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It has been proposed that the loose associations characteristic of thought disorder in schizophrenia result from an abnormal increase in the automatic spread of activation through semantic memory. We tested this hypothesis by examining the time course of neural semantic priming using event-related potentials (ERPs). ERPs were recorded to target words that were directly related, indirectly related, and unrelated to their preceding primes, while thought-disordered (TD) and non-TD schizophrenia patients and healthy controls performed an implicit semantic categorization task under experimental conditions that encouraged automatic processing. By 300-400 milliseconds after target word onset, TD patients showed increased indirect semantic priming relative to non-TD patients and healthy controls, while the degree of direct semantic priming was increased in only the most severely TD patients. By 400-500 milliseconds after target word onset, both direct and indirect semantic priming were generally equivalent across the 3 groups. These findings demonstrate for the first time at a neural level that, under automatic conditions, activation across the semantic network spreads further within a shorter period of time in specific association with positive thought disorder in schizophrenia.

The schizophrenia syndrome is clinically characterized by abnormal constructions of meaning during comprehension (delusions), perception (hallucinations), action (disorganized and non-goal-directed behavior) and language production (thought disorder). This article provides an overview of recent studies from our laboratory that have used event-related potentials and functional magnetic resonance imaging to elucidate abnormalities in temporal and spatial patterns of neural activity as meaning is built from language and real-world visual events in schizophrenia. Our findings support the hypothesis that automatic activity across semantic memory spreads further within a shorter period of time in thought-disordered patients, relative to non-thought-disordered patients and healthy controls. Neuroanatomically, increased activity to semantic associates is reflected by inappropriate recruitment of temporal cortices. In building meaning within sentences, the fine balance between semantic memory-based mechanisms and semantic-syntactic integration (dictating "who does what to whom") is disrupted, such that comprehension is driven primarily by semantic memory-based processes. Neuroanatomically, this imbalance is reflected by preserved (and sometimes increased) activity within temporal and inferior prefrontal cortices, but abnormal modulation of dorsolateral prefrontal and parietal cortices. In building meaning across sentences (discourse), patients fail to immediately construct coherence links, but may show inappropriate recruitment of temporal and inferior prefrontal cortices to incoherent discourse, again reflecting inappropriate semantic memory-based processing (abnormal inferencing). Finally, these abnormalities may generalize to real-world visual event comprehension, where patients show reduced neural activity in determining relationships around goal-directed actions, and comprehension is again dominated by semantic memory-based mechanisms.

To make sense of a sentence, we must compute morphosyntactic and semantic-thematic relationships between its verbs and arguments and evaluate the resulting propositional meaning against any preceding context and our real-world knowledge. Recent electrophysiological studies suggest that, in comparison with non-violated verbs (e.g. "...at breakfast the boys would eat..."), animacy semantic-thematically violated verbs (e.g. "...at breakfast the eggs would eat...") and morphosyntactically violated verbs (e.g. "...at breakfast the boys would eats...") evoke a similar neural response. This response is distinct from that evoked by verbs that only violate real-world knowledge (e.g. "...at breakfast the boys would plant..."). Here we used fMRI to examine the neuroanatomical regions engaged in response to these three violations. Real-world violations, relative to other sentence types, led to increased activity within the left anterior inferior frontal cortex, reflecting participants’ increased and prolonged efforts to retrieve semantic knowledge about the likelihood of events occurring in the real world. In contrast, animacy semantic-thematic violations of the actions depicted by the central verbs engaged a frontal/inferior parietal/basal ganglia network known to mediate the execution and comprehension of goal-directed action. We suggest that the recruitment of this network reflected a semantic-thematic combinatorial process that involved an attempt to determine whether the actions described by the verbs could be executed by their NP Agents. Intriguingly, this network was also activated to morphosyntactic violations between the verbs and their subject NP arguments. Our findings support the pattern of electrophysiological findings in suggesting (a) that a clear division within the semantic system plays out during sentence comprehension, and (b) that semantic-thematic and syntactic violations of verbs within simple active sentences are treated similarly by the brain.

The present studies employed event-related potentials (ERPs) to examine the time course for the integration of lexico-semantic and discourse information during the resolution of categorical anaphors. Scenarios were constructed to include three potential antecedents. Anaphors were semantically ambiguous in that two of the potential antecedents were exemplars of the anaphor. Final sentences resolved the anaphor with the correct (associatively related/contextually appropriate), incorrect (associatively related/contextually inappropriate), or control antecedent (associatively unrelated/contextually inappropriate). We examined the amplitude of the N400 component, which is thought to reflect the ease of semantic integration, at several points following the anaphor. The smallest N400 was evoked when the text referred back to a correct antecedent following an anaphor; an intermediate N400 was evoked by incorrect antecedents and the largest N400 was evoked by reinstating the control antecedent following an anaphor. Results demonstrated that, following an ambiguous anaphor, readers are able to use both lexico-semantic and discourse-level information to semantically integrate an antecedent into its larger discourse context. 

Full text

Impairments in the buildup and use of context may lead to disorders of thought and language in schizophrenia. To test this hypothesis, event-related potentials (ERPs) were measured while patients and healthy controls read sentences that were highly causally related, intermediately related, or unrelated to preceding contexts. Although patients were slower than controls, both groups used the discourse context similarly as evidenced by similar reaction time patterns across conditions. Neurally however, different patterns emerged between patients and controls: within the N400 time window, patients failed to modulate their neural responses across conditions. This failure to differentiate between conditions was specifically correlated with positive thought disorder. Results suggest that schizophrenia patients, particularly those with positive thought disorder, fail to make immediate use of discourse context to build up semantic coherence in the brain.

In 1980, the N400 event-related potential was described in association with semantic anomalies within sentences. When, in 1992, a second waveform, the P600, was reported in association with syntactic anomalies and ambiguities, the story appeared to be complete: the brain respected a distinction between semantic and syntactic representation and processes. Subsequent studies showed that the P600 to syntactic anomalies and ambiguities was modulated by lexical and discourse factors. Most surprisingly, more than a decade after the P600 was first described, a series of studies reported that semantic verb-argument violations, in the absence of any violations or ambiguities of syntax can evoke robust P600 effects and no N400 effects. These observations have raised fundamental questions about the relationship between semantic and syntactic processing in the brain. This paper provides a comprehensive review of the recent studies that have demonstrated P600s to semantic violations in light of several proposed triggers: semantic-thematic attraction, semantic associative relationships, animacy and semantic-thematic violations, plausibility, task, and context. I then discuss these findings in relation to a unifying theory that attempts to bring some of these factors together and to link the P600 produced by semantic verb-argument violations with the P600 evoked by unambiguous syntactic violations and syntactic ambiguities. I suggest that normal language comprehension proceeds along at least two competing neural processing streams: a semantic memory-based mechanism, and a combinatorial mechanism (or mechanisms) that assigns structure to a sentence primarily on the basis of morphosyntactic rules, but also on the basis of certain semantic-thematic constraints. I suggest that conflicts between the different representations that are output by these distinct but interactive streams lead to a continued combinatorial analysis that is reflected by the P600 effect. I discuss some of the implications of this non-syntactocentric, dynamic model of language processing for understanding individual differences, language processing disorders and the neuroanatomical circuitry engaged during language comprehension. Finally, I suggest that that these two processing streams may generalize beyond the language system to real-world visual event comprehension.

