The Microbiota-Gut-Brain Axis.

The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson's disease, and Alzheimer's disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.

Prevalence and management of sleep disturbance in adults with primary brain tumours and their caregivers: a systematic review.

PURPOSE: The aims of this systematic review were to (1) examine the prevalence, severity, manifestations, and clinical associations/risk factors of sleep disturbance in primary brain tumour (PBT) survivors and their caregivers; and (2) determine whether there are any sleep-focused interventons reported in the literature pertaining to people affected by PBT. METHODS: This systematic review was registered with the international register for systematic reviews (PROSPERO: CRD42022299332). PubMed, EMBASE, Scopus, PsychINFO, and CINAHL were electronically searched for relevant articles reporting sleep disturbance and/or interventions for managing sleep disturbance published between September 2015 and May 2022. The search strategy included terms focusing on sleep disturbance, primary brain tumours, caregivers of PBT survivors, and interventions. Two reviewers conducted the quality appraisal (JBI Critical Appraisal Tools) independently, with results compared upon completion. RESULTS: 34 manuscripts were eligible for inclusion. Sleep disturbance was highly prevalent in PBT survivors with associations between sleep disturbance and some treatments (e.g., surgical resection, radiotherapy, corticosteroid use), as well as other prevalent symptoms (e.g., fatigue, drowsiness, stress, pain). While the current review was unable to find any sleep-targeted interventions, preliminary evidence suggests physical activity may elicit beneficial change on subjectively reported sleep disturbance in PBT survivors. Only one manuscript that discussed caregivers sleep disturbance was identified. CONCLUSIONS: Sleep disturbance is a prevalent symptom experienced by PBT survivors, yet there is a distinct lack of sleep-focused interventions in this population. This includes a need for future research to include caregivers, with only one study identified. Future research exploring interventions directly focused on the management of sleep disturbance in the context of PBT is warranted.

Hippocampal subfield plasticity is associated with improved spatial memory.

Physical exercise studies are generally underrepresented in young adulthood. Seventeen subjects were randomized into an intervention group (24.2 ± 3.9 years; 3 trainings/week) and 10 subjects into a passive control group (23.7 ± 4.2 years), over a duration of 6 months. Every two months, performance diagnostics, computerized spatial memory tests, and 3 Tesla magnetic resonance imaging were conducted. Here we find that the intervention group, compared to controls, showed increased cardiorespiratory fitness, spatial memory performance and subregional hippocampal volumes over time. Time-by-condition interactions occurred in right cornu ammonis 4 body and (trend only) dentate gyrus, left hippocampal tail and left subiculum. Increases in spatial memory performance correlated with hippocampal body volume changes and, subregionally, with left subicular volume changes. In conclusion, findings support earlier reports of exercise-induced subregional hippocampal volume changes. Such exercise-related plasticity may not only be of interest for young adults with clinical disorders of hippocampal function, but also for sedentary normal cohorts.

Regional cortical perfusion increases induced by a 6-month endurance training in young sedentary adults.

Physical inactivity is documented as a health risk factor for chronic diseases, accelerated aging, and cognitive impairment. Physical exercise, on the other hand, plays an important role in healthy aging by promoting positive muscular, cardiovascular, and central nervous system adaptions. Prior studies on the effects of exercise training on cerebral perfusion have focused largely on elderly cohorts or patient cohorts, while perfusion effects of exercise training in young sedentary adults have not yet been fully assessed. Therefore, the present study examined the physiological consequence of a 6-month endurance exercise training on brain perfusion in 28 young sedentary adults randomly assigned to an intervention group (IG; regular physical exercise) or a control group (CG; without physical exercise). The IG performed an extensive running interval training three times per week over 6 months. Performance diagnostics and MRI were performed every 2 months, and training intensity was adapted individually. Brain perfusion measurements with pseudo-continuous arterial spin labeling were analyzed using the standard Oxford ASL pipeline. A significant interaction effect between group and time was found for right superior temporal gyrus (STG) perfusion, driven by an increase in the IG and a decrease in the CG. Furthermore, a significant time effect was observed in the right middle occipital region in the IG only. Perfusion increases in the right STG, in the ventral striatum, and in primary motor areas were significantly associated with increases in maximum oxygen uptake (VO2max). Overall, this study identified region-specific increases in local perfusion in a cohort of young adults that partly correlated with individual performance increases, hence, suggesting exercise dose dependency. Respective adaptations in brain perfusion are discussed in the context of physical exercise-induced vascular plasticity.

Variation within the visually evoked neurovascular coupling response of the posterior cerebral artery is not influenced by age or sex.

