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An estimated 30 % of Major Depressive Disorder (MDD) patients exhibit resistance to conventional antidepressant treatments. Identifying reliable biomarkers of treatment-resistant depression (TRD) represents a major goal of precision psychiatry, which is hampered by the clinical and biological heterogeneity. To uncover biologically-driven subtypes of MDD, we applied an unsupervised data-driven framework to stratify 102 MDD patients on their neuroimaging signature, including extracted measures of cortical thickness, grey matter volumes, and white matter fractional anisotropy. Our novel analytical pipeline integrated different machine learning algorithms to harmonize data, perform data dimensionality reduction, and provide a stability-based relative clustering validation. The obtained clusters were characterized for immune-inflammatory peripheral biomarkers, TRD, history of childhood trauma and depressive symptoms. Our results indicated two different clusters of patients, differentiable with 67 % of accuracy: one cluster (n = 59) was associated with a higher proportion of TRD, and higher scores of energy-related depressive symptoms, history of childhood abuse and emotional neglect; this cluster showed a widespread reduction in cortical thickness (d = 0.43-1.80) and volumes (d = 0.45-1.05), along with fractional anisotropy in the fronto-occipital fasciculus, stria terminalis, and corpus callosum (d = 0.46-0.52); the second cluster (n = 43) was associated with cognitive and affective depressive symptoms, thicker cortices and wider volumes. Multivariate analyses revealed distinct brain-inflammation relationships between the two clusters, with increase in pro-inflammatory markers being associated with decreased cortical thickness and volumes. Our stratification of MDD patients based on structural neuroimaging identified clinically-relevant subgroups of MDD with specific symptomatic and immune-inflammatory profiles, which can contribute to the development of tailored personalized interventions for MDD., Competing Interests: Conflict of interest CF was a speaker for Janssen. AS is or was a consultant/speaker for Abbott, Abbvie, Angelini, AstraZeneca, Clinical Data, Boehringer, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Innovapharma, Italfarmaco, Janssen, Lundbeck, Naurex, Pfizer, Polifarma, Sanofi, Taliaz and Servier. All other authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. and ECNP. All rights reserved.)

Background: A conspicuous consequence of gatekeeping arrangements in universal, tax-funded, single-payer health care systems is the long waiting times. Besides limiting equal access to care, long waiting times can have a negative impact on health outcomes. Long waiting times can create obstacles in a patient's care pathway. Organization for Economic Co-operation and Development (OECD) countries have implemented various strategies to tackle this issue, but there is little evidence for which approach is the most effective. This literature review examined waiting times for ambulatory care. Objective: The aim was to identify the main policies or combinations of policies universal, tax-funded, and single-payer healthcare systems have implemented to improve the governance of outpatient waiting times. Methods: Starting from 1040 potentially eligible articles, a total of 41 studies were identified via a 2-step selection process. Findings: Despite the relevance of the issue, the literature is limited. A set of 15 policies for the governance of ambulatory waiting time was identified and categorized by the type of intervention: generation of supply capacity, control of demand, and mixed interventions. Even if a primary intervention was always identifiable, rarely a policy was implemented solo. The most frequent primary strategies were: guidelines implementation and/or clinical pathways, including triage, guidelines for referral and maxim waiting times (14 studies), task shifting (9 studies), and telemedicine (6 studies). Most studies were observational, with no data on costs of intervention and impact on clinical outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The role of immunization in public health is crucial, offering widespread protection against infectious diseases and underpinning societal well-being. However, achieving optimal vaccination coverage is impeded by vaccine hesitancy, a significant challenge that necessitates comprehensive strategies to understand and mitigate its effects. We propose the integration of Population Health Management principles with Immunization Information Systems (IISs) to address vaccine hesitancy more effectively. Our approach leverages systematic health determinants analysis to identify at-risk populations and tailor interventions, thereby promoting vaccination coverage and public health responses. We call for the development of an enhanced version of the Italian National Vaccination Registry, which aims to facilitate real-time tracking of individuals' vaccination status while improving data accuracy and interoperability among healthcare systems. This registry is designed to overcome current barriers by ensuring robust data protection, addressing cultural and organizational challenges, and integrating behavioral insights to foster informed public health campaigns. Our proposal aligns with the Italian National Vaccination Prevention Plan 2023-2025 and emphasizes proactive, evidence-based strategies to increase vaccination uptake and contrast the spread of vaccine-preventable diseases. The ultimate goal is to establish a data-driven, ethically sound framework that enhances public health outcomes and addresses the complexities of vaccine hesitancy within the Italian context and beyond.

Background: Strategies of prevention for psychiatric disorders need a deep understanding of the aetiological factors involved in the psychopathological processes. Our twin study aims at disentangling the contributions of genes and environment to schizotypal and hypomanic dimensions, considering the role of stressful life events (LEs) and the quality of family relationships., Methods: The Magical Ideation Scale (MIS) and Perceptual Aberration Scale (PAS) were used to assess positive schizotypy, while Hypomanic Personality Scale (HPS) and its sub-scales were used to investigate proneness to affective disorders. 268 twins (54.5 % female; aged 18.0 ± 6.68) were included. Participants filled out a questionnaire on LEs and their parents provided an evaluation of intra-family relationship (Relationship Quality Index, RQI). Classic univariate twin models for quantitative traits were fitted for scales, and the effects of covariates (LEs and RQI) were assessed., Results: For MIS, HPS and its sub-scales, significant common and unique environmental effects were detected, with genetic factors affecting only HPS Social Vitality sub-scale. Unique environment was the only source of variance of PAS score. The number of recent LEs influenced MIS and PAS models, while RQI score affected MIS model., Limitations: The main limitation of the study is the small sample size, which reduces statistical power and may potentially lead to an underestimation of heritability. Additionally, the cross-sectional design limits the possibility to draw causal considerations., Conclusions: Findings provide preliminary evidence for a significant environmental role in modulating states of vulnerability. Moreover, the expression of positive schizotypy resulted influenced by recent stressors and intra-family relationships., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Prenatal and perinatal complications represent well-known risk factors for the future development of psychiatric disorders. Such influence might become manifested during childhood and adolescence, as key periods for brain and behavioral changes. Internalizing and externalizing behaviors in adolescence have been associated with the risk of psychiatric onset later in life. Both brain morphology and behavior seem to be affected by obstetric complications, but a clear link among these three aspects is missing. Here, we aimed at analyzing the association between prenatal and perinatal complications, behavioral issues, and brain volumes in a group of children and adolescents. Eighty-two children and adolescents with emotional-behavioral problems underwent clinical and 3 T brain magnetic resonance imaging (MRI) assessments. The former included information on behavior, through the Child Behavior Checklist/6-18 (CBCL/6-18), and on the occurrence of obstetric complications. The relationships between clinical and gray matter volume (GMV) measures were investigated through multiple generalized linear models and mediation models. We found a mutual link between prenatal complications, GMV alterations in the frontal gyrus, and withdrawn problems. Specifically, complications during pregnancy were associated with higher CBCL/6-18 withdrawn scores and GMV reductions in the right superior frontal gyrus and anterior cingulate cortex. Finally, a mediation effect of these GMV measures on the association between prenatal complications and the withdrawn dimension was identified. Our findings suggest a key role of obstetric complications in affecting brain structure and behavior. For the first time, a mediator role of frontal GMV in the relationship between prenatal complications and internalizing symptoms was suggested. Once replicated on independent cohorts, this evidence will have relevant implications for planning preventive interventions., (© 2024. The Author(s).)

