RESUMEN
47,XXX (Triple X syndrome) is a sex chromosome aneuploidy characterized by the presence of a supernumerary X chromosome in affected females and is associated with a variable cognitive, behavioral, and psychiatric phenotype. The effect of a supernumerary X chromosome in affected females on intracortical microstructure is currently unknown. Therefore, we conducted 7 Tesla structural MRI and compared T1 (ms), as a proxy for intracortical myelin (ICM), across laminae of 21 adult women with 47,XXX and 22 age-matched typically developing females using laminar analyses. Relationships between phenotypic traits and T1 values in 47,XXX were also investigated. Adults with 47,XXX showed higher bilateral T1 across supragranular laminae in the banks of the superior temporal sulcus, and in the right inferior temporal gyrus, suggesting decreases of ICM primarily within the temporal cortex in 47,XXX. Higher social functioning in 47,XXX was related to larger inferior temporal gyrus ICM content. Our findings indicate an effect of a supernumerary X chromosome in adult-aged women on ICM across supragranular laminae within the temporal cortex. These findings provide insight into the role of X chromosome dosage on ICM across laminae. Future research is warranted to further explore the functional significance of altered ICM across laminae in 47,XXX.
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Imagen por Resonancia Magnética , Vaina de Mielina , Humanos , Femenino , Adulto , Vaina de Mielina/metabolismo , Imagen por Resonancia Magnética/métodos , Adulto Joven , Aberraciones Cromosómicas Sexuales , Persona de Mediana Edad , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/metabolismo , Trastornos de los Cromosomas Sexuales del Desarrollo Sexual/genética , Trastornos de los Cromosomas Sexuales del Desarrollo Sexual/diagnóstico por imagen , Cromosomas Humanos X/genética , Trisomía/genética , Corteza Cerebral/diagnóstico por imagenRESUMEN
22q11.2 deletion syndrome (22q11DS) is the most frequently occurring microdeletion in humans. It is associated with a significant impact on brain structure, including prominent reductions in gray matter volume (GMV), and neuropsychiatric manifestations, including cognitive impairment and psychosis. It is unclear whether GMV alterations in 22q11DS occur according to distinct structural patterns. Then, 783 participants (470 with 22q11DS: 51% females, mean age [SD] 18.2 [9.2]; and 313 typically developing [TD] controls: 46% females, mean age 18.0 [8.6]) from 13 datasets were included in the present study. We segmented structural T1-weighted brain MRI scans and extracted GMV images, which were then utilized in a novel source-based morphometry (SBM) pipeline (SS-Detect) to generate structural brain patterns (SBPs) that capture co-varying GMV. We investigated the impact of the 22q11.2 deletion, deletion size, intelligence quotient, and psychosis on the SBPs. Seventeen GMV-SBPs were derived, which provided spatial patterns of GMV covariance associated with a quantitative metric (i.e., loading score) for analysis. Patterns of topographically widespread differences in GMV covariance, including the cerebellum, discriminated individuals with 22q11DS from healthy controls. The spatial extents of the SBPs that revealed disparities between individuals with 22q11DS and controls were consistent with the findings of the univariate voxel-based morphometry analysis. Larger deletion size was associated with significantly lower GMV in frontal and occipital SBPs; however, history of psychosis did not show a strong relationship with these covariance patterns. 22q11DS is associated with distinct structural abnormalities captured by topographical GMV covariance patterns that include the cerebellum. Findings indicate that structural anomalies in 22q11DS manifest in a nonrandom manner and in distinct covarying anatomical patterns, rather than a diffuse global process. These SBP abnormalities converge with previously reported cortical surface area abnormalities, suggesting disturbances of early neurodevelopment as the most likely underlying mechanism.
