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.

The Role of the Anterior Thalamic Nuclei in the Genesis of Memory Disorders in Alzheimer's Disease: An Exploratory Study.

BACKGROUND: Increasing evidence is demonstrating that degeneration of specific thalamic nuclei, in addition to the hippocampus, may occur in Alzheimer's disease (AD) from the prodromal stage (mild cognitive impairment - MCI) and contribute to memory impairment. OBJECTIVE: Here, we evaluated the presence of macro and micro structural alterations at the level of the anterior thalamic nuclei (ATN) and medio-dorsal thalamic nuclei (MDTN) in AD and amnestic MCI (aMCI) and the possible relationship between such changes and the severity of memory impairment. METHODS: For this purpose, a sample of 50 patients with aMCI, 50 with AD, and 50 age- and education-matched healthy controls (HC) were submitted to a 3-T MRI protocol with whole-brain T1-weighted and diffusion tensor imaging and a comprehensive neuropsychological assessment. RESULTS: At macro-structural level, both the ATN and MDTN were found significantly smaller in patients with aMCI and AD when compared to HC subjects. At micro-structural level, instead, diffusion alterations that significantly differentiated aMCI and AD patients from HC subjects were found only in the ATN, but not in the MDTN. Moreover, diffusion values of the ATN were significantly associated with poor episodic memory in the overall patients' group. CONCLUSIONS: These findings represent the first in vivo evidence of a relevant involvement of ATN in the AD-related neurodegeneration and memory profile and strengthen the importance to look beyond the hippocampus when considering neurological conditions characterized by memory decline.

Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study.

INTRODUCTION: Regional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool. METHODS: 15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the standardized ENIGMA-VBM tool. Statistical parametric T-maps were generated from each cohort and meta-analyzed to reveal voxel-wise differences between EOP and healthy controls as well as the individual-based association between GM volume and age of onset, chlorpromazine (CPZ) equivalent dose, and other clinical variables. RESULTS: Compared with healthy controls, individuals with EOP showed widespread lower GM volume encompassing most of the cortex, with the most marked effect in the left median cingulate (Hedges' g = 0.55, p = 0.001 corrected), as well as small clusters of lower white matter (WM), whereas no regional GM or WM volumes were higher in EOP. Lower GM volume in the cerebellum, thalamus and left inferior parietal gyrus was associated with older age of onset. Deficits in GM in the left inferior frontal gyrus, right insula, right precentral gyrus and right superior frontal gyrus were also associated with higher CPZ equivalent doses. CONCLUSION: EOP is associated with widespread reductions in cortical GM volume, while WM is affected to a smaller extent. GM volume alterations are associated with age of onset and CPZ equivalent dose but these effects are small compared to case-control differences. Mapping anatomical abnormalities in EOP may lead to a better understanding of the role of psychosis in brain development during childhood and adolescence.

Cerebellar Volume and Disease Staging in Parkinson's Disease: An ENIGMA-PD Study.

BACKGROUND: Increasing evidence points to a pathophysiological role for the cerebellum in Parkinson's disease (PD). However, regional cerebellar changes associated with motor and non-motor functioning remain to be elucidated. OBJECTIVE: To quantify cross-sectional regional cerebellar lobule volumes using three dimensional T1-weighted anatomical brain magnetic resonance imaging from the global ENIGMA-PD working group. METHODS: Cerebellar parcellation was performed using a deep learning-based approach from 2487 people with PD and 1212 age and sex-matched controls across 22 sites. Linear mixed effects models compared total and regional cerebellar volume in people with PD at each Hoehn and Yahr (HY) disease stage, to an age- and sex- matched control group. Associations with motor symptom severity and Montreal Cognitive Assessment scores were investigated. RESULTS: Overall, people with PD had a regionally smaller posterior lobe (dmax = -0.15). HY stage-specific analyses revealed a larger anterior lobule V bilaterally (dmax = 0.28) in people with PD in HY stage 1 compared to controls. In contrast, smaller bilateral lobule VII volume in the posterior lobe was observed in HY stages 3, 4, and 5 (dmax = -0.76), which was incrementally lower with higher disease stage. Within PD, cognitively impaired individuals had lower total cerebellar volume compared to cognitively normal individuals (d = -0.17). CONCLUSIONS: We provide evidence of a dissociation between anterior "motor" lobe and posterior "non-motor" lobe cerebellar regions in PD. Whereas less severe stages of the disease are associated with larger motor lobe regions, more severe stages of the disease are marked by smaller non-motor regions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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.

