Although limited and reduced connected speech production is one, if not the most, prominent feature of aphasia, few studies have examined the properties of content words produced during discourse in aphasia, in comparison to the many investigations of single-word production. In this study, we used a distributional analysis approach to investigate the properties of content word production during discourse by 46 participants spanning a wide range of chronic poststroke aphasia and 20 neurotypical adults, using different stimuli that elicited three discourse genres (descriptive, narrative, and procedural). Initially, we inspected the discourse data with respect to the quantity of production, lexical–semantic diversity, and psycholinguistic features (frequency and imageability) of content words. Subsequently, we created a “lexical–semantic landscape,” which is sensitive to subtle changes and allowed us to evaluate the pattern of changes in discourse production across groups. Relative to neurotypical adults, all persons with aphasia (both fluent and nonfluent) showed significant reduction in the quantity and diversity of production, but the lexical–semantic complexity of word production directly mirrored neurotypical performance. Specifically, persons with aphasia produced the same rate of nouns/verbs, and their discourse samples covered the full range of word frequency and imageability, albeit with reduced word quantity. These findings provide novel evidence that, unlike in other disorders (e.g., semantic dementia), discourse production in poststroke aphasia has relatively preserved lexical–semantic complexity but demonstrates significantly compromised quantity of content word production. Voxel-wise lesion-symptom mapping using both univariate and multivariate approaches revealed left frontal regions particularly the pars opercularis, insular cortex, and central and frontal opercular cortices supporting word retrieval during connected speech, irrespective of their word class or lexical–semantic complexity.

The role of the left angular gyrus (AG) in language processing remains unclear. In this study, we used TMS to test the hypothesis that the left AG causally supports the processes necessary for context-dependent integration and encoding of information during language processing. We applied on-line TMS over the left AG to disrupt the on-line context-dependent integration during a language reading task, specifically while human participants integrated information between two sequentially presented paragraphs of text (“context” and “target” paragraphs). We assessed the effect of TMS on the left AG by asking participants to retrieve integrated contextual information when given the target condition as cue in a successive memory task. Results from the memory task showed that TMS applied over the left AG during reading impaired the formation of integrated context-target representation. These results provide the first evidence of a causal link between the left AG function, on-line information integration, and associative encoding during language processing.

Studies of semantic dementia, imaging, and repetitive TMS have suggested that the bilateral anterior temporal lobes (ATLs) underpin a modality-invariant representational hub within the semantic system. Questions remain, however, regarding functional specialization across a variety of knowledge domains within the ATL region. We investigated direct evidence for the functional relevance of the superior ATL in processing social concepts. Using converging evidence from noninvasive brain stimulation and neuropsychology, we demonstrate graded differentiation of right and left superior anterior temporal areas in social cognition. Whereas the left superior ATL is necessary for processing both social and nonsocial abstract concepts, social conceptual processing predominates in the right superior ATL. This graded hemispheric specialization is mirrored in the patient results. Our data shed new light on the classic debate about hemispheric differences in semantic and social cognition. These results are considered in the context of models of semantic representation and the emerging data on connectivity for left and right ATL regions.

Despite indications that regions within the anterior temporal lobe (ATL) might make a crucial contribution to pan-modal semantic representation, to date there have been no investigations of when during semantic processing the ATL plays a critical role. To test the timing of the ATL involvement in semantic processing, we studied the effect of double-pulse TMS on behavioral responses in semantic and difficulty-matched control tasks. Chronometric TMS was delivered over the left ATL (10 mm from the tip of the temporal pole along the middle temporal gyrus). During each trial, two pulses of TMS (40 msec apart) were delivered either at baseline (before stimulus presentation) or at one of the experimental time points 100, 250, 400, and 800 msec poststimulus onset. A significant disruption to performance was identified from 400 msec on the semantic task but not on the control assessment. Our results not only reinforce the key role of the left ATL in semantic representation but also indicate that its contribution is especially important around 400 msec poststimulus onset. Together, these facts suggest that the ATL may be one of the neural sources of the N400 ERP component.