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Síndrome de DiGeorge , Trastornos Psicóticos , Femenino , Humanos , Adolescente , Masculino , Síndrome de DiGeorge/diagnóstico por imagen , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Trastornos Psicóticos/complicaciones , Sustancia Gris/diagnóstico por imagenRESUMEN
BACKGROUND: Late-life depression has been associated with volume changes of the hippocampus. However, little is known about its association with specific hippocampal subfields over time. AIMS: We investigated whether hippocampal subfield volumes were associated with prevalence, course and incidence of depressive symptoms. METHOD: We extracted 12 hippocampal subfield volumes per hemisphere with FreeSurfer v6.0 using T1-weighted and fluid-attenuated inversion recovery 3T magnetic resonance images. Depressive symptoms were assessed at baseline and annually over 7 years of follow-up (9-item Patient Health Questionnaire). We used negative binominal, logistic, and Cox regression analyses, corrected for multiple comparisons, and adjusted for demographic, cardiovascular and lifestyle factors. RESULTS: A total of n = 4174 participants were included (mean age 60.0 years, s.d. = 8.6, 51.8% female). Larger right hippocampal fissure volume was associated with prevalent depressive symptoms (odds ratio (OR) = 1.26, 95% CI 1.08-1.48). Larger bilateral hippocampal fissure (OR = 1.37-1.40, 95% CI 1.14-1.71), larger right molecular layer (OR = 1.51, 95% CI 1.14-2.00) and smaller right cornu ammonis (CA)3 volumes (OR = 0.61, 95% CI 0.48-0.79) were associated with prevalent depressive symptoms with a chronic course. No associations of hippocampal subfield volumes with incident depressive symptoms were found. Yet, lower left hippocampal amygdala transition area (HATA) volume was associated with incident depressive symptoms with chronic course (hazard ratio = 0.70, 95% CI 0.55-0.89). CONCLUSIONS: Differences in hippocampal fissure, molecular layer and CA volumes might co-occur or follow the onset of depressive symptoms, in particular with a chronic course. Smaller HATA was associated with an increased risk of incident (chronic) depression. Our results could capture a biological foundation for the development of chronic depressive symptoms, and stresses the need to discriminate subtypes of depression to unravel its biological underpinnings.
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Depresión , Hipocampo , Humanos , Femenino , Persona de Mediana Edad , Masculino , Incidencia , Prevalencia , Hipocampo/patología , Lóbulo Temporal , Imagen por Resonancia Magnética/métodos , Tamaño de los ÓrganosRESUMEN
Psychotic experiences (PEs) occur in 5-10% of the general population and are associated with exposure to childhood trauma and obstetric complications. However, the neurobiological mechanisms underlying these associations are unclear. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we studied 138 young people aged 20 with PEs (n = 49 suspected, n = 53 definite, n = 36 psychotic disorder) and 275 controls. Voxel-based morphometry assessed whether MRI measures of grey matter volume were associated with (i) PEs, (ii) cumulative childhood psychological trauma (weighted summary score of 6 trauma types), (iii) cumulative pre/peri-natal risk factors for psychosis (weighted summary score of 16 risk factors), and (iv) the interaction between PEs and cumulative trauma or pre/peri-natal risk. PEs were associated with smaller left posterior cingulate (pFWE < 0.001, Z = 4.19) and thalamus volumes (pFWE = 0.006, Z = 3.91). Cumulative pre/perinatal risk was associated with smaller left subgenual cingulate volume (pFWE < 0.001, Z = 4.54). A significant interaction between PEs and cumulative pre/perinatal risk found larger striatum (pFWE = 0.04, Z = 3.89) and smaller right insula volume extending into the supramarginal gyrus and superior temporal gyrus (pFWE = 0.002, Z = 4.79), specifically in those with definite PEs and psychotic disorder. Cumulative childhood trauma was associated with larger left dorsal striatum (pFWE = 0.002, Z = 3.65), right prefrontal cortex (pFWE < 0.001, Z = 4.63) and smaller left insula volume in all participants (pFWE = 0.03, Z = 3.60), and there was no interaction with PEs group. In summary, pre/peri-natal risk factors and childhood psychological trauma impact similar brain pathways, namely smaller insula and larger striatum volumes. The effect of pre/perinatal risk was greatest in those with more severe PEs, whereas effects of trauma were seen in all participants. In conclusion, environmental risk factors affect brain networks implicated in schizophrenia, which may increase an individual's propensity to develop later psychotic disorders.
