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Contains fulltext : 291574.pdf (Publisher’s version ) (Open Access) 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.

Background and ObjectivesDecline in everyday functioning is a key clinical change in Alzheimer disease and related disorders (ADRD). An important challenge remains the determination of what constitutes a clinically meaningful change in everyday functioning. We aimed to investigate this by establishing the minimal important change (MIC): the smallest amount of change that has a meaningful effect on patients' lives. We retrospectively investigated meaningful change in a memory clinic cohort.MethodsIn the first, qualitative part of the study, community-recruited informal caregivers of patients with ADRD and memory clinic clinicians completed a survey in which they judged various situations representing changes in everyday functioning. Their judgments of meaningful change were used to determine thresholds for MIC, both for decline and improvement, on the Amsterdam Instrumental Activities of Daily Living (IADL) Questionnaire. In the second, quantitative part, we applied these values in an independent longitudinal cohort study of unselected memory clinic patients.ResultsMIC thresholds were established at the average threshold of caregivers (N = 1,629; 62.4 ± 9.5 years; 77% female) and clinicians (N = 13): −2.2 points for clinically meaningful decline and +5.0 points for clinically meaningful improvement. Memory clinic patients (N = 230; 64.3 ± 7.7 years; 39% female; 60% dementia diagnosis) were followed for 1 year, 102 (45%) of whom showed a decline larger than the MIC, after a mean of 6.7 ± 3.5 months. Patients with a dementia diagnosis and more atrophy of the medial temporal lobe had larger odds (odds ratio [OR] = 3.4, 95% CI [1.5–7.8] and OR = 5.0, 95% CI [1.2–20.0], respectively) for passing the MIC threshold for decline than those with subjective cognitive complaints and no atrophy.DiscussionWe were able to operationalize clinically meaningful decline in IADL by determining the MIC. The usefulness of the MIC was supported by our findings from the clinical sample that nearly half of a sample of unselected memory clinic patients showed a meaningful decline in less than a year. Disease stage and medial temporal atrophy were predictors of functional decline greater than the MIC. Our findings provide guidance in interpreting changes in IADL and may help evaluate treatment effects and monitor disease progression.

Contains fulltext : 251394.pdf (Publisher’s version ) (Open Access) Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls, affecting widespread cortical regions. The possible impacts of these regional alterations in terms of structural network effects have not previously been characterized. Inter-regional morphological covariance analysis can capture network connectivity between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1455 individuals with ASD and 1560 controls, across 43 independent datasets of the ENIGMA consortium's ASD Working Group, to assess hemispheric asymmetries of intra-individual structural covariance networks, using graph theory-based topological metrics. Compared with typical features of small-world architecture in controls, the ASD sample showed significantly altered average asymmetry of networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, involving higher randomization of the corresponding right-hemispheric networks in ASD. A network involving the superior frontal cortex showed decreased right-hemisphere randomization. Based on comparisons with meta-analyzed functional neuroimaging data, the altered connectivity asymmetry particularly affected networks that subserve executive functions, language-related and sensorimotor processes. These findings provide a network-level characterization of altered left-right brain asymmetry in ASD, based on a large combined sample. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity.