Exposure to gestational diabetes mellitus in utero impacts hippocampal functional connectivity in response to food cues in children.

Objectives: Intrauterine exposure to gestational diabetes mellitus (GDM) increases the risk of obesity in the offspring, but little is known about the underlying neural mechanisms. The hippocampus is crucial for food intake regulation and is vulnerable to the effects of obesity. The purpose of the study was to investigate whether GDM exposure affects hippocampal functional connectivity during exposure to food cues using functional magnetic resonance imaging. Methods: Participants were 90 children age 7-11 years (53 females) who underwent an fMRI-based visual food cue task in the fasted state. Hippocampal functional connectivity (FC) was examined using generalized psychophysiological interaction in response to high-calorie food versus non-food cues. Food-cue induced hippocampal FC was compared between children with and without GDM exposure, while controlling for possible confounding effects of age, sex and waist-to-hip ratio. Results: Children with GDM exposure exhibited stronger hippocampal FC to the insula and striatum (i.e., putamen, pallidum and nucleus accumbens) compared to unexposed children, while viewing high caloric food cues. Conclusions: Intrauterine exposure to GDM was associated with higher food-cue induced hippocampal FC to reward processing regions. Future studies with longitudinal measurements are needed to clarify whether increased hippocampal FC to reward processing regions may raise the risk of the development of metabolic diseases later in life.

Influence of insulin sensitivity on food cue evoked functional brain connectivity in children.

Objective: Insulin resistance during childhood is a risk factor for developing type 2 diabetes and other health problems later in life. Studies in adults have shown that insulin resistance affects regional and network activity in the brain which are vital for behavior, e.g. ingestion and metabolic control. To date, no study has investigated whether brain responses to food cues in children are associated with peripheral insulin sensitivity. Methods: We included 53 children (36 girls) between the age of 7-11 years, who underwent an oral Glucose Tolerance Test (oGTT) to estimate peripheral insulin sensitivity (ISI). Brain responses were measured using functional magnetic resonance imaging (fMRI) before and after glucose ingestion. We compared food-cue task-based activity and functional connectivity (FC) between children with low and high ISI, adjusted for age and BMIz. Results: Independent of prandial state (i.e., glucose ingestion), children with lower ISI showed higher FC between the anterior insula and caudate and lower FC between the posterior insula and mid temporal cortex than children with higher ISI. Sex differences were found based on prandial state and peripheral insulin sensitivity in the insular FC. No differences were found on whole-brain food-cue reactivity. Conclusions: Children with low peripheral insulin sensitivity showed differences in food cue evoked response particularly in insula functional connectivity. These differences might influence eating behavior and future risk of developing diabetes.

Impact of maternal emotional state during pregnancy on fetal heart rate variability.

Background: The fetal autonomic nervous system (ANS) is believed to be negatively affected by maternal adverse emotional states. In this study, we evaluated how depression, anxiety and stress during pregnancy are related to fetal heart rate variability (HRV) as recorded with magnetocardiography (MCG). We also considered metabolic factors such as maternal adiposity and circulating levels of cortisol during gestation. Furthermore, we followed up these fetuses after birth, recording HRV and saliva levels of cortisol in these infants to establish any effects postpartum. Methods: We calculated HRV in spontaneous MCG recordings from 32 healthy fetuses between 32 and 38 weeks of gestational age. Maternal emotional state was assessed using standardized questionnaires about anxiety, depression and stress. An overall indicator of maternal well-being was calculated by z-scoring each individual questionnaire and summation. We used a median split to divide the group into high and low z-scores (HZS and LZS), respectively. Standard HRV measures were determined in the time and frequency domain. T-test analyses were performed between LZS and HZS, with the HRV and the metabolic measures as the dependent variables. Results: We found an impaired HRV in the HZS group both during pregnancy and after birth. No differences were observed between LZS and HZS for metabolic factors. Depression and anxiety symptoms seem to affect HRV differently. No relationship was found between maternal and infant cortisol levels. Conclusions: On the basis of our results on different HRV parameters, we propose that maternal emotional state might affect the development of the fetal nervous system in utero.

Evaluation of parameters for fetal behavioural state classification.

