Cortical morphology in patients with the deficit and non-deficit syndrome of schizophrenia: a worldwide meta- and mega-analyses.

Converging evidence suggests that schizophrenia (SZ) with primary, enduring negative symptoms (i.e., Deficit SZ (DSZ)) represents a distinct entity within the SZ spectrum while the neurobiological underpinnings remain undetermined. In the largest dataset of DSZ and Non-Deficit (NDSZ), we conducted a meta-analysis of data from 1560 individuals (168 DSZ, 373 NDSZ, 1019 Healthy Controls (HC)) and a mega-analysis of a subsampled data from 944 individuals (115 DSZ, 254 NDSZ, 575 HC) collected across 9 worldwide research centers of the ENIGMA SZ Working Group (8 in the mega-analysis), to clarify whether they differ in terms of cortical morphology. In the meta-analysis, sites computed effect sizes for differences in cortical thickness and surface area between SZ and control groups using a harmonized pipeline. In the mega-analysis, cortical values of individuals with schizophrenia and control participants were analyzed across sites using mixed-model ANCOVAs. The meta-analysis of cortical thickness showed a converging pattern of widespread thinner cortex in fronto-parietal regions of the left hemisphere in both DSZ and NDSZ, when compared to HC. However, DSZ have more pronounced thickness abnormalities than NDSZ, mostly involving the right fronto-parietal cortices. As for surface area, NDSZ showed differences in fronto-parietal-temporo-occipital cortices as compared to HC, and in temporo-occipital cortices as compared to DSZ. Although DSZ and NDSZ show widespread overlapping regions of thinner cortex as compared to HC, cortical thinning seems to better typify DSZ, being more extensive and bilateral, while surface area alterations are more evident in NDSZ. Our findings demonstrate for the first time that DSZ and NDSZ are characterized by different neuroimaging phenotypes, supporting a nosological distinction between DSZ and NDSZ and point toward the separate disease hypothesis.

The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium.

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen's d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen's d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.

A meta-analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium.

Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.

Individual differences among older adults with mild and moderate dementia in social and emotional loneliness and their associations with cognitive and psychological functioning.

BACKGROUND: Loneliness is a major health issue among older adults. The aim of this study was to assess the relationship between loneliness, in its social and emotional facets, and the cognitive (language), and behavioral/psychological functioning as well as quality of life (QoL) in people with mild and moderate dementia, i.e., considering dementia severity as an individual characteristic. METHODS: This cross-sectional study involved 58 people with mild dementia and 55 people with moderate dementia. Participants completed the Social and Emotional Loneliness scale, along with measures assessing their language skills, the frequency and severity of their behavioral and psychological symptoms, and their QoL. RESULTS: Socio-demographic characteristics and depression, but not loneliness or its social and emotional facets, contributed to explain participants' behavioral and psychological symptoms, regardless of dementia severity. Loneliness explained, though to a small extent (8% of variance), language skills in people with moderate dementia, with social loneliness only accounting for language skills (18% of variance) in this group. Loneliness also modestly accounted for dysphoria symptoms in both the mildly and moderately impaired (6% and 5% of variance, respectively) individuals with social loneliness predicting dysphoric mood in the former group only (7% of variance). Loneliness also explained, to a larger extent, QoL in both the mildly impaired and moderately impaired individuals (27% and 20% of variance, respectively), its social facet predicting QoL in the mildly impaired (30% of variance), and its emotional facet in the moderately impaired (21% of variance) group. CONCLUSION: These findings suggest that loneliness and its facets have a clear impact on perceived QoL, and influence the language skills and dysphoria symptoms of people with dementia, to a degree that depends on dementia severity. The assessment of loneliness and its facets in people with dementia considering dementia severity, and the promotion of social inclusion to reduce it should be considered by professionals.

Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium.

Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions.

Sense of external agency is sustained by multisensory functional integration in the somatosensory cortex.

