Christian Sorg

YNIMG Journal 2026 Journal Article

Diurnal changes of cerebrospinal fluid and global signal coupling

• Leander Müller
• Cornelius Berberich
• Paula Heinrich
• Rachel Nuttall
• Stefanie Pilge
• Benedikt Zott
• Christian Sorg
• Afra Wohlschlaeger

Cerebrospinal fluid (CSF) bulk movement around the brain is mediated by brain hemodynamics and has been linked to the brain´s waste clearance process and the so-called glymphatic system. Factors such as sleep have been demonstrated to influence global brain hemodynamics, including the coupling between global grey matter (gGM) BOLD and CSF signals, a measure to assess macroscopic CSF flow in relation to global oxygen fluctuations. Although diurnal changes in the amplitude of gGM also occur, whether macroscopic CSF flow couples to gGM varies across the day remains unclear. Using publicly available resting-state fMRI data from healthy adults, we examined the coupling of these signals at varying time points throughout the day. We included data from 875 healthy young adults from the Human Connectome Project, together with Pittsburgh Sleep Quality Index (PSQI) scores. Our results show that coupling strength was highest in the morning and decreased significantly across the day (r = -0.18, p < 0.001). While gGM BOLD amplitude also decreased over the day (r = -0.14, p < 0.001), CSF amplitude did not (r = 0.01, p = 0.74). Among PSQI subcomponents, only sleep duration was significantly associated with coupling (r = 0.10, p < 0.006). Furthermore, self-reported sleep duration was negatively correlated with coupling strength (r = -0.11, p < 0.01), indicating stronger coupling in those who reported shorter sleep. These findings highlight the importance of accounting for both the time of scan and individual sleep characteristics when interpreting fMRI-based gGM-CSF coupling measures.

YNIMG Journal 2026 Journal Article

Lifespan trajectory of claustrum volume in humans – effect of age, hemisphere, and sex, and association with cognitive performance

• Sevilay Ayyildiz
• Antonia Neubauer
• Melissa Thalhammer
• Hongwei Bran Li
• Jil Wendt
• Aurore Menegaux
• Rebecca Hippen
• Benita Schmitz-Koep

The human claustrum is a bilateral, thin, irregularly shaped gray matter structure located between the striatum and insula. While previous research demonstrated the effect of distinct medical conditions, such as prematurity, schizophrenia, and Alzheimer's disease, on claustrum function and structure, it is poorly understood how non-pathologic biological conditions effect the claustrum. This study aimed to investigate the lifespan trajectory of claustrum volumes including the effect of age, hemisphere, and sex and the association with cognitive performance. We used T1-weighted 3 Tesla MRI scans of 3474 healthy participants aged 1 to 80 years, using deep learning-based automated claustrum segmentation, and normative modeling to delineate lifespan trajectories of claustrum volumes for both hemispheres and sexes. Ordinary least squares regression analyses were applied to further characterize age, hemisphere, and sex effects. Cognitive performance scores were linked to claustrum volume using multiple linear regression analyses. Lifespan analysis revealed a trajectory of rapid claustrum volume increase from infancy to adolescence (∼1-15 years), a plateau phase from early to middle adulthood (∼15-40 years), and a subsequent decline from middle adulthood to old age (∼40-80 years). The right claustrum was on average larger than the left one across all ages. Overall, females had larger total intracranial volume-adjusted claustrum volumes than males across the lifespan. Claustrum volumes were associated with total cognition and attention scores in individuals from 8 to 65 years. Results demonstrate a distinct effect of age, hemisphere, and sex on claustrum volume as well as its association with general cognitive performance and attention. Data provide a comprehensive framework for claustrum lifespan trajectories relevant for studying claustrum alterations in neurodevelopmental and neurodegenerative disorders.

YNIMG Journal 2026 Journal Article

Long-term alterations of cerebellar structure after premature birth

• Marcel Daamen
• Lukas Scheef
• Aurore Menegaux
• Benita Schmitz-Koep
• Dennis M. Hedderich
• Markus Essler
• Julian Luetkens
• Claus Zimmer

BACKGROUND: Alterations of cerebellar volume were reported in prematurely-born children, adolescents and adults, suggesting long-lasting effects on cerebellar growth. However, studies mostly examined global cerebellar volumes, which could disguise focal, subregional differences. METHODS: Based on T1-/T2-weighted MRI, this voxel-based morphometry study used the SUIT toolbox for optimized analysis of cerebellar and brainstem gray matter (GM) and white matter (WM) volumes in young adults born very preterm (<32 gestational weeks) and/or with very low birth weight (<1500g; N=101, M=26.7 years) and full-term controls (N=109, M=26.8 years) from the Bavarian Longitudinal study. Voxel-wise group differences for GM and WM tissue maps, and correlation with prematurity-related variables were analyzed. For comparison, an automated, deep learning-based segmentation of cerebellar regions of interest (ROI) was performed using CerebNet. RESULTS: Preterms showed lower cerebellar (and brainstem) WM volume, which correlated with prematurity-related variables. While voxel-based analyses observed higher preterm GM volume in anterior vermal and superior-posterior foci, these were sensitive to modeling strategies for intracranial volume confounds. Among preterms, GM volume showed positive associations with GA only, in distinct inferior-posterior regions. ROI-based analyses observed no significant GM differences except for lower preterm GM volume in right lobule X, but broader associations between subregional GM volumes and prematurity-related variables. CONCLUSIONS: Present data suggest that premature birth has a long-lasting influence on cerebellar morphology, preferentially its white matter aspects. The impact on cerebellar cortex volume may be more diffuse due to differential sensitivity of the growth trajectories of cerebellar subregions to perinatal and postnatal adversities.

YNIMG Journal 2026 Journal Article

Resting-state fMRI coherence is selectively diminished around 0.1 Hz in patients with unilateral carotid artery stenosis

• Sangcheon Choi
• Gabriel Hoffmann
• Sebastian Schneider
• Stephan Kaczmarz
• Xin Yu
• Christine Preibisch
• Christian Sorg

In the brain, vasomotor dynamics at infra-slow frequencies (∼0.1 Hz), driven by synchronized oscillations of smooth muscle cells in vessel walls, are thought to play a crucial role in regulating cerebral perfusion and underlie resting-state functional connectivity (FC), typically measured by correlated time courses of functional signals. In particular, rodent studies have demonstrated that vasomotor activity contributes to the coherence of blood oxygenation level dependent (BOLD) signal fluctuations. However, in humans, detecting this contribution non-invasively remains challenging due to the limited spatiotemporal sensitivity of functional magnetic resonance imaging (fMRI) to vasomotion. Given that prior studies have identified internal carotid artery stenosis (ICAS) as an informative conditional lesion model of vasomotor and hemodynamic impairments in humans, we investigated whether ICAS affects interhemispheric BOLD coherence at ∼0.1 Hz. Using a multi-modal fMRI framework integrating resting-state fMRI with quantitative mapping of cerebral blood volume, blood flow, oxygen metabolism, and BOLD time lag, we compared BOLD coherence between patients with asymptomatic unilateral ICAS and healthy controls. Frequency-specific analysis revealed significantly diminished inter-hemispheric BOLD coherence at ∼0.1 Hz across canonical resting-state networks in ICAS patients, while ultra-slow (<0.05 Hz) coherence remained largely preserved. This reduction was spatially widespread across brain networks and particularly pronounced in watershed areas, i.e., border zones between major vascular territories, associated with significantly increased lateralization of cerebral blood volume (p < 0.01). Notably, coherence-based FC patterns at ∼0.1 Hz were heterogeneous within watershed areas but homogeneous outside, suggesting an interplay between compensatory mechanisms and cerebrovascular impairment. Taken together, our findings demonstrate that ICAS induces subtle, frequency- and region-specific alterations in interhemispheric FC, consistent with a model in which impaired vasomotor activity and hemodynamic dysfunctions impact resting-state FC in the human brain.