The emergentist-connectionist approach assumes that language processing reflects interaction between primary neural systems (Primary Systems Hypothesis). This idea offers an overarching framework that generalizes to various kinds of (English) language and nonverbal cognitive activities. The current study advances this approach with respect to language in two new and important ways. The first is the provision of a neuroanatomically constrained implementation of the theory. The second is a test of its ability to generalize to a language other than English (in this case Japanese) and, in particular, to a feature of that language (pitch accent) for which there is no English equivalent. A corpus analysis revealed the presence and distribution of typical and atypical accent forms in Japanese vocabulary, forming a quasiregular domain. Consequently, according to the Primary Systems Hypothesis, there should be a greater semantic impact on the processing of words with an atypical pitch accent. In turn, when word meaning is intrinsically less rich (e.g., abstract words), speakers should be prone to regularization errors of pitch accent. We explored these semantic-phonological interactions, first, in a neuroanatomically constrained, parallel-distributed processing model of spoken language processing. This model captured the accent typicality effect observed in nonword repetition in Japanese adults and children and exhibited the predicted semantic impact on repetition of words with atypical accent patterns. Second, also as predicted, in word repetition and immediate serial recall of spoken words, human participants exhibited reduced pitch–accent accuracy and/or slower RT for low imageability words with atypical accent patterns, and they generated accent errors reflecting the more typical accent patterns found in Japanese.

Human and animal lesion studies have shown that behavior can be catastrophically impaired after bilateral lesions but that unilateral damage often produces little or no effect, even controlling for lesion extent. This pattern is found across many different sensory, motor, and memory domains. Despite these findings, there has been no systematic, computational explanation. We found that the same striking difference between unilateral and bilateral damage emerged in a distributed, recurrent attractor neural network. The difference persists in simple feedforward networks, where it can be understood in explicit quantitative terms. In essence, damage both distorts and reduces the magnitude of relevant activity in each hemisphere. Unilateral damage reduces the relative magnitude of the contribution to performance of the damaged side, allowing the intact side to dominate performance. In contrast, balanced bilateral damage distorts representations on both sides, which contribute equally, resulting in degraded performance. The model's ability to account for relevant patient data suggests that mechanisms similar to those in the model may operate in the brain.

Semantic cognition requires a combination of semantic representations and executive control processes to direct activation in a task- and time-appropriate fashion [Jefferies, E., & Lambon Ralph, M. A. Semantic impairment in stroke aphasia versus semantic dementia: A case-series comparison. Brain, 129, 2132–2147, 2006]. We undertook a formal meta-analysis to investigate which regions within the large-scale semantic network are specifically associated with the executive component of semantic cognition. Previous studies have described in detail the role of left ventral pFC in semantic regulation. We examined 53 studies that contrasted semantic tasks with high > low executive requirements to determine whether cortical regions beyond the left pFC show the same response profile to executive semantic demands. Our findings revealed that right pFC, posterior middle temporal gyrus (pMTG) and dorsal angular gyrus (bordering intraparietal sulcus) were also consistently recruited by executively demanding semantic tasks, demonstrating patterns of activation that were highly similar to the left ventral pFC. These regions overlap with the lesions in aphasic patients who exhibit multimodal semantic impairment because of impaired regulatory control (semantic aphasia)—providing important convergence between functional neuroimaging and neuropsychological studies of semantic cognition. Activation in dorsal angular gyrus and left ventral pFC was consistent across all types of executive semantic manipulation, regardless of whether the task was receptive or expressive, whereas pMTG activation was only observed for manipulation of control demands within receptive tasks. Second, we contrasted executively demanding tasks tapping semantics and phonology. Our findings revealed substantial overlap between the two sets of contrasts within left ventral pFC, suggesting this region underpins domain-general control mechanisms. In contrast, we observed relative specialization for semantic control within pMTG as well as the most ventral aspects of left pFC (BA 47), consistent with our proposal of a distributed network underpinning semantic control.

