Does epilepsy differentially affect different types of memory?

Despite the recognition that epilepsy can substantially disrupt memory, there are few published accounts of whether and how this disruption varies across different types of memory and/or different types of epilepsy. This review explores four main questions: (1) Are working, episodic and semantic memory differentially affected by epilepsy? (2) Do various types of epilepsy, and their treatment, have different, specifiable effects on memory? (3) Are the usual forms of neuropsychological assessments of memory - many or most designed for other conditions - appropriate for patients with epilepsy? (4) How can research on epilepsy contribute to our understanding of the neuroscience of memory? We conclude that widespread and multifactorial problems are seen in working memory in all patient groups, while patients with temporal lobe epilepsy seem particularly prone to episodic memory deficit, and those with frontal lobe epilepsy to executive function deficits that may in turn impair semantic control. Currently, it is difficult to make individual patient predictions about likely memory deficits based on seizure aetiology and type, but it is possible to guide and tailor neuropsychological assessments in an individualised way. We make recommendations for future directions in validating and optimising neuropsychological assessments, and consider how to approach effective shared decision making about the pros and cons of seizure treatment strategies, especially at crucial educational stages such as adolescence.

The neural substrates of transdiagnostic cognitive-linguistic heterogeneity in primary progressive aphasia.

BACKGROUND: Clinical variants of primary progressive aphasia (PPA) are diagnosed based on characteristic patterns of language deficits, supported by corresponding neural changes on brain imaging. However, there is (i) considerable phenotypic variability within and between each diagnostic category with partially overlapping profiles of language performance between variants and (ii) accompanying non-linguistic cognitive impairments that may be independent of aphasia magnitude and disease severity. The neurobiological basis of this cognitive-linguistic heterogeneity remains unclear. Understanding the relationship between these variables would improve PPA clinical/research characterisation and strengthen clinical trial and symptomatic treatment design. We address these knowledge gaps using a data-driven transdiagnostic approach to chart cognitive-linguistic differences and their associations with grey/white matter degeneration across multiple PPA variants. METHODS: Forty-seven patients (13 semantic, 15 non-fluent, and 19 logopenic variant PPA) underwent assessment of general cognition, errors on language performance, and structural and diffusion magnetic resonance imaging to index whole-brain grey and white matter changes. Behavioural data were entered into varimax-rotated principal component analyses to derive orthogonal dimensions explaining the majority of cognitive variance. To uncover neural correlates of cognitive heterogeneity, derived components were used as covariates in neuroimaging analyses of grey matter (voxel-based morphometry) and white matter (network-based statistics of structural connectomes). RESULTS: Four behavioural components emerged: general cognition, semantic memory, working memory, and motor speech/phonology. Performance patterns on the latter three principal components were in keeping with each variant's characteristic profile, but with a spectrum rather than categorical distribution across the cohort. General cognitive changes were most marked in logopenic variant PPA. Regardless of clinical diagnosis, general cognitive impairment was associated with inferior/posterior parietal grey/white matter involvement, semantic memory deficits with bilateral anterior temporal grey/white matter changes, working memory impairment with temporoparietal and frontostriatal grey/white matter involvement, and motor speech/phonology deficits with inferior/middle frontal grey matter alterations. CONCLUSIONS: Cognitive-linguistic heterogeneity in PPA closely relates to individual-level variations on multiple behavioural dimensions and grey/white matter degeneration of regions within and beyond the language network. We further show that employment of transdiagnostic approaches may help to understand clinical symptom boundaries and reveal clinical and neural profiles that are shared across categorically defined variants of PPA.

An efficient, accurate and clinically-applicable index of content word fluency in Aphasia.