Schizophrenia and Glutathione: A Challenging Story.

Schizophrenia (SZ) is a devastating mental illness with a complex and heterogeneous clinical state. Several conditions like symptoms, stage and severity of the disease are only some of the variables that have to be considered to define the disorder and its phenotypes. SZ pathophysiology is still unclear, and the diagnosis is currently relegated to the analysis of clinical symptoms; therefore, the search for biomarkers with diagnostic relevance is a major challenge in the field, especially in the era of personalized medicine. Though the mechanisms implicated in SZ are not fully understood, some processes are beginning to be elucidated. Oxidative stress, and in particular glutathione (GSH) dysregulation, has been demonstrated to play a crucial role in SZ pathophysiology. In fact, glutathione is a leading actor of oxidative-stress-mediated damage in SZ and appears to reflect the heterogeneity of the disease. The literature reports differing results regarding the levels of glutathione in SZ patients. However, each GSH state may be a sign of specific symptoms or groups of symptoms, candidating glutathione as a biomarker useful for discriminating SZ phenotypes. Here, we summarize the literature about the levels of glutathione in SZ and analyze the role of this molecule and its potential use as a biomarker.

Two neurostructural subtypes: results of machine learning on brain images from 4,291 individuals with schizophrenia.

Machine learning can be used to define subtypes of psychiatric conditions based on shared clinical and biological foundations, presenting a crucial step toward establishing biologically based subtypes of mental disorders. With the goal of identifying subtypes of disease progression in schizophrenia, here we analyzed cross-sectional brain structural magnetic resonance imaging (MRI) data from 4,291 individuals with schizophrenia (1,709 females, age=32.5 years±11.9) and 7,078 healthy controls (3,461 females, age=33.0 years±12.7) pooled across 41 international cohorts from the ENIGMA Schizophrenia Working Group, non-ENIGMA cohorts and public datasets. Using a machine learning approach known as Subtype and Stage Inference (SuStaIn), we implemented a brain imaging-driven classification that identifies two distinct neurostructural subgroups by mapping the spatial and temporal trajectory of gray matter (GM) loss in schizophrenia. Subgroup 1 (n=2,622) was characterized by an early cortical-predominant loss (ECL) with enlarged striatum, whereas subgroup 2 (n=1,600) displayed an early subcortical-predominant loss (ESL) in the hippocampus, amygdala, thalamus, brain stem and striatum. These reconstructed trajectories suggest that the GM volume reduction originates in the Broca's area/adjacent fronto-insular cortex for ECL and in the hippocampus/adjacent medial temporal structures for ESL. With longer disease duration, the ECL subtype exhibited a gradual worsening of negative symptoms and depression/anxiety, and less of a decline in positive symptoms. We confirmed the reproducibility of these imaging-based subtypes across various sample sites, independent of macroeconomic and ethnic factors that differed across these geographic locations, which include Europe, North America and East Asia. These findings underscore the presence of distinct pathobiological foundations underlying schizophrenia. This new imaging-based taxonomy holds the potential to identify a more homogeneous sub-population of individuals with shared neurobiological attributes, thereby suggesting the viability of redefining existing disorder constructs based on biological factors.

Neural Correlates of Positive and Negative Formal Thought Disorder in Individuals with Schizophrenia: An ENIGMA Schizophrenia Working Group Study.

