Chun Meng

Link between hippocampus' raised local and eased global intrinsic connectivity in AD

The hippocampus (HP) is part of the default mode network (DMN), and both are key targets of Alzheimers disease (AD). Because of widespread network degeneration, it has been suggested that increasing HP disconnection from the DMN may lead to progressive disinhibition of intra‐HP synchronized activity.

Correspondence Between Aberrant Intrinsic Network Connectivity and Gray-Matter Volume in the Ventral Brain of Preterm Born Adults

Widespread brain changes are present in preterm born infants, adolescents, and even adults. While neurobiological models of prematurity facilitate powerful explanations for the adverse effects of preterm birth on the developing brain at microscale, convincing linking principles at large-scale level to explain the widespread nature of brain changes are still missing. We investigated effects of preterm birth on the brains large-scale intrinsic networks and their relation to brain structure in preterm born adults. In 95 preterm and 83 full-term born adults, structural and functional magnetic resonance imaging at-rest was used to analyze both voxel-based morphometry and spatial patterns of functional connectivity in ongoing blood oxygenation level-dependent activity. Differences in intrinsic functional connectivity (iFC) were found in cortical and subcortical networks. Structural differences were located in subcortical, temporal, and cingulate areas. Critically, for preterm born adults, iFC-network differences were overlapping and correlating with aberrant regional gray-matter (GM) volume specifically in subcortical and temporal areas. Overlapping changes were predicted by prematurity and in particular by neonatal medical complications. These results provide evidence that preterm birth has long-lasting effects on functional connectivity of intrinsic networks, and these changes are specifically related to structural alterations in ventral brain GM.

Based on the network degeneration hypothesis: separating individual patients with different neurodegenerative syndromes in a preliminary hybrid PET/MR study

The network degeneration hypothesis (NDH) of neurodegenerative syndromes suggests that pathologic brain changes distribute primarily along distinct brain networks, which are characteristic for different syndromes. Brain changes of neurodegenerative syndromes can be characterized in vivo by different imaging modalities. Our aim was to test the hypothesis whether multimodal imaging based on the NDH separates individual patients with different neurodegenerative syndromes. Methods: Twenty patients with Alzheimer disease (AD) and 20 patients with frontotemporal lobar degeneration (behavioral variant frontotemporal dementia [bvFTD, n = 11], semantic dementia [SD, n = 4], or progressive nonfluent aphasia [PNFA, n = 5]) underwent simultaneous MRI and 18F-FDG PET in a hybrid PET/MR scanner. The 3 outcome measures were voxelwise values of degree centrality as a surrogate for regional functional connectivity, glucose metabolism as a surrogate for regional metabolism, and volumetric-based morphometry as a surrogate for regional gray matter volume. Outcome measures were derived from predefined core regions of 4 intrinsic networks based on the NDH, which have been demonstrated to be characteristic for AD, bvFTD, SD, and PNFA, respectively. Subsequently, we applied support vector machine to classify individual patients via combined imaging measures, and results were evaluated by leave-one-out cross-validation. Results: On the basis of multimodal voxelwise regional patterns, classification accuracies for separating patients with different neurodegenerative syndromes were 77.5% for AD versus others, 82.5% for bvFTD versus others, 97.5% for SD versus others, and 87.5% for PNFA versus others. Multimodal classification results were significantly superior to unimodal approaches. Conclusion: Our finding provides initial evidence that the combination of regional metabolism, functional connectivity, and gray matter volume, which were derived from disease characteristic networks, separates individual patients with different neurodegenerative syndromes. Preliminary results suggest that employing multimodal imaging guided by the NDH may generate promising biomarkers of neurodegenerative syndromes.

How do you make me feel better? Social cognitive emotion regulation and the default mode network.

