Sitnikova, T., Goff, D., & Kuperberg, G. R. (2009). Neurocognitive abnormalities during comprehension of real-world goal-directed behaviors in schizophrenia. J Abnorm Psychol , 118 (2), 256-77. Full TextAbstract
Origins of impaired adaptive functioning in schizophrenia remain poorly understood. Behavioral disorganization may arise from an abnormal reliance on common combinations between concepts stored in semantic memory. Avolition-apathy may be related to deficits in using goal-related requirements to flexibly plan behavior. The authors recorded event-related potentials (ERPs) in 16 patients with medicated schizophrenia and 16 healthy controls in a novel video paradigm presenting congruous or incongruous objects in real-world activities. All incongruous objects were contextually inappropriate, but the incongruous scenes varied in comprehensibility. Psychopathology was assessed with the Scales for the Assessment of Positive and Negative Symptoms (SAPS/SANS) and the Brief Psychiatric Rating Scale. In patients, an N400 ERP, thought to index activity in semantic memory, was abnormally enhanced to less comprehensible incongruous scenes, and larger N400 priming was associated with disorganization severity. A P600 ERP, which may index flexible object-action integration based on goal-related requirements, was abnormally attenuated in patients, and its smaller magnitude was associated with the SANS rating of impersistence at work or school (goal-directed behavior). Thus, distinct neurocognitive abnormalities may underlie disorganization and goal-directed behavior deficits in schizophrenia.
Kreher, D. A., Goff, D., & Kuperberg, G. R. (2009). Why all the confusion? Experimental task explains discrepant semantic priming effects in schizophrenia under "automatic" conditions: evidence from Event-Related Potentials. Schizophr Res , 111 (1-3), 174-81. Full TextAbstract
The schizophrenia research literature contains many differing accounts of semantic memory function in schizophrenia as assessed through the semantic priming paradigm. Most recently, Event-Related Potentials (ERPs) have been used to demonstrate both increased and decreased semantic priming at a neural level in schizophrenia patients, relative to healthy controls. The present study used ERPs to investigate the role of behavioral task in determining neural semantic priming effects in schizophrenia. The same schizophrenia patients and healthy controls completed two experiments in which word stimuli were identical, and the time between the onset of prime and target remained constant at 350 ms: in the first, participants monitored for words within a particular semantic category that appeared only in filler items (implicit task); in the second, participants explicitly rated the relatedness of word-pairs (explicit task). In the explicit task, schizophrenia patients showed reduced direct and indirect semantic priming in comparison with healthy controls. In contrast, in the implicit task, schizophrenia patients showed normal or, in positively thought-disordered patients, increased direct and indirect N400 priming effects compared with healthy controls. These data confirm that, although schizophrenia patients with positive thought disorder may show an abnormally increased automatic spreading activation, the introduction of semantic decision-making can result in abnormally reduced semantic priming in schizophrenia, even when other experimental conditions bias toward automatic processing.
Holt, D. J., Lynn, S. K., & Kuperberg, G. R. (2009). Neurophysiological correlates of comprehending emotional meaning in context. J Cogn Neurosci , 21 (11), 2245-62. Full TextAbstract
Although the neurocognitive mechanisms of nonaffective language comprehension have been studied extensively, relatively less is known about how the emotional meaning of language is processed. In this study, electrophysiological responses to affectively positive, negative, and neutral words, presented within nonconstraining, neutral contexts, were evaluated under conditions of explicit evaluation of emotional content (Experiment 1) and passive reading (Experiment 2). In both experiments, a widely distributed Late Positivity was found to be larger to negative than to positive words (a "negativity bias"). In addition, in Experiment 2, a small, posterior N400 effect to negative and positive (relative to neutral) words was detected, with no differences found between N400 magnitudes to negative and positive words. Taken together, these results suggest that comprehending the emotional meaning of words following a neutral context requires an initial semantic analysis that is relatively more engaged for emotional than for nonemotional words, whereas a later, more extended, attention-modulated process distinguishes the specific emotional valence (positive vs. negative) of words. Thus, emotional processing networks within the brain appear to exert a continuous influence, evident at several stages, on the construction of the emotional meaning of language.
Supplementary Materials
Sitnikova, T., Holcomb, P., & Kuperberg, G. (2008). Neurocognitive Mechanisms of Human Comprehension. In T. F. Shipley & J. Zacks (Eds): Understanding Events: How Humans See, Represent, and Act on Events. (pp. 639-683) . Oxford University Press. Full Text
Osterhout, L., Kim, A., & Kuperberg, G. (2008). The neurobiology of sentence comprehension. In M. Spivey, M. Joannisse, & K. McRae (Eds): The Cambridge Handbook of Psycholinguistics (pp. 365-389) . Cambridge University Press. Full Text
Kuperberg, G. R. (2008). Building meaning in schizophrenia. Clin EEG Neurosci , 39 (2), 99-102. Full TextAbstract
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.
