Distinct roles for the anterior temporal lobe and angular gyrus in the spatiotemporal cortical semantic network.

Semantic knowledge is supported by numerous brain regions, but the spatiotemporal configuration of the network that links these areas remains an open question. The hub-and-spokes model posits that a central semantic hub coordinates this network. In this study, we explored distinct aspects that define a semantic hub, as reflected in the spatiotemporal modulation of neural activity and connectivity by semantic variables, from the earliest stages of semantic processing. We used source-reconstructed electro/magnetoencephalography, and investigated the concreteness contrast across three tasks. In a whole-cortex analysis, the left anterior temporal lobe (ATL) was the only area that showed modulation of evoked brain activity from 100 ms post-stimulus. Furthermore, using Dynamic Causal Modeling of the evoked responses, we investigated effective connectivity amongst the candidate semantic hub regions, that is, left ATL, supramarginal/angular gyrus (SMG/AG), middle temporal gyrus, and inferior frontal gyrus. We found that models with a single semantic hub showed the highest Bayesian evidence, and the hub region was found to change from ATL (within 250 ms) to SMG/AG (within 450 ms) over time. Our results support a single semantic hub view, with ATL showing sustained modulation of neural activity by semantics, and both ATL and AG underlying connectivity depending on the stage of semantic processing.

Direct Neural Evidence for the Contrastive Roles of the Complementary Learning Systems in Adult Acquisition of Native Vocabulary.

The Complementary Learning Systems (CLS) theory provides a powerful framework for considering the acquisition, consolidation, and generalization of new knowledge. We tested this proposed neural division of labor in adults through an investigation of the consolidation and long-term retention of newly learned native vocabulary with post-learning functional neuroimaging. Newly learned items were compared with two conditions: 1) previously known items to highlight the similarities and differences with established vocabulary and 2) unknown/untrained items to provide a control for non-specific perceptual and motor speech output. Consistent with the CLS, retrieval of newly learned items was supported by a combination of regions associated with episodic memory (including left hippocampus) and the language-semantic areas that support established vocabulary (left inferior frontal gyrus and left anterior temporal lobe). Furthermore, there was a shifting division of labor across these two networks in line with the items' consolidation status; faster naming was associated with more activation of language-semantic areas and lesser activation of episodic memory regions. Hippocampal activity during naming predicted more than half the variation in naming retention 6 months later.

Investigating the effect of changing parameters when building prediction models for post-stroke aphasia.

Neuroimaging has radically improved our understanding of how speech and language abilities map to the brain in normal and impaired participants, including the diverse, graded variations observed in post-stroke aphasia. A handful of studies have begun to explore the reverse inference: creating brain-to-behaviour prediction models. In this study, we explored the effect of three critical parameters on model performance: (1) brain partitions as predictive features, (2) combination of multimodal neuroimaging and (3) type of machine learning algorithms. We explored the influence of these factors while predicting four principal dimensions of language and cognition variation in post-stroke aphasia. Across all four behavioural dimensions, we consistently found that prediction models derived from diffusion-weighted data did not improve performance over models using structural measures extracted from T1 scans. Our results provide a set of principles to guide future work aiming to predict outcomes in neurological patients from brain imaging data.

Auditory, Phonological, and Semantic Factors in the Recovery From Wernicke's Aphasia Poststroke: Predictive Value and Implications for Rehabilitation.

Background. Understanding the factors that influence language recovery in aphasia is important for improving prognosis and treatment. Chronic comprehension impairments in Wernicke's aphasia (WA) are associated with impairments in auditory and phonological processing, compounded by semantic and executive difficulties. This study investigated whether the recovery of auditory, phonological, semantic, or executive factors underpins the recovery from WA comprehension impairments by charting changes in the neuropsychological profile from the subacute to the chronic phase. Method. This study used a prospective, longitudinal observational design. Twelve WA participants with superior temporal lobe lesions were recruited 2 months post-stroke onset (2 MPO). Language comprehension was measured alongside a neuropsychological profile of auditory, phonological, and semantic processing and phonological short-term memory and nonverbal reasoning at 3 poststroke time points: 2.5, 5, and 9 MPO. Results. Language comprehension displayed a strong and consistent recovery between 2.5 and 9 MPO. Improvements were also seen for slow auditory temporal processing, phonological short-term memory, and semantic processing but not for rapid auditory temporal, spectrotemporal, and phonological processing. Despite their lack of improvement, rapid auditory temporal processing at 2.5 MPO and phonological processing at 5 MPO predicated comprehension outcomes at 9 MPO. Conclusions. These results indicate that recovery of language comprehension in WA can be predicted from fixed auditory processing in the subacute stage. This suggests that speech comprehension recovery in WA results from reorganization of the remaining language comprehension network to enable the residual speech signal to be processed more efficiently, rather than partial recovery of underlying auditory, phonological, or semantic processing abilities.

