Related Functional Changes Research Articles

Brain surface area and function alterations are correlated with cognition in patients with end-stage renal disease.

Cognitive decline may occur in patients with end-stage renal disease (ESRD), and is particularly severe in patients with ESRD undergoing hemodialysis; however, the mechanism of this relationship between cognitive decline and ESRD is unclear. Cortical-based structural and functional analysis can be used to understand these cortical changes and their relationship with cognitive decline in non-dialysis and maintenance dialysis ESRD patients. This study aimed to examine whether there was any correlation between alterations in cortical and resting-state function changes and cognitive decline in patients diagnosed with ESRD. The study included a total of 126 participants who underwent laboratory assessments, neuropsychological tests, and brain magnetic resonance imaging (MRI). Of the 126 patients, 40 were ESRD without hemodialysis (ESRD-ND) patients, 40 were ESRD with hemodialysis (ESRD-HD) patients, and 46 were healthy controls (HCs). In terms of the cortical changes, the thickness and volume of the left medial temporal cortex were smaller in the ESRD-ND group than in the HC group. The thickness and volume of the double medial temporal cortex were reduced in the ESRD-HD group compared to the ESRD-ND group. The cortical volume in the anterior cingulate and medial prefrontal cortex (AntCing_MedPFC) was reduced in ESRD-HD group compared to both the ESRD-ND and HC groups. In terms of the functional changes, the regional homogeneity (ReHo) of the double medial temporal cortex was higher in the ESRD-HD group than in the ESRD-ND group, and higher in the ESRD-ND group than in the HC group. The ReHo of the AntCing_MedPFC was higher in both the ESRD-HD and ESRD-ND groups than in the HC group. The correlation analysis after covariation-correction showed that the cortical thickness (r=0.360, P=0.026) and cortical volume (r=0.440, P=0.006) of the medial temporal lobe in the ESRD-HD group were positively correlated with the Montreal Cognitive Assessment (MoCA) score. The cortical thickness (r=0.571, P<0.001) and cortical volume (r=0.529, P=0.001) of the posterior cingulated gyrus were positively correlated with the MoCA score in the ESRD-ND group. Our findings suggest that ESRD patients undergo more cognitively related cortical structural and functional changes than HCs. Dialysis can aggravate or cause changes in new brain regions. Changes in the cortex and volume of the posterior cingulate gyrus in ESRD patients is an important cause of cognitive decline. Damage to the medial temporal lobe by dialysis exacerbates this trend.

Sex differences related changes in cardiac structure and function after ST-segment elevation myocardial infarction

Abstract Background Sex disparities in presentation, treatment, and outcomes after ST-segment Elevation Myocardial Infarction (STEMI) are well recognized. However, little is known about sex related changes in cardiac structure and function following a STEMI in this contemporary era of early PCI. Purpose To compare sex differences in change of echocardiographic parameters of structure and function following a first-time STEMI. Methods This echocardiographic study involved 380 non-diabetic first-time STEMI patients. Structural and functional parameters were evaluated during initial hospitalization (median 1 day after presentation) and at 4-months. Adverse remodelling was defined as a 20% increase in left ventricular end-diastolic volume (LVEDV) at 4 months compared to the hospitalisation echo. Functional parameters included left ventricular ejection fraction (LVEF) and wall motion score index (WMSI). According to current guidelines, eccentric hypertrophy was defined as left ventricular mass index (LVMI) &amp;gt;95 g/m2 for women and &amp;gt;115 g/m2 for men with a relative wall thickness (RWT) ≤0.42; concentric hypertrophy was defined as LVMI &amp;gt;95 g/m2 for women and &amp;gt;115 g/m2 for men with RWT &amp;gt;0.42. The different patterns in geometry were assessed at 4-months. Results Among 380 patients, comprising 285 males and 95 females, females had a higher prevalence of hypertension (42% vs. 25.6%, p=0.004), lower hemoglobin levels (8.40 mmol/l vs. 9.10, p&amp;lt;0.001), and higher plasma NT-proBNP concentrations upon admission (132 ng/L vs 67, p&amp;lt;0.001) and after 24 hours (1322 ng/l vs 784, p&amp;lt;0.001). During the initial echocardiogram conducted upon hospitalization, as well as during the echocardiogram at 4 months, women had significantly lower LV diameters, LV volumes, LV mass, LAVI and wall thickness compared to man. However, during both evaluations women showed higher E/e’ ratio’s and LVEF. The change in echocardiographic variables between both timepoints did not differ significantly between sexes. Furthermore, no significant difference in LV geometry patterns (eccentric or concentric) were observed between sexes and adverse LV remodelling was similar between both groups at approximately 22-23% (p=0.991). Conclusions Although differences exist between sexes in patient characteristics and individual echocardiographic parameters, no disparity is observed in geometry patterns, adverse LV remodelling, or the change in echocardiographic parameters after STEMI.

