New resting-state fMRI related studies at PubMed

Dynamics of fMRI patterns reflect sub-second activation sequences and reveal replay in human visual cortex

Sat, 03/20/2021 - 10:00

Nat Commun. 2021 Mar 19;12(1):1795. doi: 10.1038/s41467-021-21970-2.


Neural computations are often fast and anatomically localized. Yet, investigating such computations in humans is challenging because non-invasive methods have either high temporal or spatial resolution, but not both. Of particular relevance, fast neural replay is known to occur throughout the brain in a coordinated fashion about which little is known. We develop a multivariate analysis method for functional magnetic resonance imaging that makes it possible to study sequentially activated neural patterns separated by less than 100 ms with precise spatial resolution. Human participants viewed five images individually and sequentially with speeds up to 32 ms between items. Probabilistic pattern classifiers were trained on activation patterns in visual and ventrotemporal cortex during individual image trials. Applied to sequence trials, probabilistic classifier time courses allow the detection of neural representations and their order. Order detection remains possible at speeds up to 32 ms between items (plus 100 ms per item). The frequency spectrum of the sequentiality metric distinguishes between sub- versus supra-second sequences. Importantly, applied to resting-state data our method reveals fast replay of task-related stimuli in visual cortex. This indicates that non-hippocampal replay occurs even after tasks without memory requirements and shows that our method can be used to detect such spontaneously occurring replay.

PMID:33741933 | DOI:10.1038/s41467-021-21970-2

Brain/MINDS beyond human brain MRI project: A protocol for multi-level harmonization across brain disorders throughout the lifespan

Sat, 03/20/2021 - 10:00

Neuroimage Clin. 2021 Mar 8:102600. doi: 10.1016/j.nicl.2021.102600. Online ahead of print.


Psychiatric and neurological disorders are afflictions of the brain that can affect individuals throughout their lifespan. Many brain magnetic resonance imaging (MRI) studies have been conducted; however, imaging-based biomarkers are not yet well established for diagnostic and therapeutic use. This article describes an outline of the planned study, the Brain/MINDS Beyond human brain MRI project (BMB-HBM, FY2018 ~ FY2023), which aims to establish clinically-relevant imaging biomarkers with multi-site harmonization by collecting data from healthy traveling subjects (TS) at 13 research sites. Collection of data in psychiatric and neurological disorders across the lifespan is also scheduled at 13 sites, whereas designing measurement procedures, developing and analyzing neuroimaging protocols, and databasing are done at three research sites. A high-quality scanning protocol, Harmonization Protocol (HARP), was established for five high-quality 3 T scanners to obtain multimodal brain images including T1 and T2-weighted, resting-state and task functional and diffusion-weighted MRI. Data are preprocessed and analyzed using approaches developed by the Human Connectome Project. Preliminary results in 30 TS demonstrated cortical thickness, myelin, functional connectivity measures are comparable across 5 scanners, suggesting sensitivity to subject-specific connectome. A total of 75 TS and more than two thousand patients with various psychiatric and neurological disorders are scheduled to participate in the project, allowing a mixed model statistical harmonization. The HARP protocols are publicly available online, and all the imaging, demographic and clinical information, harmonizing database will also be made available by 2024. To the best of our knowledge, this is the first project to implement a prospective, multi-level harmonization protocol with multi-site TS data. It explores intractable brain disorders across the lifespan and may help to identify the disease-specific pathophysiology and imaging biomarkers for clinical practice.

PMID:33741307 | DOI:10.1016/j.nicl.2021.102600

Functional and structural brain connectivity in congenital deafness

Fri, 03/19/2021 - 10:00

Brain Struct Funct. 2021 Mar 19. doi: 10.1007/s00429-021-02243-6. Online ahead of print.


Several studies have been carried out to verify neural plasticity and the language process in deaf individuals. However, further investigations regarding the intrinsic brain organization on functional and structural neural networks derived from congenital deafness are still an open question. The objective of this study was to investigate the main differences in brain organization manifested in congenitally deaf individuals, concerning the resting-state functional patterns, and white matter structuring. Functional and diffusion magnetic resonance imaging modalities were acquired from 18 congenitally deaf individuals and 18 age-sex-matched hearing controls. Compared to the hearing group, the deaf individuals presented higher functional connectivity among the posterior cingulate cortex node of the default mode network with visual and motor networks, lower functional connectivity between salience networks, language networks, and prominence of functional connectivity changes in the right hemisphere, mostly in the frontoparietal and temporal lobes. In terms of structural connectivity, we found changes mainly in the occipital and parietal lobes, involving both classical sign language support regions as well as concentrated networks for focus activity, attention, and cognitive filtering. Our findings demonstrated that the congenital deaf individuals who learned sign language developed significant brain functional and structural reorganization, which provides prominent support for large-scale brain networks associated with attention decision-making, environmental monitoring based on the movement of objects, and on the motor and visual controls.