YNICL Journal 2026 Journal Article

Structural network topology and cognitive control in very preterm born young adults

• Merle J. Marek
• Dieter Wolke
• Christian Sorg
• Jil Wendt
• Aurore Menegaux
• Dennis Hedderich
• Peter Bartmann
• Micha Burkhardt

This study investigates the long-term effects of very preterm (VPT) birth (<32 weeks of gestation) on cognitive control and structural brain network topology. Data were obtained from 61 very VPT and 79 full term (FT) individuals aged 26 years, who participated in the prospective Bavarian Longitudinal Study since birth (BLS, https://www.bayerische-entwicklungsstudie.de). Cognitive control ability was estimated through a multi-group confirmatory factor analysis, while the structural topology of the cognitive control brain network was analysed through diffusion-weighted magnetic resonance imaging, tractography, and graph-theoretic analysis. Brain-behaviour associations were further examined using structural equation modelling. Consistent with expectations, we observed significant group differences in cognitive control, especially in a latent speed of cognitive control factor, with FT individuals scoring 0.742 standard deviations higher than the VPT group (p = 0.001). This was statistically confirmed by a model comparison in the multi-group framework. Additionally, the VPT group exhibited lower structural network integration, as indicated by reduced global efficiency and average degree of the cognitive control brain network. Contrary to our hypothesis, we found no group differences in network segregation (average clustering coefficient), and structural network characteristics were not significantly associated with latent cognitive control. These findings indicate cognitive control deficits and reduced structural brain network integration in adulthood for VPT individuals and underscores the need for ongoing support and intervention to mitigate the lasting neurodevelopmental impacts of preterm birth.

YNIMG Journal 2025 Journal Article

Increased coupling between global grey matter and CSF-derived fMRI signal in young adults after partial sleep deprivation – evidence from the sleepy brain study

• Cornelius Berberich
• Leander Müller
• Benedikt Zott
• Rachel Nuttal
• Gerhard Schneider
• Claus Zimmer
• Christian Sorg
• Dennis M. Hedderich

Evidence indicates that brain waste clearance happens more efficiently during sleep. Recent studies suggest that the correlation, i.e., coupling, between the cortical grey matter (gGM) blood oxygenation level-dependent signal and cerebrospinal fluid (CSF) signal in the foramen magnum, measured via resting-state functional MRI (fMRI), serves as a non-invasive measure of the ventricular CSF system. Sleep deprivation has been demonstrated to affect brain function and health. Our aim is to assess gGM-CSF coupling after partial sleep deprivation, hypothesizing a change in the coupling measure relative to normal sleep. To test this hypothesis, we analyzed resting-state fMRI data from 63 healthy participants in the "The Stockholm Sleepy Brain Study", grouped according to age: younger (20 - 29 years) and older (65 - 75 years) adults. We examined gGM-CSF coupling twice in each subject, in the evening following a night of normal sleep and after a night of partial sleep deprivation (≤ 3 h of sleep). Our results revealed significantly increased gGM-CSF coupling after sleep deprivation compared to normal sleep (mean r = -0.30 ± 0.19 vs. -0.25 ± 0.14; t(62) = 2.05, p = 0.045). A linear mixed model demonstrated a significant interaction of age with the sleep condition (β = 0.0031, t = 2.73, p = 0.0083), showing significant changes only in the younger subgroup (t(35) = 2.99, p = 0.0050). These findings indicate that gGM-CSF coupling increases after partial sleep deprivation in younger adults, which may reflect compensatory mechanisms in response to reduced sleep duration. Furthermore, the results suggest that this compensatory response could be diminished in older adults.

YNIMG Journal 2024 Journal Article

Consistently lower volumes across thalamus nuclei in very premature-born adults

• Melissa Thalhammer
• Mehul Nimpal
• Julia Schulz
• Veronica Meedt
• Aurore Menegaux
• Benita Schmitz-Koep
• Marcel Daamen
• Henning Boecker

Lasting thalamus volume reduction after preterm birth is a prominent finding. However, whether thalamic nuclei volumes are affected differentially by preterm birth and whether nuclei aberrations are relevant for cognitive functioning remains unknown. Using T1-weighted MR-images of 83 adults born very preterm (≤ 32 weeks' gestation; VP) and/or with very low body weight (≤ 1,500 g; VLBW) as well as of 92 full-term born (≥ 37 weeks' gestation) controls, we compared thalamic nuclei volumes of six subregions (anterior, lateral, ventral, intralaminar, medial, and pulvinar) across groups at the age of 26 years. To characterize the functional relevance of volume aberrations, cognitive performance was assessed by full-scale intelligence quotient using the Wechsler Adult Intelligence Scale and linked to volume reductions using multiple linear regression analyses. Thalamic volumes were significantly lower across all examined nuclei in VP/VLBW adults compared to controls, suggesting an overall rather than focal impairment. Lower nuclei volumes were linked to higher intensity of neonatal treatment, indicating vulnerability to stress exposure after birth. Furthermore, we found that single results for lateral, medial, and pulvinar nuclei volumes were associated with full-scale intelligence quotient in preterm adults, albeit not surviving correction for multiple hypotheses testing. These findings provide evidence that lower thalamic volume in preterm adults is observable across all subregions rather than focused on single nuclei. Data suggest the same mechanisms of aberrant thalamus development across all nuclei after premature birth.