In recent years, multiple independent neuroscience investigations have implicated critical roles for the rostral temporal lobe in auditory and visual perception, language, and semantic memory. Although arising in the context of different cognitive functions, most of these suggest that there is a gradual convergence of sensory information in the temporal lobe that culminates in modality- and perceptually invariant representations at the most rostral aspect. Currently, however, too little is known regarding connectivity within the human temporal lobe to be sure of exactly how and where convergence occurs; existing hypotheses are primarily derived on the basis of cross-species generalizations from invasive nonhuman primate studies, the validity of which is unclear, especially where language function is concerned. In this study, we map the connectivity of the human rostral temporal lobe in vivo for the first time using diffusion-weighted imaging probabilistic tractography. The results indicate that convergence of sensory information in the temporal lobe is in fact a graded process that occurs along both its longitudinal and lateral axes and culminates in the most rostral limits. We highlight the consistency of our results with those of prior functional neuroimaging, computational modeling, and patient studies. By going beyond simple fasciculus reconstruction, we systematically explored the connectivity of specific temporal lobe areas to frontal and parietal language regions. In contrast to the graded within-temporal lobe connectivity, this intertemporal connectivity was found to dissociate across caudal, mid, and rostral subregions. Furthermore, we identified a basal rostral temporal region with very limited connectivity to areas outside the temporal lobe, which aligns with recent evidence that this subregion underpins the extraction of modality- and context-invariant semantic representations.

Most contemporary theories of semantic memory assume that concepts are formed from the distillation of information arising in distinct sensory and verbal modalities. The neural basis of this distillation or convergence of information was the focus of this study. Specifically, we explored two commonly posed hypotheses: (a) that the human middle temporal gyrus (MTG) provides a crucial semantic interface given the fact that it interposes auditory and visual processing streams and (b) that the anterior temporal region—especially its ventral surface (vATL)—provides a critical region for the multimodal integration of information. By utilizing distortion-corrected fMRI and an established semantic association assessment (commonly used in neuropsychological investigations), we compared the activation patterns observed for both the verbal and nonverbal versions of the same task. The results are consistent with the two hypotheses simultaneously: Both MTG and vATL are activated in common for word and picture semantic processing. Additional planned, ROI analyses show that this result follows from two principal axes of convergence in the temporal lobe: both lateral (toward MTG) and longitudinal (toward the anterior temporal lobe).

Aphasic patients with multimodal semantic impairment following pFC or temporo-parietal (TP) cortex damage (semantic aphasia [SA]) have deficits characterized by poor control of semantic activation/retrieval, as opposed to loss of semantic knowledge per se. In line with this, SA patients show “refractory effects”; that is, declining accuracy in cyclical word–picture matching tasks when semantically related sets are presented rapidly and repeatedly. This is argued to follow a build-up of competition between targets and distractors. However, the link between poor semantic control and refractory effects is still controversial for two reasons. (1) Some theories propose that refractory effects are specific to verbal or auditory tasks, yet SA patients show poor control over semantic processing in both word and picture semantic tasks. (2) SA can result from lesions to either the left pFC or TP cortex, yet previous work suggests that refractory effects are specifically linked to the left inferior frontal cortex. For the first time, verbal, visual, and nonverbal auditory refractory effects were explored in nine SA patients who had pFC (pFC+) or TP cortex (TP-only) lesions. In all modalities, patient accuracy declined significantly over repetitions. This refractory effect at the group level was driven by pFC+ patients and was not shown by individuals with TP-only lesions. These findings support the theory that SA patients have reduced control over multimodal semantic retrieval and, additionally, suggest there may be functional specialization within the posterior versus pFC elements of the semantic control network.

