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Henning Boecker

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16

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.

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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.

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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.

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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.

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YNICL Journal 2019 Journal Article

Disentangling motor planning and motor execution in unmedicated de novo Parkinson's disease patients: An fMRI study

  • Jason A. Martin
  • Nadine Zimmermann
  • Lukas Scheef
  • Jakob Jankowski
  • Sebastian Paus
  • Hans H. Schild
  • Thomas Klockgether
  • Henning Boecker

Many studies have used functional magnetic resonance imaging to unravel the neuronal underpinnings of motor system abnormalities in Parkinson's disease, indicating functional inhibition at the level of basal ganglia-thalamo-cortical motor networks. The study aim was to extend the characterization of functional motor changes in Parkinson's Disease by dissociating between two phases of action (i.e. motor planning and motor execution) during an automated unilateral finger movement sequence with the left and right hand, separately. In essence, we wished to identify neuronal dysfunction and potential neuronal compensation before (planning) and during (execution) automated sequential motor behavior in unmedicated early stage Parkinson's Disease patients. Twenty-two Parkinson's Disease patients (14 males; 53 ± 11 years; Hoehn and Yahr score 1.4 ± 0.6; UPDRS (part 3) motor score 16 ± 6) and 22 healthy controls (14 males; 49 ± 12 years) performed a pre-learnt four finger sequence (index, ring, middle and little finger, in order), either self-initiated (FREE) or externally triggered (REACT), within an 8-second time window. Findings were most pronounced during FREE with the clinically most affected side, where motor execution revealed significant underactivity of contralateral primary motor cortex, contralateral posterior putamen (sensorimotor territory), ipsilateral anterior cerebellum / cerebellar vermis, along with underactivity in supplementary motor area (based on ROI analyses only), corroborating previous findings in Parkinson's Disease. During motor planning, Parkinson's Disease patients showed a significant relative overactivity in dorsolateral prefrontal cortex (DLPFC), suggesting a compensatory overactivity. To a variable extent this relative overactivity in the DLPFC went along with a relative overactivity in the precuneus and the ipsilateral anterior cerebellum/cerebellar vermis Our study illustrates that a refined view of disturbances in motor function and compensatory processes can be gained from experimental designs that try to dissociate motor planning from motor execution, emphasizing that compensatory mechanisms are triggered in Parkinson's Disease when voluntary movements are conceptualized for action.

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YNICL Journal 2019 Journal Article

Subregional volume reduction of the cholinergic forebrain in subjective cognitive decline (SCD)

  • Lukas Scheef
  • Michel J. Grothe
  • Alexander Koppara
  • Marcel Daamen
  • Henning Boecker
  • Hans Biersack
  • Hans H. Schild
  • Michael Wagner

Subjective cognitive decline (SCD) patients are considered as a risk population for preclinical Alzheimer's Disease (AD). Supporting this idea, previous studies in SCD populations report subtle alterations in various cognitive and neuroimaging biomarkers that are typically affected during AD progression. To extend these observations, the present study examined whether SCD patients show atrophy of cholinergic basal forebrain nuclei (chBFN), analogous with recent findings in prodromal and clinical AD patients. We assessed volume reductions of the chBFN in 24 SCD subjects compared to 49 matched controls on 3D-T1-weighted MR images based on a postmortem derived atlas. Furthermore, we assessed whether chBFN atrophy was linked with cognitive, structural and metabolic biomarker alterations we previously reported in this SCD cohort: Using correlation analyses we tested for associations between the volumes of the chBFN with the hippocampal gray matter volume, and posterior medial glucose consumption, and the trajectory of verbal memory performance. The SCD cases showed a significant total volume reduction of the chBFN, with largest effect sizes in the Ch1/2 and Ch4p subdivisions of the chBFN. The latter was associated with a reduced glucose metabolism in the precuneus for the SCD group only. These data show an early involvement of the cholinergic basal forebrain nuclei in SCD predominantly in Ch1/2 and Ch4p which supports the conceptual link between SCD and preclinical AD.

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YNIMG Journal 2016 Journal Article

A perspective on the future role of brain pet imaging in exercise science

  • Henning Boecker
  • Alexander Drzezga

Positron Emission Tomography (PET) bears a unique potential for examining the effects of physical exercise (acute or chronic) within the central nervous system in vivo, including cerebral metabolism, neuroreceptor occupancy, and neurotransmission. However, application of Neuro-PET in human exercise science is as yet surprisingly sparse. To date the field has been dominated by non-invasive neuroelectrical techniques (EEG, MEG) and structural/functional magnetic resonance imaging (sMRI/fMRI). Despite PET having certain inherent disadvantages, in particular radiation exposure and high costs limiting applicability at large scale, certain research questions in human exercise science can exclusively be addressed with PET: The “metabolic trapping” properties of 18F-FDG PET as the most commonly used PET-tracer allow examining the neuronal mechanisms underlying various forms of acute exercise in a rather unconstrained manner, i. e. under realistic training scenarios outside the scanner environment. Beyond acute effects, 18F-FDG PET measurements under resting conditions have a strong prospective for unraveling the influence of regular physical activity on neuronal integrity and potentially neuroprotective mechanisms in vivo, which is of special interest for aging and dementia research. Quantification of cerebral glucose metabolism may allow determining the metabolic effects of exercise interventions in the entire human brain and relating the regional cerebral rate of glucose metabolism (rCMRglc) with behavioral, neuropsychological, and physiological measures. Apart from FDG-PET, particularly interesting applications comprise PET ligand studies that focus on dopaminergic and opioidergic neurotransmission, both key transmitter systems for exercise-related psychophysiological effects, including mood changes, reward processing, antinociception, and in its most extreme form ‘exercise dependence’. PET ligand displacement approaches even allow quantifying specific endogenous neurotransmitter release under acute exercise interventions, to which modern PET/MR hybrid technology will be additionally fruitful. Experimental studies exploiting the unprecedented multimodal imaging capacities of PET/MR in human exercise sciences are as yet pending.

