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1.
Proc Natl Acad Sci U S A ; 120(22): e2218565120, 2023 05 30.
Article in English | MEDLINE | ID: mdl-37216540

ABSTRACT

A long-standing topic of interest in human neurosciences is the understanding of the neurobiology underlying human cognition. Less commonly considered is to what extent such systems may be shared with other species. We examined individual variation in brain connectivity in the context of cognitive abilities in chimpanzees (n = 45) and humans in search of a conserved link between cognition and brain connectivity across the two species. Cognitive scores were assessed on a variety of behavioral tasks using chimpanzee- and human-specific cognitive test batteries, measuring aspects of cognition related to relational reasoning, processing speed, and problem solving in both species. We show that chimpanzees scoring higher on such cognitive skills display relatively strong connectivity among brain networks also associated with comparable cognitive abilities in the human group. We also identified divergence in brain networks that serve specialized functions across humans and chimpanzees, such as stronger language connectivity in humans and relatively more prominent connectivity between regions related to spatial working memory in chimpanzees. Our findings suggest that core neural systems of cognition may have evolved before the divergence of chimpanzees and humans, along with potential differential investments in other brain networks relating to specific functional specializations between the two species.


Subject(s)
Connectome , Pan troglodytes , Animals , Humans , Neurobiology , Brain , Cognition , Magnetic Resonance Imaging
2.
Proc Natl Acad Sci U S A ; 120(14): e2213880120, 2023 04 04.
Article in English | MEDLINE | ID: mdl-36976765

ABSTRACT

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.


Subject(s)
Schizophrenia , Male , Female , Humans , Schizophrenia/diagnostic imaging , Case-Control Studies , Brain/diagnostic imaging , Cerebral Cortex , Magnetic Resonance Imaging/methods , Functional Laterality
3.
Psychol Med ; 54(5): 1016-1025, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37749940

ABSTRACT

BACKGROUND: Two established staging models outline the longitudinal progression in bipolar disorder (BD) based on episode recurrence or inter-episodic functioning. However, underlying neurobiological mechanisms and corresponding biomarkers remain unexplored. This study aimed to investigate if global and (sub)cortical brain structures, along with brain-predicted age difference (brain-PAD) reflect illness progression as conceptualized in these staging models, potentially identifying brain-PAD as a biomarker for BD staging. METHODS: In total, 199 subjects with bipolar-I-disorder and 226 control subjects from the Dutch Bipolar Cohort with a high-quality T1-weighted magnetic resonance imaging scan were analyzed. Global and (sub)cortical brain measures and brain-PAD (the difference between biological and chronological age) were estimated. Associations between individual brain measures and the stages of both staging models were explored. RESULTS: A higher brain-PAD (higher biological age than chronological age) correlated with an increased likelihood of being in a higher stage of the inter-episodic functioning model, but not in the model based on number of mood episodes. However, after correcting for the confounding factors lithium-use and comorbid anxiety, the association lost significance. Global and (sub)cortical brain measures showed no significant association with the stages. CONCLUSIONS: These results suggest that brain-PAD may be associated with illness progression as defined by impaired inter-episodic functioning. Nevertheless, the significance of this association changed after considering lithium-use and comorbid anxiety disorders. Further research is required to disentangle the intricate relationship between brain-PAD, illness stages, and lithium intake or anxiety disorders. This study provides a foundation for potentially using brain-PAD as a biomarker for illness progression.


Subject(s)
Bipolar Disorder , Humans , Bipolar Disorder/complications , Lithium , Brain/diagnostic imaging , Brain/pathology , Aging , Biomarkers
4.
Article in English | MEDLINE | ID: mdl-38613677

