Noninvasive brain stimulations modulated brain modular interactions to ameliorate working memory in community-dwelling older adults.

Non-invasive brain stimulations have drawn attention in remediating memory decline in older adults. However, it remains unclear regarding the cognitive and neural mechanisms underpinning the neurostimulation effects on memory rehabilitation. We evaluated the intervention effects of 2-weeks of neurostimulations (high-definition transcranial direct current stimulation, HD-tDCS, and electroacupuncture, EA versus controls, CN) on brain activities and functional connectivity during a working memory task in normally cognitive older adults (age 60+, n = 60). Results showed that HD-tDCS and EA significantly improved the cognitive performance, potentiated the brain activities of overlapping neural substrates (i.e. hippocampus, dlPFC, and lingual gyrus) associated with explicit and implicit memory, and modulated the nodal topological properties and brain modular interactions manifesting as increased intramodular connection of the limbic-system dominated network, decreased intramodular connection of default-mode-like network, as well as stronger intermodular connection between frontal-dominated network and limbic-system-dominated network. Predictive model further identified the neuro-behavioral association between modular connections and working memory. This preliminary study provides evidence that noninvasive neurostimulations can improve older adults' working memory through potentiating the brain activity of working memory-related areas and mediating the modular interactions of related brain networks. These findings have important implication for remediating older adults' working memory and cognitive declines.

Abnormal brain activities of cognitive processes in cerebral small vessel disease: A systematic review of task fMRI studies.

Cerebral small vessel disease (CSVD) is characterized by widespread functional changes in the brain, as evident from abnormal brain activations during cognitive tasks. However, the existing findings in this area are not yet conclusive. We systematically reviewed 25 studies reporting task-related fMRI in five cognitive domains in CSVD, namely executive function, working memory, processing speed, motor, and affective processing. The findings highlighted: (1) CSVD affects cognitive processes in a domain-specific manner; (2) Compensatory and regulatory effects were observed simultaneously in CSVD, which may reflect the interplay between the negative impact of brain lesion and the positive impact of cognitive reserve. Combined with behavioral and functional findings in CSVD, we proposed an integrated model to illustrate the relationship between altered activations and behavioral performance in different stages of CSVD: functional brain changes may precede and be more sensitive than behavioral impairments in the early pre-symptomatic stage; Meanwhile, compensatory and regulatory mechanisms often occur in the early stages of the disease, while dysfunction/decompensation and dysregulation often occur in the late stages. Overall, abnormal hyper-/hypo-activations are crucial for understanding the mechanisms of small vessel lesion-induced behavioral dysfunction, identifying potential neuromarker and developing interventions to mitigate the impact of CSVD on cognitive function.

Cognitive decline is associated with frequency-specific resting state functional changes in normal aging.

Resting state low-frequency brain activity may aid in our understanding of the mechanisms of aging-related cognitive decline. Our purpose was to explore the characteristics of the amplitude of low-frequency fluctuations (ALFF) in different frequency bands of fMRI to better understand cognitive aging. Thirty-seven cognitively normal older individuals underwent a battery of neuropsychological tests and MRI scans at baseline and four years later. ALFF from five different frequency bands (typical band, slow-5, slow-4, slow-3, and slow-2) were calculated and analyzed. A two-way ANOVA was used to explore the interaction effects in voxel-wise whole brain ALFF of the time and frequency bands. Paired-sample t-test was used to explore within-group changes over four years. Partial correlation analysis was performed to assess associations between the altered ALFF and cognitive function. Significant interaction effects of time × frequency were distributed over inferior frontal gyrus, superior frontal gyrus, right rolandic operculum, left thalamus, and right putamen. Significant ALFF reductions in all five frequency bands were mainly found in the right hemisphere and the posterior cerebellum; whereas localization of the significantly increased ALFF were mainly found in the cerebellum at typical band, slow-5 and slow-4 bands, and left hemisphere and the cerebellum at slow-3, slow-2 bands. In addition, ALFF changes showed frequency-specific correlations with changes in cognition. These results suggest that changes of local brain activity in cognitively normal aging should be investigated in multiple frequency bands. The association between ALFF changes and cognitive function can potentially aid better understanding of the mechanisms underlying normal cognitive aging.