YNICL Journal 2023 Journal Article

Aberrant claustrum structure in preterm-born neonates: an MRI study

• Antonia Neubauer
• Aurore Menegaux
• Jil Wendt
• Hongwei Bran Li
• Benita Schmitz-Koep
• Tobias Ruzok
• Melissa Thalhammer
• David Schinz

The human claustrum is a gray matter structure in the white matter between insula and striatum. Previous analysis found altered claustrum microstructure in very preterm-born adults associated with lower cognitive performance. As the claustrum development is related to hypoxia-ischemia sensitive transient cell populations being at-risk in premature birth, we hypothesized that claustrum structure is already altered in preterm-born neonates. We studied anatomical and diffusion-weighted MRIs of 83 preterm- and 83 term-born neonates at term-equivalent age. Additionally, claustrum development was analyzed both in a spectrum of 377 term-born neonates and longitudinally in 53 preterm-born subjects. Data was provided by the developing Human Connectome Project. Claustrum development showed increasing volume, increasing fractional anisotropy (FA), and decreasing mean diffusivity (MD) around term both across term- and preterm-born neonates. Relative to term-born ones, preterm-born neonates had (i) increased absolute and relative claustrum volumes, both indicating increased cellular and/or extracellular matter and being in contrast to other subcortical gray matter regions of decreased volumes such as thalamus; (ii) lower claustrum FA and higher claustrum MD, pointing at increased extracellular matrix and impaired axonal integrity; and (iii) aberrant covariance between claustrum FA and MD, respectively, and that of distributed gray matter regions, hinting at relatively altered claustrum microstructure. Results together demonstrate specifically aberrant claustrum structure in preterm-born neonates, suggesting altered claustrum development in prematurity, potentially relevant for later cognitive performance.

YNIMG Journal 2023 Journal Article

Stronger influence of systemic than local hemodynamic-vascular factors on resting-state BOLD functional connectivity

• Sebastian C. Schneider
• Stephan Kaczmarz
• Jens Göttler
• Jan Kufer
• Benedikt Zott
• Josef Priller
• Michael Kallmayer
• Claus Zimmer

Correlated fluctuations in the blood oxygenation level dependent (BOLD) signal of resting-state functional MRI (i.e., BOLD-functional connectivity, BOLD-FC) reflect a spectrum of neuronal and non-neuronal processes. In particular, there are multiple hemodynamic-vascular influences on BOLD-FC on both systemic (e.g., perfusion delay) and local levels (e.g., neurovascular coupling). While the influence of individual factors has been studied extensively, combined and comparative studies of systemic and local hemodynamic-vascular factors on BOLD-FC are scarce, notably in humans. We employed a multi-modal MRI approach to investigate and compare distinct hemodynamic-vascular processes and their impact on homotopic BOLD-FC in healthy controls and patients with unilateral asymptomatic internal carotid artery stenosis (ICAS). Asymptomatic ICAS is a cerebrovascular disorder, in which neuronal functioning is largely preserved but hemodynamic-vascular processes are impaired, mostly on the side of stenosis. Investigated indicators for local hemodynamic-vascular processes comprise capillary transit time heterogeneity (CTH) and cerebral blood volume (CBV) from dynamic susceptibility contrast (DSC) MRI, and cerebral blood flow (CBF) from pseudo-continuous arterial spin labeling (pCASL). Indicators for systemic processes are time-to-peak (TTP) from DSC MRI and BOLD lags from functional MRI. For each of these parameters, their influence on BOLD-FC was estimated by a comprehensive linear mixed model. Equally across groups, we found that individual mean BOLD-FC, local (CTH, CBV, and CBF) and systemic (TTP and BOLD lag) hemodynamic-vascular factors together explain 40.7% of BOLD-FC variance, with 20% of BOLD-FC variance explained by hemodynamic-vascular factors, with an about two-times larger contribution of systemic versus local factors. We conclude that regional differences in blood supply, i.e., systemic perfusion delays, exert a stronger influence on BOLD-FC than impairments in local neurovascular coupling.

YNIMG Journal 2023 Journal Article

Targeted rhythmic visual stimulation at individual participants’ intrinsic alpha frequency causes selective increase of occipitoparietal BOLD-fMRI and EEG functional connectivity

• Cilia Jaeger
• Rachel Nuttall
• Juliana Zimmermann
• James Dowsett
• Christine Preibisch
• Christian Sorg
• Afra Wohlschlaeger

Neural oscillations in distinct frequency bands are ubiquitous in the brain and play a role in many cognitive processes. The "communication by coherence" hypothesis, poses that the synchronization through phase coupling of frequency-specific neural oscillations regulate information flow across distribute brain regions. Specifically, the posterior alpha frequency band (7-12 Hz) is thought to gate bottom-up visual information flow by inhibition during visual processing. Evidence shows that increased alpha phase coherency positively correlates with functional connectivity in resting state connectivity networks, supporting alpha mediates neural communication through coherency. However, these findings have mainly been derived from spontaneous changes in the ongoing alpha rhythm. In this study, we experimentally modulate the alpha rhythm by targeting individuals' intrinsic alpha frequency with sustained rhythmic light to investigate alpha-mediated synchronous cortical activity in both EEG and fMRI. We hypothesize increased alpha coherency and fMRI connectivity should arise from modulation of the intrinsic alpha frequency (IAF) as opposed to control frequencies in the alpha range. Sustained rhythmic and arrhythmic stimulation at the IAF and at neighboring frequencies within the alpha band range (7-12 Hz) was implemented and assessed in a separate EEG and fMRI study. We observed increased cortical alpha phase coherency in the visual cortex during rhythmic stimulation at the IAF as in comparison to rhythmic stimulation of control frequencies. In the fMRI, we found increased functional connectivity for stimulation at the IAF in visual and parietal areas as compared to other rhythmic control frequencies by correlating time courses from a set of regions of interest for the different stimulation conditions and applying network-based statistics. This suggests that rhythmic stimulation at the IAF frequency induces a higher degree of synchronicity of neural activity across the occipital and parietal cortex, which supports the role of the alpha oscillation in gating information flow during visual processing.

YNIMG Journal 2022 Journal Article

Comparing myelin-sensitive magnetic resonance imaging measures and resulting g-ratios in healthy and multiple sclerosis brains

• Ronja C. Berg
• Aurore Menegaux
• Thomas Amthor
• Guillaume Gilbert
• Maria Mora
• Sarah Schlaeger
• Viola Pongratz
• Markus Lauerer

The myelin concentration and the degree of myelination of nerve fibers can provide valuable information on the integrity of human brain tissue. Magnetic resonance imaging (MRI) of myelin-sensitive parameters can help to non-invasively evaluate demyelinating diseases such as multiple sclerosis (MS). Several different myelin-sensitive MRI methods have been proposed to determine measures of the degree of myelination, in particular the g-ratio. However, variability in underlying physical principles and different biological models influence measured myelin concentrations, and consequently g-ratio values. We therefore investigated similarities and differences between five different myelin-sensitive MRI measures and their effects on g-ratio mapping in the brains of both MS patients and healthy volunteers. We compared two different estimates of the myelin water fraction (MWF) as well as the inhomogeneous magnetization transfer ratio (ihMTR), magnetization transfer saturation (MTsat), and macromolecular tissue volume (MTV) in 13 patients with MS and 14 healthy controls. In combination with diffusion-weighted imaging, we derived g-ratio parameter maps for each of the five different myelin measures. The g-ratio values calculated from different myelin measures varied strongly, especially in MS lesions. While, compared to normal-appearing white matter, MTsat and one estimate of the MWF resulted in higher g-ratio values within lesions, ihMTR, MTV, and the second MWF estimate resulted in lower lesion g-ratio values. As myelin-sensitive measures provide rough estimates of myelin content rather than absolute myelin concentrations, resulting g-ratio values strongly depend on the utilized myelin measure and model used for g-ratio mapping. When comparing g-ratio values, it is, thus, important to utilize the same MRI methods and models or to consider methodological differences. Particular caution is necessary in pathological tissue such as MS lesions.

