Publications

2006
Holt, D. J., Titone, D., Long, S. L., Goff, D. C., Cather, C., Rauch, S. L., Judge, A., et al. (2006). The misattribution of salience in delusional patients with schizophrenia. Schizophrenia research , 83 (2), 247-256 . Elsevier. Full Text
Kuperberg, G. R., Caplan, D., Sitnikova, T., Eddy, M., & Holcomb, P. J. (2006). Neural correlates of processing syntactic, semantic, and thematic relationships in sentences. Language and cognitive processes , 21 (5), 489-530 . Taylor & Francis. Full Text
Sitnikova, T., West, C. W., Kuperberg, G. R., & Holcomb, P. J. (2006). The neural organization of semantic memory: Electrophysiological activity suggests feature-based segregation. Biol Psychol , 71 (3), 326-40. Full TextAbstract
Despite decades of research, it remains controversial whether semantic knowledge is anatomically segregated in the human brain. To address this question, we recorded event-related potentials (ERPs) while participants viewed pictures of animals and tools. Within the 200-600-ms epoch after stimulus presentation, animals (relative to tools) elicited an increased anterior negativity that, based on previous ERP studies, we interpret as associated with semantic processing of visual object attributes. In contrast, tools (relative to animals) evoked an enhanced posterior left-lateralized negativity that, according to prior research, might reflect accessing knowledge of characteristic motion and/or more general functional properties of objects. These results support the hypothesis of the neuroanatomical knowledge organization at the level of object features: the observed neurophysiological activity was modulated by the features that were most salient for object recognition. The high temporal resolution of ERPs allowed us to demonstrate that differences in processing animals and tools occurred specifically within the time-window encompassing semantic analysis.
Kuperberg, G. R., Kreher, D. A., Goff, D., McGuire, P. K., & David, A. S. (2006). Building up linguistic context in schizophrenia: evidence from self-paced reading. Neuropsychology , 20 (4), 442-52. Full TextAbstract
An impairment in the build-up and use of context has been proposed as a core feature of schizophrenia. The current study tested the hypothesis that schizophrenia patients show impairments in building up context within sentences because of abnormalities in combining semantic with syntactic information. Schizophrenia patients and healthy controls read and made acceptability judgments about sentences containing verbs that were semantically associated with individual preceding words but that violated either the meaning (animacy/semantic constraints) or the syntactic structure (morphosyntactic constraints) of their preceding contexts. To override these semantic associations and determine that such sentences are unacceptable, participants must integrate semantic with syntactic information. These sentences were compared with congruous and pragmatically/semantically violated sentences that imposed fewer semantic-syntactic integration demands. At sentence-final words and decisions, patients showed smaller reaction time differences than controls to animacy/semantically violated or morphosyntactically violated sentences relative to pragmatically/semantically violated or nonviolated sentences. The relative insensitivity to these violations in patients with schizophrenia may arise from impairments in combining semantic and syntactic information to build up sentence context.
Kreher, D. A., Holcomb, P. J., & Kuperberg, G. R. (2006). An electrophysiological investigation of indirect semantic priming. Psychophysiology , 43 (6), 550-63. Full TextAbstract
In two experiments, direct and indirect semantic priming were measured using event-related potentials. In Experiment 1, participants rated the relatedness between prime and target on a seven-point scale. In Experiment 2, participants simply read the primes and targets as they monitored for a semantic category in probe filler items. Significant direct and indirect N400 priming effects were observed in both experiments. In Experiment 1, the indirect N400 priming effect remained significant when indirectly related and unrelated word pairs were matched for participants' explicit relatedness judgments. In both experiments, the indirect N400 priming effects were preserved when indirectly related and unrelated word pairs were matched on more global and objective measures of semantic similarity. These findings are discussed in the context of current theoretical models of semantic memory and semantic priming.
Kuperberg, G. R., Lakshmanan, B. M., Caplan, D. N., & Holcomb, P. J. (2006). Making sense of discourse: an fMRI study of causal inferencing across sentences. Neuroimage , 33 (1), 343-61. Full TextAbstract
To build up coherence between sentences (comprehend discourse), we must draw inferences, i.e. activate and integrate information that is not actually stated. We used event-related fMRI to determine the localization and extent of brain activity mediating causal inferencing across short, three-sentence scenarios. Participants read and made causal coherence judgments to sentences that were highly causally related, intermediately related or unrelated to their preceding two-sentence contexts. The highly related and intermediately related scenarios were matched in terms of semantic similarities between their individual component words. A pre-rating study established that causal inferences were generated to the intermediately related but not to the highly related or unrelated scenarios. In the scanner, sentences that were intermediately related (relative to highly related or unrelated) to their preceding contexts were associated with longer judgment reaction times and sustained increases in hemodynamic activity within left lateral temporal/inferior parietal/prefrontal cortices, the right inferior prefrontal gyrus and bilateral superior medial prefrontal cortices. In contrast, sentences that were unrelated (relative to highly related) to their preceding contexts were associated with only transient increases in activity (at, but not after, the peak of the hemodynamic response) within the right lateral temporal cortex and the right inferior prefrontal gyrus. These data suggest that, to make sense of discourse, we activate a large bilateral cortical network in response to what is not explicitly stated. We suggest that this network reflects the activation, retrieval and integration of information from long-term semantic memory into incoming discourse structure during causal inferencing.