"Sense of agency" (SoA), the feeling of control for events caused by one's own actions, is deceived by visuomotor incongruence. Sensorimotor networks are implicated in SoA, however little evidence exists on brain functionality during agency processing. Concurrently, it has been suggested that the brain's intrinsic resting-state (rs) activity has a preliminary influence on processing of agency cues. Here, we investigated the relation between performance in an agency attribution task and functional interactions among brain regions as derived by network analysis of rs functional magnetic resonance imaging. The action-effect delay was adaptively increased (range 90-1,620 ms) and behavioral measures correlated to indices of cognitive processes and appraised self-concepts. They were then regressed on local metrics of rs brain functional connectivity as to isolate the core areas enabling self-agency. Across subjects, the time window for self-agency was 90-625 ms, while the action-effect integration was impacted by self-evaluated personality traits. Neurally, the brain intrinsic organization sustaining consistency in self-agency attribution was characterized by high connectiveness in the secondary visual cortex, and regional segregation in the primary somatosensory area. Decreased connectiveness in the secondary visual area, regional segregation in the superior parietal lobule, and information control within a primary visual cortex-frontal eye fields network sustained self-agency over long-delayed effects. We thus demonstrate that self-agency is grounded on the intrinsic mode of brain function designed to organize information for visuomotor integration. Our observation is relevant for current models of psychopathology in clinical conditions in which both rs activity and sense of agency are altered.

Measuring global functioning in older adults with cognitive impairments using the Rasch model.

BACKGROUND: Cognitive and functional measures are often measured and interpreted separately during the clinical evaluation of patients with cognitive impairment. This can sometimes lead to a challenging interpretation when measures do not show concordance, especially after a clinical intervention. In this study, the development and evaluation of a new approach, using the Rasch model, that combines cognitive and functional measures in one single and more powerful measure (compared to stand-alone tests) to assess global functioning in older adults with cognitive impairment (including dementia) was presented. METHODS: Clinical data from 265 older adults' subjects diagnosed with mild cognitive impairment, or dementia, included: The Mini-mental state examination (MMSE), the Esame Neuropsicologico Breve (ENB) - a neuropsychological battery used in Italy-, the Activities of Daily Living (ADL), and the Instrumental Activities of Daily Living (IADL) questionnaires. RESULTS: Patients with severe cognitive impairment showed lower global functioning score compared to patients with moderate impairment. Receiver Operating Characteristic (ROC) curve analyses were performed to determine sensitivity and specificity of the global functioning score resulting from the combined measure. Results showed that the global functioning score discriminates better between patients with severe and moderate cognitive impairment compared to the ENB, ADL, and IADL when considered separately. CONCLUSIONS: The Rasch model was able to combine cognitive and functional measures into a single score (global functioning score). All together, these results suggest that the diverse cognitive and functional measures can be considered part of one single dimension (global functioning) and that this dimension can be measured as a single construct and score. This study offers an alternative perspective for future development of instruments that would help clinicians in measuring global functioning in older adults' patients at different stages of cognitive impairments and different baseline level of performance.

Cognitive stimulation therapy in the Italian context: its efficacy in cognitive and non-cognitive measures in older adults with dementia.

OBJECTIVE: Cognitive stimulation therapy (CST) has been shown to have significant benefits in enhancing cognitive functioning and improving the quality of life of people with mild to moderate dementia. The present study examines the efficacy of the Italian version of the therapy (CST-IT). METHODS: Older adults with mild to moderate dementia (n = 39) were randomly assigned to two programs: one group participated in the CST-IT, consisting of 14 sessions (twice a week for 7 weeks) and the active control group took part in alternative general activities. The outcome measures were cognitive functioning (measured by the Mini-Mental State Examination-MMSE-, the Alzheimer's Disease Assessment scale-cognitive subscale, the backward digit span test, and a narrative language test); quality of life (Quality of life--Alzheimer's Disease scale); mood (Cornell scale for depression in dementia and the social and emotional loneliness scale); functional activities in daily living (Disability Assessment for Dementia); and behavior (neuropsychiatric inventory). RESULTS: After the intervention, only the CST-IT group maintained its MMSE score, while the control group displayed deterioration. The CST-IT group also performed better in some of the cognitive measures (Alzheimer's Disease Assessment Scale-Cognitive subscale and narrative language), mood measures (Cornell scale, social and emotional loneliness scale with a decrease in reported loneliness), and the Quality of life--Alzheimer's Disease scale. No other treatment effect was observed. CONCLUSIONS: The findings confirm the efficacy, at least in the short term, of the CST in sustaining cognitive functions and perceived quality of life in older adults with dementia in the Italian care setting as well.