Fetal behavioural states (fBS) describe periods of fetal wakefulness and sleep and are commonly defined by features such as body and eye movements and heart rate. Automatic state detection through algorithms relies on different parameters and thresholds derived from both the heart rate variability (HRV) and the actogram, which are highly dependent on the specific datasets and are prone to artefacts. Furthermore, the development of the fetal states is dynamic over the gestational period and the evaluation usually only separated into early and late gestation (before and after 32 weeks). In the current work, fBS detection was consistent between the classification algorithm and visual inspection in 87 fetal magnetocardiographic data segments between 27 and 39 weeks of gestational age. To identify how automated fBS detection could be improved, we first identified commonly used parameters for fBS classification in both the HRV and the actogram, and investigated their distribution across the different fBS. Then, we calculated a receiver operating characteristics (ROC) curve to determine the performance of each parameter in the fBS classification. Finally, we investigated the development of parameters over gestation through linear regression. As a result, the parameters derived from the HRV have a higher classification accuracy compared to those derived from the body movement as defined by the actogram. However, the overlapping distributions of several parameters across states limit a clear separation of states based on these parameters. The changes over gestation of the HRV parameters reflect the maturation of the fetal autonomic nervous system. Given the higher classification accuracy of the HRV in comparison to the actogram, we suggest to focus further research on the HRV. Furthermore, we propose to develop probabilistic fBS classification approaches to improve classification in less prototypical datasets.

Optically pumped magnetometers detect altered maximal muscle activity in neuromuscular disease.

Optically pumped magnetometers (OPM) are quantum sensors that enable the contactless, non-invasive measurement of biomagnetic muscle signals, i.e., magnetomyography (MMG). Due to the contactless recording, OPM-MMG might be preferable to standard electromyography (EMG) for patients with neuromuscular diseases, particularly when repetitive recordings for diagnostic and therapeutic monitoring are mandatory. OPM-MMG studies have focused on recording physiological muscle activity in healthy individuals, whereas research on neuromuscular patients with pathological altered muscle activity is non-existent. Here, we report a proof-of-principle study on the application of OPM-MMG in patients with neuromuscular diseases. Specifically, we compare the muscular activity during maximal isometric contraction of the left rectus femoris muscle in three neuromuscular patients with severe (Transthyretin Amyloidosis in combination with Pompe's disease), mild (Charcot-Marie-Tooth disease, type 2), and without neurogenic, but myogenic, damage (Myotonia Congenita). Seven healthy young participants served as the control group. As expected, and confirmed by using simultaneous surface electromyography (sEMG), a time-series analysis revealed a dispersed interference pattern during maximal contraction with high amplitudes. Furthermore, both patients with neurogenic damage (ATTR and CMT2) showed a reduced variability of the MMG signal, quantified as the signal standard deviation of the main component of the frequency spectrum, highlighting the reduced possibility of motor unit recruitment due to the loss of motor neurons. Our results show that recording pathologically altered voluntary muscle activity with OPM-MMG is possible, paving the way for the potential use of OPM-MMG in larger studies to explore the potential benefits in clinical neurophysiology.

Magnetoencephalographic signatures of conscious processing before birth.

The concept of fetal consciousness is a widely discussed topic. In this study, we applied a hierarchical rule learning paradigm to investigate the possibility of fetal conscious processing during the last trimester of pregnancy. We used fetal magnetoencephalography, to assess fetal brain activity in 56 healthy fetuses between gestational week 25 and 40, during an auditory oddball paradigm containing first- and second-order regularities. The comparison of fetal brain responses towards standard and deviant tones revealed that the investigated fetuses show signs of hierarchical rule learning, and thus the formation of a memory trace for the second-order regularity. This ability develops over the course of the last trimester of gestation, in accordance with processes in physiological brain development and was only reliably present in fetuses older than week 35 of gestation. Analysis of fetal autonomic nervous system activity replicates findings in newborns, showing importance of activity state for cognitive processes. On the whole, our results support the assumption that fetuses in the last weeks of gestation are capable of consciously processing stimuli that reach them from outside the womb.

Muscle Fatigue Revisited - Insights From Optically Pumped Magnetometers.

So far, surface electromyography (sEMG) has been the method of choice to detect and evaluate muscle fatigue. However, recent advancements in non-cryogenic quantum sensors, such as optically pumped magnetometers (OPMs), enable interesting possibilities to flexibly record biomagnetic signals. Yet, a magnetomyographic investigation of muscular fatigue is still missing. Here, we simultaneously used sEMG (4 surface electrode) and OPM-based magnetomyography (OPM-MMG, 4 sensors) to detect muscle fatigue during a 3 × 1-min isometric contractions of the left rectus femoris muscle in 7 healthy participants. Both signals exhibited the characteristic spectral compression distinctive for muscle fatigue. OPM-MMG and sEMG slope values, used to quantify the spectral compression of the signals, were positively correlated, displaying similarity between the techniques. Additionally, the analysis of the different components of the magnetic field vector enabled speculations regarding the propagation of the muscle action potentials (MAPs). Altogether these results show the feasibility of the magnetomyographic approach with OPMs and propose a potential alternative to sEMG for the study of muscle fatigue.