To understand the meanings of words and objects, we need to have knowledge about these items themselves plus executive mechanisms that compute and manipulate semantic information in a task-appropriate way. The neural basis for semantic control remains controversial. Neuroimaging studies have focused on the role of the left inferior frontal gyrus (LIFG), whereas neuropsychological research suggests that damage to a widely distributed network elicits impairments of semantic control. There is also debate about the relationship between semantic and executive control more widely. We used TMS in healthy human volunteers to create “virtual lesions” in structures typically damaged in patients with semantic control deficits: LIFG, left posterior middle temporal gyrus (pMTG), and intraparietal sulcus (IPS). The influence of TMS on tasks varying in semantic and nonsemantic control demands was examined for each region within this hypothesized network to gain insights into (i) their functional specialization (i.e., involvement in semantic representation, controlled retrieval, or selection) and (ii) their domain dependence (i.e., semantic or cognitive control). The results revealed that LIFG and pMTG jointly support both the controlled retrieval and selection of semantic knowledge. IPS specifically participates in semantic selection and responds to manipulations of nonsemantic control demands. These observations are consistent with a large-scale semantic control network, as predicted by lesion data, that draws on semantic-specific (LIFG and pMTG) and domain-independent executive components (IPS).

Hub-and-spoke models of semantic representation suggest that coherent concepts are formed from the integration of multiple, modality-specific information sources with additional modality-invariant representations—most likely stored in the ventrolateral anterior temporal lobe (vATL). As well as providing the necessary computational mechanisms for the complexities of feature integration, these modality-invariant representations also license a key aspect of semantic memory—semantic-based generalization. Semantic dementia allows us to investigate this aspect of conceptual knowledge because (a) the patients have a selective and progressive semantic degradation and (b) this is associated with profound ventrolateral ATL atrophy. Specifically, the boundaries between concepts become degraded in semantic dementia and, when tested using the appropriate materials, the patients make simultaneous under- and overgeneralization errors. We found that the rate of these errors were a function of typicality and psuedotypicality of the items as well as the severity of the patients' semantic impairment. Following the modality-invariant nature of the vATL hub representation, we also confirmed that the patients were impaired on both verbal- and picture-based versions of the same task.

Word frequency is a powerful predictor of language processing efficiency in healthy individuals and in computational models. Puzzlingly, frequency effects are often absent in stroke aphasia, challenging the assumption that word frequency influences the behavior of any computational system. To address this conundrum, we investigated divergent effects of frequency in two comprehension-impaired patient groups. Patients with semantic dementia have degraded conceptual knowledge as a consequence of anterior temporal lobe atrophy and show strong frequency effects. Patients with multimodal semantic impairments following stroke (semantic aphasia [SA]), in contrast, show little or no frequency effect. Their deficits arise from impaired control processes that bias activation toward task-relevant aspects of knowledge. We hypothesized that high-frequency words exert greater demands on cognitive control because they are more semantically diverse—they tend to appear in a broader range of linguistic contexts and have more variable meanings. Using latent semantic analysis, we developed a new measure of semantic diversity that reflected the variability of a word's meaning across different context. Frequency, but not diversity, was a significant predictor of comprehension in semantic dementia, whereas diversity was the best predictor of performance in SA. Most importantly, SA patients did show typical frequency effects but only when the influence of diversity was taken into account. These results are consistent with the view that higher-frequency words place higher demands on control processes, so that when control processes are damaged the intrinsic processing advantages associated with higher-frequency words are masked.

Semantic cognition, which encompasses all conceptually based behavior, is dependent on the successful interaction of two key components: conceptual representations and regulatory control. Qualitatively distinct disorders of semantic knowledge follow damage to the different parts of this system. Previous studies have shown that patients with multimodal semantic impairment following CVA—a condition referred to as semantic aphasia (SA)—perform poorly on a range of conceptual tasks due to a failure of executive control following prefrontal and/or temporo-parietal infarction [Jefferies, E., & Lambon Ralph, M. A. Semantic impairment in stroke aphasia versus semantic dementia: A case-series comparison. Brain, 129, 2132–2147, 2006]. Although a deficit of core semantic control would be expected to impair all modalities in parallel, most research exploring this condition has focused on tasks in the verbal domain. In a novel exploration of semantic control in the nonverbal domain, therefore, we assessed eight patients with SA on two experiments that examined object use knowledge under different levels of task constraint. Patients exhibited three key characteristics of semantic deregulation: (a) difficulty using conceptual knowledge flexibly to support the noncanonical uses of everyday objects; (b) poor inhibition of semantically related distractor items; and (c) improved object use with the provision of more tightly constraining task conditions following verbal and pictorial cues. Our findings are consistent with the notion that a neural network incorporating the left inferior prefrontal and temporo-parietal areas (damaged in SA) underpins regulation of semantic activation across both verbal and nonverbal modalities.