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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.

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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.

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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.

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YNIMG Journal 2005 Journal Article

COMT Val108/158Met genotype affects the mu-opioid receptor system in the human brain: Evidence from ligand-binding, G-protein activation and preproenkephalin mRNA expression

  • Achim Berthele
  • Stefan Platzer
  • Burkard Jochim
  • Henning Boecker
  • Andreas Buettner
  • Bastian Conrad
  • Matthias Riemenschneider
  • Thomas R. Toelle

Recent data from [11C]carfentanil ligand-PET indicate that in the human brain, the availability of mu-opioid (MOP) receptor binding sites is affected by the Val108/158Met polymorphism of the catechol-O-methyltransferase (COMT) gene. This prompted us to validate the impact of COMT Val108/158Met on MOP receptors in human post-mortem brain. [3H]DAMGO receptor autoradiography was performed in frontal cortex, basal ganglia, thalamus and cerebellum (8 Met/Met, 6 Met/Val, 3 Val/Val). With respect to genotype, numbers of MOP binding sites in COMT Met108/158 homozygous and Val108/158Met heterozygous cases were higher than in Val108/158 homozygous. Differences were significant in the caudate nucleus (Val/Met vs. Val/Val), nucleus accumbens (Val/Met vs. Val/Val) and the mediodorsal nucleus of the thalamus (Met/Met vs. Val/Val). In the thalamus, this was corroborated by DAMGO-stimulated [35S]GTPγS autoradiography. Moreover, stepwise multiple regression taking into account various covariables allowed to confirm the COMT genotype as the most predictive factor in this structure. As a mechanism how COMT might exert its action on MOP receptors, it has been suggested that at least in striatopallidal circuits COMT Val108/158Met impacts on enkephalin, which is capable of reciprocally regulating MOP receptor expression. Thus, we assessed preproenkephalin mRNA by in situ hybridization. In the striatum, mRNA levels were significantly higher in COMT Met108/158 homozygous cases indicating that MOP binding sites and enkephalin are regulated in parallel. Moreover, the transcript was not detectable in the thalamus. Thus, mechanisms other than an enkephalin-dependent receptor turnover must be responsible for COMT-related differences in MOP binding site availability in the human brain.

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YNIMG Journal 2005 Journal Article

Frequency-correlated decreases of motor cortex activity associated with subthalamic nucleus stimulation in Parkinson's disease

  • Bernhard Haslinger
  • Karin Kalteis
  • Henning Boecker
  • Francois Alesch
  • Andrés O. Ceballos-Baumann

According to the classical model of basal ganglia organization, deep brain stimulation (DBS) in the subthalamic nucleus (STN) for the treatment of Parkinson's disease (PD) blocks overactive excitatory projections to inhibitory basal ganglia output structures. This would release the break on thalamofrontal neurons alleviating the poverty of movement, the hallmark of PD. Such parallels to a functional lesion certainly simplify the mechanism of STN DBS. Here, we applied parametric analyses of H2 15O positron emission tomography (PET) scans at rest while systematically varying stimulation frequency in 6 patients with STN DBS for akinetic PD. A strong positive correlation of rCBF to increasing stimulation frequency was detected around the STN bilaterally. More importantly, we show that gradual increases in STN stimulation frequency are tightly correlated with decreases in motor cortex activity. This demonstrates an active modulation of resting activity within the subcortical stimulation target and within motor cortex by STN DBS. Rather than a possible downstream effect, we propose to consider the tight correlations between DBS frequency and motor cortex activity in the context of an upstream modulation of direct efferents to the STN from primary motor and premotor cortices.

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YNIMG Journal 2004 Journal Article

Quantification of [18F]diprenorphine kinetics in the human brain with compartmental and non-compartmental modeling approaches

  • Mary E Spilker
  • Till Sprenger
  • Michael Valet
  • Gjermund Henriksen
  • Klaus Wagner
  • Hans-J Wester
  • Thomas R Toelle
  • Henning Boecker

6-O-(2-[18F]fluoroethyl)-6-O-desmethyldiprenorphine ([18F]FDPN) is a nonselective opiate ligand that binds to postsynaptic μ, κ and δ opiate receptors. Due to the longer half-life of F-18, compared to C-11, labeling DPN with F-18 allows for alternative experimental protocols and potentially the evaluation of endogenous opioid release. The applicability of this compound to assorted experimental protocols motivated the evaluation of [18F]FDPN kinetics with compartmental and non-compartmental models. The results indicate that a two-tissue compartmental model best characterizes the data obtained following a bolus injection of [18F]FDPN (120-min scanning protocol). Estimates of distribution volume (DV) were robust, being highly correlated for the one-tissue compartmental model as well as the invasive Logan model and the basis function method. Furthermore, the DV estimates were also stable under a shortened protocol of 60 min, showing a significant correlation with the full protocol. The binding potential (BP) values showed more variability between methods and in some cases were more sensitive to protocol length. In conclusion, this evaluation of [18F]FDPN kinetics illustrates that DV values can be estimated robustly using compartmental modeling, the basis function method or the invasive Logan modeling approach on a volume of interest level. BP values were also found to correlate with DV values; however, these results should be interpreted with the understanding that specific binding in the reference region (occipital region) may exist.

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