Performance-based everyday functional competence measures across the adult lifespan: the role of cognitive abilities.

BACKGROUND: The effects of age on the ability to manage everyday functioning, crucial to ensure a healthy aging process, have been rarely examined and when, self-report measures have been used. The aim of the present study was to examine age effects across the adult lifespan in everyday functioning with two performance-based measures: the Everyday Problems Test (EPT), and the Timed Instrumental Activities of Daily Living (TIADL) tasks. The role of some crucial cognitive abilities, i.e. working memory (WM), processing speed, reasoning, vocabulary, and text comprehension in the EPT and the TIADL were also assessed to see whether or not they have a similar influence (and to what extent) in accounting for age-related effects in these two performance-based measures. METHOD: Two hundred and seventy-six healthy participants, from 40 to 89 years of age were presented with the EPT, the TIADL, as well as WM, processing speed, reasoning, text comprehension, and vocabulary tasks. RESULTS: Path models indicated an indirect effect of age and education on the EPT, which was mediated by all the cognitive variables considered, with WM and reasoning being the strongest predictors of performance. An indirect quadratic effect of age, but not of education, was found on the TIADL score, and an accelerated decline in processing speed mediated the relationship between age and the TIADL score. CONCLUSION: This study revealed age-related effects in performance-based measures, which are mediated by different cognitive abilities depending on the measure considered. The findings highlight the importance of assessing everyday functioning even in healthy older adults.

Finding my own way: an fMRI single case study of a subject with developmental topographical disorientation.

Developmental topographical disorientation (DTD) causes impaired spatial orientation and navigation from early childhood with no evidence of cerebral damage. Using fMRI and a landmark sequencing task, we investigated the hypothesis that Dr Wai's abnormal cerebral activation pattern was related to his peculiar behavioral profile. Although Dr Wai was able to correctly perform landmark sequencing, he showed a lack of activity in regions activated in all control subjects and activity in areas that were not activated in any control subject. These results are discussed in light of cognitive and functional model of navigation, with relevant implications for DTD physiology.

The structural neuroanatomy of metacognitive insight in schizophrenia and its psychopathological and neuropsychological correlates.

Lack of insight into illness is a multidimensional phenomenon that has relevant implications on clinical course and therapy compliance. Here, we focused on metacognitive insight in schizophrenia, that is, the ability to monitor one's changes in state of mind and sensations, with the aim of investigating its neuroanatomical, psychopathological, and neuropsychological correlates. Fifty-seven consecutive patients with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) diagnosis of schizophrenia were administered the Insight Scale, and comprehensive psychopathological and neuropsychological batteries. They underwent a high-resolution T1-weighted magnetic resonance imaging investigation. Gray matter (GM) and white matter (WM) volumes were analyzed on a voxel-by-voxel basis using Statistical Parametric Mapping 8. Reduced metacognitive insight was related to reduced GM volumes in the left ventrolateral prefrontal cortex, right dorsolateral prefrontal cortex and insula, and bilateral premotor area and putamen. Further, it was related to reduced WM volumes of the right superior longitudinal fasciculum, left corona radiata, left forceps minor, and bilateral cingulum. Increased metacognitive insight was related to increased depression severity and attentional control impairment, while the latter was related to increased GM volumes in brain areas linked to metacognitive insight. Results of this study suggest that prefrontal GM and WM bundles, all implied in cognitive control and self-reflection, may be the neuroanatomical correlates of metacognitive insight in schizophrenia. Further, higher metacognitive insight is hypothesized to be a risk factor for depression which may subsequently impair attention. This line of research may provide the basis for the development of cognitive interventions aimed at improving self-monitoring and compliance to treatment.

Reliability of clinical judgment for evaluation of informed consent in mental health settings and the validation of the Evaluation of Informed Consent to Treatment (EICT) scale.