ABSTRACT

Over 50% of children with a parent with severe mental illness will develop mental illness by early adulthood. However, intergenerational transmission of risk for mental illness in one's children is insufficiently considered in clinical practice, nor is it sufficiently utilised into diagnostics and care for children of ill parents. This leads to delays in diagnosing young offspring and missed opportunities for protective actions and resilience strengthening. Prior twin, family, and adoption studies suggest that the aetiology of mental illness is governed by a complex interplay of genetic and environmental factors, potentially mediated by changes in epigenetic programming and brain development. However, how these factors ultimately materialise into mental disorders remains unclear. Here, we present the FAMILY consortium, an interdisciplinary, multimodal (e.g., (epi)genetics, neuroimaging, environment, behaviour), multilevel (e.g., individual-level, family-level), and multisite study funded by a European Union Horizon-Staying-Healthy-2021 grant. FAMILY focuses on understanding and prediction of intergenerational transmission of mental illness, using genetically informed causal inference, multimodal normative prediction, and animal modelling. Moreover, FAMILY applies methods from social sciences to map social and ethical consequences of risk prediction to prepare clinical practice for future implementation. FAMILY aims to deliver: (i) new discoveries clarifying the aetiology of mental illness and the process of resilience, thereby providing new targets for prevention and intervention studies; (ii) a risk prediction model within a normative modelling framework to predict who is at risk for developing mental illness; and (iii) insight into social and ethical issues related to risk prediction to inform clinical guidelines.

5.
J Neurosci ; 42(18): 3704-3715, 2022 05 04.
Article in English | MEDLINE | ID: mdl-35318286

ABSTRACT

Scaling between subcomponents of folding and total brain volume (TBV) in healthy individuals (HIs) is allometric. It is unclear whether this is true in schizophrenia (SZ) or first-episode psychosis (FEP). This study confirmed normative allometric scaling norms in HIs using discovery and replication samples. Cross-sectional and longitudinal diagnostic differences in folding subcomponents were then assessed using an allometric framework. Structural imaging from a longitudinal (Sample 1: HI and SZ, nHI Baseline = 298, nSZ Baseline = 169, nHI Follow-up = 293, nSZ Follow-up = 168, totaling 1087 images, all individuals ≥ 2 images, age 16-69 years) and a cross-sectional sample (Sample 2: nHI = 61 and nFEP = 89, age 10-30 years), all human males and females, is leveraged to calculate global folding and its nested subcomponents: sulcation index (SI, total sulcal/cortical hull area) and determinants of sulcal area: sulcal length and sulcal depth. Scaling of SI, sulcal area, and sulcal length with TBV in SZ and FEP was allometric and did not differ from HIs. Longitudinal age trajectories demonstrated steeper loss of SI and sulcal area through adulthood in SZ. Longitudinal allometric analysis revealed that both annual change in SI and sulcal area was significantly stronger related to change in TBV in SZ compared with HIs. Our results detail the first evidence of the disproportionate contribution of changes in SI and sulcal area to TBV changes in SZ. Longitudinal allometric analysis of sulcal morphology provides deeper insight into lifespan trajectories of cortical folding in SZ.SIGNIFICANCE STATEMENT Psychotic disorders are associated with deficits in cortical folding and brain size, but we lack knowledge of how these two morphometric features are related. We leverage cross-sectional and longitudinal samples in which we decompose folding into a set of nested subcomponents: sulcal and hull area, and sulcal depth and length. We reveal that, in both schizophrenia and first-episode psychosis, (1) scaling of subcomponents with brain size is different from expected scaling laws and (2) caution is warranted when interpreting results from traditional methods for brain size correction. Longitudinal allometric scaling points to loss of sulcal area as a principal contributor to loss of brain size in schizophrenia. These findings advance the understanding of cortical folding atypicalities in psychotic disorders.


Subject(s)
Psychotic Disorders , Schizophrenia , Adolescent , Adult , Aged , Brain/anatomy & histology , Cerebral Cortex , Child , Cross-Sectional Studies , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging/methods , Male , Middle Aged , Schizophrenia/diagnostic imaging , Young Adult
6.
Psychol Med ; 53(3): 741-749, 2023 02.
Article in English | MEDLINE | ID: mdl-34078485