YNIMG Journal 2022 Journal Article

Resting-state BOLD functional connectivity depends on the heterogeneity of capillary transit times in the human brain A combined lesion and simulation study about the influence of blood flow response timing

• Sebastian C. Schneider
• Mario E. Archila-Meléndez
• Jens Göttler
• Stephan Kaczmarz
• Benedikt Zott
• Josef Priller
• Michael Kallmayer
• Claus Zimmer

Functional connectivity (FC) derived from blood oxygenation level dependent (BOLD) functional magnetic resonance imaging at rest (rs-fMRI), is commonly interpreted as indicator of neuronal connectivity. In a number of brain disorders, however, metabolic, vascular, and hemodynamic impairments can be expected to alter BOLD-FC independently from neuronal activity. By means of a neurovascular coupling (NVC) model of BOLD-FC, we recently demonstrated that aberrant timing of cerebral blood flow (CBF) responses may influence BOLD-FC. In the current work, we support and extend this finding by empirically linking BOLD-FC with capillary transit time heterogeneity (CTH), which we consider as an indicator of delayed and broadened CBF responses. We assessed 28 asymptomatic patients with unilateral high-grade internal carotid artery stenosis (ICAS) as a hemodynamic lesion model with largely preserved neurocognitive functioning and 27 age-matched healthy controls. For each participant, we obtained rs-fMRI, arterial spin labeling, and dynamic susceptibility contrast MRI to study the dependence of left-right homotopic BOLD-FC on local perfusion parameters. Additionally, we investigated the dependency of BOLD-FC on CBF response timing by detailed simulations. Homotopic BOLD-FC was negatively associated with increasing CTH differences between homotopic brain areas. This relation was more pronounced in asymptomatic ICAS patients even after controlling for baseline CBF and relative cerebral blood volume influences. These findings match simulation results that predict an influence of delayed and broadened CBF responses on BOLD-FC. Results demonstrate that increasing CTH differences between homotopic brain areas lead to BOLD-FC reductions. Simulations suggest that CTH increases correspond to broadened and delayed CBF responses to fluctuations in ongoing neuronal activity.

YNICL Journal 2021 Journal Article

Within amygdala: Basolateral parts are selectively impaired in premature-born adults

• Benita Schmitz-Koep
• Juliana Zimmermann
• Aurore Menegaux
• Rachel Nuttall
• Josef G. Bäuml
• Sebastian C. Schneider
• Marcel Daamen
• Henning Boecker

While it is known that whole amygdala volume is lastingly reduced after premature birth, it is unknown whether different amygdala nuclei are distinctively affected by prematurity. This question is motivated by two points: First, the observation that developmental trajectories of superficial, centromedial and basolateral amygdala nuclei are different. And second, the expectation that these different developmental pathways are distinctively affected by prematurity. Furthermore, we stated the question whether alterations in amygdala nuclei are associated with increased adults' anxiety traits after premature birth. We investigated 101 very premature-born adults (<32 weeks of gestation and/or birth weight below 1500 g) and 108 full-term controls of a prospectively and longitudinally collected cohort at 26 years of age using automated amygdala nuclei segmentation based on structural MRI. We found selectively reduced volumes of bilateral accessory basal nuclei (pertaining to the basolateral amygdala of claustral developmental trajectory) adjusted for whole amygdala volume. Volumes of bilateral accessory basal nuclei were positively associated with gestational age and negatively associated with duration of ventilation. Furthermore, structural covariance within the basolateral amygdala was increased in premature-born adults. We did not find an association between reduced volumes of basolateral amygdala and increased social anxiety in the prematurity group. These results demonstrate specifically altered basolateral amygdala structure in premature-born adults. Data suggest that prematurity has distinct effects on amygdala nuclei.

YNIMG Journal 2020 Journal Article

An analysis of MRI derived cortical complexity in premature-born adults: Regional patterns, risk factors, and potential significance

• Dennis M. Hedderich
• Josef G. Bäuml
• Aurore Menegaux
• Mihai Avram
• Marcel Daamen
• Claus Zimmer
• Peter Bartmann
• Lukas Scheef

Premature birth bears an increased risk for aberrant brain development concerning its structure and function. Cortical complexity (CC) expresses the fractal dimension of the brain surface and changes during neurodevelopment. We hypothesized that CC is altered after premature birth and associated with long-term cognitive development. One-hundred-and-one very premature-born adults (gestational age <32 weeks and/or birth weight <1500 ​g) and 111 term-born adults were assessed by structural MRI and cognitive testing at 26 years of age. CC was measured based on MRI by vertex-wise estimation of fractal dimension. Cognitive performance was measured based on Griffiths-Mental-Development-Scale (at 20 months) and Wechsler-Adult-Intelligence-Scales (at 26 years). In premature-born adults, CC was decreased bilaterally in large lateral temporal and medial parietal clusters. Decreased CC was associated with lower gestational age and birth weight. Furthermore, decreased CC in the medial parietal cortices was linked with reduced full-scale IQ of premature-born adults and mediated the association between cognitive development at 20 months and IQ in adulthood. Results demonstrate that CC is reduced in very premature-born adults in temporoparietal cortices, mediating the impact of prematurity on impaired cognitive development. These data indicate functionally relevant long-term alterations in the brain's basic geometry of cortical organization in prematurity.

YNIMG Journal 2020 Journal Article

Human subsystems of medial temporal lobes extend locally to amygdala nuclei and globally to an allostatic-interoceptive system

• Adriana L. Ruiz-Rizzo
• Florian Beissner
• Kathrin Finke
• Hermann J. Müller
• Claus Zimmer
• Lorenzo Pasquini
• Christian Sorg

In mammals, the hippocampus, entorhinal, perirhinal, and parahippocampal cortices (i. e. , core regions of the human medial temporal lobes, MTL) are locally interlaced with the adjacent amygdala nuclei at the structural and functional levels. At the global brain level, the human MTL has been described as part of the default mode network and amygdala nuclei as parts of the salience network, with both networks collectively forming a large-scale brain system supporting allostatic-interoceptive functions. We hypothesized (i) that intrinsic functional connectivity of slow activity fluctuations would reveal human MTL subsystems locally extending to the amygdala; and (ii) that these extended local subsystems would be globally embedded in large-scale brain systems supporting allostatic-interoceptive functions. Capitalizing on resting-state fMRI data of three independent samples of cognitively healthy adults (one main and two replication samples: N ​= ​101, 60, and 29, respectively), we analyzed the functional connectivity of fluctuating ongoing BOLD-activity within and outside the amygdala-MTL in a data-driven way using masked independent component and dual-regression analyses. We found that at the local level, MTL subsystems extend to the amygdala and are functionally organized along the longitudinal amygdala-MTL axis. These subsystems are characterized by consistent involvement of amygdala, hippocampus, and entorhinal cortex, but variable participation of perirhinal and parahippocampal regions. At the global level, amygdala-MTL subsystems selectively connect to salience, thalamic-brainstem, and default mode networks – the major cortical and subcortical components of the allostatic-interoceptive system. These findings provide evidence for integrated amygdala-MTL subsystems in humans, which are embedded within a larger allostatic-interoceptive system.

