Daniela Vecchio
@hsantalucia.it
Department of Clinical and Behavioural Neurology - Laboratory of Neuropsychyatry
IRCCS Santa Lucia Foundation
EDUCATION
MS Cognitive Neuroscience
PhD Behavioural Neuroscience
RESEARCH INTERESTS
Neuroimaging, Connectivity, Network Analysis, Machine Learning, Mental Disorder, Neurodegenerative Disorder
Scopus Publications
Scopus Publications
Ruiyang Ge, Yuetong Yu, Yi Xuan Qi, Yu-nan Fan, Shiyu Chen, Chuntong Gao, Shalaila S Haas, Faye New, Dorret I Boomsma, Henry Brodaty,et al.
Elsevier BV
Shuqing Si, Anbreen Bi, Zhaoying Yu, Cheryl See, Sinead Kelly, Sonia Ambrogi, Celso Arango, Inmaculada Baeza, Nerisa Banaj, Michael Berk,et al.
Springer Science and Business Media LLC
Abstract 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.
Rebecca Kerestes, Max A. Laansma, Conor Owens‐Walton, Andrew Perry, Eva M. van Heese, Sarah Al‐Bachari, Tim J. Anderson, Francesca Assogna, Ítalo K. Aventurato, Tim D. van Balkom,et al.
Wiley
AbstractBackgroundIncreasing 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.ObjectiveTo quantify cross‐sectional regional cerebellar lobule volumes using three dimensional T1‐weighted anatomical brain magnetic resonance imaging from the global ENIGMA‐PD working group.MethodsCerebellar 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.ResultsOverall, 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).ConclusionsWe 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.
Nerisa Banaj, Daniela Vecchio, Fabrizio Piras, Pietro De Rossi, Juan Bustillo, Simone Ciufolini, Paola Dazzan, Marta Di Forti, Erin W. Dickie, Judith M. Ford,et al.
Springer Science and Business Media LLC
AbstractConverging 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.
Huu Kim Le, Angelica B. Ortiz de Gortari, Annabel Callan, Daragh Poynton, Daniela Vecchio, and Wai Chen
MDPI AG
Little is known about the interplay of Gaming Disorder (GD) with psychotic processes in schizophrenia. Only a few clinical cases involving video game playing and psychotic symptoms have been previously reported in literature. This case report describes a 24-year-old male diagnosed with paranoid schizophrenia and GD. Our case, Patient G, had premorbid excessive video game playing and Game Transfer Phenomena (GTP) prior to the onset of his schizophrenia illness. GTP are common among gamers and are characterised by abnormal perceptions, intrusive thoughts, and temporal change on behaviours related to the content of video games. However, GTP are not necessarily of delusional intensity for meeting the threshold of psychosis. The relapse in Patient G’s paranoid schizophrenia was associated with recent cannabis use, social withdrawal, and excessive video game playing. Patient G’s psychotic symptoms were influenced by video game themes and the movie “Matrix”, including the delusion that he was in a video game and that people around him were “non-playable characters”. Awareness of GTP can help clinicians to demarcate GTP from psychotic features and identify their interactions, given the ensuing treatment implications. Our case report highlights the importance of GTP, which in some cases may be an early sign of developing mental illness and could have implications for early intervention and prevention of illness onset and complications.
Sook-Lei Liew, Nicolas Schweighofer, James H. Cole, Artemis Zavaliangos-Petropulu, Bethany P. Lo, Laura K.M. Han, Tim Hahn, Lianne Schmaal, Miranda R. Donnelly, Jessica N. Jeong,et al.