ABSTRACT

BACKGROUND: Childhood trauma increases risk for psychopathology and cognitive impairment. Prior research mainly focused on the hippocampus and amygdala in single diagnostic categories. However, other brain regions may be impacted by trauma as well, and effects may be independent of diagnosis. This cross-sectional study investigated cortical and subcortical gray matter volume in relation to childhood trauma severity. METHODS: We included 554 participants: 250 bipolar-I patients, 84 schizophrenia-spectrum patients and 220 healthy individuals without a psychiatric history. Participants filled in the Childhood Trauma Questionnaire. Anatomical T1 MRI scans were acquired at 3T, regional brain morphology was assessed using Freesurfer. RESULTS: In the total sample, trauma-related gray matter reductions were found in the frontal lobe (ß = -0.049, p = 0.008; q = 0.048), this effect was driven by the right medial orbitofrontal, paracentral, superior frontal regions and the left precentral region. No trauma-related volume reductions were observed in any other (sub)cortical lobes nor the hippocampus or amygdala, trauma-by-group (i.e. both patient groups and healthy subjects) interaction effects were absent. A categorical approach confirmed a pattern of more pronounced frontal gray matter reductions in individuals reporting multiple forms of trauma and across quartiles of cumulative trauma scores. Similar dose-response patterns were revealed within the bipolar and healthy subgroups, but did not reach significance in schizophrenia-spectrum patients. CONCLUSIONS: Findings show that childhood trauma is linked to frontal gray matter reductions, independent of psychiatric morbidity. Our results indicate that childhood trauma importantly contributes to the neurobiological changes commonly observed across psychiatric disorders. Frontal volume alterations may underpin affective and cognitive disturbances observed in trauma-exposed individuals.


Subject(s)
Adverse Childhood Experiences , Gray Matter , Humans , Gray Matter/diagnostic imaging , Gray Matter/pathology , Cross-Sectional Studies , Brain/pathology , Magnetic Resonance Imaging/methods
7.
Dev Med Child Neurol ; 65(12): 1557-1572, 2023 12.
Article in English | MEDLINE | ID: mdl-37035939

ABSTRACT

AIM: To investigate the association between early brain magnetic resonance imaging (MRI) findings and neurodevelopmental outcome (NDO) in children with congenital heart disease (CHD). METHOD: A search for studies was conducted in Embase, Medline, Web of Science, Cochrane Central, PsycINFO, and Google Scholar. Observational and interventional studies were included, in which patients with CHD underwent surgery before 2 months of age, a brain MRI scan in the first year of life, and neurodevelopmental assessment beyond the age of 1 year. RESULTS: Eighteen studies were included. Thirteen found an association between either quantitative or qualitative brain metrics and NDO: 5 out of 7 studies showed decreased brain volume was significantly associated with worse NDO, as did 7 out of 10 studies on brain injury. Scanning protocols and neurodevelopmental tests varied strongly. INTERPRETATION: Reduced brain volume and brain injury in patients with CHD can be associated with impaired NDO, yet standardized scanning protocols and neurodevelopmental assessment are needed to further unravel trajectories of impaired brain development and its effects on outcome.


Subject(s)
Brain Injuries , Heart Defects, Congenital , Humans , Child , Heart Defects, Congenital/complications , Heart Defects, Congenital/diagnostic imaging , Heart Defects, Congenital/surgery , Magnetic Resonance Imaging , Brain/pathology , Brain Injuries/complications , Brain Injuries/diagnostic imaging , Brain Injuries/pathology
8.
Dev Med Child Neurol ; 65(11): 1493-1500, 2023 11.
Article in English | MEDLINE | ID: mdl-37072934

ABSTRACT

AIM: To identify meaningful outcomes of children and their caregivers attending a paediatric brain centre. METHOD: We compiled a long list of outcomes of health and functioning of children with brain-related disorders such as cerebral palsy, spina bifida, (genetic) neurodevelopmental disorders, and acquired brain injury. We incorporated three perspectives: patients, health care professionals, and published outcome sets. An aggregated list was categorized using the International Classification of Functioning, Disability, and Health: Children and Youth version in a patient validation survey for children and parent-caregivers to prioritize outcomes. Outcomes were considered meaningful when ranked 'very important' by 70% or more of the participants. RESULTS: We identified 104 outcomes from the three perspectives. After categorizing, 59 outcomes were included in the survey. Thirty-three surveys were completed by children (n = 4), caregivers (n = 24), and parent-caregivers together with their child (n = 5). Respondents prioritized 27 meaningful outcomes covering various aspects of health and functioning: emotional well-being, quality of life, mental and sensory functions, pain, physical health, and activities (communication, mobility, self-care, interpersonal relationships). Parent-caregiver concerns and environmental factors were newly identified outcomes. INTERPRETATION: Children and parent-caregivers identified meaningful outcomes covering various aspects of health and functioning, including caregiver concerns and environmental factors. We propose including those in future outcome sets for children with neurodisability. WHAT THIS PAPER ADDS: Outcomes that children with brain-related disorders and their parent-caregivers consider to be the most meaningful cover a wide range of aspects of functioning. Involving these children and their parent-caregivers resulted in the identification of important outcomes that were not covered by professionals and the literature. Parent-caregiver-related factors (coping, burden of care) and environmental factors (support, attitudes, and [health care] services) were identified as meaningful.


Subject(s)
Caregivers , Disabled Children , Adolescent , Child , Humans , Caregivers/psychology , Disabled Children/psychology , Quality of Life , Health Personnel , Brain
9.
Eur J Pediatr ; 182(3): 1057-1066, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36565322

ABSTRACT

Previous studies have frequently reported neurocognitive deficits in children born with congenital diaphragmatic hernia (CDH) at school age, which may contribute to academic difficulties. Yet, age at onset of these deficits is currently unknown. We evaluated neurocognitive skills with possible determinants in preschool children born with CDH. Eligible 5-year-old children born with CDH (2010-2015) who participated in our prospective structural follow-up program were included. We used the WPPSI-III to assess intelligence, subtests of the Kaufman-ABC for memory, and NEPSY-II to assess inhibition and attention. We included 63 children. Their test scores generally were within or significantly above normal range: total IQ = 103.4 (15.7) (p = 0.13); Verbal memory = 10.2 (2.8) (p = 0.61); Visuospatial memory = 11.4 (2.6) (p < 0.01); Inhibition = 10.5 (2.2), (p = 0.10). In univariable analyses, length of ICU-stay was negatively associated with IQ, and maximum vasoactive inotropic score and open repair were negatively associated with inhibition skills. In multivariable regression analysis, the latter association remained (B = 5.52, p = 0.04 (CI 0.32-10.72)).   Conclusions: In these tested 5-year-old children born with CDH, neuropsychological outcome was normal on average. While problems in 8-year-olds are common, we did not detect onset of these problems at age 5. Yet, we cannot rule out that this cohort had a relatively mild level of disease severity; therefore, conclusions should be interpreted with caution. However, given the growing-into-deficit hypothesis, meaning that deviant brain development in early life is revealed once higher cognitive brain functions are demanded, follow-up should be conducted up to school age, and preferably beyond. What is Known: • Children born with CDH are at risk for academic difficulties at school age. • Whether these difficulties can be detected already before school age is unknown. What is New: • At age 5 years, intelligence, inhibition, attention, and memory skills were all within normal range, or even above, in children with CDH. This is supportive of the growing-into-deficit hypothesis in this patient population. • Those who underwent open surgical correction had poorer inhibition skills than those who were corrected with minimal access surgery.


Subject(s)
Hernias, Diaphragmatic, Congenital , Child, Preschool , Humans , Hernias, Diaphragmatic, Congenital/complications , Prospective Studies , Brain , Neuropsychological Tests , Survivors
10.
Hum Brain Mapp ; 43(1): 56-82, 2022 01.
Article in English | MEDLINE | ID: mdl-32725849

ABSTRACT

MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.


Subject(s)
Bipolar Disorder , Cerebral Cortex , Magnetic Resonance Imaging , Neuroimaging , Bipolar Disorder/diagnostic imaging , Bipolar Disorder/pathology , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Humans , Meta-Analysis as Topic , Multicenter Studies as Topic
11.
Cereb Cortex ; 31(11): 5107-5120, 2021 10 01.
Article in English | MEDLINE | ID: mdl-34179960