Background: Despite the clinical importance of assessing the efficiency and accuracy of fluency in terms of content words production during connected speech, assessments based on discourse tasks are very time-consuming and thus not clinically feasible. Aims: (1) Examine the relationship between single-word naming and word retrieval during discourse production. (2) Investigate the relationship between word retrieval and content word fluency derived from a simple versus naturalistic discourse tasks. (3) Develop and validate an efficient and accurate index of content word fluency that is clinically viable. Methods: Two discourse tasks (simple picture description and naturalistic storytelling narrative) were collected from 46 participants with post-stroke aphasia, and 20 age/education matched neuro-typical controls. Each discourse sample was fully transcribed and quantitative analysis was applied to each sample to measure word retrieval and content word fluency. Three single-word naming tasks were also administered to each participant with aphasia. Results: Correlational analyses between single-word naming and word retrieval in connected speech revealed weak/moderate relationships. Conversely, strong correlations were found between measures derived from simple picture description against naturalistic storytelling discourse tasks. Moreover, we derived a novel, transcription-less index of content word fluency from the discourse samples of an independent group (neuro-typical controls), and then we validated this index across two discourse tasks in the tested group (persons with aphasia). Correlation and regression analyses revealed extremely strong relationships between participants' (neuro-typical controls and persons with aphasia) scores on the novel index and measures of content word fluency derived from the formal transcription and quantitative analyses of discourse samples, indicating high accuracy and validity of the new index. Conclusions: Simple picture description rather than picture naming provides a better estimate of word retrieval in naturalistic connected speech. The novel developed index is transcription-less and can be implemented online to provide an accurate and efficient measure of content word fluency. Thus, it is viable during clinical practice for assessment purposes, and possibly as an outcome measure to monitor therapy effectiveness, which can also be used in randomised clinical trials.

Distinct and common neural coding of semantic and non-semantic control demands.

The flexible retrieval of knowledge is critical in everyday situations involving problem solving, reasoning and social interaction. Current theories emphasise the importance of a left-lateralised semantic control network (SCN) in supporting flexible semantic behaviour, while a bilateral multiple-demand network (MDN) is implicated in executive functions across domains. No study, however, has examined whether semantic and non-semantic demands are reflected in a common neural code within regions specifically implicated in semantic control. Using functional MRI and univariate parametric modulation analysis as well as multivariate pattern analysis, we found that semantic and non-semantic demands gave rise to both similar and distinct neural responses across control-related networks. Though activity patterns in SCN and MDN could decode the difficulty of both semantic and verbal working memory decisions, there was no shared common neural coding of cognitive demands in SCN regions. In contrast, regions in MDN showed common patterns across manipulations of semantic and working memory control demands, with successful cross-classification of difficulty across tasks. Therefore, SCN and MDN can be dissociated according to the information they maintain about cognitive demands.

RELEASE: a protocol for a systematic review based, individual participant data, meta- and network meta-analysis, of complex speech-language therapy interventions for stroke-related aphasia.

Background: Speech and language therapy (SLT) benefits people with aphasia following stroke. Group level summary statistics from randomised controlled trials hinder exploration of highly complex SLT interventions and a clinically relevant heterogeneous population. Creating a database of individual participant data (IPD) for people with aphasia aims to allow exploration of individual and therapy-related predictors of recovery and prognosis. Aim: To explore the contribution that individual participant characteristics (including stroke and aphasia profiles) and SLT intervention components make to language recovery following stroke. Methods and procedures: We will identify eligible IPD datasets (including randomised controlled trials, non-randomised comparison studies, observational studies and registries) and invite their contribution to the database. Where possible, we will use meta- and network meta-analysis to explore language performance after stroke and predictors of recovery as it relates to participants who had no SLT, historical SLT or SLT in the primary research study. We will also examine the components of effective SLT interventions. Outcomes and results: Outcomes include changes in measures of functional communication, overall severity of language impairment, auditory comprehension, spoken language (including naming), reading and writing from baseline. Data captured on assessment tools will be collated and transformed to a standardised measure for each of the outcome domains. Conclusion: Our planned systematic-review-based IPD meta- and network meta-analysis is a large scale, international, multidisciplinary and methodologically complex endeavour. It will enable hypotheses to be generated and tested to optimise and inform development of interventions for people with aphasia after stroke. Systematic review registration: The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42018110947).

The neural and computational bases of semantic cognition.

Semantic cognition refers to our ability to use, manipulate and generalize knowledge that is acquired over the lifespan to support innumerable verbal and non-verbal behaviours. This Review summarizes key findings and issues arising from a decade of research into the neurocognitive and neurocomputational underpinnings of this ability, leading to a new framework that we term controlled semantic cognition (CSC). CSC offers solutions to long-standing queries in philosophy and cognitive science, and yields a convergent framework for understanding the neural and computational bases of healthy semantic cognition and its dysfunction in brain disorders.

Disorders of representation and control in semantic cognition: Effects of familiarity, typicality, and specificity.