Kuperberg, G. R., Sitnikova, T., Goff, D., & Holcomb, P. J. (2006). Making sense of sentences in schizophrenia: electrophysiological evidence for abnormal interactions between semantic and syntactic processing. J Abnorm Psychol , 115 (2), 251-65. Full TextAbstract
Event-related potentials to critical verbs were measured as patients with schizophrenia and healthy controls read sentences word by word. Relative to their preceding context, critical verbs were (a) congruous, (b) incongruous and semantically unrelated to individual preceding words (pragmatic-semantic violations), (c) incongruous but semantically related to individual preceding words (animacy-semantic violations), or (d) syntactically anomalous. The N400 was modulated normally in patients, suggesting that semantic integration between individual words within sentences was normal in schizophrenia. The amplitude of the P600 to both syntactic and animacy-semantic violations was reduced in patients relative to controls. The authors suggest that, in schizophrenia, an abnormality in combining semantic and syntactic information online to build up propositional meaning leaves sentence processing to be primarily driven by semantic relationships between individual words.
2005
Ditman, T., & Kuperberg, G. R. (2005). A source-monitoring account of auditory verbal hallucinations in patients with schizophrenia. Harv Rev Psychiatry , 13 (5), 280-99. Full TextAbstract
Auditory verbal hallucinations are a common and distressing symptom experienced by patients with schizophrenia. They can be understood as arising from an impairment in reality monitoring-the process by which internally and externally generated events are distinguished. This impairment might arise through primary abnormalities in the reality-monitoring mechanism or through secondary mechanisms (abnormalities in the perceptual characteristics of internally generated events or in the perception of externally generated events). This article examines evidence for and against an association between abnormalities in reality monitoring and auditory verbal hallucinations in schizophrenia. A comprehensive review of the psychological literature suggests that there is little evidence for an association between auditory verbal hallucinations and secondary mechanisms leading to abnormalities in reality monitoring. There is some evidence suggesting that hallucinators show a primary reality-monitoring abnormality that is most apparent when patients are required to distinguish self from other in real time. To draw firmer conclusions, however, it is imperative that future studies select patient populations precisely, match control groups, and use consistent criteria for defining hallucinators.
2004
Kuperberg, G. (2004). EEG, ERPs, MEG and multimodal imaging: Applications in Psychiatry. In S Rauch and D Doughtery (Eds): Psychiatric Neuroimaging: A Primer for Clinicians (1st ed. pp. 117-128) . American Psychiatric Publishing. Full Text
2003
Kuperberg, G., & Caplan, D. (2003). Language dysfunction in schizophrenia. In R.B. Schiffer, S.M. Rao, and B.S. Fogel (eds): Neuropsychiatry (2nd ed. pp. 444-466) . Lippincott Williams and Wilkins, Philadelphia. Full Text
Sitnikova, T., Kuperberg, G., & Holcomb, P. J. (2003). Semantic integration in videos of real–world events: An electrophysiological investigation. Psychophysiology , 40 (1), 160-164 . Wiley Online Library. Full Text
Kuperberg, G. R., Holcomb, P. J., Sitnikova, T., Greve, D., Dale, A. M., & Caplan, D. (2003). Distinct patterns of neural modulation during the processing of conceptual and syntactic anomalies. J Cogn Neurosci , 15 (2), 272-93. Full TextAbstract
The aim of this study was to gain further insights into how the brain distinguishes between meaning and syntax during language comprehension. Participants read and made plausibility judgments on sentences that were plausible, morphosyntactically anomalous, or pragmatically anomalous. In an event-related potential (ERP) experiment, morphosyntactic and pragmatic violations elicited significant P600 and N400 effects, respectively, replicating previous ERP studies that have established qualitative differences in processing conceptually and syntactic anomalies. Our main focus was a functional magnetic resonance imaging (fMRI) study in which the same subjects read the same sentences presented in the same pseudorandomized sequence while performing the same task as in the ERP experiment. Rapid-presentation event-related fMRI methods allowed us to estimate the hemodynamic response at successive temporal windows as the sentences unfolded word by word, without assumptions about the shape of the underlying response function. Relative to nonviolated sentences, the pragmatic anomalies were associated with an increased hemodynamic response in left temporal and inferior frontal regions and a decreased response in the right medial parietal cortex. Relative to nonviolated sentences, the morphosyntactic anomalies were associated with an increased response in bilateral medial and lateral parietal regions and a decreased response in left temporal and inferior frontal regions. Thus, overlapping neural networks were modulated in opposite directions to the two types of anomaly. These fMRI findings document both qualitative and quantitative differences in how the brain distinguishes between these two types of anomalies. This suggests that morphosyntactic and pragmatic information can be processed in different ways but by the same neural systems.
