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Stress matters: Randomized controlled trial on the effect of probiotics on neurocognition.
Papalini, S, Michels, F, Kohn, N, Wegman, J, van Hemert, S, Roelofs, K, Arias-Vasquez, A, Aarts, E
Neurobiology of stress. 2019;10:100141
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Plain language summary
Increasing animal studies indicate the role of probiotics in regulating mood and cognition through the gut-brain axis, however in human studies evidence of this causal association is lacking. The aim of this double-blind, randomised, placebo-controlled intervention was to investigate the effects of probiotics on neurocognitive measures in 58 healthy participants. Participants were randomly assigned to either probiotic or placebo group and were tested once before and after the 28-day intervention. The neurocognitive outcomes measured included emotion reactivity, emotion regulation, cognitive control and the effects of acute stress on working memory. These were assessed through functional MRI (fMRI) and questionnaires. This study found when stress was induced, probiotic supplementation led to a significant improvement in working memory performance. Without stress, there was no causal association between neurocognitive outcomes and probiotic intake. Based on these results, the authors conclude that during challenging situations, probiotics can aid in buffering the detrimental effects of stress on cognition.
Abstract
Probiotics are microorganisms that provide health benefits when consumed. In animals, probiotics reverse gut microbiome-related alterations in depression-like symptoms, in cognition, and in hormonal stress response. However, in humans, a causal understanding of the gut-brain link in emotion and cognition is lacking. Additionally, whether the effects of probiotics on neurocognition are visible only in presence of stress, remains unclear. We investigated the effects of a multispecies probiotic (EcologicĀ®Barrier) on specific neurocognitive measures of emotion reactivity, emotion regulation, and cognitive control using fMRI. Critically, we also tested whether probiotics can buffer against the detrimental effects of acute stress on working memory. In a double blind, randomized, placebo-controlled, between-subjects intervention study, 58 healthy participants were tested once before and once after a 28-day intervention. Without stress induction, probiotics did not affect brain, behavioral, or related self-report measures. However, relative to placebo, the probiotics group did show a significant stress-related increase in working memory performance after supplementation. This change was associated with intervention-related neural changes in frontal cortex during cognitive control exclusively in the probiotics group. Overall, our results show neurocognitive effects of a multispecies probiotic in healthy women only under challenging situations, buffering against the detrimental effects of stress on cognition.
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Investigating the impact of overnight fasting on intrinsic functional connectivity: a double-blind fMRI study.
Orfanos, S, Toygar, T, Berthold-Losleben, M, Chechko, N, Durst, A, Laoutidis, ZG, Vocke, S, Weidenfeld, C, Schneider, F, Karges, W, et al
Brain imaging and behavior. 2018;(4):1150-1159
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Abstract
The human brain depends mainly on glucose supply from circulating blood as an energy substrate for its metabolism. Most of the energy produced by glucose catabolism in the brain is used to support intrinsic communication purposes in the absence of goal-directed activity. This intrinsic brain function can be detected with fMRI as synchronized fluctuations of the BOLD signal forming functional networks. Here, we report results from a double-blind, placebo controlled, cross-over study addressing changes in intrinsic brain activity in the context of very low, yet physiological, blood glucose levels after overnight fasting. Comparison of four major resting state networks in a fasting state and a state of elevated blood glucose levels after glucagon infusion revealed altered patterns of functional connectivity only in a small region of the posterior default mode network, while the rest of the networks appeared unaffected. Furthermore, low blood glucose was associated with changes in the right frontoparietal network after cognitive effort. Our results suggest that fasting has only limited impact on intrinsic brain activity, while a detrimental impact on a network related to attention is only observable following cognitive effort, which is in line with ego depletion and its reliance on glucose.
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Prolonged fasting impairs neural reactivity to visual stimulation.
Kohn, N, Wassenberg, A, Toygar, T, Kellermann, T, Weidenfeld, C, Berthold-Losleben, M, Chechko, N, Orfanos, S, Vocke, S, Laoutidis, ZG, et al
Brain structure & function. 2016;(1):147-58
Abstract
Previous literature has shown that hypoglycemia influences the intensity of the BOLD signal. A similar but smaller effect may also be elicited by low normal blood glucose levels in healthy individuals. This may not only confound the BOLD signal measured in fMRI, but also more generally interact with cognitive processing, and thus indirectly influence fMRI results. Here we show in a placebo-controlled, crossover, double-blind study on 40 healthy subjects, that overnight fasting and low normal levels of glucose contrasted to an activated, elevated glucose condition have an impact on brain activation during basal visual stimulation. Additionally, functional connectivity of the visual cortex shows a strengthened association with higher-order attention-related brain areas in an elevated blood glucose condition compared to the fasting condition. In a fasting state visual brain areas show stronger coupling to the inferior temporal gyrus. Results demonstrate that prolonged overnight fasting leads to a diminished BOLD signal in higher-order occipital processing areas when compared to an elevated blood glucose condition. Additionally, functional connectivity patterns underscore the modulatory influence of fasting on visual brain networks. Patterns of brain activation and functional connectivity associated with a broad range of attentional processes are affected by maturation and aging and associated with psychiatric disease and intoxication. Thus, we conclude that prolonged fasting may decrease fMRI design sensitivity in any task involving attentional processes when fasting status or blood glucose is not controlled.