Neurovascular coupling (NVC) is the temporal and spatial coordination between local neuronal activity and regional cerebral blood flow. The literature is unsettled on whether age and/or sex affect NVC, which may relate to differences in methodology and the quantification of NVC in small sample-sized studies. The aim of this study was to 1) determine the relative and combined contribution of age and sex to the variation observed across several distinct NVC metrics (n = 125, 21-66 yr; 41 males) and 2) present an approach for the comprehensive systematic assessment of the NVC response using transcranial Doppler ultrasound. NVC was measured as the relative change from baseline (absolute and percent change) assessing peak, mean, and total area under the curve (tAUC) of cerebral blood velocity through the posterior cerebral artery (PCAv) during intermittent photic stimulation. In addition, the NVC waveform was compartmentalized into distinct regions, acute (0-9 s), mid (10-19 s), and late (20-30 s), following the onset of photic stimulation. Hierarchical multiple regression modeling was used to determine the extent of variation within each NVC metric attributable to demographic differences in age and sex. After controlling for differences in baseline PCAv, the R2 data suggest that 1.6%, 6.1%, 1.1%, 3.4%, 2.5%, and 4.2% of the variance observed within mean, peak, tAUC, acute, mid, and late response magnitude is attributable to the combination of age and sex. Our study reveals that variability in NVC response magnitude is independent of age and sex in healthy human participants, aged 21-66 yr.NEW & NOTEWORTHY We assessed the variability within the neurovascular coupling response attributable to age and sex (n = 125, 21-66 yr; 41 male). Based on the assessment of posterior cerebral artery responses to visual stimulation, 0%-6% of the variance observed within several metrics of NVC response magnitude are attributable to the combination of age and sex. Therefore, observed differences between age groups and/or sexes are likely a result of other physiological factors.

Voxel-based morphometry studies of personality: issue of statistical model specification--effect of nuisance covariates.

There are an increasing number of studies on the localization of personality using voxel-based morphometry. Due to the complex analytic challenge in volumetric studies, the specification and treatment of the nuisance covariate (such as age, gender, and global measures) is currently not consistent. Here, we present a study in which we conducted voxel-based morphometry with Five-Factor Model (FFM) of personality traits (extraversion, neuroticism, openness to experience, agreeableness, and conscientiousness) that aimed to test the influence of NC specification in the determination of the results. In this study, 62 healthy subjects underwent MRI investigation and completed a German version of the FFM personality questionnaire. Voxel-based morphometry was used to investigate the correlation between the FFM personality traits and subtle brain structure. Different NC combinations were used during the model specification. Significant clusters were found only under the condition of some of the NC combinations but not under the others. In addition, we use the structure equation modeling (automated specification search from AMOS) to narrow down the possible choices of NC combinations according to a set of goodness-of-fit indices to identify well-fitted statistic models. As a final step, theoretical implications of the results are discussed, before accepting the selected model.

The effect of exercise interventions on inflammatory markers in major depressive disorder: protocol for a systematic review and meta-analysis.

Background: Depression currently affects 4.4% of the global population, and 93.7% of this population suffer from major depressive disorder (MDD) according to 2017 statistics. MDD patients are more likely to suffer from co-morbidities such as cardiovascular disease and high body mass index (BMI), thus contributing to its large cost to society. Throughout the literature, there are known links between inflammation and MDD. Interestingly, while exercise is considered a promising intervention for MDD, the mechanism(s) of action remain unclear, thereby preventing the creation of optimal, cost-saving, exercise "prescriptions" for those with MDD. Thus, the aim of this review and meta-analysis is to summarize and analyse the current literature exploring how quantified exercise interventions modulate inflammatory molecules in MDD patients. Methods: Electronic databases (APA PsycINFO, and PubMed/MEDLINE (EBSCO interface), EMBASE) will be searched using a detailed search strategy comprised of three search term themes: exercise, depression/MDD, and inflammation/inflammatory molecules. Only quantified exercise interventions performed in adult humans with MDD validated via a recognized diagnostic criterion will be included. Studies should also include a MDD control group and explore changes in inflammatory molecules. Examples of these molecules include: C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1 beta (IL-1b), tumour necrosis factor-alpha (TNF-a), homocysteine, d-dimer and myeloperoxidase (MPO). After eligible studies are identified, standardized data extraction will be employed and the risk of bias in each study will be appraised using the Cochrane handbook checklists. In the event of two or more homogenous studies exploring exercise effects over a similar time period, raw mean differences or standardized mean differences will be pooled using random effects analysis. This systematic review and meta-analysis will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Dissemination: This systematic review and meta-analysis will be disseminated in peer-reviewed journals. PROSPERO registration: CRD42020186006 (31/08/2020).

Investigating causality with fecal microbiota transplantation in rodents: applications, recommendations and pitfalls.

In recent years, studies investigating the role of the gut microbiota in health and diseases have increased enormously - making it essential to deepen and question the research methodology employed. Fecal microbiota transplantation (FMT) in rodent studies (either from human or animal donors) allows us to better understand the causal role of the intestinal microbiota across multiple fields. However, this technique lacks standardization and requires careful experimental design in order to obtain optimal results. By comparing several studies in which rodents are the final recipients of FMT, we summarize the common practices employed. In this review, we document the limitations of this method and highlight different parameters to be considered while designing FMT Studies. Standardizing this method is challenging, as it differs according to the research topic, but avoiding common pitfalls is feasible. Several methodological questions remain unanswered to this day and we offer a discussion on issues to be explored in future studies.

Disentangling motor planning and motor execution in unmedicated de novo Parkinson's disease patients: An fMRI study.

Many studies have used functional magnetic resonance imaging to unravel the neuronal underpinnings of motor system abnormalities in Parkinson's disease, indicating functional inhibition at the level of basal ganglia-thalamo-cortical motor networks. The study aim was to extend the characterization of functional motor changes in Parkinson's Disease by dissociating between two phases of action (i.e. motor planning and motor execution) during an automated unilateral finger movement sequence with the left and right hand, separately. In essence, we wished to identify neuronal dysfunction and potential neuronal compensation before (planning) and during (execution) automated sequential motor behavior in unmedicated early stage Parkinson's Disease patients. Twenty-two Parkinson's Disease patients (14 males; 53 ±â€¯11 years; Hoehn and Yahr score 1.4 ±â€¯0.6; UPDRS (part 3) motor score 16 ±â€¯6) and 22 healthy controls (14 males; 49 ±â€¯12 years) performed a pre-learnt four finger sequence (index, ring, middle and little finger, in order), either self-initiated (FREE) or externally triggered (REACT), within an 8-second time window. Findings were most pronounced during FREE with the clinically most affected side, where motor execution revealed significant underactivity of contralateral primary motor cortex, contralateral posterior putamen (sensorimotor territory), ipsilateral anterior cerebellum / cerebellar vermis, along with underactivity in supplementary motor area (based on ROI analyses only), corroborating previous findings in Parkinson's Disease. During motor planning, Parkinson's Disease patients showed a significant relative overactivity in dorsolateral prefrontal cortex (DLPFC), suggesting a compensatory overactivity. To a variable extent this relative overactivity in the DLPFC went along with a relative overactivity in the precuneus and the ipsilateral anterior cerebellum/cerebellar vermis Our study illustrates that a refined view of disturbances in motor function and compensatory processes can be gained from experimental designs that try to dissociate motor planning from motor execution, emphasizing that compensatory mechanisms are triggered in Parkinson's Disease when voluntary movements are conceptualized for action.

Focus on the essentials: tryptophan metabolism and the microbiome-gut-brain axis.

The gut-brain axis is a bidirectional communication system between the central nervous system and the gastrointestinal tract, in which serotonin (5-HT) functions as a key neurotransmitter. Recent research has increasingly concentrated on tryptophan, the precursor to 5-HT and on the microbial regulation of tryptophan metabolism, with an emphasis on host-microbe control over kynurenine pathway metabolism and microbial-specific pathways that generate bioactive tryptophan metabolites. Here, we critically assess recent progress made towards a mechanistic understanding of the microbial regulation of tryptophan metabolism and microbiota-gut-brain axis homeostasis highlighting the role tryptophan metabolism plays in preclinical and clinical neuroscience and in the challenge to improve our understanding of how perturbed tryptophan metabolism contributes to stress-related psychiatric disorders.

A Reduction in Delay Discounting by Using Episodic Future Imagination and the Association with Episodic Memory Capacity.

Delay discounting (DD) refers to the phenomenon that individuals discount future consequences. Previous studies showed that future imagination reduces DD, which was mediated by functional connectivity between medial prefrontal valuation areas and a key region for episodic memory (hippocampus). Future imagination involves an initial period of construction and a later period of elaboration, with the more elaborative latter period recruiting more cortical regions. This study examined whether elaborative future imagination modulated DD, and if so, what are the underlying neural substrates. It was assumed that cortical areas contribute to the modulation effect during the later period of imagination. Since future imagination is supported by episodic memory capacity, we additionally hypothesize that the neural network underlying the modulation effect is related to individual episodic memory capacity. Twenty-two subjects received an extensive interview on personal future events, followed by an fMRI DD experiment with and without the need to perform elaborative future imagination simultaneously. Subjects' episodic memory capacity was also assessed. Behavioral results replicate previous findings of a reduced discount rate in the DD plus imagination condition compared to the DD only condition. The behavioral effect positively correlated with: (i) subjective value signal changes in midline brain structures during the initial imagination period; and (ii) signal changes in left prefrontoparietal areas during the later imagination period. Generalized psychophysiological interaction (gPPI) analyses reveal positive correlations between the behavioral effect and functional connectivity among the following areas: right anterior cingulate cortex (ACC) and left hippocampus; left inferior parietal cortex (IPC) and left hippocampus; and left IPC and bilateral occipital cortices. These changes in functional connectivity are also associated with episodic memory capacity. A hierarchical multiple regression indicates that the model with both the valuation related signal changes in the right ACC and the imagination related signal changes in the left IPC best predicts the reduction in DD. This study illustrates interactions between the left hippocampus and multiple cortical regions underlying the modulation effect of elaborative episodic future imagination, demonstrating, for the first time, empirical support for a relation to individual episodic memory capacity.

Revisiting the cortical system for peripheral reaching at the parieto-occipital junction.

Optic ataxia (OA) is a neurological disorder that is characterised by misreaching to targets in the visual periphery. The anatomy of OA thus provides important information for the neural representation of visually guided reaching in humans. In 2005 a lesion mapping analysis of OA localised the critical lesion site at the parieto-occipital junction (POJ) (Karnath & Perenin, 2005). This work was accompanied by the discovery of a peripheral reaching module at the POJ in an fMRI study (Prado et al., 2005). The ostensible overlap between the territory typically affected in patients with OA and the findings of Prado et al. (2005) had a tremendous influence on the search for a cortical peripheral reaching module. However, a close inspection of the functional Magnetic Resonance Imaging (fMRI) study revealed that a comparison between reaching towards visible targets in the peripheral visual field and reaching to visible targets in the central visual field--which is the key aspect in clinical examinations of OA--was not conducted. Moreover, whereas main effects of reaching overlapped with the OA lesion site, specific interaction effects did not overlap. We performed a direct comparison between reaching to visible peripheral targets and reaching to visible central targets to address the inconsistencies between the aforementioned studies. Our analysis shows that Prado et al.'s study cannot be taken as evidence for a delineated module for peripheral reaching. In contrast to Prado et al. we found a combined system of POJ, IPS and SPL areas--the posterior human 7A, mIPS, V6A and the posterior IPS--with increased signals during reaching to peripheral targets.

Age and grip strength predict hand dexterity in adults.

In the scientific literature, there is much evidence of a relationship between age and dexterity, where increased age is related to slower, less nimble and less smooth, less coordinated and less controlled performances. While some suggest that the relationship is a direct consequence of reduced muscle strength associated to increased age, there is a lack of research that has systematically investigated the relationships between age, strength and hand dexterity. Therefore, the aim of this study was to examine the associations between age, grip strength and dexterity. 107 adults (range 18-93 years) completed a series of hand dexterity tasks (i.e. steadiness, line tracking, aiming, and tapping) and a test of maximal grip strength. We performed three phases of analyses. Firstly, we evaluated the simple relationships between pairs of variables; replicating the existing literature; and found significant relationships of increased age and reduced strength; increased age and reduced dexterity, and; reduced strength and reduced dexterity. Secondly, we used standard Multiple Regression (MR) models to determine which of the age and strength factors accounted for the greater variance in dexterity. The results showed that both age and strength made significant contributions to the data variance, but that age explained more of the variance in steadiness and line tracking dexterity, whereas strength explained more of the variance in aiming and tapping dexterity. In a third phase of analysis, we used MR analyses to show an interaction between age and strength on steadiness hand dexterity. Simple Slopes post-hoc analyses showed that the interaction was explained by the middle to older aged adults showing a relationship between reduced strength and reduced hand steadiness, whereas younger aged adults showed no relationship between strength and steadiness hand dexterity. The results are discussed in terms of how age and grip strength predict different types of hand dexterity in adults.

Language aptitude for pronunciation in advanced second language (L2) learners: behavioural predictors and neural substrates.

Individual differences in second language (L2) aptitude have been assumed to depend upon a variety of cognitive and personality factors. Especially, the cognitive factor phonological working memory has been conceptualised as language learning device. However, strong associations between phonological working memory and L2 aptitude have been previously found in early-stage learners only, not in advanced learners. The current study aimed at investigating the behavioural and neurobiological predictors of advanced L2 learning. Our behavioural results showed that phonetic coding ability and empathy, but not phonological working memory, predict L2 pronunciation aptitude in advanced learners. Second, functional neuroimaging revealed this behavioural trait to be correlated with hemodynamic responses of the cerebral network of speech motor control and auditory-perceptual areas. We suggest that the acquisition of L2 pronunciation aptitude is a dynamic process, requiring a variety of neural resources at different processing stages over time.