Mapping the intersection of language and reading: the neural bases of the primary systems hypothesis.

The primary systems framework has been used to relate behavioural performance across many different language activities to the status of core underpinning domain-general cognitive systems. This study provided the first quantitative investigation of this account at both behavioural and neural levels in a group of patients with chronic post-stroke aphasia. Principal components analysis was used to distil orthogonal measures of phonological and semantic processing, which were then related to reading performance and the underlying lesion distributions using voxel-based correlational methodology. Concrete word reading involved both a ventral semantic pathway, and inferior and anterior aspects of the dorsal phonological pathway. Abstract word reading overlapped with the ventral semantic pathway but also drew more extensively on the superior and posterior aspects of the dorsal phonological pathway. Nonword reading was related to phonological processing along the dorsal pathway and was also supported by a more superior set of regions previously associated with speech motor output. The use of continuous measures of behavioural performance and neural integrity allowed us to elucidate for the first time both the lesion and behavioural correlates for the semantic and phonological components of the primary systems hypothesis and to extend these by identifying the importance of an additional dorsal speech motor output system. These results provide a target for future neuroanatomically constrained computational models of reading.

Predicting the pattern and severity of chronic post-stroke language deficits from functionally-partitioned structural lesions.

There is an ever-increasing wealth of knowledge arising from basic cognitive and clinical neuroscience on how speech and language capabilities are organised in the brain. It is, therefore, timely to use this accumulated knowledge and expertise to address critical research challenges, including the ability to predict the pattern and level of language deficits found in aphasic patients (a third of all stroke cases). Previous studies have mainly focused on discriminating between broad aphasia dichotomies from purely anatomically-defined lesion information. In the current study, we developed and assessed a novel approach in which core language areas were mapped using principal component analysis in combination with correlational lesion mapping and the resultant 'functionally-partitioned' lesion maps were used to predict a battery of 21 individual test scores as well as aphasia subtype for 70 patients with chronic post-stroke aphasia. Specifically, we used lesion information to predict behavioural scores in regression models (cross-validated using 5-folds). The winning model was identified through the adjusted R2 (model fit to data) and performance in predicting holdout folds (generalisation to new cases). We also used logistic regression to predict fluent/non-fluent status and aphasia subtype. Functionally-partitioned models generally outperformed other models at predicting individual tests, fluency status and aphasia subtype.

Cognitive consequences of the left-right asymmetry of atrophy in semantic dementia.

Semantic dementia (SD) is a condition in which atrophy to the anterior temporal lobes (ATL) produces a selective deterioration of conceptual knowledge. As this atrophy is always bilateral but usually asymmetrical, differences in performance of the two SD subgroups-with left > right (L > R) versus right > left (R > L) atrophy-constitute a major source of evidence regarding the roles of the left and right sides of this region. We explored this issue using large scale case-series methodology, with a pool of 216 observations of neuropsychological data from 72 patients with SD. Anomia was significantly more severe in the L > R subgroup, even when cases from the two subgroups were matched on severity of comprehension deficits. For subgroups matched on the degree of anomia, we show that asymmetry of atrophy also affected both the nature of the naming errors produced, and the degree of a semantic category effect (living things vs artefacts). A comparison across tasks varying in their loading on verbal and visual processing revealed a greater deficit in object naming for L > R cases and in a picture-based semantic association test for R > L cases; this held true whether severity across subgroups was controlled using pairwise matching or statistically via principal components analysis. Importantly, the size of our sample allowed us to demonstrate considerable individual variation within each of the L > R and R > L subgroups, with consequent overlap between them. Our results paint a clear picture of how asymmetry of atrophy affects cognitive performance in SD, and we discuss the results in terms of two mechanisms that could contribute to these differences: variation in the information involved in semantic representations in the left and right ATL, and preferential connectivity between each ATL and other more modality specific intra-hemispheric regions.