YNIMG Journal 2020 Journal Article

Linking the impact of aging on visual short-term memory capacity with changes in the structural connectivity of posterior thalamus to occipital cortices

• Aurore Menegaux
• Felix J.B. Bäuerlein
• Aliki Vania
• Natan Napiorkowski
• Julia Neitzel
• Adriana L. Ruiz-Rizzo
• Hermann J. Müller
• Christian Sorg

Aging impacts both visual short-term memory (vSTM) capacity and thalamo-cortical connectivity. According to the Neural Theory of Visual Attention, vSTM depends on the structural connectivity between posterior thalamus and visual occipital cortices (PT-OC). We tested whether aging modifies the association between vSTM capacity and PT-OC structural connectivity. To do so, 66 individuals aged 20–77 years were assessed by diffusion-weighted imaging used for probabilistic tractography and performed a psychophysical whole-report task of briefly presented letter arrays, from which vSTM capacity estimates were derived. We found reduced vSTM capacity, and aberrant PT-OC connection probability in aging. Critically, age modified the relationship between vSTM capacity and PT-OC connection probability: in younger adults, vSTM capacity was negatively correlated with PT-OC connection probability while in older adults, this association was positive. Furthermore, age modified the microstructure of PT-OC tracts suggesting that the inversion of the association between PT-OC connection probability and vSTM capacity with aging might reflect age-related changes in white-matter properties. Accordingly, our results demonstrate that age-related differences in vSTM capacity links with the microstructure and connectivity of PT-OC tracts.

YNIMG Journal 2020 Journal Article

Modeling the impact of neurovascular coupling impairments on BOLD-based functional connectivity at rest

• Mario E. Archila-Meléndez
• Christian Sorg
• Christine Preibisch

Functional magnetic resonance imaging (fMRI) of blood oxygenation level dependent (BOLD) signals during the resting-state is widely used to study functional connectivity (FC) of slowly fluctuating ongoing brain activity (BOLD-FC) in humans with and without brain diseases. While physiological impairments, e. g. aberrant perfusion or vascular reactivity, are common in neurological and psychiatric disorders, their impact on BOLD-FC is widely unknown and ignored. The aim of our simulation study, therefore, was to investigate the influence of impaired neurovascular coupling on resting-state BOLD-FC. Simulated BOLD signals comprising intra- and extravascular contributions were derived from an adjusted balloon model, which allows for independent definitions of cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) responses, being elicited by a synthetic oscillatory input signal with low frequency (0. 05 ​Hz) amplitude modulations. BOLD-FC was then defined by correlations between physiological reference BOLD time curves (seeds of seed-based BOLD-FC) and the test BOLD time curves (targets of BOLD-FC) featuring altered physiological variables (CMRO2, CBF, cerebral blood volume (CBV)). Impact of impaired neurovascular coupling on BOLD-FC was investigated for three different scenarios with independent changes in (1) CBF and CMRO2 amplitudes, (2) CBF and CMRO2 delays, and (3) coupling between CBF and CBV. For scenario 1, we found ‘linear’ influences of CMRO2 and CBF amplitudes on BOLD-FC: for a given CMRO2 amplitude, BOLD-FC changes from negative to positive FC with increasing CBF amplitude, and increasing CMRO2 amplitude simply shifts this dependence linearly. For scenario 2, CMRO2 and CBF delays had a complex ‘non-linear’ effect on BOLD-FC: for small CMRO2 delays, we found that BOLD-FC changes from positive to negative BOLD-FC with increasing CBF delays, but for large CMRO2 delays positive BOLD-FC simply diminishes with increasing CBF delay. For scenario 3, changes in CBF-CBV coupling have almost no effect on BOLD-FC. All these changes were not critically influenced by both signal-to-noise-ratio and temporal resolution modulations. Our results demonstrate the importance of alterations in neurovascular coupling for aberrant resting-state BOLD-FC. Based on our data, we suggest to complement BOLD-FC studies, at least of at-risk patient populations, with perfusion and oxygenation sensitive MRI. In cases where this is not available, we recommend careful interpretation of BOLD-FC results considering previous findings about hemodynamic-metabolic changes. In the future, accurate modeling of the hemodynamic-metabolic context might improve both our understanding of the crucial interplay between vascular-hemodynamic-neuronal components of intrinsic BOLD-FC and the evaluation of aberrant BOLD-FC in brain diseases with vascular-hemodynamic impairments.

YNIMG Journal 2019 Journal Article

Cognitive reward control recruits medial and lateral frontal cortices, which are also involved in cognitive emotion regulation: A coordinate-based meta-analysis of fMRI studies

• Felix Brandl
• Zarah Le Houcq Corbi
• Satja Mulej Bratec
• Christian Sorg

Cognitive reward control (CRC) refers to the cognitive control of one’s craving for hedonic stimuli, like food, sex, or drugs. Numerous functional magnetic resonance imaging (fMRI) studies have investigated neural sources of CRC. However, a consistent pattern of brain activation across stimulus types has not been identified so far. We addressed this question using coordinate-based meta-analysis of task-fMRI studies during CRC. To further characterize such a potential common CRC activation pattern, we extended our approach to three additional questions: (i) Do CRC meta-analytic results overlap with those during the control of emotional states, such as in cognitive regulation of aversive emotions (cognitive emotion regulation, CER)? (ii) How does the control of motivational/emotional states link to the control of action states with less motivational/emotional valence such as in response inhibition paradigms, i. e. , do meta-anyltic result maps overlap? (iii) Does the control of motivational/emotional states constitute a consistent pattern of organized (i. e. , coherent) ongoing or intrinsic brain activity? This question was tested by a seed-based intrinsic functional connectivity (iFC) analysis in an independent data set of resting-state fMRI. We found consistent CRC activation mainly in supplementary motor, dorsolateral prefrontal, and ventrolateral prefrontal cortices across studies. This activation pattern overlapped largely with CER-related activation, except for left-sided lateral temporal and parietal cortex activation, which was more pronounced during CER. It overlapped partly with activation during response inhibition in (pre-)supplementary motor, insular, and parietal cortices, but differed from it in dorsolateral and ventrolateral prefrontal cortices. Furthermore, it remarkably defined an iFC network covering activation patterns of both CRC and CER. Results demonstrate a consistent activation pattern of CRC across stimulus types, which overlaps largely with those of CER but only partly with those of response inhibition and constitutes an intrinsic co-activity network. These data suggest a common mechanism for the cognitive control of both motivational and emotional stimuli.