Otolith assessment in elderly using combined vestibular-evoked myogenic potentials and subjective visual vertical test

BackgroundDizziness in elderly patients is classified as a multifactorial geriatric syndrome leading to pathological conditions or changes endemic to the aging process, it is characterized by increased susceptibility to accidents and instability. This is considered a major public health problem. In our study, we assessed age related changes in vestibular function via measurement of combined Vestibular-Evoked Myogenic potentials (VEMPs) as well as Static Subjective Visual Vertical Test (SVVT) for otolith function.MethodsSeventy-five subjects (150 ears) were enrolled in this research. They were categorized into a control group composed of twenty-five adults from 18–40 years and a study group which divided into symptomatic and asymptomatic groups, each group consisted of twenty-five subjects, fifteen subjects aged 55- < 65 years & ten subjects aged 65 to 85 years. All subjects were submitted to combined VEMPs and static SVVT.ResultsDetectability of combined VEMPs decreased with age with significant difference among the older age group (> 65- < 85 years) and the subjects aged (55- < 65 years). Percentage of abnormal cVEMPs & oVEMPs latencies and amplitudes was more detected in the older age group than subjects aged (55- < 65 years). The symptomatic group aged > 65 years showed higher percentage of affection of both cVEMPs & oVEMPs, while the younger group aged 55- < 65 showed higher absence of bilateral oVEMPs. There were no statistically significant differences in the asymmetrical ratio of cVEMPs & oVEMPs between elderly and adults. Static SVV perception does not change with age.ConclusionsThe elderly showed variable degrees of otolith dysfunction with a high percentage of affection in cVEMPs and oVEMPs. Also, they showed symptoms of imbalance and light-headedness. Static SVVT perception doesn’t change with age.

COVID-19 related cognitive, structural and functional brain changes among Italian adolescents and young adults: a multimodal longitudinal case-control study

Coronavirus disease 2019 (COVID-19) has been associated with brain functional, structural, and cognitive changes that persist months after infection. Most studies of the neurologic outcomes related to COVID-19 focus on severe infection and aging populations. Here, we investigated the neural activities underlying COVID-19 related outcomes in a case-control study of mildly infected youth enrolled in a longitudinal study in Lombardy, Italy, a global hotspot of COVID-19. All participants (13 cases, 27 controls, mean age 24 years) completed resting-state functional (fMRI), structural MRI, cognitive assessments (CANTAB spatial working memory) at baseline (pre-COVID) and follow-up (post-COVID). Using graph theory eigenvector centrality (EC) and data-driven statistical methods, we examined differences in ECdelta (i.e., the difference in EC values pre- and post-COVID-19) and Volumetricdelta (i.e., the difference in cortical volume of cortical and subcortical areas pre- and post-COVID) between COVID-19 cases and controls. We found that ECdelta significantly between COVID-19 and healthy participants in five brain regions; right intracalcarine cortex, right lingual gyrus, left hippocampus, left amygdala, left frontal orbital cortex. The left hippocampus showed a significant decrease in Volumetricdelta between groups (p = 0.041). The reduced ECdelta in the left amygdala associated with COVID-19 status mediated the association between COVID-19 and disrupted spatial working memory. Our results show persistent structural, functional and cognitive brain changes in key brain areas associated with olfaction and cognition. These results may guide treatment efforts to assess the longevity, reversibility and impact of the observed brain and cognitive changes following COVID-19.