PMID:33740108 | DOI:10.1007/s00429-021-02243-6

Large-scale functional network connectivity mediate the associations of gut microbiota with sleep quality and executive functions

Fri, 03/19/2021 - 10:00

Hum Brain Mapp. 2021 Mar 19. doi: 10.1002/hbm.25419. Online ahead of print.


Network neuroscience has broadly conceptualized the functions of the brain as complex communication within and between large-scale neural networks. Nevertheless, whether and how the gut microbiota influence functional network connectivity that in turn impact human behaviors has yet to be determined. We collected fecal samples from 157 healthy young adults and used 16S sequencing to assess gut microbial diversity and enterotypes. Large-scale inter- and intranetwork functional connectivity was measured using a combination of resting-state functional MRI data and independent component analysis. Sleep quality and core executive functions were also evaluated. Then, we tested for potential associations between gut microbiota, functional network connectivity and behaviors. We found significant associations of gut microbial diversity with internetwork functional connectivity between the executive control, default mode and sensorimotor systems, and intranetwork connectivity of the executive control system. Moreover, some internetwork functional connectivity mediated the relations of microbial diversity with sleep quality, working memory, and attention. In addition, there was a significant effect of enterotypes on intranetwork connectivity of the executive control system, which could mediate the link between enterotypes and executive function. Our findings not only may expand existing biological knowledge of the gut microbiota-brain-behavior relationships from the perspective of large-scale functional network organization, but also may ultimately inform a translational conceptualization of how to improve sleep quality and executive functions through the regulation of gut microbiota.

PMID:33739571 | DOI:10.1002/hbm.25419

Affective Neural Mechanisms of a Parenting-Focused Mindfulness Intervention

Fri, 03/19/2021 - 10:00

Mindfulness (N Y). 2021 Feb;12(2):392-404. doi: 10.1007/s12671-019-01118-6. Epub 2019 Feb 16.


OBJECTIVES: Behavioral evidence suggests that parenting-focused mindfulness interventions can improve parenting practices and enhance family wellbeing, potentially operating through altered emotional processing in parents. However, the mechanisms through which parent mindfulness interventions achieve their positive benefits have not yet been empirically tested, knowledge which is key to refine and maximize intervention effects. Thus, as part of a randomized controlled trial, the present study examined the affective mechanisms of an 8-week parenting-focused mindfulness intervention, the Parenting Mindfully (PM) intervention, versus a minimal-intervention parent education control.

METHODS: Twenty highly stressed mothers of adolescents completed pre- and post-intervention behavioral and fMRI sessions, in which mothers completed a parent-adolescent conflict interaction, fMRI emotion task, and fMRI resting state scan. Mothers reported on their mindful parenting, and maternal emotional reactivity to the parent-adolescent conflict task was assessed via observed emotion expression, self-reported negative emotion, and salivary cortisol reactivity.

RESULTS: Results indicated that the PM intervention increased brain responsivity in left posterior insula in response to negative affective stimuli, and altered resting state functional connectivity in regions involved in self-reference, behavioral regulation, and social-emotional processing. Changes in mothers' brain function and connectivity were associated with increased mindful parenting and decreased emotional reactivity to the parent-adolescent conflict task.

CONCLUSIONS: Findings suggest that mindfulness-based changes in maternal emotional awareness at the neurobiological level are associated with decreased emotional reactivity in parenting interactions, illuminating potential neurobiological targets for future parent-focused intervention.

PMID:33737986 | PMC:PMC7962669 | DOI:10.1007/s12671-019-01118-6

Flexible annotation atlas of the mouse brain: combining and dividing brain structures of the Allen Brain Atlas while maintaining anatomical hierarchy

Fri, 03/19/2021 - 10:00

Sci Rep. 2021 Mar 18;11(1):6234. doi: 10.1038/s41598-021-85807-0.


