ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

RELIABILITY OF THE BICAUDATE PARAMETER IN THE REVEALING OF THE ENLARGED LATERAL VENTRICLES IN SCHIZOPHRENIA PATIENTS

Introduction: In schizophrenia patients the lateral ventricle enlargement has mostly been reported in relationship with smaller cortical and/or subcortical brain volumes; and it has been observed that ventricular system growth may be a consequence of the smaller caudate nucleus volume. Bicaudate parameters have been used in the Alzheimer dementia and Huntington’s chorea diagnosing in order to evaluate brain changes and the enlargement of the lateral ventricles. Subjects and methods: This study has been carried out on 140 patients out of which 70 patients (30 men and 40 women) who met the ICD 10 criteria for schizophrenia and 70 healthy controls (30 men and 40 women) matched on sex and age with the studied group. All of them underwent direct caudatometry and volume computation based on MRI scans. Results: Except for the bicorporal line, for all the parameters were obtained the statistically highly significant differences between the examined and control groups. Significant correlation was established for the majority of bicaudate parameters and volumes of the caudate nuclei and lateral ventricles. Discussion: Enlargement of the lateral ventricles is one of the most frequent MRI finding in schizophrenia patients. Ventricles are enlarging gradually and frontal horns are more affected than other parts. The increased volumes of the caudate nuclei signalized that ventricular enlargement is not the consequence of the caudate atrophy. Conclusion: Bicaudate parameters are reliable parameters for the quick orientation in order to assess the enlarged ventricles in schizophrenia patients

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Increased hippocampal shape asymmetry and volumetric ventricular asymmetry in autism spectrum disorder

Autism spectrum disorder (ASD) is a prevalent and fast-growing pervasive neurodevelopmental disorder worldwide. Despite the increasing prevalence of ASD and the breadth of research conducted on the disorder, a conclusive etiology has yet to be established and controversy still exists surrounding the anatomical abnormalities in ASD. In particular, structural asymmetries have seldom been investigated in ASD, especially in subcortical regions. Additionally, the majority of studies for identifying structural biomarkers associated with ASD have focused on small sample sizes. Therefore, the present study utilizes a large-scale, multi-site database to investigate asymmetries in the amygdala, hippocampus, and lateral ventricles, given the potential involvement of these regions in ASD. Contrary to prior work, we are not only computing volumetric asymmetries, but also shape asymmetries, using a new measure of asymmetry based on spectral shape descriptors. This measure represents the magnitude of the asymmetry and therefore captures both directional and undirectional asymmetry. The asymmetry analysis is conducted on 437 individuals with ASD and 511 healthy controls using T1-weighted MRI scans from the Autism Brain Imaging Data Exchange (ABIDE) database. Results reveal significant asymmetries in the hippocampus and the ventricles, but not in the amygdala, in individuals with ASD. We observe a significant increase in shape asymmetry in the hippocampus, as well as increased volumetric asymmetry in the lateral ventricles in individuals with ASD. Asymmetries in these regions have not previously been reported, likely due to the different characterization of neuroanatomical asymmetry and smaller sample sizes used in previous studies. Given that these results were demonstrated in a large cohort, such asymmetries may be worthy of consideration in the development of neurodiagnostic classification tools for ASD

Do the asymmetry and the size of the structures of the temporal lobe persist in early stages of schizophrenia?

A total of 14 patients of various ages diagnosed with schizophrenia and, as an age-matched control group, 12 healthy subjects were examined using the MRI method of neuro-imaging. The volume of the following structures was evaluated in the right and left hemispheres: the superior temporal gyrus, the basolateral temporal area (the region including the middle temporal gyrus, inferior temporal gyrus and fusiform gyrus), the parahippocampal gyrus, the hippocampal head, the amygdaloid body and the inferior horn of the lateral ventricle. In schizophrenia a significant increase in the volume of the amygdaloid body on both the left and right sides was observed. In the patients, as in the control group, we noticed significant asymmetry between the left and right sides in the volume of the structures studied. The left amygdaloid body was significantly larger than the right, whereas the left hippocampal head and the temporal horn of the lateral ventricle were smaller than the right. Our findings suggest that in the early stages of schizophrenia, despite the increased volume of the amygdaloid body, the asymmetry between the structures of the temporal lobe is still present. However, the changes observed in the temporal lobe could be related to the functional disturbances observed in this disease