Socially-induced cognitive emotion regulation (Social-Reg) is crucial for emotional well-being and social functioning; however, its brain mechanisms remain poorly understood. Given that both social cognition and cognitive emotion regulation engage key regions of the default-mode network (DMN), we hypothesized that Social-Reg would rely on the DMN, and that its effectiveness would be associated with social functioning. During functional MRI, negative emotions were elicited by pictures, and - via short instructions - a psychotherapist either down-regulated participants emotions by employing reappraisal (Reg), or asked them to simply look at the pictures (Look). Adult Attachment Scale was used to measure social functioning. Contrasting Reg versus Look, aversive emotions were successfully reduced during Social-Reg, with increased activations in the prefrontal and parietal cortices, precuneus and the left temporo-parietal junction. These activations covered key nodes of the DMN and were associated with Social-Reg success. Furthermore, participants attachment security was positively correlated with both Social-Reg success and orbitofrontal cortex involvement during Social-Reg. In addition, specificity of the neural correlates of Social-Reg was confirmed by comparisons with participants DMN activity at rest and their brain activations during a typical emotional self-regulation task based on the same experimental paradigm without a psychotherapist. Our results provide first evidence for the specific involvement of the DMN in Social-Reg, and the association of Social-Reg with individual differences in attachment security. The findings suggest that DMN dysfunction, found in many neuropsychiatric disorders, may impair the ability to benefit from Social-Reg.

Reduced Cholinergic Basal Forebrain Integrity Links Neonatal Complications and Adult Cognitive Deficits After Premature Birth.

BACKGROUNDnPrematurely born individuals have an increased risk for long-term neurocognitive impairments. In animal models, development of the cholinergic basal forebrain (cBF) is selectively vulnerable to adverse effects of perinatal stressors, and impaired cBF integrity results in lasting cognitive deficits. We hypothesized that cBF integrity is impaired in prematurely born individuals and mediates adult cognitive impairments associated with prematurity.nnnMETHODSnWe used magnetic resonance imaging-based volumetric assessments of a cytoarchitectonically defined cBF region of interest to determine differences in cBF integrity between 99 adults who were born very preterm and/or with very low birth weight and 106 term-born control subjects from the same birth cohort. Magnetic resonance imaging-derived cBF volumes were studied in relation to neonatal clinical complications after delivery and intelligence measures (IQ) in adulthood.nnnRESULTSnIn adults who were born very preterm and/or with very low birth weight, cBF volumes were significantly reduced compared with term-born adults (-4.5% [F1,202 = 11.82, p = .001]). Lower cBF volume in adults who were born very preterm and/or with very low birth weight was specifically associated with both neonatal complications (rpart,92 = -.35, p < .001) and adult IQ (rpart,88 = .33, p = .001) even after controlling for global gray matter and white matter volume. In a path analytic model, cBF volume significantly mediated the association between neonatal complications and adult cognitive deficits.nnnCONCLUSIONSnWe provide first-time evidence in humans that cBF integrity is impaired after premature birth and links neonatal complications with long-term cognitive outcome. Data suggest that cholinergic system abnormalities may play a relevant role for long-term neurocognitive impairments associated with premature delivery.

White matter alterations of the corticospinal tract in adults born very preterm and/or with very low birth weight.

White matter (WM) injury, either visible on conventional magnetic resonance images (MRI) or measurable by diffusion tensor imaging (DTI), is frequent in preterm born individuals and often affects the corticospinal tract (CST). The relation between visible and invisible white mater alterations in the reconstructed CST of preterm subjects has so far been studied in infants, children and up to adolescence. Therefore, we probabilistically tracked the CST in 53 term‐born and 56 very preterm and/or low birth weight (VP/VLBW,u2009<u200932 weeks of gestation and/or birth weightu2009<u20091,500 g) adults (mean age 26 years) and compared their DTI parameters (axial, radial, mean diffusivity—AD, RD, MD, fractional anisotropy—FA) in the whole CST and slice‐wise along the CST. Additionally, we used the automatic, tract‐based‐spatial‐statistics (TBSS) as an alternative to tractography. We compared control and VP/VLBW and subgroups with and without CST WM lesions visible on conventional MRI. Compared to controls, VP/VLBW subjects had significantly higher diffusivity (AD, RD, MD) in the whole CST, slice‐wise along the CST, and in multiple regions along the TBSS skeleton. VP/VLBW subjects also had significantly lower (TBSS) and higher (tractography) FA in regions along the CST, but no different mean FA in the tracked CST as a whole. Diffusion changes were weaker, but remained significant for both, tractography and TBSS, when excluding subjects with visible CST lesions. Chronic CST injury persists in VP/VLBW adults even in the absence of visible WM lesions, indicating long‐term structural WM changes induced by premature birth. Hum Brain Mapp 37:289–299, 2016.

