Dual-Process Model in Semantic Priming: A Functional Imaging Perspective

Research indicates that the anterior temporal lobes (ATLs) in the left and right hemispheres constitute a supramodal hub for verbal and nonverbal semantic information. However, it remains unclear whether (1) left and right ATLs are respectively specialized for verbal and nonverbal semantic processing (functional specialization models) or (2) bilateral ATLs equally contribute to multimodal semantic processing (unitary "hub-and-spoke" models). The present study examined the question using repetitive transcranial magnetic stimulation (rTMS) with an implicit semantic priming paradigm minimizing top-down influences from cognitive control mechanisms. After receiving rTMS over the left ATL, right ATL or vertex, healthy human adults of either sex made real-versus-unreal judgments about visual words or objects each preceded by semantically related or unrelated primes. While a similar amount of semantic priming survived vertex stimulation for both words and objects, we found that left ATL stimulation, but not right ATL stimulation, eliminated semantic priming for words, suggesting that the verbal semantics is represented in the left ATL. In contrast, rTMS over the ATL eliminated semantic priming for objects irrespective of the side of stimulation. This latter finding suggests a twofold mechanism whereby semantic processing of visual objects depends on semantic computations in the right ATL as well as automatic activation of semantic word representations in the left ATL generating "verbal label" feedback. The observed functional asymmetry of the semantic ATL hub overall supports functional specialization models enriched by verbal label feedback accounts, unveiling that verbal semantic knowledge plays a guiding role in the semantic analysis of visual objects.

The anterior temporal lobes (ATLs) have been consistently associated with semantic processing which, in turn, has a key role in reading aloud single words. This study aimed to investigate (1) the reading abilities in patients with the semantic variant of primary progressive aphasia (svPPA), and (2) the relationship between gray matter (GM) volume of the left ATL and word reading performance using voxel-based morphometry (VBM). Three groups of participants (svPPA, Alzheimer’s Disease, AD and healthy elderly adults) performed a reading task with exception words, regular words and pseudowords, along with a structural magnetic resonance imaging scan. For exception words, the svPPA group had a lower accuracy and a greater number of regularization errors as compared to the control groups of healthy participants and AD patients. Similarly, for regular words, svPPA patients had a lower accuracy in comparison with AD patients, and a greater number of errors related to complex orthography-to-phonology mappings (OPM) in comparison to both control groups. VBM analyses revealed that GM volume of the left ATL was associated with the number of regularization errors. Also, GM volume of the left lateral ATL was associated with the number of errors with complex OPM during regular word reading. Our results suggest that the left ATL might play a role in the reading of exception words, in accordance with its role in semantic processing. Results further support the involvement of the left lateral ATL in combinatorial processes, including the integration of semantic and phonological information, for both exception and regular words.

Complementary hemispheric asymmetries in object naming and recognition: A voxel-based correlational study

Mild traumatic brain injury (mTBI) in athletes, including concussion, is increasingly being found to have long-term sequelae. Current imaging techniques have not been able to identify early damage caused by mTBI that is predictive of long-term symptoms or chronic traumatic encephalopathy. In this preliminary feasibility study, the authors investigated the use of an emerging magnetic resonance imaging (MRI) technique, multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT), in visualizing acute and chronic white matter changes after mTBI in collegiate football and rugby players. This study was a nonrandomized, nonblinded prospective trial designed to quantify changes in the myelin water fraction (MWF), used as a surrogate MRI measure of myelin content, in a group of male collegiate football and rugby players, classified here as a contact sport player (CSP) cohort, at the time of mTBI diagnosis and 3 months after injury when the acute symptoms of the injury had resolved. In addition, differences in the MWF between the CSP cohort and a control cohort of noncontact sport players (NCSPs) were quantified. T-tests and a threshold-free cluster enhancement (TFCE) statistical analysis technique were used to identify brain structures with significant changes in the MWF between the CSP and NCSP cohorts and between immediately postinjury and follow-up images obtained in the CSP cohort. Brain MR images of 12 right-handed male CSPs were analyzed and compared with brain images of 10 right-handed male NCSPs from the same institution. A comparison of CSP and NCSP baseline images using TFCE showed significantly higher MWFs in the bilateral basal ganglia, anterior and posterior corpora callosa, left corticospinal tract, and left anterior and superior temporal lobe (p < 0.05). At the 3-month follow-up examination, images from the CSP cohort still showed significantly higher MWFs than those identified on baseline images from the NCSP cohort in the bilateral basal ganglia, anterior and posterior corpora callosa, and left anterior temporal lobe, and also in the bilateral corticospinal tracts, parahippocampal gyrus, and bilateral juxtapositional (previously known as supplemental motor) areas (p < 0.05). In the CSP cohort, a t-test comparing the MWF at the time of injury and 3 months later showed a significant increase in the overall MWF at follow-up (p < 0.005). These increases were greatest in the bilateral basal ganglia and deep white matter. MWF decreases were seen in more superficial white matter (p < 0.005). In this preliminary study, MWF was found to be increased in the brains of CSPs compared with the brains of controls, suggesting acute/chronic MWF alterations in CSPs from previous injuries. Increases in the MWF were also demonstrated in the brains of CSPs 3 months after the players sustained an mTBI. The full clinical significance of an increased MWF and whether this reflects axon neuropathology or disorderly remyelination leading to hypermyelination has yet to be determined.

