publications

Papers and preprints

1. Microstructural asymmetry in the human cortex Wan B^*, Saberi A, Paquola C, Schaare H, Hettwer M, Royer J, John A, Dorfschmidt L, Bayrak Ş, Bethlehem R, Eickhoff S, Bernhardt B, and Valk S^* Nature Communications 2024 [abstract] [url] [pdf]

   The human cerebral cortex shows hemispheric asymmetry, yet the microstructural basis of this asymmetry remains incompletely understood. Here, we probe layer-specific microstructural asymmetry using one post-mortem male brain. Overall, anterior and posterior regions show leftward and rightward asymmetry respectively, but this pattern varies across cortical layers. A similar anterior-posterior pattern is observed using in vivo Human Connectome Project (N = 1101) T1w/T2w microstructural data, with average cortical asymmetry showing the strongest similarity with post-mortem-based asymmetry of layer III. Moreover, microstructural asymmetry is found to be heritable, varies as a function of age and sex, and corresponds to intrinsic functional asymmetry. We also observe a differential association of language and markers of mental health with microstructural asymmetry patterns at the individual level, illustrating a functional divergence between inferior-superior and anterior-posterior microstructural axes, possibly anchored in development. Last, we could show concordant evidence with alternative in vivo microstructural measures: magnetization transfer (N = 286) and quantitative T1 (N = 50). Together, our study highlights microstructural asymmetry in the human cortex and its functional and behavioral relevance.

2. Bias-accounting meta-analyses overcome cerebellar neglect to refine the cerebellar behavioral topography Magielse N^*, Manoli A, Eickhoff S, Fox P, Saberi A^†, and Valk S^*† bioRxiv 2024 [abstract] [url] [pdf]

   The cerebellum plays important roles in motor, cognitive, and emotional behaviors. Previous cerebellar coordinate-based meta-analyses and mappings have attributed different behaviors to cerebellar subareas, but an accurate behavioral topography is lacking. Here, we show overrepresentation of superior activation foci, which may be exacerbated by historical cerebellar neglect. Unequal foci distributions render the null hypothesis of standard activation likelihood estimation unsuitable. Our new method, cerebellum-specific activation-likelihood estimation (C-SALE), finds behavioral convergence beyond baseline activation rates. It does this by testing experimental foci versus null models sampled from a data-driven, biased probability distribution of finding foci at any cerebellar location. Cerebellar mappings were made across five BrainMap task domains and thirty-five subdomains, illustrating improved specificity of the new method. Twelve of forty (sub)domains reached convergence in specific cerebellar subregions, supporting dual motor representations and placing cognition in posterior-lateral regions. Repeated subsampling revealed that whereas action, language and working memory were relatively stable, other behaviors produced unstable meta-analytic maps. Lastly, meta-analytic connectivity modeling in the same debiased framework was used to reveal coactivation networks of cerebellar behavioral clusters. In sum, we created a new method for cerebellar meta-analysis that accounts for data biases and can be flexibly adapted to any part of the brain. Our findings provide a refined understanding of cerebellar involvement in human behaviors, highlighting regions for future investigation in both basic and clinical applications.

3. Convergent functional effects of antidepressants in major depressive disorder: a neuroimaging meta-analysis Saberi A, Ebneabbasi A, Rahimi S, Sarebannejad S, Sen Z, Graf H, Walter M, Sorg C, Camilleri J, Laird A, Fox P, Valk S, Eickhoff S, and Tahmasian M^* Molecular Psychiatry 2024 [abstract] [url] [pdf]

   Neuroimaging studies have provided valuable insights into the macroscale impacts of antidepressants on brain functions in patients with major depressive disorder. However, the findings of individual studies are inconsistent. Here, we aimed to provide a quantitative synthesis of the literature to identify convergence of the reported findings at both regional and network levels and to examine their associations with neurotransmitter systems.

4. Regional patterns of human cortex development correlate with underlying neurobiology Lotter L, Saberi A, Hansen J, Misic B, Paquola C, Barker G, Bokde A, Desrivières S, Flor H, Grigis A, Garavan H, Gowland P, Heinz A, Brühl R, Martinot J, Paillère M, Artiges E, Papadopoulos Orfanos D, Paus T, Poustka L, Hohmann S, Fröhner J, Smolka M, Vaidya N, Walter H, Whelan R, Schumann G, Nees F, Banaschewski T, Eickhoff S, and Dukart J^* Nature Communications 2024 [abstract] [url] [pdf]

   Human brain morphology undergoes complex changes over the lifespan. Despite recent progress in tracking brain development via normative models, current knowledge of underlying biological mechanisms is highly limited. We demonstrate that human cortical thickness development and aging trajectories unfold along patterns of molecular and cellular brain organization, traceable from population-level to individual developmental trajectories. During childhood and adolescence, cortex-wide spatial distributions of dopaminergic receptors, inhibitory neurons, glial cell populations, and brain-metabolic features explain up to 50% of the variance associated with a lifespan model of regional cortical thickness trajectories. In contrast, modeled cortical thickness change patterns during adulthood are best explained by cholinergic and glutamatergic neurotransmitter receptor and transporter distributions. These relationships are supported by developmental gene expression trajectories and translate to individual longitudinal data from over 8000 adolescents, explaining up to 59% of developmental change at cohort- and 18% at single-subject level. Integrating neurobiological brain atlases with normative modeling and population neuroimaging provides a biologically meaningful path to understand brain development and aging in living humans.

5. Relating sex-bias in human cortical and hippocampal microstructure to sex hormones Küchenhoff S, Bayrak Ş, Zsido R, Saberi A, Bernhardt B, Weis S, Schaare H, Sacher J, Eickhoff S, and Valk S^* Nature Communications 2024 [abstract] [url] [pdf]

   Determining sex-bias in brain structure is of great societal interest to improve diagnostics and treatment of brain-related disorders. So far, studies on sex-bias in brain structure predominantly focus on macro-scale measures, and often ignore factors determining this bias. Here we study sex-bias in cortical and hippocampal microstructure in relation to sex hormones. Investigating quantitative intracortical profiling in-vivo using the T1w/T2w ratio in 1093 healthy females and males of the cross-sectional Human Connectome Project young adult sample, we find that regional cortical and hippocampal microstructure differs between males and females and that the effect size of this sex-bias varies depending on self-reported hormonal status in females. Microstructural sex-bias and expression of sex hormone genes, based on an independent post-mortem sample, are spatially coupled. Lastly, sex-bias is most pronounced in paralimbic areas, with low laminar complexity, which are predicted to be most plastic based on their cytoarchitectural properties. Albeit correlative, our study underscores the importance of incorporating sex hormone variables into the investigation of brain structure and plasticity. Here, the authors demonstrate that cortical microstructure in young adults shows marked sex bias, which is most pronounced in paralimbic areas. The effects are put into context with variations in sex hormones and local cytoarchitecture.