Mental imagery plays an important role in cognitive and emotional processes, therefore it might contribute to psychopathology in affective disorders. Distressive intrusive imagery is a core feature of anxiety disorders, but the underlying neurobiology remains unexplored. Here, we examined the functional brain mechanisms involved in state/psychological imagery in individuals with anxiety disorders. Functional Magnetic Resonance Imaging (fMRI) was used to assess the brain circuits involved in state/psychological (vs. action) imagery controlled by letter detection on the same stimuli in 33 individuals with anxiety disorders relative to 33 healthy controls. Patients were faster than controls in processing state/psychological stimuli and in general in the imagery task. We found that the left superior frontal gyrus was differentially activated by the state/psychological (vs. action) imagery (vs. letter detection) in the anxious individuals vs. healthy controls. We suggest that this area, which is involved in processing of state/psychological semantic information, appears deregulated during imagery in subjects with anxiety disorders. Our study provided the first evidence of both behavioral and brain functional alterations during imagery, highlighting a key role of the left superior frontal gyrus., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Studies investigating cognitive impairments in psychosis and depression have typically compared the average performance of the clinical group against healthy controls (HC), and do not report on the actual prevalence of cognitive impairments or strengths within these clinical groups. This information is essential so that clinical services can provide adequate resources to supporting cognitive functioning. Thus, we investigated this prevalence in individuals in the early course of psychosis or depression., Methods: A comprehensive cognitive test battery comprising 12 tests was completed by 1286 individuals aged 15-41 (mean age 25.07, s.d. 5.88) from the PRONIA study at baseline: HC ( N = 454), clinical high risk for psychosis (CHR; N = 270), recent-onset depression (ROD; N = 267), and recent-onset psychosis (ROP; N = 295). Z-scores were calculated to estimate the prevalence of moderate or severe deficits or strengths (>2 s.d. or 1-2 s.d. below or above HC, respectively) for each cognitive test., Results: Impairment in at least two cognitive tests was as follows: ROP (88.3% moderately, 45.1% severely impaired), CHR (71.2% moderately, 22.4% severely impaired), ROD (61.6% moderately, 16.2% severely impaired). Across clinical groups, impairments were most prevalent in tests of working memory, processing speed, and verbal learning. Above average performance (>1 s.d.) in at least two tests was present for 40.5% ROD, 36.1% CHR, 16.1% ROP, and was >2 SDs in 1.8% ROD, 1.4% CHR, and 0% ROP., Conclusions: These findings suggest that interventions should be tailored to the individual, with working memory, processing speed, and verbal learning likely to be important transdiagnostic targets.

Background: Neurocognitive deficits are a core feature of psychosis and depression. Despite commonalities in cognitive alterations, it remains unclear if and how the cognitive deficits in patients at clinical high risk for psychosis (CHR) and those with recent-onset psychosis (ROP) are distinct from those seen in recent-onset depression (ROD)., Aims: This study was carried out within the European project 'Personalized Prognostic Tools for Early Psychosis Management', and aimed to characterise the cognitive profiles of patients with psychosis or depression., Method: We examined cognitive profiles for patients with ROP ( n = 105), patients with ROD ( n = 123), patients at CHR ( n = 116) and healthy controls ( n = 372) across seven sites in five European countries. Confirmatory factor analysis identified four cognitive factors independent of gender, education and site: speed of processing, attention and working memory, verbal learning and spatial learning., Results: Patients with ROP performed worse than healthy controls in all four domains ( P < 0.001), whereas performance of patients with ROD was not affected ( P > 0.05). Patients at CHR performed worse than healthy controls in speed of processing ( P = 0.001) and spatial learning ( P = 0.003), but better than patients with ROP across all cognitive domains (all P ≤ 0.01). CHR and ROD groups did not significantly differ in any cognitive domain. These findings were independent of comorbid depressive symptoms, substance consumption and illness duration., Conclusions: These results show that neurocognitive abilities are affected in CHR and ROP, whereas ROD seems spared. Although our findings may support the notion that those at CHR have a specific vulnerability to psychosis, future studies investigating broader transdiagnostic risk cohorts in longitudinal designs are needed.