Acupuncture Modulation of Chronic Neuropathic Pain and Its Association With Brain Functional Properties

Chronic neuropathic pain has been one of the prominent causes of disability, and acupuncture has shown promise in treatment. The present study aimed to characterize acupuncture modulation of chronic neuropathic pain and explore the related functional brain changes. Sixty chronic sciatica patients were divided into acupuncture- or sham acupuncture groups and received 10 sessions of treatment during 4 weeks. The visual analog scale for leg pain, oswestry disability index (ODI), and resting-state functional magnetic resonance images were assessed at baseline and after treatment. Then, fractional amplitudes of low-frequency fluctuations (fALFF) and support vector regression analyses were performed. Compared with sham acupuncture, acupuncture significantly improved symptoms, including visual analog scale for leg pain and ODI. In addition, acupuncture exhibited increased fALFF of the right superior parietal lobule (SPL) and right postcentral gyrus. Furthermore, the actual 4-week ODI values were positively correlated with the support vector regression-predicted values based on the right SPL fALFF and baseline clinical measurements. These results indicate that the spontaneous neural activity of the right SPL and right postcentral gyrus may be involved in the modulation of acupuncture in chronic neuropathic pain. In addition, the spontaneous neural activity of the right SPL might be used as the predictor of response to acupuncture therapy. PerspectiveThis clinical neuroimaging study elucidated the neural basis of acupuncture in chronic sciatica. Neurological indicators and clinical measurements could be used as potential predictors of acupuncture response. This study combines neuroimaging and artificial intelligence techniques to highlight the potential of acupuncture for the treatment of chronic neuropathic pain. Trial registration numberChinese Clinical Trial Registry, ChiCTR2100044585, http://www.chictr.org.cn.

Resting-State Changes in Aging and Parkinson’s Disease Are Shaped by Underlying Neurotransmission: A Normative Modeling Study

BackgroundHuman healthy and pathological aging is linked to a steady decline in brain resting-state activity and connectivity measures. The neurophysiological mechanisms that underlie these changes remain poorly understood. MethodsMaking use of recent developments in normative modeling and availability of in vivo maps for various neurochemical systems, we tested in the UK Biobank cohort (n = 25,917) whether and how age- and Parkinson’s disease–related resting-state changes in commonly applied local and global activity and connectivity measures colocalize with underlying neurotransmitter systems. ResultsWe found that the distributions of several major neurotransmitter systems including serotonergic, dopaminergic, noradrenergic, and glutamatergic neurotransmission correlated with age-related changes across functional activity and connectivity measures. Colocalization patterns in Parkinson’s disease deviated from normative aging trajectories for these, as well as for cholinergic and GABAergic (gamma-aminobutyric acidergic) neurotransmission. The deviation from normal colocalization of brain function and GABAA correlated with disease duration. ConclusionsThese findings provide new insights into molecular mechanisms underlying age- and Parkinson’s-related brain functional changes by extending the existing evidence elucidating the vulnerability of specific neurochemical attributes to normal aging and Parkinson’s disease. The results particularly indicate that alongside dopamine and serotonin, increased vulnerability of glutamatergic, cholinergic, and GABAergic systems may also contribute to Parkinson’s disease–related functional alterations. Combining normative modeling and neurotransmitter mapping may aid future research and drug development through deeper understanding of neurophysiological mechanisms that underlie specific clinical conditions.

Cellular senescence induced by down-regulation of PTBP1 correlates with exon skipping of mitochondrial-related gene NDUFV3.

As the most prevalent type of alternative splicing in animal cells, exon skipping plays an important role in expanding the diversity of transcriptome and proteome, thereby participating in the regulation of diverse physiological and pathological processes such as development, aging, and cancer. Cellular senescence serving as an anti-cancer mechanism could also contribute to individual aging. Although the dynamic changes of exon skipping during cellular senescence were revealed, its biological consequence and upstream regulator remain poorly understood. Here, by using human foreskin fibroblasts (HFF) replicative senescence as a model, we discovered that splicing factor PTBP1 was an important contributor for global exon skipping events during senescence. Down-regulated expression of PTBP1 induced senescence-associated phenotypes and related mitochondrial functional changes. Mechanistically, PTBP1 binds to the third exon of mitochondrial complex I subunit coding gene NDUFV3 and protects the exon from skipping. We further confirmed that exon skipping of NDUFV3 correlates with and partially contributes to cellular senescence and related mitochondrial functional changes upon PTBP1 knockdown. Together, we revealed for the first time that mitochondrial-related gene NDUFV3 is a new downstream target for PTBP1-regulated exon skipping to mediate cellular senescence and mitochondrial functional changes.