YNICL Journal 2019 Journal Article

Low-rank network signatures in the triple network separate schizophrenia and major depressive disorder

• Wei Han
• Christian Sorg
• Changgang Zheng
• Qinli Yang
• Xiaosong Zhang
• Arvid Ternblom
• Cobbinah Bernard Mawuli
• Lianli Gao

Brain imaging studies have revealed that functional and structural brain connectivity in the so-called triple network (i.e., default mode network (DMN), salience network (SN) and central executive network (CEN)) are consistently altered in schizophrenia. However, similar changes have also been found in patients with major depressive disorder, prompting the question of specific triple network signatures for the two disorders. In this study, we proposed Supervised Convex Nonnegative Matrix Factorization (SCNMF) to extract distributed multi-modal brain patterns. These patterns distinguish schizophrenia and major depressive disorder in a latent low-dimensional space of the triple brain network. Specifically, 21 patients of schizophrenia and 25 patients of major depressive disorder were assessed by T1-weighted, diffusion-weighted, and resting-state functional MRIs. Individual structural and functional connectivity networks, based on pre-defined regions of the triple network were constructed, respectively. Afterwards, SCNMF was employed to extract the discriminative patterns. Experiments indicate that SCNMF allows extracting the low-rank discriminative patterns between the two disorders, achieving a classification accuracy of 82.6% based on the extracted functional and structural abnormalities with support vector machine. Experimental results show the specific brain patterns for schizophrenia and major depressive disorder that are multi-modal, complex, and distributed in the triple network. Parts of the prefrontal cortex including superior frontal gyri showed variation between patients with schizophrenia and major depression due to structural properties. In terms of functional properties, the middle cingulate cortex, inferior parietal lobule, and cingulate cortex were the most discriminative regions.

YNIMG Journal 2019 Journal Article

Phasic alerting effects on visual processing speed are associated with intrinsic functional connectivity in the cingulo-opercular network

• Marleen Haupt
• Adriana L. Ruiz-Rizzo
• Christian Sorg
• Kathrin Finke

Phasic alertness refers to short-lived increases in the brain's “state of readiness”, and thus to optimized performance following warning cues. Parametric modelling of whole report task performance based on the computational theory of visual attention (TVA) has demonstrated that visual processing speed is increased in such cue compared to no-cue conditions. Furthermore, with respect to the underlying neural mechanisms, individual visual processing speed has been related to intrinsic functional connectivity (iFC) within the cingulo-opercular network, suggesting that this network's iFC is relevant for the tonic maintenance of an appropriate readiness or alertness state. In the present study, we asked whether iFC in the cingulo-opercular network is also related to the individual ability to actively profit from warning cues, i. e. to the degree of phasic alerting. We obtained resting-state functional magnetic resonance imaging (rs-fMRI) data from 32 healthy young participants and combined an independent component analysis of rs-fMRI time courses and dual regression approach to determine iFC in the cingulo-opercular network. In a separate behavioural testing session, we parametrically assessed the effects of auditory phasic alerting cues on visual processing speed in a TVA-based whole report paradigm. A voxel-wise multiple regression revealed that higher individual phasic alerting effects on visual processing speed were significantly associated with lower iFC in the cingulo-opercular network, with a peak in the left superior orbital gyrus. As phasic alertness was neither related to iFC in other attention-relevant, auditory, or visual networks nor associated with any inter-network connectivity pattern, the results suggest that the individual profit in visual processing speed gained from phasic alerting is primarily associated with iFC in the cingulo-opercular network.

YNIMG Journal 2019 Journal Article

Theory of visual attention thalamic model for visual short-term memory capacity and top-down control: Evidence from a thalamo-cortical structural connectivity analysis

• Aurore Menegaux
• Natan Napiorkowski
• Julia Neitzel
• Adriana L. Ruiz-Rizzo
• Anders Petersen
• Hermann J. Müller
• Christian Sorg
• Kathrin Finke

In the theory of visual attention (TVA), it is suggested that objects in a visual scene compete for representation in a visual short-term memory (vSTM) store. The race towards the store is assumed to be biased by top-down controlled weighting of the objects according to their task relevance. Only objects that reach the store before its capacity limitation is reached are represented consciously in a given instant. TVA-based computational modeling of participants’ performance in whole- and partial-report tasks permits independent parameters of individual efficiency of top-down control α and vSTM storage capacity K to be extracted. The neural interpretation of the TVA proposes recurrent loops between the posterior thalamus and posterior visual cortices to be relevant for generating attentional weights for competing objects and for maintaining selected objects in vSTM. Accordingly, we tested whether structural connectivity between posterior thalamus and occipital cortices (PT-OC) is associated with estimates of top-down control and vSTM capacity. We applied whole- and partial-report tasks and probabilistic tractography in a sample of 37 healthy adults. We found vSTM capacity K to be associated with left PT-OC structural connectivity and a trend-wise relation between top-down control α and right PT-OC structural connectivity. These findings support the assumption of the relevance of thalamic structures and their connections to visual cortex for top-down control and vSTM capacity.

YNIMG Journal 2017 Journal Article

Cognitive emotion regulation modulates the balance of competing influences on ventral striatal aversive prediction error signals

• Satja Mulej Bratec
• Xiyao Xie
• Yijun Wang
• Leonhard Schilbach
• Claus Zimmer
• Afra M. Wohlschläger
• Valentin Riedl
• Christian Sorg

Cognitive emotion regulation (CER) is a critical human ability to face aversive emotional stimuli in a flexible way, via recruitment of specific prefrontal brain circuits. Animal research reveals a central role of ventral striatum in emotional behavior, for both aversive conditioning, with striatum signaling aversive prediction errors (aPE), and for integrating competing influences of distinct striatal inputs from regions such as the prefrontal cortex (PFC), amygdala, hippocampus and ventral tegmental area (VTA). Translating these ventral striatal findings from animal research to human CER, we hypothesized that successful CER would affect the balance of competing influences of striatal afferents on striatal aPE signals, in a way favoring PFC as opposed to ‘subcortical’ (i. e. , non-isocortical) striatal inputs. Using aversive Pavlovian conditioning with and without CER during fMRI, we found that during CER, superior regulators indeed reduced the modulatory impact of ‘subcortical’ striatal afferents (hippocampus, amygdala and VTA) on ventral striatal aPE signals, while keeping the PFC impact intact. In contrast, inferior regulators showed an opposite pattern. Our results demonstrate that ventral striatal aPE signals and associated competing modulatory inputs are critical mechanisms underlying successful cognitive regulation of aversive emotions in humans.

YNIMG Journal 2017 Journal Article

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

• Aurore Menegaux
• Chun Meng
• Julia Neitzel
• Josef G. Bäuml
• Hermann J. Müller
• Peter Bartmann
• Dieter Wolke
• Afra M. Wohlschläger

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.