6. The interplay between insomnia symptoms and Alzheimer’s Disease across three main brain networks Elberse J, Saberi A, Ahmadi R, Changizi M, Bi H, Hoffstaedter F, Mander B, Eickhoff S, Tahmasian M^*, and Alzheimer’s Disease Neuroimaging Initiative Sleep 2024 [abstract] [url]

   Insomnia symptoms are prevalent along the trajectory of Alzheimer’s disease (AD), but the neurobiological underpinning of their interaction is poorly understood. Here, we assessed structural and functional brain measures within and between the default mode network (DMN), salience network (SN), and central executive network (CEN).We selected 320 subjects from the ADNI database and divided by their diagnosis: cognitively normal (CN), Mild Cognitive Impairment (MCI), and AD, with and without self-reported insomnia symptoms. We measured the gray matter volume (GMV), structural covariance (SC), degrees centrality (DC), and functional connectivity (FC), testing the effect and interaction of insomnia symptoms and diagnosis on each index. Subsequently, we performed a within-group linear regression across each network and ROI. Finally, we correlated observed abnormalities with changes in cognitive and affective scores.Insomnia symptoms were associated with FC alterations across all groups. The AD group also demonstrated an interaction between insomnia and diagnosis. Within-group analyses revealed that in CN and MCI, insomnia symptoms were characterised by within-network hyperconnectivity, while in AD, within- and between-network hypoconnectivity was ubiquitous. SC and GMV alterations were non-significant in the presence of insomnia symptoms, and DC indices only showed network-level alterations in the CEN of AD individuals. Abnormal FC within and between DMN and CEN hubs was additionally associated with reduced cognitive function across all groups, and increased depressive symptoms in AD.We conclude that patients with clinical AD present with a unique pattern of insomnia-related functional alterations, highlighting the profound interaction between both conditions.

7. Adolescent Maturation of Cortical Excitation-Inhibition Balance Based on Individualized Biophysical Network Modeling Saberi A, Wischnewski K, Jung K, Lotter L, Schaare H, Banaschewski T, Barker G, Bokde A, Desrivières S, Flor H, Grigis A, Garavan H, Gowland P, Heinz A, Brühl R, Martinot J, Martinot M, Artiges E, Nees F, Orfanos D, Lamaitre H, Poustka L, Hohmann S, Holz N, Baeuchl C, Smolka M, Vaidya N, Walter H, Whelan R, Schumann G, Consortium I, Paus T, Dukart J, Bernhardt B, Popovych O, Eickhoff S, and Valk S^* bioRxiv 2024 [abstract] [url] [pdf]

   The balance of excitation and inhibition is a key functional property of cortical microcircuits which changes through the lifespan. Adolescence is considered a crucial period for the maturation of excitation-inhibition balance. This has been primarily observed in animal studies, yet human in vivo evidence on adolescent maturation of the excitation-inhibition balance at the individual level is limited. Here, we developed an individualized in vivo marker of regional excitation-inhibition balance in human adolescents, estimated using large-scale simulations of biophysical network models fitted to resting-state functional magnetic resonance imaging data from two independent cross-sectional (N = 752) and longitudinal (N = 149) cohorts. We found a widespread relative increase of inhibition in association cortices paralleled by a relative age-related increase of excitation, or lack of change, in sensorimotor areas across both datasets. This developmental pattern co-aligned with multiscale markers of sensorimotor-association differentiation. The spatial pattern of excitation-inhibition development in adolescence was robust to inter-individual variability of structural connectomes and modeling configurations. Notably, we found that alternative simulation-based markers of excitation-inhibition balance show a variable sensitivity to maturational change. Taken together, our study highlights an increase of inhibition during adolescence in association areas using cross sectional and longitudinal data, and provides a robust computational framework to estimate microcircuit maturation in vivo at the individual level.

8. A Multimodal Characterization of Low-Dimensional Thalamocortical Structural Connectivity Patterns John A, Hettwer M, Schaare H, Saberi A, Bayrak Ş, Wan B, Royer J, Bernhardt B, and Valk S^* bioRxiv 2024 [abstract] [url] [pdf]

   The human thalamus is a bilateral and heterogeneous grey matter structure that plays a crucial role in coordinating whole-brain activity. Investigations of its complex structural and functional internal organization revealed to a certain degree overlapping parcellations, however, a consensus on thalamic subnuclei boundaries remains absent. Recent work suggests that thalamic organization might additionally reflect continuous axes transcending nuclear boundaries. In this study, we used a multimodal approach to uncover how low-dimensional axes that describe thalamic connectivity patterns to the cortex are related to internal thalamic microstructural features, functional connectivity, and structural covariance. We computed a thalamocortical structural connectome via probabilistic tractography on diffusion MRI and derived two main axes of thalamic organization. The principal thalamic gradient, extending from medial to lateral and differentiating between transmodal and unimodal nuclei, was related to intrathalamic myelin profiles, and patterns of functional connectivity, while the secondary axis showed correspondence to core-matrix cell type distributions. Lastly, exploring multimodal thalamocortical associations on a global scale, we observed that the medial-to- lateral gradient consistently differentiated limbic, frontoparietal, and default mode network nodes from dorsal and ventral attention networks across modalities. However, the link with sensory modalities varied. In sum, we show the coherence between lower dimensional patterns of thalamocortical structural connectivity and various modalities, shedding light on multiscale thalamic organization.