Semantic cognition—semantically driven verbal and nonverbal behavior—is composed of at least two interactive principal components: conceptual representations and executive control processes that regulate and shape activation within the semantic system. Previous studies indicate that semantic dementia follows from a progressive yet specific degradation of conceptual knowledge. In contrast, multimodal semantic impairment in aphasic patients (semantic aphasia [SA]) reflects damage to the control component of semantic cognition [Jefferies, E., & Lambon Ralph, M. A. Semantic impairment in stroke aphasia versus semantic dementia: A case-series comparison. Brain, 129 , 2132–2147, 2006]. The purpose of the present study was to examine the nature of the semantic control deficits in SA in detail for the first time. Seven patients with SA were tested on four comprehension and naming tasks that directly manipulated the requirement for executive control in different ways. In line with many theories of cognitive control, the SA patients demonstrated three core features of impaired control: (i) they exhibited poor on-line manipulation and exploration of semantic knowledge; (ii) they exhibited poor inhibition of strongly associated distractors; and (iii) they exhibited reduced ability to focus on or augment less dominant aspects of semantic information, although the knowledge itself remained and could be successfully cued by external constraints provided by the examiner. Our findings are consistent with the notion that the anterior temporal lobes are crucial for conceptual knowledge whereas the left prefrontal and temporo-parietal cortices, damaged in patients with SA, play a critical role in regulating semantic activation in a task-appropriate fashion.

PMSP96 [Plaut, D. C., McClelland, J. L., Seidenberg, M. S., & Patterson, K. Understanding normal and impaired word reading: Computational principles in quasi-regular domains. Psychological Review, 103 , 56–115, 1996, Simulation 4] is an implementation of the triangle model of reading, which was able to simulate effects found in normal and surface dyslexic readers. This study replicated the original findings and explored the possibility that damage to the phonological portion of the model might produce symptoms of phonological dyslexia. The first simulation demonstrated that this implementation of PMSP96 was able to reproduce the standard effects of reading, and that when damaged by removal of the semantic input to phonology, it produced the kind of frequency/consistency interactions and regularization errors typical of surface dyslexia. The second simulation explored the effect of phonological damage. Phonological damage alone did not result in a convincing simulation of phonological dyslexia. However, when the damage was followed by a period of recovery, the network was able to simulate large lexicality and imageability effects characteristic of phonological dyslexia-the first time that both surface and phonological dyslexia have been simulated in the same parallel distributed processing network. This result supports the view that plasticity-related changes should be a significant factor in our understanding of chronic behavioral dissociations.

It has been argued that normal reading and acquired dyslexias reflect the role of three underlying primary systems (phonology, semantics, and vision) rather than neural mechanisms dedicated to reading. This proposal is potentially consistent with the suggestion that phonological and deep dyslexia represent variants of a single reading disorder rather than two separate entities. The current study explored this possibility, the nature of any continuum between the disorders, and the possible underlying bases of it. A case series of patients were given an assessment battery to test for the characteristics of phonological and deep dyslexia. The status of their underlying phonological and semantic systems was also investigated. The majority of participants exhibited many of the symptoms associated with deep dyslexia whether or not they made semantic errors. Despite wide variation in word and nonword reading accuracy, there was considerable symptom overlap across the cohort and, thus, no sensible dividing line to separate the participants into distinct groups. The patient data indicated that the deep-phonological continuum might best be characterized according to the severity of the individual's reading impairment rather than in terms of a strict symptom succession. Assessments of phonological and semantic impairments suggested that the integrity of these primary systems underpinned the patients' reading performance. This proposal was supported by eliciting the symptoms of deep-phonological dyslexia in nonreading tasks.