Introduction: The competence assessment to give informed consent in the legal and healthcare settings is often performed merely through clinical judgment. Given the acknowledged limited reliability of clinician-based evaluation in the mental health sector, particularly for the assessment of competence to consent, our objective was to ascertain the dependability of clinical judgment when evaluating the ability of schizophrenia patients to make choices about their health. Methods: The potential convergence between clinical evaluation and scores from a new standardized assessment (the "Evaluation of Informed Consent to Treatment" - "EICT" scale) was therefore tested. The scale assesses four dimensions of competence, specifically how patients normally understand information relating to care (Understanding); how they evaluate the choice of treatment in terms of risk/benefit ratio (Evaluating); how they reason coherently in the decision-making process (Reasoning); and, finally, their ability to make a choice between treatment alternatives (Expressing a choice). Thirty-four outpatients with schizophrenia were evaluated for their competence to consent by five referring clinicians with different backgrounds (psychiatrist, forensic psychiatrist, geriatrician, anesthetist, and medico-legal doctor). Inter-raters variability was tested through correlation analyses between the scores obtained by the clinicians on a modified version of the Global Assessment of Functioning scale (GAF) designed specifically to subjectively assess functioning in each of the four competence dimensions. Two validated competence scales (Mac-CAT-T, SICIATRI-R), and a neuropsychological battery were also administered along with scales for evaluating neuropsychiatric symptoms severity and side effects of medication. Results: Clinical judgments of the individual specialists showed great inter-rater variability. Likewise, only weak/non-significant correlations were found between the EICT subscales and the respective clinicians-rated GAF scales. Conversely, solid correlations were found between the EICT and MacCAT-T subscales. As expected, healthy controls performed better in the ability to give informed consent to treatment, as measured by the three scales (i.e., EICT, MacCAT-T, and SICIATRI-R), and neuropsychological test performance. In the comparisons between patients who, according to the administered EICT, were able or not able to give informed consent to treatment, significant differences emerged for the Phonemic verbal fluency task (p = 0.038), Verbal judgments (p = 0.048), MacCAT-T subscales, and SICIATRI-R total score. Moreover, EICT exhibited excellent internal consistency (Cronbach's alphas ranging from 0.96 to 0.98 for the four subscales) while the Item Analysis, by measuring the correlation between each item of the EICT and the total score, was excellent for all items of all subscales (alphas ranging from 0.86 to 0.98). Discussion: In conclusion, our findings highlighted that the assessment of competence exclusively through clinical judgment is not fully reliable and needs the support of standardized tools. The EICT scale could therefore be useful in assessing general competence to consent both in healthcare and legal contexts, where it might be necessary to evaluate the effective competence of patients with psychiatric disorders. Finally, this scale could serve as a valuable tool for decisions regarding whether and to what extent a patient needs support.

Medical Information Extraction With NLP-Powered QABots: A Real-World Scenario.

The advent of computerized medical recording systems in healthcare facilities has made data retrieval tasks easier, compared to manual recording. Nevertheless, the potential of the information contained within medical records remains largely untapped, mostly due to the time and effort required to extract data from unstructured documents. Natural Language Processing (NLP) represents a promising solution to this challenge, as it enables the use of automated text-mining tools for clinical practitioners. In this work, we present the architecture of the Virtual Dementia Institute (IVD), a consortium of sixteen Italian hospitals, using the NLP Extraction and Management Tool (NEMT), a (semi-) automated end-to-end pipeline that extracts relevant information from clinical documents and stores it in a centralized REDCap database. After defining a common Case Report Form (CRF) across the IVD hospitals, we implemented NEMT, the core of which is a Question Answering Bot (QABot) based on a modern NLP model. This QABot is fine-tuned on thousands of examples from IVD centers. Detailed descriptions of the process to define a common minimum dataset, Inter-Annotator Agreement calculated on clinical documents, and NEMT results are provided. The best QABot performance show an Exact Match score (EM) of 78.1%, a F1-score of 84.7%, a Lenient Accuracy (LAcc) of 0.834, and a Mean Reciprocal Rank (MRR) of 0.810. EM and F1 scores outperform the same metrics obtained with ChatGPTv3.5 (68.9% and 52.5%, respectively). With NEMT the IVD has been able to populate a database that will contain data from thousands of Italian patients, all screened with the same procedure. NEMT represents an efficient tool that paves the way for medical information extraction and exploitation for new research studies.