9. The regional variation of laminar thickness in the human isocortex is related to cortical hierarchy and interregional connectivity Saberi A, Paquola C, Wagstyl K, Hettwer M, Bernhardt B, Eickhoff S, and Valk S^* PLOS Biology 2023 [abstract] [url] [pdf]

   The human isocortex consists of tangentially organized layers with unique cytoarchitectural properties. These layers show spatial variations in thickness and cytoarchitecture across the neocortex, which is thought to support function through enabling targeted corticocortical connections. Here, leveraging maps of the 6 cortical layers based on 3D human brain histology, we aimed to quantitatively characterize the systematic covariation of laminar structure in the cortex and its functional consequences. After correcting for the effect of cortical curvature, we identified a spatial pattern of changes in laminar thickness covariance from lateral frontal to posterior occipital regions, which differentiated the dominance of infra- versus supragranular layer thickness. Corresponding to the laminar regularities of cortical connections along cortical hierarchy, the infragranular-dominant pattern of laminar thickness was associated with higher hierarchical positions of regions, mapped based on resting-state effective connectivity in humans and tract-tracing of structural connections in macaques. Moreover, we show that regions with similar laminar thickness patterns have a higher likelihood of structural connections and strength of functional connections. In sum, here, we characterize the organization of laminar thickness in the human isocortex and its association with cortico-cortical connectivity, illustrating how laminar organization may provide a foundational principle of cortical function.

10. Hippocampal metabolic subregions and networks: Behavioral, molecular, and pathological aging profiles Maleki Balajoo S, Eickhoff S, Masouleh S, Plachti A, Waite L, Saberi A, Bahri M, Bastin C, Salmon E, Hoffstaedter F, Palomero-Gallagher N, and Genon S^* Alzheimer’s & Dementia 2023 [abstract] [url] [pdf]

    INTRODUCTION Hippocampal local and network dysfunction is the hallmark of Alzheimer’s disease (AD). METHODS We characterized the spatial patterns of hippocampus differentiation based on brain co-metabolism in healthy elderly participants and demonstrated their relevance to study local metabolic changes and associated dysfunction in pathological aging. RESULTS The hippocampus can be differentiated into anterior/posterior and dorsal cornu ammonis (CA)/ventral (subiculum) subregions. While anterior/posterior CA show co-metabolism with different regions of the subcortical limbic networks, the anterior/posterior subiculum are parts of cortical networks supporting object-centered memory and higher cognitive demands, respectively. Both networks show relationships with the spatial patterns of gene expression pertaining to cell energy metabolism and AD’s process. Finally, while local metabolism is generally lower in posterior regions, the anterior–posterior imbalance is maximal in late mild cognitive impairment with the anterior subiculum being relatively preserved. DISCUSSION Future studies should consider bidimensional hippocampal differentiation and in particular the posterior subicular region to better understand pathological aging.

11. Schizophrenia and Macroscale Brain Structure: Genes in Context Hettwer M, Saberi A, Fan Y, and Valk S^* Biological Psychiatry 2022 [url]
12. Convergent regional brain abnormalities in behavioral variant frontotemporal dementia: A neuroimaging meta-analysis of 73 studies Kamalian A^†, Khodadadifar T^†, Saberi A, Masoudi M, Camilleri J, Eickhoff C, Zarei M, Pasquini L, Laird A, Fox P, Eickhoff S, and Tahmasian M^* Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring 2022 [abstract] [url] [pdf]

    Introduction Numerous studies have reported brain alterations in behavioral variant frontotemporal dementia (bvFTD). However, they pointed to inconsistent findings. Methods We used a meta-analytic approach to identify the convergent structural and functional brain abnormalities in bvFTD. Following current best-practice neuroimaging meta-analysis guidelines, we searched PubMed and Embase databases and performed reference tracking. Then, the coordinates of group comparisons between bvFTD and controls from 73 studies were extracted and tested for convergence using activation likelihood estimation. Results We identified convergent abnormalities in the anterior cingulate cortices, anterior insula, amygdala, paracingulate, striatum, and hippocampus. Task-based and resting-state functional connectivity pointed to the networks that are connected to the obtained consistent regions. Functional decoding analyses suggested associated dysfunction of emotional processing, interoception, reward processing, higher-order cognitive functions, and olfactory and gustatory perceptions in bvFTD. Discussion Our findings highlighted the key role of the salience network and subcortical regions in the pathophysiology of bvFTD.

13. Evaluation of curcumin as add-on therapy in patients with Parkinson’s disease: A pilot randomized, triple-blind, placebo-controlled trial Ghodsi H, Rahimi H, Aghili S, Saberi A, and Shoeibi A^* Clinical Neurology and Neurosurgery 2022 [abstract] [url]

    Background and objective Preclinical studies suggest that curcumin might be a potential neuroprotective agent in Parkinson’s disease (PD). This clinical trial aimed to evaluate the efficacy of adding nanomicelle curcumin on improving the motor and non-motor symptoms of PD patients and their quality of life. Material and methods Idiopathic PD patients aged ≥30 whose symptoms were under control were included in this pilot, randomized, triple-blind, placebo-controlled, add-on trial. Eligible patients were randomly assigned to either the curcumin (n= 30, 80mg/day) or placebo (n= 30) groups and were followed for nine months. Primary outcomes were the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Parkinson’s Disease Questionnaire (PDQ-39). These variables, along with demographic data, drug history, and possible side effects of curcumin, were gathered at the beginning of the study and every three months. A mixed effects model was used to compare the group-by-time interaction, followed by post hoc analysis. Results Although the mean MDS-UPDRS and PDQ-39 scores were not significantly different between the curcumin and placebo groups at any time points, MDS-UPDRS part III (P=0.04) showed a significant difference in its overall trend between the study groups. However, post hoc analysis failed to spot this difference at study time points. The most common side effects of curcumin were nausea and vomiting (P=0.25) and gastroesophageal reflux (P=0.42). Conclusion While curcumin is a well-tolerated natural compound, this trial was unsuccessful in showing its efficacy in quality of life and clinical symptoms of PD patients.

14. Is there any consistent structural and functional brain abnormality in narcolepsy? A meta-analytic perspective Rahimi Jafari S^†, Sareban Nejad S^†, Saberi A, Khazaie H, Camilleri J, Eickhoff C, Eickhoff S, and Tahmasian M^* Neuroscience & Biobehavioral Reviews 2021 [url]
15. Structural and functional neuroimaging of late-life depression: a coordinate-based meta-analysis Saberi A, Mohammadi E, Zarei M, Eickhoff S, and Tahmasian M^* Brain Imaging and Behavior 2021 [abstract] [url] [pdf]

    Several neuroimaging studies have investigated localized aberrations in brain structure, function or connectivity in late-life depression, but the ensuing results are equivocal and often conflicting. Here, we provide a quantitative consolidation of neuroimaging in late-life depression using coordinate-based meta-analysis by searching multiple databases up to March 2020. Our search revealed 3252 unique records, among which we identified 32 eligible whole-brain neuroimaging publications comparing 674 patients with 568 controls. The peak coordinates of group comparisons between the patients and the controls were extracted and then analyzed using activation likelihood estimation method. Our sufficiently powered analysis on all the experiments, and more homogenous subsections of the data (patients \textgreater controls, controls \textgreater patients, and functional imaging experiments) revealed no significant convergent regional abnormality in late-life depression. This inconsistency might be due to clinical and biological heterogeneity of LLD, as well as experimental (e.g., choice of tasks, image modalities) and analytic flexibility (e.g., preprocessing and analytic parameters), and distributed patterns of neural abnormalities. Our findings highlight the importance of clinical/biological heterogeneity of late-life depression, in addition to the need for more reproducible research by using pre-registered and standardized protocols on more homogenous populations to identify potential consistent brain abnormalities in late-life depression.