ABSTRACT

Sex differences in the development and aging of human sulcal morphology have been understudied. We charted sex differences in trajectories and inter-individual variability of global sulcal depth, width, and length, pial surface area, exposed (hull) gyral surface area, unexposed sulcal surface area, cortical thickness, gyral span, and cortex volume across the lifespan in a longitudinal sample (700 scans, 194 participants 2 scans, 104 three scans, age range: 16-70 years) of neurotypical males and females. After adjusting for brain volume, females had thicker cortex and steeper thickness decline until age 40 years; trajectories converged thereafter. Across sexes, sulcal shortening was faster before age 40, while sulcal shallowing and widening were faster thereafter. Although hull area remained stable, sulcal surface area declined and was more strongly associated with sulcal shortening than with sulcal shallowing and widening. Males showed greater variability for cortex volume and lower variability for sulcal width. Our findings highlight the association between loss of sulcal area, notably through sulcal shortening, with cortex volume loss. Studying sex differences in lifespan trajectories may improve knowledge of individual differences in brain development and the pathophysiology of neuropsychiatric conditions.


Subject(s)
Longevity , Sex Characteristics , Adolescent , Adult , Aged , Aging/physiology , Cerebral Cortex , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Young Adult
12.
Health Expect ; 25(5): 2235-2245, 2022 10.
Article in English | MEDLINE | ID: mdl-35084076

ABSTRACT

INTRODUCTION: Paediatric patients with disorders that involve brain functioning are particularly vulnerable with respect to including them in shared decision-making. Current tools are mostly paper or digital patient information. We lay the groundwork for improving engagement with a concept that we coined 'the Self-Portrait'. The main goals were to identify (1) obstacles and (2) design parameters that enable patient participation. METHODS: A research-through-design approach was utilized in nine patients with brain-related disorders (4-12 years), 15 parents and 15 medical professionals, involving contextual research (interviews and observations) within the paediatric hospital and patients' homes and codesign. Sensitizing materials and early instances of design solutions were deployed as catalysts for communication. Five rounds of enriched interviews and design reviews were thematically analysed to answer the research questions. RESULTS: Obstacles to child involvement were related to children's level of understanding, the time and energy necessary for information processing and lack of perceived relevance of the information. Patients' engagement is supported by design features that extend the time frame of interaction beyond the consultation, transfer information interactively and give control and influence during the consultation. CONCLUSION: Obstacles were detected that complicate child engagement, which differ between stakeholders. Promising design features were identified that have the potential to play an important role in enabling active child involvement. These findings show that applying principles of human-centred design research and codesign can bring together patients, parents and medical professionals around a tool that provides a shared language and focus, which are prerequisites to increase child engagement. PATIENT OR PUBLIC CONTRIBUTION: Patients, parents and clinicians contributed as design informants during contextual research and design reviews. Clinicians provided feedback on the initial outcomes of thematic analysis. Two researchers assisted in consensus sessions during the thematic analysis.


Subject(s)
Decision Making , Patient Participation , Child , Humans , Communication , Parents , Brain
13.
Hum Brain Mapp ; 42(11): 3643-3655, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33973694

ABSTRACT

Surface rendering of MRI brain scans may lead to identification of the participant through facial characteristics. In this study, we evaluate three methods that overwrite voxels containing privacy-sensitive information: Face Masking, FreeSurfer defacing, and FSL defacing. We included structural T1-weighted MRI scans of children, young adults and older adults. For the young adults, test-retest data were included with a 1-week interval. The effects of the de-identification methods were quantified using different statistics to capture random variation and systematic noise in measures obtained through the FreeSurfer processing pipeline. Face Masking and FSL defacing impacted brain voxels in some scans especially in younger participants. FreeSurfer defacing left brain tissue intact in all cases. FSL defacing and FreeSurfer defacing preserved identifiable characteristics around the eyes or mouth in some scans. For all de-identification methods regional brain measures of subcortical volume, cortical volume, cortical surface area, and cortical thickness were on average highly replicable when derived from original versus de-identified scans with average regional correlations >.90 for children, young adults, and older adults. Small systematic biases were found that incidentally resulted in significantly different brain measures after de-identification, depending on the studied subsample, de-identification method, and brain metric. In young adults, test-retest intraclass correlation coefficients (ICCs) were comparable for original scans and de-identified scans with average regional ICCs >.90 for (sub)cortical volume and cortical surface area and ICCs >.80 for cortical thickness. We conclude that apparent visual differences between de-identification methods minimally impact reliability of brain measures, although small systematic biases can occur.


