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The neuroscientific study of conceptual representation has largely focused on categories of concrete entities (biological entities, tools…), while abstract knowledge has been less extensively investigated. The possible presence of a categorical organization of abstract knowledge is a debated issue. An embodied cognition framework predicts an organization of the abstract domain into different dimensions, grounded in the brain regions engaged by the corresponding experience. Here we review the types of experience that have been proposed to characterize different categories of abstract concepts, and the evidence supporting a corresponding organization derived from behavioural, neuroimaging (i.e., fMRI, MRI, PET, SPECT), EEG, and neurostimulation (i.e., TMS) studies in healthy and clinical populations. The available data provide substantial converging evidence in favour of the presence of distinct neural representations of social and emotional knowledge, mental states and magnitude concepts, engaging brain systems involved in the corresponding experiences. This evidence is supporting an extension of embodied models of semantic memory organization to several types of abstract knowledge.

Background The evidence about the language performance profile of multiple system atrophy (MSA) is limited, but its definition may lead to a more comprehensive characterization of the disorder and contribute to clarify the involvement of the basal ganglia in language abilities. Objective The objectives of the study were: (1) to evaluate the reliability of the Screening for Aphasia in NeuroDegeneration (SAND) in MSA patients; (2) compare the linguistic profiles among MSA and Parkinson’s disease (PD) patients and healthy controls (HC), and (3) assess relationships between language impairment and cognitive status and MSA motor subtypes. Methods and results Forty patients with a diagnosis of MSA, 22 HC and 17 patients with PD were enrolled in the present study. By excluding the writing task that showed a poor acceptability, we showed that the MSA-tailored SAND Global Score is an acceptable, consistent and reliable tool to screen language disturbances in MSA. MSA patients performed worse than HC, but not than PD, in MSA-tailored SAND Global Score, repetition, reading and semantic association tasks. We did not find significant differences between MSA phenotypes. MSA patients with mild cognitive impairment-multiple domain presented worse language performances as compared to MSA patients with normal cognition and mild cognitive impairment-single domain. Conclusion The MSA-tailored SAND Global Score is a consistent and reliable tool to screen language disturbances in MSA. Language disturbances characterize MSA patients irrespective of disease phenotype, and parallel the decline of global cognitive functions.

The linguistic and anatomical variability of the logopenic variant of Primary Progressive Aphasia (lv-PPA) as defined by current diagnostic criteria has been the topic of an intense debate. The present review and meta-analysis aims at characterizing the profile of lv-PPA, by a comprehensive analysis of the available literature on the neuropsychological, neuroimaging, electrophysiological, pathological, and genetic features of lv-PPA. We conducted a systematic bibliographic search, leading to the inclusion of 207 papers. Of them, 12 were used for the Anatomical Likelihood Estimation meta-analysis on grey matter revealed by magnetic resonance imaging data. The results suggest that the current guidelines outline a relatively consistent syndrome, characterized by a core set of linguistic and, to a lesser extent, non-linguistic deficits, mirroring the involvement of left temporal and parietal regions typically affected by Alzheimer Disease pathology. Variations of the lv-PPA profile are discussed in terms of heterogeneity of the neuropsychological instruments and the diagnostic criteria adopted.

Neuroscience research has provided evidence that semantic information is stored in a distributed brain network involved in sensorimotor and linguistic processing. More specifically, according to the Embodied Cognition account, the representation of concepts is deemed as grounded in our bodily states. For these reasons, normative measures of words should provide relevant information about the extent to which each word embeds perceptual and action properties. In the present study, we collected ratings for 959 Italian nouns and verbs from 398 volunteers, recruited via an online platform. The words were mostly taken from the Italian adaptation of the Affective Norms for English Words (ANEW). A pool of 145 verbs was added to the original set. All the words were rated on 11 sensorimotor dimensions: 6 perceptual modalities (vision, audition, taste, smell, touch, and interoception) and 5 effectors (hand-arm, foot-leg, torso, mouth, head). The new verbs were also rated on the ANEW dimensions. Results showed good reliability and consistency with previous studies. Relations between perceptual and motor dimensions are described and interpreted, along with relations between the sensorimotor and the affective dimensions. The currently developed dataset represents an important novelty, as it includes different word classes, i.e. both nouns and verbs, and integrates ratings of both sensorimotor and affective dimensions, along with other psycholinguistic parameters; all features only partially accomplished in previous studies.The data are available within the Open Science Framework at this link: https://osf.io/rcsnm/

Concrete conceptual knowledge is supported by a distributed neural network representing different semantic features according to the neuroanatomy of sensory and motor systems. If and how this framework applies to abstract knowledge is currently debated. Here we investigated the specific brain correlates of different abstract categories. After a systematic a priori selection of brain regions involved in semantic cognition, i.e. responsible of, respectively, semantic representations and cognitive control, we used a fMRI-adaptation paradigm with a passive reading task, in order to modulate the neural response to abstract (emotions, cognitions, attitudes, human actions) and concrete (biological entities, artefacts) categories. Different portions of the left anterior temporal lobe responded selectively to abstract and concrete concepts. Emotions and attitudes adapted the left middle temporal gyrus, whereas concrete items adapted the left fusiform gyrus. Our results suggest that, similarly to concrete concepts, some categories of abstract knowledge have specific brain correlates corresponding to the prevalent semantic dimensions involved in their representation.