16. The Accuracy of Visceral Adiposity Index for the Screening of Metabolic Syndrome: A Systematic Review and Meta-Analysis Bijari M, Jangjoo S, Emami N, Raji S, Mottaghi M, Moallem R, Jangjoo A, and Saberi A^* International Journal of Endocrinology 2021 [abstract] [url] [pdf]

    Background and Aims. Visceral adiposity index (VAI) is a novel marker of fat distribution and function which incorporates both anthropometric and laboratory measures. Recently, several studies have suggested VAI as a screening tool for metabolic syndrome (MetS). Here, we aimed to consolidate the results of these studies by performing a systematic review and meta-analysis. Methods and Results. We searched PubMed and EMBASE online databases for eligible studies that investigated the association of VAI and MetS. After reviewing 294 records, we included 33 eligible papers with a sum of 20516 MetS and 53242 healthy participants. The risk of bias in the included studies was assessed, and the relevant data was extracted. All included studies reported a significant association between VAI and MetS screening, but were highly heterogeneous in their reported effects. We pooled the diagnostic test accuracy metrics of VAI for MetS screening and showed that it has a moderate-to-high accuracy with an area under the summary receiver operating characteristics curve of 0.847, a pooled sensitivity of 78%, and a pooled specificity of 79%. Besides, we pooled the difference in means of VAI between patients with MetS and healthy controls, revealing that VAI was 2.15 units higher in MetS patients. Conclusions. VAI is an accurate, low-cost, and widely available screening marker for MetS. However, further studies are needed to evaluate its applicability in clinical practice, determine an optimal cut-off, and identify populations that would benefit the most from it.

17. Chest computed tomography findings of COVID-19 in children younger than 1 year: a systematic review Ghodsi A, Bijari M, Alamdaran S, Saberi A, Mahmoudabadi E, Balali M, and Ghahremani S^* World Journal of Pediatrics 2021 [abstract] [url] [pdf]

    BACKGROUND: The aim of this systematic review is to evaluate the chest computed tomography (CT) findings in infants with confirmed COVID-19 infection by providing a comprehensive review of the existing literature. DATA SOURCES: A systematic search was conducted on PubMed and Embase from the onset of the COVID-19 outbreak to October 20, 2020, for studies that discussed the chest CT findings in infants younger than 1 year with COVID-19 infection. RESULTS: A total of 35 studies comprising 70 COVID-19 (58.5% boys) confirmed infants were included. The mean age of the included patients was 4.1 months with a range of 1 day to 12 months. Chest CT scans showed bilateral abnormalities in 34 patients, and unilateral lung involvement in 25 patients. Ground-glass opacities (GGO) (71.43%) were found to be the most prevalent chest CT manifestation, followed by peribronchial thickening (60%), linear or band-shaped opacities (32.8%), consolidation (28.57%), nodule (18.57%), effusion (7.14%) and focal lucency (7.14%). CONCLUSIONS: GGO and peribronchial thickening were the most prevalent findings in the infants’ chest CT scans. Linear or band-shaped opacities, consolidation, and pulmonary nodules are more common in infants than in adults. These findings suggest that the disease is more likely to be presented as an atypical pneumonia (peribronchial thickening and linear or band-shaped opacities) in this age group. Other chest CT scan manifestations can be classified as typical COVID-19 infection (peripheral GGO), lobar pneumonia (consolidation) and opportunistic infections (pulmonary nodules).

18. ENIGMA-Sleep: Challenges, opportunities, and the road map Tahmasian M^*, Aleman A, Andreassen O, Arab Z, Baillet M, Benedetti F, Bresser T, Bright J, Chee M, Chylinski D, Cheng W, Deantoni M, Dresler M, Eickhoff S, Eickhoff C, Elvsåshagen T, Feng J, Foster‐Dingley J, Ganjgahi H, Grabe H, Groenewold N, Ho T, Hong S, Houenou J, Irungu B, Jahanshad N, Khazaie H, Kim H, Koshmanova E, Kocevska D, Kochunov P, Lakbila‐Kamal O, Leerssen J, Li M, Luik A, Muto V, Narbutas J, Nilsonne G, O’Callaghan V, Olsen A, Osorio R, Poletti S, Poudel G, Reesen J, Reneman L, Reyt M, Riemann D, Rosenzweig I, Rostampour M, Saberi A, Schiel J, Schmidt C, Schrantee A, Sciberras E, Silk T, Sim K, Smevik H, Soares J, Spiegelhalder K, Stein D, Talwar P, Tamm S, Teresi G, Valk S, Someren E, Vandewalle G, Egroo M, Völzke H, Walter M, Wassing R, Weber F, Weihs A, Westlye L, Wright M, Wu M, Zak N, and Zarei M Journal of Sleep Research 2021 [abstract] [url] [pdf]

    Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.

19. Thalamic shape abnormalities in patients with multiple sclerosis-related fatigue Saberi A, Abdolalizadeh A, Mohammadi E, Nahayati M, Bagheri H, Shekarchi B, and Kargar J^* Neuroreport 2021 [abstract] [url] [pdf]

    Thalamus plays an important role in the pathogenesis of multiple sclerosis-related fatigue (MSrF). However, the thalamus is a heterogeneous structure and the specific thalamic subregions that are involved in this condition are unclear. Here, we used thalamic shape analysis for the detailed localization of thalamic abnormalities in MSrF. Using the Modified Fatigue Impact Scale, we measured fatigue in 42 patients with relapsing-remitting multiple sclerosis (MS). The thalamic shape was extracted from T1w images using an automated pipeline. We investigated the association of thalamic surface deviations with the severity of global fatigue and its cognitive, physical and psychosocial subdomains. Cognitive fatigue was correlated with an inward deformity of the left anteromedial thalamic surface, but no other localized shape deviation was observed in correlation with global, physical or psychosocial fatigue. Our findings indicate that the left anteromedial thalamic subregions are implicated in cognitive fatigue, possibly through their role in reward processing and cognitive and executive functions.

20. Predictive value of inflammatory markers for functional outcomes in patients with ischemic stroke Rezaeitalab F, Esmaeili M^*, Saberi A, Vahidi Z, Emadzadeh M, Rahimi H, Ramezani N, and Mirshabani-Toloti S Current Journal of Neurology 2020 [abstract] [url] [pdf]

    Background: Inflammatory processes have been proposed in the pathophysiology of ischemic stroke. The present study was designed to evaluate the relationship between tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), IL 1 beta (IL-1β), and high sensitivity C-reactive protein (hsCRP) with the prognosis and functional outcome in patients with less severe ischemic stroke., Methods: We measured the level of IL-1β, IL-6, hsCRP, and TNF-α on days 1 and 5 after stroke onset by enzyme-linked immunosorbent assay (ELISA). The infarct volume was assessed using Alberta Stroke Program Early CT Score (ASPECTS) and posterior circulation ASPECTS (pcASPECTS) score in brain computed tomography (CT) scan and magnetic resonance imaging (MRI). The severity of stroke was assessed by applying the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (MRS) in 24 hours on day 5 and after 3 months from stroke onset. Good outcome was defined as the third month MRS ≤ 2. The association of inflammatory markers and the course of stroke symptoms over time was examined., Results: Forty-four first-ever stroke patients without concurrent inflammatory diseases with a mean age of 65 years were included. The mean NIHSS and MRS in admission time were 6.5 ± 3.5 and 3.07, respectively. The day 1 and the day 5 levels of IL-1β, IL-6, hsCRP, and TNF-α were not significantly different in good and poor outcome groups (all P-values \textgreater 0.05). In addition, they were not significantly associated with the ASPECTS, pcASPECTS, and changes of NIHSS and MRS over time., Conclusion: The levels of hsCRP, IL-1β, IL-6, and TNF-α are not reliable predictors of functional outcomes in patients with less severe acute ischemic stroke (AIS).

21. Predictive value of red blood cell distribution width for mortality in patients with acute pancreatitis: A systematic review and meta-analysis Ganji A, Esmaeilzadeh A, Ghanaei O, Saberi A^*, Taherzadeh D, Sazgarnia S, Mayabi Joghal Z, Zirak M, AbdolahRamazani S, and Zarifmahmoudi L Medical Journal of the Islamic Republic of Iran 2017 [abstract] [url] [pdf]

    Background: Red blood cell distribution width (RDW) is a quantitative measure of variability in the size of circulating erythrocytes. It has been recently identified as a prognostic marker in several diseases including acute pancreatitis (AP). In this systematic review the prognostic value of RDW in predicting mortality of AP patients will be assessed.
    Methods: PubMed, Scopus, EMBASE, and ISI databases were searched until September 2016 using the following search strategy: (pancreatitis OR pancreatitides) AND (RDW OR "red cell distribution width" OR "red blood cell distribution width" OR anisocytosis). Four authors independently reviewed the retrieved articles. Studies were included if they had evaluated the association between RDW value and mortality of acute pancreatitis patients. Case reports, comments, letters to the editor, reviews, study protocols, and experimental studies were not included. Data abstraction and quality assessment for the included studies was independently performed by two authors. Quality of studies was assessed using Oxford Center for Evidence-Based Medicine checklist for prognostic studies. Data were synthesized qualitatively, and a meta-analysis was performed on the diagnostic performance of RDW to predict mortality in AP patients.
    Results: Seven studies (976 patients) were included in the systematic review. Six studies reported a statistically significant association between RDW value and mortality. Meta-analysis was performed on four studies (487 patients) using a bivariate model and a summary receiver operating characteristic (sROC) curve was plotted with an area under the curve (AUC) of 0.757. The pooled diagnostic odds ratio (DOR), sensitivity and specificity was 19.51 (95% CI: 5.26-72.30), 67% (95% CI: 51%-80%) and 90% (95% CI: 73%-96%), respectively.
    Conclusion: RDW is an easy to use and an inexpensive marker with a moderate prognostic value to predict death in AP patients. Clinicians should be more alert when a patient with AP has an increased RDW. Investigation of possible combinations of other prognostic markers with RDW is recommended.

^* corresponding author, ^† equal contribution

Conference Presentations

1. cuBNM: GPU-Accelerated Biophysical Network Modeling. 8th BigBrain Workshop (Padua, Italy) 2024 Talk
2. cuBNM: GPU-Accelerated Biophysical Network Modeling. 30th Annual Meeting of the Organization for Human Brain Mapping (Seoul, South Korea) 2024 [poster]
3. Adolescent maturation of cortical excitation-inhibition balance based on individualized biophysical network modeling. 30th Annual Meeting of the Organization for Human Brain Mapping (Seoul, South Korea) 2024 [poster]
4. Adolescent maturation of cortical excitation-inhibition balance based on individualized and GPU-accelerated biophysical network modeling. Gradients of Brain Organization Workshop (Seoul, South Korea) 2024 Invited Talk
5. Laminar thickness covariance in the BigBrain in association to cortical hierarchy and connectivity. qMRI 2023 Conference (Online) 2023 [abstract] [video] Talk