Don’t be late! Postponing cognitive decline and preventing early unemployment in people with multiple sclerosis: a study protocol

BackgroundUp to 65% of people with multiple sclerosis (PwMS) develop cognitive deficits, which hampers their ability to work, participating in day-to-day life and ultimately reducing quality of life (QoL). Early cognitive symptoms are often less tangible to PwMS and their direct environment and are noticed only when symptoms and work functioning problems become more advanced, i.e., when (brain) damage is already advanced. Treatment of symptoms at a late stage can lead to cognitive impairment and unemployment, highlighting the need for preventative interventions in PwMS.AimsThis study aims to evaluate the (cost-) effectiveness of two innovative preventative interventions, aimed at postponing cognitive decline and work functioning problems, compared to enhanced usual care in improving health-related QoL (HRQoL).MethodsRandomised controlled trial including 270 PwMS with mild cognitive impairment, who have paid employment ≥ 12 h per week and are able to participate in physical exercise (Expanded Disability Status Scale < 6.0). Participants are randomised across three study arms: 1) ‘strengthening the brain’ – a lifestyle intervention combining personal fitness, mental coaching, dietary advice, and cognitive training; 2) ‘strengthening the mind’ – a work-focused intervention combining the capability approach and the participatory approach in one-on-one coaching by trained work coaches who have MS themselves; 3) Control group—receiving general information about cognitive impairment in MS and receiving care as usual. Intervention duration is four months, with short-term and long-term follow-up measurements at 10 and 16 months, respectively. The primary outcome measure of the Don’t be late! intervention study will be HRQoL as measured with the 36-item Short Form. Secondary outcomes include cognition, work related outcomes, physical functioning, structural and functional brain changes, psychological functioning, and societal costs. Semi-structured interviews and focus groups with stakeholders will be organised to qualitatively reflect on the process and outcome of the interventions.DiscussionThis study seeks to prevent (further) cognitive decline and job loss due to MS by introducing tailor-made interventions at an early stage of cognitive symptoms, thereby maintaining or improving HRQoL. Qualitative analyses will be performed to allow successful implementation into clinical practice.Trial registrationRetrospectively registered at ClinicalTrials.gov with reference number NCT06068582 on 10 October 2023.

COVID-19 INFORMATION ELICITING STEREOTYPE THREAT CAN HARM OLDER ADULTS’ COGNITIVE FUNCTION

Abstract During the COVID-19 pandemic, older adults were identified as an at-risk group for developing severe physical symptoms. In addition to physical presentations, evidence indicated COVID-19 related changes in cognitive and neurological function; specifically, increased risk of stroke, reduced attention, concentration, and memory problems. Given that older adults remain particularly vulnerable to severe symptoms, exposure to information about COVID-19 and the associated cognitive symptoms may have adverse effects on their cognitive performance. This phenomenon, known as stereotype threat, describes situations in which negative stereotypes about a particular group can impair functioning. The current study aims to examine how exposure to adverse age-related information about the pandemic may impact cognitive performance compared to more neutral age-related information. 484 older adults were recruited February through July 2023 via Amazon Mechanical Turk and Cloud Research Connect. Participants were randomly assigned to a neutral or threat condition and read a paragraph related to aging or COVID-19, respectively. Afterwards, participants completed a memory task followed by a series of questionnaires to assess demographics, mood, depression, and COVID-19 health history. A one-way ANCOVA was conducted to evaluate the effect of COVID-19 threat on memory performance while controlling for history of COVID diagnosis. Findings indicate a significant difference in scores such that individuals in the threat condition had worse memory performance, compared to those in the neutral condition. This suggests that just reading information about COVID-19 may pose a threat to older adults’ cognitive abilities and further demonstrates the far-reaching effect the pandemic has had on individuals.

Houttuynia cordata thunb. alleviates inflammatory bowel disease by modulating intestinal microenvironment: a research review.

Inflammatory bowel disease (IBD) is a complex group of chronic intestinal diseases, the cause of which has not yet been clarified, but it is widely believed that the disorder of the intestinal microenvironment and its related functional changes are key factors in the development of the disease. Houttuynia cordata thunb. is a traditional plant with abundant resources and long history of utilization in China, which has attracted widespread attention in recent years due to its potential in the treatment of IBD. However, its development and utilization are limited owing to the aristolochic acid alkaloids contained in it. Therefore, based on the relationship between the intestinal microenvironment and IBD, this article summarizes the potential mechanisms by which the main active ingredients of Houttuynia cordata thunb., such as volatile oils, polysaccharides, and flavonoids, and related traditional Chinese medicine preparations, such as Xiezhuo Jiedu Formula, alleviate IBD by regulating the intestinal microenvironment. At the same time, combined with current reports, the medicinal and edible safety of Houttuynia cordata thunb. is explained for providing ideas for further research and development of Houttuynia chordate thunb. in IBD disease, more treatment options for IBD patients, and more insights into the therapeutic potential of plants with homology of medicine and food in intestinal diseases, and even more diseases.

