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Background & Aims: Elevated liver stiffness has been associated with atrial fibrillation (AFib) in the general population. The mechanism underlying this association is unclear. Methods: Participants were recruited from the general population and prospectively enrolled with follow-up for 5 years. The fibrosis-4 (FIB-4) index was used as a surrogate marker for liver fibrosis. Proteomics analysis was performed using the 92-target Olink inflammation panel. Validation was performed using the NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet index (APRI), and repeat confirmation proteomics. Results: A sample of 11,509 participants with a mean age of 54.0 ± 11.1 years, 51.3% women, and a median FIB-4 index of 0.85 (0.65/1.12), was used. The FIB-4 index was predictive for prevalent (FIB-4 index adjusted odds ratio (aOR) per SD: 1.100 with 95% CI 1.011-1.196; p = 0.026), but not incident AFib (log[FIB-4 index]) adjusted hazard ratio: 1.125 with 95% CI 0.943-1.342, p = 0.19). Elastic net regularized regression identified CCL20, DNER, and CXCL10 for prevalent AFib, and AXIN1, CXCL10, and Flt3L for the log(FIB-4 index) (per SD) as most important in common regulated proteins. The relationship between the FIB-4 index, the identified proteins, and AFib was relevant and reproduced at the 5-year follow-up for CXCL10 after adjusting for confounders (log[FIB-4 index] per SD - CXCL10 [per SD] adjusted β 0.160 with 95% CI 0.127-0.194, p

Acute strokes can affect heart rate variability (HRV), the mechanisms how are not well understood. We included 42 acute stroke patients (2–7 days after ischemic stroke, mean age 66 years, 16 women). For analysis of HRV, 20 matched controls (mean age 60.7, 10 women) were recruited. HRV was assessed at rest, in a supine position and individual breathing rhythmus for 5 min. The coefficient of variation (VC), the root mean square of successive differences (RMSSD), the powers of low (LF, 0.04–0.14 Hz) and high (HF, 0.15–0.50 Hz) frequency bands were extracted. HRV parameters were z-transformed related to age- and sex-matched normal subjects. Z-values -1). No different connectivity could be found for the respective VC groups. Our results suggest that HRV alteration after acute stroke might be due to affecting resting-state brain networks.

Summary: Background: People with complex symptomatology but unclear diagnosis presenting to a centre for rare diseases (CRD) may present with mental (co-)morbidity. We hypothesised that combining an expert in somatic medicine with a mental health specialist working in tandem will improve the diagnostic outcome. Methods: Patients aged 12 years and older who presented to one of the 11 participating German CRDs with an unknown diagnosis were recruited into this prospective cohort trial with a two-phase cohort design. From October 1, 2018 to September 30, 2019, participants were allocated to standard care (SC, N = 684), and from October 1, 2019 to January 31, 2021 to innovative care (IC, N = 695). The cohorts consisted mainly of adult participants with only a minority of children included (N = 67). IC included the involvement of a mental health specialist in all aspects of care (e.g., assessing medical records, clinic visits, telehealth care, and case conferences). Clinicaltrials.gov identifier: NCT03563677. Findings: The proportion of patients with diagnoses established within 12 months after the first visit to the CRD explaining the entire symptomatology (primary outcome) was 19% (N = 131 of 672) in the SC and 42% (N = 286 of 686) in the IC cohort (OR adjusted for centre effects 3.45 [95% CrI: 1.99–5.65]). The difference was mainly due to a higher prevalence of mental disorders and non-rare somatic diseases in the IC cohort. The median time to explaining diagnoses was one month shorter with IC (95% CrI: 1–2), and significantly more patients could be referred to local regular care in the IC (27.5%; N = 181 of 659) compared to the SC (12.3%; N = 81 of 658) cohort (OR adjusted for centre effects 2.70 [95% CrI: 2.02–3.60]). At 12-month follow-up, patient satisfaction with care was significantly higher in the IC compared to the SC cohort, while quality of life was not different between cohorts. Interpretation: Our findings suggested that including a mental health specialist in the entire evaluation process of CRDs for undiagnosed adolescents and adults should become an integral part of the assessment of individuals with a suspected rare disease. Funding: The study was funded by the Global Innovation Fund from the Joint Federal Committee in Germany (Innovationsfonds des Gemeinsamen Bundesausschusses), grant number 01NVF17031.

The structural and functional degradation of the corpus callosum (CC) has been shown to play an important role in the context of cognitive aging (Reuter-Lorenz and Stanczak, 2000). This is also reflected by findings of elongated interhemispheric transfer time (IHTT) in older adults (Riedel et al., 2022). At the same time, a protective effect of physical activity (PA) and cardiorespiratory fitness (CRF) on brain health including the CC is widely accepted (Hillman et al., 2008; Loprinzi et al., 2020). Based on this idea, the present study investigated the relationship between IHTT and PA/CRF in 107 healthy older adults (m: 64, f: 43) aged 67.69 ± 5.18. IHTT was calculated detecting event-related potentials (ERPs) using an established Dimond-Task. PA was evaluated using accelerometry resulting in estimates of overall bodily motion and time spent at higher intensity PA. CRF was estimated using graded exercise testing, approximating running speed at 4 mmol/l blood lactate concentration. The results showed a negative correlation between IHTTright→left and PA overall as well as in the male subgroup and between IHTTleft→right and CRF in women. This indicates a potential relationship between IHTT and PA/CRF. While the present investigation is only the first to hint at such a relationship taking into account the differential effects with regards to sex, mode of PA/CRF and IHTT direction, it is in line with previous findings and theoretical suggestions linking brain health to PA/CRF in the context of aging. Further research is needed in order to increase our understanding of the underlying mechanisms and of the influence of sex, PA intensity, degree of CRF and significance of IHTT direction.