The impact of phonological versus semantic repetition training on generalisation in chronic stroke aphasia reflects differences in dorsal pathway connectivity.

It has been suggested that neuroimaging can be used to inform therapeutic intervention. The current study aimed to determine whether an individual would benefit more from training engaging their intact or their damaged neural pathway. Two males with chronic stroke aphasia participated, with DM showing milder disruption of connectivity along the dorsal language pathway relative to JS, according to distortion corrected diffusion-weighted magnetic resonance imaging. Each patient received two blocks of six repetition training sessions over two weeks, one of which was "phonological" and the other "semantic" in nature. Both phonological and semantic training produced significant gains for both patients for trained items. For the untrained control items, significant gains were specific to training type for each patient. Only phonological training elicited significant generalisation for DM, which was greater than that seen for JS. Conversely, only semantic training elicited significant generalisation for JS, which was greater than that seen for DM. This double dissociation in generalisation effects suggests that a restitutive approach is more effective for patients with milder damage while a compensatory approach may be more effective for those with more severe damage. These results indicate the utility of neuroimaging to optimise relearning strategies and promote generalisation to untrained items.

Triangulation of language-cognitive impairments, naming errors and their neural bases post-stroke.

In order to gain a better understanding of aphasia one must consider the complex combinations of language impairments along with the pattern of paraphasias. Despite the fact that both deficits and paraphasias feature in diagnostic criteria, most research has focused only on the lesion correlates of language deficits, with minimal attention on the pattern of patients' paraphasias. In this study, we used a data-driven approach (principal component analysis - PCA) to fuse patient impairments and their pattern of errors into one unified model of chronic post-stroke aphasia. This model was subsequently mapped onto the patients' lesion profiles to generate the triangulation of language-cognitive impairments, naming errors and their neural correlates. Specifically, we established the pattern of co-occurrence between fifteen error types, which avoids focussing on a subset of errors or the use of experimenter-derived methods to combine across error types. We obtained five principal components underlying the patients' errors: omission errors; semantically-related responses; phonologically-related responses; dysfluent responses; and a combination of circumlocutions with mixed errors. In the second step, we aligned these paraphasia-related principal components with the patients' performance on a detailed language and cognitive assessment battery, utilising an additional PCA. This omnibus PCA revealed seven unique fused impairment-paraphasia factors: output phonology; semantics; phonological working memory; speech quanta; executive-cognitive skill; phonological (input) discrimination; and the production of circumlocution errors. In doing so we were able to resolve the complex relationships between error types and impairments. Some are relatively straightforward: circumlocution errors formed their own independent factor; there was a one-to-one mapping for phonological errors with expressive phonological abilities and for dysfluent errors with speech fluency. In contrast, omission-type errors loaded across both semantic and phonological working memory factors, whilst semantically-related errors had the most complex relationship by loading across four factors (phonological ability, speech quanta, executive-cognitive skills and circumlocution-type errors). Three components had unique lesion correlates: phonological working memory with the primary auditory region; semantics with the anterior temporal region; and fluency with the pre-central gyrus, converging with existing literature. In conclusion, the data-driven approach allowed derivation of the triangulation of deficits, error types and lesion correlates in post-stroke aphasia.

Using neurostimulation to understand the impact of pre-morbid individual differences on post-lesion outcomes.

Neuropsychological data have proven invaluable in advancing our understanding of higher cognition. The interpretation of such data is, however, complicated by the fact that post-lesion behavioral abnormalities could reflect pre-morbid individual differences in the cognitive domain of interest. Here we exploited the virtual lesion methodology offered by transcranial magnetic stimulation (TMS) to explore the impact of pre-morbid individual differences on post-lesion performance. We applied this approach to the domain of reading, a crucial ability in which there are known to be considerable individual differences in the normal population. As predicted by neuropsychological studies of surface dyslexia in semantic dementia and the connectionist triangle model of reading, previous empirical work has shown that healthy participants vary in their reliance on meaning for reading words with atypical correspondences between spelling and sound. We therefore selected participants who varied along this dimension and applied a virtual lesion to the left anterior temporal lobe. As expected, we observed a significant three-way interaction between "pre-morbid" reading status, stimulation, and word type, such that TMS increased the disadvantage for spelling-sound atypical words more for the individuals with stronger semantic reliance. This successful test-case study provides an approach to understanding the impact of pre-morbid individual variation on post-lesion outcomes that could be fruitfully applied to a variety of cognitive domains.

