William W. Graves

Where Is the Semantic System? A Critical Review and Meta-Analysis of 120 Functional Neuroimaging Studies

Semantic memory refers to knowledge about people, objects, actions, relations, self, and culture acquired through experience. The neural systems that store and retrieve this information have been studied for many years, but a consensus regarding their identity has not been reached. Using strict inclusion criteria, we analyzed 120 functional neuroimaging studies focusing on semantic processing. Reliable areas of activation in these studies were identified using the activation likelihood estimate (ALE) technique. These activations formed a distinct, left-lateralized network comprised of 7 regions: posterior inferior parietal lobe, middle temporal gyrus, fusiform and parahippocampal gyri, dorsomedial prefrontal cortex, inferior frontal gyrus, ventromedial prefrontal cortex, and posterior cingulate gyrus. Secondary analyses showed specific subregions of this network associated with knowledge of actions, manipulable artifacts, abstract concepts, and concrete concepts. The cortical regions involved in semantic processing can be grouped into 3 broad categories: posterior multimodal and heteromodal association cortex, heteromodal prefrontal cortex, and medial limbic regions. The expansion of these regions in the human relative to the nonhuman primate brain may explain uniquely human capacities to use language productively, plan, solve problems, and create cultural and technological artifacts, all of which depend on the fluid and efficient retrieval and manipulation of semantic knowledge.

Neural Systems for Reading Aloud: A Multiparametric Approach

Reading aloud involves computing the sound of a word from its visual form. This may be accomplished 1) by direct associations between spellings and phonology and 2) by computation from orthography to meaning to phonology. These components have been studied in behavioral experiments examining lexical properties such as word frequency; length in letters or phonemes; spelling–sound consistency; semantic factors such as imageability, measures of orthographic, or phonological complexity; and others. Effects of these lexical properties on specific neural systems, however, are poorly understood, partially because high intercorrelations among lexical factors make it difficult to determine if they have independent effects. We addressed this problem by decorrelating several important lexical properties through careful stimulus selection. Functional magnetic resonance imaging data revealed distributed neural systems for mapping orthography directly to phonology, involving left supramarginal, posterior middle temporal, and fusiform gyri. Distinct from these were areas reflecting semantic processing, including left middle temporal gyrus/inferior-temporal sulcus, bilateral angular gyrus, and precuneus/posterior cingulate. Left inferior frontal regions generally showed increased activation with greater task load, suggesting a more general role in attention, working memory, and executive processes. These data offer the first clear evidence, in a single study, for the separate neural correlates of orthography–phonology mapping and semantic access during reading aloud.

The left posterior superior temporal gyrus participates specifically in accessing lexical phonology

Impairments in phonological processing have been associated with damage to the region of the left posterior superior temporal gyrus (pSTG), but the extent to which this area supports phonological processing, independent of semantic processing, is less clear. We used repetition priming and neural repetition suppression during functional magnetic resonance imaging (fMRI) in an auditory pseudoword repetition task as a semantics-free model of lexical (whole-word) phonological access. Across six repetitions, we observed repetition priming in terms of decreased reaction time and repetition suppression in terms of reduced neural activity. An additional analysis aimed at sublexical phonology did not show significant effects in the areas where repetition suppression was observed. To test if these areas were relevant to real word production, we performed a conjunction analysis with data from a separate fMRI experiment which manipulated word frequency (a putative index of lexical phonological access) in picture naming. The left pSTG demonstrated significant effects independently in both experiments, suggesting that this area participates specifically in accessing lexical phonology.

A Neural Signature of Phonological Access: Distinguishing the Effects of Word Frequency from Familiarity and Length in Overt Picture Naming

Cognitive models of word production correlate the word frequency effect (i.e., the fact that words which appear with less frequency take longer to produce) with an increased processing cost to activate the whole-word (lexical) phonological representation. We performed functional magnetic resonance imaging (fMRI) while subjects produced overt naming responses to photographs of animals and manipulable objects that had high name agreement but were of varying frequency, with the purpose of identifying neural structures participating specifically in activating whole-word phonological representations, as opposed to activating lexical semantic representations or articulatory-motor routines. Blood oxygen level-dependent responses were analyzed using a parametric approach based on the frequency with which each word produced appears in the language. Parallel analyses were performed for concept familiarity and word length, which provided indices of semantic and articulatory loads. These analyses permitted us to identify regions related to word frequency alone, and therefore, likely to be related specifically to activation of phonological word forms. We hypothesized that the increased processing cost of producing lower-frequency words would correlate with activation of the left posterior inferotemporal (IT) cortex, the left posterior superior temporal gyrus (pSTG), and the left inferior frontal gyrus (IFG). Scan-time response latencies demonstrated the expected word frequency effect. Analysis of the fMRI data revealed that activity in the pSTG was modulated by frequency but not word length or concept familiarity. In contrast, parts of IT and IFG demonstrated conjoint frequency and familiarity effects, and parts of both primary motor regions demonstrated conjoint effects of frequency and word length. The results are consistent with a model of word production in which lexical-semantic and lexical-phonological information are accessed by overlapping neural systems within posterior and anterior language-related cortices, with pSTG specifically involved in accessing lexical phonology.