Deciphering Age Differences in Experience-Based Decision-Making: The Role of Sleep.

OBJECTIVE: Recent studies have demonstrated that sleep not only facilitates memory consolidation but also benefits more complex cognitive skills such as decision-making in young adults. Older adults use different decision strategies compared with young adults, which leaves the role of sleep in older adults' decision-making unclear. We investigated the age-by-sleep effect on decision-making. METHODS: We recruited 67 young adults (ages 18 to 29 years) and 66 older adults (ages 60 to 79 years) and randomly assigned them into the "sleep" or "wake" study condition. They were given a modified Iowa gambling task to perform before and after a 12-hour interval with sleep or wakefulness. RESULTS: Using the typical model-free analysis, we found that young adults' between-session performance improved greater than that of older adults regardless of the sleep/wake condition. Furthermore, older adults with longer total sleep time showed a greater improvement in the selection of one "good" deck. To further examine the sleep effect on age-related differences in cognitive processes underlying decision-making, we conducted computational modelling. This more fine-grained analysis revealed that sleep improved feedback sensitivity for both young and older adults while it increased loss aversion for older adults but not for young adults. CONCLUSION: These findings indicate that sleep promotes learning-based decision-making performance via facilitating value representation, and such modulation is distinct in young compared to older adults.

The influence of hypoglycemia and hyperglycemia on the adverse outcome of COVID-19 combined with diabetes mellitus: A protocol for systematic review and meta-analysis.

BACKGROUND: COVID-19 has become a global epidemic, causing huge loss of life and property. Diabetes will affect the prognosis of COVID-19 patients in many ways. Both hyperglycemia and hypoglycemia can affect oxidative stress and lead to the release of inflammatory mediators, leading to multiple organ damage and chronic inflammation. Here, we want to know whether hyperglycemia or hypoglycemia will adversely affect patients with diabetes and COVID-19 comorbidities. This has very important practical significance for the control of blood glucose in the treatment of diabetes combined with SARS-COV-2 infection. METHODS: We will search electronic databases including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang database using keywords related to COVID-19, diabetes mellitus, hyperglycemia and hypoglycemia. We will manually search gray literature, such as conference proceedings and academic degree dissertations, and trial registries. Two independent reviewers will screen studies, extract data, and evaluate risk of bias. Data analysis will be conducted using the Review Manager software version 5.3.5 and STATA4.0 software for Mac. The main outcome was the mortality of COVID-19 which was included in meta-analysis and subgroup analysis. The bias of the study was evaluated independently by NOS scale, and published by funnel chart. The sensitivity was analyzed row by row. RESULTS: This study will provide a high-quality synthesis of hyperglycemia and hypoglycemia in patients with COVID-19 combined with diabetes mellitus. To provide evidence for clinical treatment of diabetes mellitus combined with COVID-19. And the results will be published at a peer-reviewed journal.INPLASY registration number INPLASY 202080096.

Electroacupuncture Modulates Resting-State Functional Connectivity in the Default Mode Network for Healthy Older Adults.

Aging involves cognitive decline and prominent alterations in brain activity. Electroacupuncture (EA), a traditional Chinese medicine approach, is demonstrated to be effective in improving cognitive function of older adults. However, the specific neural mechanism underlying this modulation effect remains unclear. In this study, we used functional magnetic resonance imaging (fMRI) to investigate whether EA could improve cognitive performance of community-dwelling older adults and whether these potential improvements are associated with the EA-induced brain functional connectivity alterations. Thirty healthy older adults were recruited and randomly assigned to the EA group and the control group. Behaviorally, we observed an EA-induced improvement in cognitive performance of older adults in the Montreal Cognitive Assessment. On a neural perspective, the EA intervention significantly increased the functional connectivity within the default mode network. Moreover, we found a positive association between the improvement in delayed memory performance and the alterations in the ventral medial prefrontal cortex-hippocampal formation connectivity in the EA group. This study extends previous findings by showing that healthy older adults exhibit neural plasticity manifested as increased functional connectivity after EA sessions, which could induce therapeutic effects in the treatment of neurodegenerative diseases.