Kuperberg, G. R., West, C. W., Lakshmanan, B. M., & Goff, D. (2008). Functional magnetic resonance imaging reveals neuroanatomical dissociations during semantic integration in schizophrenia. Biol Psychiatry , 64 (5), 407-18. Full TextAbstract
BACKGROUND: Schizophrenia symptoms can be conceptualized in terms of a breakdown of a balance between 1) activating, retrieving, and matching stored representations to incoming information (semantic memory-based processing) and 2) fully integrating activated semantic representations with one another and with other types of representations to form a gestalt representation of meaning (semantic integration). Semantic memory-based processes are relatively more dependent on inferior frontal and temporal cortices, whereas particularly demanding integrative processes additionally recruit the dorsolateral prefrontal cortex (DLPFC) and sometimes parietal cortices. We used functional magnetic resonance imaging (fMRI) to determine whether the modulation of temporal/inferior frontal cortices and the DLPFC can be neuroanatomically dissociated in schizophrenia, as semantic integration demands increase. Integration demands were manipulated by varying the nature (concrete vs. abstract) and the congruity (incongruous vs. congruous) of words within sentences. METHODS: Sixteen right-handed schizophrenia patients and 16 healthy volunteers, matched on age and parental socioeconomic status, underwent event-related fMRI scanning while they read sentences. Blood oxygen level dependent (BOLD) effects were contrasted to words within sentences that were 1) concrete versus abstract and 2) semantically incongruous versus congruous with their preceding contexts. RESULTS: In both contrasts, large networks mediating the activation and retrieval of verbal and imagistic representations were normally modulated in patients. However, unlike control subjects, patients failed to recruit the DLPFC, medial frontal and parietal cortices to incongruous (relative to congruous) sentences, and failed to recruit the DLPFC to concrete (relative to abstract) sentences. CONCLUSIONS: As meaning is built from language, schizophrenia patients demonstrate a neuroanatomical dissociation in the modulation of temporal/inferior frontal cortices and the DLPFC.
Kreher, D. A., Holcomb, P. J., Goff, D., & Kuperberg, G. R. (2008). Neural evidence for faster and further automatic spreading activation in schizophrenic thought disorder. Schizophr Bull , 34 (3), 473-82. Full TextAbstract
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.
Kuperberg, G. R., Sitnikova, T., & Lakshmanan, B. M. (2008). Neuroanatomical distinctions within the semantic system during sentence comprehension: evidence from functional magnetic resonance imaging. Neuroimage , 40 (1), 367-88. Full TextAbstract
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. " breakfast the boys would eat..."), animacy semantic-thematically violated verbs (e.g. " breakfast the eggs would eat...") and morphosyntactically violated verbs (e.g. " 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. " 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.
Kuperberg, G. R., Lakshmanan, B. M., Greve, D. N., & West, C. W. (2008). Task and semantic relationship influence both the polarity and localization of hemodynamic modulation during lexico-semantic processing. Hum Brain Mapp , 29 (5), 544-61. Full TextAbstract
This study examined how task (implicit vs. explicit) and semantic relationship (direct vs. indirect) modulated hemodynamic activity during lexico-semantic processing. Participants viewed directly related, indirectly related, and unrelated prime-target word-pairs as they performed (a) an implicit lexical decision (LD) task in which they decided whether each target was a real word or a nonword, and (b) an explicit relatedness judgment (RJ) task in which they determined whether each word-pair was related or unrelated in meaning. Task influenced both the polarity and neuroanatomical localization of hemodynamic modulation. Semantic relationship influenced the neuroanatomical localization of hemodynamic modulation. The implicit LD task was primarily associated with inferior prefrontal and ventral inferior temporal/fusiform hemodynamic response suppression to directly related (relative to unrelated) word-pairs, and with more widespread temporal-occipital response suppression to indirectly related (relative to unrelated) word-pairs. In contrast, the explicit RJ task was primarily associated with left inferior parietal hemodynamic response enhancement to both directly and indirectly related (relative to unrelated) word-pairs, as well as with additional left inferior prefrontal hemodynamic response enhancement to indirectly related (relative to unrelated) word-pairs. These findings are discussed in relation to the specific neurocognitive processes thought to underlie implicit and explicit semantic processes. Hum Brain Mapp, 2008. (c) 2007 Wiley-Liss, Inc.