Functional network-level alterations in the semantic variant of Primary Progressive Aphasia (sv-PPA) are relevant to understanding the clinical features and the neural spreading of the pathology. We assessed the effect of neurodegeneration on brain systems reorganization in early sv-PPA, using advanced brain metabolic connectivity approaches. Forty-four subjects with sv-PPA and forty-four age-matched healthy controls (HC) were included. We applied two multivariate approaches to [18F]FDG-PET data - i.e., sparse inverse covariance estimation and seed-based interregional correlation analysis - to assess the integrity of (i) the whole-brain metabolic connectivity and (ii) the connectivity of brain regions relevant for cognitive and behavioral functions. Whole-brain analysis revealed a global-scale connectivity reconfiguration in sv-PPA, with widespread changes in metabolic connections of frontal, temporal, and parietal regions. In comparison to HC, the seed-based analysis revealed a) functional isolation of the left anterior temporal lobe (ATL), b) decreases in temporo-occipital connections and contralateral homologous regions, c) connectivity increases to the dorsal parietal cortex from the spared posterior temporal cortex, d) a disruption of the large-scale limbic brain networks. In sv-PPA, the severe functional derangement of the left ATL may lead to an extensive connectivity reconfiguration, encompassing several brain regions, including those not yet affected by neurodegeneration. These findings support the hypothesis that in sv-PPA the focal vulnerability of the core region (i.e., ATL) can potentially drive the widespread cerebral connectivity changes, already present in the early phase.

The observation of neurological patients showing selective impairments for specific conceptual categories contributed in the development of semantic memory theories. Here, we studied two patients (P01, P02), affected, respectively, by the semantic variant of Primary Progressive Aphasia (sv-PPA) and Cortico-Basal Syndrome (CBS). An implicit lexical decision task, including concrete (animals, tools) and abstract (emotions, social, quantity) concepts, was administered to patients and healthy controls.P01 and P02 showed an abolished priming effect for social and quantity-related concepts, respectively. This double dissociation suggests a role of different brain areas in representing specific abstract categories, giving insights for current semantic memory theories.

Background: There are few available methods for qualitatively evaluating patients with primary progressive aphasia (PPA). Commonly adopted approaches are time-consuming, of limited accuracy, or designed to assess different patient populations. This paper introduces a new clinical test - the Mini Linguistic State Examination (MLSE) - which was designed uniquely to enable a clinician to assess and subclassify both classical and mixed presentations of PPA. The adoption of a novel assessment method (error classification) greatly amplifies the clinical information that can be derived from a set of standard linguistic tasks and allows a five-dimensional profile to be defined. Methods: Fifty-four patients and 30 matched controls were recruited. Five domains of language competence (motor speech, phonology, semantics, syntax, and working memory) were assessed using a sequence of 11 distinct linguistic assays. A random forest classification was used to assess the diagnostic accuracy for predicting PPA subtypes and create a decision tree as a guide to clinical classification. Findings: The random forest prediction model was 96% accurate overall (92% for logopenic variant, 93% for semantic variant, and 98% for non-fluent variant PPA). The derived decision tree produced a correct classification of 91% of participants whose data were not included in the training set. Interpretation: The MLSE is a new cognitive test incorporating a novel and powerful, yet straightforward, approach to scoring. Rigorous assessment of its diagnostic accuracy confirmed excellent matching of PPA syndromes to clinical gold standard diagnoses. Adoption of the MLSE by clinicians will have a decisive impact on the consistency and uniformity with which patients can be described clinically. It will also facilitate screening for cohort-based research, including future therapeutic trials, and is suitable for describing, quantifying and monitoring language deficits in other brain disorders. Funding Information: The research was funded by a Medical Research Council Research Grant award (Ref MR/N025881/1) to PG, MLR JR, KP and SC. Additional support was provided through grants from the MRC (UAG051 and G101400), Wellcome Trust (103838) and ERC (GAP: 670428), and through funding awarded to the National Institute for Health Research Cambridge Biomedical Research Centre and to the MRC CBU (MC_UU_00005/18). Declaration of Interests: JBR reports consultancy unrelated to the work with Biogen, UCB, Asceneuron and Althira; and receipt of research grants, unrelated to this work, from Janssen, AZ-Medimmune, and Lilly. The other authors declare no conflicts of interest. Ethics Approval Statement: Written informed consent was provided by all participants. The study protocol was reviewed and approved by the London (Chelsea) Research Ethics Committee [Ref. 16/LO/1735].

