Correction:The dentate gyrus in depression: directions for future research (Molecular Psychiatry, (2021), 26, 6, (1720-1722), 10.1038/s41380-020-0678-8)

This article was originally published under Nature Research’s License to Publish, but has now been made available under a [CC BY 4.0] license. The PDF and HTML versions of the article have been modified accordingly

Lower fractional anisotropy without evidence for neuro-inflammation in patients with early-phase schizophrenia spectrum disorders

Various lines of research suggest immune dysregulation as a potential therapeutic target for negative and cognitive symptoms in schizophrenia spectrum disorders (SSD). Immune dysregulation would lead to higher extracellular free-water (EFW) in cerebral white matter (WM), which may partially underlie the frequently reported lower fractional anisotropy (FA) in SSD. We aim to investigate differences in EFW concentrations – a presumed proxy for neuro-inflammation – between early-phase SSD patients (n = 55) and healthy controls (HC; n = 37), and to explore immunological and cognitive correlates. To increase specificity for EFW, we study several complementary magnetic resonance imaging contrasts that are sensitive to EFW. FA, mean diffusivity (MD), magnetization transfer ratio (MTR), myelin water fraction (MWF) and quantitative T1 and T2 were calculated from diffusion-weighted imaging (DWI), magnetization transfer imaging (MTI) and multicomponent driven equilibrium single-pulse observation of T1/T2 (mcDESPOT). For each measure, WM skeletons were constructed with tract-based spatial statistics. Multivariate SSD-HC comparisons with WM skeletons and their average values (i.e. global WM) were not statistically significant. In voxel-wise analyses, FA was significantly lower in SSD in the genu of the corpus callosum and in the left superior longitudinal fasciculus (p < 0.04). Global WM measures did not correlate with immunological markers (i.e. IL1-RA, IL-6, IL-8, IL-10 and CRP) or cognition in HC and SSD after corrections for multiple comparisons. We confirmed lower FA in early-phase SSD patients. However, non–FA measures did not provide additional evidence for immune dysregulation or for higher EFW as the primary mechanism underlying the reported lower FA values in SSD

Changes in perfusion, and structure of hippocampal subfields related to cognitive impairment after ECT:A pilot study using ultra high field MRI

Background: Electroconvulsive therapy (ECT) in patients with major depression is associated with volume changes and markers of neuroplasticity in the hippocampus, in particular in the dentate gyrus. It is unclear if these changes are associated with cognitive side effects. Objectives: We investigated whether changes in cognitive functioning after ECT were associated with hippocampal structural changes. It was hypothesized that 1) volume increase of hippocampal subfields and 2) changes in perfusion and diffusion of the hippocampus correlated with cognitive decline. Methods: Using ultra high field (7 T) MRI, intravoxel incoherent motion and volumetric data were acquired and neurocognitive functioning was assessed before and after ECT in 23 patients with major depression. Repeated measures correlation analysis was used to examine the relation between cognitive functioning and structural characteristics of the hippocampus. Results: Left hippocampal volume, left and right dentate gyrus and right CA1 volume increase correlated with decreases in verbal memory functioning. In addition, a decrease of mean diffusivity in the left hippocampus correlated with a decrease in letter fluency. Limitations: Due to methodological restrictions direct study of neuroplasticity is not possible. MRI is used as an indirect measure. Conclusion: As both volume increase in the hippocampus and MD decrease can be interpreted as indirect markers for neuroplasticity that co-occur with a decrease in cognitive functioning, our results may indicate that neuroplastic processes are affecting cognitive processes after ECT.</p

Author Correction:Functional connectome differences in individuals with hallucinations across the psychosis continuum (Scientific Reports, (2021), 11, 1, (1108), 10.1038/s41598-020-80657-8)

The Supplementary Information published with this Article contained an error, where an old version of Figure S5 was used. This error has now been corrected in the Supplementary Information file that accompanies the original Article. The corrected Supplementary Information file is also linked to this correction notices.</p

Author Correction:Functional connectome differences in individuals with hallucinations across the psychosis continuum (Scientific Reports, (2021), 11, 1, (1108), 10.1038/s41598-020-80657-8)

The Supplementary Information published with this Article contained an error, where an old version of Figure S5 was used. This error has now been corrected in the Supplementary Information file that accompanies the original Article. The corrected Supplementary Information file is also linked to this correction notices

Interhemispheric connectivity and hemispheric specialization in schizophrenia patients and their unaffected siblings