We present a case-series comparison of patients with cross-modal semantic impairments consequent on either (a) bilateral anterior temporal lobe atrophy in semantic dementia (SD) or (b) left-hemisphere fronto-parietal and/or posterior temporal stroke in semantic aphasia (SA). Both groups were assessed on a new test battery designed to measure how performance is influenced by concept familiarity, typicality and specificity. In line with previous findings, performance in SD was strongly modulated by all of these factors, with better performance for more familiar items (regardless of typicality), for more typical items (regardless of familiarity) and for tasks that did not require very specific classification, consistent with the gradual degradation of conceptual knowledge in SD. The SA group showed significant impairments on all tasks but their sensitivity to familiarity, typicality and specificity was more variable and governed by task-specific effects of these factors on controlled semantic processing. The results are discussed with reference to theories about the complementary roles of representation and manipulation of semantic knowledge.

Using a combination of fMRI and anterior temporal lobe rTMS to measure intrinsic and induced activation changes across the semantic cognition network.

By developing and applying a method which combines fMRI and rTMS to explore semantic cognition, we identified both intrinsic (related to automatic changes in task/stimulus-related processing) and induced (i.e., associated with the effect of TMS) activation changes in the core, functionally-coupled network elements. Low-frequency rTMS applied to the human anterior temporal lobe (ATL) induced: (a) a local suppression at the site of stimulation; (b) remote suppression in three other ipsilateral semantic regions; and (c) a compensatory up-regulation in the contralateral ATL. Further examination of activity over time revealed that the compensatory changes appear to be a modulation of intrinsic variations that occur within the unperturbed network. As well as providing insights into the dynamic collaboration between core regions, the ability to observe intrinsic and induced changes in vivo may provide an important opportunity to understand the key mechanisms that underpin recovery of function in neurological patient groups.

Time- but not sleep-dependent consolidation promotes the emergence of cross-modal conceptual representations.

Conceptual knowledge about objects comprises a diverse set of multi-modal and generalisable information, which allows us to bring meaning to the stimuli in our environment. The formation of conceptual representations requires two key computational challenges: integrating information from different sensory modalities and abstracting statistical regularities across exemplars. Although these processes are thought to be facilitated by offline memory consolidation, investigations into how cross-modal concepts evolve offline, over time, rather than with continuous category exposure are still missing. Here, we aimed to mimic the formation of new conceptual representations by reducing this process to its two key computational challenges and exploring its evolution over an offline retention period. Participants learned to distinguish between members of two abstract categories based on a simple one-dimensional visual rule. Underlying the task was a more complex hidden indicator of category structure, which required the integration of information across two sensory modalities. In two experiments we investigated the impact of time- and sleep-dependent consolidation on category learning. Our results show that offline memory consolidation facilitated cross-modal category learning. Surprisingly, consolidation across wake, but not across sleep showed this beneficial effect. By demonstrating the importance of offline consolidation the current study provided further insights into the processes that underlie the formation of conceptual representations.

The degraded concept representation system in semantic dementia: damage to pan-modal hub, then visual spoke.

The core clinical feature of semantic dementia is a progressive yet selective degradation of conceptual knowledge. Understanding the cognitive and neuroanatomical basis for this deficit is a key challenge for both clinical and basic science. Some researchers attribute the deficit to damage to pan-modal conceptual representations that are independent of any particular sensory-motor modality and are represented in the ventrolateral anterior temporal lobes. Others claim that damage to modality-specific visual feature representations in the occipitotemporal 'ventral stream' is responsible. In the present study, we tested the hypothesis that concept degradation in semantic dementia involves a combination of these pan-modal and modality-specific elements. We investigated factors influencing knowledge of object concepts by analysing 43 sets of picture-naming data from patients with semantic dementia. We found a strong influence of two pan-modal factors: highly familiar and typical items were named more accurately than less familiar/atypical items at all stages of the disorder. Items associated with rich sensory-motor information were also named more successfully at all stages, and this effect was present for sound/motion knowledge and tactile/action knowledge when these modalities were studied separately. However, there was no advantage for items rich in visual colour/form characteristics; instead, this factor had an increasingly negative impact in the later stages of the disorder. We propose that these results are best explained by a combination of (i) degradation of modality-independent conceptual representations, which is present throughout the disorder and is a consequence of atrophy focused on the ventrolateral anterior temporal lobes; and (ii) a later additional deficit for concepts that depend heavily on visual colour/form information, caused by the spreading of atrophy to posterior ventral temporal regions specialized for representing this information. This explanation is consistent with a graded hub-and-spoke model of conceptual knowledge, in which there is a gradual convergence of information along the temporal lobes, with visual attributes represented in the posterior cortex giving way to pan-modal representations in the anterior areas.