A brain atlas is necessary for analyzing structure and function in neuroimaging research. Although various annotation volumes (AVs) for the mouse brain have been proposed, it is common in magnetic resonance imaging (MRI) of the mouse brain that regions-of-interest (ROIs) for brain structures (nodes) are created arbitrarily according to each researcher's necessity, leading to inconsistent ROIs among studies. One reason for such a situation is the fact that earlier AVs were fixed, i.e. combination and division of nodes were not implemented. This report presents a pipeline for constructing a flexible annotation atlas (FAA) of the mouse brain by leveraging public resources of the Allen Institute for Brain Science on brain structure, gene expression, and axonal projection. A mere two-step procedure with user-specified, text-based information and Python codes constructs FAA with nodes which can be combined or divided objectively while maintaining anatomical hierarchy of brain structures. Four FAAs with total node count of 4, 101, 866, and 1381 were demonstrated. Unique characteristics of FAA realized analysis of resting-state functional connectivity (FC) across the anatomical hierarchy and among cortical layers, which were thin but large brain structures. FAA can improve the consistency of whole brain ROI definition among laboratories by fulfilling various requests from researchers with its flexibility and reproducibility.

PMID:33737651 | DOI:10.1038/s41598-021-85807-0

Correlation of abnormalities in resting state fMRI with executive functioning in chronic schizophrenia

Thu, 03/18/2021 - 10:00

Psychiatry Res. 2021 Mar 8;299:113862. doi: 10.1016/j.psychres.2021.113862. Online ahead of print.


BACKGROUND: Although previous studies have consistently demonstrated that neurocognitive and social cognitive impairments are commonly observed in schizophrenia, the neural substrates of deficits of cognitive function remain unclear, especially for the chronic schizophrenia. There has been little resting-state functional magnetic resonance imaging (rs-fMRI) study of cognitive function in chronic schizophrenia. In this study we aimed to investigate the changes of rs-fMRI signals with regional homogeneity (ReHo), and explore the correlations between abnormal regional activity and cognitive function in chronic schizophrenia.

METHODS: Altogether 76 subjects, 37 patients with chronic schizophrenia and 39 normal controls matched approximately for age, gender and education level were enrolled. All subjects were evaluated psychotic symptoms by Positive and Negative Syndrome Scale (PANSS) and cognitive function by Wisconsin Card Sorting Test (WCST). Conventional MRI and rs-fMRI were performed in all subjects. ReHo was calculated to measure the temporal synchronization of a given voxel and its neighboring voxels based on Kendall coefficient of concordance (KCC) in the rs-fMRI.

RESULTS: For the numbers of achieved categories, percentage of conceptual level response in the scores of WCST, the patient group was significantly lower than the control group (p<0.05). For the total errors, perseverative errors, non-perseverative errors, the patient group was significantly higher than the control group (p<0.05). Significant differences in ReHo were found in 11 regions (included five activated and five with decreased activity in the cerebrum and one with decreased activity in the cerebellum) in the chronic schizophrenia patients when compared with the normal controls. The ReHo map clusters that were significantly different between the two groups showed no significant correlation with clinical symptoms. Correlation of the whole brain with subscores of PANSS-T, PANSS-P, PANSS-N and WCST were significantly found in some regions.

CONCLUSIONS: The study identified five increased and six decreased spontaneous synchrony in the cerebrum and cerebellum in chronic schizophrenia patients compared to the normal matched controls, which were associated with positive, negative symptoms, and deficits of executive functioning.

PMID:33735738 | DOI:10.1016/j.psychres.2021.113862

From local to global and back: An exploratory study on cross-scale desynchronization in schizophrenia and its relation to thought disorders

Thu, 03/18/2021 - 10:00

Schizophr Res. 2021 Mar 15;231:10-12. doi: 10.1016/j.schres.2021.02.021. Online ahead of print.


PMID:33735688 | DOI:10.1016/j.schres.2021.02.021

Resting-state functional nuclear magnetic resonance imaging in patients with bipolar disorder: beyond euthymia

Thu, 03/18/2021 - 10:00

Rev Colomb Psiquiatr. 2020 Dec 11:S0034-7450(20)30088-3. doi: 10.1016/j.rcp.2020.10.011. Online ahead of print.


INTRODUCTION: Functional nuclear magnetic resonance imaging in the resting state (R-fMRI) allows the identification of complete functional connectivity networks and the possible neuronal correlations of psychiatric disorders. The literature on R-fMRI and bipolar disorder (BD) will be reviewed, emphasising the findings in the phases of mania, hypomania and depression.