Clinical validity of the Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB) in Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: The identification and staging of Alzheimer's Disease (AD) represent a challenge, especially in the prodromal stage of Mild Cognitive Impairment (MCI), when cognitive changes can be subtle. Worldwide efforts were dedicated to select and harmonize available neuropsychological instruments. In Italy, the Italian Network of Neuroscience and Neuro-Rehabilitation has promoted the adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB), collecting normative data from 433 healthy controls (HC). Here, we aimed to explore the ability of I-UDSNB to differentiate between a) MCI and HC, b) AD and HC, c) MCI and AD. METHODS: One hundred thirty-seven patients (65 MCI, 72 AD) diagnosed after clinical-neuropsychological assessment, and 137 HC were included. We compared the I-UDSNB scores between a) MCI and HC, b) AD and HC, c) MCI and AD, with t-tests. To identify the test(s) most capable of differentiating between groups, significant scores were entered in binary logistic and in stepwise regressions, and then in Receiver Operating Characteristic curve analyses. RESULTS: Two episodic memory tests (Craft Story and Five Words test) differentiated MCI from HC subjects; Five Words test, Semantic Fluency (vegetables), and TMT-part B differentiated AD from, respectively, HC and MCI. CONCLUSIONS: Our findings indicate that the I-UDSNB is a suitable tool for the harmonized and concise assessment of patients with cognitive decline, showing high sensitivity and specificity for the diagnosis of MCI and AD.

A worldwide study of white matter microstructural alterations in people living with Parkinson's disease.

The progression of Parkinson's disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts worldwide, to identify stage-specific profiles of white matter differences. Diffusion-weighted MRI data from 1654 participants diagnosed with PD (age: 20-89 years; 33% female) and 885 controls (age: 19-84 years; 47% female) were analyzed using the ENIGMA-DTI protocol to evaluate white matter microstructure. Skeletonized maps of fractional anisotropy (FA) and mean diffusivity (MD) were compared across Hoehn and Yahr (HY) disease groups and controls to reveal the profile of white matter alterations at different stages. We found an enhanced, more widespread pattern of microstructural alterations with each stage of PD, with eventually lower FA and higher MD in almost all regions of interest: Cohen's d effect sizes reached d = -1.01 for FA differences in the fornix at PD HY Stage 4/5. The early PD signature in HY stage 1 included higher FA and lower MD across the entire white matter skeleton, in a direction opposite to that typical of other neurodegenerative diseases. FA and MD were associated with motor and non-motor clinical dysfunction. While overridden by degenerative changes in the later stages of PD, early PD is associated with paradoxically higher FA and lower MD in PD, consistent with early compensatory changes associated with the disorder.

Narrative discourse production in Parkinson's disease: Decoupling the role of cognitive-linguistic and motor speech changes.

Introduction: the interplay between neuropsychological and communicative abilities in Parkinson's disease (PD) has been relatively overlooked, and it is not entirely understood which difficulties are consequent to impaired motor control, and which have a linguistic/cognitive basis. Here, we examined narrative discourse in PD using a multi-level analysis procedure considering sentence-level (productivity, lexical-grammatical processing) and discourse-level processes (narrative organization, informativeness), and partialling out patients' motor speech impairments. The interaction between cognitive (i.e. linguistic and executive) and communication abilities was also investigated. Methods: Twenty-nine PD subjects in the mild stage of the disease were compared to 29 matched healthy comparators (HC) on quantitative measures of narrative discourse derived from two picture description tasks. Multivariate (considering articulation rate and educational attainment as covariates) and univariate (with group membership as independent variable) analyses of variance were conducted on separate linguistic domains. The contribution of executive/linguistic abilities to PD's narrative performance was explored by multiple regression analyses on narrative measures significantly differentiating patients from HC. Results: significant reductions in patients were observed on measures of productivity (less well-formed words, shorter sentences) and informativeness (fewer conceptual units, less informative elements, lower number of details) and these alterations were explained by variations in linguistic abilities (action and object naming) rather than executive abilities. Articulation rate and educational attainment did not impact the observed reduced productivity and under-informativeness. Conclusion: referential narrative discourse is altered in PD, regardless of motor impairments in speech production. The observed reductions in productivity/informativeness aspects of narratives were related to naming abilities and in particular to verbs processing, consistently with the neurocognitive model of motor language coupling. Since narratives are amenable to recurrent and automated analysis for the identification of linguistic patterns potentially anticipating the development of PD and the onset of cognitive deterioration, discourse abilities should be quantitatively and repeatedly profiled in the disorder.