Semantic categorization is a fundamental ability in language as well as in interaction with the environment. However, it is unclear what cognitive and neural basis generates this flexible and context dependent categorization of semantic information. We performed behavioral and fMRI experiments with a semantic priming paradigm to clarify this. Participants conducted semantic decision tasks in which a prime word preceded target words, using names of animals (mammals, birds, or fish). We focused on the categorization of unique marine mammals, having characteristics of both mammals and fish. Behavioral experiments indicated that marine mammals were semantically closer to fish than terrestrial mammals, inconsistent with the category membership. The fMRI results showed that the left anterior temporal lobe was sensitive to the semantic distance between prime and target words rather than category membership, while the left ventrolateral prefrontal cortex was sensitive to the consistency of category membership of word pairs. We interpreted these results as evidence of existence of dual processes for semantic categorization. The combination of bottom-up processing based on semantic characteristics in the left anterior temporal lobe and top-down processing based on task and/or context specific information in the left ventrolateral prefrontal cortex is required for the flexible categorization of semantic information.

Considerable evidence from different methodologies has identified the anterior temporal lobes (ATLs) as key regions for the representation of semantic knowledge. Research interest is now shifting to investigate the roles of different ATL subregions in semantic representation, with particular emphasis on the functions of the left versus right ATLs. In this review, we provide evidence for graded specializations both between and within the ATLs. We argue (1) that multimodal, pan‐category semantic representations are supported jointly by both left and right ATLs, yet (2) that the ATLs are not homogeneous in their function. Instead, subtle functional gradations both between and within the ATLs emerge as a consequence of differential connectivity with primary sensory/motor/limbic regions. This graded specialization account of semantic representation provides a compromise between theories that posit no differences between the functions of the left and right ATLs and those that posit that the left and right ATLs are entirely segregated in function. Evidence for this graded account comes from converging sources, and its benefits have been exemplified in formal computational models. We propose that this graded principle is not only a defining feature of the ATLs but is also a more general neurocomputational principle found throughout the temporal lobes.

Prosopagnosia has been considered for a long period of time as the most important and almost exclusive disorder in the recognition of familiar people. In recent years, however, this conviction has been undermined by the description of patients showing a concomitant defect in the recognition of familiar faces and voices as a consequence of lesions encroaching upon the right anterior temporal lobe (ATL). These new data have obliged researchers to reconsider on one hand the construct of ‘associative prosopagnosia’ and on the other hand current models of people recognition. A systematic review of the patterns of familiar people recognition disorders observed in patients with right and left ATL lesions has shown that in patients with right ATL lesions face familiarity feelings and the retrieval of person-specific semantic information from faces are selectively affected, whereas in patients with left ATL lesions the defect selectively concerns famous people naming. Furthermore, some patients with right ATL lesions and intact face familiarity feelings show a defect in the retrieval of person-specific semantic knowledge greater from face than from name. These data are at variance with current models assuming: (a) that familiarity feelings are generated at the level of person identity nodes (PINs) where information processed by various sensory modalities converge, and (b) that PINs provide a modality-free gateway to a single semantic system, where information about people is stored in an amodal format. They suggest, on the contrary: (a) that familiarity feelings are generated at the level of modality-specific recognition units; (b) that face and voice recognition units are represented more in the right than in the left ATLs; (c) that in the right ATL are mainly stored person-specific information based on a convergence of perceptual information, whereas in the left ATLs are represented verbally-mediated person-specific information.