   Introduction: The cerebral cortex is a layered structure, and the cortical layers show spatial variations in thickness and cytoarchitecture across the neocortex, which is thought to support function through enabling targeted corticocortical connections [1–3]. Specifically, the inter-regional variation of cortical cytoarchitecture is suggested to relate to the likelihood and laminar pattern of cortico-cortical connections organized along a cortical hierarchy [2,4,5]. Here, we aimed to study the organization of laminar profiles across the cortical mantle and its relevance to cortical hierarchy and inter-regional connectivity to further understand the relationship between human intra-cortical structure and function. Methods: We used the maps of cortical layers based on the BigBrain, an ultra-high-resolution post-mortem histological atlas of a 65 year old male [6,7], to study laminar thickness covariation across the cerebral cortex (Fig 1a). We first excluded agranular, dysgranular and allocortical regions given their lack of a clear six-layer structure. To reduce the local effects of curvature on laminar thickness, we smoothed laminar thickness maps using a moving disk. Following, the laminar thickness maps were normalized by the total cortical thickness and parcellated using the Schaefer-1000 parcellation (Fig 1b,c). We next calculated the laminar thickness covariance (LTC) matrix, showing the similarity of laminar thickness patterns between cortical areas. Principal component analysis was then applied to the LTC matrix to identify the principal axis of laminar thickness covariation (LTC G1). We evaluated the association of LTC G1 with layer-/depth-wise measures of neuronal density and size in the BigBrain. Following, we assessed the relation of LTC G1 to two maps of cortical hierarchy, based on the asymmetry of effective connectivity in humans and the pattern of laminar projections in macaques. Lastly, we studied whether the similarity of regions in laminar thickness relates to their functional and structural connectivity using the data from the Human Connectome Project. Results: LTC G1 characterized a shift from the dominance of supragranular towards infragranular layers thickness from the occipital to lateral frontal areas. Along this axis we observed increased grey-matter density of all the layers with layer IV showing the strongest effect (r = 0.74, p < 0.001). In addition, the ratio of average neuronal size in layer III to layer V, as a proxy for externopyramidization, was increased along the axis (rho = 0.27, p = 0.01). We observed that the LTC G1 was aligned with the maps of asymmetry-based (r = -0.40, p < 0.001) and laminar-based hierarchy (r = -0.54, p < 0.001; Fig 2). In addition, LTC was correlated with the increased likelihood of SC (R2 = 0.082, p < 0.00) and increased strength of FC (r = 0.15, p < 0.001; Fig 3). Conclusions: We described an axis of laminar thickness covariation in the BigBrain, which characterized a structural shift from supra- to infragranular layer thickness. This shift was co-aligned with the asymmetry- and laminar-based maps of cortical hierarchy, with infragranular-dominant regions positioned higher across the hierarchy. Future work may help further understand the relevance of laminar structural variation to human brain function across the lifespan, ultimately providing insights into how the anatomy of the human brain supports human cognition.

6. Whole-brain dynamical modeling of the adolescent developing brain. 7th BigBrain Workshop (Reykjavík, Iceland) 2023 [abstract] [video] Talk

   Regulation of cortical microcircuits is crucial for optimal neural processing. Adolescence involves substantial macro- and microscale changes in the brain, including maturation of cortical microcircuits. Evidence from animal studies suggests a calibration of cortical microcircuits and excitation-to-inhibition (E-I) ratio during adolescence. However, in-vivo measurement of cortical microcircuits in the human developing brain is challenging, and therefore the supporting in-vivo evidence on maturation of E-I ratio in humans is limited. Whole-brain dynamical modeling is a promising approach that enables mechanistic inferences about hidden brain features, such as estimated properties of cortical microcircuits and E-I ratio. Here, we used whole-brain dynamical modeling to study age-related changes of whole-brain model parameters during adolescence. We simulated cortical activity based on a mean-field model of excitatory and inhibitory neuronal ensembles in regions connected based on subject-specific or group-averaged structural connectomes. The fit of simulations to empirical resting-state functional images of each subject was evaluated based on comparison of simulated and empirical functional connectivity as well as functional connectivity dynamics matrices. We identified optimal model parameters for each subject using covariance matrix adaptation evolution strategy as well as GPU-accelerated grid search of the whole parameter space. Based on the simulations performed with the optimal parameters, we calculated the regional E-I ratios in the simulation as their time-averaged simulated excitatory firing rates. We observed region-specific changes of E-I ratio with age, which was decreased in parietal and frontal regions and increased in occipital regions. In addition, we observed association of grey-white matter contrast with E-I ratio in specifc regions. Following, we aim to increase regional specificity of the simulations by introducing heterogeneity in the model parameters based on biological maps of receptors as well as myelo- and cytoarchitecture. Overall, we present a whole-brain modeling approach to estimate E-I ratio in developing adolescents which revealed region-specific changes of E-I ratio with age and its links to cortical microstructure.

7. Whole-brain dynamical modeling of the adolescent developing brain. 32nd Annual Computational Neuroscience Meeting / 29th Annual Meeting of the Organization for Human Brain Mapping (Leipzig, Germany / Montreal, Canada) 2023 [abstract] [poster]

   Introduction. Adolescence is a critical period of development which involves substantial macro- and microscale changes in the brain, including maturation of cortical microcircuits (Sydnor, 2021). Measuring properties of cortical microcircuitry in the developing brain is challenging, and the evidence supporting its maturation is mainly based on animal and post-mortem studies with limited in-vivo human evidence (Ghisleni, 2015; Larsen, 2022; Perica, 2022). Whole-brain dynamical modeling is a promising approach that enables mechanistic inferences about hidden brain features, such as estimated properties of cortical microcircuits (Park, 2021). Here, we used dynamical modeling to study age-related changes of whole-brain model parameters during adolescence.
   Methods. We studied adolescents from the Philadelphia Neurodevelopmental Cohort (N = 627, 364 females, age: 15.2±2.4 [10-19]). The T1w, rs-fMRI and DWI imaging data were preprocessed using FreeSurfer, fMRIPrep, micapipe and in-house scripts, resulting in the following for each subject: 1) structural connectome as the normalized number of streamlines between pairs of regions, 2) empirical functional connectome (FC) as the correlation of BOLD signals between regions, and 3) empirical functional connectivity dynamics (FCD) matrix, calculated by correlation of FC patterns between the time windows in time-resolved FC, parcellated based on the Schaefer-100 scheme. Next, we used a whole-brain dynamical modeling approach (Wong and Wang, 2006; Deco, 2014) to estimate subject-specific hidden parameters of cortical microcircuits by performing model inversion (Fig. 1). The model consists of ensembles of excitatory and inhibitory neurons in each region, with a set of stochastic differential equations governing their dynamics, and regions connected according to the SC. The model is controlled by free parameters including global coupling (G) as well as local excitatory-to-excitatory (wEE) and inhibitory-to-excitatory (wIE) connection weights. Given a set of parameters, the synaptic activity of neuronal ensembles was simulated for 450 seconds and converted to BOLD signal using the Balloon-Windkessel model. The simulated BOLD was used to calculate simulated FC and FCD, which were used to assess the simulation fit to empirical data. The simulations were performed based on subject-specific as well as group-averaged structural connectomes. Model optimization was performed using grid search and covariance matrix adaptation evolution strategy (Wischnewski, 2022). For each subject, we used simulated excitatory firing rate of the nodes from the optimal simulations as the measure of excitation-inhibition (E-I) ratio. Lastly, we studied age-related variation of regional E-I ratio, as well as their association with regional grey-white matter contrast as a measure of intracortical myelination.
   Results. The simulations using group-averaged SC led to an optimal fit of 0.21±0.7 across the subjects, which was higher than the optimal goodness of fits when subject-specific SCs were used. The goodness of fit significantly decreased with age (r = -0.15, p < 0.05). We observed a significant increase of optimal G with age (r = 0.10, p<0.05) in the group-SC models but no significant age-related changes of model parameters in the subject-SC models. The regional in silico excitatory firing rates showed region-specific changes with age, with decreased firing rate in parietal and frontal regions and increased firing rate of occipital regions. Grey-white matter contrast was was positively correlated with in silico excitatory firing rates in specific regions.
   Conclusions. Our whole-brain dynamical modeling approach revealed age-related region-specific changes of E-I ratio and its links to cortical microstructure. We observed decreased E-I ratio in frontal and parietal regions while it increased in occipital regions. This was in line with previous studies indicating decreased E-I ratio predominantly in association regions (Caballero, 2016; Larsen, 2022). We found association of grey-white matter contrast with E-I ratio, overall indicating increased inhibition with higher intracortical myelin, which was in line with findings on interactions of myelination and inhibitory activity and maturation (Stedehouder, 2017). Future work is needed to assess replicability of our findings using longitudinal samples and alternative models.