BackgroundThis paper introduces a new clinical test, the Mini Linguistic State Examination (MLSE), as a short assessment for screening and classification of the different manifestations of primary progressive aphasia (PPA). Differentiation and monitoring of PPA variants are vital for management, planning and development of new treatments. The MLSE is designed to improve the uniformity of testing, screening for recruitment to clinical trials, and consistency of research results. It is a brief but effective test which can be adapted to the world’s major languages.MethodsFifty-four patients and 30 age-, sex- and education-matched controls completed testing with the MLSE and components of the Boston Diagnostic Aphasia Examination in addition to their standard clinical diagnostic assessment. The MLSE includes five domains (motor speech, phonology, semantics, syntax and working memory) that were compared across groups. A random forest classification was used to learn the relationship between these five domains and assess the power of the diagnostic accuracy for predicting PPA subtypes. The final machine learning model was used to create a decision tree to guide the optimal manual classification of patients.ResultsOn average, the test took less than 20 minutes to administer. Significant group differences were found across all five domains, in terms of the distributions of error-types. These differences mirror the well-known language profiles for the three main PPA variants, which typically require an extended neuropsychology and speech pathology assessment. The random forest prediction model had an overall classification accuracy of 96% (92% for logopenic variant PPA, 93% for semantic variant PPA and 98% for non-fluent variant PPA). The derived decision tree for manual classification produced correct classification of 91% of participants whose data were not included in the training set.ConclusionsThe MLSE is a new short cognitive test, with a scoring system that is easy to learn and apply. It is accurate for classifying PPA syndromes, and has potential to screen and monitor language deficits that occur in other focal and neurodegenerative brain disorders associated with language impairment. With increasing importance of language assessment in clinical research, the MLSE’s linguistic assessment tool enables the essential profiling of language deficits in a wide clinical community.

ObjectiveTo investigate the types of errors produced in a picture naming task by patients with neurodegenerative dementia due to different etiologies and their neural correlates.MethodsThe same standardized picture naming test was administered to a consecutive sample of patients (n = 148) who had been studied with [18F] FDG-PET. The errors were analyzed in 3 categories (visual, semantic, and phonologic). The PET data were analyzed using an optimized single-subject procedure, and the statistical parametric mapping multiple regression design was used to explore the correlation between each type of error and brain hypometabolism in the whole group. Metabolic connectivity analyses were run at the group level on 7 left hemisphere cortical areas corresponding to an a priori defined naming network.ResultsSemantic errors were predominant in most patients, independent of clinical diagnosis. In the whole group analysis, visual errors correlated with hypometabolism in the right inferior occipital lobe and in the left middle occipital lobe. Semantic errors correlated with hypometabolism in the left fusiform gyrus, the inferior and middle temporal gyri, and the temporal pole. Phonologic errors were associated with hypometabolism in the left superior and middle temporal gyri. Both positive (occipital–posterior fusiform) and negative (anterior fusiform gyrus and the superior anterior temporal lobe) connectivity changes were associated with semantic errors.ConclusionsNaming errors reflect the dysfunction of separate stages of the naming process and are specific markers for different patterns of brain involvement. These correlations are not limited to primary progressive aphasia but extend to other neurodegenerative dementias.

According with a featural organization of semantic memory, this work is aimed at investigating, through an attractor network, the role of different kinds of features in the representation of concepts, both in normal and neurodegenerative conditions. We implemented new synaptic learning rules in order to take into account the role of partially shared features and of distinctive features with different saliency. The model includes semantic and lexical layers, coding, respectively for object features and word-forms. Connections among nodes are strongly asymmetrical. To account for the feature saliency, asymmetrical synapses were created using Hebbian rules of potentiation and depotentiation, setting different pre-synaptic and post-synaptic thresholds. A variable post-synaptic threshold, which automatically changed to reflect the feature frequency in different concepts (i.e., how many concepts share a feature), was used to account for partially shared features. The trained network solved naming tasks and word recognition tasks very well, exploiting the different role of salient versus marginal features in concept identification. In the case of damage, superordinate concepts were preserved better than the subordinate ones. Interestingly, the degradation of salient features, but not of marginal ones, prevented object identification. The model suggests that Hebbian rules, with adjustable post-synaptic thresholds, can provide a reliable semantic representation of objects exploiting the statistics of input features. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11571-018-9494-0) contains supplementary material, which is available to authorized users.

