Does Feedback-Related Brain Response during Reinforcement Learning Predict Socio-motivational (In-)dependence in Adolescence?

This multi-methodological study applied functional magnetic resonance imaging to investigate neural activation in a group of adolescent students (N = 88) during a probabilistic reinforcement learning task. We related patterns of emerging brain activity and individual learning rates to socio-motivational (in-)dependence manifested in four different motivation types (MTs): (1) peer-dependent MT, (2) teacher-dependent MT, (3) peer-and-teacher-dependent MT, (4) peer-and-teacher-independent MT. A multinomial regression analysis revealed that the individual learning rate predicts students’ membership to the independent MT, or the peer-and-teacher-dependent MT. Additionally, the striatum, a brain region associated with behavioral adaptation and flexibility, showed increased learning-related activation in students with motivational independence. Moreover, the prefrontal cortex, which is involved in behavioral control, was more active in students of the peer-and-teacher-dependent MT. Overall, this study offers new insights into the interplay of motivation and learning with (1) a focus on inter-individual differences in the role of peers and teachers as source of students’ individual motivation and (2) its potential neurobiological basis

Association between DRD2/ANKK1 TaqIA Allele Status and Striatal Dopamine D2/3 Receptor Availability in Alcohol Use Disorder

Background: The association between blunted dopaminergic neurotransmission and alcohol use disorder (AUD) is well-known. In particular, the impairment of postsynaptic dopamine 2 and 3 receptors (DRD2/3) in the ventral and dorsal striatum during the development and maintenance of alcohol addiction has been investigated in several positron emission tomography (PET) studies. However, it is unclear whether these changes are the result of adaptation or genetic predisposition. Methods: Here we investigated the association between DRD2/ankyrin repeat and kinase domain-containing 1 (ANKK1) TaqIA allele (rs1800497) status and striatal DRD2/3 availability measured by 18F-fallypride PET in 12 AUD patients and 17 sex-matched healthy controls. Age and smoking status were included as covariates. Results: Contrary to our expectations, TaqIA allele status was not associated with striatal DRD2/3 availability in either group and there was no significant difference between groups, possibly due to the relatively small sample size (N = 29). Conclusions: Nonetheless, this is the first in vivo study investigating the relationship between dopamine receptor availability and genetic factors in AUD. The pitfalls of assessing such relationships in a relatively small sample are discussed. Clinical Trial Registration: The published analysis is an additional, post hoc analysis to the preregistered trial with clinical trial number NCT01679145 available on https://clinical - trials.gov/ct2/show/NCT01679145

Dopamine D2/3 receptor availability in alcohol use disorder and individuals at high risk: Towards a dimensional approach

Alcohol use disorder (AUD) is the most common substance use disorder worldwide. Although dopamine-related findings were often observed in AUD, associated neurobiological mechanisms are still poorly understood. Therefore, in the present study, we investigate D2/3 receptor availability in healthy participants, participants at high risk (HR) to develop addiction (not diagnosed with AUD), and AUD patients in a detoxified stage, applying F-18-fallypride positron emission tomography (F-18-PET). Specifically, D2/3 receptor availability was investigated in (1) 19 low-risk (LR) controls, (2) 19 HR participants, and (3) 20 AUD patients after alcohol detoxification. Quality and severity of addiction were assessed with clinical questionnaires and (neuro)psychological tests. PET data were corrected for age of participants and smoking status. In the dorsal striatum, we observed significant reductions of D2/3 receptor availability in AUD patients compared with LR participants. Further, receptor availability in HR participants was observed to be intermediate between LR and AUD groups (linearly decreasing). Still, in direct comparison, no group difference was observed between LR and HR groups or between HR and AUD groups. Further, the score of the Alcohol Dependence Scale (ADS) was inversely correlated with D2/3 receptor availability in the combined sample. Thus, in line with a dimensional approach, striatal D2/3 receptor availability showed a linear decrease from LR participants to HR participants to AUD patients, which was paralleled by clinical measures. Our study shows that a core neurobiological feature in AUD seems to be detectable in an early, subclinical state, allowing more individualized alcohol prevention programs in the future

X-ray dark-field imaging of the human lung-A feasibility study on a deceased body