8. Organization of laminar thickness covariance in the human cortex 6th BigBrain Workshop (Zadar, Croatia) 2022 [abstract] [video] Talk

   The cerebral cortex is made up of roughly six horizontally organized layers with unique cytoarchitectural properties distributed across the cortical mantle. This gradual variation of laminar structure is a fundamental principle of cortical organization. The similarity of regions in their laminar structure, with roots in development, is suggested to relate to the likelihood, strength and direction of their connectivity. Current accounts of laminar structure variation are mainly based on theory-driven approaches in which histological samples of the cortex are labeled into discrete types based on visual inspection of laminar features. Here, leveraging on a data-driven map of the six cortical layers in the BigBrain, we aimed to quantitatively characterize the gradual variation of laminar structure in the cortex. We identified an organizational axis of laminar thickness covariance which differentiated the dominance of infragranular and supragranular layer thickness and in general followed a rostro-caudal trajectory. This axis was co-aligned with the cortical hierarchy such that infragranular-dominant regions towards the rostral pole of the cortex were overall higher up this functional hierarchy. Furthermore, laminar thickness variation was linked to connectivity, with regions with similar laminar thickness showed higher likelihood and strength of connectivity. Laminar thickness covariance was also related to structural covariance, reflecting shared developmental/maturational and genetics effects of the regions with similar laminar structure, which hints at developmental origins of laminar structure variability. In sum, we describe the organization of layer-wise thickness covariation in the cortical mantle and how it relates to structure and function.

9. Principal axis of laminar thickness covariance in the human cortex 28th Annual Meeting of the Organization for Human Brain Mapping (Glasgow, United Kingdom) 2022 [abstract] [poster] [video]

   The cerebral cortex consists of layers with unique properties that vary along the cortical mantle. The Structural Model proposes that similarity of regions in their laminar structure is related to the strength and direction of their connectivity, in addition to their degree of plasticity and disease vulnerability. In addition, there are several subtypes of excitatory and inhibitory neurons which have specific laminar and regional distributions, which may relate to the laminar structure variations. Here, we quantitatively characterized the main axis of laminar thickness covariance, leveraging a deep-learning based approximation of six cortical layers in the BigBrain, and studied its relation to connectivity, disease vulnerability and microcircuitry. We found that the main axis of cortical laminar thickness covariance differentiates the dominance of infragranular and supragranular layers, spanning from frontal to temporal, occipital and parietal regions. In support of the Structural Model, we showed that regions with similar laminar structure tend to connect together. In addition, regions with more prominent infragranular layers have higher hierarchy, i.e., influence the activity in other regions, which may relate to the laminar pattern of feedback/-forward connections. We also showed that disease vulnerability of regions relate to their laminar structure, as the main axis of laminar thickness covariance was correlated with the main axis of disease co-alteration. However, we found no significant correlation between the main axes of covariance in excitatory and inhibitory neuronal subtypes and the main axis of laminar thickness covariance.

10. Characterising the cortical gradients of laminar thickness similarity 5th BigBrain Workshop (Online) 2021 [abstract] [url] [poster]

    The cerebral cortex consists of distinct layers with unique properties and functions. Previous work has shown that the laminar architecture of cortical regions varies in a spatially ordered fashion along a ‘‘sensory-fugal’’ axis, with decreasing laminar differentiation from the unimodal to transmodal areas. Indeed, the “Structural Model” proposes that the isocortex can be divided into regions with comparable laminar structures, or cortical types, with links to their connections, plasticity and development. In this study, we leveraged the BigBrain map of cortical layers and used a non-linear manifold learning approach to probe along which organisational axes laminar structure covaries in the cortex.

11. Brain mediators of the vicarious facilitation of pain 7th Iranian Human Brain Mapping Congress (Tehran, Iran) 2020 [abstract] [video] Talk Best Presentation Award

    Introduction: The response to noxious stimuli can be facilitated by observing another person in pain [1]. This effect has been suggested to result from a sensorimotor resonance through the mirror neurons, or an increased level of arousal [2,3]. In this study, we used mediation effect parametric mapping (MEPM) to understand which regions of the brain mediate this effect. Method: We scanned 21 pain-free volunteers (10 females; mean age = 25.2±4.1) using fMRI while performing a vicarious pain facilitation paradigm. In each trial (N=24) participants observed neutral, fearful, or painful facial expressions, before receiving a shock that elicited the nociceptive flexion reflex (NFR), an objective indicative of nociceptive processing in the spinal cord and recorded their subjective pain ratings. We used multi-level MEPM to test the mediation effect of trial-by-trial voxel-wise brain activity in response to shocks for the relationship between the emotional valence of the observed facial expressions and pain ratings or NFR responses, after FDR correction (p<0.05, k=10). Results: The inferior frontal gyrus, inferior parietal lobe, ventromedial prefrontal cortex, paracentral lobule, cerebellum, and anterior cingulate cortex were significant mediators of vicarious facilitation of pain after observing both fearful and painful facial expressions. With the painful facial expressions, more widespread regions of the brain mediated this effect, additionally including precentral gyrus, superior frontal gyrus, superior temporal gyrus, the temporoparietal junction, superior parietal lobule, insula and thalamus. The increase in NFR after observing painful facial expressions was mediated by the putamen and superior temporal gyrus. Conclusions: The vicarious facilitation of pain is mediated by regions that are part of the human motor neuron system, or are involved in affective theory of mind, in addition to the regions involved in the emotional modulation of pain.