Emerging evidence suggests distinct neurobiological correlates of alcohol use disorder (AUD) between sexes, which however remain largely unexplored. This work from ENIGMA Addiction Working Group aimed to characterize the sex differences in gray matter (GM) and white matter (WM) correlates of AUD using a whole-brain, voxel-based, multi-tissue mega-analytic approach, thereby extending our recent surface-based region of interest findings on a nearly matching sample using a complementary methodological approach. T1-weighted magnetic resonance imaging (MRI) data from 653 people with AUD and 326 controls was analyzed using voxel-based morphometry. The effects of group, sex, group-by-sex, and substance use severity in AUD on brain volumes were assessed using General Linear Models. Individuals with AUD relative to controls had lower GM volume in striatal, thalamic, cerebellar, and widespread cortical clusters. Group-by-sex effects were found in cerebellar GM and WM volumes, which were more affected by AUD in females than males. Smaller group-by-sex effects were also found in frontotemporal WM tracts, which were more affected in AUD females, and in temporo-occipital and midcingulate GM volumes, which were more affected in AUD males. AUD females but not males showed a negative association between monthly drinks and precentral GM volume. Our results suggest that AUD is associated with both shared and distinct widespread effects on GM and WM volumes in females and males. This evidence advances our previous region of interest knowledge, supporting the usefulness of adopting an exploratory perspective and the need to include sex as a relevant moderator variable in AUD., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Deficits in executive functions (EF) and social cognition (SC) are often observed in bipolar disorder (BD), leading to a severe impairment in engaging a functional interaction with the others and the surrounding environment. Therefore, in recent years, resting-state functional magnetic resonance imaging (rs-fMRI) studies on BD tried to identify the neural underpinnings of these cognitive domains by exploring the association between the intrinsic functional connectivity (FC) and the scores in clinical scales evaluating these domains., Methods: A bibliographic search on PubMed and Scopus of studies evaluating the correlations between rs-fMRI findings and EF and/or SC in BD was conducted until March 2022. Ten studies met the inclusion criteria., Results: Overall, the results of the reviewed studies showed that BD patients had FC deficits compared to healthy controls (HC) in selective resting-state networks involved in EF and SC, which include the default mode network, especially the link between medial prefrontal cortex and posterior cingulate cortex, and the sensory-motor network. Finally, it also emerged the predominant role of alterations in prefrontal connections in explaining the cognitive deficits in BD patients., Limitations: The heterogeneity of the reviewed studies, in terms of the cognitive domains explored and the neuroimaging acquisitions employed, limited the comparability of the findings., Conclusions: rs-fMRI studies could help deepen the brain network alterations underlying EF and SC deficits in BD, pointing the attention on the neuronal underpinning of cognition, whose knowledge may lead to the development of new neurobiological-based approaches to improve the quality of life of these patients., Competing Interests: Conflict of interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The brain's intrinsic organization into large-scale functional networks, the resting state networks (RSN), shows complex inter-individual variability, consolidated during development. Nevertheless, the role of gene and environment on developmental brain functional connectivity (FC) remains largely unknown. Twin design represents an optimal platform to shed light on these effects acting on RSN characteristics. In this study, we applied statistical twin methods to resting-state functional magnetic resonance imaging (rs-fMRI) scans from 50 young twin pairs (aged 10-30 years) to preliminarily explore developmental determinants of brain FC. Multi-scale FC features were extracted and tested for applicability of classical ACE and ADE twin designs. Epistatic genetic effects were also assessed. In our sample, genetic and environmental effects on the brain functional connections largely varied between brain regions and FC features, showing good consistency at multiple spatial scales. Although we found selective contributions of common environment on temporo-occipital connections and of genetics on frontotemporal connections, the unique environment showed a predominant effect on FC link- and node-level features. Despite the lack of accurate genetic modeling, our preliminary results showed complex relationships between genes, environment, and functional brain connections during development. A predominant role of the unique environment on multi-scale RSN characteristics was suggested, which needs replications on independent samples. Future investigations should especially focus on nonadditive genetic effects, which remain largely unexplored., (© 2023. The Author(s).)

In recent years, machine learning (ML) has been a promising approach in the research of treatment outcome prediction in psychosis. In this study, we reviewed ML studies using different neuroimaging, neurophysiological, genetic, and clinical features to predict antipsychotic treatment outcomes in patients at different stages of schizophrenia. Literature available on PubMed until March 2022 was reviewed. Overall, 28 studies were included, among them 23 using a single-modality approach and 5 combining data from multiple modalities. The majority of included studies considered structural and functional neuroimaging biomarkers as predictive features used in ML models. Specifically, functional magnetic resonance imaging (fMRI) features contributed to antipsychotic treatment response prediction of psychosis with good accuracies. Additionally, several studies found that ML models based on clinical features might present adequate predictive ability. Importantly, by examining the additive effects of combining features, the predictive value might be improved by applying multimodal ML approaches. However, most of the included studies presented several limitations, such as small sample sizes and a lack of replication tests. Moreover, considerable clinical and analytical heterogeneity among included studies posed a challenge in synthesizing findings and generating robust overall conclusions. Despite the complexity and heterogeneity of methodology, prognostic features, clinical presentation, and treatment approaches, studies included in this review suggest that ML tools may have the potential to predict treatment outcomes of psychosis accurately. Future studies need to focus on refining feature characterization, validating prediction models, and evaluate their translation in real-world clinical practice., (© 2023. The Author(s).)