Effectiveness of enhanced communication therapy in the first four months after stroke for aphasia and dysarthria: a randomised controlled trial.

OBJECTIVE: To assess the effectiveness of enhanced communication therapy in the first four months after stroke compared with an attention control (unstructured social contact). DESIGN: Externally randomised, pragmatic, parallel, superiority trial with blinded outcome assessment. SETTING: Twelve UK hospital and community stroke services. PARTICIPANTS: 170 adults (mean age 70 years) randomised within two weeks of admission to hospital with stroke (December 2006 to January 2010) whom speech and language therapists deemed eligible, and 135 carers. INTERVENTIONS: Enhanced, agreed best practice, communication therapy specific to aphasia or dysarthria, offered by speech and language therapists according to participants' needs for up to four months, with continuity from hospital to community. Comparison was with similarly resourced social contact (without communication therapy) from employed visitors. OUTCOME MEASURES: Primary outcome was blinded, functional communicative ability at six months on the Therapy Outcome Measure (TOM) activity subscale. Secondary outcomes (unblinded, six months): participants' perceptions on the Communication Outcomes After Stroke scale (COAST); carers' perceptions of participants from part of the Carer COAST; carers' wellbeing on Carers of Older People in Europe Index and quality of life items from Carer COAST; and serious adverse events. RESULTS: Therapist and visitor contact both had good uptake from service users. An average 22 contacts (intervention or control) over 13 weeks were accepted by users. Impairment focused therapy was the approach most often used by the speech and language therapists. Visitors most often provided general conversation. In total, 81/85 of the intervention group and 72/85 of the control group completed the primary outcome measure. Both groups improved on the TOM activity subscale. The estimated six months group difference was not statistically significant, with 0.25 (95% CI -0.19 to 0.69) points in favour of therapy. Sensitivity analyses that adjusted for chance baseline imbalance further reduced this difference. Per protocol analyses rejected a possible dilution of treatment effect from controls declining their allocation and receiving usual care. There was no added benefit of therapy on secondary outcome measures, subgroup analyses (such as aphasia), or serious adverse events, although the latter were less common after intervention (odds ratio 0.42 (95% CI 0.16 to 1.1)). CONCLUSIONS: Communication therapy had no added benefit beyond that from everyday communication in the first four months after stroke. Future research should evaluate reorganised services that support functional communication practice early in the stroke pathway. This project was funded by the NIHR Health Technology Assessment programme (project No 02/11/04) and is published in full in Health Technology Assessment 2012;16(26):1-160. TRIAL REGISTRATION: ISRCTN78617680.

Unpicking the semantic impairment in Alzheimer's disease: qualitative changes with disease severity.

Despite a vast literature examining semantic impairment in Alzheimer's disease (AD), consensus regarding the nature of the deficit remains elusive. We re-considered this issue in the context of a framework that assumes semantic cognition can break down in two ways: (1) core semantic representations can degrade or (2) cognitive control mechanisms can become impaired. We hypothesised and confirmed that the nature of semantic impairment in AD changes with disease severity. Patients at mild or severe stages of the disorder exhibited impairment across various semantic tasks but the nature of those deficits differed qualitatively for the two groups. Commensurate with early dysfunction of the cognitive control, temporoparietal-frontal-cingulate network, characteristics of deregulated semantic cognition were exhibited by the mild AD cases. In contrast, the severe AD group reproduced features of additional degradation of core semantic representations. These results suggest that spread of pathology into lateral anterior temporal lobes in later stage AD produces degradation of semantic representations, exacerbating the already deregulated system. Moreover, the dual nature of severe patients' impairment was highlighted by disproportionately poor performance on tasks placing high demand on both conceptual knowledge and control processes--e.g., category fluency.

Revealing and quantifying the impaired phonological analysis underpinning impaired comprehension in Wernicke's aphasia.