Hemispheric integration and specialization are two prominent organizational principles for macroscopic brain function. Impairments of interhemispheric cooperation have been reported in schizophrenia patients, but whether such abnormalities should be attributed to effects of illness or familial risk remains inconclusive. Moreover, it is unclear how abnormalities in interhemispheric connectivity impact hemispheric specialization. To address these questions, we performed magnetic resonance imaging (MRI) in a large cohort of 253 participants, including 84 schizophrenia patients, 106 of their unaffected siblings and 63 healthy controls. Interhemispheric connectivity and hemispheric specialization were calculated from resting-state functional connectivity, and compared across groups. Results showed that schizophrenia patients exhibit lower interhemispheric connectivity as compared to controls and siblings. In addition, patients showed higher levels of hemispheric specialization as compared to siblings. Level of interhemispheric connectivity and hemispheric specialization correlated with duration of illness in patients. No significant alterations were identified in siblings relative to controls on both measurements. Furthermore, alterations in interhemispheric connectivity correlated with changes in hemispheric specialization in patients relative to controls and siblings. Taken together, these results suggest that lower interhemispheric connectivity and associated abnormalities in hemispheric specialization are features of established illness, rather than an expression of preexistent familial risk for schizophrenia. Keywords: Schizophrenia, Unaffected relative, Interhemispheric connectivity, Hemispheric specialization, Resting-state fMR

Functionally linked resting-state networks reflect the underlying structural connectivity architecture of the human brain

During rest, multiple cortical brain regions are functionally linked forming resting-state networks. This high level of functional connectivity within resting-state networks suggests the existence of direct neuroanatomical connections between these functionally linked brain regions to facilitate the ongoing interregional neuronal communication. White matter tracts are the structural highways of our brain, enabling information to travel quickly from one brain region to another region. In this study, we examined both the functional and structural connections of the human brain in a group of 26 healthy subjects, combining 3 Tesla resting-state functional magnetic resonance imaging time-series with diffusion tensor imaging scans. Nine consistently found functionally linked resting-state networks were retrieved from the resting-state data. The diffusion tensor imaging scans were used to reconstruct the white matter pathways between the functionally linked brain areas of these resting-state networks. Our results show that well-known anatomical white matter tracts interconnect at least eight of the nine commonly found resting-state networks, including the default mode network, the core network, primary motor and visual network, and two lateralized parietal-frontal networks. Our results suggest that the functionally linked resting-state networks reflect the underlying structural connectivity architecture of the human brain

Structural and functional aspects relating to cost and benefit of rich club organization in the human cerebral cortex

Recent findings have demonstrated that a small set of highly connected brain regions may play a central role in enabling efficient communication between cortical regions, together forming a densely interconnected "rich club." However, the density and spatial layout of the rich club also suggest that it constitutes a costly feature of brain architecture. Here, combining anatomical T1, diffusion tensor imaging, magnetic transfer imaging, and functional MRI, several aspects of structural and functional connectivity of the brain's rich club were examined. Our findings suggest that rich club regions and rich club connections exhibit high levels of wiring volume, high levels of white matter organization, high levels of metabolic energy usage, long maturational trajectories, more variable regional time series, and more inter-regional functional couplings. Taken together, these structural and functional measures extend the notion that rich club organization represents a high-cost feature of brain architecture that puts a significant strain on brain resources. The high cost of the rich club may, however, be offset by significant functional benefits that the rich club confers to the brain network as a whole

Comparing free water imaging and magnetization transfer measurements in schizophrenia

Diffusion weighted imaging (DWI) has been extensively used to study the microarchitecture of white matter in schizophrenia. However, popular DWI-derived measures such as fractional anisotropy (FA) may be sensitive to many types of pathologies, and thus the interpretation of reported differences in these measures remains difficult. Combining DWI with magnetization transfer ratio (MTR) - a putative measure of white matter myelination - can help us reveal the underlying mechanisms. Previous findings hypothesized that MTR differences in schizophrenia are associated with free water concentrations, which also affect the DWIs. In this study we use a recently proposed DWI-derived method called free-water imaging to assess this hypothesis. We have reanalysed data from a previous study by using a fiber-based analysis of free water imaging, providing a free-water fraction, as well as mean diffusivity and FA corrected for free water, in addition to MTR along twelve major white matter fiber bundles in 40 schizophrenia patients and 40 healthy controls. We tested for group differences in each fiber bundle and for each measure separately and computed correlations between the MTR and the DWI-derived measures separately for both groups. Significant higher average MTR values in patients were found for the right uncinate fasciculus, the right arcuate fasciculus and the right inferior-frontal occipital fasciculus. No significant results were found for the other measures. No significant differences in correlations were found between MTR and the DWI-derived measures. The results suggest that MTR and freewater imaging measures can be considered complementary, promoting the acquisition of MTR in addition to DWI to identify group differences, as well as to better understand the underlying mechanisms in schizophrenia