CONTEXT: Loosening of associations has long been considered a core feature of schizophrenia, but its neural correlate remains poorly understood. OBJECTIVE: To test the hypothesis that, in comparison with healthy control subjects, patients with schizophrenia show increased neural activity within inferior prefrontal and temporal cortices in response to directly and indirectly semantically related (relative to unrelated) words. DESIGN: A functional neuroimaging study using a semantic priming paradigm. SETTING: Lindemann Mental Health Center, Boston, Mass. PARTICIPANTS: Seventeen right-handed medicated outpatients with chronic schizophrenia and 15 healthy volunteers, matched for age and parental socioeconomic status. INTERVENTIONS: Functional magnetic resonance imaging as participants viewed directly related, indirectly related, and unrelated word pairs and performed a lexical decision task. MAIN OUTCOME MEASURES: Event-related functional magnetic resonance imaging measures of blood oxygenation level-dependent activity (1) within a priori temporal and prefrontal anatomic regions of interest and (2) at all voxels across the cortex. RESULTS: Patients and controls showed no behavioral differences in priming but opposite patterns of hemodynamic modulation in response to directly related (relative to unrelated) word pairs primarily within inferior prefrontal cortices, and to indirectly related (relative to unrelated) word pairs primarily within temporal cortices. Whereas controls showed the expected decreases in activity in response to semantic relationships (hemodynamic response suppression), patients showed inappropriate increases in response to semantic relationships (hemodynamic response enhancement) in many of the same regions. Moreover, hemodynamic response enhancement within the temporal fusiform cortices to indirectly related (relative to unrelated) word pairs predicted positive thought disorder. CONCLUSION: Medicated patients with chronic schizophrenia, particularly those with positive thought disorder, show inappropriate increases in activity within inferior prefrontal and temporal cortices in response to semantic associations.

Traditionally, event-related brain potential (ERP) studies of language processing have presented words at a fixed rate using rapid serial visual presentation. Recent studies suggest, however, that the processes engaged during sentence comprehension are contingent on word presentation rate. These findings underscore the importance of allowing participants to read at a natural pace. The present study employed simultaneous self-paced reading and ERP methodologies to examine behavioral and neural responses while participants read sentences containing pragmatic or morphosyntactic violations or no violations. ERP and self-paced reading results replicated previous findings. This novel combination of behavioral and ERP methodologies combines the high temporal resolution and direct neural measures offered by ERPs with the more natural reading environment and information about processing load provided by self-paced reading.

Recent event-related potential studies report a P600 effect to incongruous verbs preceded by semantically associated inanimate noun-phrase (NP) arguments, e.g., "eat" in "At breakfast the eggs would eat...". This P600 effect may reflect the processing cost incurred when semantic-thematic relationships between critical verbs and their preceding NP argument(s) bias towards different interpretations to those dictated by their sentences’ syntactic structures. We have termed such violations of alternative thematic roles, ’thematic role violations.’ Semantic-thematic relationships are influenced both by semantic associations and by more basic semantic features, such as a noun’s animacy. This study determined whether a P600 effect can be evoked by verbs whose thematic structures are violated by their preceding inanimate NP arguments, even in the absence of close semantic-associative relationships with these arguments or their preceding contexts. ERPs were measured to verbs under four conditions: (1) non-violated ("At breakfast the boys would eat..."); (2) preceded by introductory clauses and animate NPs that violated their pragmatic expectations but not their thematic structures ("At breakfast the boys would plant..."); (3) preceded by semantically related contexts but inanimate NPs that violated their thematic structures ("At breakfast the eggs would eat..."); (4) preceded by semantically unrelated contexts and inanimate NPs that also violated their thematic structures ("At breakfast the eggs would plant..."). Pragmatically non-thematic role violated verbs preceded by unrelated contexts and animate NPs evoked robust N400 effects and small P600 effects. Thematically violated verbs preceded by inanimate argument NPs evoked robust P600 effects but no N400 effects, regardless of whether these inanimate arguments or their preceding contexts were semantically related or unrelated to these verbs. These findings suggest that semantic-thematic relations, related to animacy constraints on verbs’ arguments, are computed online and can immediately impact verb processing within active, English sentences.