METHODS: It is a narrative review of the literature in which articles were searched in PubMed and Embase, with the key words in English "bipolar disorder" AND "resting state", without limit on the date of publication.

RESULTS: The studies of BD patients in the mania and hypomania phases who underwent R-fMRI show concordant results in terms of decreased functional cerebral connectivity between the amygdala and some cortical regions, which indicates that this functional connection would have some implication in the normal affect regulation. Patients in the depressive phase show a decrease in functional brain connectivity, but as there are several anatomical structures involved and neural networks reported in the studies, it is not possible to compare them.

CONCLUSIONS: There is a decrease in functional connectivity in patients with BD, but current evidence does not allow establishing specific changes in specific functional brain connectivity networks. However, there are already some findings that show correlation with the patients' symptoms.

PMID:33735024 | DOI:10.1016/j.rcp.2020.10.011

Mapping default mode connectivity alterations following a single season of subconcussive impact exposure in youth football

Thu, 03/18/2021 - 10:00

Hum Brain Mapp. 2021 Mar 18. doi: 10.1002/hbm.25384. Online ahead of print.


Repetitive head impact (RHI) exposure in collision sports may contribute to adverse neurological outcomes in former players. In contrast to a concussion, or mild traumatic brain injury, "subconcussive" RHIs represent a more frequent and asymptomatic form of exposure. The neural network-level signatures characterizing subconcussive RHIs in youth collision-sport cohorts such as American Football are not known. Here, we used resting-state functional MRI to examine default mode network (DMN) functional connectivity (FC) following a single football season in youth players (n = 50, ages 8-14) without concussion. Football players demonstrated reduced FC across widespread DMN regions compared with non-collision sport controls at postseason but not preseason. In a subsample from the original cohort (n = 17), players revealed a negative change in FC between preseason and postseason and a positive and compensatory change in FC during the offseason across the majority of DMN regions. Lastly, significant FC changes, including between preseason and postseason and between in- and off-season, were specific to players at the upper end of the head impact frequency distribution. These findings represent initial evidence of network-level FC abnormalities following repetitive, non-concussive RHIs in youth football. Furthermore, the number of subconcussive RHIs proved to be a key factor influencing DMN FC.

PMID:33734521 | DOI:10.1002/hbm.25384

The Developing Human Connectome Project: typical and disrupted perinatal functional connectivity

Thu, 03/18/2021 - 10:00

Brain. 2021 Mar 17:awab118. doi: 10.1093/brain/awab118. Online ahead of print.


The Developing Human Connectome Project (dHCP) is an Open Science project which provides the first large sample of neonatal functional MRI (fMRI) data with high temporal and spatial resolution. This data enables mapping of intrinsic functional connectivity between spatially distributed brain regions under normal and adverse perinatal circumstances, offering a framework to study the ontogeny of large-scale brain organisation in humans. Here, we characterise in unprecedented detail the maturation and integrity of resting-state networks (RSNs) at term-equivalent age in 337 infants (including 65 born preterm). First, we applied group independent component analysis (ICA) to define 11 RSNs in term-born infants scanned at 43.5-44.5 weeks postmenstrual age (PMA). Adult-like topography was observed in RSNs encompassing primary sensorimotor, visual and auditory cortices. Among six higher-order, association RSNs, analogues of the adult networks for language and ocular control were identified, but a complete default mode network precursor was not. Next, we regressed the subject-level datasets from an independent cohort of infants scanned at 37-43.5 weeks PMA against the group-level RSNs to test for the effects of age, sex and preterm birth. Brain mapping in term-born infants revealed areas of positive association with age across four of six association RSNs, indicating active maturation in functional connectivity from 37 to 43.5 weeks PMA. Female infants showed increased connectivity in inferotemporal regions of the visual association network. Preterm birth was associated with striking impairments of functional connectivity across all RSNs in a dose-dependent manner; conversely, connectivity of the superior parietal lobules within the lateral motor network was abnormally increased in preterm infants, suggesting a possible mechanism for specific difficulties such as developmental coordination disorder which occur frequently in preterm children. Overall, we find a robust, modular, symmetrical functional brain organisation at normal term age. A complete set of adult-equivalent primary RSNs is already instated, alongside emerging connectivity in immature association RSNs, consistent with a primary-to-higher-order ontogenetic sequence of brain development. The early developmental disruption imposed by preterm birth is associated with extensive alterations in functional connectivity.