Neural correlates of implicit and explicit combinatorial semantic processing

Language consists of sequences of words, but comprehending phrases involves more than concatenating meanings: A boat house is a shelter for boats, whereas a summer house is a house used during summer, and a ghost house is typically uninhabited. Little is known about the brain bases of combinatorial semantic processes. We performed two fMRI experiments using familiar, highly meaningful phrases (lake house) and unfamiliar phrases with minimal meaning created by reversing the word order of the familiar items (house lake). The first experiment used a 1-back matching task to assess implicit semantic processing, and the second used a classification task to engage explicit semantic processing. These conditions required processing of the same words, but with more effective combinatorial processing in the meaningful condition. The contrast of meaningful versus reversed phrases revealed activation primarily during the classification task, to a greater extent in the right hemisphere, including right angular gyrus, dorsomedial prefrontal cortex, and bilateral posterior cingulate/precuneus, areas previously implicated in semantic processing. Positive correlations of fMRI signal with lexical (word-level) frequency occurred exclusively with the 1-back task and to a greater spatial extent on the left, including left posterior middle temporal gyrus and bilateral parahippocampus. These results reveal strong effects of task demands on engagement of lexical versus combinatorial processing and suggest a hemispheric dissociation between these levels of semantic representation.

The delayed effects of DTG and MK-801 on latent inhibition in a conditioned taste-aversion paradigm.

The delayed effects of phencyclidine (PCP) have been shown to disrupt latent inhibition (LI) in a conditioned taste-aversion paradigm. In an attempt to understand the mechanism of this disruption, the delayed effects of the selective sigma receptor agonist 1,3-Di(2-tolyl)guanidine (DTG) and the selective NMDA receptor antagonist MK-801 on latent inhibition were assessed in the same paradigm. Water-deprived male rats were allowed access to either water (nonpreexposed; NPE) or 5% sucrose (preexposed; PE) for 30 min on 2 consecutive days. On the third day, animals were allowed access to sucrose and subsequently injected with lithium chloride. On the forth day, animals were allowed access to both sucrose and water. LI was assessed by comparing the percent sucrose consumed in PE and NPE groups on the fourth day. DTG (1.0, 5.0, or 10.0 mg/kg), MK-801 (0.5, 1.0, or 2.0 mg/kg), or vehicle was administered IP 20 h before preexposure (days 1 and 2) and conditioning (day 3). In vehicle-treated groups, PE animals consumed a significantly higher percent sucrose on the test day than NPE animals, indicating the presence of LI. DTG (10.0 mg/kg) and MK-801 (2.0 mg/kg) decreased the percent sucrose consumed by animals in the PE group to the level observed in the NPE group, indicating disrupted LI. However, this dose of MK-801 was found to produce a decrease in percent sucrose consumed in PE animals not treated with lithium chloride, indicating that the decrease observed in the LI paradigm could be due to MK-801-induced decrease in taste preference for sucrose rather than a disruption of LI. Lower doses of MK-801 that did not produce a decrease in taste preference for sucrose did not significantly disrupt LI. None of the doses of DTG tested altered taste preference for sucrose. These data suggest a role for sigma receptors in the previously observed PCP-induced disruption of LI. Published by Elsevier Science Inc., 2000

Anatomy is Strategy: Skilled Reading Differences Associated with Structural Connectivity Differences in the Reading Network

Are there multiple ways to be a skilled reader? To address this longstanding, unresolved question, we hypothesized that individual variability in using semantic information in reading aloud would be associated with neuroanatomical variation in pathways linking semantics and phonology. Left-hemisphere regions of interest for diffusion tensor imaging analysis were defined based on fMRI results, including two regions linked with semantic processing - angular gyrus (AG) and inferior temporal sulcus (ITS) - and two linked with phonological processing - posterior superior temporal gyrus (pSTG) and posterior middle temporal gyrus (pMTG). Effects of imageability (a semantic measure) on response times varied widely among individuals and covaried with the volume of pathways through the ITS and pMTG, and through AG and pSTG, partially overlapping the inferior longitudinal fasciculus and the posterior branch of the arcuate fasciculus. These results suggest strategy differences among skilled readers associated with structural variation in the neural reading network.