Advances in understanding the pathogenesis of post-traumatic epilepsy: a literature review.

Severe head trauma can lead to seizures. Persistent epileptic seizures and their progression are associated with the severity of trauma. Although case reports have revealed that early use of anti-seizure drugs after trauma can prevent epilepsy, clinical case-control studies have failed to confirm this phenomenon. To date, many brain trauma models have been used to study the correlation between post-traumatic seizures and related changes in neural circuit function. According to these studies, neuronal and glial responses are activated immediately after brain trauma, usually leading to significant cell loss in injured brain regions. Over time, long-term changes in neural circuit tissues, especially in the neocortex and hippocampus, lead to an imbalance between excitatory and inhibitory neurotransmission and an increased risk of spontaneous seizures. These changes include alterations in inhibitory interneurons and the formation of new, over-recurrent excitatory synaptic connections. In this study, we review the progress of research related to post-traumatic epilepsy to better understand the mechanisms underlying the initiation and development of post-traumatic seizures and to provide theoretical references for the clinical treatment of post-traumatic seizures.

Successful secukinumab therapy in plaque psoriasis is associated with altered gut microbiota and related functional changes.

The role of gut microbiome dysbiosis in the pathogenesis of psoriasis has gained increasing attention in recent years. Secukinumab, targeting interleukin (IL)-17, has a promising efficacy in psoriasis treatment. However, it remains unclear the gut microbiota alteration and related functional changes caused by successful secukinumab therapy in psoriatic patients. In our study, we compared the fecal microbiome profile between psoriatic patients after secukinumab successful treatment (AT) and the other two groups, psoriatic patients without therapy (BT) and healthy people (H), respectively, by using next-generation sequencing targeting 16S ribosomal RNA. Then, shotgun metagenomic sequencing was first used to characterize bacterial gut microbial communities and related functional changes in the AT group. We found that the diversity and structure of the microbial community in the AT group were significantly changed compared to those in the BT group and the H group. The AT group showed a microbiota profile characterized by increased proportions of the phylum Firmicute, families Ruminococcaceae, and a reduction in the phylum Bacteroidota (elevated F/B ratio). To detect functional alteration, we discovered that secukinumab treatment may construct a more stable homeostasis of the gut microbiome with functional alteration. There were different KEGG pathways, such as the downregulated cardiovascular diseases pathway and the upregulated infectious diseases in the AT group. By metagenomic analysis, the metabolic functional pathway was changed after secukinumab therapy. It seems that gut microbiota investigation during biologic drug treatment is useful for predicting the efficacy and risks of drug treatment in disease.

Assessment of postural balance in patients with stroke

The Cerebral Vascular Accident (CVA) results in disabilities of paretic limbs, but few studies have investigated the impacts of CVA on perception deficits as well as related functional changes. Motor function alterations caused by CVA, such as the presence of associated reactions, loss of postural control mechanisms, and tone disorders, shift the body's center of gravity, generating a risk of falls. The aim of the present study was to evaluate postural balance changes in patients affected by CVA using the POMA-Brazil Scale (Performance Oriented Mobility Assessment). A cross-sectional study was conducted to assess postural balance changes in patients diagnosed with CVA undergoing rehabilitation at the UNIT Health Center, CEMISE Physiotherapy Service, and Maria Virgínia Leite Franco Rehabilitation Center in Aracaju, Sergipe. The B-POMA subscale consists of 13 tasks (sitting balance, rising from a chair, immediate standing balance, standing balance, eyes closed balance, 360-degree turning balance, resistance to displacement (Nudge Test), neck turning, unipedal stance balance, spinal extension, reaching upward, leaning forward, and sitting), aimed at detecting fall risk factors in elderly individuals with disabilities or chronic illnesses. Descriptive statistics were used for numerical variables, frequency distribution for demographic and clinical variables, and individuals per task, with the application of the chi-square test and the Student's t-test. Among the tasks measured according to the B-POMA subscale, sitting balance was the most frequent qualitative response (97.5%), followed by immediate standing, eyes closed, and leaning forward. Unipedal stance balance was the least common normal task (25%), and 360-degree turning was the most adaptive (62.5%). Balance changes are associated with cerebral vascular accidents in terms of dynamic equilibrium. This study demonstrated that unipedal stance balance was the most affected task, 360-degree turning balance was the most adaptive, and sitting balance was the least affected. There were no significant differences in balance scores based on sex, age, and time of injury.

