Search

The human dorsolateral prefrontal cortex (DLPFC; approximately corresponding to Brodmann areas 9 and 46) has demonstrable roles in diverse executive functions such as working memory, cognitive flexibility, planning, inhibition, and abstract reasoning. However, it remains unclear whether this is the result of one functionally homogeneous region or whether there are functional subdivisions within the DLPFC. Here, we divided the DLPFC into seven areas along rostral-caudal and dorsal-ventral axes anatomically and explored their respective patterns of structural and functional connectivity. In vivo probabilistic tractography (11 females and 13 males) and resting-state functional magnetic resonance imaging (fMRI; 57 females and 21 males) were employed to map out the patterns of connectivity from each DLPFC subregion. Structural connectivity demonstrated graded intraregional connectivity within the DLPFC. The patterns of structural connectivity between the DLPFC subregions and other cortical areas revealed that the dorsal-rostral subregions connections were restricted to other frontal and limbic areas, whereas the ventral-caudal region was widely connected to frontal, parietal, and limbic cortex. Functional connectivity analyses demonstrated that subregions of DLPFC were strongly interconnected to each other. The dorsal subregions were associated with the default mode network (DMN), while middle dorsal-rostral subregions were linked with the multiple demand network (MDN). The ventral-caudal subregion showed increased functional coupling with both DMN and MDN. Our results suggest that the connectivity of the DLPFC may be subdivided along a dorsorostral-ventrocaudal axis with differing (albeit graded) patterns of connectivity reflecting the integrative executive function of the DLPFC.SIGNIFICANCE STATEMENTResearch has shown that the dorsolateral prefrontal cortex (DLPFC) plays a role in various executive functions. By dividing the DLPFC into seven areas along rostral-caudal and dorsal-ventral axes anatomically, we explored their patterns of structural and functional connectivity. The patterns of connectivity within DLPFC subregions demonstrated graded intraregional connectivity. There were distinctive patterns of connectivity with other cortical areas in dorsal-rostral and ventral-caudal DLPFC subregions. Divisions across DLPFC subregions seem to align with their structural and functional connectivity. Our results suggest that DLPFC may be subdivided by the diagonal axis of the dorsal-ventral axis and rostral-caudal axis, supporting the framework of a functional organization along the anterior-posterior axis in the lateral PFC.

Background and Purpose:\ud The factors associated with recovery of language domains after stroke remain uncertain. We described recovery of overall-language-ability, auditory comprehension, naming, and functional-communication across participants’ age, sex, and aphasia chronicity in a large, multilingual, international aphasia dataset.\ud \ud Methods:\ud Individual participant data meta-analysis of systematically sourced aphasia datasets described overall-language ability using the Western Aphasia Battery Aphasia-Quotient; auditory comprehension by Aachen Aphasia Test (AAT) Token Test; naming by Boston Naming Test and functional-communication by AAT Spontaneous-Speech Communication subscale. Multivariable analyses regressed absolute score-changes from baseline across language domains onto covariates identified a priori in randomized controlled trials and all study types. Change-from-baseline scores were presented as estimates of means and 95% CIs. Heterogeneity was described using relative variance. Risk of bias was considered at dataset and meta-analysis level.\ud \ud Results:\ud Assessments at baseline (median=43.6 weeks poststroke; interquartile range [4–165.1]) and first-follow-up (median=10 weeks from baseline; interquartile range [3–26]) were available for n=943 on overall-language ability, n=1056 on auditory comprehension, n=791 on naming and n=974 on functional-communication. Younger age (

Multiple language assessments are necessary for diagnosing, characterising and quantifying the multifaceted deficits observed in many patients’ post-stroke. Current language batteries, however, tend to be an imperfect trade-off between time and sensitivity of assessment. There have hitherto been two main types of battery. Extensive batteries provide thorough information but are impractically long for application in clinical settings or large-scale research studies. Clinically-targeted batteries tend to provide superficial information about a large number of language skills in a relatively short period of time by reducing the depth of each test but, consequently, can struggle to identify mild deficits, qualify the level of each impairment or reveal the underlying component structure. In the current study, we compared these batteries across a large group of individuals with chronic stroke aphasia to determine their utility. In addition, we developed a data-driven reduced version of an extensive battery that maintained sensitivity to mild impairment, ability to grade deficits and the component structure. The underlying structure of these three language batteries (extensive, shallow and data-reduced) was analysed using cross-validation analysis and principal component analysis. This revealed a four-factor solution for the extensive and data-reduced batteries, identifying phonology, semantic skills, fluency and executive function in contrast to a two-factor solution using the shallow battery (phonological/language severity and cognitive severity). Lesion symptom mapping using participants’ factor scores identified convergent neural structures based on existing language models for phonology (superior temporal gyrus), semantics (inferior temporal gyrus), speech fluency (precentral gyrus) and executive function (lateral occipitotemporal cortex) based on the extensive and data-reduced batteries. The two components in the shallow battery converged with the phonology and executive function clusters. In addition, we show that multivariate prediction models could be utilised to predict the component scores using neural data, however not for every component score within every test battery. Overall, the data-reduced battery appears to be an effective way to save assessment time yet retain the underlying structure of language and cognitive deficits observed in post stroke aphasia.

