Semantic Priming

Sharpe, V., Weber, K., & Kuperberg, G. R. (2020). Impairments in probabilistic prediction and Bayesian learning can explain reduced neural semantic priming in schizophrenia. Schizophrenia Bulletin , 46 (6), 1558-1566.Abstract

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.

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Kuperberg, G. R., Weber, K., Delaney-Busch, N., Ustine, C., Stillerman, B., Hamalainen, M., & Lau, E. (2019). Multimodal neuroimaging evidence for looser lexico-semantic networks in schizophrenia: Evidence from masked indirect semantic priming. Neuropsychologia , 124, 337-349.Abstract
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.
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Delaney-Busch, N., Morgan, E., Lau, E., & Kuperberg, G. R. (2019). Neural evidence for Bayesian trial-by-trial adaptation on the N400 during semantic priming. Cognition , 187, 10-20.Abstract

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.

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Kuperberg, G. R., Delaney-Busch, N., Fanucci, K., & Blackford, T. (2018). Priming Production: Neural evidence for enhanced automatic semantic activity immediately preceding language production in schizophrenia. NeuroImage:Clinical , 18, 74-85. Full TextAbstract

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.

Supplementary Materials
Delaney-Busch, N., Wilkie, G., & Kuperberg, G. R. (2016). Vivid: How valence and arousal influence word processing under different task demands. Cognitive, Affective, & Behavioral Neuroscience , 16 (3), 413-432. Full textAbstract
In this study, we used event-related potentials to examine how different dimensions of emotion—valence and arousal—influence different stages of word processing under different task demands. In two experiments, two groups of participants viewed the same single emotional and neutral words while carrying out different tasks. In both experiments, valence (pleasant, unpleasant, and neutral) was fully crossed with arousal (high and low). We found that the task made a substantial contribution to how valence and arousal modulated the late positive complex (LPC), which is thought to reflect sustained evaluative processing (particularly of emotional stimuli). When participants performed a semantic categorization task in which emotion was not directly relevant to task performance, the LPC showed a larger amplitude for high-arousal than for low-arousal words, but no effect of valence. In contrast, when participants performed an overt valence categorization task, the LPC showed a large effect of valence (with unpleasant words eliciting the largest positivity), but no effect of arousal. These data show not only that valence and arousal act independently to influence word processing, but that their relative contributions to prolonged evaluative neural processes are strongly influenced by the situational demands (and by individual differences, as revealed in a subsequent analysis of subjective judgments).
Supplementary Materials
Lau, E. F., Weber, K., Gramfort, A., Hämäläinen, M. S., & Kuperberg, G. R. (2016). Spatiotemporal Signatures of Lexical-Semantic Prediction. Cerebral Cortex , 26 (4), 1377-87. Epub 2014 Oct 14. Full TextAbstract
Although there is broad agreement that top-down expectations can facilitate lexical-semantic processing, the mechanisms driving these effects are still unclear. In particular, while previous electroencephalography (EEG) research has demonstrated a reduction in the N400 response to words in a supportive context, it is often challenging to dissociate facilitation due to bottom-up spreading activation from facilitation due to top-down expectations. The goal of the current study was to specifically determine the cortical areas associated with facilitation due to top-down prediction, using magnetoencephalography (MEG) recordings supplemented by EEG and functional magnetic resonance imaging (fMRI) in a semantic priming paradigm. In order to modulate expectation processes while holding context constant, we manipulated the proportion of related pairs across 2 blocks (10 and 50% related). Event-related potential results demonstrated a larger N400 reduction when a related word was predicted, and MEG source localization of activity in this time-window (350-450 ms) localized the differential responses to left anterior temporal cortex. fMRI data from the same participants support the MEG localization, showing contextual facilitation in left anterior superior temporal gyrus for the high expectation block only. Together, these results provide strong evidence that facilitatory effects of lexical-semantic prediction on the electrophysiological response 350-450 ms postonset reflect modulation of activity in left anterior temporal cortex.
Supplementary figures Supplementary materials
Weber, K., Lau, E. F., Stillerman, B., & Kuperberg, G. R. (2016). The Yin and the Yang of Prediction: An fMRI Study of Semantic Predictive Processing. PLoS One , 11 (3), e0148637. Full textAbstract