Effect of Cognitive Load on Anticipatory Postural Adjustment Latency and its Relationship with Pain-Related Dysfunction in Non-specific Chronic Low Back Pain: A Cross-Sectional Study.

This study aimed to investigate the effect of cognitive load on anticipatory postural adjustment (APA) latency in patients with non-specific chronic low back pain (NCLBP) and its relationship with pain-related functional changes. A cross-sectional study was conducted from December 15, 2022 to January 25, 2023. Participants were divided into a healthy control group (n = 29) and an NCLBP group (n = 29). Each group was assigned a single task of rapid arm raising and a dual task of rapid arm raising combined with a cognitive load. The cognitive load task was conducted using visual conflict. The APA latency for bilateral trunk muscles was observed using electromyography. The duration of electromyography recording in each task cycle was 28s. Pain related-functional changes were evaluated using Roland-Morris Disability Questionnaire (RMDQ) before all tasks. The APA latency for the right multifidus was significantly delayed in the NCLBP group [25.38, 95% confidence interval (CI) 13.41-37.35] than in the healthy control group (- 5.80, 95% CI - 19.28 to 7.68) during dual task (p = 0.0416). The APA latency for the right multifidus (25.38, 95% CI 13.41-37.35) and transverse abdominis/internal oblique (29.15, 95% CI 18.81-39.50) were significantly delayed compared with on the left side in the NCLBP group during dual task (- 3.03, 95% CI - 15.18-9.13, p = 0.0220; 3.69, 95% CI - 6.81 to 14.18, p = 0.0363). The latency delay of the right and left multifidus APA in the NCLBP group under the dual-task was positively correlated with RMDQ scores (r = 0.5560, p = 0.0017; r = 0.4010, p = 0.0311). Cognitive load could induce APA delay in the right trunk muscles and co-activation pattern changes in bilateral trunk muscle APA in patients with NCLBP. The APA onset delay in multifidus is positively related to pain-related daily dysfunction. Trial Registration ChiCTR2300068580 (retrospectively registered in February 23, 2023).

Age-related changes in basal forebrain afferent activation in response to food paired stimuli

The basal forebrain contains a phenotypically-diverse assembly of neurons, including those using acetylcholine as their neurotransmitter. This basal forebrain cholinergic system projects to the entire neocortical mantle as well as subcortical limbic structures that include the hippocampus and amygdala. Basal forebrain pathology, including cholinergic dysfunction, is thought to underlie the cognitive impairments associated with several age-related neurodegenerative conditions, including Alzheimer’s disease. Basal forebrain dysfunction may stem, in part, from a failure of normal afferent regulation of cholinergic and other neurons in this area. However, little is understood regarding how aging, alone, affects the functional regulation of basal forebrain afferents in the context of motivated behavior. Here, we used neuronal tract-tracing combined with motivationally salient stimuli in an aged rodent model to examine how aging alters activity in basal forebrain inputs arising from several cortical, limbic and brainstem structures. Young rats showed greater stimulus-associated activation of basal forebrain inputs arising from prelimbic cortex, nucleus accumbens and the ventral tegmental area compared with aged rats. Aged rats also showed increased latency to respond to palatable food presentation compared to young animals. Changes in activation of intrinsic basal forebrain cell populations or afferents were also observed as a function of age or experimental condition. These data further demonstrate that age-related changes in basal forebrain activation and related behavioral and cognitive functions reflect a failure of afferent regulation of this important brain region.