Evidence from both neuropsychology and neuroimaging suggests that different types of information are necessary for representing and processing concrete and abstract word meanings. Both abstract and concrete concepts, however, conjointly rely on perceptual, verbal and contextual knowledge, with abstract concepts characterized by low values of imageability (IMG) (low sensory-motor grounding) and low context availability (CA) (more difficult to contextualize). Imaging studies supporting differences between abstract and concrete concepts show a greater recruitment of the left inferior frontal gyrus (LIFG) for abstract concepts, which has been attributed either to the representation of abstract-specific semantic knowledge or to the request for more executive control than in the case of concrete concepts. We conducted an fMRI study on 27 participants, using a lexical decision task involving both abstract and concrete words, whose IMG and CA values were explicitly modelled in separate parametric analyses. The LIFG was significantly more activated for abstract than for concrete words, and a conjunction analysis showed a common activation for words with low IMG or low CA only in the LIFG, in the same area reported for abstract words. A regional template map of brain activations was then traced for words with low IMG or low CA, and BOLD regional time-series were extracted and correlated with the specific LIFG neural activity elicited for abstract words. The regions associated to low IMG, which were functionally correlated with LIFG, were mainly in the left hemisphere, while those associated with low CA were in the right hemisphere. Finally, in order to reveal which LIFG-related network increased its connectivity with decreases of IMG or CA, we conducted generalized psychophysiological interaction analyses. The connectivity strength values extracted from each region connected with the LIFG were correlated with specific LIFG neural activity for abstract words, and a regression analysis was conducted to highlight which areas recruited by low IMG or low CA predicted the greater activation of the IFG for abstract concepts. Only the left middle temporal gyrus/angular gyrus, known to be involved in semantic processing, was a significant predictor of LIFG activity differentiating abstract from concrete words. The results show that the abstract conceptual processing requires the interplay of multiple brain regions, necessary for both the intrinsic and extrinsic properties of abstract knowledge. The LIFG can be thus identified as the neural crossroads between different types of information equally necessary for representing processing and differentiating abstract concepts from concrete ones.

Amyotrophic lateral sclerosis (ALS) can be associated with a spectrum of cognitive and behavioural symptoms, but the related patterns of focal cortical atrophy in non-demented ALS patients remain largely unknown. We enrolled 48 non-demented ALS patients and 26 healthy controls for a comprehensive neuropsychological assessment and a magnetic resonance exam. Behavioural and cognitive impairment was defined on the basis of a data-driven multi-domain approach in 21 ALS patients. Averaged cortical thickness of 74 bilateral brain regions was used as a measure of cortical atrophy. Cortical thinning in a fronto-parietal network, suggesting a disease-specific pattern of neurodegeneration, was present in all patients, independent of cognitive and behavioural status. Between-group and correlational analyses revealed that inferior frontal, temporal, cingular and insular thinning are markers for cognitive and behavioural deficits, with language impairment mainly related to left temporal pole and insular involvement. These specific correlates support the concept of a spectrum of deficits, with an overlap between the ALS cognitive phenotypes and the syndromes of frontotemporal dementia., Highlights • Language, social cognition and executive dysfunctions are frequent symptoms in ALS. • Fronto-parietal cortical thinning is present in non-demented ALS patients. • Temporal, cingular and insular thinning are markers for cognitive impairment in ALS. • Left temporal pole and insular thinning is linked to language impairment in ALS.

Background: Speech and language impairments are the key clinical feature in several neurodegenerative disorders and primary progressive aphasia (PPA) is the syndrome where they are the prominent features. Their accurate and early identification may increase the diagnosis in the clinical setting. This approach may allow a better discrimination between the different neurodegenerative disorders and the PPA variants, i.e., nonfluent, semantic, logopenic.Aims: The aim of this work is twofold: (1) to provide an overview of the available neuropsychological tests for the diagnosis of PPA and/or for the differentiation among the PPA variants and (2) to evaluate the methodological quality and the psychometric characteristics of these tests.Methods & Procedures: This review was conducted following PRISMA guidelines. Search terms were chosen based on the research questions and used in a search in two databases. Then, inclusion criteria were formulated and papers meeting the criteria were reviewed. The methodo...

Language assessment has a critical role in the clinical diagnosis of neurodegenerative diseases, in particular, in the case of Primary Progressive Aphasia (PPA). The current diagnostic criteria (Gorno-Tempini et al., 2011) identify three main variants on the basis of clinical features and patterns of brain atrophy. Widely accepted tools to diagnose, clinically classify, and follow up the heterogeneous language profiles of PPA are still lacking. In this study, we develop a screening battery, composed of nine tests (picture naming, word and sentence comprehension, word and sentence repetition, reading, semantic association, writing and picture description), following the recommendations of current diagnostic guidelines and taking into account recent research on the topic. All tasks were developed with consideration of the psycholinguistic factors that can affect performance, with the aim of achieving sensitivity to the language deficit to which each task was relevant, and to allow identification of the selective characteristic impairments of each PPA variant. Normative data on 134 Italian subjects pooled across homogeneous subgroups for age, sex, and education are reported. Although further work is still needed, this battery represents a first step towards a concise multilingual standard language examination, a fast and simple tool to help clinicians and researchers in the diagnosis of PPA.