Impaired visual short-term memory capacity is distinctively associated with structural connectivity of the posterior thalamic radiation and the splenium of the corpus callosum in preterm-born adults

Abstract Preterm birth is associated with an increased risk for lasting changes in both the cortico‐thalamic system and attention; however, the link between cortico‐thalamic and attention changes is as yet little understood. In preterm newborns, cortico‐cortical and cortico‐thalamic structural connectivity are distinctively altered, with increased local clustering for cortico‐cortical and decreased integrity for cortico‐thalamic connectivity. In preterm‐born adults, among the various attention functions, visual short‐term memory (vSTM) capacity is selectively impaired. We hypothesized distinct associations between vSTM capacity and the structural integrity of cortico‐thalamic and cortico‐cortical connections, respectively, in preterm‐born adults. A whole‐report paradigm of briefly presented letter arrays based on the computationally formalized Theory of Visual Attention (TVA) was used to quantify parameter vSTM capacity in 26 preterm‐ and 21 full‐term‐born adults. Fractional anisotropy (FA) of posterior thalamic radiations and the splenium of the corpus callosum obtained by diffusion tensor imaging were analyzed by tract‐based spatial statistics and used as proxies for cortico‐thalamic and cortico‐cortical structural connectivity. The relationship between vSTM capacity and cortico‐thalamic and cortico‐cortical connectivity, respectively, was significantly modified by prematurity. In full‐term‐born adults, the higher FA in the right posterior thalamic radiation the higher vSTM capacity; in preterm‐born adults this FA‐vSTM‐relationship was inversed. In the splenium, higher FA was correlated with higher vSTM capacity in preterm‐born adults, whereas no significant relationship was evident in full‐term‐born adults. These results indicate distinct associations between cortico‐thalamic and cortico‐cortical integrity and vSTM capacity in preterm‐and full‐term‐born adults. Data suggest compensatory cortico‐cortical fiber re‐organization for attention deficits after preterm delivery. HighlightsPreterm born adults have impaired visual short term memory (vSTM) capacity.vSTM capacity is distinctively linked with white matter in preterm and full‐term born adults.Posterior thalamic radiation linked with higher vSTM capacity in full but not preterm born adults.Splenium associated with higher vSTM capacity in preterm but not full‐term adults.Splenium connectivity indicates compensatory potential for vSTM after preterm delivery.

The association of children’s mathematic abilities with both adults’ cognitive abilities and intrinsic fronto-parietal networks is altered in preterm-born individuals

Mathematic abilities in childhood are highly predictive for long-term neurocognitive outcomes. Preterm-born individuals have an increased risk for both persistent cognitive impairments and long-term changes in macroscopic brain organization. We hypothesized that the association of childhood mathematic abilities with both adulthood general cognitive abilities and associated fronto-parietal intrinsic networks is altered after preterm delivery. 72 preterm- and 71 term-born individuals underwent standardized mathematic and IQ testing at 8xa0years and resting-state fMRI and full-scale IQ testing at 26xa0years of age. Outcome measure for intrinsic networks was intrinsic functional connectivity (iFC). Controlling for IQ at age eight, mathematic abilities in childhood were significantly stronger positively associated with adults’ IQ in preterm compared with term-born individuals. In preterm-born individuals, the association of children’s mathematic abilities and adults’ fronto-parietal iFC was altered. Likewise, fronto-parietal iFC was distinctively linked with preterm- and term-born adults’ IQ. Results provide evidence that preterm birth alters the link of mathematic abilities in childhood and general cognitive abilities and fronto-parietal intrinsic networks in adulthood. Data suggest a distinct functional role of intrinsic fronto-parietal networks for preterm individuals with respect to mathematic abilities and that these networks together with associated children’s mathematic abilities may represent potential neurocognitive targets for early intervention.