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Experiencias Adversas de la Infancia , Trastornos Psicóticos , Esquizofrenia , Niño , Humanos , Adolescente , Estudios Longitudinales , Imagen por Resonancia Magnética , EncéfaloRESUMEN
Pleiotropy occurs when a genetic variant influences more than one trait. This is a key property of the genomic architecture of psychiatric disorders and has been observed for rare and common genomic variants. It is reasonable to hypothesize that the microscale genetic overlap (pleiotropy) across psychiatric conditions and cognitive traits may lead to similar overlaps at the macroscale brain level such as large-scale brain functional networks. We took advantage of brain connectivity, measured by resting-state functional MRI to measure the effects of pleiotropy on large-scale brain networks, a putative step from genes to behaviour. We processed nine resting-state functional MRI datasets including 32 726 individuals and computed connectome-wide profiles of seven neuropsychiatric copy-number-variants, five polygenic scores, neuroticism and fluid intelligence as well as four idiopathic psychiatric conditions. Nine out of 19 pairs of conditions and traits showed significant functional connectivity correlations (rFunctional connectivity), which could be explained by previously published levels of genomic (rGenetic) and transcriptomic (rTranscriptomic) correlations with moderate to high concordance: rGenetic-rFunctional connectivity = 0.71 [0.40-0.87] and rTranscriptomic-rFunctional connectivity = 0.83 [0.52; 0.94]. Extending this analysis to functional connectivity profiles associated with rare and common genetic risk showed that 30 out of 136 pairs of connectivity profiles were correlated above chance. These similarities between genetic risks and psychiatric disorders at the connectivity level were mainly driven by the overconnectivity of the thalamus and the somatomotor networks. Our findings suggest a substantial genetic component for shared connectivity profiles across conditions and traits, opening avenues to delineate general mechanisms-amenable to intervention-across psychiatric conditions and genetic risks.
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Conectoma , Trastornos Mentales , Humanos , Pleiotropía Genética , Imagen por Resonancia Magnética , Trastornos Mentales/diagnóstico por imagen , Trastornos Mentales/genética , Encéfalo/diagnóstico por imagenRESUMEN
The survival and well-being of humans require solving the patch-switching problem: we must decide when to stop collecting rewards in a current patch and travel somewhere else where gains may be higher. Previous studies suggested that frontal regions are underpinned by several processes in the context of foraging decisions such as tracking task difficulty, and/or the value of exploring the environment. To dissociate between these processes, participants completed an fMRI patch-switching learning task inspired by behavioral ecology. By analyzing >11,000 trials collected across 21 participants, we found that the activation in the cingulate cortex was closely related to several patch-switching-related variables including the decision to leave the current patch, the encounter of a new patch, the harvest value, and the relative forage value. Learning-induced changes in the patch-switching threshold were tracked by activity within frontoparietal regions including the superior frontal gyrus and angular gyrus. Our findings suggest that frontoparietal regions shape patch-switching learning apart from encoding classical non-learning foraging processes. These findings provide a novel neurobiological understanding of how learning emerges neurocomputationally shaping patch-switching behavior with implications in real-life choices such as job selection and pave the way for future studies to probe the causal role of these neurobiological mechanisms.
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Lóbulo Frontal , Giro del Cíngulo , Humanos , Lóbulo Frontal/fisiología , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/fisiología , Corteza Prefrontal , Aprendizaje , Imagen por Resonancia MagnéticaRESUMEN
Triple X syndrome is a sex chromosomal aneuploidy characterized by the presence of a supernumerary X chromosome, resulting in a karyotype of 47,XXX in affected females. It has been associated with a variable cognitive, behavioral, and psychiatric phenotype, but little is known about its effects on brain function. We therefore conducted 7 T resting-state functional magnetic resonance imaging and compared data of 19 adult individuals with 47,XXX and 21 age-matched healthy control women using independent component analysis and dual regression. Additionally, we examined potential relationships between social cognition and social functioning scores, and IQ, and mean functional connectivity values. The 47,XXX group showed significantly increased functional connectivity of the fronto-parietal resting-state network with the right postcentral gyrus. Resting-state functional connectivity (rsFC) variability was not associated with IQ and social cognition and social functioning deficits in the participants with 47,XXX. We thus observed an effect of a supernumerary X chromosome in adult women on fronto-parietal rsFC. These findings provide additional insight into the role of the X chromosome on functional connectivity of the brain. Further research is needed to understand the clinical implications of altered rsFC in 47,XXX.