© 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Purpose: Speech and language pathology (SLP) for aphasia is a complex intervention delivered to a heterogeneous population within diverse settings. Simplistic descriptions of participants and interventions in research hinder replication, interpretation of results, guideline and research developments through secondary data analyses. This study aimed to describe the availability of participant and intervention descriptors in existing aphasia research datasets. Method: We systematically identified aphasia research datasets containing ≥10 participants with information on time since stroke and language ability. We extracted participant and SLP intervention descriptions and considered the availability of data compared to historical and current reporting standards. We developed an extension to the Template for Intervention Description and Replication checklist to support meaningful classification and synthesis of the SLP interventions to support secondary data analysis. Result: Of 11, 314 identified records we screened 1131 full texts and received 75 dataset contributions. We extracted data from 99 additional public domain datasets. Participant age (97.1%) and sex (90.8%) were commonly available. Prior stroke (25.8%), living context (12.1%) and socio-economic status (2.3%) were rarely available. Therapy impairment target, frequency and duration were most commonly available but predominately described at group level. Home practice (46.3%) and tailoring (functional relevance 46.3%) were inconsistently available. Conclusion : Gaps in the availability of participant and intervention details were significant, hampering clinical implementation of evidence into practice and development of our field of research. Improvements in the quality and consistency of participant and intervention data reported in aphasia research are required to maximise clinical implementation, replication in research and the generation of insights from secondary data analysis. Systematic review registration: PROSPERO CRD42018110947.

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. \ud \ud Aim: To explore the contribution that individual participant characteristics (including stroke and aphasia profiles) and SLT intervention components make to language recovery following stroke.\ud \ud 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 metaand 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.\ud \ud 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.\ud \ud 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.\ud \ud Systematic review registration: The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42018110947

The anterior temporal lobes (ATLs) play a key role in conceptual knowledge representation. The hub-and-spoke theory suggests that the contribution of the ATLs to semantic representation is (a) transmodal, i.e., integrating information from multiple sensorimotor and verbal modalities, and (b) pan-categorical, representing concepts from all categories. Another literature, however, suggests that this region’s responses are modality- and category-selective; prominent examples include category selectivity for socially-relevant concepts and face recognition. The predictions of each approach have never been directly compared. We used data from three studies to compare category-selective responses within the ATLs. Study 1 compared ATL responses to famous people vs. another conceptual category (landmarks) from visual vs. auditory inputs. Study 2 compared ATL responses to famous people from pictorial and written word inputs. Study 3 compared ATL responses to a different kind of socially-relevant stimuli, namely abstract non-person related words, in order to ascertain whether ATL subregions are engaged for social concepts more generally or only for person-related knowledge. Across all three studies a dominant bilateral ventral ATL cluster responded to all categories in all modalities. Anterior to this “pan-category” transmodal region, a second cluster responded more weakly overall yet selectively for people, but did so equally for spoken names and faces (Study 1). A third region in the anterior superior temporal gyrus responded selectively to abstract socially-relevant words (Study 3), but did not respond to socially-relevant concrete words (i.e., written names; Study 2). These findings can be accommodated by the graded hub-and-spoke model of concept representation. On this view, the ventral ATL is the centrepoint of a bilateral ATL hub which contributes to conceptual representation through transmodal distillation of information arising from multiple modality-specific association cortices. Partial specialisation occurs across the graded ATL hub as a consequence of gradedly-differential connectivity across the region.

It is now ten years since a 'ventral language pathway'€™ was demonstrated in vivo in the human brain. In the intervening decade, this result has been replicated and expanded to include multiple possible pathways and functions. Despite this considerable level of research interest, age-old debates regarding the origin, course, termination and, indeed, the very existence of the tracts identified still remain. The current review examines four major tracts associated with the ventral 'semantic'€™ language network, with the aim of elucidating and clarifying their structural and functional roles. Historical and modern conceptualisations of the tracts' neuroanatomical origins and terminations will be discussed, and key discrepancies and debates examined. It is argued that much of the controversy regarding the language pathways has resulted from inconsistencies in terminology, and the lack of a white matter '€˜lingua franca'€™.