Gut microbiome signatures reflect different subtypes of irritable bowel syndrome

ABSTRACT Irritable bowel syndrome (IBS) is a heterogeneous condition with multifactorial pathogenesis. We studied deeply phenotyped individuals with microbiota sequencing enrolled in the American Gut Project. The IBS subjects were matched by age, gender, body mass index, geography, and dietary patterns with non-IBS controls. A total of 942 subjects with IBS-Diarrhea (IBS-D), IBS-Constipation (IBS-C), unclassified IBS (IBS-U), and 942 non-IBS controls were included. We compared taxonomic and functional composition of gut microbiota based on 16S sequencing data and linked them with clinical characteristics and dietary factors. Subjects with IBS-D or IBS-U but not IBS-C showed significantly reduced bacterial diversity (Shannon; p < .01). Distinct bacterial signatures were associated with different IBS subtypes, and the related functional changes were related to IBS pathogenesis, such as the increased hydrogen sulfide production pathway in IBS-D and the increased palmitoleate biosynthesis pathway in IBS-C. IBS subjects with depression showed lower abundance of Bifidobacterium, Sutterella, Butyricimonas and higher abundance of Proteus than those without depression. The relative abundance of microbial short-chain fatty acid production pathways was significantly lower in IBS patients with depression than those without depression in all three subtypes. Female, younger age in IBS-D, and older age in IBS-C were associated with more severe microbiota dysbiosis, and distinct dietary factors had significant effects on the gut microbiota in different IBS subtypes. Our analysis identified the compositional uniqueness of gut microbiota in different IBS subtypes. Distinct associations of the gut microbiota with depression in IBS provide insights into shared pathways in disease pathogenesis. These findings highlight the importance of personalized gut microbiome modulation approaches in different subtypes for optimal therapeutic effects.

Accelerated amyloid angiopathy and related vascular alterations in a mixed murine model of Alzheimer´s disease and type two diabetes

BackgroundWhile aging is the main risk factor for Alzheimer´s disease (AD), emerging evidence suggests that metabolic alterations such as type 2 diabetes (T2D) are also major contributors. Indeed, several studies have described a close relationship between AD and T2D with clinical evidence showing that both diseases coexist. A hallmark pathological event in AD is amyloid-β (Aβ) deposition in the brain as either amyloid plaques or around leptomeningeal and cortical arterioles, thus constituting cerebral amyloid angiopathy (CAA). CAA is observed in 85–95% of autopsy cases with AD and it contributes to AD pathology by limiting perivascular drainage of Aβ.MethodsTo further explore these alterations when AD and T2D coexist, we have used in vivo multiphoton microscopy to analyze over time the Aβ deposition in the form of plaques and CAA in a relevant model of AD (APPswe/PS1dE9) combined with T2D (db/db). We have simultaneously assessed the effects of high-fat diet-induced prediabetes in AD mice. Since both plaques and CAA are implicated in oxidative-stress mediated vascular damage in the brain, as well as in the activation of matrix metalloproteinases (MMP), we have also analyzed oxidative stress by Amplex Red oxidation, MMP activity by DQ™ Gelatin, and vascular functionality.ResultsWe found that prediabetes accelerates amyloid plaque and CAA deposition, suggesting that initial metabolic alterations may directly affect AD pathology. T2D significantly affects vascular pathology and CAA deposition, which is increased in AD-T2D mice, suggesting that T2D favors vascular accumulation of Aβ. Moreover, T2D synergistically contributes to increase CAA mediated oxidative stress and MMP activation, affecting red blood cell velocity.ConclusionsOur data support the cross-talk between metabolic disease and Aβ deposition that affects vascular integrity, ultimately contributing to AD pathology and related functional changes in the brain microvasculature.

The Effect of Limosilactobacillus reuteri on Social Behavior Is Independent of the Adaptive Immune System.

Gut microbes can modulate almost all aspects of host physiology throughout life. As a result, specific microbial interventions are attracting considerable attention as potential therapeutic strategies for treating a variety of conditions. Nonetheless, little is known about the mechanisms through which many of these microbes work. Recently, we and others have found that the commensal bacterium Limosilactobacillus reuteri (formerly Lactobacillus reuteri) reverses social deficits in several mouse models (genetic, environmental, and idiopathic) for neurodevelopmental disorders in a vagus nerve-, oxytocin-, and biopterin-dependent manner. Given that gut microbes can signal to the brain through the immune system and L. reuteri promotes wound healing via the adaptive immune response, we sought to determine whether the prosocial effect mediated by L. reuteri also depends on adaptive immunity. Here, we found that the effects of L. reuteri on social behavior and related changes in synaptic function are independent of the mature adaptive immune system. Interestingly, these findings indicate that the same microbe (L. reuteri) can affect different host phenotypes through distinct mechanisms. IMPORTANCE Because preclinical animal studies support the idea that gut microbes could represent novel therapeutics for brain disorders, it is essential to fully understand the mechanisms by which gut microbes affect their host's physiology. Previously, we discovered that treatment with Limosilactobacillus reuteri selectively improves social behavior in different mouse models for autism spectrum disorder through the vagus nerve, oxytocin reward signaling in the brain, and biopterin metabolites (BH4) in the gut. However, given that (i) the immune system remains a key pathway for host-microbe interactions and that (ii) L. reuteri has been shown to facilitate wound healing through the adaptive immune system, we examined here whether the prosocial effects of L. reuteri require immune signaling. Unexpectedly, we found that the mature adaptive immune system (i.e., conventional B and T cells) is not required for L. reuteri to reverse social deficits and related changes in synaptic function. Overall, these findings add new insight into the mechanism through which L. reuteri modulates brain function and behavior. More importantly, they highlight that a given bacterial species can modulate different phenotypes (e.g., wound healing versus social behavior) through separate mechanisms.

