Network Constraints on Longitudinal Grey Matter Changes in First Episode Psychosis

Background: Different regions of the brain's grey matter are connected by a complex structural network of white matter fibres which are responsible for the propagation of action potentials and the transport of trophic and other molecules. In neurodegenerative disease, these connections constrain the way in which grey matter volume loss progresses. Here, we investigated whether connectome architecture also shapes the spatial pattern of longitudinal grey matter volume changes attributable to illness and antipsychotic medication in first episode psychosis (FEP). Methods: We conducted a triple-blind randomised placebo-control MRI study where 62 young adults with first episode psychosis received either an atypical antipsychotic or placebo over 6-months. A healthy control group was also recruited. Anatomical MRI scans were acquired at baseline, 3-months and 12-months. Deformation-based morphometry was used to estimate illness-related and antipsychotic-related grey matter volume changes over time. Representative functional and structural brain connectivity patterns were derived from an independent healthy control group using resting-state functional MRI and diffusion-weighted imaging. We used neighbourhood deformation models to predict the extent of brain change in a given area by the changes observed in areas to which it is either structurally connected or functionally coupled. Results: At baseline, we found that empirical illness-related regional volume differences were strongly correlated with predicted differences using a model constrained by structural connectivity weights (ρ = .541; p < .001). At 3-months and 12-months, we also found a strong correlation between longitudinal regional illness-related (ρ > .516; p < .001) and antipsychotic-related volume change (ρ > .591; p < .001) with volumetric changes in structurally connected areas. These correlations were significantly greater than those observed across various null models accounting for lower-order spatial and network properties of the data. Associations between empirical and predicted volume change estimates were much lower for models that only considered binary structural connectivity (all ρ < .376), or which were constrained by inter-regional functional coupling (all ρ < .436). Finally, we found that potential epicentres of volume change emerged posteriorly early in the illness and shifted to the prefrontal cortex by later illness stages. Conclusion: Psychosis- and antipsychotic-related grey matter volume changes are strongly shaped by anatomical brain connectivity. This result is consistent with findings in other neurological disorders and implies that such connections may constrain pathological processes causing brain dysfunction in FEP.

A pilot exploration of multi-omics research of gut microbiome in major depressive disorders

The pathophysiology of major depressive disorder (MDD) remains obscure. Recently, the microbiota-gut-brain (MGB) axis’s role in MDD has an increasing attention. However, the specific mechanism of the multi-level effects of gut microbiota on host metabolism, immunity, and brain structure is unclear. Multi-omics approaches based on the analysis of different body fluids and tissues using a variety of analytical platforms have the potential to provide a deeper understanding of MGB axis disorders. Therefore, the data of metagenomics, metabolomic, inflammatory factors, and MRI scanning are collected from the two groups including 24 drug-naïve MDD patients and 26 healthy controls (HCs). Then, the correlation analysis is performed in all omics. The results confirmed that there are many markedly altered differences, such as elevated Actinobacteria abundance, plasma IL-1β concentration, lipid, vitamin, and carbohydrate metabolism disorder, and diminished grey matter volume (GMV) of inferior frontal gyrus (IFG) in the MDD patients. Notably, three kinds of discriminative bacteria, Ruminococcus bromii, Lactococcus chungangensis, and Streptococcus gallolyticus have an extensive correlation with metabolome, immunology, GMV, and clinical symptoms. All three microbiota are closely related to IL-1β and lipids (as an example, phosphoethanolamine (PEA)). Besides, Lactococcus chungangensis is negatively related to the GMV of left IFG. Overall, this study demonstrate that the effects of gut microbiome exert in MDD is multifactorial.