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Effects of overnight fasting on working memory-related brain network: an fMRI study.
Chechko, N, Vocke, S, Habel, U, Toygar, T, Kuckartz, L, Berthold-Losleben, M, Laoutidis, ZG, Orfanos, S, Wassenberg, A, Karges, W, et al
Human brain mapping. 2015;(3):839-51
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Abstract
Glucose metabolism serves as the central source of energy for the human brain. Little is known about the effects of blood glucose level (BGL) on higher-order cognitive functions within a physiological range (e.g., after overnight fasting). In this randomized, placebo-controlled, double blind study, we assessed the impact of overnight fasting (14 h) on brain activation during a working memory task. We sought to mimic BGLs that occur naturally in healthy humans after overnight fasting. After standardized periods of food restriction, 40 (20 male) healthy participants were randomly assigned to receive either glucagon to balance the BGL or placebo (NaCl). A parametric fMRI paradigm, including 2-back and 0-back tasks, was used. Subclinically low BGL following overnight fasting was found to be linked to reduced involvement of the bilateral dorsal midline thalamus and the bilateral basal ganglia, suggesting high sensitivity of those regions to minimal changes in BGLs. Our results indicate that overnight fasting leads to physiologically low levels of glucose, impacting brain activation during working memory tasks even when there are no differences in cognitive performance.
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In a sweet mood? Effects of experimental modulation of blood glucose levels on mood-induction during fMRI.
Kohn, N, Toygar, T, Weidenfeld, C, Berthold-Losleben, M, Chechko, N, Orfanos, S, Vocke, S, Durst, A, Laoutidis, ZG, Karges, W, et al
NeuroImage. 2015;:246-56
Abstract
Glucose is the primary source of energy for the human brain. Previous literature has shown that varying blood glucose levels may have a strong impact on behaviour, subjective mood, and the intensity of the BOLD signal measured in fMRI. Therefore, blood glucose levels varying even within the normal range may interact with cognitive and emotional processing as well as BOLD signal. Here, in a placebo-controlled, double-blind crossover study on 20 healthy women, we show that overnight fasting, compared to an elevated glucose condition, influences brain activation and the affective state during mood induction. Results indicate that our brain may compensate for low glucose levels during fasting by stronger recruitment of the brain areas relevant to the task at hand. Additionally, we systematically tested the effect of prior cognitive effort on behavioural and neural patterns and found that elevated activation is only associated with maintained performance as long as no prior cognitively challenging task is administered. Prior cognitive effort leads to deteriorated performance and a further increase in emotion-associated brain activation in the pregenual anterior and posterior cingulate, the superior frontal gyrus, and the pre-SMA. These results are in line with the strength model of self-regulation. Our results corroborate the strength model of self-regulation and extend it to affect regulation processes. Additionally, our observations suggest that experimentally controlling for fasting state or glucose levels may be beneficial, especially when studying processes that involve self-regulation.
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Predictors of positive immunofixation testing in patients with acute kidney injury.
Mattana, J, Govindappa, V, Adamidis, A, Kohn, N
The American journal of the medical sciences. 2013;(3):185-9
Abstract
INTRODUCTION Acute kidney injury may be the presenting manifestation of multiple myeloma, although optimal use of immunofixation testing in this setting is incompletely defined. The authors attempted to determine clinical and laboratory predictors of positive immunofixation testing in patients with acute kidney injury. PATIENTS AND METHODS The authors did a retrospective study of hospitalized patients with acute kidney injury who had immunofixation studies done. Various clinical and laboratory variables that may be predictive of the presence of multiple myeloma were evaluated and correlations with immunofixation test results determined. RESULTS One hundred twenty-eight patients were studied. Thirteen had a monoclonal paraprotein detected by immunofixation testing (positive result). Patients with positive testing had higher total, ionized and corrected calcium levels, although the median total calcium in immunofixation-positive patients was normal at 9.7 mg/dL. Patients with positive testing also had lower hemoglobin and platelet counts. An anion gap of <7 mmol/L and total protein-albumin gap >4 g/dL were also associated with positive results. CONCLUSIONS In patients with acute kidney injury, relatively higher total, ionized and corrected calcium levels and lower hemoglobin and platelet counts may predict the presence of a monoclonal paraprotein. An anion gap of <7 mmol/L and total protein-albumin gap >4 g/dL may also be predictors. The metabolic consequences of acute kidney injury may attenuate some of these abnormalities as well. These findings may help guide optimal use of immunofixation testing and hence help potentially identify patients who may have multiple myeloma.