Functional changes in the auditory cortex and associated regions caused by different acoustic stimuli in patients with presbycusis and tinnitus.

Presbycusis and tinnitus are the two most common hearing related pathologies. Although both of these conditions presumably originate in the inner ear, there are several reports concerning their central components. Interestingly, the onset of presbycusis coincides with the highest occurrence of tinnitus. The aim of this study was to identify age, hearing loss, and tinnitus related functional changes, within the auditory system and its associated structures. Seventy-eight participants were selected for the study based on their age, hearing, and tinnitus, and they were divided into six groups: young controls (Y-NH-NT), subjects with mild presbycusis (O-NH-NT) or expressed presbycusis (O-HL-NT), young subjects with tinnitus (Y-NH-T), subjects with mild presbycusis and tinnitus (O-NH-T), and subjects with expressed presbycusis and tinnitus (O-HL-T). An MRI functional study was performed with a 3T MRI system, using an event related design (different types of acoustic and visual stimulations and their combinations). The amount of activation of the auditory cortices (ACs) was dependent on the complexity of the stimuli; higher complexity resulted in a larger area of the activated cortex. Auditory stimulation produced a slightly greater activation in the elderly, with a negative effect of hearing loss (lower activation). The congruent audiovisual stimulation led to an increased activity within the default mode network, whereas incongruent stimulation led to increased activation of the visual cortex. The presence of tinnitus increased activation of the AC, specifically in the aged population, with a slight prevalence in the left AC. The occurrence of tinnitus was accompanied by increased activity within the insula and hippocampus bilaterally. Overall, we can conclude that expressed presbycusis leads to a lower activation of the AC, compared to the elderly with normal hearing; aging itself leads to increased activity in the right AC. The complexity of acoustic stimuli plays a major role in the activation of the AC, its support by visual stimulation leads to minimal changes within the AC. Tinnitus causes changes in the activity of the limbic system, as well as in the auditory AC, where it is bound to the left hemisphere.

Characterization of Early Stage Parkinson's Disease From Resting-State fMRI Data Using a Long Short-Term Memory Network.

Parkinson's disease (PD) is a common and complex neurodegenerative disorder with five stages on the Hoehn and Yahr scaling. Characterizing brain function alterations with progression of early stage disease would support accurate disease staging, development of new therapies, and objective monitoring of disease progression or treatment response. Functional magnetic resonance imaging (fMRI) is a promising tool in revealing functional connectivity (FC) differences and developing biomarkers in PD. While fMRI and FC data have been utilized for diagnosis of PD through application of machine learning approaches such as support vector machine and logistic regression, the characterization of FC changes in early-stage PD has not been investigated. Given the complexity and non-linearity of fMRI data, we propose the use of a long short-term memory (LSTM) network to distinguish the early stages of PD and understand related functional brain changes. The study included 84 subjects (56 in stage 2 and 28 in stage 1) from the Parkinson's Progression Markers Initiative (PPMI), the largest-available public PD dataset. Under a repeated 10-fold stratified cross-validation, the LSTM model reached an accuracy of 71.63%, 13.52% higher than the best traditional machine learning method and 11.56% higher than a CNN model, indicating significantly better robustness and accuracy compared with other machine learning classifiers. Finally, we used the learned LSTM model weights to select the top brain regions that contributed to model prediction and performed FC analyses to characterize functional changes with disease stage and motor impairment to gain better insight into the brain mechanisms of PD.