Syntax is a species-specific component of human language combining a finite set of words in a potentially infinite number of sentences. Since words are by definition expressed by sound, factoring out syntactic information is normally impossible. Here, we circumvented this problem in a novel way by designing phrases with exactly the same acoustic content but different syntactic structures depending on the other words they occur with. By performing stereo- electroencephalographic (SEEG) recordings in epileptic patients we measured a different electrophysiological correlate of verb phrases vs. noun phrases by analyzing the high gamma band activity (150-300Hz frequency), in multiple cortical areas in both hemispheres, including language areas and their homologous in the non-dominant hemisphere. Our findings contribute to the ultimate goal of a complete neural decoding of linguistic structures from the brain.

Syntax is traditionally defined as a specifically human way to pair sound with meaning: words are assembled in a recursive way generating a potentially infinite set of sentences1,2. There can be different phrasal structures depending on the types of words involved, for example, “noun phrases” (NP), combining an article and a noun, vs. “verb phrases” (VP), combining a verb and a complement. Although it is known that the combination of an increasing number of words in sequences correlates with an increasing electrophysiological activity3,4, the specific electrophysiological correlates of the syntactic operation generating NPs vs. VPs remain unknown. A major confounding factor is the fact that syntactic information is inevitably intertwined with the acoustic information contained in words even during inner speech5. Here, we addressed this issue in a novel way by designing a paradigm to factor out acoustic information and isolate the syntactic component. In particular, we construed phrases that have exactly the same acoustic content but that are interpreted as NPs or VPs depending on their syntactic context (homophonous phrases). By performing stereo-electro-encephalographic (SEEG) recordings in epileptic patients6we show that VPs are associated with a higher activity in the high gamma band (150-300Hz frequency), an index of cortical activity associated with linguistic processing, with respect to NPs in multiple cortical areas in both hemispheres, including language areas and their homologous in the non-dominant hemisphere. Our findings pave the way to a deeper understanding of the electrophysiological mechanisms underlying syntax and contribute to the ultimate far reaching goal of a complete neural decoding of linguistic structures from the brain2.

The neural representation of abstract concepts is a current matter of debate. While social concepts have been associated to superior anterior temporal lobe (sATL), the neural correlates of quantity-related concepts have seldom been investigated. The right intraparietal sulcus (IPS) is known to be involved in the processing of numerical information and of quantifiers. In the present study, we investigated the causal role of right sATL and right IPS in representing social and quantity-related concepts, using a state-dependent transcranial magnetic stimulation (TMS)-priming paradigm. We modulated the neural activation by priming to a category label (either SOCIAL or QUANTITY), before applying TMS and presenting the target (i.e., an exemplar of one of the two abstract classes). When the target word belonged to the quantity category, TMS applied over the IPS (but not sATL) abolished the expected priming effect by speeding up reaction times (RTs) in incongruent trials. For the social category, both IPS and sATL stimulation abolished the priming effect, by reducing RTs in incongruent trials. Our results suggest a specialization of distinct brain areas in processing different classes of abstract concepts. The right IPS contains neuronal representations tuned to quantity-related concepts, in line with its well-known role in numerical and magnitude representation. Social concepts, in contrast, are represented in both the right sATL and the right IPS, known to be involved in social cognition and person-related knowledge.

During picture naming, the ease with which humans generate words is dependent upon the context in which they are named. For instances, naming previously presented items results in facilitation. Instead, naming a picture semantically related to previous items displays persistent interference effects (i.e., cumulative semantic interference, CSI). The neural correlates of CSI are still unclear and it is a matter of debate whether semantic control, or cognitive control more in general, is necessary for the resolution of CSI. We carried out an event-related fMRI experiment to assess the neural underpinnings of the CSI effect and the involvement and nature of semantic control. Both left inferior frontal gyrus (LIFG) and the left caudate nucleus (LCN) showed a linear increase of BOLD response positively associated with the consecutive number of presentations of semantically related pictures independently of task-load. The generalized psychophysiological interaction analysis showed that LIFG demonstrated a quantitative neural connectivity difference with the left supramarginal and angular gyri for increases of task-load and with the fusiform gyri for linear CSI increases. Furthermore, seed-to-voxel functional connectivity showed that LIFG activity coupled with different regions involved in cognitive control and lexicosemantic processing when semantic interference was elicited to a minimum or maximum degree. Our results are consistent with the lexical-competitive nature of the CSI effect, and we provide novel evidence that semantic control lies upon a more general cognitive control network (i.e., LIFG and LCN) responsible for resolving interference between competing semantically related items through connectivity with different brain areas in order to guarantee the correct response.