Background: Major Depressive Disorder (MDD) is a psychiatric disorder characterized by functional brain deficits, as documented by resting-state functional magnetic resonance imaging (rs-fMRI) studies., Aims: In recent years, some studies used machine learning (ML) approaches, based on rs-fMRI features, for classifying MDD from healthy controls (HC). In this context, this review aims to provide a comprehensive overview of the results of these studies., Design: The studies research was performed on 3 online databases, examining English-written articles published before August 5, 2022, that performed a two-class ML classification using rs-fMRI features. The search resulted in 20 eligible studies., Results: The reviewed studies showed good performance metrics, with better performance achieved when the dataset was restricted to a more homogeneous group in terms of disease severity. Regions within the default mode network, salience network, and central executive network were reported as the most important features in the classification algorithms., Limitations: The small sample size together with the methodological and clinical heterogeneity limited the generalizability of the findings., Conclusions: In conclusion, ML applied to rs-fMRI features can be a valid approach to classify MDD and HC subjects and to discover features that can be used for additional investigation of the pathophysiology of the disease., Competing Interests: Conflicts of interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Parkinson's disease (PD) patients display a combination of motor and non-motor symptoms. The most common non-motor symptom is scent (olfactory) impairment, occurring at least four years prior to motor symptom onset. Recent and growing interest in digital healthcare technology used in PD has resulted in more technologies developed for motor rather than non-motor symptoms. Human-computer interaction (HCI), which uses computer technology to explore human activity and work, could be combined with digital healthcare technologies to better understand and support olfaction via scent training - leading to the development of a scent-delivery device (SDD). In this pilot study, three PD patients were invited to an online focus group to explore the association between PD and olfaction, understand HCI and sensory technologies and were demonstrated a new multichannel SDD with an associated mobile app. Participants had a preconceived link, a result of personal experience, between olfactory impairment and PD. Participants felt that healthcare professionals did not take olfactory dysfunction concerns seriously prior to PD diagnosis. Two were not comfortable with sharing scent loss experiences with others. Participants expected the multichannel SDD to be small, portable and easy-to-use, with customisable cartridges to deliver chosen scents and the mobile app to create a sense of community. None of the participants regularly performed scent training but would consider doing so if some scent function could be regained. Standardised digital SDDs for regular healthcare check-ups may facilitate improvement in olfactory senses in PD patients and potential earlier PD diagnosis, allowing earlier therapeutic and symptomatic PD management., Competing Interests: Conflict of interest: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Mental imagery is part of people's own internal processing and plays an important role in everyday life, cognition and pathology. The neural network supporting mental imagery is bottom-up modulated by the imagery content. Here, we examined the complex associations of gender and age with the neural mechanisms underlying emotion imagery. We assessed the brain circuits involved in emotion mental imagery (vs. action imagery), controlled by a letter detection task on the same stimuli, chosen to ensure attention to the stimuli and to discourage imagery, in 91 men and women aged 14-65 years using fMRI. In women, compared with men, emotion imagery significantly increased activation within the right putamen, which is involved in emotional processing. Increasing age, significantly decreased mental imagery-related activation in the left insula and cingulate cortex, areas involved in awareness of ones' internal states, and it significantly decreased emotion verbs-related activation in the left putamen, which is part of the limbic system. This finding suggests a top-down mechanism by which gender and age, in interaction with bottom-up effect of type of stimulus, or directly, can modulate the brain mechanisms underlying mental imagery., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Early-onset bipolar disorder (BD) is a complex psychiatric illness characterized by mood swings, irritability and functional impairments. To improve our understanding of the pathophysiology of the disorder, we collected the existing resting-state functional Magnetic Resonance Imaging (rs-fMRI) studies exploring resting-state functional connectivity (rs-FC) and spontaneous activity alterations in children and adolescents with BD., Methods: A search on PubMed, Web of Science and Scopus was conducted to identify all the relevant rs-fMRI investigations conducted in early-onset BD. A total of 14 studies employing different methodological approaches to explore rs-FC and spontaneous activity in early-onset BD were included (independent component analysis, n = 1; seed-based analysis, n = 7; amplitude of low frequency fluctuations analysis, n = 2; regional homogeneity analysis, n = 4)., Results: Overall, the studies showed abnormalities within the Default Mode Network (DMN) and between the DMN and the Salience Network (SN). Moreover, widespread alterations in rs-FC and spontaneous brain activity within and between cortico-limbic structures, involving primarily the occipital and frontal lobes, amygdala, hippocampus, insula, thalamus and striatum were also reported., Limitations: The small sample sizes, the use of medications, the presence of comorbidities and the heterogeneity in methods hamper the integration of the study findings., Conclusions: Early-onset BD seems to be characterized by selective rs-FC and spontaneous activity dysfunctions in DMN and SN as well as in the cortico-limbic and cortico-striatal circuits, which could explain the emotive and cognitive deficits observed in this disabling psychiatric illness., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Cognitive Remediation (CR) is designed to halt the pathological neural systems that characterize major psychotic disorders (MPD), and its main objective is to improve cognitive functioning. The magnitude of CR-induced cognitive gains greatly varies across patients with MPD, with up to 40% of patients not showing gains in global cognitive performance. This is likely due to the high degree of heterogeneity in neural activation patterns underlying cognitive endophenotypes, and to inter-individual differences in neuroplastic potential, cortical organization and interaction between brain systems in response to learning. Here, we review studies that used neuroimaging to investigate which biomarkers could potentially serve as predictors of treatment response to CR in MPD., Methods: This systematic review followed the PRISMA guidelines. An electronic database search (Embase, Elsevier; Scopus, PsycINFO, APA; PubMed, APA) was conducted in March 2021. peer-reviewed, English-language studies were included if they reported data for adults aged 18+ with MPD, reported findings from randomized controlled trials or single-arm trials of CR; and presented neuroimaging data., Results: Sixteen studies were included and eight neuroimaging-based biomarkers were identified. Auditory mismatch negativity (3 studies), auditory steady-state response (1), gray matter morphology (3), white matter microstructure (1), and task-based fMRI (7) can predict response to CR. Efference copy corollary/discharge, resting state, and thalamo-cortical connectivity (1) require further research prior to being implemented., Conclusions: Translational research on neuroimaging-based biomarkers can help elucidate the mechanisms by which CR influences the brain's functional architecture, better characterize psychotic subpopulations, and ultimately deliver CR that is optimized and personalized., (Copyright © 2021. Published by Elsevier B.V.)

Olfaction is the most ancient sense and is directly connected with emotional areas in the brain. It gives rise to perception linked to emotion both in everyday life and in memory-recall activities. Despite its emotional primacy in perception and its role in sampling the real physical world, olfaction is rarely used in clinical psychological settings because it relies on stimuli that are difficult to deliver. However, recent developments in virtual-reality tools are creating novel possibilities for the engagement of the sense of smell in this field. In this article, we present the relevant features of olfaction for relaxation purposes and then discuss possible future applications of involving olfaction in virtual-reality interventions for relaxation. We also discuss clinical applications, the potential of new tools, and current obstacles and limitations.

Background: Major depressive disorder (MDD) is a severe psychiatric condition characterized by selective cognitive dysfunctions. In this regard, functional Magnetic Resonance Imaging (fMRI) studies showed, both at resting state and during tasks, alterations in the brain functional networks involved in cognitive processes in MDD patients compared to controls. Among those, it seems that the attention network may have a role in the disease pathophysiology. Therefore, in this review we aim at summarizing the current fMRI evidence investigating sustained attention in MDD patients., Methods: We conducted a search on PubMed on case-control studies on MDD employing fMRI acquisitions during Go/No-Go and continuous performance tasks. A total of 12 studies have been included in the review., Results: Overall, the majority of fMRI studies reported quantitative alterations in the response to attentive tasks in selective brain regions, including the prefrontal cortex, the cingulate cortex, the temporal and parietal lobes, the insula and the precuneus, which are key nodes of the attention, the executive, and the default mode networks., Limitations: The heterogeneity in the study designs, fMRI acquisition techniques and processing methods have limited the generalizability of the results., Conclusions: The results from the included studies showed the presence of alterations in the activation patterns of regions involved in sustained attention in MDD, which are in line with current evidence and seemed to explain some of the key symptoms of depression. However, given the paucity and heterogeneity of studies available, it may be worthwhile to continue investigating the attentional domain in MDD with ad-hoc study designs to retrieve more robust evidence., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Major Depressive Disorder (MDD) is a disabling illness affecting more than 5% of the elderly population. Higher female prevalence and sex-specific symptomatology have been observed, suggesting that biologically-determined dimensions might affect the disease onset and outcome. Rumination and executive dysfunction characterize adult-onset MDD, but sex differences in these domains and in the related brain mechanisms are still largely unexplored. The present pilot study aimed to explore any interactions between adult-onset MDD and sex on brain morphology and brain function during a Go/No-Go paradigm. We hypothesized to detect diagnosis by sex effects on brain regions involved in self-referential processes and cognitive control. Twenty-four subjects, 12 healthy (HC) (mean age 68.7 y, 7 females and 5 males) and 12 affected by adult-onset MDD (mean age 66.5 y, 5 females and 7 males), underwent clinical evaluations and a 3T magnetic resonance imaging (MRI) session. Diagnosis and diagnosis by sex effects were assessed on regional gray matter (GM) volumes and task-related functional MRI (fMRI) activations. The GM volume analyses showed diagnosis effects in left mid frontal cortex ( p < 0.01), and diagnosis by sex effects in orbitofrontal, olfactory, and calcarine regions ( p < 0.05). The Go/No-Go fMRI analyses showed MDD effects on fMRI activations in left precuneus and right lingual gyrus, and diagnosis by sex effects on fMRI activations in right parahippocampal gyrus and right calcarine cortex ( p < 0.001, ≥ 40 voxels). Our exploratory results suggest the presence of sex-specific brain correlates of adult-onset MDD-especially in regions involved in attention processing and in the brain default mode-potentially supporting cognitive and symptom differences between sexes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Piani, Maggioni, Delvecchio, Ferro, Gritti, Pozzoli, Fontana, Enrico, Cinnante, Triulzi, Stanley, Battaglioli and Brambilla.)