Ovid Technologies (Wolters Kluwer Health)
Background and ObjectivesFunctional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in the context of stroke as younger brain age given matched lesion damage, would differentiate people with good vs poor outcomes.MethodsWe conducted a cross-sectional observational study using a multisite dataset of 3-dimensional brain structural MRIs and clinical measures from the ENIGMA Stroke Recovery. Brain age was calculated from 77 neuroanatomical features using a ridge regression model trained and validated on 4,314 healthy controls. We performed a 3-step mediation analysis with robust mixed-effects linear regression models to examine relationships between brain age, lesion damage, and stroke outcomes. We used propensity score matching and logistic regression to examine whether brain resilience predicts good vs poor outcomes in patients with matched lesion damage.ResultsWe examined 963 patients across 38 cohorts. Greater lesion damage was associated with older brain age (β = 0.21; 95% CI 0.04–0.38,p= 0.015), which in turn was associated with poorer outcomes, both in the sensorimotor domain (β = −0.28; 95% CI −0.41 to −0.15,p< 0.001) and across multiple domains of function (β = −0.14; 95% CI −0.22 to −0.06,p< 0.001). Brain age mediated 15% of the impact of lesion damage on sensorimotor performance (95% CI 3%–58%,p= 0.01). Greater brain resilience explained why people have better outcomes, given matched lesion damage (odds ratio 1.04, 95% CI 1.01–1.08,p= 0.004).DiscussionWe provide evidence that younger brain age is associated with superior poststroke outcomes and modifies the impact of focal damage. The inclusion of imaging-based assessments of brain age and brain resilience may improve the prediction of poststroke outcomes compared with focal injury measures alone, opening new possibilities for potential therapeutic targets.
Daniela Vecchio, Fabrizio Piras, Valentina Ciullo, Federica Piras, Federica Natalizi, Giuseppe Ducci, Sonia Ambrogi, Gianfranco Spalletta, and Nerisa Banaj
MDPI AG
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).
Dick Schijven, Merel C. Postema, Masaki Fukunaga, Junya Matsumoto, Kenichiro Miura, Sonja M. C. de Zwarte, Neeltje E. M. van Haren, Wiepke Cahn, Hilleke E. Hulshoff Pol, René S. Kahn,et al.
Proceedings of the National Academy of Sciences
Left–right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case–control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case–control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case–control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case–control status. Subtle case–control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
Claudia Barth, Sinead Kelly, Stener Nerland, Neda Jahanshad, Clara Alloza, Sonia Ambrogi, Ole A. Andreassen, Dimitrios Andreou, Celso Arango, Inmaculada Baeza,et al.
Springer Science and Business Media LLC
AbstractEmerging 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.
Constantinos Constantinides, Laura K. M. Han, Clara Alloza, Linda Antonella Antonucci, Celso Arango, Rosa Ayesa-Arriola, Nerisa Banaj, Alessandro Bertolino, Stefan Borgwardt, Jason Bruggemann,et al.
Springer Science and Business Media LLC
AbstractSchizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18–72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18–73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen’s d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.
Adrian I. Campos, Laura S. Van Velzen, Dick J. Veltman, Elena Pozzi, Sonia Ambrogi, Elizabeth D. Ballard, Nerisa Banaj, Zeynep Başgöze, Sophie Bellow, Francesco Benedetti,et al.
American Psychological Association (APA)
Cees J. Weeland, Selina Kasprzak, Niels T. de Joode, Yoshinari Abe, Pino Alonso, Stephanie H. Ameis, Alan Anticevic, Paul D. Arnold, Srinivas Balachander, Nerisa Banaj,et al.
Springer Science and Business Media LLC
AbstractLarger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered (https://osf.io/73dvy) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = −0.15 to −0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status.
V. Ciullo, F. Piras, N. Banaj, D. Vecchio, F. Piras, G. Sani, G. Ducci and G. Spalletta
Federica Natalizi, Federica Piras, Daniela Vecchio, Gianfranco Spalletta, and Fabrizio Piras
MDPI AG
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.
Artemis Zavaliangos‐Petropulu, Bethany Lo, Miranda R. Donnelly, Nicolas Schweighofer, Keith Lohse, Neda Jahanshad, Giuseppe Barisano, Nerisa Banaj, Michael R. Borich, Lara A. Boyd,et al.