A progressive speech/language disorder, such as the non fluent/agrammatic variant of primary progressive aphasia and progressive apraxia of speech, can be due to neuropathologically verified Progressive Supranuclear Palsy (PSP). The prevalence of linguistic deficits and the linguistic profile in PSP patients who present primarily with a movement disorder is unknown. In the present study, we investigated speech and language performance in a sample of clinically diagnosed PSP patients using a comprehensive language battery, including, besides traditional language tests, a detailed analysis of connected speech (picture description task assessing 26 linguistic features). The aim was to identify the most affected linguistic levels in seventeen PSP with a movement disorder presentation, compared to 21 patients with Parkinson's disease and 27 healthy controls. Machine learning methods were used to detect the most relevant language tests and linguistic features characterizing the language profile of PSP patients. Our results indicate that even non-clinically aphasic PSP patients have subtle language deficits, in particular involving the lexical-semantic and discourse levels. Patients with the Richardson's syndrome showed a lower performance in the word comprehension task with respect to the other PSP phenotypes with predominant frontal presentation, parkinsonism and progressive gait freezing. The present findings support the usefulness of a detailed language assessment in all patients in the PSP spectrum.

Background: We evaluated the psychometric proprieties of the Screening for Aphasia in NeuroDegeneration (SAND) battery in Italian primary progressive aphasia (PPA) and movement disorder (MD) patients. Methods: The sample included 30 consecutive PPA and 45 MD patients who completed the SAND battery together with a clinical interview and a neurological/neuropsychological examination and 130 healthy controls (HC). Results: The SAND battery showed good internal consistency and good convergent and divergent validity. receiver operating characteristic analysis revealed an area under the curve of 0.978 for PPA versus HC and of 0.786 for PPA versus MD. A cutoff ≥3 gave a sensitivity of 0.933% and a specificity of 0.946% for discriminating PPA versus HC, whereas a cutoff ≥5 gave a sensitivity of 0.767% and a specificity of 0.667% for discriminating PPA versus MD. Conclusion: These results indicate that the SAND battery is an adequate, reliable, and valid diagnostic tool for PPA.

Amnestic mild cognitive impairment (aMCI) is a clinical condition characterized by memory impairment in the absence of any other cognitive impairment and is commonly associated with high conversion to Alzheimer's disease. Recent evidence shows that executive functions and selective attention mechanisms could also be impaired in aMCI. In this study, we investigated performance differences (i.e., reaction times [RTs] and accuracy) between a group of aMCI participants and a group of age-matched healthy individuals on the attentional network task (ANT) focusing on situations with increased interference. In particular, we assessed the relationship between interference and conflict effects and grey matter volumes (GMVs) of the anterior cingulate cortex (ACC)/pre-supplementary motor area in the entire sample because of its crucial role in conflict monitoring. When compared with controls, aMCI participants were less accurate on the ANT, showing increased interference and conflict effects, but no differences in RTs. In addition, aMCI participants exhibited lower GMV in the ACC than controls. While better accuracy for interference and conflict effects was associated with an increase of GMV in the ACC for both groups, RTs from the interference effect were negatively correlated with GMV of the ACC only in aMCI participants. In other words, lower GMV values of the ACC were paralleled with significantly impaired performance in terms of interference resolution. In conclusion, our study suggests the presence of a selective impairment in interference and conflict monitoring in aMCI, which in turn is associated with decreased GMVs in the ACC.

Language assessment has a crucial role in the clinical diagnosis of several neurodegenerative diseases. The analysis of extended speech production is a precious source of information encompassing the phonetic, phonological, lexico-semantic, morpho-syntactic, and pragmatic levels of language organization. The knowledge about the distinctive linguistic variables identifying language deficits associated to different neurodegenerative diseases has progressively improved in the last years. However, the heterogeneity of such variables and of the way they are measured and classified limits any generalization and makes the comparison among studies difficult. Here we present an exhaustive review of the studies focusing on the linguistic variables derived from the analysis of connected speech samples, with the aim of characterizing the language disorders of the most prevalent neurodegenerative diseases, including primary progressive aphasia, Alzheimer's disease, movement disorders, and amyotrophic lateral sclerosis. A total of 61 studies have been included, considering only those reporting group analysis and comparisons with a group of healthy persons. This review first analyzes the differences in the tasks used to elicit connected speech, namely picture description, story narration, and interview, considering the possible different contributions to the assessment of different linguistic domains. This is followed by an analysis of the terminologies and of the methods of measurements of the variables, indicating the need for harmonization and standardization. The final section reviews the linguistic domains affected by each different neurodegenerative disease, indicating the variables most consistently impaired at each level and suggesting the key variables helping in the differential diagnosis among diseases. While a large amount of valuable information is already available, the review highlights the need of further work, including the development of automated methods, to take advantage of the richness of connected speech analysis for both research and clinical purposes.