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background and Aim: As recently outlined in the WHO-ECDC Indicator framework (1) to evaluate the public health effectiveness of digital proximity tracing solutions, one of the main barriers to digital contact tracing (DCT) is population acceptance, which, in turns, is influenced by digital literacy, attitudes and practice. DCT came to public prominence during the COVID-19 pandemic but evidence on its population acceptance have not been comprehensively analyzed.  Methods: We carried out a systematic review (PROSPERO: CRD42021253668) following the PRISMA guidelines to collect, systematize and critically appraise the available evidence on population DCT acceptance.  Original studies reporting on different measures of population DCT acceptance were included., Conclusions: The systematic review was based on 41 articles meeting our a priori defined inclusion criteria, comprising aa total of 186144 surveyed subjects, 50000 tweets, 5025 Reddit posts and 714 written comments. Data extraction and synthesis required a qualitative outcome grouping, performed ex-post, in 14 different benchmarks components. They constitute a narrative analysis of actionable points for public health policy. Population acceptance is a key component of  DCT effective adoption and infection control during infectious diseases outbreaks. Assessing DCT acceptance's determinants in different settings, populations an cultural contexts it is of fundamental importance to inform the planning, implementation and monitoring of public health interventions. The results of our in-depth qualitative and quantitative analysis  will provide context for prospective improvements and actionable items and should guide future research aimed at exploring how digitalization can serve people-centred care.

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5-90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

This study aims to investigate the genetic and neural determinants of attention and hyperactivity problems. Using a proof-of-concept imaging genetics mediation design, we explore the relationship between the glutamatergic GRIN2B gene variants and inattention/hyperactivity with neuroanatomical measures as intermediates. Fifty-eight children and adolescents were evaluated for behavioral problems at three time points over approximately 7 years. The final assessment included blood drawing for genetic analyses and 3T magnetic resonance imaging. Attention/hyperactivity problems based on the Child Behavior Checklist/6-18, six GRIN2B polymorphisms and regional cortical thickness, and surface area and volume were estimated. Using general linear model (GLM) and mediation analyses, we tested whether GRIN2B exerted an influence on stable inattention/hyperactivity over development, and to what extent this effect was mediated by brain morphology. GLM results enlightened the relation between GRIN2B rs5796555-/A, volume in the left cingulate isthmus and inferior parietal cortices and inattention/hyperactivity. The mediation results showed that rs5796555-/A effect on inattention/hyperactivity was partially mediated by volume in the left isthmus of the cingulate cortex, suggesting a key role of this region in translating glutamatergic GRIN2B variations to attention/hyperactivity problems. This evidence can have important implications in the management of neurodevelopmental and psychiatric disorders.

When interacting with technology, attention is mainly driven by audiovisual and increasingly haptic stimulation. Olfactory stimuli are widely neglected, although the sense of smell influences many of our daily life choices, affects our behavior, and can catch and direct our attention. In this study, we investigated the effect of smell and sound on visuospatial attention in a virtual environment. We implemented the Bells Test, an established neuropsychological test to assess attentional and visuospatial disorders, in virtual reality (VR). We conducted an experiment with 24 participants comparing the performance of users under three experimental conditions (smell, sound, and smell and sound). The results show that multisensory stimuli play a key role in driving the attention of the participants and highlight asymmetries in directing spatial attention. We discuss the relevance of the results within and beyond human-computer interaction (HCI), particularly with regard to the opportunity of using VR for rehabilitation and assessment procedures for patients with spatial attention deficits., Competing Interests: DP is employed by the company Ultraleap Ltd., but the research was carried out as part of his PhD at the University of Sussex. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MC declared a shared affiliation with one of the authors ND to the handling editor at time of review., (Copyright © 2021 Dozio, Maggioni, Pittera, Gallace and Obrist.)

Background: Major depressive disorder (MDD) is a severe and pervasive psychiatric condition with a lifetime prevalence of 15-25%. Numerous Magnetic Resonance Imaging (MRI) studies employing scans at field strengths of 1.5T or 3T have been carried out in the last decades, providing an unprecedented insight into the neural correlates of MDD. However, in recent years, MRI technology has largely progressed and the use of scans at ultra-high field (≥ 7T) has improved the sensitivity and the resolution of MR images. In this context, with this review we aim to summarize evidence of structural and functional brain mechanisms underlying MDD obtained with ultra-high field MRI., Methods: We conducted a search on PubMed, Scopus and Web of Science of neuroimaging studies on MDD patients, which employed ultra-high field MRI. We detected six structural MRI studies, two Diffusion Tensor Imaging (DTI) studies and five functional MRI (fMRI) studies., Results: Overall, the MRI and DTI studies showed volumetric and structural connectivity alterations in the hippocampus and, to a lesser extent, in the amygdala. In contrast, more heterogeneous results were reported by fMRI studies, which, though, described functional abnormalities in the cingulate cortex, thalamus and several other brain areas., Limitations: The small sample size and the heterogeneity in patients' samples, processing and study design limit the conclusion of the present review., Conclusions: Studies employing scans at ultra-high magnetic field may provide a useful contribution to the mixed body of literature on MDD. This preliminary but promising evidence confirms the importance of performing ultra-high field MRI investigations in order to detect and better characterize subtle brain abnormalities in MDD., (Copyright © 2021. Published by Elsevier B.V.)