PMID:33734321 | DOI:10.1093/brain/awab118

Association of Olfactory Training With Neural Connectivity in Adults With Postviral Olfactory Dysfunction

Thu, 03/18/2021 - 10:00

JAMA Otolaryngol Head Neck Surg. 2021 Mar 18. doi: 10.1001/jamaoto.2021.0086. Online ahead of print.


IMPORTANCE: Viral upper respiratory tract infections are a major cause of olfactory loss. Olfactory training (OT) is a promising intervention for smell restoration; however, a mechanistic understanding of the changes in neural plasticity induced by OT is absent.

OBJECTIVE: To evaluate functional brain connectivity in adults with postviral olfactory dysfunction (PVOD) before and after OT using resting-state functional magnetic resonance imaging.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study, conducted from September 1, 2017, to November 30, 2019, recruited adults with clinically diagnosed or self-reported PVOD of 3 months or longer. Baseline olfaction was measured using the University of Pennsylvania Smell Identification Test (UPSIT) and the Sniffin' Sticks test. Analysis was performed between December 1, 2020, and July 1, 2020.

INTERVENTIONS: Participants completed 12 weeks of OT using 4 essential oils: rose, eucalyptus, lemon, and clove. The resting-state functional magnetic resonance imaging measurements were obtained before and after intervention.

MAIN OUTCOME AND MEASURES: The primary outcome measure was the change in functional brain connectivity before and after OT. Secondary outcome measures included changes in UPSIT and Sniffin' Sticks test scores, as well as patient-reported changes in treatment response as measured by subjective changes in smell and quality-of-life measures.

RESULTS: A total of 16 participants with PVOD (11 female [69%] and 14 White [88%]; mean [SD] age, 60.0 [10.5] years; median duration of smell loss, 12 months [range, 3-240 months]) and 20 control participants (15 [75%] female; 17 [85%] White; mean [SD] age, 55.0 [9.2] years; median UPSIT score, 37 [range, 34-39]) completed the study. At baseline, participants had increased connectivity within the visual cortex when compared with normosmic control participants, a connection that subsequently decreased after OT. Furthermore, 4 other network connectivity values were observed to change after OT, including an increase in connectivity between the left parietal occipital junction, a region of interest associated with olfactory processing, and the cerebellum.

CONCLUSIONS AND RELEVANCE: The use of OT is associated with connectivity changes within the visual cortex. This case-control cohort study suggests that there is a visual connection to smell that has not been previously explored with OT and that further studies examining the efficacy of a bimodal visual and OT program are needed.

PMID:33734298 | DOI:10.1001/jamaoto.2021.0086

Sex differences in functional network dynamics observed using coactivation pattern analysis

Thu, 03/18/2021 - 10:00

Cogn Neurosci. 2021 Mar 18:1-10. doi: 10.1080/17588928.2021.1880383. Online ahead of print.


Sex differences in the organization of large-scale resting-state brain networks have been identified using traditional static measures, which average functional connectivity over extended time periods. In contrast, emerging dynamic measures have the potential to define sex differences in network changes over time, providing additional understanding of neurobiological sex differences. To meet this goal, we used a Coactivation Pattern Analysis (CAP) using resting-state functional magnetic resonance imaging data from 181 males and 181 females from the Human Connectome Project. Significant main effects of sex were observed across two independent imaging sessions. Relative to males, females spent more total time in two transient network states (TNSs) spatially overlapping with the dorsal attention network and occipital/sensory-motor network. Greater time spent in these TNSs was related to females making more frequent transitions into these TNSs compared to males. In contrast, males spent more total time in TNSs spatially overlapping with the salience network, which was related to males staying for longer periods once entering these TNSs compared to females. State-to-state transitions also significantly differed between sexes: females transitioned more frequently from default mode network (DMN) states to the dorsal attention network state, whereas males transitioned more frequently from DMN states to salience network states. Results show that males and females spend differing amounts of time at rest in two distinct attention-related networks and show sex-specific transition patterns from DMN states into these attention-related networks. This work lays the groundwork for future investigations into the cognitive and behavioral implications of these sex-specific network dynamics.

PMID:33734028 | DOI:10.1080/17588928.2021.1880383

Pain stickiness in pediatric complex regional pain syndrome: A role for the nucleus accumbens

Thu, 03/18/2021 - 10:00

Neurobiol Pain. 2021 Feb 19;9:100062. doi: 10.1016/j.ynpai.2021.100062. eCollection 2021 Jan-Jul.


