[Balancing Family and Career in Medicine: Greatly Desired but Given Little Consideration Results of the Study Arm VI of the KARiMED Study]. / Vereinbarkeit von Familie und Beruf in der Medizin: vom großen Wunsch und wenig Berücksichtigung.

AIM OF THE STUDY: Family life and professional practice are both highly important for young physicians. Accordingly, a good balancing of both areas of life is necessary. Despite political framework conditions and legal requirements that have been in place for years, implementation of measures to achieve this seems to be difficult, especially in medicine, and is associated with great reservations and problems on the part of those involved. METHODS: By means of an online survey, the medical mid-level staff from university and peripheral hospitals was questioned on topics related to family, children and professional biographical as well as career-relevant topics and subsequently analyzed on a gender-specific basis. RESULTS: Of the study participants, 65.1% were married and already had children or expressed a desire to have children (86.0%). Most were employed full-time (80.8%). The majority of part-time employees were female (87.4%). For 34.6%, there was a career break of 18.5±21.3 months, 87.8% of which were taken due to pregnancy or children. Female physicians generally took significantly more parental leave than male physicians (6-12 months: females 62.2%; males 22.4%; 12 months or more: females 25.2%; males 6.6%). Family planning received little support from superiors (21.2% much to very much support) and 45.6% reported having experienced problems with their return to work or career advancement. Almost 60% of the participants did not have any specific working time models in their own hospital for employees with children who need to be cared for. CONCLUSION: In order to implement a work-life balance for physicians, changes are first and foremost necessary on the part of the institutions. In addition, the respective superiors must rethink in order to enable a parallelization of these two areas of their employees' lives. However, young physicians must also rethink their view of this issue. Demanding changes in labor law while continuing traditional family constellations at home does not seem to do address this issue adequately.

Lower hypothalamus subunit volumes link with impaired long-term body weight gain after preterm birth.

Introduction: Preterm birth is associated with an increased risk for impaired body weight gain. While it is known that in prematurity several somatic and environmental factors (e.g., endocrine factors, nutrition) modulate short- and long-term body weight gain, the contribution of potentially impaired body weight control in the brain remains elusive. We hypothesized that the structure of hypothalamic nuclei involved in body weight control is altered after preterm birth, with these alterations being associated with aberrant body weight development into adulthood. Materials and methods: We assessed 101 very preterm (i.e., <32 weeks of gestational age) and/or very low birth weight (i.e., <1500g; VP/VLBW) and 110 full-term born (FT) adults of the population-based Bavarian Longitudinal Study with T1-weighted MRI, deep learning-based hypothalamus subunit segmentation, and multiple body weight assessments from birth into adulthood. Results: Volumes of the whole hypothalamus and hypothalamus subunits relevant for body weight control were reduced in VP/VLBW adults and associated with birth variables (i.e., gestational age and intensity of neonatal treatment), body weight (i.e., weight at birth and adulthood), and body weight trajectories (i.e., trajectory slopes and cluster/types such as long-term catch-up growth). Particularly, VP/VLBW subgroups, whose individuals showed catch-up growth and/or were small for gestational age, were mostly associated with volumes of distinct hypothalamus subunits such as lateral or infundibular/ventromedial hypothalamus. Conclusion: Results demonstrate lower volumes of body weight control-related hypothalamus subunits after preterm birth that link with long-term body weight gain. Data suggest postnatal development of body weight -related hypothalamic nuclei in VP/VLBW individuals that corresponds with distinct body weight trajectories into adulthood.

Aberrant cortico-thalamic structural connectivity in premature-born adults.

Premature birth is associated with alterations in brain structure, particularly in white matter. Among white matter, alterations in cortico-thalamic connections are present in premature-born infants, and they have been suggested both to last until adulthood and to contribute to impaired cognitive functions. To test these hypotheses, 70 very premature-born adults and 67 full-term controls underwent cognitive testing and diffusion-weighted imaging. Each cortical hemisphere was parcellated into six lobes, from which probabilistic tractography was performed to the thalamus. Connection probability was chosen as metric of structural connectivity. We found increased cortico-thalamic connection probability between left prefrontal cortices and left medio-dorsal thalamus and reduced connection probability between bilateral temporal cortices and bilateral anterior thalami in very premature-born adults. Aberrant prefronto- and temporo-thalamic connection probabilities were correlated with birth weight and days on ventilation, respectively, supporting the suggestion that these connectivity changes relate with the degree of prematurity. Moreover, an increase in left prefronto-thalamic connection probability also correlated with lower verbal comprehension index indicating its relevance for verbal cognition. Together, our results demonstrate that cortico-thalamic structural connectivity is aberrant in premature-born adults, with these changes being linked with impairments in verbal cognitive abilities. Due to corresponding findings in infants, data suggest aberrant development of cortico-thalamic connectivity after premature birth with lasting effects into adulthood.