Ditman, T., Holcomb, P. J., & Kuperberg, G. R. (2008). Time travel through language: temporal shifts rapidly decrease information accessibility during reading. Psychon Bull Rev , 15 (4), 750-6. Full TextAbstract
The present study dissociated the immediate neural costs from the subsequent neural consequences of integrating time shifts into our mental representations of events. Event-related potentials were recorded as participants read scenarios that included words referring to short temporal shifts (e.g., after one second), moderate temporal shifts (e.g., after one hour), or long temporal shifts (e.g., after one year). These words were followed by repeated noun-phrase anaphors, which are preferred as referents for information no longer in attentional focus. The N400 was measured as an index of online conceptual integration. As the discourse unfolded, the N400 was larger for long- (e.g.,year) than for short- (e.g., second) shift words. For the anaphor, the N400 was modulated in the opposite direction. Thus, the introduction of a temporal discontinuity leads to immediate neural integration costs, as well as to decreased accessibility of earlier information.
Sitnikova, T., Holcomb, P. J., Kiyonaga, K. A., & Kuperberg, G. R. (2008). Two neurocognitive mechanisms of semantic integration during the comprehension of visual real-world events. J Cogn Neurosci , 20 (11), 2037-57. Full TextAbstract
How do comprehenders build up overall meaning representations of visual real-world events? This question was examined by recording event-related potentials (ERPs) while participants viewed short, silent movie clips depicting everyday events. In two experiments, it was demonstrated that presentation of the contextually inappropriate information in the movie endings evoked an anterior negativity. This effect was similar to the N400 component whose amplitude has been previously reported to inversely correlate with the strength of semantic relationship between the context and the eliciting stimulus in word and static picture paradigms. However, a second, somewhat later, ERP component--a posterior late positivity--was evoked specifically when target objects presented in the movie endings violated goal-related requirements of the action constrained by the scenario context (e.g., an electric iron that does not have a sharp-enough edge was used in place of a knife in a cutting bread scenario context). These findings suggest that comprehension of the visual real world might be mediated by two neurophysiologically distinct semantic integration mechanisms. The first mechanism, reflected by the anterior N400-like negativity, maps the incoming information onto the connections of various strengths between concepts in semantic memory. The second mechanism, reflected by the posterior late positivity, evaluates the incoming information against the discrete requirements of real-world actions. We suggest that there may be a tradeoff between these mechanisms in their utility for integrating across people, objects, and actions during event comprehension, in which the first mechanism is better suited for familiar situations, and the second mechanism is better suited for novel situations.
Movie: Congruous Movie: Incongruous
Nieuwland, M. S., & Kuperberg, G. R. (2008). When the truth is not too hard to handle: an event-related potential study on the pragmatics of negation. Psychol Sci , 19 (12), 1213-8. Full TextAbstract
Our brains rapidly map incoming language onto what we hold to be true. Yet there are claims that such integration and verification processes are delayed in sentences containing negation words like not. However, studies have often confounded whether a statement is true and whether it is a natural thing to say during normal communication. In an event-related potential (ERP) experiment, we aimed to disentangle effects of truth value and pragmatic licensing on the comprehension of affirmative and negated real-world statements. As in affirmative sentences, false words elicited a larger N400 ERP than did true words in pragmatically licensed negated sentences (e.g., "In moderation, drinking red wine isn't bad/good..."), whereas true and false words elicited similar responses in unlicensed negated sentences (e.g., "A baby bunny's fur isn't very hard/soft..."). These results suggest that negation poses no principled obstacle for readers to immediately relate incoming words to what they hold to be true.
Supplementary Materials
Ditman, T., Holcomb, P. J., & Kuperberg, G. R. (2007). The contributions of lexico-semantic and discourse information to the resolution of ambiguous categorical anaphors. Language and Cognitive Processes , 22 (6), 793-827 . Taylor & Francis. Full text
Wisco, J. J., Kuperberg, G., Manoach, D., Quinn, B. T., Busa, E., Fischl, B., Heckers, S., et al. (2007). Abnormal cortical folding patterns within Broca's area in schizophrenia: evidence from structural MRI. Schizophrenia research , 94 (1), 317-327 . Elsevier. Full text
Kuperberg, G. R., Deckersbach, T., Holt, D. J., Goff, D., & West, C. W. (2007). Increased temporal and prefrontal activity in response to semantic associations in schizophrenia. Arch Gen Psychiatry , 64 (2), 138-51. Full TextAbstract
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.
Ditman, T., Holcomb, P. J., & Kuperberg, G. R. (2007). An investigation of concurrent ERP and self-paced reading methodologies. Psychophysiology , 44 (6), 927-35. Full TextAbstract
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.
Kuperberg, G. R. (2007). Neural mechanisms of language comprehension: challenges to syntax. Brain Res , 1146, 23-49. Full TextAbstract
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.
Kuperberg, G. R., Kreher, D. A., Sitnikova, T., Caplan, D. N., & Holcomb, P. J. (2007). The role of animacy and thematic relationships in processing active English sentences: evidence from event-related potentials. Brain Lang , 100 (3), 223-37. Full TextAbstract
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.
Ditman, T., & Kuperberg, G. R. (2007). The time course of building discourse coherence in schizophrenia: an ERP investigation. Psychophysiology , 44 (6), 991-1001. Full TextAbstract
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.