Some individuals with chronic pain experience improvement in their pain with treatment, whereas others do not. The neurobiological reason is unclear, but an understanding of brain structure and functional patterns may provide insights into pain's responsivity to treatment. In this investigation, we used magnetic resonance imaging (MRI) techniques to determine grey matter density alterations on resting functional connectivity (RFC) strengths between pain responders and nonresponders in patients with complex regional pain syndrome. Brain metrics of pediatric patients at admission to an intensive pain rehabilitative treatment program were evaluated. Pain responders reported significant pain improvement at discharge and/or follow-up whereas nonresponders reported no improvements in pain, increases in pain, or emergence of new pain symptoms. The pain (responder/nonresponder) groups were compared with pain-free healthy controls to examine predictors of pain responder status via brain metrics. Our results show: (1) on admission, pain nonresponders had decreased grey matter density (GMD) within the nucleus accumbens (NAc) and reduced RFC strength between the NAc and the dorsolateral prefrontal cortex vs. responders; (2) Connectivity strength was positively correlated with change in pain intensity from admission to discharge; (3) Compared with pain-free controls, grey matter and RFC differences emerged only among pain nonresponders; and (4) Using a discriminative model, combining GMD and RFC strengths assessed at admission showed the highest prediction estimate (87%) on potential for pain improvement, warranting testing in a de novo sample. Taken together, these results support the idea that treatment responsiveness on pain is underpinned by concurrent brain structure and resting brain activity.

PMID:33732954 | PMC:PMC7941018 | DOI:10.1016/j.ynpai.2021.100062

Elamipretide (SS-31) Improves Functional Connectivity in Hippocampus and Other Related Regions Following Prolonged Neuroinflammation Induced by Lipopolysaccharide in Aged Rats

Thu, 03/18/2021 - 10:00

Front Aging Neurosci. 2021 Mar 1;13:600484. doi: 10.3389/fnagi.2021.600484. eCollection 2021.


Neuroinflammation has been recognized as a major cause for neurocognitive diseases. Although the hippocampus has been considered an important region for cognitive dysfunction, the influence of hippocampal neuroinflammation on brain functional connectivity (FC) has been rarely studied. In this study, lipopolysaccharide (LPS) was used to induce systemic inflammation and neuroinflammation in the aged rat brain, while elamipretide (SS-31) was used for treatment. Systemic and hippocampal inflammation were determined using ELISA, while astrocyte responses during hippocampal neuroinflammation were determined by interleukin 1 beta (IL-1β)/tumor necrosis factor alpha (TNFα) double staining immunofluorescence. Oxidative stress was determined by reactive oxidative species (ROS), electron transport chain (ETC) complex, and superoxide dismutase (SOD). Short- (<7 days) and long-term (>30 days) learning and spatial working memory were tested by the Morris water maze (MWM). Resting-state functional magnetic resonance imaging (rs-fMRI) was used to analyze the brain FC by placing seed voxels on the left and right hippocampus. Compared with the vehicle group, rats with the LPS exposure showed an impaired MWM performance, higher oxidative stress, higher levels of inflammatory cytokines, and astrocyte activation in the hippocampus. The neuroimaging examination showed decreased FC on the right orbital cortex, right olfactory bulb, and left hippocampus on day 3, 7, and 31, respectively, after treatment. In contrast, rats with SS-31 treatment showed lower levels of inflammatory cytokines, less astrocyte activation in the hippocampus, and improved MWM performance. Neuroimaging examination showed increased FC on the left-parietal association cortex (L-PAC), left sensory cortex, and left motor cortex on day 7 with the right flocculonodular lobe on day 31 as compared with those without SS-31 treatment. Our study demonstrated that inhibiting neuroinflammation in the hippocampus not only reduces inflammatory responses in the hippocampus but also improves the brain FC in regions related to the hippocampus. Furthermore, early anti-inflammatory treatment with SS-31 has a long-lasting effect on reducing the impact of LPS-induced neuroinflammation.

PMID:33732135 | PMC:PMC7956963 | DOI:10.3389/fnagi.2021.600484

Dorsolateral Prefrontal Functional Connectivity Predicts Working Memory Training Gains

Thu, 03/18/2021 - 10:00

Front Aging Neurosci. 2021 Mar 1;13:592261. doi: 10.3389/fnagi.2021.592261. eCollection 2021.