Degraded semantic memory is a prominent feature of frontotemporal dementia (FTD). It is classically associated with semantic dementia and anterior temporal lobe (ATL) atrophy, but semantic knowledge can also be compromised in behavioural variant FTD. Motivated by understanding behavioural change in FTD, recent research has focused selectively on social-semantic knowledge, with proposals that the right ATL is specialized for social concepts. Previous studies have assessed very different types of social concepts and have not compared performance with that of matched non-social concepts. Consequently, it remains unclear to what extent various social concepts are (i) concurrently impaired in FTD, (ii) distinct from general semantic memory and (iii) differentially supported by the left and right ATL. This study assessed multiple aspects of social-semantic knowledge and general conceptual knowledge across cohorts with ATL damage arising from either neurodegeneration or resection. We assembled a test battery measuring knowledge of multiple types of social concept. Performance was compared with non-social general conceptual knowledge, measured using the Cambridge Semantic Memory Test Battery and other matched non–social-semantic tests. Our trans-diagnostic approach included behavioural variant FTD, semantic dementia and ‘mixed’ intermediate cases to capture the FTD clinical spectrum, as well as age-matched healthy controls. People with unilateral left or right ATL resection for temporal lobe epilepsy were also recruited to assess how selective damage to the left or right ATL impacts social- and non–social-semantic knowledge. Social- and non–social-semantic deficits were severe and highly correlated in FTD. Much milder impairments were found after unilateral ATL resection, with no left versus right differences in social-semantic knowledge or general semantic processing and with only naming showing a greater deficit following left versus right damage. A principal component analysis of all behavioural measures in the FTD cohort extracted three components, interpreted as capturing (i) FTD severity, (ii) semantic memory and (iii) executive function. Social and non-social measures both loaded heavily on the same semantic memory component, and scores on this factor were uniquely associated with bilateral ATL grey matter volume but not with the degree of ATL asymmetry. Together, these findings demonstrate that both social- and non–social-semantic knowledge degrade in FTD (semantic dementia and behavioural variant FTD) following bilateral ATL atrophy. We propose that social-semantic knowledge is part of a broader conceptual system underpinned by a bilaterally implemented, functionally unitary semantic hub in the ATLs. Our results also highlight the value of a trans-diagnostic approach for investigating the neuroanatomical underpinnings of cognitive deficits in FTD.

There is considerable debate about the neuroanatomic localization of semantic memory, the knowledge of culturally shared elements such as objects, concepts, and people. Two recent meta-analyses of functional imaging studies (fMRI and PET) sought to identify cortical regions involved in semantic processing. Binder and colleagues (Binder et al., 2009) identified several regions of interest, widely distributed throughout the frontal, parietal, and temporal cortices. In contrast, Lambon Ralph and colleagues (2010) focused on the anterior temporal lobe, and found that when the potential for signal loss is accounted for (due, for example, to distortion artifact or field of view restriction), significant regional activation is detected. We set out to determine whether the anterior temporal lobe plays a significant role in picture naming, a task which relies on semantic memory. We examined a relatively large sample of patients with early Alzheimer's disease (N=145), a multifocal disease process typically characterized in the early stages by problems with episodic memory and executive function. Hypothesis-driven analyses based on regions of interest derived from the meta-analyses as well as exploratory analyses across the entire cerebral cortex demonstrated a highly specific correlation between cortical thinning of the left anterior temporal lobe and impaired naming performance. These findings lend further support to theories that include a prominent role for the anterior temporal lobe in tasks that rely on semantic memory.

The role of the left anterior temporal lobe in semantic composition vs. semantic memory

In recent years, numerous studies have provided converging evidence that word meaning is partially stored in modality-specific cortical networks. However, little is known about the mechanisms supporting the integration of this distributed semantic content into coherent conceptual representations. In the current study we aimed to address this issue by using EEG to look at the spatial and temporal dynamics of feature integration during word comprehension. Specifically, participants were presented with two modality-specific features (i.e., visual or auditory features such as silver and loud) and asked to verify whether these two features were compatible with a subsequently presented target word (e.g., WHISTLE). Each pair of features described properties from either the same modality (e.g., silver, tiny = visual features) or different modalities (e.g., silver, loud = visual, auditory). Behavioral and EEG data were collected. The results show that verifying features that are putatively represented in the same modality-specific network is faster than verifying features across modalities. At the neural level, integrating features across modalities induces sustained oscillatory activity around the theta range (4–6 Hz) in left anterior temporal lobe (ATL), a putative hub for integrating distributed semantic content. In addition, enhanced long-range network interactions in the theta range were seen between left ATL and a widespread cortical network. These results suggest that oscillatory dynamics in the theta range could be involved in integrating multimodal semantic content by creating transient functional networks linking distributed modality-specific networks and multimodal semantic hubs such as left ATL.