On the basis of a theory about the role of semantic knowledge in the recognition and production of familiar words and objects, we predicted that patients with semantic dementia would reveal a specific pattern of impairment on six different tasks typically considered “pre-” or “non-” semantic: reading aloud, writing to dictation, inflecting verbs, lexical decision, object decision, and delayed copy drawing. The prediction was that all tasks would reveal a frequency-by-typicality interaction, with patients performing especially poorly on lower-frequency items with atypical structure (e.g., words with an atypical spelling-to-sound relationship; objects with an atypical feature for their class, such as the hump on a camel, etc). Of 84 critical observations (14 patients performing 6 tasks), this prediction was correct in 84/84 cases; and a single component in a factor analysis accounted for 87% of the variance across seven measures: each patient's degree of impairment on atypical items in the six experimental tasks and a separate composite score reflecting his or her degree of semantic impairment. Errors also consistently conformed to the predicted pattern for both expressive and receptive tasks, with responses reflecting residual knowledge about the typical surface structure of each domain. We argue that these results cannot be explained as associated but unrelated deficits but instead are a principled consequence of a primary semantic impairment.

Previous studies of patients with phonological and surface alexia have demonstrated a double dissociation between the reading of pseudo words and words with atypical spelling-to-sound relationships. A corresponding double dissociation in the neuronal activation patterns for pseudo words and exception words has not, however, been consistently demonstrated in normal subjects. Motivated by the literature on acquired alexia, the present study contrasted pseudo words to exception words and explored how neuronal interactions within the reading system are influenced by word type. Functional magnetic resonance imaging was used to measure neuronal responses during reading in 22 healthy volunteers. The direct comparison of reading pseudo words and exception words revealed a double dissociation within the left frontal cortex. Pseudo words preferentially increased left dorsal premotor activation, whereas exception words preferentially increased left pars triangularis activation. Critically, these areas correspond to those previously associated with phonological and semantic processing, respectively. Word-type dependent interactions between brain areas were then investigated using dynamic causal modeling. This revealed that increased activation in the dorsal premotor cortex for pseudo words was associated with a selective increase in effective connectivity from the posterior fusiform gyrus. In contrast, increased activation in the pars triangularis for exception words was associated with a selective increase in effective connectivity from the anterior fusiform gyrus. The present investigation is the first to identify distinct neuronal mechanisms for semantic and phonological contributions to reading.

Two types of theoretical account have been proposed to explain the phenomenon of category-specific impairment in tests of semantic memory: One stresses the importance of different cortical regions to the representation of living and nonliving categories, while the other emphasize the importance of statistical relationships among features of concepts belonging to these two broad semantic domains. Theories of the latter kind predict that the direction of a domain advantage will be determined in large part by the overall damage to the semantic system, and that the profiles of patients with progressive impairments of semantic memory are likely to include a point at which an advantage for one domain changes to an advantage for the other. The present series of three studies employed semantic test data from two separate cohorts of patients with probable dementia of Alzheimer's type (DAT) to look for evidence of such a crossover. In the first study, longitudinal test scores from a cohort of 58 patients were examined to confirm the presence of progressive semantic deterioration in this group. In the second study, Kaplan-Meier survival curves based on serial naming responses and plotted separately for items belonging to living and nonliving domains indicated that the representations of living concepts (as measured by naming) deteriorated at a consistently and significantly faster rate than those of nonliving concepts. A third study, carried out to look in detail at the performance of mildly affected patients, employed an additional cross-sectional cohort of 20 patients with mild DAT and utilized a graded naming assessment. This study also revealed no evidence for a crossover in the advantage of one domain over the other as a function of disease severity. Taken together with the model of anatomical progression in DAT based on the work of Braak and Braak (1991), these findings are interpreted as evidence for the importance of regional cerebral anatomy to the genesis of semantic domain effects in DAT.