Wernicke's aphasia is a condition which results in severely disrupted language comprehension following a lesion to the left temporo-parietal region. A phonological analysis deficit has traditionally been held to be at the root of the comprehension impairment in Wernicke's aphasia, a view consistent with current functional neuroimaging which finds areas in the superior temporal cortex responsive to phonological stimuli. However behavioural evidence to support the link between a phonological analysis deficit and auditory comprehension has not been yet shown. This study extends seminal work by Blumstein, Baker, and Goodglass (1977) to investigate the relationship between acoustic-phonological perception, measured through phonological discrimination, and auditory comprehension in a case series of Wernicke's aphasia participants. A novel adaptive phonological discrimination task was used to obtain reliable thresholds of the phonological perceptual distance required between nonwords before they could be discriminated. Wernicke's aphasia participants showed significantly elevated thresholds compared to age and hearing matched control participants. Acoustic-phonological thresholds correlated strongly with auditory comprehension abilities in Wernicke's aphasia. In contrast, nonverbal semantic skills showed no relationship with auditory comprehension. The results are evaluated in the context of recent neurobiological models of language and suggest that impaired acoustic-phonological perception underlies the comprehension impairment in Wernicke's aphasia and favour models of language which propose a leftward asymmetry in phonological analysis.

Wernicke's aphasia reflects a combination of acoustic-phonological and semantic control deficits: a case-series comparison of Wernicke's aphasia, semantic dementia and semantic aphasia.

Wernicke's aphasia (WA) is the classical neurological model of comprehension impairment and, as a result, the posterior temporal lobe is assumed to be critical to semantic cognition. This conclusion is potentially confused by (a) the existence of patient groups with semantic impairment following damage to other brain regions (semantic dementia and semantic aphasia) and (b) an ongoing debate about the underlying causes of comprehension impairment in WA. By directly comparing these three patient groups for the first time, we demonstrate that the comprehension impairment in Wernicke's aphasia is best accounted for by dual deficits in acoustic-phonological analysis (associated with pSTG) and semantic cognition (associated with pMTG and angular gyrus). The WA group were impaired on both nonverbal and verbal comprehension assessments consistent with a generalised semantic impairment. This semantic deficit was most similar in nature to that of the semantic aphasia group suggestive of a disruption to semantic control processes. In addition, only the WA group showed a strong effect of input modality on comprehension, with accuracy decreasing considerably as acoustic-phonological requirements increased. These results deviate from traditional accounts which emphasise a single impairment and, instead, implicate two deficits underlying the comprehension disorder in WA.

The role of plasticity-related functional reorganization in the explanation of central dyslexias.

This investigation explored the hypothesis that patterns of acquired dyslexia may reflect, in part, plasticity-driven relearning that dynamically alters the division of labour (DOL) between the direct, orthography → phonology (O → P) pathway and the semantically mediated, orthography → semantics → phonology (O → S → P) pathway. Three simulations were conducted using a variant of the triangle model of reading. The model demonstrated core characteristics of normal reading behaviour in its undamaged state. When damage was followed by reoptimization (mimicking spontaneous recovery), the model reproduced the deficits observed in the central dyslexias-acute phonological damage combined with recovery matched data taken from a series of 12 phonological dyslexic patients-whilst progressive semantic damage interspersed with recovery reproduced data taken from 100 observations of semantic dementia patients. The severely phonologically damaged model also produced symptoms of deep dyslexia (imageability effects, production of semantic and mixed semantic/visual errors). In all cases, the DOL changed significantly in the recovery period, suggesting that postmorbid functional reorganization is important in understanding behaviour in chronic-stage patients.

Relearning in semantic dementia reflects contributions from both medial temporal lobe episodic and degraded neocortical semantic systems: evidence in support of the complementary learning systems theory.

When relearning words, patients with semantic dementia (SD) exhibit a characteristic rigidity, including a failure to generalise names to untrained exemplars of trained concepts. This has been attributed to an over-reliance on the medial temporal region which captures information in sparse, non-overlapping and therefore rigid representations. The current study extends previous investigations of SD relearning by re-examining the additional contribution made by the degraded cortical semantic system. The standard relearning protocol was modified by careful selection of foils to show that people with semantic dementia were sometimes able to extend their learning appropriately but that this correct generalisation was minimal (i.e. the patients under-generalised their learning). The revised assessment procedure highlighted the fact that, after relearning, the participants also incorrectly over-generalised the learned label to closely related concepts. It is unlikely that these behaviours would occur if the participants had only formed sparse hippocampal representations. These novel data build on the notion that people with semantic dementia engage both the degraded cortical semantic (neocortex) and the episodic (medial temporal) systems to learn. Because of neocortical damage to the anterior temporal lobes, relearning is disordered with a characteristic pattern of under- and over-generalisation.