BackgroundProgressive Supranuclear Palsy (PSP) patients present language disturbances in tasks like naming, repetition, reading, word comprehension and semantic association compared to Parkinson's disease (PD) and healthy controls (HC).ObjectiveIn the present study we sought to validate a Screening for Aphasia in NeuroDegeneration (SAND) battery version specifically tailored on PSP patients and to describe language impairment in relation to PSP disease phenotype and cognitive status.Methods and resultsFifty-one PSP [23 with Richardson's syndrome (PSP-RS), 10 with predominant parkinsonism (PSP-P) and 18 with the other variant syndromes of PSP (vPSP)], 28 PD and 30 HC were enrolled in the present study. By excluding the tasks with poor acceptability (i.e., writing and picture description tasks) and increasing the items related to the remaining tasks, we showed that the PSP-tailored SAND Global Score is an acceptable, consistent and reliable tool to screen language disturbances in PSP. However, we failed to detect major differences in language involvement according to disease phenotype. Differently, we showed that patients with dementia present worse language performances.ConclusionsTaking into account specific disease features, the combination of the SAND subscores included in the PSP-tailored SAND better represents language abilities in PSP. Furthermore, we showed that language disturbances feature PSP patients irrespective of disease phenotype, but parallels the deterioration of the global cognitive function.

There is a growing interest in the use of functional imaging to assess brain activity in the absence of behavioural responses in patients with disorders of consciousness (DOC). In the present study, we applied a hierarchical auditory stimulation paradigm to functional magnetic resonance (fMRI) in a group of long-term DOC adult patients. Brain response to pairs of pseudowords, of unrelated words and of semantically related words, i.e. stimuli differing in lexical status (words vs. pseudowords) and semantic relatedness (related vs. unrelated) was assessed. The former contrast was considered to reflect the automatic brain response to the passive presentation of meaningful real words, while the latter aimed to assess the response to meaning relationships. The results of the study indicate that automatic lexical processing can be observed in minimally conscious state (MCS), but also in vegetative state/unresponsive wakefulness syndrome (VS/UWS) patients, as indicated by increase in blood oxygenation level dependent (BOLD) activity in the linguistic networks. DOC patients, for some task conditions, recruited additional areas in comparison to healthy participants. Furthermore this study provides additional evidence of the potential role of fMRI in the assessment of residual cognitive processing in some of these patients, which may not be evident at the clinical level.

International audience; During picture naming, the ease with which humans generate words is dependent upon the context in which they are named. For instances, naming previously presented items results in facilitation. Instead, naming a picture semantically related to previous items displays persistent interference effects (i.e., cumulative semantic interference, CSI). The neural correlates of CSI are still unclear and it is a matter of debate whether semantic control, or cognitive control more in general, is necessary for the resolution of CSI. We carried out an event-related fMRI experiment to assess the neural underpinnings of the CSI effect and the involvement and nature of semantic control. Both left inferior frontal gyrus (LIFG) and the left caudate nucleus (LCN) showed a linear increase of BOLD response positively associated with the consecutive number of presentations of semantically related pictures independently of task-load. The generalized psychophysiological interaction analysis showed that LIFG demonstrated a quantitative neural connectivity difference with the left supramarginal and angular gyri for increases of task-load and with the fusiform gyri for linear CSI increases. Furthermore, seed-to-voxel functional connectivity showed that LIFG activity coupled with different regions involved in cognitive control and lexicosemantic processing when semantic interference was elicited to a minimum or maximum degree. Our results are consistent with the lexical-competitive nature of the CSI effect, and we provide novel evidence that semantic control lies upon a more general cognitive control network (i.e., LIFG and LCN) responsible for resolving interference between competing semantically related items through connectivity with different brain areas in order to guarantee the correct response.

We report the construction and standardization of a new comprehensive battery of tests for the assessment of semantic memory disorders. The battery is constructed on a common set of 48 stimuli, belonging to both living and non-living categories, rigidly controlled for several confounding variables, and is based on an empirically derived corpus of semantic features. It includes six tasks, in order to assess semantic memory through different modalities of input and output: two naming tasks, one with colored pictures and the other in response to an oral description, a word-picture matching task, a picture sorting task, a free generation of features task and a sentence verification task. Normative data on 106 Italian subjects pooled across homogenous subgroups for age, sex and education are reported. The new battery allows an in-depth investigation of category-specific disorders and of progressive semantic memory deficits at features level, overcoming some of the limitations of existing tests.

The presence of episodic memory impairment is required for the diagnosis of Alzheimer's dementia by all current diagnostic criteria. The new research criteria proposed by Dubois et al. (Lancet Neurol 6:734-746, 2007) require that the impairment should not improve significantly with cueing, recognition testing nor after the control of effective encoding. This is considered to be the core deficit of "prodromal Alzheimer's disease". The Free and Cued Selective Reminding Test (FCSRT) is a memory test that allows in assessing these specific features of memory impairment. Here, we report normative data for an Italian version of the FCSRT. The test is based on the 12 pictorial stimuli, 6 belonging to the living domain, and 6 to the non-living domain. Six scores were derived from the performance of 227 healthy Italian adults, with age, sex and education homogenously distributed across subgroups: immediate free recall (IFR), immediate total recall (ITR), delayed-free recall (DFR), delayed total recall (DTR), Index of Sensitivity of Cueing (ISC), number of intrusions. In multiple regression analyses, age emerged as an influencing factor for both IFR and DFR, with older people obtaining lower scores. Education and gender appear to influence only IFR, with better performance by more educated subjects and females. Adjusted scores were used to determine inferential cutoff scores and to compute equivalent scores.

