Semantic representations in inferior frontal and lateral temporal cortex during picture naming, reading, and repetition.

Reading, naming, and repetition are classical neuropsychological tasks widely used in the clinic and psycholinguistic research. While reading and repetition can be accomplished by following a direct or an indirect route, pictures can be named only by means of semantic mediation. By means of fMRI multivariate pattern analysis, we evaluated whether this well-established fundamental difference at the cognitive level is associated at the brain level with a difference in the degree to which semantic representations are activated during these tasks. Semantic similarity between words was estimated based on a word association model. Twenty subjects participated in an event-related fMRI study where the three tasks were presented in pseudo-random order. Linear discriminant analysis of fMRI patterns identified a set of regions that allow to discriminate between words at a high level of word-specificity across tasks. Representational similarity analysis was used to determine whether semantic similarity was represented in these regions and whether this depended on the task performed. The similarity between neural patterns of the left Brodmann area 45 (BA45) and of the superior portion of the left supramarginal gyrus correlated with the similarity in meaning between entities during picture naming. In both regions, no significant effects were seen for repetition or reading. The semantic similarity effect during picture naming was significantly larger than the similarity effect during the two other tasks. In contrast, several regions including left anterior superior temporal gyrus and left ventral BA44/frontal operculum, among others, coded for semantic similarity in a task-independent manner. These findings provide new evidence for the dynamic, task-dependent nature of semantic representations in the left BA45 and a more task-independent nature of the representational activation in the lateral temporal cortex and ventral BA44/frontal operculum.

Independency of Coding for Affective Similarities and for Word Co-occurrences in Temporal Perisylvian Neocortex.

Word valence is one of the principal dimensions in the organization of word meaning. Co-occurrence-based similarities calculated by predictive natural language processing models are relatively poor at representing affective content, but very powerful in their own way. Here, we determined how these two canonical but distinct ways of representing word meaning relate to each other in the human brain both functionally and neuroanatomically. We re-analysed an fMRI study of word valence. A co-occurrence-based model was used and the correlation with the similarity of brain activity patterns was compared to that of affective similarities. The correlation between affective and co-occurrence-based similarities was low (r = 0.065), confirming that affect was captured poorly by co-occurrence modelling. In a whole-brain representational similarity analysis, word embedding similarities correlated significantly with the similarity between activity patterns in a region confined to the superior temporal sulcus to the left, and to a lesser degree to the right. Affective word similarities correlated with the similarity in activity patterns in this same region, confirming previous findings. The affective similarity effect extended more widely beyond the superior temporal cortex than the effect of co-occurrence-based similarities did. The effect of co-occurrence-based similarities remained unaltered after partialling out the effect of affective similarities (and vice versa). To conclude, different aspects of word meaning, derived from affective judgements or from word co-occurrences, are represented in superior temporal language cortex in a neuroanatomically overlapping but functionally independent manner.

Representations of conceptual information during automatic and active semantic access.

When we read a word or see an object, conceptual meaning is automatically accessed. However, previous research investigating non-perceptual sensitivity to semantic class has employed active tasks. In this fMRI study, we tested whether conceptual representations in regions constituting the semantic network are invoked during passive semantic access and whether these representations are modulated by the need to access deeper knowledge. Seventeen healthy subjects performed a semantically active typicality judgment task and a semantically passive phonetic decision task, in both the written and the spoken input-modalities. Stimuli consisted of one hundred forty-four concepts drawn from six semantic categories. Multivariate Pattern Analysis (MVPA) revealed that the left posterior middle temporal gyrus (pMTG), posterior ventral temporal cortex (pVTC) and pars triangularis of the left inferior frontal gyrus (IFG) showed a stronger sensitivity to semantic category when active rather than passive semantic access is required. Using a cross-task training/testing classifier, we determined that conceptual representations were not only active in these regions during passive semantic access but that the neural representation of these categories was common to both active and passive access. Collectively, these results show that while representations in the pMTG, pVTC and IFG are strongly modulated by active conceptual access, consistent representational patterns are present during active and passive conceptual access in these same regions.