Several practices contribute to low replication rates in neuroimaging; unreported analytical flexibility, publication biases, the lack of data sharing, the use of underpowered samples, and many more. In the current study, we tried to replicate emotional interference during motor response inhibition in a sample of N = 57 healthy students at a different study site. The failure to inhibit impulses in highly emotional situations is a characteristic of many mental disorders. Apart from this, exaggerated emotional responses can debilitate social and cognitive functioning in healthy participants. Functional magnetic resonance imaging was acquired while participants performed a combined stop signal and Simon task with neutral and negative, visual primes. Negative, visual primes led to prolonged reaction times and stopping latencies. FMRI data showed that negative, visual primes led to increased activation in the bilateral amygdala and enhanced visual processing. Consistent with other studies on emotional interference, we observed decreased activation in regions of the central-executive network and reduced deactivation in the ventromedial prefrontal cortex for negative trials. Replicating the results of our former studies (Kampa et al., 2018, 2020), we found an interaction effect in the right amygdala. Concurrent inhibition of motor responses thus seemed to downregulate the processing of negative stimuli in the right amygdala. We performed exploratory brain-behavior correlation analyses to test if increased right amygdala activation to negative primes was associated with a decrement in performance. We found no such relationship; however, because of the low statistical power, we cannot decide conclusively on the relationship between the right amygdala, and behavioral interference. We discuss potential solutions for overcoming the power problem associated with brain-behavior correlation analyses.

Age-related cognitive decline has been attributed to degeneration of the corpus callosum (CC), which allows for interhemispheric integration and information processing [22,69]. Along with decreased structural integrity, altered functional properties of the CC may cause impaired cognitive performance in older adults, yet this aspect of age-related decline remains insufficiently researched [59]. In this context, potential sex-related differences have been proposed [31,58]. A promising parameter, which has been suggested to estimate functional properties of the CC is the interhemispheric transfer time (IHTT), which is ideally obtained from event-related potentials (ERP) evoked by lateralized stimuli [45]. To examine the possible functional consequences of aging with regards to the CC, the present study investigated the IHTT of 107 older (67.69 ± 5.18y) as well as of 23 younger participants (25.09 ± 2.59y). IHTT was obtained using an established letter matching task and targeting early N170 ERP components at posterior electrode sites. The results revealed significantly elongated IHTT in older compared to younger participants, but no significant sex differences. Furthermore, there was a significant positive correlation between IHTT and age, predominantly driven by the female participants. The present findings add support to the notion, that IHTT is subject to age-related elongation reflecting impaired interhemispheric transmission. Age-related decline in women appears to occur at a different age range compared to men.

Motivated by the recent replicability crisis we tested replicability of functional magnetic resonance imaging (fMRI) group activations in two independent samples. An identical behavioral and fMRI test battery for the longitudinal investigation of stress resilience mechanisms was developed for the Mainz Resilience Project (MARP) and conducted in a discovery (N = 54) and a replication sample (N = 103). The test battery consisted of a stress reactivity task, a reward sensitivity task, a fear conditioning and extinction paradigm, two volitional reappraisal tasks and an emotional interference inhibition task. Replicability of group activations was tested with the Jaccard index and the Intra Class Correlation (ICC). Overall, we observed good to excellent replicability of activations at the whole brain level. Only a minority of contrasts showed unsatisfactory replicability. Replicability at the level of individual regions of interest (ROIs) was generally lower. Tasks with stronger activation in the discovery sample showed better replicability.

Initial historical accounts as well as recent data suggest that emotion processing is dysfunctional in conversion disorder patients and that this alteration may be the pathomechanistic neurocognitive basis for symptoms in conversion disorder. However, to date evidence of direct interaction of altered negative emotion processing with motor control networks in conversion disorder is still lacking. To specifically study the neural correlates of emotion processing interacting with motor networks we used a task combining emotional and sensorimotor stimuli both separately as well as simultaneously during functional magnetic resonance imaging in a well characterized group of 13 conversion disorder patients with functional hemiparesis and 19 demographically matched healthy controls. We performed voxelwise statistical parametrical mapping for a priori regions of interest within emotion processing and motor control networks. Psychophysiological interaction (PPI) was used to test altered functional connectivity of emotion and motor control networks. Only during simultaneous emotional stimulation and passive movement of the affected hand patients displayed left amygdala hyperactivity. PPI revealed increased functional connectivity in patients between the left amygdala and the (pre-)supplemental motor area and the subthalamic nucleus, key regions within the motor control network. These findings suggest a novel mechanistic direct link between dysregulated emotion processing and motor control circuitry in conversion disorder. Keywords: Amygdala, Emotion processing, fMRI, Motor network, Psychogenic paresis, Conversion disorder