Non-modifiable factors as moderators of the relationship between physical activity and brain volume: A cross-sectional UK Biobank study

Background: Grey matter atrophy occurs as a function of ageing and is accelerated in dementia. Previous research suggests physical activity attenuates grey matter loss; however, there appears to be individual variability in this effect. Understanding factors that can affect the relationship between physical activity and brain volume may enable prediction of individual response, and aid in identifying those that gain the greatest neural benefits from physical activity. The current study examined the relationship between objectively-measured physical activity and brain volume; and whether this relationship is moderated by age, sex, or a priori candidate genetic factors. Methods: Data from 10,083 men and women (50 years and over) of the UK Biobank were used to examine: 1) the relationship between objectively-measured physical activity and brain volume; and 2) whether the relationship between objectively-measured physical activity and brain volume is moderated by age, sex, brain-derived neurotrophic factor (BDNF) Val66Met, or apolipoprotein (APOE) e4 allele carriage. All participants underwent a magnetic resonance imaging scan to quantify grey matter volumes, physical activity monitoring via accelerometry, and genotyping. Results: Physical activity was associated with total grey matter volume (B = 0.14, p = 0.001, q = 0.005) and right hippocampal volume (B = 1.45, p = 0.008, q = 0.016). The physical activity*sex interaction predicted cortical grey matter (B = 0.22, p = 0.003, q = 0.004), total grey matter (B = 0.30, p < 0.001, q = 0.001), and right hippocampal volume (B = 3.60, p = 0.001, q = 0.002). Post-hoc analyses revealed males received benefit from higher physical activity levels, in terms of greater cortical grey matter volume (B = 0.13, p = 0.01), total grey matter volume (B=0.23, p < 0.001), and right hippocampal volume (B = 3.05, p = 0.008). No moderating effects of age, APOE e4 allele carriage, or BDNF Val66Met genotype were observed. Discussion: Our results indicate that in males, but not females, an association exists between objectively-measured physical activity and grey matter volume. Future research should evaluate longitudinal brain volumetrics to better understand the nature of sex-effects on the relationship between physical activity and brain volume.

Usefulness of two-dimensional measurements for the evaluation of brain volume and disability in multiple sclerosis

Background Two-dimensional (2D) measures have been proposed as potential proxies for whole-brain volume in multiple sclerosis (MS). Objective To verify whether 2D measurements by routine MRI are useful in predicting brain volume or disability in MS. Methods In this cross-sectional analysis, eighty-five consecutive Japanese MS patients—relapsing-remitting MS (81%) and progressive MS (19%)—underwent 1.5 Tesla T1-weighted 3D MRI examinations to measure whole-brain and grey matter volume. 2D measurements, namely, third ventricle width, lateral ventricle width (LVW), brain width, bicaudate ratio, and corpus callosum index (CCI), were obtained from each scan. Correlations between 2D measurements and 3D measurements, the Expanded Disability Status Scale (EDSS), or processing speed were analysed. Results The third and lateral ventricle widths were well-correlated with the whole-brain volume ( p < 0.0001), grey matter volume ( p < 0.0001), and EDSS scores ( p = 0.0001, p = .0004, respectively).The least squares regression model revealed that 78% of the variation in whole-brain volume could be explained using five explanatory variables, namely, LVW, CCI, age, sex, and disease duration. By contrast, the partial correlation coefficient excluding the effect of age showed that the CCI was significantly correlated with the EDSS and processing speed ( p < 0.0001). Conclusion Ventricle width correlated well with brain volumes, while the CCI correlated well with age-independent (i.e. disease-induced) disability.

The neurobiology of smartphone addiction in emerging adults evaluated using brain morphometry and resting-state functional MRI