High definition-transcranial direct current stimulation changes older adults' subjective sleep and corresponding resting-state functional connectivity.

With advanced age, older adults show functional deterioration in sleep. Transcranial direct current stimulation (tDCS), a noninvasive brain stimulation, modulates individuals' behavioral performance in various cognitive domains. However, the modulation effect and neural mechanisms of tDCS on sleep, especially for the elderly population are not clear. Here, we aimed to investigate whether high-definition transcranial direct current stimulation (HD-tDCS) could modulate community-dwelling older adults' subjective sleep and whether these potential improvements are associated with the large-scale brain activity alterations recorded by functional magnetic resonance imaging. Thirty-one older adults were randomly allocated to the HD-tDCS group and the control group. HD-tDCS was applied for 25 min at 1.5 mA per day for two weeks. The anode electrode was placed over the left dorsolateral prefrontal cortex, surrounded by 4 cathodes at 7 cm radius. All participants completed sleep neuropsychological assessments and fMRI scans individually before and after intervention. Behaviorally, we observed a HD-tDCS-induced enhancement of older adults' sleep duration. On the aspect of the corresponding neural alterations, we observed that HD-tDCS decreased the functional connectivity between the default mode network (DMN) and subcortical network. More importantly, the decoupling connectivity of the DMN-subcortical network was correlated with the improvements of subjective sleep in the HD-tDCS group. Our findings add novel behavioral and neural evidences about tDCS-induced sleep improvement in community-dwelling older adults. With further development, tDCS may be used as an alternative treatment for sleep disorders and alleviate the dysfunction of brain networks induced by aging.

Sleep-related brain atrophy and disrupted functional connectivity in older adults.

Aging associates with sleep dysfunction as well as brain alterations. However, the association between age-related brain alterations and their subjective sleep changes is less understood. To address this issue, we recorded T1 weighted structural and resting-state functional magnetic resonance imaging from both young (n = 62) and older adults (n = 108). In addition, all participants completed a battery of psychometric tests, including the Pittsburg Sleep Quality Index. We found that the age-related atrophy of cerebral gray matter, hippocampal and thalamic volume were associated with subjective sleep decline, and the atrophy of cerebral gray matter mediated the age effect on sleep. In addition, older adults exhibited decreased functional connectivity within the medial temporal lobe subsystem than their young counterparts. Moreover, there is a significant positive association between sleep and functional connectivity in young but not in older adults. In light of our findings, we suggest a neuropathological model in which age-related brain alterations may partially explain the well-documented declines in sleep with aging.

Modulation of Brain Activity with Noninvasive Transcranial Direct Current Stimulation (tDCS): Clinical Applications and Safety Concerns.

Transcranial direct current stimulation (tDCS) is a widely-used tool to induce neuroplasticity and modulate cortical function by applying weak direct current over the scalp. In this review, we first introduce the underlying mechanism of action, the brief history from discovery to clinical scientific research, electrode positioning and montages, and parameter setup of tDCS. Then, we review tDCS application in clinical samples including people with drug addiction, major depression disorder, Alzheimer's disease, as well as in children. This review covers the typical characteristics and the underlying neural mechanisms of tDCS treatment in such studies. This is followed by a discussion of safety, especially when the current intensity is increased or the stimulation duration is prolonged. Given such concerns, we provide detailed suggestions regarding safety procedures for tDCS operation. Lastly, future research directions are discussed. They include foci on the development of multi-tech combination with tDCS such as with TMS and fMRI; long-term behavioral and morphological changes; possible applications in other research domains, and more animal research to deepen the understanding of the biological and physiological mechanisms of tDCS stimulation.