Recent activation studies have suggested different neural correlates for processing concrete and abstract words. However, the precise localization is far from being defined. One reason for the heterogeneity of these results could lie in the extreme variability of experimental paradigms, ranging from explicit semantic judgments to lexical decision tasks (auditory and/or visual). The present study explored the processing of abstract/concrete nouns by using repetitive Transcranial Magnetic Stimulation (rTMS) and a lexical decision paradigm in neurologically-unimpaired subjects. Four sites were investigated: left inferior frontal, bilaterally posterior-superior temporal and left posterior-inferior parietal. An interference on accuracy was found for abstract words when rTMS was applied over the left temporal site, while for concrete words accuracy decreased when rTMS was applied over the right temporal site. Accuracy for abstract words, but not for concrete words, decreased after frontal stimulation as compared to the sham condition. These results suggest that abstract lexical entries are stored in the posterior part of the left temporal superior gyrus and possibly in the left frontal inferior gyrus, while the regions involved in storing concrete items include the right temporal cortex. It cannot be excluded, however, that additional areas, not tested in this experiment, are involved in processing both, concrete and abstract nouns. © 2008 Elsevier B.V. All rights reserved.

The organization and representation of conceptual knowledge in the brain remains a controversial issue in terms of both neuropsychological and imaging evidence. We report the results of a functional magnetic resonance study in which the role of the most debated dimensions (domain and feature type) was evaluated through a concept-feature verification task. The scope of the task was to eliminate serious methodological concerns that weighed down previous imaging research in this area, and to allow more definitive conclusions regarding the specific contribution of these dimensions. The results show differential patterns of brain activity according to feature type (both motion and visual form/surface features) but not according to concept domain (living vs. nonliving things). These findings are in accord with a modality-specific account of conceptual knowledge organization in the brain, in which specific kinds of features (e.g. form, color, motion, etc) have differential importance for representing different concepts.

The Strong consensus recommendations (2009) propose behavioural (ALSbi) and/or dysexecutive (ALSci) impairment as the two main clinical profiles of non-motor manifestations in non-demented amyotrophic lateral sclerosis (ALS) patients. We aimed at assessing whether clustering pattern of neuropsychological performance of ALS patients suggest the existence of additional clinical syndromes beyond the currently recognized phenotypes. We applied principal component analysis (PCA) to a comprehensive neuropsychological evaluation of 71 non-demented ALS patients in order to identify clusters of variables correlating highly with each other, with the aim of detecting distinct patterns of neuropsychological test performance. The outcome of PCA demonstrated the existence of three main test clusters. Two, accounting for 27% of the patients, were compatible with the recognised ALSbi and ALSci profiles. An additional third cluster loaded on social cognition, language and memory tests and accounted for 24% of the patients. Of these, 15% had defective performance on at least two tests belonging to the latter non-executive cluster, and were thus unclassifiable according to current criteria. Our data-driven approach indicated a third dimension of cognitive impairment, including language, social cognition and episodic memory, as a distinct pattern of non-motor manifestations in ALS patients, in addition to the recognized ALSci and ALSbi profiles.

Naming abilities are typically preserved in amnestic Mild Cognitive Impairment (aMCI), a condition associated with increased risk of progression to Alzheimer's disease (AD). We compared the functional correlates of covert picture naming and word reading between a group of aMCI subjects and matched controls. Unimpaired picture naming performance was associated with more extensive activations, in particular involving the parietal lobes, in the aMCI group. In addition, in the condition associated with higher processing demands (blocks of categorically homogeneous items, living items), increased activity was observed in the aMCI group, in particular in the left fusiform gyrus. Graph analysis provided further evidence of increased modularity and reduced integration for the homogenous sets in the aMCI group. The functional modifications associated with preserved performance may reflect, in the case of more demanding tasks, compensatory mechanisms for the subclinical involvement of semantic processing areas by AD pathology.

Naming abilities are typically preserved in amnestic Mild Cognitive Impairment (aMCI), a condition associated with increased risk of progression to Alzheimer's disease (AD). We compared the functional correlates of covert picture naming and word reading between a group of aMCI subjects and matched controls. Unimpaired picture naming performance was associated with more extensive activations, in particular involving the parietal lobes, in the aMCI group. In addition, in the condition associated with higher processing demands (blocks of categorically homogeneous items, living items), increased activity was observed in the aMCI group, in particular in the left fusiform gyrus. Graph analysis provided further evidence of increased modularity and reduced integration for the homogenous sets in the aMCI group. The functional modifications associated with preserved performance may reflect, in the case of more demanding tasks, compensatory mechanisms for the subclinical involvement of semantic processing areas by AD pathology.