General and feature-based semantic representations in the semantic network.

How semantic representations are manifest over the brain remains a topic of active debate. A semantic representation may be determined by specific semantic features (e.g. sensorimotor information), or may abstract away from specific features and represent generalized semantic characteristics (general semantic representation). Here we tested whether nodes of the semantic system code for a general semantic representation and/or possess representational spaces linked to particular semantic features. In an fMRI study, eighteen participants performed a typicality judgment task with written words drawn from sixteen different categories. Multivariate pattern analysis (MVPA) and representational similarity analysis (RSA) were adopted to investigate the sensitivity of the brain regions to semantic content and the type of semantic representation coded (general or feature-based). We replicated previous findings of sensitivity to general semantic similarity in posterior middle/inferior temporal gyrus (pMTG/ITG) and precuneus (PC) and additionally observed general semantic representations in ventromedial prefrontal cortex (PFC). Finally, two brain regions of the semantic network were sensitive to semantic features: the left pMTG/ITG was sensitive to haptic perception and the left ventral temporal cortex (VTC) to size. This finding supports the involvement of both general semantic representation and feature-based representations in the brain's semantic system.

Representation of associative and affective semantic similarity of abstract words in the lateral temporal perisylvian language regions.

The examination of semantic cognition has traditionally identified word concreteness as well as valence as two of the principal dimensions in the representation of conceptual knowledge. More recently, corpus-based vector space models as well as graph-theoretical analysis of large-scale task-related behavioural responses have revolutionized our insight into how the meaning of words is structured. In this fMRI study, we apply representational similarity analysis to investigate the conceptual representation of abstract words. Brain activity patterns were related to a cued-association based graph as well as to a vector-based co-occurrence model of word meaning. Twenty-six subjects (19 females and 7 males) performed an overt repetition task during fMRI. First, we performed a searchlight classification procedure to identify regions where activity is discriminable between abstract and concrete words. These regions were left inferior frontal gyrus, the upper and lower bank of the superior temporal sulcus bilaterally, posterior middle temporal gyrus and left fusiform gyrus. Representational Similarity Analysis demonstrated that for abstract words, the similarity of activity patterns in the cortex surrounding the superior temporal sulcus bilaterally and in the left anterior superior temporal gyrus reflects the similarity in word meaning. These effects were strongest for semantic similarity derived from the cued association-based graph and for affective similarity derived from either of the two models. The latter effect was mainly driven by positive valence words. This research highlights the close neurobiological link between the information structure of abstract and affective word content and the similarity in activity pattern in the lateral and anterior temporal language system.

The medial temporal written word processing system.

Traditional neuroanatomical models of written word processing have proposed multiple parallel routes from the visual word form area to lateral temporal, inferior parietal and inferior frontal cortex. Here we hypothesize the existence of an alternative ventromedial occipitotemporal route that culminates in the left perirhinal cortex which codes for the learned association between a concrete written word and the entity it refers to. The hypothesis fits in a broader context that considers perirhinal cortex as a connector hub connecting sensory input with more widespread representations of its content. According to the hypothesis, perirhinal coding of the association between a concrete word and its referent relies on the same operational principles as the coding of paired associates by perirhinal neurons documented by electrophysiological recordings in nonhuman primates. The evidence for a role of human left perirhinal cortex in written word processing is primarily based on two sources: Direct electrophysiological recordings reveal responses to concrete written words compared to function words or nonword stimuli. Secondly, in humans, the conceptual similarity between concrete written words is reflected in the similarity of the activity patterns evoked by these words in perirhinal cortex. The hypothesis has clinical relevance: Patients with the semantic variant of primary progressive aphasia who have damage of the left perirhinal cortex among other anterior temporal regions, have surface alexia as one of their defining features, i.e. the inability to access meaning from written words. The hypothesis of an alternative, ventral occipitotemporal written word processing pathway aligns with the concept that written language processing builds upon pre-existing visual object processing mechanisms.