Formal thought disorder (FTD) is a key clinical factor in schizophrenia, but the neurobiological underpinnings remain unclear. In particular, relationship between FTD symptom dimensions and patterns of regional brain volume deficiencies in schizophrenia remain to be established in large cohorts. Even less is known about the cellular basis of FTD. Our study addresses these major obstacles based on a large multi-site cohort through the ENIGMA Schizophrenia Working Group (752 individuals with schizophrenia and 1256 controls), to unravel the neuroanatomy of positive, negative and total FTD in schizophrenia and their cellular bases. We used virtual histology tools to relate brain structural changes associated with FTD to cellular distributions in cortical regions. We identified distinct neural networks for positive and negative FTD. Both networks encompassed fronto-occipito-amygdalar brain regions, but negative FTD showed a relative sparing of orbitofrontal cortical thickness, while positive FTD also affected lateral temporal cortices. Virtual histology identified distinct transcriptomic fingerprints associated for both symptom dimensions. Negative FTD was linked to neuronal and astrocyte fingerprints, while positive FTD was also linked to microglial cell types. These findings relate different dimensions of FTD to distinct brain structural changes and their cellular underpinnings, improve our mechanistic understanding of these key psychotic symptoms.

The Italian Validation of the Beck Cognitive Insight Scale: Underlying Factor Structure in Psychotic Patients and the General Population.

Cognitive insight refers to the ability to question one's judgments and cognitive biases and is underpinned by specific metacognitive processes. The Beck Cognitive Insight Scale was developed to assess cognitive insight and includes two subscales, Self-Reflectiveness and Self-Certainty (SC). The present study aimed to investigate the underlying factor structure of the Italian version of the BCIS in patients with schizophrenia (SZ) and in the general population (GP) for the first time. A cross-sectional design was adopted and a GP sample of 624 subjects and an SZ sample of 130 patients were enrolled. In the SZ group, a two-factor solution was supported. The internal reliability of each factor was satisfactory. Two items were eliminated and one item moved from the SC to the SR subscale. In the GP group, a two-factor solution was highlighted. The internal reliability of each factor was satisfactory. However, four items of the SR subscale were deleted. The Italian-validated version of the BCIS shows different structures for the SZ and the GP and is characterized by different features concerning previous studies. This evidence suggests new interpretations of metacognitive processes in the two populations and implies specific therapeutic approaches.

Data-driven biomarkers outperform theory-based biomarkers in predicting stroke motor outcomes.

Chronic motor impairments are a leading cause of disability after stroke. Previous studies have predicted motor outcomes based on the degree of damage to predefined structures in the motor system, such as the corticospinal tract. However, such theory-based approaches may not take full advantage of the information contained in clinical imaging data. The present study uses data-driven approaches to predict chronic motor outcomes after stroke and compares the accuracy of these predictions to previously-identified theory-based biomarkers. Using a cross-validation framework, regression models were trained using lesion masks and motor outcomes data from 789 stroke patients (293 female/496 male) from the ENIGMA Stroke Recovery Working Group (age 64.9±18.0 years; time since stroke 12.2±0.2 months; normalised motor score 0.7±0.5 (range [0,1]). The out-of-sample prediction accuracy of two theory-based biomarkers was assessed: lesion load of the corticospinal tract, and lesion load of multiple descending motor tracts. These theory-based prediction accuracies were compared to the prediction accuracy from three data-driven biomarkers: lesion load of lesion-behaviour maps, lesion load of structural networks associated with lesion-behaviour maps, and measures of regional structural disconnection. In general, data-driven biomarkers had better prediction accuracy - as measured by higher explained variance in chronic motor outcomes - than theory-based biomarkers. Data-driven models of regional structural disconnection performed the best of all models tested (R2 = 0.210, p < 0.001), performing significantly better than predictions using the theory-based biomarkers of lesion load of the corticospinal tract (R2 = 0.132, p< 0.001) and of multiple descending motor tracts (R2 = 0.180, p < 0.001). They also performed slightly, but significantly, better than other data-driven biomarkers including lesion load of lesion-behaviour maps (R2 =0.200, p < 0.001) and lesion load of structural networks associated with lesion-behaviour maps (R2 =0.167, p < 0.001). Ensemble models - combining basic demographic variables like age, sex, and time since stroke - improved prediction accuracy for theory-based and data-driven biomarkers. Finally, combining both theory-based and data-driven biomarkers with demographic variables improved predictions, and the best ensemble model achieved R2 = 0.241, p < 0.001. Overall, these results demonstrate that models that predict chronic motor outcomes using data-driven features, particularly when lesion data is represented in terms of structural disconnection, perform better than models that predict chronic motor outcomes using theory-based features from the motor system. However, combining both theory-based and data-driven models provides the best predictions.