YNICL Journal 2017 Journal Article

Multicenter stability of resting state fMRI in the detection of Alzheimer's disease and amnestic MCI

• Stefan J. Teipel
• Alexandra Wohlert
• Coraline Metzger
• Timo Grimmer
• Christian Sorg
• Michael Ewers
• Eva Meisenzahl
• Stefan Klöppel

BACKGROUND: In monocentric studies, patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia exhibited alterations of functional cortical connectivity in resting-state functional MRI (rs-fMRI) analyses. Multicenter studies provide access to large sample sizes, but rs-fMRI may be particularly sensitive to multiscanner effects. METHODS: We used data from five centers of the "German resting-state initiative for diagnostic biomarkers" (psymri.org), comprising 367 cases, including AD patients, MCI patients and healthy older controls, to assess the influence of the distributed acquisition on the group effects. We calculated accuracy of group discrimination based on whole brain functional connectivity of the posterior cingulate cortex (PCC) using pooled samples as well as second-level analyses across site-specific group contrast maps. RESULTS: We found decreased functional connectivity in AD patients vs. controls, including clusters in the precuneus, inferior parietal cortex, lateral temporal cortex and medial prefrontal cortex. MCI subjects showed spatially similar, but less pronounced, differences in PCC connectivity when compared to controls. Group discrimination accuracy for AD vs. controls (MCI vs. controls) in the test data was below 76% (72%) based on the pooled analysis, and even lower based on the second level analysis stratified according to scanner. Only a subset of quality measures was useful to detect relevant scanner effects. CONCLUSIONS: Multicenter rs-fMRI analysis needs to employ strict quality measures, including visual inspection of all the data, to avoid seriously confounded group effects. While pending further confirmation in biomarker stratified samples, these findings suggest that multicenter acquisition limits the use of rs-fMRI in AD and MCI diagnosis.

YNIMG Journal 2016 Journal Article

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

• Xiyao Xie
• Satja Mulej Bratec
• Gabriele Schmid
• Chun Meng
• Anselm Doll
• Afra Wohlschläger
• Kathrin Finke
• Hans Förstl

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.

YNIMG Journal 2016 Journal Article

Mindful attention to breath regulates emotions via increased amygdala–prefrontal cortex connectivity

• Anselm Doll
• Britta K. Hölzel
• Satja Mulej Bratec
• Christine C. Boucard
• Xiyao Xie
• Afra M. Wohlschläger
• Christian Sorg

Mindfulness practice is beneficial for emotion regulation; however, the neural mechanisms underlying this effect are poorly understood. The current study focuses on effects of attention-to-breath (ATB) as a basic mindfulness practice on aversive emotions at behavioral and brain levels. A key finding across different emotion regulation strategies is the modulation of amygdala and prefrontal activity. It is unclear how ATB relevant brain areas in the prefrontal cortex integrate with amygdala activation during emotional stimulation. We proposed that, during emotional stimulation, ATB down-regulates activation in the amygdala and increases its integration with prefrontal regions. To address this hypothesis, 26 healthy controls were trained in mindfulness-based attention-to-breath meditation for two weeks and then stimulated with aversive pictures during both attention-to-breath and passive viewing while undergoing fMRI. Data were controlled for breathing frequency. Results indicate that (1) ATB was effective in regulating aversive emotions. (2) Left dorso-medial prefrontal cortex was associated with ATB in general. (3) A fronto-parietal network was additionally recruited during emotional stimulation. (4) ATB down regulated amygdala activation and increased amygdala–prefrontal integration, with such increased integration being associated with mindfulness ability. Results suggest amygdala–dorsal prefrontal cortex integration as a potential neural pathway of emotion regulation by mindfulness practice.

YNIMG Journal 2015 Journal Article

Cognitive emotion regulation enhances aversive prediction error activity while reducing emotional responses

• Satja Mulej Bratec
• Xiyao Xie
• Gabriele Schmid
• Anselm Doll
• Leonhard Schilbach
• Claus Zimmer
• Afra Wohlschläger
• Valentin Riedl

Cognitive emotion regulation is a powerful way of modulating emotional responses. However, despite the vital role of emotions in learning, it is unknown whether the effect of cognitive emotion regulation also extends to the modulation of learning. Computational models indicate prediction error activity, typically observed in the striatum and ventral tegmental area, as a critical neural mechanism involved in associative learning. We used model-based fMRI during aversive conditioning with and without cognitive emotion regulation to test the hypothesis that emotion regulation would affect prediction error-related neural activity in the striatum and ventral tegmental area, reflecting an emotion regulation-related modulation of learning. Our results show that cognitive emotion regulation reduced emotion-related brain activity, but increased prediction error-related activity in a network involving ventral tegmental area, hippocampus, insula and ventral striatum. While the reduction of response activity was related to behavioral measures of emotion regulation success, the enhancement of prediction error-related neural activity was related to learning performance. Furthermore, functional connectivity between the ventral tegmental area and ventrolateral prefrontal cortex, an area involved in regulation, was specifically increased during emotion regulation and likewise related to learning performance. Our data, therefore, provide first-time evidence that beyond reducing emotional responses, cognitive emotion regulation affects learning by enhancing prediction error-related activity, potentially via tegmental dopaminergic pathways.

YNICL Journal 2015 Journal Article

Neural correlates of executive attention in adults born very preterm

• Marcel Daamen
• Josef G. Bäuml
• Lukas Scheef
• Chun Meng
• Alina Jurcoane
• Julia Jaekel
• Christian Sorg
• Barbara Busch

Very preterm birth is associated with an increased prevalence of attention problems and may especially impair executive attention, i.e., top-down control of attentional selection in situations where distracting information interferes with the processing of task-relevant stimuli. While there are initial findings linking structural brain alterations in preterm-born individuals with attention problems, the functional basis of these problems are not well understood. The present study used an fMRI adaptation of the Attentional Network Test to examine the neural correlates of executive attention in a large sample of N = 86 adults born very preterm and/or with very low birth weight (VP/VLBW), and N = 100 term-born controls. Executive attention was measured by comparing task behavior and brain activations associated with the processing of incongruent vs. congruent arrow flanker stimuli. Consistent with subtle impairments of executive attention, the VP/VLBW group showed lower accuracy and a tendency for increased response times during the processing of incongruent stimuli. Both groups showed similar activation patters, especially within expected fronto-cingulo-parietal areas, but no significant between-group differences. Our results argue for a maintained attention-relevant network organization in high-functioning preterm born adults in spite of subtle deficits in executive attention. Gestational age and neonatal treatment variables showed associations with task behavior, and brain activation in the dorsal ACC and lateral occipital areas, suggesting that the degree of prematurity (and related neonatal complications) has subtle modulatory influences on executive attention processing.