Music-based interventions seem to enhance motor, sensory and cognitive functions in Parkinson's disease (PD), but the underlying action mechanisms are still largely unknown. This electroencephalography (EEG) study aimed to investigate the effective connectivity patterns characterizing PD in the resting state and during music listening. EEG recordings were obtained from fourteen non-demented PD patients and 12 healthy controls, at rest and while listening to three music tracks. Theta- and alpha-band power spectral density and multivariate partial directed coherence were computed. Power and connectivity measures were compared between patients and controls in the four conditions and in music vs. rest. Compared to controls, patients showed enhanced theta-band power and slightly enhanced alpha-band power, but markedly reduced theta- and alpha-band interactions among EEG channels, especially concerning the information received by the right central channel. EEG power differences were partially reduced by music listening, which induced power increases in controls but not in patients. Connectivity differences were slightly compensated by music, whose effects largely depended on the track. In PD, music enhanced the frontotemporal inter-hemispheric communication. Our findings suggest that PD is characterized by enhanced activity but reduced information flow within the EEG network, being only partially normalized by music. Nevertheless, music capability to facilitate inter-hemispheric communication might underlie its beneficial effects on PD pathophysiology and should be further investigated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Maggioni, Arienti, Minella, Mameli, Borellini, Nigro, Cogiamanian, Bianchi, Cerutti, Barbieri, Brambilla and Ardolino.)

Background: Patterns of coordinated variations of gray matter (GM) morphology across individuals are promising indicators of disease. However, it remains unclear if they can help characterize first-episode psychosis (FEP) and symptoms' severity., Methods: Sixty-seven FEP and 67 matched healthy controls (HC) were assessed with structural MRI to evaluate the existence of distributed GM structural covariance patterns associated to brain areas belonging to salience network. Voxel-based morphometry (VBM) and structural covariance differences, investigated with salience network seed-based Partial Least Square, were applied to explore differences between groups. GM density associations with Raven's intelligent quotient (IQ) and Positive and Negative Syndrome Scale (PANSS) scores were investigated., Results: Univariate VBM results gave trend without significant GM differences across groups. GM and IQ correlated positively in both groups: in FEP, mostly in hippocampus, insula, and fronto-temporal structures, while in HC mostly in amygdala, thalamus and fronto-temporal regions. GM and PANSS scores correlated negatively in FEP, with widespread clusters located in limbic regions. Multivariate analysis showed strong and opposite structural GM covariance with salience network for FEP and HC. Moreover, structural covariance of the salience network in FEP correlated negatively with severity of clinical symptoms., Conclusion: Our study provides evidence supporting the insular dysfunction model of psychosis. Reduced structural GM covariance of the salience network, with its association to symptom's severity, appears a promising morphometry feature for FEP detection., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Sex-related differences are tied into neurodevelopmental and lifespan processes, beginning early in the perinatal and developmental phases and continue into adulthood. The present study was designed to investigate sexual dimorphism of changes in gray matter (GM) volume in post-adolescence, with a focus on early and middle-adulthood using a structural magnetic resonance imaging (MRI) dataset of healthy controls from the European Network on Psychosis, Affective disorders and Cognitive Trajectory (ENPACT). Three hundred and seventy three subjects underwent a 3.0 T MRI session across four European Centers. Age by sex effects on GM volumes were investigated using voxel-based morphometry (VBM) and the Automated Anatomical Labeling atlas regions (ROI). Females and males showed overlapping and non-overlapping patterns of GM volume changes during aging. Overlapping age-related changes emerged in bilateral frontal and temporal cortices, insula and thalamus. Both VBM and ROI analyses revealed non-overlapping changes in multiple regions, including cerebellum and vermis, bilateral mid frontal, mid occipital cortices, left inferior temporal and precentral gyri. These findings highlight the importance of accounting for sex differences in cross-sectional analyses, not only in the study of normative changes, but particularly in the context of psychiatric and neurologic disorders, wherein sex effects may be confounded with disease-related changes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Delvecchio, Maggioni, Pigoni, Crespo-Facorro, Nenadić, Benedetti, Gaser, Sauer, Roiz-Santiañez, Poletti, Rossetti, Bellani, Perlini, Ruggeri, Diwadkar and Brambilla.)

Background: Schizophrenia (SCZ) and Bipolar Disorder (BD) are severe psychiatric illnesses often characterized by mild-to-severe cognitive deficits. Since available pharmacotherapy showed poor efficacy in treating these cognitive impairments, new strategies are needed. Repeated Transcranial Magnetic Stimulation (rTMS) represents a safe non-invasive technique that has been hypothesized to improve cognitive symptoms in these pathologies. Therefore, our brief review aims at summarizing the results of Randomized Controlled Trials (RCTs) using rTMS for improving cognitive symptoms in SCZ and BD., Methods: We performed a bibliographic research on PubMed, Google Scholar and Medline of RCTs conducted in patients with BD and SCZ, which evaluated cognitive outcomes after rTMS treatment., Results: The inclusion criteria were met by fifteen RCTs, twelve in SCZ and three in BD. Regarding patients with SCZ, the results showed that rTMS seemed to have poor effects on improving cognitive performances, with mixed results also observed for schizoaffective patients. In BD, overall the RCTs showed that rTMS in these patients seemed to improve cognitive domains in euthymic patients, while its effect during acute phases, especially depression, appeared limited., Limitations: Studies employed different rTMS protocols and evaluated different cognitive domains., Conclusions: Although the available evidence from RCTs evaluating the efficacy of rTMS on cognitive deficits in SCZ and BD are still mixed and heterogenous, overall they suggest that rTMS represents a potential clinical tool that could ameliorate cognitive symptoms, especially in specific patients' subtypes. However, standardized protocols and further research are still necessary to evaluate the real efficacy of rTMS., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Children with attention deficit hyperactivity disorder (ADHD) exhibit behavioral inhibition deficits, which often lead to emotional dysregulation (ED) affecting individual ability to control emotions and behavioral responses. In ADHD, ED is associated with poor outcomes and comorbidities, with both externalizing and internalizing disorders. This work aims to evaluate sensitivity to emotional stimuli in children with ADHD using functional Near Infrared Spectroscopy (fNIRS)., Methods: During frontal fNIRS recording, 20 children with ADHD and 25 typically developing (TD) peers performed a visual continuous performance task with stimuli of different emotional content (i.e., positive, negative, neutral, and control stimuli without emotional content). This is a cognitive task designed to evaluate the ability to recognize emotional stimuli and to deal with emotional interference., Results: The ADHD sample showed more variability in response time to stimuli and more false alarms compared to TD group. fNIRS data showed between-group differences in right prefrontal and frontal cortices, with wider hemoglobin concentration changes in the TD group, during positive, negative, and neutral conditions., Limitations: Owing to the limited possibility of near infrared light to penetrate tissue, fNIRS can only measure cortical activations, while it would be of interest to identify the subcortical areas linked to emotional processing, too., Conclusions: Findings suggest the presence of emotional processing deficits in children with ADHD, as suggested by poor performances on the e-CPT task, and of peculiar sensitivity to emotional stimuli, linked to atypical hemodynamics of right prefrontal and frontal areas., (Copyright © 2020. Published by Elsevier B.V.)