Brain Network Topology in Deficit and Non-Deficit Schizophrenia: Application of Graph Theory to Local and Global Indices.

Patients with deficit schizophrenia (SZD) suffer from primary and enduring negative symptoms. Limited pieces of evidence and neuroimaging studies indicate they differ from patients with non-deficit schizophrenia (SZND) in neurobiological aspects, but the results are far from conclusive. We applied for the first time, graph theory analyses to discriminate local and global indices of brain network topology in SZD and SZND patients compared with healthy controls (HC). High-resolution T1-weighted images were acquired for 21 SZD patients, 21 SZND patients, and 21 HC to measure cortical thickness from 68 brain regions. Graph-based metrics (i.e., centrality, segregation, and integration) were computed and compared among groups, at both global and regional networks. When compared to HC, at the regional level, SZND were characterized by temporoparietal segregation and integration differences, while SZD showed widespread alterations in all network measures. SZD also showed less segregated network topology at the global level in comparison to HC. SZD and SZND differed in terms of centrality and integration measures in nodes belonging to the left temporoparietal cortex and to the limbic system. SZD is characterized by topological features in the network architecture of brain regions involved in negative symptomatology. Such results help to better define the neurobiology of SZD (SZD: Deficit Schizophrenia; SZND: Non-Deficit Schizophrenia; SZ: Schizophrenia; HC: healthy controls; CC: clustering coefficient; L: characteristic path length; E: efficiency; D: degree; CCnode: CC of a node; CCglob: the global CC of the network; Eloc: efficiency of the information transfer flow either within segregated subgraphs or neighborhoods nodes; Eglob: efficiency of the information transfer flow among the global network; FDA: Functional Data Analysis; and Dmin: estimated minimum densities).

Estimating multimodal brain variability in schizophrenia spectrum disorders: A worldwide ENIGMA study.

Objective: Schizophrenia is a multifaceted disorder associated with structural brain heterogeneity. Despite its relevance for identifying illness subtypes and informative biomarkers, structural brain heterogeneity in schizophrenia remains incompletely understood. Therefore, the objective of this study was to provide a comprehensive insight into the structural brain heterogeneity associated with schizophrenia. Methods: This meta- and mega-analysis investigated the variability of multimodal structural brain measures of white and gray matter in individuals with schizophrenia versus healthy controls. Using the ENIGMA dataset of MRI-based brain measures from 22 international sites with up to 6139 individuals for a given brain measure, we examined variability in cortical thickness, surface area, folding index, subcortical volume and fractional anisotropy. Results: We found that individuals with schizophrenia are distinguished by higher heterogeneity in the frontotemporal network with regard to multimodal structural measures. Moreover, individuals with schizophrenia showed higher homogeneity of the folding index, especially in the left parahippocampal region. Conclusions: Higher multimodal heterogeneity in frontotemporal regions potentially implies different subtypes of schizophrenia that converge on impaired frontotemporal interaction as a core feature of the disorder. Conversely, more homogeneous folding patterns in the left parahippocampal region might signify a consistent characteristic of schizophrenia shared across subtypes. These findings underscore the importance of structural brain variability in advancing our neurobiological understanding of schizophrenia, and aid in identifying illness subtypes as well as informative biomarkers.

Preoperative Navigated Transcranial Magnetic Stimulation: New Insight for Brain Tumor-Related Language Mapping.

Preoperative brain mapping methods are particularly important in modern neuro-oncology when a tumor affects eloquent language areas since damage to parts of the language circuits can cause significant impairments in daily life. This narrative review examines the literature regarding preoperative and intraoperative language mapping using repetitive navigated transcranial magnetic stimulation (rnTMS) with or without direct electrical stimulation (DES) in adult patients with tumors in eloquent language areas. The literature shows that rnTMS is accurate in detecting preexisting language disorders and positive intraoperative mapping regions. In terms of the region extent and clinical outcomes, rnTMS has been shown to be accurate in identifying positive sites to guide resection, reducing surgery duration and craniotomy size and thus improving clinical outcomes. Before incorporating rnTMS into the neurosurgical workflow, the refinement of protocols and a consensus within the neuro-oncology community are required.