Schizophrenia

In people with schizophrenia and related disorders, impairments in communication and social functioning can negatively impact social interactions and quality of life. In the present study, we investigated the cognitive basis of a specific aspect of linguistic communication—lexical alignment— in people with schizophrenia and bipolar disorder. We probed lexical alignment as participants played a collaborative picture-naming game with the experimenter, in which the two players alternated between naming a dual-name picture (e.g., rabbit/bunny) and listening to their partner name a picture. We found evidence of lexical alignment in all three groups, with no differences between the patient groups and the controls. We argue that these typical patterns of lexical alignment in patients were supported by preserved—and in some cases increased—bottom-up mechanisms, which balanced out impairments in top-down perspective-taking.

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.

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.

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.

Language and thought dysfunction are central to the schizophrenia syndrome. They are evident in the major symptoms of psychosis itself, particularly as disorganized language output (positive thought disorder) and auditory verbal hallucinations (AVHs), and they also manifest as abnormalities in both high-level semantic and contextual processing and low-level perception. However, the literatures characterizing these abnormalities have largely been separate and have sometimes provided mutually exclusive accounts of aberrant language in schizophrenia. In this review, we propose that recent generative probabilistic frameworks of language processing can provide crucial insights that link these four lines of research. We first outline neural and cognitive evidence that real-time language comprehension and production normally involve internal generative circuits that propagate probabilistic predictions to perceptual cortices - predictions that are incrementally updated based on prediction error signals as new inputs are encountered. We then explain how disruptions to these circuits may compromise communicative abilities in schizophrenia by reducing the efficiency and robustness of both high-level language processing and low-level speech perception. We also argue that such disruptions may contribute to the phenomenology of thought-disordered speech and false perceptual inferences in the language system (i.e., AVHs). This perspective suggests a number of productive avenues for future research that may elucidate not only the mechanisms of language abnormalities in schizophrenia, but also promising directions for cognitive rehabilitation.

The present study investigated the contribution of lexico-semantic associations to impairments in establishing reference in schizophrenia. We examined event-related potentials as schizophrenia patients and healthy, demographically matched controls read five-sentence scenarios. Sentence 4 introduced a noun that referred back to three possible referents introduced in Sentences 1-3. These referents were contextually appropriate, contextually inappropriate but lexico-semantically associated, and contextually inappropriate and lexico-semantically nonassociated. In order to determine whether participants had correctly linked the anaphor to its referent, the final sentence reintroduced each referent, and participants indicated whether the last two sentences referred to the same entity. Results indicated that between 300 and 400 ms, patients, like healthy controls, used discourse context to link the noun with its preceding referent. However, between 400 and 500 ms, neural activity in patients was modulated only by lexico-semantic associations, rather than by discourse context. Moreover, patients were also more likely than controls to incorrectly link the noun with contextually inappropriate but lexico-semantically associated referents. These results suggest that at least some types of referential impairments may be driven by sustained activation of contextually inappropriate lexico-semantic associations.

A cardinal feature of schizophrenia is the poor comprehension, or misinterpretation, of the emotional meaning of social interactions and events, which can sometimes take the form of a persecutory delusion. It has been shown that the comprehension of the emotional meaning of the social world involves a midline paralimbic cortical network. However, the function of this network during emotional appraisals in patients with schizophrenia is not well understood. In this study, hemodynamic responses were measured in 14 patients with schizophrenia and 18 healthy subjects during the evaluation of descriptions of social situations with negative, positive, and neutral affective valence. The healthy and schizophrenia groups displayed opposite patterns of responses to emotional and neutral social situations within the medial prefrontal and posterior cingulate cortices—healthy participants showed greater activity to the emotional compared to the neutral situations, while patients exhibited greater responses to the neutral compared to the emotional situations. Moreover, the magnitude of the response within bilateral cingulate gyri to the neutral social stimuli predicted delusion severity in the patients with schizophrenia. These findings suggest that impaired functioning of cortical midline structures in schizophrenia may underlie faulty interpretations of social events, contributing to delusion formation.

Schizophrenia is associated with abnormalities in emotional processing and social cognition. However, it remains unclear whether patients show abnormal neurophysiological responses during fast, online appraisals of the emotional meaning of social information. To examine this question, event-related potentials (ERPs) were collected while 18 schizophrenia patients and 18 demographically matched controls evaluated 2-sentence vignettes describing negative, positive, or neutral social situations. ERPs were time locked to a critical word (CW) in the second sentence that conferred emotional valence. A late positivity effect to emotional (vs neutral) CWs was seen in both groups (in controls, to negative and positive CWs; in patients, to negative CWs only). However, the controls showed a greater late positivity effect to the negative and positive (vs neutral) CWs than the schizophrenia patients at mid-posterior (negative vs neutral) and at right posterior peripheral (positive vs neutral) sites. These between-group differences arose from reduced amplitudes of the late positivity to the negative and positive CWs in the patients relative to the controls; there was no difference between the 2 groups in the amplitude of the late positivity to the neutral CWs. These findings suggest that schizophrenia is associated with a specific neural deficit during the online evaluation of emotionally valent, socially relevant information.