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Mapeo Encefálico , Encéfalo , Femenino , Animales , Mapeo Encefálico/métodos , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: Deep brain stimulation (DBS) is a highly efficient, evidence-based therapy to alleviate symptoms and improve quality of life in movement disorders such as Parkinson's disease, essential tremor, and dystonia, which is also being applied in several psychiatric disorders, such as obsessive-compulsive disorder and depression, when they are otherwise resistant to therapy. SUMMARY: At present, DBS is clinically applied in the so-called open-loop approach, with fixed stimulation parameters, irrespective of the patients' clinical state(s). This approach ignores the brain states or feedback from the central nervous system or peripheral recordings, thus potentially limiting its efficacy and inducing side effects by stimulation of the targeted networks below or above the therapeutic level. KEY MESSAGES: The currently emerging closed-loop (CL) approaches are designed to adapt stimulation parameters to the electrophysiological surrogates of disease symptoms and states. CL-DBS paves the way for adaptive personalized DBS protocols. This review elaborates on the perspectives of the CL technology and discusses its opportunities as well as its potential pitfalls for both clinical and research use in neuropsychiatric disorders.
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Estimulación Encefálica Profunda , Trastornos Mentales , Enfermedad de Parkinson , Humanos , Estimulación Encefálica Profunda/métodos , Calidad de Vida , Encéfalo , Trastornos Mentales/terapia , Enfermedad de Parkinson/terapiaRESUMEN
Human individuality is likely underpinned by the constitution of functional brain networks that ensure consistency of each person's cognitive and behavioral profile. These functional networks should, in principle, be detectable by noninvasive neurophysiology. We use a method that enables the detection of dominant frequencies of the interaction between every pair of brain areas at every temporal segment of the recording period, the dominant coupling modes (DoCM). We apply this method to brain oscillations, measured with magnetoencephalography (MEG) at rest in two independent datasets, and show that the spatiotemporal evolution of DoCMs constitutes an individualized brain fingerprint. Based on this successful fingerprinting we suggest that DoCMs are important targets for the investigation of neural correlates of individual psychological parameters and can provide mechanistic insight into the underlying neurophysiological processes, as well as their disturbance in brain diseases.
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Encefalopatías , Encéfalo , Humanos , Encéfalo/fisiología , Magnetoencefalografía/métodos , Mapeo Encefálico/métodosRESUMEN
BACKGROUND: Copy number variants (CNVs) have been associated with the risk of schizophrenia, autism and intellectual disability. However, little is known about their spectrum of psychopathology in adulthood. METHODS: We investigated the psychiatric phenotypes of adult CNV carriers and compared probands, who were ascertained through clinical genetics services, with carriers who were not. One hundred twenty-four adult participants (age 18-76), each bearing one of 15 rare CNVs, were recruited through a variety of sources including clinical genetics services, charities for carriers of genetic variants, and online advertising. A battery of psychiatric assessments was used to determine psychopathology. RESULTS: The frequencies of psychopathology were consistently higher for the CNV group compared to general population rates. We found particularly high rates of neurodevelopmental disorders (NDDs) (48%), mood disorders (42%), anxiety disorders (47%) and personality disorders (73%) as well as high rates of psychiatric multimorbidity (median number of diagnoses: 2 in non-probands, 3 in probands). NDDs [odds ratio (OR) = 4.67, 95% confidence interval (CI) 1.32-16.51; p = 0.017) and psychotic disorders (OR = 6.8, 95% CI 1.3-36.3; p = 0.025) occurred significantly more frequently in probands (N = 45; NDD: 39[87%]; psychosis: 8[18%]) than non-probands (N = 79; NDD: 20 [25%]; psychosis: 3[4%]). Participants also had somatic diagnoses pertaining to all organ systems, particularly conotruncal cardiac malformations (in individuals with 22q11.2 deletion syndrome specifically), musculoskeletal, immunological, and endocrine diseases. CONCLUSIONS: Adult CNV carriers had a markedly increased rate of anxiety and personality disorders not previously reported and high rates of psychiatric multimorbidity. Our findings support in-depth psychiatric and medical assessments of carriers of CNVs and the establishment of multidisciplinary clinical services.