Probabilistic prediction plays a crucial role in language comprehension. When predictions are fulfilled, the resulting facilitation allows for fast, efficient processing of ambiguous, rapidly-unfolding input; when predictions are not fulfilled, the resulting error signal allows us to adapt to broader statistical changes in this input. We used functional Magnetic Resonance Imaging to examine the neuroanatomical networks engaged in semantic predictive processing and adaptation. We used a relatedness proportion semantic priming paradigm, in which we manipulated the probability of predictions while holding local semantic context constant. Under conditions of higher (versus lower) predictive validity, we replicate previous observations of reduced activity to semantically predictable words in the left anterior superior/middle temporal cortex, reflecting facilitated processing of targets that are consistent with prior semantic predictions. In addition, under conditions of higher (versus lower) predictive validity we observed significant differences in the effects of semantic relatedness within the left inferior frontal gyrus and the posterior portion of the left superior/middle temporal gyrus. We suggest that together these two regions mediated the suppression of unfulfilled semantic predictions and lexico-semantic processing of unrelated targets that were inconsistent with these predictions. Moreover, under conditions of higher (versus lower) predictive validity, a functional connectivity analysis showed that the left inferior frontal and left posterior superior/middle temporal gyrus were more tightly interconnected with one another, as well as with the left anterior cingulate cortex. The left anterior cingulate cortex was, in turn, more tightly connected to superior lateral frontal cortices and subcortical regions-a network that mediates rapid learning and adaptation and that may have played a role in switching to a more predictive mode of processing in response to the statistical structure of the wider environmental context. Together, these findings highlight close links between the networks mediating semantic prediction, executive function and learning, giving new insights into how our brains are able to flexibly adapt to our environment.

Lau, E. F., Holcomb, P. J., & Kuperberg, G. R. (2013). Dissociating N400 effects of prediction from association in single-word contexts. J Cogn Neurosci , 25 (3), 484-502. Full TextAbstract
When a word is preceded by a supportive context such as a semantically associated word or a strongly constraining sentence frame, the N400 component of the ERP is reduced in amplitude. An ongoing debate is the degree to which this reduction reflects a passive spread of activation across long-term semantic memory representations as opposed to specific predictions about upcoming input. We addressed this question by embedding semantically associated prime-target pairs within an experimental context that encouraged prediction to a greater or lesser degree. The proportion of related items was used to manipulate the predictive validity of the prime for the target while holding semantic association constant. A semantic category probe detection task was used to encourage semantic processing and to preclude the need for a motor response on the trials of interest. A larger N400 reduction to associated targets was observed in the high than the low relatedness proportion condition, consistent with the hypothesis that predictions about upcoming stimuli make a substantial contribution to the N400 effect. We also observed an earlier priming effect (205-240 msec) in the high-proportion condition, which may reflect facilitation because of form-based prediction. In summary, the results suggest that predictability modulates N400 amplitude to a greater degree than the semantic content of the context.
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Lau, E. F., Gramfort, A., Hämäläinen, M. S., & Kuperberg, G. R. (2013). Automatic semantic facilitation in anterior temporal cortex revealed through multimodal neuroimaging. J Neurosci , 33 (43), 17174-81. Full TextAbstract
A core property of human semantic processing is the rapid, facilitatory influence of prior input on extracting the meaning of what comes next, even under conditions of minimal awareness. Previous work has shown a number of neurophysiological indices of this facilitation, but the mapping between time course and localization-critical for separating automatic semantic facilitation from other mechanisms-has thus far been unclear. In the current study, we used a multimodal imaging approach to isolate early, bottom-up effects of context on semantic memory, acquiring a combination of electroencephalography (EEG), magnetoencephalography (MEG), and functional magnetic resonance imaging (fMRI) measurements in the same individuals with a masked semantic priming paradigm. Across techniques, the results provide a strikingly convergent picture of early automatic semantic facilitation. Event-related potentials demonstrated early sensitivity to semantic association between 300 and 500 ms; MEG localized the differential neural response within this time window to the left anterior temporal cortex, and fMRI localized the effect more precisely to the left anterior superior temporal gyrus, a region previously implicated in semantic associative processing. However, fMRI diverged from early EEG/MEG measures in revealing semantic enhancement effects within frontal and parietal regions, perhaps reflecting downstream attempts to consciously access the semantic features of the masked prime. Together, these results provide strong evidence that automatic associative semantic facilitation is realized as reduced activity within the left anterior superior temporal cortex between 300 and 500 ms after a word is presented, and emphasize the importance of multimodal neuroimaging approaches in distinguishing the contributions of multiple regions to semantic processing.
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.
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., 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.
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.
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.
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.