Redefining the resolution of semantic knowledge in the brain: Advances made by the introduction of models of semantics in neuroimaging.

The boundaries of our understanding of conceptual representation in the brain have been redrawn since the introduction of explicit models of semantics. These models are grounded in vast behavioural datasets acquired in healthy volunteers. Here, we review the most important techniques which have been applied to detect semantic information in neuroimaging data and argue why semantic models are possibly the most valuable addition to the research of semantics in recent years. Using multivariate analysis, predictions based on patient lesion data have been confirmed during semantic processing in healthy controls. Secondly, this new method has given rise to new research avenues, e.g. the detection of semantic processing outside of the temporal cortex. As a future line of work, the same research strategy could be useful to study neurological conditions such as the semantic variant of primary progressive aphasia, which is characterized by pathological semantic processing.

Left perirhinal cortex codes for semantic similarity between written words defined from cued word association.

Knowledge of visual and nonvisual attributes of concrete entities is distributed over neocortical uni- and polymodal association cortex. Here we investigated the role of left perirhinal cortex in explicit knowledge retrieval from written words. We examined whether it extended across visual and nonvisual properties, animate and inanimate entities, how this differed from picture input and how specific it was for perirhinal cortex compared to surrounding structures. The semantic similarity between stimuli was determined on the basis of a word association-based model. Eighteen participants participated in this event-related fMRI experiment. During property verification, the left perirhinal cortex coded for the similarity in meaning between written words. No differences were found between visual and nonvisual properties or between animate and inanimate entities. Among the surrounding regions, a semantic similarity effect for written words was also present in the left parahippocampal gyrus, but not in the hippocampus nor in the right perirhinal cortex. Univariate analysis revealed higher activity for visual property verification in visual processing regions and for nonvisual property verification in an extended system encompassing the superior temporal sulcus along its anterior-posterior axis, the inferior and the superior frontal gyrus. The association strength between the concept and the property correlated positively with fMRI response amplitude in visual processing regions, and negatively with response amplitude in left inferior and superior frontal gyrus. The current findings establish that input-modality determines the semantic similarity effect in left perirhinal cortex more than the content of the knowledge retrieved or the semantic control demand do. We propose that left perirhinal cortex codes for the association between a concrete written word and the object it refers to and operates as a connector hub linking written word input to the distributed cortical representation of word meaning.

Single-word comprehension deficits in the nonfluent variant of primary progressive aphasia.

BACKGROUND: A subset of patients with the nonfluent variant of primary progressive aphasia (PPA) exhibit concomitant single-word comprehension problems, constituting a 'mixed variant' phenotype. This phenotype is rare and currently not fully characterized. The aim of this study was twofold: to assess the prevalence and nature of single-word comprehension problems in the nonfluent variant and to study multimodal imaging characteristics of atrophy, tau, and amyloid burden associated with this mixed phenotype. METHODS: A consecutive memory-clinic recruited series of 20 PPA patients (12 nonfluent, five semantic, and three logopenic variants) were studied on neurolinguistic and neuropsychological domains relative to 64 cognitively intact healthy older control subjects. The neuroimaging battery included high-resolution volumetric magnetic resonance imaging processed with voxel-based morphometry, and positron emission tomography with the tau-tracer [18F]-THK5351 and amyloid-tracer [11C]-Pittsburgh Compound B. RESULTS: Seven out of 12 subjects who had been classified a priori with nonfluent variant PPA showed deficits on conventional single-word comprehension tasks along with speech apraxia and agrammatism, corresponding to a mixed variant phenotype. These mixed variant cases included three females and four males, with a mean age at onset of 65 years (range 44-77 years). Object knowledge and object recognition were additionally affected, although less severely compared with the semantic variant. The mixed variant was characterized by a distributed atrophy pattern in frontal and temporoparietal regions. A more focal pattern of elevated [18F]-THK5351 binding was present in the supplementary motor area, the left premotor cortex, midbrain, and basal ganglia. This pattern was closely similar to that seen in pure nonfluent variant PPA. At the individual patient level, elevated [18F]-THK5351 binding in the supplementary motor area and premotor cortex was present in six out of seven mixed variant cases and in five and four of these cases, respectively, in the thalamus and midbrain. Amyloid biomarker positivity was present in two out of seven mixed variant cases, compared with none of the five pure nonfluent cases. CONCLUSIONS: A substantial proportion of PPA patients with speech apraxia and agrammatism also have single-word comprehension deficits. At the neurobiological level, the mixed variant shows a high degree of similarity with the pure nonfluent variant of PPA. TRIAL REGISTRATION: EudraCT, 2014-002976-10 . Registered on 13-01-2015.