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Trastornos Psicóticos , Esquizofrenia , Humanos , Variaciones en el Número de Copia de ADN/genética , Esquizofrenia/epidemiología , Esquizofrenia/genética , Trastornos Psicóticos/epidemiología , Psicopatología , Trastornos del Humor/epidemiología , Trastornos del Humor/genéticaRESUMEN
Copy Number Variation (CNV) at the 1q21.1 locus is associated with a range of neurodevelopmental and psychiatric disorders in humans, including abnormalities in head size and motor deficits. Yet, the functional consequences of these CNVs (both deletion and duplication) on neuronal development remain unknown. To determine the impact of CNV at the 1q21.1 locus on neuronal development, we generated induced pluripotent stem cells from individuals harbouring 1q21.1 deletion or duplication and differentiated them into functional cortical neurons. We show that neurons with 1q21.1 deletion or duplication display reciprocal phenotype with respect to proliferation, differentiation potential, neuronal maturation, synaptic density and functional activity. Deletion of the 1q21.1 locus was also associated with an increased expression of lower cortical layer markers. This difference was conserved in the mouse model of 1q21.1 deletion, which displayed altered corticogenesis. Importantly, we show that neurons with 1q21.1 deletion and duplication are associated with differential expression of calcium channels and demonstrate that physiological deficits in neurons with 1q21.1 deletion or duplication can be pharmacologically modulated by targeting Ca2+ channel activity. These findings provide biological insight into the neuropathological mechanism underlying 1q21.1 associated brain disorder and indicate a potential target for therapeutic interventions.
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Variaciones en el Número de Copia de ADN , Células Madre Pluripotentes Inducidas , Anomalías Múltiples , Animales , Deleción Cromosómica , Cromosomas Humanos Par 1 , Variaciones en el Número de Copia de ADN/genética , Humanos , Megalencefalia , Ratones , Neuronas , FenotipoRESUMEN
In the absence of sensory stimulation, the brain transits between distinct functional networks. Network dynamics such as transition patterns and the time the brain stays in each network link to cognition and behavior and are subject to much investigation. Auditory verbal hallucinations (AVH), the temporally fluctuating unprovoked experience of hearing voices, are associated with aberrant resting state network activity. However, we lack a clear understanding of how different networks contribute to aberrant activity over time. An accurate characterization of latent network dynamics and their relation to neurocognitive changes necessitates methods that capture the sub-second temporal fluctuations of the networks' functional connectivity signatures. Here, we critically evaluate the assumptions and sensitivity of several approaches commonly used to assess temporal dynamics of brain connectivity states in M/EEG and fMRI research, highlighting methodological constraints and their clinical relevance to AVH. Identifying altered brain connectivity states linked to AVH can facilitate the detection of predictive disease markers and ultimately be valuable for generating individual risk profiles, differential diagnosis, targeted intervention, and treatment strategies.
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Esquizofrenia , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Alucinaciones/diagnóstico por imagen , Humanos , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies. METHODS: Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes. RESULTS: The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses. CONCLUSIONS: Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.
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Cannabis , Esquizofrenia , Productos de Tabaco , Esquizofrenia/epidemiología , Esquizofrenia/genética , Nicotiana , Estudios Longitudinales , Predisposición Genética a la Enfermedad , Factores de RiesgoRESUMEN
Quality control of brain segmentation is a fundamental step to ensure data quality. Manual quality control strategies are the current gold standard, although these may be unfeasible for large neuroimaging samples. Several options for automated quality control have been proposed, providing potential time efficient and reproducible alternatives. However, those have never been compared side to side, which prevents consensus in the appropriate quality control strategy to use. This study aimed to elucidate the changes manual editing of brain segmentations produce in morphological estimates, and to analyze and compare the effects of different quality control strategies on the reduction of the measurement error. Structural brain MRI from 259 participants of The Maastricht Study were used. Morphological estimates were automatically extracted using FreeSurfer 6.0. Segmentations with inaccuracies were manually edited, and morphological estimates were compared before and after editing. In parallel, 12 quality control strategies were applied to the full sample. Those included: two manual strategies, in which images were visually inspected and either excluded or manually edited; five automated strategies, where outliers were excluded based on the tools "MRIQC" and "Qoala-T", and the metrics "morphological global measures", "Euler numbers" and "Contrast-to-Noise ratio"; and five semi-automated strategies, where the outliers detected through the mentioned tools and metrics were not excluded, but visually inspected and manually edited. In order to quantify the effects of each quality control strategy, the proportion of unexplained variance relative to the total variance was extracted after the application of each strategy, and the resulting differences compared. Manually editing brain surfaces produced particularly large changes in subcortical brain volumes and moderate changes in cortical surface area, thickness and hippocampal volumes. The performance of the quality control strategies depended on the morphological measure of interest. Overall, manual quality control strategies yielded the largest reduction in relative unexplained variance. The best performing automated alternatives were those based on Euler numbers and MRIQC scores. The exclusion of outliers based on global morphological measures produced an increase of relative unexplained variance. Manual quality control strategies are the most reliable solution for quality control of brain segmentation and parcellation. However, measures must be taken to prevent the subjectivity associated with these strategies. The detection of inaccurate segmentations based on Euler numbers or MRIQC provides a time efficient and reproducible alternative. The exclusion of outliers based on global morphological estimates must be avoided.