Premorbid expertise produces category-specific impairment in a domain-general semantic disorder.

For decades, category-specific semantic impairment - i.e., better comprehension of items from one semantic category than another - has been the driving force behind many claims about the organisation of conceptual knowledge in the brain. Double dissociations between patients with category-specific disorders are widely interpreted as showing that different conceptual domains are necessarily supported by functionally independent systems. We show that, to the contrary, even strong or classical dissociations can also arise from individual differences in premorbid expertise. We examined two patients with global and progressive semantic degradation who, unusually, had known areas of premorbid expertise. Patient 1, a former automotive worker, showed selective preservation of car knowledge, whereas Patient 2, a former botanist, showed selective preservation of information about plants. In non-expert domains, these patients showed the typical pattern: i.e., an inability to differentiate between highly similar concepts (e.g., rose and daisy), but retention of broader distinctions (e.g., between rose and cat). Parallel distributed processing (PDP) models of semantic cognition show that expertise in a particular domain increases the differentiation of specific-level concepts, such that the semantic distance between these items resembles non-expert basic-level distinctions. We propose that these structural changes interact with global semantic degradation, particularly when expert knowledge is acquired early and when exposure to expert concepts continues during disease progression. Therefore, category-specific semantic impairment can arise from at least two distinct mechanisms: damage to representations that are critical for a particular category (e.g., knowledge of hand shape and action for the category 'tools') and differences in premorbid experience.

Remembering 'zeal' but not 'thing': reverse frequency effects as a consequence of deregulated semantic processing.

More efficient processing of high frequency (HF) words is a ubiquitous finding in healthy individuals, yet frequency effects are often small or absent in stroke aphasia. We propose that some patients fail to show the expected frequency effect because processing of HF words places strong demands on semantic control and regulation processes, counteracting the usual effect. This may occur because HF words appear in a wide range of linguistic contexts, each associated with distinct semantic information. This theory predicts that in extreme circumstances, patients with impaired semantic control should show an outright reversal of the normal frequency effect. To test this prediction, we tested two patients with impaired semantic control with a delayed repetition task that emphasised activation of semantic representations. By alternating HF and low frequency (LF) trials, we demonstrated a significant repetition advantage for LF words, principally because of perseverative errors in which patients produced the previous LF response in place of the HF target. These errors indicated that HF words were more weakly activated than LF words. We suggest that when presented with no contextual information, patients generate a weak and unstable pattern of semantic activation for HF words because information relating to many possible contexts and interpretations is activated. In contrast, LF words are associated with more stable patterns of activation because similar semantic information is activated whenever they are encountered.

Explaining semantic short-term memory deficits: evidence for the critical role of semantic control.

Patients with apparently selective short-term memory (STM) deficits for semantic information have played an important role in developing multi-store theories of STM and challenge the idea that verbal STM is supported by maintaining activation in the language system. We propose that semantic STM deficits are not as selective as previously thought and can occur as a result of mild disruption to semantic control processes, i.e., mechanisms that bias semantic processing towards task-relevant aspects of knowledge and away from irrelevant information. We tested three semantic STM patients with tasks that tapped four aspects of semantic control: (i) resolving ambiguity between word meanings, (ii) sensitivity to cues, (iii) ignoring irrelevant information and (iv) detecting weak semantic associations. All were impaired in conditions requiring more semantic control, irrespective of the STM demands of the task, suggesting a mild, but task-general, deficit in regulating semantic knowledge. This mild deficit has a disproportionate effect on STM tasks because they have high intrinsic control demands: in STM tasks, control is required to keep information active when it is no longer available in the environment and to manage competition between items held in memory simultaneously. By re-interpreting the core deficit in semantic STM patients in this way, we are able to explain their apparently selective impairment without the need for a specialised STM store. Instead, we argue that semantic STM patients occupy the mildest end of spectrum of semantic control disorders.

Semantic diversity accounts for the "missing" word frequency effect in stroke aphasia: insights using a novel method to quantify contextual variability in meaning.

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.