Exaggerated effects of word length upon reading aloud performance define Pure Alexia, but have also been observed in Semantic Dementia. Some researchers have proposed a reading-specific account, whereby performance in these two disorders reflects the same cause: impaired orthographic processing. In contrast, according to the primary systems view of acquired reading disorders, Pure Alexia results from a basic visual processing deficit, whereas degraded semantic knowledge undermines reading performance in Semantic Dementia. To explore the source of reading deficits in these two disorders, we compared the reading performance of 10 Pure Alexic and 10 Semantic Dementia patients, matched in terms of overall severity of reading deficit. The results revealed comparable frequency effects on reading accuracy, but weaker effects of regularity in Pure Alexia than Semantic Dementia. Analysis of error types revealed a higher rate of letter-based errors and a lower rate of regularisation responses in Pure Alexia than Semantic Dementia. Error responses were most often words in Pure Alexia but most often nonwords in Semantic Dementia. Although all patients made some letter substitution errors, these were characterised by visual similarity in Pure Alexia and phonological similarity in Semantic Dementia. Overall, the data indicate that the reading deficits in Pure Alexia and Semantic Dementia arise from impairments of visual processing and knowledge of word meaning, respectively. The locus and mechanisms of these impairments are placed within the context of current connectionist models of reading.

Recent evidence from multiple neuroscience techniques indicates that regions within the anterior temporal lobes (ATLs) are a critical node in the neural network for representing conceptual knowledge, yet their function remains elusive. The hub-and-spoke model holds that ATL regions act as a transmodal conceptual hub, distilling the various sensory-motor features of objects and words into integrated, coherent conceptual representations. Single-cell recordings in monkeys suggest that the ATLs are critically involved in visual associative learning; however, investigations of this region in humans have focused on existing knowledge rather than learning. We studied acquisition of new concepts in semantic dementia patients, who have cortical damage centred on the ventrolateral aspects of the ATLs. Patients learned to assign abstract visual stimuli to two categories. The categories conformed to a family resemblance structure in which no individual stimulus features were fully diagnostic; thus the task required participants to form representations that integrate multiple features into a single concept. Patients were unable to do this, instead responding only on the basis of individual features. The study reveals that integrating disparate sources of information into novel coherent concepts is a critical computational function of the ATLs. This explains the central role of this region in conceptual representation and the catastrophic breakdown of concepts in semantic dementia.

The parcellation of the cortex via its anatomical properties has been an important research endeavor for over a century. To date, however, a universally accepted parcellation scheme for the human brain still remains elusive. In the current review, we explore the use of in vivo diffusion imaging and white matter tractography as a non-invasive method for the structural and functional parcellation of the human cerebral cortex, discussing the strengths and limitations of the current approaches. Cortical parcellation via white matter connectivity is based on the premise that, as connectional anatomy determines functional organization, it should be possible to segregate functionally-distinct cortical regions by identifying similarities and differences in connectivity profiles. Recent studies have provided initial evidence in support of the efficacy of this connectional parcellation methodology. Such investigations have identified distinct cortical subregions which correlate strongly with functional regions identified via fMRI and meta-analyses. Furthermore, a strong parallel between the cortical regions defined via tractographic and more traditional cytoarchitectonic parcellation methods has been observed. However, the degree of correspondence and relative functional importance of cytoarchitectonic- versus connectivity-derived parcellations still remains unclear. Diffusion tractography remains one of the only methods capable of visualizing the structural networks of the brain in vivo. As such, it is of vital importance to continue to improve the accuracy of the methodology and to extend its potential applications in the study of cognition in neurological health and disease.

Context: Proneness to overgeneralization of self-blame is a core part of cognitive vulnerability to major depressive disorder (MDD) and remains dormant after remission of symptoms. Current neuroanatomical models of MDD, however, assume general increases of negative emotions and are unable to explain biases towards emotions entailing self-blame (e.g. guilt) relative to those associated with blaming others (e.g. indignation). Recent fMRI studies in healthy participants have shown that moral feelings such as guilt activate representations of social meaning within the right superior anterior temporal lobe (ATL). Furthermore, this area was selectively coupled with the subgenual cingulate cortex and the adjacent septal region (SCSR) during the experience of guilt compared with indignation. Despite its psychopathological importance, the functional neuroanatomy of guilt in MDD is unknown. Objective: Use fMRI to test the hypothesis that in comparison with controls, participants with remitted MDD exhibit guilt-selective SCSR-ATL decoupling as a marker of deficient functional integration. Design: Case-control study from 2008 to 2009. Setting: Clinical Research Facility. Participants: 25 patients with remitted MDD (no medication in 16) with no current co-morbid axis-I disorders, and 22 control participants with no personal or family history of MDD. Main outcome measures: Between-group difference of ATL-coupling with a priori SCSR region of interest (ROI) for guilt vs. indignation. Results: We corroborated the prediction of a guilt-selective reduction in ATL-SCSR coupling in MDD vs. controls (Family-Wise-Error-corrected p=.001 over ROI) and revealed additional medial frontopolar, right hippocampal and lateral hypothalamic areas of decoupling while controlling for medication status and intensity of negative emotions. Lower levels of ATL-SCSR coupling were associated with higher scores on a validated measure of overgeneralized self-blame (Interpersonal Guilt Questionnaire). Conclusions: Vulnerability to MDD is associated with temporo-fronto-limbic decoupling that is selective for self-blaming feelings. This provides the first neural mechanism of MDD vulnerability that accounts for self-blaming biases.