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Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Imagen por Resonancia Magnética/normas , Neuroimagen/métodos , Neuroimagen/normas , Control de Calidad , Adulto , Anciano , Estudios Transversales , Femenino , Guías como Asunto , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana EdadRESUMEN
22q11.2 deletion syndrome (22q11DS)-a neurodevelopmental condition caused by a hemizygous deletion on chromosome 22-is associated with an elevated risk of psychosis and other developmental brain disorders. Prior single-site diffusion magnetic resonance imaging (dMRI) studies have reported altered white matter (WM) microstructure in 22q11DS, but small samples and variable methods have led to contradictory results. Here we present the largest study ever conducted of dMRI-derived measures of WM microstructure in 22q11DS (334 22q11.2 deletion carriers and 260 healthy age- and sex-matched controls; age range 6-52 years). Using harmonization protocols developed by the ENIGMA-DTI working group, we identified widespread reductions in mean, axial and radial diffusivities in 22q11DS, most pronounced in regions with major cortico-cortical and cortico-thalamic fibers: the corona radiata, corpus callosum, superior longitudinal fasciculus, posterior thalamic radiations, and sagittal stratum (Cohen's d's ranging from -0.9 to -1.3). Only the posterior limb of the internal capsule (IC), comprised primarily of corticofugal fibers, showed higher axial diffusivity in 22q11DS. 22q11DS patients showed higher mean fractional anisotropy (FA) in callosal and projection fibers (IC and corona radiata) relative to controls, but lower FA than controls in regions with predominantly association fibers. Psychotic illness in 22q11DS was associated with more substantial diffusivity reductions in multiple regions. Overall, these findings indicate large effects of the 22q11.2 deletion on WM microstructure, especially in major cortico-cortical connections. Taken together with findings from animal models, this pattern of abnormalities may reflect disrupted neurogenesis of projection neurons in outer cortical layers.
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Síndrome de DiGeorge/diagnóstico por imagen , Síndrome de DiGeorge/patología , Imagen de Difusión por Resonancia Magnética , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Adolescente , Adulto , Anisotropía , Niño , Síndrome de DiGeorge/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion size. To address these issues, we developed the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta-Analysis) 22q11.2 Working Group, representing the largest analysis of brain structural alterations in 22q11DS to date. The imaging data were collected from 10 centers worldwide, including 474 subjects with 22q11DS (age = 18.2 ± 8.6; 46.9% female) and 315 typically developing, matched controls (age = 18.0 ± 9.2; 45.9% female). Compared to controls, 22q11DS individuals showed thicker cortical gray matter overall (left/right hemispheres: Cohen's d = 0.61/0.65), but focal thickness reduction in temporal and cingulate cortex. Cortical surface area (SA), however, showed pervasive reductions in 22q11DS (left/right hemispheres: d = -1.01/-1.02). 22q11DS cases vs. controls were classified with 93.8% accuracy based on these neuroanatomic patterns. Comparison of 22q11DS-psychosis to idiopathic schizophrenia (ENIGMA-Schizophrenia Working Group) revealed significant convergence of affected brain regions, particularly in fronto-temporal cortex. Finally, cortical SA was significantly greater in 22q11DS cases with smaller 1.5 Mb deletions, relative to those with typical 3 Mb deletions. We found a robust neuroanatomic signature of 22q11DS, and the first evidence that deletion size impacts brain structure. Psychotic illness in this highly penetrant deletion was associated with similar neuroanatomic abnormalities to idiopathic schizophrenia. These consistent cross-site findings highlight the homogeneity of this single genetic etiology, and support the suitability of 22q11DS as a biological model of schizophrenia.