Studies of semantic dementia and repetitive TMS have suggested that the bilateral anterior temporal lobes (ATLs) underpin a modality-invariant representational hub within the semantic system. However, it is not clear whether all ATL subregions contribute in the same way. We utilized distortion-corrected fMRI to investigate the pattern of activation in the left and right ATL when participants performed a semantic decision task on auditory words, environmental sounds, or pictures. This showed that the ATL is not functionally homogeneous but is more graded. Both left and right ventral ATL (vATL) responded to all modalities in keeping with the notion that this region underpins multimodality semantic processing. In addition, there were graded differences across the hemispheres. Semantic processing of both picture and environmental sound stimuli was associated with equivalent bilateral vATL activation, whereas auditory words generated greater activation in left than right vATL. This graded specialization for auditory stimuli would appear to reflect the input from the left superior ATL, which responded solely to semantic decisions on the basis of spoken words and environmental sounds, suggesting that this region is specialized to auditory stimuli. A final noteworthy result was that these regions were activated for domain level decisions to singly presented stimuli, which appears to be incompatible with the hypotheses that the ATL is dedicated (a) to the representation of specific entities or (b) for combinatorial semantic processes.

Electrophysiological correlates of auditory semantic priming in 24-month-olds

Background: Case 1: a 59-year old man presented to our service with 4 years of progressive cognitive and behavioral symptoms. He became forgetful and experienced difficulties managing his payments. After 4 years he could no longer recognise his relatives. Cognitive assessment showed a mini-mental status examination of 17/30. MRI and SPECT revealed respectively focal atrophy and hipoperfusion of the frontal regions and anterior right temporal lobe. Case 2: a 72-year-old woman was brought to evaluation with a 5-years history of progressive language and behavioral deterioration. Her family reported early speech errors and behavioral changes, with a marked aggressiveness, ritualistic behaviors and hyperorality. Cognitive evaluation revealed a MMSE of 6/30 mainly due to a relatively fluent afasia. Brain MRI showed asymmetric cerebral atrophy, more prominent in the anterior left temporal lobe. Objective: N/H Methods: N/H Results: N/H Conclusion: We describe two cases of suspected frontotemporal dementia (FTD) syndromes. The left ATL may receive proportionately more input from the lexical and phonological centers subserving word processing. The right ATL may receive more input from right-lateralized emotion processing hubs. Focal atrophy of the left anterior temporal lobe has been associated with the semantic type of primary progressive aphasia evolving to semantic dementia. In contrast, focal atrophy of the right temporal lobe has recently been described as a controversial entity reported as the right temporal variant of FTD.

Humans often utilize past experience to solve difficult problems. However, if past experience is insufficient to solve a problem, solvers may reach an impasse. Insight can be valuable for breaking an impasse, enabling the reinterpretation or re-representation of a problem. Previous studies using between-subjects designs have revealed a causal relationship between the anterior temporal lobes (ATLs) and non-verbal insight, by enhancing the right ATL while inhibiting the left ATL using transcranial direct current stimulation (tDCS). In addition, neuroimaging studies have reported a correlation between right ATL activity and verbal insight. Based on these findings, we hypothesized that the right ATL is causally related to both non-verbal and verbal insight. To test this hypothesis, we conducted an experiment with 66 subjects using a within-subjects design, which typically has greater statistical power than a between-subjects design. Subjects participated in tDCS experiments across 2 days, in which they solved both non-verbal and verbal insight problems under active or sham stimulation conditions. To dissociate the effects of right ATL stimulation from those of left ATL stimulation, we used two montage types; anodal tDCS of the right ATL together with cathodal tDCS of the left ATL (stimulating both ATLs) and anodal tDCS of the right ATL with cathodal tDCS of the left cheek (stimulating only the right ATL). The montage used was counterbalanced across subjects. Statistical analyses revealed that, regardless of the montage type, there were no significant differences between the active and sham conditions for either verbal or non-verbal insight, although the finding for non-verbal insight was inconclusive because of a lack of statistical power. These results failed to support previous findings suggesting that the right ATL is the central locus of insight.