Subject(s)
Brain/diagnostic imaging , Data Anonymization , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Neuroimaging , Adult , Age Factors , Aged , Aged, 80 and over , Cerebral Cortex , Child , Female , Humans , Male , Middle Aged , Young Adult
14.
Psychol Med ; 51(2): 340-350, 2021 01.
Article in English | MEDLINE | ID: mdl-31858920

ABSTRACT

BACKGROUND: Neuroanatomical abnormalities in first-episode psychosis (FEP) tend to be subtle and widespread. The vast majority of previous studies have used small samples, and therefore may have been underpowered. In addition, most studies have examined participants at a single research site, and therefore the results may be specific to the local sample investigated. Consequently, the findings reported in the existing literature are highly heterogeneous. This study aimed to overcome these issues by testing for neuroanatomical abnormalities in individuals with FEP that are expressed consistently across several independent samples. METHODS: Structural Magnetic Resonance Imaging data were acquired from a total of 572 FEP and 502 age and gender comparable healthy controls at five sites. Voxel-based morphometry was used to investigate differences in grey matter volume (GMV) between the two groups. Statistical inferences were made at p < 0.05 after family-wise error correction for multiple comparisons. RESULTS: FEP showed a widespread pattern of decreased GMV in fronto-temporal, insular and occipital regions bilaterally; these decreases were not dependent on anti-psychotic medication. The region with the most pronounced decrease - gyrus rectus - was negatively correlated with the severity of positive and negative symptoms. CONCLUSIONS: This study identified a consistent pattern of fronto-temporal, insular and occipital abnormalities in five independent FEP samples; furthermore, the extent of these alterations is dependent on the severity of symptoms and duration of illness. This provides evidence for reliable neuroanatomical alternations in FEP, expressed above and beyond site-related differences in anti-psychotic medication, scanning parameters and recruitment criteria.


Subject(s)
Brain/pathology , Psychotic Disorders/pathology , Adolescent , Adult , Case-Control Studies , Cerebral Cortex/pathology , Female , Gray Matter/pathology , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Organ Size , Psychiatric Status Rating Scales , Young Adult
15.
Brain ; 142(12): 3991-4002, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31724729

ABSTRACT

The genetic basis and human-specific character of schizophrenia has led to the hypothesis that human brain evolution may have played a role in the development of the disorder. We examined schizophrenia-related changes in brain connectivity in the context of evolutionary changes in human brain wiring by comparing in vivo neuroimaging data from humans and chimpanzees, one of our closest living evolutionary relatives and a species with which we share a very recent common ancestor. We contrasted the connectome layout between the chimpanzee and human brain and compared differences with the pattern of schizophrenia-related changes in brain connectivity as observed in patients. We show evidence of evolutionary modifications of human brain connectivity to significantly overlap with the cortical pattern of schizophrenia-related dysconnectivity (P < 0.001, permutation testing). We validated these effects in three additional, independent schizophrenia datasets. We further assessed the specificity of effects by examining brain dysconnectivity patterns in seven other psychiatric and neurological brain disorders (including, among others, major depressive disorder and obsessive-compulsive disorder, arguably characterized by behavioural symptoms that are less specific to humans), which showed no such associations with modifications of human brain connectivity. Comparisons of brain connectivity across humans, chimpanzee and macaques further suggest that features of connectivity that evolved in the human lineage showed the strongest association to the disorder, that is, brain circuits potentially related to human evolutionary specializations. Taken together, our findings suggest that human-specific features of connectome organization may be enriched for changes in brain connectivity related to schizophrenia. Modifications in human brain connectivity in service of higher order brain functions may have potentially also rendered the brain vulnerable to brain dysfunction.