Kuperberg, G. R., Sitnikova, T., Caplan, D., & Holcomb, P. J. (2003). Electrophysiological distinctions in processing conceptual relationships within simple sentences. Brain Res Cogn Brain Res , 17 (1), 117-29. Full TextAbstract
The aim of this study was to determine whether or not the brain distinguishes between two types of conceptual relationships between noun-phrases (NPs) and verbs during online processing of simple, unambiguous English sentences. A total of 15 participants read and made plausibility judgments on sentences that were presented word-by-word. Event-related potentials elicited by critical verbs were measured. In all cases, the critical verb assigned a thematic role of 'agent' to its subject NP. In non-violated sentences (e.g. "For breakfast the boys would only eat em leader"), the preceding NP was animate ("boys") and was a likely agent for a given verb ("eat") given its preceding context ("For breakfast"). In both types of conceptually violated sentences, the NPs were unlikely agents for the verbs given their preceding contexts. In 'thematic role animacy violations' (e.g. "For breakfast the eggs would only eat em leader"), the NP was inanimate ("eggs") and was therefore more likely to occupy the role of 'theme' than 'agent', i.e. eggs, being inanimate, cannot eat but they can be eaten. In 'non-thematic role pragmatic violations' (e.g. "For breakfast the boys would only bury em leader"), the thematic role of agent assigned by the verb ("bury") to its preceding NP ("boys") is inherently acceptable (boys can bury), but the sentence is still pragmatically incongruous given the preceding context ("At breakfast"). As expected, the non-thematic role pragmatic violations elicited a significant N400 effect. The thematic role animacy violations elicited a smaller N400 effect that only approached significance across all participants. The thematic role animacy violations, however, elicited a significant P600 effect-an ERP component that is most commonly associated with processing syntactic information during language comprehension. We discuss the possibility that the P600 was elicited by the thematic role animacy violations (but not by the non-thematic role pragmatic violations) because, in the former but not the latter, there was an online attempt to structurally repair and make sense of the sentences by reassigning the thematic role of the NP that preceded the critical verb from 'agent' to 'theme'. Our findings suggest a qualitative neural distinction in processing these two types of conceptual anomalies within simple, unambiguous sentences.
Kuperberg, G. R., Broome, M. R., McGuire, P. K., David, A. S., Eddy, M., Ozawa, F., Goff, D., et al. (2003). Regionally localized thinning of the cerebral cortex in schizophrenia. Arch Gen Psychiatry , 60 (9), 878-88. Full TextAbstract
BACKGROUND: Schizophrenia is characterized by small reductions in cortical gray matter volume, particularly in the temporal and prefrontal cortices. The question of whether cortical thickness is reduced in schizophrenia has not been addressed using magnetic resonance imaging (MRI) techniques. Our objectives were to test the hypothesis that cortical thinning in patients with schizophrenia (relative to control subjects) is greater in temporal and prefrontal regions of interest (ROIs) than in control ROIs (superior parietal, calcarine, postcentral, central, and precentral cortices), and to obtain an unbiased estimate of the distribution of cortical thinning in patients (relative to controls) by constructing mean and statistical cortical thickness difference maps. METHODS: Participants included 33 right-handed outpatients receiving medication and meeting DSM-IV criteria for schizophrenia and 32 healthy volunteers, matched on age and parental socioeconomic status. After high-resolution MRI scans, models of the gray-white and pial surfaces were generated for each individual's cortex, and the distance between these 2 surfaces was used to compute cortical thickness. A surface-based averaging technique that aligned the main cortical folds across individuals allowed between-group comparisons of thickness within ROIs, and at multiple, uniformly sampled loci across the cortical ribbon. RESULTS: Relative to controls, patients showed greater cortical thinning in temporal-prefrontal ROIs than in control ROIs, as revealed by a significant (P<.009) interaction between group and region type. Cortical thickness difference maps revealed significant (at P<.05, corrected) thinning within the orbitofrontal cortices bilaterally; the inferior frontal, inferior temporal, and occipitotemporal cortices on the left; and within the medial temporal and medial frontal cortices on the right. Superior parietal and primary somatosensory and motor cortices were relatively spared, even at subthreshold significance levels. CONCLUSIONS: Patients with chronic schizophrenia showed widespread cortical thinning that particularly affected the prefrontal and temporal cortices. This thinning might reflect underlying neuropathological abnormalities in cortical structure.