Ovid Technologies (Wolters Kluwer Health)
Background Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper‐limb sensorimotor impairment. We investigated associations between non‐lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. Methods and Results Cross‐sectional T1‐weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta‐Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA‐UE (Fugl‐Meyer Assessment of Upper Extremity). Robust mixed‐effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni‐corrected, P <0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional ( P =0.005; β=0.16) but not contralesional ( P =0.96; β=0.003) hippocampal volume, independent of lesion volume and other covariates ( P =0.001; β=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional ( P =0.008; β=−0.26) and contralesional ( P =0.006; β=−0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size ( P <0.001; β=−0.21) and extent of sensorimotor damage ( P =0.003; β=−0.15). Conclusions The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women.
Sook‐Lei Liew, Artemis Zavaliangos‐Petropulu, Neda Jahanshad, Catherine E. Lang, Kathryn S. Hayward, Keith R. Lohse, Julia M. Juliano, Francesca Assogna, Lee A. Baugh, Anup K. Bhattacharya,et al.
Human Brain Mapping Wiley
Eleonora Picerni, Daniela Laricchiuta, Fabrizio Piras, Daniela Vecchio, Laura Petrosini, Debora Cutuli, and Gianfranco Spalletta
Springer Science and Business Media LLC
AbstractFew investigations have analyzed the neuroanatomical substrate of empathic capacities in healthy subjects, and most of them have neglected the potential involvement of cerebellar structures. The main aim of the present study was to investigate the associations between bilateral cerebellar macro- and micro-structural measures and levels of cognitive and affective trait empathy (measured by Interpersonal Reactivity Index, IRI) in a sample of 70 healthy subjects of both sexes. We also estimated morphometric variations of cerebral Gray Matter structures, to ascertain whether the potential empathy-related peculiarities in cerebellar areas were accompanied by structural differences in other cerebral regions. At macro-structural level, the volumetric differences were analyzed by Voxel-Based Morphometry (VBM)- and Region of Interest (ROI)-based approaches, and at a micro-structural level, we analyzed Diffusion Tensor Imaging (DTI) data, focusing in particular on Mean Diffusivity and Fractional Anisotropy. Fantasy IRI-subscale was found to be positively associated with volumes in right cerebellar Crus 2 and pars triangularis of inferior frontal gyrus. The here described morphological variations of cerebellar Crus 2 and pars triangularis allow to extend the traditional cortico-centric view of cognitive empathy to the cerebellar regions and indicate that in empathizing with fictional characters the cerebellar and frontal areas are co-recruited.
Fabrizio Piras, , Federica Piras, Yoshinari Abe, Sri Mahavir Agarwal, Alan Anticevic, Stephanie Ameis, Paul Arnold, Nerisa Banaj, Núria Bargalló,et al.
Translational Psychiatry Springer Science and Business Media LLC
AbstractMicrostructural alterations in cortico-subcortical connections are thought to be present in obsessive–compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen’s d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = −0.21, z = −3.21, p = 0.001) and posterior thalamic radiation (d = −0.26, z = −4.57, p < 0.0001). In the sagittal stratum, lower FA was associated with a younger age of onset (z = 2.71, p = 0.006), longer duration of illness (z = −2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = −1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.
Valentina Ciullo, Gianfranco Spalletta, Carlo Caltagirone, Nerisa Banaj, Daniela Vecchio, Fabrizio Piras, and Federica Piras
SAGE Publications
Transcranial direct current stimulation (tDCS) has been implemented in neuropsychiatric disorders characterized by cognitive impairment. However, methodological heterogeneity challenges conclusive remarks. Through a critical analysis of previous conflicting findings and in the light of current neurobiological models of pathophysiology, we qualitatively assessed the effects of tDCS in neuropsychiatric disorders that share neurobiological underpinnings, as to evaluate whether stimulation can improve cognitive deficits in patients’ cohorts. We performed a systematic review of tDCS studies targeting cognitive functions in mental disorders and pathological cognitive aging. Data from 41 studies, comprising patients with diagnosis of mood disorders, schizophrenia-spectrum disorders, Alzheimer’s disease (AD), and mild cognitive impairment (MCI), were included. Results indicate that tDCS has the capacity to enhance processing speed, working memory, and executive functions in patients with mood and schizophrenia-spectrum disorders. The evidence of a positive effect on general cognitive functioning and memory is either inconclusive in AD, or weak in MCI. Future directions are discussed for developing standardized stimulation protocols and for translating the technique therapeutic potential into effective clinical practice.