Subject(s)
Biological Evolution , Brain/physiopathology , Nerve Net/physiopathology , Schizophrenia/physiopathology , Adult , Animals , Brain/diagnostic imaging , Connectome , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Nerve Net/diagnostic imaging , Pan troglodytes , Schizophrenia/diagnostic imaging
16.
Pediatr Res ; 85(1): 43-49, 2019 01.
Article in English | MEDLINE | ID: mdl-30254237

ABSTRACT

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) in term-born infants can lead to memory problems. The hippocampus is important for long-term episodic memory. The primary aim was to investigate the effect of HIE on hippocampal volumes in 9- to 10-year-old children. The secondary aim was to investigate the association between hippocampal volumes and previously found impaired memory and cognitive functions in the current cohort. METHODS: In total 26 children with mild HIE, 26 with moderate HIE, and 37 controls were included. The intelligence quotient (IQ) and memory were tested. A 3D-volumetric MRI was obtained. Brain segmentation was performed for hippocampal volumes and intracranial volume. The differences in hippocampal volumes, memory, and IQ between the groups were determined. Multivariable linear regression analyses were performed, including hippocampal volume as a percentage of intracranial volume as a dependent variable. RESULTS: Smaller hippocampal volumes were found in moderate HIE (p < 0.001), with a trend toward smaller volumes in mild HIE, compared to controls. In multivariable linear regression analysis, hippocampal volume as a percentage of intracranial volume was significantly associated with long-term visuospatial memory. CONCLUSION: Children with moderate HIE had smaller hippocampal volumes than controls, with a trend toward smaller volumes following mild HIE. Reduced hippocampal volumes were associated with poorer long-term visuospatial memory.


Subject(s)
Child Development , Hippocampus/diagnostic imaging , Hypoxia-Ischemia, Brain/diagnostic imaging , Magnetic Resonance Imaging , Age Factors , Case-Control Studies , Child , Child Behavior , Cognition , Female , Hippocampus/growth & development , Humans , Hypoxia-Ischemia, Brain/complications , Hypoxia-Ischemia, Brain/physiopathology , Hypoxia-Ischemia, Brain/psychology , Intelligence Tests , Male , Memory , Memory Disorders/diagnosis , Memory Disorders/etiology , Memory Disorders/psychology , Predictive Value of Tests , Time Factors
17.
J Psychiatry Neurosci ; 44(3): 177-184, 2019 05 01.
Article in English | MEDLINE | ID: mdl-30525317

ABSTRACT

Background: Schizophrenia is a disorder of basic self-disturbance. Evidence suggests that people with schizophrenia may have aberrant experiences of body ownership: they may feel that they are not the subject of their own body experiences. However, little is known about the development of such disturbances. Methods: Using a rubber hand illusion paradigm, we assessed body ownership in patients with schizophrenia (n = 54), healthy controls (n = 56), children/adolescents at increased familial risk of developing schizophrenia (n = 24) or mood disorders (n = 33), and children/adolescents without this risk (n = 18). In this paradigm, a rubber hand (visible) and a participant's real hand (invisible) were stroked synchronously and asynchronously; we then measured subjective illusory experiences and proprioceptive drift. Results: All groups showed the expected effect of the rubber hand illusion: stronger proprioceptive drift and increased subjective illusory experiences after synchronous versus asynchronous stroking. The effect of synchronicity on subjective experiences was significantly weaker in patients with schizophrenia than in healthy controls, and subjective ratings were positively correlated with delusions in patients. We found no significant differences between children/adolescents with and without increased familial risk. Limitations: Large individual differences raised questions for future research. Conclusion: We found subtle disturbances in body-ownership experiences in patients with schizophrenia, which were associated with delusions. We found no evidence for impairments in children/adolescents at increased familial risk of developing schizophrenia or a mood disorder. Longitudinal data might reveal whether impairments in body ownership are predictive of psychosis onset.


Subject(s)
Child of Impaired Parents , Illusions/physiology , Perceptual Disorders/physiopathology , Proprioception/physiology , Schizophrenia/physiopathology , Sensation Disorders/physiopathology , Touch Perception/physiology , Visual Perception/physiology , Adolescent , Adult , Child , Cohort Studies , Female , Hand/physiopathology , Humans , Male , Middle Aged , Perceptual Disorders/etiology , Risk , Schizophrenia/complications , Sensation Disorders/etiology , Young Adult
18.
Psychol Res ; 83(5): 842-851, 2019 Jul.
Article in English | MEDLINE | ID: mdl-28840393

ABSTRACT

When interacting with others, people represent their own as well as their interaction partners' actions. Such joint action representation is essential for action coordination, but may also interfere with action control. We investigated how joint action representations affect experienced control over people's own actions and their interaction partners' actions. Participants performed a joint go/no-go task, which is commonly used to measure to what extent people represent their own actions in spatial reference to their interaction partner (e.g., as 'left' vs. 'right'). After each second trial, participants indicated experienced control over their own action, their interaction partner's action, or over action inhibition. Despite this frequent interruption of the go/no-go task, we found strong evidence for the spatial representation of joint actions. However, this joint action representation did not affect experiences of control. Possible explanations and implications of these findings are discussed.