Cross-modal representation of spoken and written word meaning in left pars triangularis.

The correspondence in meaning extracted from written versus spoken input remains to be fully understood neurobiologically. Here, in a total of 38 subjects, the functional anatomy of cross-modal semantic similarity for concrete words was determined based on a dual criterion: First, a voxelwise univariate analysis had to show significant activation during a semantic task (property verification) performed with written and spoken concrete words compared to the perceptually matched control condition. Second, in an independent dataset, in these clusters, the similarity in fMRI response pattern to two distinct entities, one presented as a written and the other as a spoken word, had to correlate with the similarity in meaning between these entities. The left ventral occipitotemporal transition zone and ventromedial temporal cortex, retrosplenial cortex, pars orbitalis bilaterally, and the left pars triangularis were all activated in the univariate contrast. Only the left pars triangularis showed a cross-modal semantic similarity effect. There was no effect of phonological nor orthographic similarity in this region. The cross-modal semantic similarity effect was confirmed by a secondary analysis in the cytoarchitectonically defined BA45. A semantic similarity effect was also present in the ventral occipital regions but only within the visual modality, and in the anterior superior temporal cortex only within the auditory modality. This study provides direct evidence for the coding of word meaning in BA45 and positions its contribution to semantic processing at the confluence of input-modality specific pathways that code for meaning within the respective input modalities.

Left perirhinal cortex codes for similarity in meaning between written words: Comparison with auditory word input.

Left perirhinal cortex has been previously implicated in associative coding. According to a recent experiment, the similarity of perirhinal fMRI response patterns to written concrete words is higher for words which are more similar in their meaning. If left perirhinal cortex functions as an amodal semantic hub, one would predict that this semantic similarity effect would extend to the spoken modality. We conducted an event-related fMRI experiment and evaluated whether a same semantic similarity effect could be obtained for spoken as for written words. Twenty healthy subjects performed a property verification task in either the written or the spoken modality. Words corresponded to concrete animate entities for which extensive feature generation was available from more than 1000 subjects. From these feature generation data, a concept-feature matrix was derived which formed the basis of a cosine similarity matrix between the entities reflecting their similarity in meaning (called the "semantic cossimilarity matrix"). Independently, we calculated a cosine similarity matrix between the left perirhinal fMRI activity patterns evoked by the words (called the "fMRI cossimilarity matrix"). Next, the similarity was determined between the semantic cossimilarity matrix and the fMRI cossimilarity matrix. This was done for written and spoken words pooled, for written words only, for spoken words only, as well as for crossmodal pairs. Only for written words did the fMRI cossimilarity matrix correlate with the semantic cossimilarity matrix. Contrary to our prediction, we did not find any such effect for auditory word input nor did we find cross-modal effects in perirhinal cortex between written and auditory words. Our findings situate the contribution of left perirhinal cortex to word processing at the top of the visual processing pathway, rather than at an amodal stage where visual and auditory word processing pathways have already converged.