Fabrizio Piras, Daniela Vecchio, Florian Kurth, Federica Piras, Nerisa Banaj, Valentina Ciullo, Eileen Luders, and Gianfranco Spalletta
Oxford University Press (OUP)
Abstract Mental disorders diagnosis is based on specific clinical criteria. However, clinical studies found similarities and overlapping phenomenology across a variety of disorders, which suggests a common neurobiological substrate. Thus, there is a need to measure disease-related neuroanatomical similarities and differences across conditions. While structural alterations of the corpus callosum have been investigated in obsessive-compulsive disorder, schizophrenia, major depressive disorder and bipolar disorder, no study has addressed callosal aberrations in all diseases in a single study. Moreover, results from pairwise comparisons (patients vs. controls) show some inconsistencies, possibly related to the parcellation methods to divide the corpus callosum into subregions. The main aim of the present paper was to uncover highly localized callosal characteristics for each condition (i.e. obsessive-compulsive disorder, schizophrenia, major depressive disorder and bipolar disorder) as compared either to healthy control subjects or to each other. For this purpose, we did not rely on any sub-callosal parcellation method, but applied a well-validated approach measuring callosal thickness at 100 equidistant locations along the whole midline of the corpus callosum. One hundred and twenty patients (30 in each disorder) as well as 30 controls were recruited for the study. All groups were closely matched for age and gender, and the analyses were performed controlling for the impact of antipsychotic treatment and illness duration. There was a significant main effect of group along the whole callosal surface. Pairwise post hoc comparisons revealed that, compared to controls, patients with obsessive-compulsive disorder had the thinnest corpora callosa with significant effects almost on the entire callosal structure. Patients with schizophrenia also showed thinner corpora callosa than controls but effects were confined to the isthmus and the anterior part of the splenium. No significant differences were found in both major depressive disorder and bipolar disorder patients compared to controls. When comparing the disease groups to each other, the corpus callosum was thinner in obsessive-compulsive disorder patients than in any other group. The effect was evident across the entire corpus callosum, with the exception of the posterior body. Altogether, our study suggests that the corpus callosum is highly changed in obsessive-compulsive disorder, selectively changed in schizophrenia and not changed in bipolar disorder and major depressive disorder. These results shed light on callosal similarities and differences among mental disorders providing valuable insights regarding the involvement of the major brain commissural fibre tract in the pathophysiology of each specific mental illness.
Sook-Lei Liew, Artemis Zavaliangos-Petropulu, Nicolas Schweighofer, Neda Jahanshad, Catherine E Lang, Keith R Lohse, Nerisa Banaj, Giuseppe Barisano, Lee A Baugh, Anup K Bhattacharya,et al.
Oxford University Press (OUP)
Abstract Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Deep grey matter structures play a critical role in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behaviour at different timepoints after stroke. We pooled high-resolution T1-weighted MRI brain scans and behavioural data in 828 individuals with unilateral stroke from 28 cohorts worldwide. Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behaviour to non-lesioned subcortical volumes (Bonferroni-corrected, P &lt; 0.004). We tested subacute (≤90 days) and chronic (≥180 days) stroke subgroups separately, with exploratory analyses in early stroke (≤21 days) and across all time. Sub-analyses in chronic stroke were also performed based on class of sensorimotor deficits (impairment, activity limitations) and side of lesioned hemisphere. Worse sensorimotor behaviour was associated with a smaller ipsilesional thalamic volume in both early (n = 179; d = 0.68) and subacute (n = 274, d = 0.46) stroke. In chronic stroke (n = 404), worse sensorimotor behaviour was associated with smaller ipsilesional putamen (d = 0.52) and nucleus accumbens (d = 0.39) volumes, and a larger ipsilesional lateral ventricle (d = −0.42). Worse chronic sensorimotor impairment specifically (measured by the Fugl-Meyer Assessment; n = 256) was associated with smaller ipsilesional putamen (d = 0.72) and larger lateral ventricle (d = −0.41) volumes, while several measures of activity limitations (n = 116) showed no significant relationships. In the full cohort across all time (n = 828), sensorimotor behaviour was associated with the volumes of the ipsilesional nucleus accumbens (d = 0.23), putamen (d = 0.33), thalamus (d = 0.33) and lateral ventricle (d = −0.23). We demonstrate significant relationships between post-stroke sensorimotor behaviour and reduced volumes of deep grey matter structures that were spared by stroke, which differ by time and class of sensorimotor measure. These findings provide additional insight into how different cortico-thalamo-striatal circuits support post-stroke sensorimotor outcomes.