Common and distinct changes of default mode and salience network in schizophrenia and major depression

Brain imaging reveals schizophrenia as a disorder of macroscopic brain networks. In particular, default mode and salience network (DMN, SN) show highly consistent alterations in both interacting brain activity and underlying brain structure. However, the same networks are also altered in major depression. This overlap in network alterations induces the question whether DMN and SN changes are different across both disorders, potentially indicating distinct underlying pathophysiological mechanisms. To address this question, we acquired T1-weighted, diffusion-weighted, and resting-state functional MRI in patients with schizophrenia, patients with major depression, and healthy controls. We measured regional gray matter volume, inter-regional structural and intrinsic functional connectivity of DMN and SN, and compared these measures across groups by generalized Wilcoxon rank tests, while controlling for symptoms and medication. When comparing patients with controls, we found in each patient group SN volume loss, impaired DMN structural connectivity, and aberrant DMN and SN functional connectivity. When comparing patient groups, SN gray matter volume loss and DMN structural connectivity reduction did not differ between groups, but in schizophrenic patients, functional hyperconnectivity between DMN and SN was less in comparison to depressed patients. Results provide evidence for distinct functional hyperconnectivity between DMN and SN in schizophrenia and major depression, while structural changes in DMN and SN were similar. Distinct hyperconnectivity suggests different pathophysiological mechanism underlying aberrant DMN-SN interactions in schizophrenia and depression.

The Role of Brain Connectome Imaging in the Estimation of Depressive Relapse Risk

BACKGROUNDnu2002About two-thirds of all patients with major depressive disorder (MDD) suffer from depressive relapse, the mechanisms of which are still poorly understood. In recent years, analyses of the brains connectome have increasingly been employed to identify potential biomarkers of depressive relapse. The term connectome refers to the map of all structural or functional connections in the brain. Itxa0can be investigated by structural or functional magnetic resonance imaging followed by graph theory-based analysis to characterize network topology on the global and regional level.nnnMETHODSnu2002This review is based on a selective literature search in PubMed representing the current state of research, as well as on an already published study which was awarded the Promotionspreis of the Deutsche Röntgengesellschaft.nnnRESULTS AND CONCLUSIONnu2002Numerous studies point to altered network topology, e.u200ag., of default-mode network and striatum, as being crucial for the pathophysiology of MDD. Our group was able to show that striatal centrality (or hubness) is associated with the number of depressive episodes, which is one of the best predictors for depressive relapse. These data suggest aberrant striatal network topology as a potential biomarker for depressive relapse risk. The translation of these promising findings into clinical routine diagnostics is promoted by several methodological advantages, while some unresolved issues still hinder this process.nnnKEY POINTSnu2002 · About two-thirds of all patients with MDD suffer from depressive relapse.. · The mechanisms of depressive relapse are still poorly understood.. · Imaging the brains connectome can contribute to better understanding of depressive relapse.. · The term connectome comprises all structural and functional connections of the brain.. · Altered striatal network topology could be associated with depressive relapse risk..nnnCITATION FORMATn· Brandl F, Meng C, Zimmer C etu200aal. The Role of Brain Connectome Imaging in the Estimation of Depressive Relapse Risk. Fortschr Röntgenstr 2018; 190: 1036u200a-u200a1043.