Sleep disturbances are highly prevalent across all stages of Bipolar Disorder. Despite a wealth of research on the neurophysiological features of sleep in this population, progress in this field has been slow. We aimed to review the literature on sleep electroencephalography (EEG) studies in Bipolar Disorder, considering sleep architecture and microstructural oscillatory activity. We included a total of 22 studies: six on sleep during manic episodes, seven during depressive episodes, seven in euthymic patients and two in high-risk individuals. The most consistent findings were increased SOL and REM density across all stages of the disorder. Only two studies reported a reduced spindle count during bipolar depression and euthymia, respectively. Although not specific for Bipolar Disorder, SOL and REM density have been repeatedly found to be increased across all stages of illness in this population. Whereas the former reflects a difficulty initiating sleep, the latter can be considered a neurophysiological signature of patients' overall reduced sleep need, independent of illness stage., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Since its discovery in 1997, the default mode network (DMN) and its components have been extensively studied in both healthy individuals and psychiatric patients. Several studies have investigated possible DMN alterations in specific mental conditions such as bipolar disorder (BD). In this review, we describe current evidence from resting-state functional magnetic resonance imaging studies with the aim to understand possible changes in the functioning of the DMN in BD. Overall, several types of analyses including seed-based and independent component have been conducted on heterogeneous groups of patients highlighting different results. Despite the differences, findings seem to indicate that BD is associated with alterations in both frontal and posterior DMN structures, mainly in the prefrontal, posterior cingulate and inferior parietal cortices. We conclude this review by suggesting possible future research directions.

In this study, a semi-automatic, easy-to-use classification method for the identification and removal of fMRI noise is proposed and tested. The method relies on subject-level spatial independent component analysis (ICA) of fMRI data. Starting from a reference set of labeled independent components (ICs), novel ICs are classified as physiological/artefactual by combining a spatial correlation (SC) analysis with the reference ICs and relative power spectral (PS) analysis. Here, ICs from a task-based fMRI dataset were used as reference. SC and SP thresholds were set using a test dataset (5 subjects, same fMRI protocol) based on Receiving Operating Characteristic curves. The tool performance and versatility were measured on a resting-state fMRI dataset (5 subjects). Our results show that the method can automatically identify noise-related ICs with accuracy, specificity and sensitivity higher than 80% across different fMRI protocols. These findings also suggest that the reference set provided in the present study might be used to mark ICs coming from independent taskrelated or resting-state fMRI datasets.Clinical relevance- The new method will be included in a userfriendly, open-source tool for removal of noisy contributions from fMRI datasets to be used in clinical and research practices.

Background: Serious mental illnesses may be characterized by accelerated biological aging, and over the last years the research on the topic has been stimulated by studies exploring the molecular underpinnings of senescence., Methods: In the present manuscript we propose that measuring frailty, a general product of organismal ageing, through the "Frailty Index" (FI), a recently-emerged macroscopic indicator of functional status and biological age, adds an important marker to the measurements currently implemented in the study of accelerated biological age in psychiatric illnesses., Results: The FI quantifies functional negative health attributes and measures their cumulative effect, thus providing a useful estimate of the individual's biological age and risk profile. Recent studies in older adults have observed significant associations between FI and molecular measures of aging., Limitations: High FI values can be driven by causes different from aging per se, so FI may be a sensitive but not specific measure of biological aging., Conclusions: FI, which is extensively used in geriatrics and gerontology but it has rarely been used in relation to mental health, may be of relevance in the evaluation of age-related phenomena associated with psychiatric diseases., Competing Interests: Declaration of Competing Interest All authors have no actual or past potential conflict of interest to disclose, including any financial, personal or other relationships with other people or organizations that could inappropriately have influenced the results presented in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Aim: To evaluate outcomes related to antiplatelet therapy in patients with ST-elevation myocardial infarction (STEMI) admitted to the San Gerardo Hospital in Monza, an extracorporeal membrane oxygenation (ECMO) reference center in the Monza-Brianza area., Methods: This retrospective study enrolled patients with STEMI hospitalized between 2013 and 2017., Results: This study included 653 patients (mean age: 67.5 years, 71% male). Across the study period, ticagrelor use showed consistent increases, from 22% of patients during 2013 to 85% in 2017. Cardiac arrest prehospitalization occurred in 100 patients (15.3%), either at home (n = 85, 13.0%) or during transfer (n = 15, 2.3%); 46 patients underwent ECMO for refractory cardiac arrest. Rates of 90-day survival (hazard ratio [HR]: 2.4, 95% confidence interval [CI]: 1.3-4.4, P = .004) and ST resolution (odds ratio [OR]: 2.5, 95% CI: 1.6-4.1, P = .000) were higher with ticagrelor than with other antiplatelet agents. When analyzed by each agent, patients on ticagrelor had longer survival (HR: 0.4, 95% CI: 0.2-0.8, P = .008) than patients on clopidogrel and more frequent ST resolution than those on clopidogrel or prasugrel (OR: 0.4, 95% CI: 0.2-0.7, P = .002 and OR: 0.4, 95% CI: 0.2-0.7, P = .006). There was no difference in mortality between ticagrelor and prasugrel., Conclusions: Changes in the treatment of high-risk patients with STEMI over time are in line with changes in treatment guidelines. In these patients, ticagrelor is associated with significantly improved 90-day mortality compared with clopidogrel.

Background: Transcranial Magnetic Stimulation (TMS) has emerged as a valid therapeutic option in the treatment of depression, especially in cases of inadequate response to antidepressant agents. Despite the recognized efficacy of this technique, its mechanisms of action are still debated and optimal protocols have not yet been established., Methods: The present review focuses on TMS protocols that either engage the targeted brain circuits or synchronize the stimulation frequency to individual neuronal oscillations to increase the antidepressant efficacy., Results: TMS efficacy was found to be enhanced by preliminary or concomitant modulation of the functional state of the targeted brain networks. Conversely, there is not enough evidence of higher efficacy of TMS protocols with individual selection of the stimulation frequency compared to standard ones., Limitations: Most studies included small patient samples., Conclusions: Our results suggest that a good option to enhance rTMS efficacy might be to follow synaptic potentiation and depression rules., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2020. Published by Elsevier B.V.)

Neurodevelopment represents a period of increased opportunity and vulnerability, during which a complex confluence of genetic and environmental factors influences brain growth trajectories, cognitive and mental health outcomes. Recently, magnetic resonance imaging (MRI) studies on twins have increased our knowledge of the extent to which genes, the environment and their interactions shape inter-individual brain variability. The present review draws from highly salient MRI studies in young twin samples to provide a robust assessment of the heritability of structural and functional brain changes during development. The available studies suggest that (as with many other traits), global brain morphology and network organization are highly heritable from early childhood to young adulthood. Conversely, genetic correlations among brain regions exhibit heterogeneous trajectories, and this heterogeneity reflects the progressive, experience-related increase in brain network complexity. Studies also support the key role of environment in mediating brain network differentiation via changes of genetic expression and hormonal levels. Thus, rest- and task-related functional brain circuits seem to result from a contextual and dynamic expression of heritability., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: A multiscale functional clustering approach is proposed to investigate the organization of the epileptic networks during different sleep stages and in relation with the occurrence of seizures., Method: Stereo-electroencephalographic signals from seven pharmaco-resistant epileptic patients (focal cortical dysplasia type II) were analyzed. The discrete wavelet transform provided a multiscale framework on which a data-driven functional clustering procedure was applied, based on multivariate measures of integration and mutual information. The most interacting functional clusters (FCs) within the sampled brain areas were extracted., Results: FCs characterized by strongly integrated activity were observed mostly in the beta and alpha frequency bands, immediately before seizure onset and in deep sleep stages. These FCs generally included the electrodes from the epileptogenic zone. Furthermore, repeatable patterns were found across ictal events in the same patient., Conclusion: In line with previous studies, our findings provide evidence of the important role of beta and alpha activity in seizures generation and support the relation between epileptic activity and sleep stages., Significance: Despite the small number of subjects included in the study, the present results suggest that the proposed multiscale functional clustering approach is a useful tool for the identification of the frequency-dependent mechanisms underlying seizure generation.

Although anxiety and depression often co-occur and share some clinical features, it is still unclear if they are neurobiologically distinct or similar processes. In this study, we explored common and specific cortical morphology alterations in depression and anxiety disorders. Magnetic Resonance Imaging data were acquired from 13 Major Depressive Disorder (MDD), 11 Generalized Anxiety Disorder (GAD), 11 Panic Disorder (PD) patients and 21 healthy controls (HC). Regional cortical thickness, surface area (SA), volume and gyrification were measured and compared among groups. We found left orbitofrontal thinning in all patient groups, as well as disease-specific alterations. MDD showed volume deficits in left precentral gyrus compared to all groups, volume and area deficits in right fusiform gyrus compared to GAD and HC. GAD showed lower SA than MDD and PD in right superior parietal cortex, higher gyrification than HC in right frontal gyrus. PD showed higher gyrification in left superior parietal cortex when compared to MDD and higher SA in left postcentral gyrus compared to all groups. Our results suggest that clinical phenotypic similarities between major depression and anxiety disorders might rely on common prefrontal alterations. Frontotemporal and parietal abnormalities may represent unique biological signatures of depression and anxiety., (Copyright © 2019. Published by Elsevier B.V.)

Background: Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by deficits in self-controlling attention, behavior, and emotions. In recent years, noninvasive optical techniques, such as near infrared spectroscopy (NIRS), have been used to measure the neural correlates of pharmacological-therapy outcomes in children and adolescents with ADHD., Methods: We reviewed a short series of articles that investigated the results of functional NIRS (fNIRS) on developmental-age ADHD. The review was limited to fNIRS studies that investigated the cortical responses that occurred during neuropsychological tasks in ADHD patients who received methylphenidate or atomoxetine., Results: The majority of the reviewed studies revealed the presence of increased oxygenated hemoglobin concentrations in the prefrontal cortex following pharmacotherapy in ADHD samples. A higher frequency of right-lateralized results was found., Limitations: The considered studies are characterized by substantial methodological heterogeneity in terms of the patients' medication status and washout period, explored cerebral regions, and neuropsychological tasks., Conclusions: fNIRS seems to be a promising tool for the detection of pharmacological-treatment biomarkers in samples of children and adolescents with ADHD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The prompt recognition of pleasant and unpleasant odors is a crucial regulatory and adaptive need of humans. Reactive answers to unpleasant odors ensure survival in many threatening situations. Notably, although humans typically react to certain odors by modulating their distance from the olfactory source, the effect of odor pleasantness over the orienting of visuospatial attention is still unknown. To address this issue, we first trained participants to associate visual shapes with pleasant and unpleasant odors, and then we assessed the impact of this association on a visuospatial task. Results showed that the use of trained shapes as flankers modulates performance in a line bisection task. Specifically, it was found that the estimated midpoint was shifted away from the visual shape associated with the unpleasant odor, whereas it was moved toward the shape associated with the pleasant odor. This finding demonstrates that odor pleasantness selectively shifts human attention in the surrounding space. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Background: Although the study of the neuroanatomical correlates of generalized anxiety disorder (GAD) is gaining increasing interest, up to now the cortical anatomy of GAD patients has been poorly investigated and still no data on cortical gyrification are available. The aim of the present study is to quantitatively examine the cortical morphology in patients with GAD compared with healthy controls (HC) using magnetic resonance imaging (MRI). To the best of our knowledge, this is the first study analyzing the gyrification patterns in GAD., Methods: A total of 31 GAD patients and 31 HC underwent 3 T structural MRI. For each subject, cortical surface area (CSA), cortical thickness (CT), gray matter volume (GMV), and local gyrification index (LGI) were estimated in 19 regions of interest using the Freesurfer software. These parameters were then compared between the two groups using General Linear Model designs., Results: Compared with HC, GAD patients showed: (1) reduced CT in right caudal middle frontal gyrus (p < 0.05, Bonferroni corrected), (2) hyper-gyrification in right fusiform, inferior temporal, superior parietal and supramarginal gyri and in left supramarginal and superior frontal gyri (p < 0.05, Bonferroni corrected). No significant alterations in CSA and GMV were observed., Conclusions: Our findings support the hypothesis of a neuroanatomical basis for GAD, highlighting a possible key role of the right hemisphere. The alterations of CT and gyrification in GAD suggest a neurodevelopmental origin of the disorder. Further studies on GAD are needed to understand the evolution of the cerebral morphology with age and during the clinical course of the illness.