Disorders of the lungs such as chronic obstructive pulmonary disease (COPD) are a major cause of chronic morbidity and mortality and the third leading cause of death in the world. The absence of sensitive diagnostic tests for early disease stages of COPD results in under-diagnosis of this treatable disease in an estimated 60-85% of the patients. In recent years a grating-based approach to X-ray dark-field contrast imaging has shown to be very sensitive for the detection and quantification of pulmonary emphysema in small animal models. However, translation of this technique to imaging systems suitable for humans remains challenging and has not yet been reported. In this manuscript, we present the first X-ray dark-field images of in-situ human lungs in a deceased body, demonstrating the feasibility of X-ray dark-field chest radiography on a human scale. Results were correlated with findings of computed tomography imaging and autopsy. The performance of the experimental radiography setup allows acquisition of multi-contrast chest X-ray images within clinical boundary conditions, including radiation dose. Upcoming clinical studies will have to demonstrate that this technology has the potential to improve early diagnosis of COPD and pulmonary diseases in general

In-vivo X-ray Dark-Field Chest Radiography of a Pig

X-ray chest radiography is an inexpensive and broadly available tool for initial assessment of the lung in clinical routine, but typically lacks diagnostic sensitivity for detection of pulmonary diseases in their early stages. Recent X-ray dark-field (XDF) imaging studies on mice have shown significant improvements in imaging-based lung diagnostics. Especially in the case of early diagnosis of chronic obstructive pulmonary disease (COPD), XDF imaging clearly outperforms conventional radiography. However, a translation of this technique towards the investigation of larger mammals and finally humans has not yet been achieved. In this letter, we present the first in-vivo XDF full-field chest radiographs (32 x 35 cm(2)) of a living pig, acquired with clinically compatible parameters (40 s scan time, approx. 80 mu Sv dose). For imaging, we developed a novel high-energy XDF system that overcomes the limitations of currently established setups. Our XDF radiographs yield sufficiently high image quality to enable radiographic evaluation of the lungs. We consider this a milestone in the bench-to-bedside translation of XDF imaging and expect XDF imaging to become an invaluable tool in clinical practice, both as a general chest X-ray modality and as a dedicated tool for high-risk patients affected by smoking, industrial work and indoor cooking

Die Bedeutung von Dopamin und Glutamat für neuronale Belohnungsverarbeitung über die Lebensspanne