Neural networks underlying contributions from semantics in reading aloud

Reading is an essential part of contemporary society, yet much is still unknown about the physiological underpinnings of its information processing components. Two influential cognitive models of reading, the connectionist and dual-route cascaded models, offer very different accounts, yet evidence for one or the other remains equivocal. These models differ in several ways, including the role of semantics (word meaning) in mapping spelling to sound. We used a new effective connectivity algorithm, IMaGES, to provide a network-level perspective on these network-level models. Left hemisphere regions of interest were defined based on main effects in functional magnetic resonance imaging and included two regions linked with semantic processing—angular gyrus (AG) and inferior temporal sulcus (ITS)—and two regions linked with phonological processing—posterior superior temporal gyrus (pSTG) and posterior middle temporal gyrus (pMTG). Participants read aloud words of high or low spelling-sound consistency, word frequency, and imageability. Only the connectionist model predicted increased contributions from semantic areas with those computing phonology for low-consistency words. Effective connectivity analyses revealed that areas supporting semantic processing (e.g., the ITS) interacted with phonological areas (e.g., the pSTG), with the pattern changing as a function of word properties. Connectivity from semantic to phonological areas emerged for high- compared to low-imageability words, and a similar pattern emerged for low-consistency words, though only under certain conditions. Analyses of individual differences also showed that variation in the strength of modulation of ITS by AG was associated with reading aloud performance. Overall, these results suggest that connections with semantic processing areas are not only associated with reading aloud, but that these connections are also associated with optimal reading performance.

Noun-noun combination: Meaningfulness ratings and lexical statistics for 2,160 word pairs

The combining of individual concepts to form an emergent concept is a fundamental aspect of language, yet much less is known about it than about processing isolated words or sentences. To facilitate research on conceptual combination, we provide meaningfulness ratings for a large set of (2,160) noun–noun pairs. Half of these pairs (1,080) are reversed versions of the other half (e.g., ski jacket and jacket ski), to facilitate the comparison of successful and unsuccessful conceptual combination independently of constituent lexical items. The computer code used for obtaining these ratings through a Web interface is provided. To further enhance the usefulness of this resource, ancillary measures obtained from other sources are also provided for each pair. These measures include associate production norms, contextual relatedness in terms of latent semantic analysis distance, total number of letters, phrase-level usage frequency, and word-level usage frequency summed across the words in each pair. Results of correlation and regression analyses are also provided for a quantitative description of the stimulus set. A subset of these stimuli was used to identify neural correlates of successful conceptual combination Graves, Binder, Desai, Conant, & Seidenberg, (NeuroImage 53:638–646, 2010). The stimuli can be used in other research and also provide benchmark data for evaluating the effectiveness of computational algorithms for predicting meaningfulness of noun–noun pairs.

Reversing the standard neural signature of the word-nonword distinction

The distinction between letter strings that form words and those that look and sound plausible but are not meaningful is a basic one. Decades of functional neuroimaging experiments have used this distinction to isolate the neural basis of lexical (word level) semantics, associated with areas such as the middle temporal, angular, and posterior cingulate gyri that overlap the default mode network. In two fMRI experiments, a different set of findings emerged when word stimuli were used that were less familiar (measured by word frequency) than those typically used. Instead of activating default mode network areas often associated with semantic processing, words activated task-positive areas such as the inferior pFC and SMA, along with multifunctional ventral occipitotemporal cortices related to reading, whereas nonwords activated default mode areas previously associated with semantics. Effective connectivity analyses of fMRI data on less familiar words showed activation driven by task-positive and multifunctional reading-related areas, whereas highly familiar words showed bottom–up activation flow from occipitotemporal cortex. These findings suggest that functional neuroimaging correlates of semantic processing are less stable than previously assumed, with factors such as word frequency influencing the balance between task-positive, reading-related, and default mode networks. More generally, this suggests that results of contrasts typically interpreted in terms of semantic content may be more influenced by factors related to task difficulty than is widely appreciated.