Background: Normal aging is associated with working memory decline. A decrease in working memory performance is associated with age-related changes in functional activation patterns in the dorsolateral prefrontal cortex (DLPFC). Cognitive training can improve cognitive performance in healthy older adults. We implemented a cognitive training study to assess determinants of generalization of training gains to untrained tasks, a key indicator for the effectiveness of cognitive training. We aimed to investigate the association of resting-state functional connectivity (FC) of DLPFC with working memory performance improvement and cognitive gains after the training. Method: A sample of 60 healthy older adults (mean age: 68 years) underwent a 4-week neuropsychological training, entailing a working memory task. Baseline resting-state functional MRI (rs-fMRI) images were acquired in order to investigate the FC of DLPFC. To evaluate training effects, participants underwent a neuropsychological assessment before and after the training. A second follow-up assessment was applied 12 weeks after the training. We used cognitive scores of digit span backward and visual block span backward tasks representing working memory function. The training group was divided into subjects who had and who did not have training gains, which was defined as a higher improvement in working memory tasks than the control group (N = 19). Results: A high FC of DLPFC of the right hemisphere was significantly associated with training gains and performance improvement in the visuospatial task. The maintenance of cognitive gains was restricted to the time period directly after the training. The training group showed performance improvement in the digit span backward task. Conclusion: Functional activation patterns of the DLPFC were associated with the degree of working memory training gains and visuospatial performance improvement. Although improvement through cognitive training and acquisition of training gains are possible in aging, they remain limited.

PMID:33732134 | PMC:PMC7956962 | DOI:10.3389/fnagi.2021.592261

Exosomal MicroRNAs Contribute to Cognitive Impairment in Hypertensive Patients by Decreasing Frontal Cerebrovascular Reactivity

Thu, 03/18/2021 - 10:00

Front Neurosci. 2021 Mar 1;15:614220. doi: 10.3389/fnins.2021.614220. eCollection 2021.


Mechanisms underlying cognitive impairment (CI) in hypertensive patients remain relatively unclear. The present study aimed to explore the relationship among serum exosomal microRNAs (miRNAs), cerebrovascular reactivity (CVR), and cognitive function in hypertensive patients. Seventy-three hypertensive patients with CI (HT-CI), 67 hypertensive patients with normal cognition (HT-NC), and 37 healthy controls underwent identification of exosomal miRNA, multimodal magnetic resonance imaging (MRI) scans, and neuropsychological tests. CVR mapping was investigated based on resting-state functional MRI data. Compared with healthy subjects and HT-NC subjects, HT-CI subjects displayed decreased serum exosomal miRNA-330-3p. The group difference of CVR was mainly found in the left frontal lobe and demonstrated that HT-CI group had a lower CVR than both HT-NC group and control group. Furthermore, both the CVR in the left medial superior frontal gyrus and the miRNA-330-3p level were significantly correlated with executive function (r = -0.275, P = 0.021, and r = -0.246, P = 0.04, respectively) in HT-CI subjects, and the CVR was significantly correlated with the miRNA-330-3p level (r = 0.246, P = 0.040). Notably, path analysis showed that the CVR mediated the association between miRNA-330-3p and executive function. In conclusion, decreased miRNA-330-3p might contribute to CI in hypertensive patients by decreasing frontal CVR and could be a biomarker of early diagnosis.

PMID:33732103 | PMC:PMC7957933 | DOI:10.3389/fnins.2021.614220

Abnormal Brain Connectivity in Carpal Tunnel Syndrome Assessed by Graph Theory

Thu, 03/18/2021 - 10:00

J Pain Res. 2021 Mar 11;14:693-701. doi: 10.2147/JPR.S289165. eCollection 2021.


INTRODUCTION: Numerous resting-state functional magnetic resonance imaging (fMRI) researches have indicated that large-scale functional and structural remodeling occurs in the whole brain despite an intact sensorimotor network after carpal tunnel syndrome (CTS). Investigators aimed to explore alterations of the global and nodal properties that occur in the whole brain network of patients with CTS based on topographic theory.

METHODS: Standard-compliant fMRI data were collected from 27 patients with CTS in bilateral hands and 19 healthy control subjects in this cross-sectional study. The statistics based on brain networks were calculated the differences between the patients and the healthy. Several topological properties were computed, such as the small-worldness, nodal clustering coefficient, characteristic path length, and degree centrality.

