisms of referential processing, reflected by the Nref effect, are impaired in schizophrenia, while reactive mechanisms, reflected by the positivity effects, are relatively spared. Indeed, patients may compensate for proactive deficits by retro-actively engaging with context to influence the processing of inputs at a later stage of analysis.

We used Magnetoencephalography (MEG) in combination with Representational Similarity Analysis to probe neural activity associated with distinct, item-specific lexico-semantic predictions during language comprehension. MEG activity was measured as participants read highly constraining sentences in which the final words could be predicted. Before the onset of the predicted words, both the spatial and temporal patterns of brain activity were more similar when the same words were predicted than when different words were predicted. The temporal patterns localized to the left inferior and medial temporal lobe. These findings provide evidence that unique spatial and temporal patterns of neural activity are associated with item-specific lexico-semantic predictions. We suggest that the unique spatial patterns reflected the prediction of spatially distributed semantic features associated with the predicted word, and that the left inferior/medial temporal lobe played a role in temporally “binding” these features, giving rise to unique lexico-semantic predictions.

BackgroundPeople with schizophrenia process language in unusual ways, but the causes of these abnormalities are unclear. In particular, it has proven difficult to empirically disentangle explanations based on impairments in the top-down processing of higher-level information from those based on the bottom-up processing of lower-level information.MethodsTo distinguish these accounts, we used visual world eye-tracking, a paradigm that measures spoken language processing during real-world interactions. Participants listened to and then acted out syntactically ambiguous spoken instructions (e.g., “tickle the frog with the feather”, which could either specify how to tickle a frog, or which frog to tickle). We contrasted how 24 people with schizophrenia and 24 demographically-matched controls used two types of lower-level information (prosody and lexical representations) and two types of higher-level information (pragmatic and discourse-level representations) to resolve the ambiguous meanings of these instructions. Eye-tracking allowed us to assess how participants arrived at their interpretation in real time, while recordings of participants’ actions measured how they ultimately interpreted the instructions.ResultsWe found a striking dissociation in participants’ eye movements: the two groups were similarly adept at using lower-level information to immediately constrain their interpretations of the instructions, but only controls showed evidence of fast top-down use of higher-level information. People with schizophrenia, nonetheless, did eventually reach the same interpretations as controls.ConclusionsThese data suggest that language abnormalities in schizophrenia partially result from a failure to use higher-level information in a top-down fashion, to constrain the interpretation of language as it unfolds in real time.

The extent to which language processing involves prediction of upcoming inputs remains a question of ongoing debate. One important data point comes from DeLong et al. (2005) who reported that an N400-like event-related potential correlated with a probabilistic index of upcoming input. This result is often cited as evidence for gradient probabilistic prediction of form and/or semantics, prior to the bottom-up input becoming available. However, a recent multi-lab study reports a failure to find these effects (Nieuwland et al., 2017). We review the evidence from both studies, including differences in the design and analysis approach between them. Building on over a decade of research on prediction since DeLong et al. (2005)’s original study, we also begin to spell out the computational nature of predictive processes that one might expect to correlate with ERPs that are evoked by a functional element whose form is dependent on an upcoming predicted word. For paradigms with this type of design, we propose an index of anticipatory processing, Bayesian surprise, and apply it to the updating of semantic predictions. We motivate this index both theoretically and empirically. We show that, for studies of the type discussed here, Bayesian surprise can be closely approximated by another, more easily estimated information theoretic index, the surprisal (or Shannon information) of the input. We re-analyze the data from Nieuwland and colleagues using surprisal rather than raw probabilities as an index of prediction. We find that surprisal is gradiently correlated with the amplitude of the N400, even in the data shared by Nieuwland and colleagues. Taken together, our review suggests that the evidence from both studies is compatible with anticipatory semantic processing. We do, however, emphasize the need for future studies to further clarify the nature and degree of form prediction, as well as its neural signatures, during language comprehension.