Federica Piras, Daniela Vecchio, Francesca Assogna, Clelia Pellicano, Valentina Ciullo, Nerisa Banaj, Richard A. E. Edden, Francesco E. Pontieri, Fabrizio Piras, and Gianfranco Spalletta
MDPI AG
The neuroanatomical and molecular substrates for cognitive impairment in Parkinson Disease (PD) are far from clear. Evidence suggests a non-dopaminergic basis, and a crucial role for cerebellum in cognitive control in PD. We investigated whether a PD cognitive marker (response inhibition) was differently controlled by g-amino butyric acid (GABA) and/or by glutamate-glutamine (Glx) levels in the cerebellum of idiopathic PD patients, and healthy comparators (HC). Magnetic resonance spectroscopy of GABA/Glx (MEGA-PRESS acquisition sequence) was performed at 3 Tesla, and response inhibition assessed by the Stroop Word-Color Test (SWCT) and the Wisconsin Card Sorting Test (WCST). Linear correlations between cerebellar GABA/Glx levels, SWCT time/error interference effects and WCST perseverative errors were performed to test differences between correlation coefficients in PD and HC. Results showed that higher levels of mean cerebellar GABA were associated to SWCT increased time and error interference effects in PD, and the contrary in HC. Such effect dissociated by hemisphere, while correlation coefficients differences were significant in both right and left cerebellum. We conclude that MRS measured levels of cerebellar GABA are related in PD patients with decreased efficiency in filtering task-irrelevant information. This is crucial for developing pharmacological treatments for PD to potentially preserve cognitive functioning.
, Yash Patel, Nadine Parker, Jean Shin, Derek Howard, Leon French, Sophia I. Thomopoulos, Elena Pozzi, Yoshinari Abe, Christoph Abé,et al.
JAMA Psychiatry American Medical Association (AMA)
Importance
Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood.
Objective
To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia.
Design, Setting, and Participants
Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244.
Main Outcomes and Measures
Interregional profiles of group difference in cortical thickness between cases and controls.
Results
A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders.
Conclusions and Relevance
In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.
Gianfranco Spalletta, Mariangela Iorio, Daniela Vecchio, Federica Piras, Valentina Ciullo, Nerisa Banaj, Stefano L. Sensi, Walter Gianni, Francesca Assogna, Carlo Caltagirone,et al.
MDPI AG
White matter hyperintensities (WMH) are associated with brain aging and behavioral symptoms as a possible consequence of disrupted white matter pathways. In this study, we investigated, in a cohort of asymptomatic subjects aged 50 to 80, the relationship between WMH, hippocampal atrophy, and subtle, preclinical cognitive and neuropsychiatric phenomenology. Thirty healthy subjects with WMH (WMH+) and thirty individuals without (WMH−) underwent comprehensive neuropsychological and neuropsychiatric evaluations and 3 Tesla Magnetic Resonance Imaging scan. The presence, degree of severity, and distribution of WMH were evaluated with a semi-automated algorithm. Volumetric analysis of hippocampal structure was performed through voxel-based morphometry. A multivariable logistic regression analysis indicated that phenomenology of subclinical apathy and anxiety was associated with the presence of WMH. ROI-based analyses showed a volume reduction in the right hippocampus of WMH+. In healthy individuals, WMH are associated with significant preclinical neuropsychiatric phenomenology, as well as hippocampal atrophy, which are considered as risk factors to develop cognitive impairment and dementia.