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Corteza Cerebral/patología , Deleción Cromosómica , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/patología , Adolescente , Adulto , Femenino , Sustancia Gris/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Trastornos Psicóticos/genética , Adulto JovenRESUMEN
Neurofeedback has begun to attract the attention and scrutiny of the scientific and medical mainstream. Here, neurofeedback researchers present a consensus-derived checklist that aims to improve the reporting and experimental design standards in the field.
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Lista de Verificación/métodos , Neurorretroalimentación/métodos , Adulto , Consenso , Femenino , Humanos , Masculino , Persona de Mediana Edad , Revisión de la Investigación por Pares , Proyectos de Investigación/normas , Participación de los InteresadosRESUMEN
The thickness of the cerebral cortical sheet and its surface area are highly heritable traits thought to have largely distinct polygenic architectures. Despite large-scale efforts, the majority of their genetic determinants remain unknown. Our ability to identify causal genetic variants can be improved by employing brain measures that better map onto the biology we seek to understand. Such measures may have fewer variants but with larger effects, that is, lower polygenicity and higher discoverability. Using Gaussian mixture modeling, we estimated the number of causal variants shared between mean cortical thickness and total surface area, as well as the polygenicity and discoverability of regional measures. We made use of UK Biobank data from 30 880 healthy White European individuals (mean age 64.3, standard deviation 7.5, 52.1% female). We found large genetic overlap between total surface area and mean thickness, sharing 4016 out of 7941 causal variants. Regional surface area was more discoverable (P = 2.6 × 10-6) and less polygenic (P = 0.004) than regional thickness measures. These findings may serve as a roadmap for improved future GWAS studies; knowledge of which measures are most discoverable may be used to boost identification of genetic predictors and thereby gain a better understanding of brain morphology.
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Corteza Cerebral/anatomía & histología , Herencia Multifactorial , Anciano , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tamaño de los Órganos/genéticaRESUMEN
INTRODUCTION: Alcohol dependence is one of the most common substance use disorders, and novel treatment options are urgently needed. Neurofeedback training (NFT) based on real-time functional magnetic resonance imaging (rtf-MRI) has emerged as an attractive candidate for add-on treatments in psychiatry, but its use in alcohol dependence has not been formally investigated in a clinical trial. We investigated the use of rtfMRI-based NFT to prevent relapse in alcohol dependence. METHODS: Fifty-two alcohol-dependent patients from the UK who had completed a detoxification program were randomly assigned to a treatment group (receiving rtfMRI NFT in addition to standard care) or the control group (receiving standard care only). At baseline, alcohol consumption was assessed as the primary outcome measure and a variety of psychological, behavioral, and neural parameters as secondary outcome measures to determine feasibility and secondary training effects. Participants in the treatment group underwent 6 NFT sessions over 4 months and were trained to downregulate their brain activation in the salience network in the presence of alcohol stimuli and to upregulate frontal activation in response to pictures related to positive goals. Four, 8, and 12 months after baseline assessment, both groups were followed up with a battery of clinical and psychometric tests. RESULTS: Primary outcome measures showed very low relapse rates for both groups. Analysis of neural secondary outcome measures indicated that the majority of patients modulated the salience system in the desired directions, by decreasing activity in response to alcohol stimuli and increasing activation in response to positive goals. The intervention had a good safety and acceptability profile. CONCLUSION: We demonstrated that rtfMRI-neurofeedback targeting hyperactivity of the salience network in response to alcohol cues is feasible in currently abstinent patients with alcohol dependence.
Asunto(s)
Alcoholismo , Neurorretroalimentación , Alcoholismo/diagnóstico por imagen , Alcoholismo/terapia , Encéfalo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , NeuroimagenRESUMEN
fMRI Neurofeedback research employs many different control conditions. Currently, there is no consensus as to which control condition is best, and the answer depends on what aspects of the neurofeedback-training design one is trying to control for. These aspects can range from determining whether participants can learn to control brain activity via neurofeedback to determining whether there are clinically significant effects of the neurofeedback intervention. Lack of consensus over criteria for control conditions has hampered the design and interpretation of studies employing neurofeedback protocols. This paper presents an overview of the most commonly employed control conditions currently used in neurofeedback studies and discusses their advantages and disadvantages. Control conditions covered include no control, treatment-as-usual, bidirectional-regulation control, feedback of an alternative brain signal, sham feedback, and mental-rehearsal control. We conclude that the selection of the control condition(s) should be determined by the specific research goal of the study and best procedures that effectively control for relevant confounding factors.