Rewards are considered as crucial factor for adaptive behavior of the human being. Further, behavioral and neuronal processing of rewards may be influenced by developmental changes. Interestingly, dopaminergic and glutamatergic factors in the striatum may also change during the lifespan, and are involved in learning processes. Therefore, we investigated adolescents, younger adults, and older adults by mean of a reward task during functional magnetic resonance imaging (fMRI). Core reward areas like the ventral striatum (VS) were characterized by a hyperactivation in adolescents compared with both adult groups. We interpreted these findings as the result of an asymmetric (protracted) development of the “frontal inhibition system” in comparison to the (faster) development of the VS in adolescents. Further, frontal areas showed hyperactivation in older adults compared with younger groups. These findings were interpreted as compensatory age-specific effects in fronto- parietal regions. In a second study, we additionally focused on the impact of frontal glutamate concentrations on reward processing in healthy adolescents and observed an inverse coupling of glutamate concentrations in the anterior cingulate cortex (ACC) and neuronal activation of the VS. This finding demonstrates the important role of glutamate in reward processing and as a potential vulnerability factor for mental disorders starting in adolescence. The striatum may also be involved in reward associated response inhibition modulated by dopamine. Therefore, in a trimodal imaging approach [using F18-DOPA positron emission tomography, magnetic resonance spectroscopy (MRS) and fMRI] we investigated a response inhibition task in healthy participants between 20 and 80 years of age. We observed a positive association between dopamine synthesis capacity and inhibition-related neural activity in the caudate nucleus. This relationship was further mediated by striatal glutamate. However, age did not affect response inhibition-related neurofunctional or neurochemical parameters. Taken together, in the present dissertation I demonstrate the importance of dopamineglutamate interactions with regard to reward processing in striatal areas in aging. Further, glutamatergic factor in fronto-limbic networks may also be related to increased risk and onset of psychiatric diseases (e.g. schizophrenia) during adolescence. Additionally, neuronal factors of response inhibition seem to be associated to striatal dopamine and glutamate, but those findings may not be associated to aging. Globally, the present results add to the understanding of reward processing and associated inhibition processing as well as associated neurochemical and neurofunctional properties in the eyes of lifelong changes. The present findings may further stimulate age related research on neurochemical and neurofunctional characteristics of mental disease like schizophrenia or addiction.Belohnungen sind ein wichtiger und basaler Faktor für Anpassungsverhalten bei Menschen. Weiterhin scheinen Verhalten und neuronale Verarbeitung von Belohnungen durch entwicklungsspezifische Aspekte beeinflusst zu sein. Die Neurotransmitter Dopamin und Glutamat sind eng mit Belohnungsverarbeitung assoziiert und durchlaufen altersabhängige Veränderungen. Aus diesem Grund wurden in den hier durchgeführten Studien gesunde Adoleszente, junge Erwachsene und ältere Erwachsene während der Durchführung einer Belohnungsaufgabe mittels funktioneller Kernspintomographie (fMRT) untersucht. Die Ergebnisse zeigten eine erhöhte Aktivierung der KernBelohnungszentren [z.B. das ventrale Striatum (VS)] bei Adoleszenten im Vergleich zu jungen und älteren Erwachsenen. Diese Ergebnisse wurden interpretiert als Resultat einer verzögerten Entwicklung des „frontalen Inhibitionssystems“ im Verhältnis zum (sich schneller entwickelnden) VS. Weiterhin beobachteten wir eine erhöhte Aktivierung in frontalen Gebieten bei älteren Erwachsenen im Vergleich zu den beiden jüngeren Gruppen. Diese Ergebnisse sprechen für einen kompensatorischen, altersspezifischen Effekt in frontal-parietalen Regionen. In einer zweiten Studie konzentrierten wir uns zusätzlich auf die Bedeutung von frontalem Glutamat-Konzentrationen für Belohnungsverarbeitung bei gesunden Adoleszenten und beobachteten einen negativen Zusammenhang zwischen Glutamat- Konzentrationen im anterioren Zingulum (ACC) und neuronaler Verarbeitung im VS bei Adoleszenten. Diese Ergebnisse zeigen welche wichtige Rolle Glutamat während neuronaler Belohnungsverarbeitung spielt. Außerdem könnten die Ergebnisse eine entwicklungsspezifische Vulnerabilität für geistige Krankheiten wiederspiegeln. Das Striatum scheint weiterhin mit der Inhibition von belohnungsabhängigem Verhalten („response inhibition“) verknüpft zu sein, welche von dem Neurotransmitter Dopamin moduliert wird. Aus diesem Grund wurde in einem trimodalen Bildgebungsprojekt [F18-DOPA Positronen- EmissionsTomographie, Magnetresonanzspektroskopie (MRS) und fMRT] eine „response inhibition“ Aufgabe von Personen zwischen 20 und 80 Jahren durchgeführt. Wir beobachteten einen positiven Zusammenhang zwischen Dopamin- Synthese-Kapazität und neuronaler Aktivität im Nucleus caudatus während Inhibitionsprozesse aktiv waren. Dieser Zusammenhang war auch assoziiert mit striataler Glutamat-Konzentration. Altersfaktoren schienen diese Prozesse jedoch nicht zu beeinflussen. In der gegenwärtigen Dissertation untersuche und beschreibe ich die Relevanz von DopaminGlutamat Interaktionen in Verbindung mit Belohnungsverarbeitung in striatalen Gebieten in Abhängigkeit des Alters der Probanden. Die Ergebnisse liefern Hinweise dass Dopamin-Glutamat Interaktionen mit der erhöhten Vulnerabilität für geistige Krankheiten (z.B. Schizophrenie) während der Adoleszenz in Verbindung stehen könnten. Zusätzlich scheint die neuronale Verarbeitung von Inhibition mit Dopamin und Glutamat in Verbindung zu stehen, diese Zusammenhänge scheinen jedoch unabhängig von Altersprozessen zu sein. Die hier gezeigten Ergebnisse erweitern das Verständnis von Belohnungsverarbeitung und Inhibitionsprozessen, sowie die damit assoziierten neurofunktionale und neurochemischen Veränderungen, insbesondere im Rahmen von Veränderungen über die Lebensspanne. Weiterhin könnten die hier gezeigten Ergebnisse die Erforschung von neurochemischen und neurofunktionalen Aspekten von geistigen Krankheiten (z.B. Schizophrenie oder Sucht) im Rahmen von Altersprozessen weiter stimulieren