Subject(s)
Cooperative Behavior , Inhibition, Psychological , Psychomotor Performance , Choice Behavior , Humans
19.
Behav Res Methods ; 51(5): 2059-2073, 2019 10.
Article in English | MEDLINE | ID: mdl-30937848

ABSTRACT

Reverse correlation is an influential psychophysical paradigm that uses a participant's responses to randomly varying images to build a classification image (CI), which is commonly interpreted as a visualization of the participant's mental representation. It is unclear, however, how to statistically quantify the amount of signal present in CIs, which limits the interpretability of these images. In this article, we propose a novel metric, infoVal, which assesses informational value relative to a resampled random distribution and can be interpreted like a z score. In the first part, we define the infoVal metric and show, through simulations, that it adheres to typical Type I error rates under various task conditions (internal validity). In the second part, we show that the metric correlates with markers of data quality in empirical reverse-correlation data, such as the subjective recognizability, objective discriminability, and test-retest reliability of the CIs (convergent validity). In the final part, we demonstrate how the infoVal metric can be used to compare the informational value of reverse-correlation datasets, by comparing data acquired online with data acquired in a controlled lab environment. We recommend a new standard of good practice in which researchers assess the infoVal scores of reverse-correlation data in order to ensure that they do not read signal in CIs where no signal is present. The infoVal metric is implemented in the open-source rcicr R package, to facilitate its adoption.


Subject(s)
Computer Simulation , Adult , Female , Humans , Male , Reproducibility of Results , Young Adult
20.
Neuroimage ; 124(Pt A): 1044-1053, 2016 Jan 01.
Article in English | MEDLINE | ID: mdl-26424180

ABSTRACT

Intelligence is associated with a network of distributed gray matter areas including the frontal and parietal higher association cortices and primary processing areas of the temporal and occipital lobes. Efficient information transfer between gray matter regions implicated in intelligence is thought to be critical for this trait to emerge. Genetic factors implicated in intelligence and gray matter may promote a high capacity for information transfer. Whether these genetic factors act globally or on local gray matter areas separately is not known. Brain maps of phenotypic and genetic associations between gray matter volume and intelligence were made using structural equation modeling of 3T MRI T1-weighted scans acquired in 167 adult twins of the newly acquired U-TWIN cohort. Subsequently, structural connectivity analyses (DTI) were performed to test the hypothesis that gray matter regions associated with intellectual ability form a densely connected core. Gray matter regions associated with intellectual ability were situated in the right prefrontal, bilateral temporal, bilateral parietal, right occipital and subcortical regions. Regions implicated in intelligence had high structural connectivity density compared to 10,000 reference networks (p=0.031). The genetic association with intelligence was for 39% explained by a genetic source unique to these regions (independent of total brain volume), this source specifically implicated the right supramarginal gyrus. Using a twin design, we show that intelligence is genetically represented in a spatially distributed and densely connected network of gray matter regions providing a high capacity infrastructure. Although genes for intelligence have overlap with those for total brain volume, we present evidence that there are genes for intelligence that act specifically on the subset of brain areas that form an efficient brain network.


Subject(s)
Gray Matter/anatomy & histology , Gray Matter/physiology , Intelligence/genetics , Intelligence/physiology , Nerve Net/anatomy & histology , Nerve Net/physiology , Adult , Brain/anatomy & histology , Brain/physiology , Brain Mapping , Diffusion Tensor Imaging , Female , Humans , Image Processing, Computer-Assisted , Intelligence Tests , Male , Models, Genetic , Phenotype , Twins , Twins, Dizygotic , Twins, Monozygotic
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