Aberrant striatal dopamine links topographically with cortico-thalamic dysconnectivity in schizophrenia.

Aberrant dopamine function in the dorsal striatum and aberrant intrinsic functional connectivity (iFC) between distinct cortical networks and thalamic nuclei are among the most consistent large-scale brain imaging findings in schizophrenia. A pathophysiological link between these two alterations is suggested by theoretical models based on striatal dopamine's topographic modulation of cortico-thalamic connectivity within cortico-basal-ganglia-thalamic circuits. We hypothesized that aberrant striatal dopamine links topographically with aberrant cortico-thalamic iFC, i.e. aberrant associative striatum dopamine is associated with aberrant iFC between the salience network and thalamus, and aberrant sensorimotor striatum dopamine with aberrant iFC between the auditory-sensorimotor network and thalamus. Nineteen patients with schizophrenia during remission of psychotic symptoms and 19 age- and sex-comparable control subjects underwent simultaneous fluorodihydroxyphenyl-l-alanine PET (18F-DOPA-PET) and resting state functional MRI (rs-fMRI). The influx constant kicer based on 18F-DOPA-PET was used to measure striatal dopamine synthesis capacity; correlation coefficients between rs-fMRI time series of cortical networks and thalamic regions of interest were used to measure iFC. In the salience network-centred system, patients had reduced associative striatum dopamine synthesis capacity, which correlated positively with decreased salience network-mediodorsal-thalamus iFC. This correlation was present in both patients and healthy controls. In the auditory-sensorimotor network-centred system, patients had reduced sensorimotor striatum dopamine synthesis capacity, which correlated positively with increased auditory-sensorimotor network-ventrolateral-thalamus iFC. This correlation was present in patients only. Results demonstrate that reduced striatal dopamine synthesis capacity links topographically with cortico-thalamic intrinsic dysconnectivity in schizophrenia. Data suggest that aberrant striatal dopamine and cortico-thalamic dysconnectivity are pathophysiologically related within dopamine-modulated cortico-basal ganglia-thalamic circuits in schizophrenia.

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

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.

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

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.

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

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.

Cortico-thalamic hypo- and hyperconnectivity extend consistently to basal ganglia in schizophrenia.

Schizophrenia is characterized by hypoconnectivity or decreased intrinsic functional connectivity (iFC) between prefrontal-limbic cortices and thalamic nuclei, as well as hyperconnectivity or increased iFC between primary-sensorimotor cortices and thalamic nuclei. However, cortico-thalamic iFC overlaps with larger, structurally defined cortico-striato-pallido-thalamo-cortical (CSPTC) circuits. If such an overlap is relevant for intrinsic hypo-/hyperconnectivity, it suggests (i) that patterns of cortico-subcortical hypo-/hyperconnectivity extend consistently from thalamus to basal ganglia nuclei; and (ii) such consistent hypo-/hyperconnectivity might link distinctively but consonant with different symptom dimensions, namely cognitive and psychotic impairments. To test this hypothesis, 57 patients with schizophrenia and 61 healthy controls were assessed by resting-state functional magnetic resonance imaging (fMRI) and clinical-behavioral testing. IFC from intrinsic cortical networks into thalamus, striatum, and pallidum was estimated by partial correlations between fMRI time courses. In patients, the salience network covering prefrontal-limbic cortices was hypoconnected with the mediodorsal thalamus and ventral parts of striatum and pallidum; these iFC-hypoconnectivity patterns were correlated both among each other and specifically with patients' impaired cognition. In contrast, the auditory-sensorimotor network covering primary-sensorimotor cortices was hyperconnected with the anterior ventral nucleus of the thalamus and dorsal parts of striatum and pallidum; these iFC-hyperconnectivity patterns were likewise correlated among each other and specifically with patients' psychotic symptoms. The results demonstrate that prefrontal-limbic hypoconnectivity and primary-sensorimotor hyperconnectivity extend consistently across subcortical nuclei and specifically across distinct symptom dimensions. Data support the model of consistent cortico-subcortical hypo-/hyperconnectivity within CSPTC circuits in schizophrenia.

Frontoparietal areas link impairments of large-scale intrinsic brain networks with aberrant fronto-striatal interactions in OCD: a meta-analysis of resting-state functional connectivity.