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.

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.

Neural Correlates of Positive and Negative Formal Thought Disorder in Individuals with Schizophrenia: An ENIGMA Schizophrenia Working Group Study.

Formal thought disorder (FTD) is a key clinical factor in schizophrenia, but the neurobiological underpinnings remain unclear. In particular, relationship between FTD symptom dimensions and patterns of regional brain volume deficiencies in schizophrenia remain to be established in large cohorts. Even less is known about the cellular basis of FTD. Our study addresses these major obstacles based on a large multi-site cohort through the ENIGMA Schizophrenia Working Group (752 individuals with schizophrenia and 1256 controls), to unravel the neuroanatomy of positive, negative and total FTD in schizophrenia and their cellular bases. We used virtual histology tools to relate brain structural changes associated with FTD to cellular distributions in cortical regions. We identified distinct neural networks for positive and negative FTD. Both networks encompassed fronto-occipito-amygdalar brain regions, but negative FTD showed a relative sparing of orbitofrontal cortical thickness, while positive FTD also affected lateral temporal cortices. Virtual histology identified distinct transcriptomic fingerprints associated for both symptom dimensions. Negative FTD was linked to neuronal and astrocyte fingerprints, while positive FTD was also linked to microglial cell types. These findings relate different dimensions of FTD to distinct brain structural changes and their cellular underpinnings, improve our mechanistic understanding of these key psychotic symptoms.

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.

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).

In vivo white matter microstructure in adolescents with early-onset psychosis: a multi-site mega-analysis.

Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls using diffusion tensor imaging (DTI). Our sample included 321 adolescents with EOP (median age = 16.6 years, interquartile range (IQR) = 2.14, 46.4% females) and 265 adolescent healthy controls (median age = 16.2 years, IQR = 2.43, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. We found widespread lower FA in EOP compared to healthy controls, with the largest effect sizes in the superior longitudinal fasciculus (Cohen's d = 0.37), posterior corona radiata (d = 0.32), and superior fronto-occipital fasciculus (d = 0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. Using the largest EOP DTI sample to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male individuals with early-onset schizophrenia and individuals with a shorter duration of illness.

Educational interventions to improve detection and management of cognitive decline in primary care-An Italian multicenter pragmatic study.

Introduction: Timely detection of cognitive decline in primary care is essential to promote an appropriate care pathway and enhance the benefits of interventions. We present the results of a study aimed to evaluate the effectiveness of an educational intervention addressed to Italian family physicians (FPs) to improve timely detection and management of cognitive decline. Materials and methods: We conducted a pre-post study in six Italian health authorities (HAs) involving 254 FPs and 3,736 patients. We measured process and outcome indicators before the intervention (1 January 2014 to 31 December 2016) and after the intervention (1 January 2018 to 31 December 2019). One interactive face-to-face session workshop was delivered by local cognitive disorders and dementia specialists and FP advisors at each HA, in the period September 2017-December 2017. The session focused on key messages of the local Diagnostic and Therapeutic Care Pathway (DTCP) or regional guidelines: (a) the role of the FP for a timely suspicion of cognitive decline is fundamental; (b) when cognitive decline is suspected, the role of the FP is active in the diagnostic work-up; (c) FP's knowledge on pharmacological and non-pharmacological interventions is essential to improve the management of patients with cognitive decline. Results: An overall improvement in diagnostic procedures and management of patients with cognitive decline by FPs after the intervention was observed. The number of visits per year performed by FPs increased, and the time interval between the first FP consultation and the diagnosis was optimized. Neuroleptic use significantly decreased, whereas the use of benzodiazepines remained steadily high. Non-pharmacological interventions, or use of support services, were underrepresented even in the post-intervention. Differences among the participating HAs were identified and discussed. Discussion: Results from this study suggest the success of the educational intervention addressed to FPs in improving early detection and management of cognitive decline, highlighting the importance to continue medical education in this field. At the same time, further initiatives of care pathway dissemination and implementation should promote strategies to enhance interactions between primary and secondary care optimizing the collaboration between FPs and specialists.

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.