OBJECTIVE: To determine the clinical effectiveness, cost-effectiveness and service users' views of enhanced early communication therapy by speech and language (SL) therapists compared with attention control (AC). DESIGN: Successful feasibility study followed by a randomised trial with economic evaluation, and nested qualitative study using 32 individual interviews. SETTING: Twelve English NHS hospital and community stroke services. PARTICIPANTS: One hundred and seventy adults with aphasia or dysarthria admitted to hospital with stroke, December 2006 to January 2010. Eligibility determined by NHS SL therapists. Seventeen people declined follow-up. INTERVENTIONS: A best-practice, flexible intervention by NHS SL therapists, up to three contacts per week for up to 16 weeks compared with a similar number of AC contacts by employed visitors. MAIN OUTCOME MEASURES: Primary outcome was blinded, functional communicative ability 6 months post randomisation on the Therapy Outcome Measure activity subscale (TOM). Secondary outcomes were participants' perceptions on the Communication Outcomes After Stroke scale (COAST); carers' perceptions of participants from part of the Carer COAST; carer well-being on Carers of Older People in Europe Index and quality-of-life items from Carer COAST. Serious adverse events (SAEs) were recorded. Economic evaluation: participants' utility (European Quality of Life-5 Dimensions), service use and cost data from medical records and carers, and a discrete choice experiment. RESULTS: Intervention typically started after 2 weeks, providing 22 contacts. Both groups improved on the TOM. The estimated 6 months' group difference [95% confidence interval (CI)] was 0.25 (-0.19 to 0.69) points in favour of SL therapy. Sensitivity analyses adjusting for baseline chance imbalance or not imputing values for decedents further reduced this difference. Per-protocol analyses rejected a possible dilution of therapy from controls refusing allocation and receiving NHS SL therapy. There was no evidence of added benefit of therapy on any secondary outcome measure or SAEs, although the latter were less frequent in the therapy group [odds ratio 0.42 (95% CI 0.16 to 1.1)]. Regardless of group allocation, interviewed participants reported positive impacts on their confidence and mood, identified drivers for change and valued early and sustained contact. Health economic analysis indicated a high level of uncertainty. Early enhanced SL therapy for communication is likely to be cost-effective only if decision-makers are prepared to pay ? �25,000 to gain one unit of utility. CONCLUSIONS: These findings exclude the possibility of a clinically significant difference of 0.5 points on the TOM. There was no evidence, on any measure, of added benefit of early communication therapy beyond that from AC. It is unclear whether therapy is more or less cost-effective than AC. Early, frequent contact was highly valued by users and had good uptake. Functional communication improved for both groups, plausibly due to natural recovery and early and regular opportunity to practise everyday communication with a professional (therapist/visitor). There is no evidence to recommend enhancing the provision of early communication therapy by a qualified SL therapist over and above usual care. SL therapy service reorganisation should consider skill mix and timing within a stepped care model and should take place within the context of a trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN78617680. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 26. See the HTA programme website for further project information. The Stroke Association funded part of the excess treatment costs.

A comprehensive battery of neuropsychological tests designed to assess primary cognitive functions, including language and semantic memory, was given to MG, a patient with confirmed herpes simplex virus encephalitis. MG's initial jargon aphasia resolved over time to leave her with a mild phonological impairment. She had a very mild amnesia that was worse for verbal material and a category-specific impairment of semantic memory. This latter impairment resulted in a significant anomia that was worse for manmade/artefact items than for animate kinds. Her naming difficulties were associated with a mild impairment in comprehension that was not specific to category or feature type. MRI revealed a strongly asymmetric and atypical distribution of pathology in MG with the disease affecting the left medial temporal lobe, temporal pole, left frontotemporal and temporoparietal regions. Copyright © Taylor & Francis Inc.