Laterality of anterior temporal lobe repetitive transcranial magnetic stimulation determines the degree of disruption in picture naming.

The bilateral anterior temporal lobes play a key role in semantic representation. This is clearly demonstrated by the performance of patients with semantic dementia, a disorder characterised by a progressive and selective decline in semantic memory over all modalities as a result of anterior temporal atrophy. Although all patients exhibit a progressive decline in both single-word production and comprehension, those with greater atrophy to the left anterior temporal lobe show a stronger decline in word production than comprehension. This asymmetry has been attributed to the greater connectivity of the left anterior temporal lobe with left-lateralised speech production mechanisms. Virtual lesioning of the left ATL using offline repetitive transcranial magnetic stimulation (rTMS) has been shown to disrupt picture naming, but, the impact of right ATL rTMS is yet to be explored. We tested the prediction that disruption of picture naming in normal participants by rTMS should be greater for the left than the right ATL. We found a significant increase in picture naming latencies specifically for stimulation of the left ATL only. Neither left nor right ATL TMS slowed performance in a number naming control task. These results support the hypothesis that although both temporal lobes are part of a widespread semantic network in the human brain, the left anterior temporal lobe possesses a stronger connection to left-lateralised speech production areas than the right temporal lobe.

Seeing the Meaning: Top-Down Effects on Letter Identification.

Most models of reading agree that visual word recognition is underpinned by a highly interactive network in which both bottom-up and top-down processes contribute. What remains unknown is whether evidence of top-down effects upon letter processing are restricted to word-form level information, or whether meaning-level information also plays a role. Here we sought to investigate top-down semantic influences upon letter detection using semantic manipulations of real word imageability and semantic priming, as well as a manipulation of nonword orthographic and phonological composition which varied degree of similarity to real words. A continuous adaptive staircase procedure was used, allowing us to assess the exposure duration needed for accurate letter perception in different stimulus types. Results revealed that in terms of both exposure duration and decision reaction times, words showed an advantage over pseudohomophones and pseudowords, which in turn showed advantages over consonant strings. High imageability words were processed more efficiently than low imageability words, both in terms of the exposure duration required for accurate letter identification and also decision reaction times. The presence of a related as opposed to unrelated semantic prime significantly shortened exposure duration, but also lengthened decision reaction times. This inhibitory semantic priming effect in reaction time was attributed to the interference at the decision stage by stronger activation of the prime letters in the case of related relative to unrelated trials. Taken together, the present results establish for the first time that the semantic dimensions of imageability and semantic priming exert significant effects on letter identification, indicating meaning-level influences on the very earliest stages of written word recognition.

Using principal component analysis to capture individual differences within a unified neuropsychological model of chronic post-stroke aphasia: Revealing the unique neural correlates of speech fluency, phonology and semantics.

Individual differences in the performance profiles of neuropsychologically-impaired patients are pervasive yet there is still no resolution on the best way to model and account for the variation in their behavioural impairments and the associated neural correlates. To date, researchers have generally taken one of three different approaches: a single-case study methodology in which each case is considered separately; a case-series design in which all individual patients from a small coherent group are examined and directly compared; or, group studies, in which a sample of cases are investigated as one group with the assumption that they are drawn from a homogenous category and that performance differences are of no interest. In recent research, we have developed a complementary alternative through the use of principal component analysis (PCA) of individual data from large patient cohorts. This data-driven approach not only generates a single unified model for the group as a whole (expressed in terms of the emergent principal components) but is also able to capture the individual differences between patients (in terms of their relative positions along the principal behavioural axes). We demonstrate the use of this approach by considering speech fluency, phonology and semantics in aphasia diagnosis and classification, as well as their unique neural correlates. PCA of the behavioural data from 31 patients with chronic post-stroke aphasia resulted in four statistically-independent behavioural components reflecting phonological, semantic, executive-cognitive and fluency abilities. Even after accounting for lesion volume, entering the four behavioural components simultaneously into a voxel-based correlational methodology (VBCM) analysis revealed that speech fluency (speech quanta) was uniquely correlated with left motor cortex and underlying white matter (including the anterior section of the arcuate fasciculus and the frontal aslant tract), phonological skills with regions in the superior temporal gyrus and pars opercularis, and semantics with the anterior temporal stem.