YNIMG Journal 2015 Journal Article

Visual attention in preterm born adults: Specifically impaired attentional sub-mechanisms that link with altered intrinsic brain networks in a compensation-like mode

• Kathrin Finke
• Julia Neitzel
• Josef G. Bäuml
• Petra Redel
• Hermann J. Müller
• Chun Meng
• Julia Jaekel
• Marcel Daamen

Although pronounced and lasting deficits in selective attention have been observed for preterm born individuals it is unknown which specific attentional sub-mechanisms are affected and how they relate to brain networks. We used the computationally specified ‘Theory of Visual Attention’ together with whole- and partial-report paradigms to compare attentional sub-mechanisms of pre- (n=33) and full-term (n=32) born adults. Resting-state fMRI was used to evaluate both between-group differences and inter-individual variance in changed functional connectivity of intrinsic brain networks relevant for visual attention. In preterm born adults, we found specific impairments of visual short-term memory (vSTM) storage capacity while other sub-mechanisms such as processing speed or attentional weighting were unchanged. Furthermore, changed functional connectivity was found in unimodal visual and supramodal attention-related intrinsic networks. Among preterm born adults, the individual pattern of changed connectivity in occipital and parietal cortices was systematically associated with vSTM in such a way that the more distinct the connectivity differences, the better the preterm adults' storage capacity. These findings provide first evidence for selectively changed attentional sub-mechanisms in preterm born adults and their relation to altered intrinsic brain networks. In particular, data suggest that cortical changes in intrinsic functional connectivity may compensate adverse developmental consequences of prematurity on visual short-term storage capacity.

YNICL Journal 2014 Journal Article

LRP-1 polymorphism is associated with global and regional amyloid load in Alzheimer's disease in humans in-vivo

• Timo Grimmer
• Oliver Goldhardt
• Liang-Hao Guo
• Behrooz H. Yousefi
• Stefan Förster
• Alexander Drzezga
• Christian Sorg
• Panagiotis Alexopoulos

OBJECTIVE: Impaired amyloid clearance has been proposed to contribute to β-amyloid deposition in sporadic late-onset Alzheimer's disease (AD). Low density lipoprotein receptor-related protein 1 (LRP-1) is involved in the active outward transport of β-amyloid across the blood-brain barrier (BBB). The C667T polymorphism (rs1799986) of the LRP-1 gene has been inconsistently associated with AD in genetic studies. We aimed to elucidate the association of this polymorphism with in-vivo brain amyloid load of AD patients using amyloid PET with [(11)C]PiB. MATERIALS AND METHODS: 72 patients with very mild to moderate AD were examined with amyloid PET and C667T polymorphism was obtained using TaqMan PCR assays. The association of C667T polymorphism with global and regional amyloid load was calculated using linear regression and voxel based analysis, respectively. The effect of the previously identified modulator of amyloid uptake, the apolipoprotein E genotype, on this association was also determined. RESULTS: The regression analysis between amyloid load and C667T polymorphism was statistically significant (p = 0.046, β = 0.236). In an additional analysis ApoE genotype and gender were identified to explain further variability of amyloid load. Voxel based analysis revealed a significant (p < 0.05) association between C667T polymorphism and amyloid uptake in the temporo-parietal cortex bilaterally. ApoE did not interact significantly with the LRP-1 polymorphism. DISCUSSION: In conclusion, C667T polymorphism of LRP-1 is moderately but significantly associated with global and regional amyloid deposition in AD. The relationship appears to be independent of the ApoE genotype. This finding is compatible with the hypothesis that impaired amyloid clearance contributes to amyloid deposition in late-onset sporadic AD.

YNIMG Journal 2013 Journal Article

Selectively and progressively disrupted structural connectivity of functional brain networks in Alzheimer's disease — Revealed by a novel framework to analyze edge distributions of networks detecting disruptions with strong statistical evidence

• Klaus Hahn
• Nicholas Myers
• Sergei Prigarin
• Karsten Rodenacker
• Alexander Kurz
• Hans Förstl
• Claus Zimmer
• Afra M. Wohlschläger

Alzheimer's disease (AD) disrupts selectively and progressively (increasing with severity) functional connectivity of intrinsic brain networks (IBNs), most prominent in the default mode network. Given that IBNs' functional connectivity depends on structural connectivity, we hypothesize for our study selective and progressive changes of IBN based structural connectivity in AD. To achieve strong statistical evidence, we introduce a novel statistical method based on the edge frequency distributions of structural connectivity networks. Such non-Gaussian distributions are compared in a multiple testing scheme, combining a flexible nonparametric test statistic with permutation based strong control of the family wise error rate. We assessed 26 healthy elderly, 23 patients with AD-dementia, and 28 patients with mild cognitive impairment (MCI) by resting-state functional MRI, diffusion tensor imaging, and clinical–neuropsychological testing including annual follow-up assessment. After 3years, 50% of the patients with MCI converted to AD. Tractography of diffusion tensor data identifies structural connectivity networks between regions of IBNs, which are detected by an independent component analysis of resting state fMRI data. We find that IBNs' structural connectivity is selectively and progressively disrupted with primary changes in the default mode network. Correspondent results are found for IBNs' functional connectivity. In addition, structural connectivity across the nodes of all IBNs separated individual MCI patients converting to AD from non-converters. Conclusively, our study provides a new approach to analyze connectivity networks by their non-Gaussian edge frequency distributions and achieves strong statistical evidence by application of the family wise error rate. Data analysis provides selective and progressive disruptions of IBN's structural connectivity in AD and demonstrates the increased power of our method compared to recent studies.

YNIMG Journal 2012 Journal Article

Corrigendum to ‘Repeated pain induces adaptations of intrinsic brain activity to reflect past and predict future pain’ [NeuroImage 57/1 (2011) 206–213]

• Valentin Riedl
• Michael Valet
• Andreas Wöller
• Christian Sorg
• Dominik Vogel
• Till Sprenger
• Henning Boecker
• Afra M. Wohlschläger

YNIMG Journal 2011 Journal Article

Repeated pain induces adaptations of intrinsic brain activity to reflect past and predict future pain

• Valentin Riedl
• Michael Valet
• Andreas Wöller
• Christian Sorg
• Dominik Vogel
• Till Sprenger
• Henning Boecker
• Afra M. Wohlschläger

Recent neuroimaging studies have revealed a persistent architecture of intrinsic connectivity networks (ICNs) in the signal of functional magnetic resonance imaging (fMRI) of humans and other species. ICNs are characterized by coherent ongoing activity between distributed brain regions during rest, in the absence of externally oriented behavior. While these networks strongly reflect anatomical connections, the relevance of ICN activity for human behavior remains unclear. Here, we investigated whether intrinsic brain activity adapts to repeated pain and encodes an individual's experience. Healthy subjects received a short episode of heat pain on 11 consecutive days. Across this period, subjects either habituated or sensitized to the painful stimulation. This adaptation was reflected in plasticity of a sensorimotor ICN (SMN) comprising pain related brain regions: coherent intrinsic activity of the somatosensory cortex retrospectively mirrored pain perception; on day 11, intrinsic activity of the prefrontal cortex was additionally synchronized with the SMN and predicted whether an individual would experience more or less pain during upcoming stimulation. Other ICNs of the intrinsic architecture remained unchanged. Due to the ubiquitous occurrence of ICNs in several species, we suggest intrinsic brain activity as an integrative mechanism reflecting accumulated experiences.