2002
Sitnikova, T., Salisbury, D. F., Kuperberg, G., & Holcomb, P. J. (2002). Electrophysiological insights into language processing in schizophrenia. Psychophysiology , 39 (6), 851-860 . Cambridge University Press. Full Text
Kuperberg, G., Kerwin, R., & Murray, R. (2002). Developments in the pharmacological treatment of schizophrenia. Expert opinion on investigational drugs , 11 (10), 1335-1341 . Taylor & Francis. Full Text
2001
Caplan, D., Vijayan, S., Kuperberg, G., West, C., Waters, G., Greve, D., & Dale, A. M. (2001). Vascular responses to syntactic processing: Event‐related fMRI study of relative clauses. Human brain mapping , 15 (1), 26-38 . Wiley Online Library. Full Text
2000
Kuperberg, G., & Heckers, S. (2000). Schizophrenia and cognitive function. Current opinion in neurobiology , 10 (2), 205-210 . Elsevier. Full Text
Kuperberg, G., McGuire, P. K., Bullmore, E. T., Brammer, M. J., Rabe-Hesketh, S., Wright, I. C., Lythgoe, D. J., et al. (2000). Common and distinct neural substrates for pragmatic, semantic, and syntactic processing of spoken sentences: an fMRI study. J Cogn Neurosci , 12 (2), 321-41. Full TextAbstract
Extracting meaning from speech requires the use of pragmatic, semantic, and syntactic information. A central question is: Does the processing of these different types of linguistic information have common or distinct neuroanatomical substrates? We addressed this issue using functional magnetic resonance imaging (fMRI) to measure neural activity when subjects listened to spoken normal sentences contrasted with sentences that had either (A) pragmatical, (B) semantic (selection restriction), or (C) syntactic (subcategorical) violations sentences. All three contrasts revealed robust activation of the left-inferior-temporal/fusiform gyrus. Activity in this area was also observed in a combined analysis of all three experiments, suggesting that it was modulated by all three types of linguistic violation. Planned statistical comparisons between the three experiments revealed (1) a greater difference between conditions in activation of the left-superior-temporal gyrus for the pragmatic experiment than the semantic/syntactic experiments; (2) a greater difference between conditions in activation of the right-superior and middle-temporal gyrus in the semantic experiment than in the syntactic experiment; and (3) no regions activated to a greater degree in the syntactic experiment than in the semantic experiment. These data show that, while left- and right-superior-temporal regions may be differentially involved in processing pragmatic and lexico-semantic information within sentences, the left-inferior-temporal/fusiform gyrus is involved in processing all three types of linguistic information. We suggest that this region may play a key role in using pragmatic, semantic (selection restriction), and subcategorical information to construct a higher representation of meaning of sentences.
Kuperberg, G., McGuire, P. K., & David, A. S. (2000). Sensitivity to linguistic anomalies in spoken sentences: a case study approach to understanding thought disorder in schizophrenia. Psychol Med , 30 (2), 345-57. Full TextAbstract
BACKGROUND: As a group, positively thought-disordered (TD) schizophrenic patients are relatively impaired in their ability to use linguistic context to process sentences online (Kuperberg et al. 1998). This study investigates the heterogeneity in the use of linguistic context both between individual TD patients and within the individual patients as severity of thought disorder changes over time. METHODS: Seventeen TD schizophrenics performed an online word-monitoring task on four separate occasions. In each patient, baseline reaction time (RTs) to target words in normal sentences were subtracted from RTs to target words in pragmatically-, semantically- and syntactically-violated sentences to obtain a measure of online sensitivity to each type of linguistic violation, and these were compared with normative data of a healthy volunteer and a non-TD schizophrenic control group. In addition, the co-variation of severity of thought disorder and sensitivity to linguistic context within all individual TD patients over the four testing sessions, was examined. RESULTS: There was marked heterogeneity between individual TD patients in their sensitivity to different types of linguistic violations: some were selectively insensitive to pragmatic violations, while others were insensitive to semantic and syntactic (subcategorization) violations. There was also an inverse relationship between severity of thought disorder and sensitivity to linguistic violations within individual patients over the four sessions. CONCLUSIONS: It is likely that a single cognitive deficit does not account for all types of schizophrenic thought disorder, but rather that there are multiple deficits affecting specific levels of linguistic processing. In these schizophrenic patients, impairment in the use of linguistic context was related to the state, rather than the trait, of thought disorder.

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