Neuroimaging studies report evidence for two distinct pathophysiological models of obsessive-compulsive disorder (OCD): disrupted fronto-striatal circuits and impaired large-scale fronto-parietal-limbic intrinsic brain networks, defined by functionally connected (FC) infra-slow oscillations in ongoing brain activity. To synthesize this literature and overcome inconsistencies, we conducted a coordinate-based meta-analysis of 18 whole-brain resting-state functional magnetic resonance imaging (fMRI) studies (541 patients, 572 healthy controls) comparing seed-based FC between OCD patients and healthy controls. In patients, the meta-analysis revealed (1) consistent hypoconnectivity within frontoparietal and salience network, and between salience, frontoparietal and default-mode network, and (2) consistent general dysconnectivity (no specific direction of connectivity change) within default-mode and frontoparietal network, as well as between frontoparietal, default-mode, and salience networks. Between-network hypoconnectivity provides evidence for the triple-network model in OCD, while aberrant within-network connectivity of frontoparietal and striatal regions supports reports of aberrant fronto-striatal circuitry. Therefore, results corroborate both models of OCD pathophysiology and link them by underlining the importance of intrinsic connectivity of frontoparietal regions which are common to both models.

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.

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.

Mindfulness-Based Stress Reduction, Fear Conditioning, and The Uncinate Fasciculus: A Pilot Study.

Mindfulness has been suggested to impact emotional learning, but research on these processes is scarce. The classical fear conditioning/extinction/extinction retention paradigm is a well-known method for assessing emotional learning. The present study tested the impact of mindfulness training on fear conditioning and extinction memory and further investigated whether changes in white matter fiber tracts might support such changes. The uncinate fasciculus (UNC) was of particular interest in the context of emotional learning. In this pilot study, 46 healthy participants were quasi-randomized to a Mindfulness-Based Stress Reduction (MBSR, N = 23) or waitlist control (N = 23) group and underwent a two-day fear conditioning, extinction learning, and extinction memory protocol before and after the course or control period. Skin conductance response (SCR) data served to measure the physiological response during conditioning and extinction memory phases. Diffusion tensor imaging (DTI) data were analyzed with probabilistic tractography and analyzed for changes of fractional anisotropy in the UNC. During conditioning, participants were able to maintain a differential response to conditioned vs. not conditioned stimuli following the MBSR course (i.e., higher sensitivity to the conditioned stimuli), while controls dropped the response. Extinction memory results were not interpretable due to baseline differences. MBSR participants showed a significant increase in fractional anisotropy in the UNC, while controls did not (group by time interaction missed significance). Pre-post changes in UNC were correlated with changes in the response to the conditioned stimuli. The findings suggest effects of mindfulness practice on the maintenance of sensitivity of emotional responses and suggest underlying neural plasticity. (ClinicalTrials.gov, Identifier NCT01320969, https://clinicaltrials.gov/ct2/show/NCT01320969).

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

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.

Mindfulness is associated with intrinsic functional connectivity between default mode and salience networks.

Mindfulness is attention to present moment experience without judgment. Mindfulness practice is associated with brain activity in areas overlapping with the default mode, salience, and central executive networks (DMN, SN, CEN). We hypothesized that intrinsic functional connectivity (iFC; i.e., synchronized ongoing activity) across these networks is associated with mindfulness scores. After 2 weeks of daily 20 min attention to breath training, healthy participants were assessed by mindfulness questionnaires and resting-state functional MRI. Independent component analysis (ICA) of imaging data revealed networks of interest, whose activity time series defined inter-network intrinsic functional connectivity (inter-iFC) by temporal correlation. Inter-iFC between subnetworks of the DMN and SN-and inter-iFC between subnetworks of the SN and left CEN at trend-was correlated with mindfulness scores. Additional control analyses about visual networks' inter-iFC support the specificity of our findings. Results provide evidence that mindfulness is associated with iFC between DMN and SN. Data suggest that ongoing interactions among central intrinsic brain networks link with the ability to attend to current experience without judgment.

Cerebrospinal fluid BACE1 activity and brain amyloid load in Alzheimer's disease.

The secretase BACE1 is fundamentally involved in the development of cerebral amyloid pathology in Alzheimer's disease (AD). It has not been studied so far to what extent BACE1 activity in cerebrospinal fluid (CSF) mirrors in vivo amyloid load in AD. We explored associations between CSF BACE1 activity and fibrillar amyloid pathology as measured by carbon-11-labelled Pittsburgh Compound B positron emission tomography ([¹¹C]PIB PET). [¹¹C]PIB and CSF studies were performed in 31 patients with AD. Voxel-based linear regression analysis revealed significant associations between CSF BACE1 activity and [¹¹C]PIB tracer uptake in the bilateral parahippocampal region, the thalamus, and the pons. Our study provides evidence for a brain region-specific correlation between CSF BACE1 activity and in-vivo fibrillar amyloid pathology in AD. Associations were found in areas close to the brain ventricles, which may have important implications for the use of BACE1 in CSF as a marker for AD pathology and for antiamyloid treatment monitoring.