The characteristics of smartphone addiction (SPA) can be evaluated by neuroimaging studies. Information on the brain structural alterations, and effects on psychosocial wellbeing, however, have not been concurrently evaluated. The aim of this study was to identify abnormalities in gray matter volume using voxel-based morphometry (VBM) and neuronal functional alterations using resting-state functional MRI (rs-fMRI) in emerging adults with SPA. We correlated the neuroimaging parameters with indices for psychosocial wellbeing such as depression, anxiety, stress, and impulsivity. Forty participants (20 SPA and 20 age-matched healthy controls) were assessed using VBM and rs-fMRI. The smartphone addiction scale – Malay version (SAS-M) questionnaire scores were used to categorize the SPA and healthy control groups. DASS-21 and BIS-11 questionnaires were used to assess for psychosocial wellbeing and impulsivity, respectively. VBM identified the SPA group to have reduced gray matter volume in the insula and precentral gyrus; and increased grey matter volume in the precuneus relative to controls. Moderate correlation was observed between the precuneus volume and the SAS-M scores. Individuals with SPA showed significant rs-fMRI activations in the precuneus, and posterior cingulate cortex (FWE uncorrected, p<0.001). The severity of SPA was correlated with depression. Anxiety score was moderately correlated with reduced GMV at the precentral gyrus. Collectively, these results can be used to postulate that the structural and neuronal functional changes in the insula are linked to the neurobiology of SPA that shares similarities with other behavioural addictions.

Sex Differences in Brain Structure Account for the Sexual Distinction on Balanced Time Perspective

Sex differences in behaviour and cognition have been widely observed, however, little is known about such differences in maintaining a balanced time perspective or their potential underlying neural substrates. To answer the above questions, two studies were conducted. In Study 1, time perspective was assessed in 1,913 college students, including 771 males and 1,092 females, and demonstrated that females had a significantly more balanced time perspective than males. In Study 2, 58 males and 47 females underwent assessment of time perspective and structural brain imaging. Voxel-based morphometry analysis and cortical thickness analysis were used to analyse the structural imaging data. Results showed that compared with males, females demonstrated a more balanced time perspective, which primarily related to lower grey matter volume in left precuneus, right cerebellum, right putamen and left supplementary motor area. Analysis of cortical thickness failed to reveal any significant sex differences. Furthermore, the sex difference in grey matter volume of left precuneus, right cerebellum, right putamen and left supplementary motor area could account for the difference in balanced time perspective between males and females. The findings deepen our understanding of sex differences in human cognition and their potential neural signature, and may inform tailored interventions to support a balanced time perspective in daily life.

Rapid volumetric brain changes after acute psychosocial stress

Rapid structural brain plasticity after acute stress has been shown in animals. It is unknown whether such stress-related brain changes also occur in humans, in which they have been found, using structural magnetic resonance imaging (MRI), after motor learning and visual stimulation. We here investigated grey matter volume (GMV) changes after acute stress in humans and tested their relation to psychophysiological stress measures. Sixty-seven healthy men (25.8 +/- 2.7 years) completed a standardized psychosocial laboratory stressor (Trier Social Stress Test) or a control version while blood, saliva, heart rate, and psychometrics were sampled. T1-weighted MP2RAGE images at 3T MRI were acquired 45 min before and 90 min after intervention onset. GMV changes were analysed using voxel-based morphometry. Associations with endocrine, autonomic, and subjective stress measures were tested with linear models. We found significant group-by-time interactions in several brain clusters including anterior/mid-cingulate cortices and bilateral insula: GMV was increased in the stress group relative to the control group, in which several clusters showed a GMV decrease. We found no significant group-by-time interaction for other MRI parameters, including cerebral blood flow, but a significant association of GMV changes with state anxiety and heart rate variability changes. In summary, we show rapid GMV changes following acute psychosocial stress in humans. The results suggest that endogenous circadian brain changes are counteracted by acute stress and generally emphasize the influence of stress on the brain.

Musical experience relates to functional connectivity in older adults

Previous studies have shown that engaging in musical activities throughout the lifespan may buffer age-related decline in auditory and motor function, as well as in general cognitive function. MRI studies have demonstrated that individuals with musical training and experience exhibited greater grey matter volume and functional connectivity in extensive brain regions, especially in auditory and motor systems, compared to matched controls with no particular musical training or experience. Therefore, musical activity is a potential protective factor for brain health across lifespan. However, how lifespan musical experience shapes functional connectivity in older adults is still unknown. The current analysis investigated whether general musical experience (Goldsmith Music Sophistication Index) is associated with functional connectivity in older adults (age=65.7±4.4, n=69), focusing on seed regions in primary motor areas (bilateral precentral gyrus) and primary auditory regions (bilateral anterior/posterior superior temporal gyrus) and their functional connectivity towards other areas throughout the whole brain. We found that older adults with more musical experience showed greater functional connectivity between anterior superior temporal gyrus and insula (R2=0.10, p=0.01), and between posterior superior temporal gyrus and cerebellum (R2=0.08, p=0.02). However, musical experience and music-related functional connectivity was not significantly correlated with general cognitive functions in our sample. Overall, our findings suggest that older adults with more musical experience might be more efficient in some aspects of auditory processing and auditory-motor skills, but this may not transfer towards domain-general cognitive tests. Our results support the notion that even non-professional engagement in musical experiences may afford benefits to the aging brain.

The Effect of Olfactory Training on Olfaction, Cognition, and Brain Function in Patients with Mild Cognitive Impairment

Background: The olfactory system is affected very early in Alzheimer’s disease and olfactory loss can already be observed in patients with mild cognitive impairment (MCI), an early stage of AD. Objective: The aim of this randomized, prospective, controlled, blinded study was to evaluate whether olfactory training (OT) may have an effect on olfactory function, cognitive impairment, and brain activation in MCI patients after a 4-month period of frequent short-term exposure to various odors. Methods: A total of 38 MCI outpatients were randomly assigned to OT or a control training condition, which were performed twice a day for 4 months. Olfactory testing, comprehensive neuropsychological assessment, and magnetic resonance imaging were performed before and after training. Results: The results suggested that OT exhibited no significant effect on olfaction and cognitive function. However, OT exhibited a positive effect on frontal lobe activation (left middle frontal gyrus and orbital-frontal cortex) but exhibited no effect on grey matter volume. Moreover, the change of olfactory scores was positively associated with the change of frontal activation. Conclusion: OT was found to have a limited effect on olfaction and cognition in patients with MCI compared to a non-OT condition but increased their functional response to odors in frontal area.

Causal effects of atrial fibrillation on brain white and gray matter volume: a Mendelian randomization study

Background Atrial fibrillation (AF) and brain volume loss are prevalent in older individuals. We aimed to assess the causal effect of atrial fibrillation on brain volume phenotypes by Mendelian randomization (MR) analysis. Methods The genetic instrument for AF was constructed from a previous genome-wide association study (GWAS) meta-analysis (15,993 AF patients and 113,719 controls of European ancestry). The outcome summary statistics for head-size-normalized white or gray matter volume measured by magnetic resonance imaging were provided by a previous GWAS of 33,224 white British participants in the UK Biobank. Two-sample MR by the inverse variance–weighted method was performed, supported by pleiotropy-robust MR sensitivity analysis. The causal estimates for the effect of AF on ischemic stroke were also investigated in a dataset that included the findings from the MEGASTROKE study (34,217 stroke patients and 406,111 controls of European ancestry). The direct effects of AF on brain volume phenotypes adjusted for the mediating effect of ischemic stroke were studied by multivariable MR. Results A higher genetic predisposition for AF was significantly associated with lower grey matter volume [beta −0.040, standard error (SE) 0.017, P=0.017], supported by pleiotropy-robust MR sensitivity analysis. Significant causal estimates were identified for the effect of AF on ischemic stroke (beta 0.188, SE 0.026, P=1.03E−12). The total effect of AF on lower brain grey matter volume was attenuated by adjusting for the effect of ischemic stroke (direct effects, beta −0.022, SE 0.033, P=0.528), suggesting that ischemic stroke is a mediator of the identified causal pathway. The causal estimates were nonsignificant for effects on brain white matter volume as an outcome. Conclusions This study identified that genetic predisposition for AF is significantly associated with lower gray matter volume but not white matter volume. The results indicated that the identified total effect of AF on gray matter volume may be mediated by ischemic stroke.