Abnormalities of brain structure and lateralisation in schizophrenia

Researchers have proposed that schizophrenia is a disease related to abnormal cerebral lateralisation following findings of increased "schizophrenia-like" symptoms in left-hemisphere epileptics. Theories regarding abnormal brain structural asymmetries in schizophrenia suggest either ambiguous or extreme motor asymmetry. These theories are conceptually similar to ones proposed to explain non-right-handedness in normal subjects. In this thesis I objectively evaluate these hypotheses. Firstly, I critically survey the neuropsychological literature and find the evidence for lateralised cognitive deficit to be inconclusive. Next, a meta-analysis of studies reporting the finding of ventricular enlargement in schizophrenia is carried out and it is found that findings are highly influenced by methodological factors. A review of the literature concerning lateralised neuropathologies from brain imaging and postmortem studies similarly finds the evidence to be hindered by differences in experimental methodology. Furthermore, there is much disagreement between researchers regarding which asymmetries are empirically or theoretically meaningful. The next chapter concentrates exclusively with the experimental measurement of hand performance. The Annett pegboard, the Tapley and Bryden circle marking, and the Bishop square tracing tasks of hand performance are extended and used to test hand performance in normal subjects as a function of increasing task difficulty. Pursuit tracking is used to consider the Fourier spectrum and sub-components of relative hand performance. The differences between the hands on the conventional and tracking tasks are then subjected to factor analyses. Surprising results are obtained in which performance tasks show moderate-to-high internal reliability but correlate poorly with one another. Their relevance to handedness and motor research is then discussed. Schizophrenic hand preference is investigated in a meta-analytic assessment of studies reporting an increased incidence of non-dextral hand preference in schizophrenia. This is examined with respect to the definition and methods of measurement in these studies. Finally, the hand performance of schizophrenics is investigated. Testing hand performance, in conjunction with hand preference measures, allows for greater reliability in the evaluation of the notion of abnormal handedness in schizophrenia. Patients show poorer overall performance on all of the tasks, but show no significant differences in their degree of handedness as compared to normals. Conclusions are drawn that associations between abnormal handedness and disorders of brain structural asymmetry in schizophrenic patients are unlikely. Further implications for abnormalities of cerebral dominance and schizophrenia are considered

Psychiatric Epidemiology and Neuroscience Unite in the Pursuit of Reformulated Schizophrenia Nosologies

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Image databases in medical applications

The number of medical images acquired yearly in hospitals increases all the time. These imaging data contain lots of information on the characteristics of anatomical structures and on their variations. This information can be utilized in numerous medical applications. In deformable model-based segmentation and registration methods, the information in the image databases can be used to give a priori information on the shape of the object studied and the gray-level values in the image, and on their variations. On the other hand, by studying the variations of the object of interest in different populations, the effects of, for example, aging, gender, and diseases on anatomical structures can be detected. In the work described in this Thesis, methods that utilize image databases in medical applications were studied. Methods were developed and compared for deformable model-based segmentation and registration. Model selection procedure, mean models, and combination of classifiers were studied for the construction of a good a priori model. Statistical and probabilistic shape models were generated to constrain the deformations in segmentation and registration so that only the shapes typical to the object studied were accepted. In the shape analysis of the striatum, both volume and local shape changes were studied. The effects of aging and gender, and also the asymmetries were examined. The results proved that the segmentation and registration accuracy of deformable model-based methods can be improved by utilizing the information in image databases. The databases used were relatively small. Therefore, the statistical and probabilistic methods were not able to model all the population-specific variation. On the other hand, the simpler methods, the model selection procedure, mean models, and combination of classifiers, gave good results also with the small image databases. Two main applications were the reconstruction of 3-D geometry from incomplete data and the segmentation of heart ventricles and atria from short- and long-axis magnetic resonance images. In both applications, the methods studied provided promising results. The shape analysis of the striatum showed that the volume of the striatum decreases in aging. Also, the shape of the striatum changes locally. Asymmetries in the shape were found, too, but any gender-related local shape differences were not found.reviewe