12. A Coordinate Based Meta-Analysis on the Brain Functional and Structural Changes in Late Life Depression 6th Iranian Human Brain Mapping Congress (Tehran, Iran) 2019 [abstract] Talk Best Presentation Award

    Late life depression (LLD) is turning into a health concern with the aging of the population. Its unique presentation with somatic symptoms and cognitive dysfunction highlights the need to study LLD as a distinct disease process from depression in younger adults. Numerous functional and structural neuroimaging studies have investigated the neural correlates of LLD, but have reported inconsistent results. In this study, we aimed to identify locations in the brain that were most consistently altered across the existing studies.Method We searched PubMed, Embase, and Web of Knowledge for relevant studies published until July 2019 and retrieved 2657 potential studies. All whole-brain voxel-based morphometry (VBM), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI) studies comparing patients with LLD and healthy controls (HC) were included. Two authors independently extracted the data and the peak coordinates of the significant foci. Coordinate-based meta-analysis was performed using the revised activation likelihood estimation (ALE) method according to the current best-practice guidelines.Results We identified 23 eligible studies (eight VBM, one PET, five resting-state fMRI, and ten task-based fMRI) including 516 LLD patients and 490 HCs. No significant converging structural and functional brain abnormalities between LLD and HC (27 experiments) was observed after controlling for multiple comparisons using a stringent cluster-level family-wise error correction (pcFWE = 0.680). Additionally, the meta-analysis on LLD > HC with 13 experiments (pcFWE = 0.069) and LLD < HC with 14 experiments (pcFWE = 0.357) revealed no significant convergent abnormalities.Conclusions The lack of convergence across individual studies might be related to the differences in experimental designs and statistical approaches, heterogeneity of clinical populations, and small sample sizes of the individual studies. Currently, there is not enough evidence available to pinpoint a specific underlying neural pathology associated with LLD.

13. Neutrophil to Lymphocyte Ratio as a Prognostic Marker in Glioblastoma Multiforme: a Systematic Review and Meta-Analysis 1st International Neuroinflammation Congress (Mashhad, Iran) 2017 [abstract] [url] [poster]

    Introduction: Glioblastoma multiforem (GBM) is the most common primary malignant brain tumor in adults and it is important to identify biomarkers that can predict its prognosis. The aim of this study was to systematically review the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in patients with GBM.
    Materials and Methods: PubMed, Scopus and EMBASE databases were searched until February 2016 using the following search strategy: neutrophil* AND lymphocyte* AND (glioma OR glioblastoma OR astrocytoma). Two authors independently screened the retrieved articles to find all the studies that evaluated the prognostic value of NLR in GBM patients. Data extraction and quality assessment for the included studies was performed independently by two authors. Studies using Cox proportional hazards model to compare overall survival (OS) in patients with low and high values of NLR were included in the meta-analysis.
    Results: Six studies and 827 patients were included in the systematic review. Progression-free survival (PFS) was the primary outcome in two studies. One study identified lower values of NLR as a significant predictor of better PFS, but the other one showed the opposite effect. Performing a meta-analysis was not possible on these two studies. The primary outcome in six studies was OS, four of which reported NLR as a significant prognostic marker. Pooled univariate hazard ratios (HRs) of two studies for predicting OS was 1.903 (95% CI: 1.420-2.551) and pooled multivariate HRs of four studies for predicting OS was 1.564 (95% CI: 1.208-2.024). Negligible heterogeneity was observed between studies.
    Conclusion: Overall survival of GBM patients can be predicted using NLR, but its application as a predictive marker of PFS is uncertain.

14. Cerebral blood volume as a prognostic marker in glioblastoma patients treated with bevacizumab: a systematic review 1st International Razavi Cancer Congress (Mashhad, Iran) 2016 [abstract] [url] [poster]

    Context: Bevacizumab is an FDA approved antiangiogenic agent for the treatment of recurrent glioblastoma. Patients have varied response to this treatment and it is important to identify biomarkers that can predict responders.
    Objective: To systematically review the prognostic value of cerebral blood volume (CBV) in glioblastoma patients treated with bevacizumab.
    Data sources: PubMed, Scopus and EMBASE databases were searched until March 2016 using the following search strategy: “glioblastoma AND bevacizumab AND (‘cerebral blood volume’ OR ‘relative blood volume’ OR CBV OR rCBV or RBV)”.
    Study Selection: Two authors independently reviewed the retrieved articles. All studies that evaluated the prognostic value of cerebral blood volume in glioblastoma patients treated with bevacizumab were included. Case reports, letters to editor and review articles were excluded.
    Data Extraction: Data extraction for included studies was performed independently by two authors. Quality of studies was assessed using Oxford Center for Evidence-Based Medicine checklist for prognostic studies.
    Results: Eight studies (303 patients) were included. In six studies all the patients had recurrent glioblastoma and in one study patients with grade III glioma were included as well. OS and PFS were the outcomes of interest in 7 and 8 studies, respectively. To evaluate the prognostic value of cerebral blood volume, six studies performed log-rank survival analysis and five studies used univariate or multivariate Cox proportional hazards model, three of which reported hazard ratios. Cerebral blood volume was reported as a significant predictor of OS and PFS in 4 studies (173 patients).
    Conclusions: The conflicting results of included studies indicate that the application of cerebral blood volume as a prognostic factor in glioblastoma patients treated with bevacizumab is uncertain. We suggest performing a meta-analysis to further explore this prognostic role.

15. The effect of stress on working memory in individuals with different personality traits 1st Razavi International Anxiety Congress (Mashhad, Iran) 2012 [abstract]

    Stress affects working memory based on plenty of evidences and in most cases its effect is impairing. It seems that severity of this effect depends on multiple factors. One of the possible factors may be personality traits. Current study is designed to examine probable vulnerability of some personality traits to the effect of social stress on working memory. In this study, performance of individuals in working memory test will be compared before and after the treatment with Trier Social Stress Test (TSST). Individuals’ personality will be evaluated based on NEO-FFI (NEO-Five Factor Inventory). Salivary Cortisol levels will be measured before and after the treatment as a marker of HPAA (Hypothalamic-Pituatury-Adrenal axis) activity. Finally, we will analyze the correlation between data obtained from working memory test and NEO-FFI.