Osseous microarchitecture in frequent fracture zones of the distal clavicle.

BACKGROUND Fracture classifications of the distal clavicle are based on ligamentous integrity. The influence of osseous microarchitecture on fracture occurrence, morphology, and the lesion's stability has not yet been investigated. We aimed to characterize osseous microarchitecture according to common fracture classification systems based on ligamentous integrity and investigated the possible effects of age, gender, and osteoporosis in distal clavicle fractures. METHODS N = 20 human cadaveric distal clavicles were scanned using XtremeCT with an isometric voxel size of 82 μm. In the sagittal plane, each data set was evaluated in 11 sections of approximately 7 mm thickness. Three topographic regions were defined: the bone lateral to the trapezoid (LTR), intertubercular (ITR), and medial to the conoid (MCR) ligament. Cortical bone mineral density (BMD) [mgHA/cm3] and cortical porosity (1- (BV/TV) [%]) were determined and evaluated relative to age and gender. RESULTS Along the mediolateral axis, there was an >20-fold increase in median cortical porosity (P ≤ .001). There were significant differences in cortical porosity between LTR and ITR (P ≤ .001) but not between ITR and MCR (P = .09). In ITR, cortical porosity was significantly greater in >60-year-old compared to younger donors (P = .01). For BMD, there was an >2-fold decrease toward the distal apex (P ≤ .001). BMD was significantly greater in ITR compared to LTR (P ≤ .001) and in MCR compared to ITR (P = .02). In ITR and MCR, clavicles of >60-year-old donors had significantly lower BMD values compared to younger donors (P 60-year-olds (P > .6). CONCLUSION The distal clavicle features a characteristic bony microarchitecture. The present study revealed a significant difference in bone quality of lateral, intertubercular, and medial zones of the distal clavicle and could specify target areas and strategies for surgical treatment of unstable fractures. Age, gender, and osteoporosis have a limited effect on bone quality and fracture genesis. In contrast, ligamentous quality is supposed to exert a substantial influence on fracture characteristics, especially in ITR. Fracture morphology of the distal clavicle is determined by a bony-ligamentous conjunction, which remains to be characterized

The Accuracy of Distal Clavicle Fracture Classifications—Do We Need an Amendment to Imaging Modalities or Fracture Typing?

Background: Despite its fair-to-moderate reliability, the “modified Neer classification” is widely accepted and used. The purpose of this study was to reevaluate its applicability. Methods: Of n = 59 patients with distal clavicle fractures, fractures were classified on standard radiographs. Afterwards, an MRI examination was performed, and fractures reclassified. The primary outcome parameter was quantifying the rate of misclassification. The secondary outcome parameters were the evaluation of the ligamentous injury constellations. Results: In all cases, the fracture course and ligamental integrity could be assigned to the fracture type. Correction of the classification was necessary in n = 5 (8.5%) cases. In n = 3 (5%) cases, a correction was necessary from Neer I to Craig IIc and thus from conservative to operative treatment. Mean coracoclavicular distance (CCD) in Neer I was 10.2 ± 2.1 mm versus 14.2 ± 3.9 mm in Craig IIc (p = 0.02). The mean fracture angle in Neer I was 25.1 ± 3.3° versus 36.8 ± 4.4° in Craig IIc (p = 0.02). Conclusion: Cross-sectional imaging resulted in higher precision. Nevertheless, recommendations remain for standard radiographs. The CCD and fracture angle should be considered. An angle of >30° can be assumed as a parameter of instability. A previously undescribed fracture type does not seem to exist. The modified Neer classification is an appropriate and complete fracture classification