Do You Read How I Read? Systematic Individual Differences in Semantic Reliance amongst Normal Readers.

The extent to which meaning is involved in reading aloud has proven an area of longstanding debate, and current computational models differ on this dimension. The connectionist triangle model proposes that normal individuals rely on semantic information for correct reading of words with atypical spelling-sound relationships, but to varying degrees. This proposed individual difference would account for the varying stage of decline at which patients with semantic dementia first show the reading impairment known as surface dyslexia. Recent neuroimaging data has provided validation of this view, showing that individual differences in degree of semantic reliance during exception word reading predict the amount of activation in left anterior temporal regions associated with semantic processing. This study aimed to establish the cognitive correlates of individual differences in semantic reliance during exception word reading. Experiment 1 used a subgrouping approach with 32 participants and found larger imageability and semantic priming effects specifically for exception word reading amongst high relative to low semantic reliance readers. High semantic reliance readers also tended to read nonwords more slowly than low semantic reliance readers. A second experiment used a regression approach with 129 readers and confirmed the relationship of degree of semantic reliance both to imageability effects in exception word reading and speed of nonword reading. Further, while the performance of the higher semantic readers revealed no significant association with semantic processing tasks, there was a negative relationship with rhyme processing tasks. We therefore speculate that differences in phonological abilities may be responsible for varying degrees of semantic reliance in reading aloud. This proposal accords with the results of functional imaging showing that higher semantic reliance during exception word reading corresponds to lower activation in left pre-central gyrus, an area associated with direct spelling sound mapping and phonological processing. Our results therefore establish the nature of systematic individual differences in degree of semantic involvement amongst normal readers, and suggest directions for future neuroimaging and computational modeling research to uncover their origins.

Taking Sides: An Integrative Review of the Impact of Laterality and Polarity on Efficacy of Therapeutic Transcranial Direct Current Stimulation for Anomia in Chronic Poststroke Aphasia.

Anomia is a frequent and persistent symptom of poststroke aphasia, resulting from damage to areas of the brain involved in language production. Cortical neuroplasticity plays a significant role in language recovery following stroke and can be facilitated by behavioral speech and language therapy. Recent research suggests that complementing therapy with neurostimulation techniques may enhance functional gains, even amongst those with chronic aphasia. The current review focuses on the use of transcranial Direct Current Stimulation (tDCS) as an adjunct to naming therapy for individuals with chronic poststroke aphasia. Our survey of the literature indicates that combining therapy with anodal (excitatory) stimulation to the left hemisphere and/or cathodal (inhibitory) stimulation to the right hemisphere can increase both naming accuracy and speed when compared to the effects of therapy alone. However, the benefits of tDCS as a complement to therapy have not been yet systematically investigated with respect to site and polarity of stimulation. Recommendations for future research to help determine optimal protocols for combined therapy and tDCS are outlined.

Triangulation of the neurocomputational architecture underpinning reading aloud.

The goal of cognitive neuroscience is to integrate cognitive models with knowledge about underlying neural machinery. This significant challenge was explored in relation to word reading, where sophisticated computational-cognitive models exist but have made limited contact with neural data. Using distortion-corrected functional MRI and dynamic causal modeling, we investigated the interactions between brain regions dedicated to orthographic, semantic, and phonological processing while participants read words aloud. We found that the lateral anterior temporal lobe exhibited increased activation when participants read words with irregular spellings. This area is implicated in semantic processing but has not previously been considered part of the reading network. We also found meaningful individual differences in the activation of this region: Activity was predicted by an independent measure of the degree to which participants use semantic knowledge to read. These characteristics are predicted by the connectionist Triangle Model of reading and indicate a key role for semantic knowledge in reading aloud. Premotor regions associated with phonological processing displayed the reverse characteristics. Changes in the functional connectivity of the reading network during irregular word reading also were consistent with semantic recruitment. These data support the view that reading aloud is underpinned by the joint operation of two neural pathways. They reveal that (i) the ATL is an important element of the ventral semantic pathway and (ii) the division of labor between the two routes varies according to both the properties of the words being read and individual differences in the degree to which participants rely on each route.