RESULTS: Compared to those of the healthy controls, the global properties of the CTS group exhibited a decreased characteristic path length. Changes in the local-level properties included a decreased nodal clustering coefficient in 6 separate brain regions and significantly different degree centrality in several brain regions that were related to sensorimotor function and pain.

DISCUSSION: The study suggested that CTS reinforces global connections and makes their networks more random. The changed nodal properties were affiliated with basal ganglia-thalamo-cortical circuits and the pain matrix. These results provided new insights for improving our understanding of abnormal topological theory in relation to the functional brain networks of CTS patients.

PERSPECTIVE: This article presents that the CTS patients' brain with a higher global efficiency. And the significant alterations in several brain regions which are more related to pain and motor processes. The results provided effective complements to the neural mechanisms underlying CTS.

PMID:33732015 | PMC:PMC7959208 | DOI:10.2147/JPR.S289165

Repetitive transcranial magnetic stimulation restores altered functional connectivity of central poststroke pain model monkeys

Thu, 03/18/2021 - 10:00

Sci Rep. 2021 Mar 17;11(1):6126. doi: 10.1038/s41598-021-85409-w.


Central poststroke pain (CPSP) develops after a stroke around the somatosensory pathway. CPSP is hypothesized to be caused by maladaptive reorganization between various brain regions. The treatment for CPSP has not been established; however, repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex has a clinical effect. To verify the functional reorganization hypothesis for CPSP development and rTMS therapeutic mechanism, we longitudinally pursued the structural and functional changes of the brain by using two male CPSP model monkeys (Macaca fuscata) developed by unilateral hemorrhage in the ventral posterolateral nucleus of the thalamus. Application of rTMS to the ipsilesional primary motor cortex relieved the induced pain of the model monkeys. A tractography analysis revealed a decrease in the structural connectivity in the ipsilesional thalamocortical tract, and rTMS had no effect on the structural connectivity. A region of interest analysis using resting-state functional magnetic resonance imaging revealed inappropriately strengthened functional connectivity between the ipsilesional mediodorsal nucleus of the thalamus and the amygdala, which are regions associated with emotion and memory, suggesting that this may be the cause of CPSP development. Moreover, rTMS normalizes this strengthened connectivity, which may be a possible therapeutic mechanism of rTMS for CPSP.

PMID:33731766 | DOI:10.1038/s41598-021-85409-w

The additive effect of late-life depression and olfactory dysfunction on the risk of dementia was mediated by hypersynchronization of the hippocampus/fusiform gyrus

Thu, 03/18/2021 - 10:00

Transl Psychiatry. 2021 Mar 17;11(1):172. doi: 10.1038/s41398-021-01291-0.


Early detection of patients with late-life depression (LLD) with a high risk of developing dementia contributes to early intervention. Odor identification (OI) dysfunction serves as a marker for predicting dementia, but whether OI dysfunction increases the risk of dementia in LLD patients remains unclear. The present study aimed to explore the interactive effect of LLD and OI dysfunction on the risk of dementia and its underlying neuroimaging changes. One hundred and fifty-seven LLD patients and 101 normal controls were recruited, and data on their OI, cognition, activity of daily living (ADL), and resting-state functional magnetic resonance imaging were collected. Two × two factorial analyses were used to analyze the interactive effects of LLD and OI dysfunction on neuropsychological and neuroimaging abnormalities. Mediation analyses were used to explore whether abnormalities detected by neuroimaging mediated the the associations between OI and cognition/ADL. The results suggested that LLD and OI dysfunction exhibited additive effects on reduced ADL, global cognition and memory scores, as well as neuroimaging variables including (i) increased fractional amplitude of low-frequency fluctuation (fALFF) in the right orbitofrontal cortex and right precentral cortex, and (ii) increased regional homogeneity (ReHo) in the left hippocampus/fusiform gyrus, etc. In addition, these increased fALFF and ReHo values were associated with reduced neuropsychological scores (ADL, global cognition, memory, and language). Moreover, ReHo of the left hippocampus/fusiform gyrus completely mediated the relationship between OI and ADL, and partially mediated the relationship between OI and global cognition. Overall, mediated by the hypersynchronization of the left hippocampus/fusiform gyrus, OI dysfunction may increase the risk of dementia in LLD patients.

PMID:33731679 | DOI:10.1038/s41398-021-01291-0