Processing deficits for familiar and novel faces in patients with left posterior fusiform lesions.

Pure alexia (PA) arises from damage to the left posterior fusiform gyrus (pFG) and the striking reading disorder that defines this condition has meant that such patients are often cited as evidence for the specialisation of this region to processing of written words. There is, however, an alternative view that suggests this region is devoted to processing of high acuity foveal input, which is particularly salient for complex visual stimuli like letter strings. Previous reports have highlighted disrupted processing of non-linguistic visual stimuli after damage to the left pFG, both for familiar and unfamiliar objects and also for novel faces. This study explored the nature of face processing deficits in patients with left pFG damage. Identification of famous faces was found to be compromised in both expressive and receptive tasks. Discrimination of novel faces was also impaired, particularly for those that varied in terms of second-order spacing information, and this deficit was most apparent for the patients with the more severe reading deficits. Interestingly, discrimination of faces that varied in terms of feature identity was considerably better in these patients and it was performance in this condition that was related to the size of the length effects shown in reading. This finding complements functional imaging studies showing left pFG activation for faces varying only in spacing and frontal activation for faces varying only on features. These results suggest that the sequential part-based processing strategy that promotes the length effect in the reading of these patients also allows them to discriminate between faces on the basis of feature identity, but processing of second-order configural information is most compromised due to their left pFG lesion. This study supports a view in which the left pFG is specialised for processing of high acuity foveal visual information that supports processing of both words and faces.

Lexical is as lexical does: computational approaches to lexical representation.

In much of neuroimaging and neuropsychology, regions of the brain have been associated with 'lexical representation', with little consideration as to what this cognitive construct actually denotes. Within current computational models of word recognition, there are a number of different approaches to the representation of lexical knowledge. Structural lexical representations, found in original theories of word recognition, have been instantiated in modern localist models. However, such a representational scheme lacks neural plausibility in terms of economy and flexibility. Connectionist models have therefore adopted distributed representations of form and meaning. Semantic representations in connectionist models necessarily encode lexical knowledge. Yet when equipped with recurrent connections, connectionist models can also develop attractors for familiar forms that function as lexical representations. Current behavioural, neuropsychological and neuroimaging evidence shows a clear role for semantic information, but also suggests some modality- and task-specific lexical representations. A variety of connectionist architectures could implement these distributed functional representations, and further experimental and simulation work is required to discriminate between these alternatives. Future conceptualisations of lexical representations will therefore emerge from a synergy between modelling and neuroscience.

For richer or poorer? Imageability effects in semantic dementia patients' reading aloud.

The degree to which a word's meaning evokes a mental image exerts an influence on performance across a variety of conceptual and linguistic tasks. In normal healthy participants, this effect takes the form of an advantage for high over low imageability words. Consideration of the influence of imageability on performance of patients with semantic dementia can provide information concerning its cognitive and neural bases. Semantic dementia patients show deficits in conceptual processing tasks, and an associated enhancement of the advantage for high over low imageability words. Semantic dementia patients also show deficits in linguistic processing tasks, including reading aloud words with inconsistent spelling-sound correspondences. This study provides the first systematic exploration of the influence of imageability on semantic dementia patients' reading aloud performance. Over 10 cases, the imageability effect seen for inconsistent words was actually reversed in reaction times, with faster performance for low than high imageability items. The same reversal was observed for inconsistent words when the frequency of legitimate alternative reading of components errors was considered, and this reversed effect grew larger with increasing semantic impairment. This result is interpreted in terms of the development of stronger connections along the direct pathway between spelling and sound for low than high imageability items that are then revealed under diminished semantic activation. This interpretation emphasises the interaction between form and meaning that occurs throughout learning in connectionist models.