Neurocognitive disorders in the elderly: altered functional resting-state hyperconnectivities in postoperative delirium patients.
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ABSTRACT:
SUBMITTER: Winterer JM
PROVIDER: S-EPMC8041755 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Apathy is defined as reduction of goal-directed behaviors and a common nuisance syndrome of neurodegenerative and psychiatric disease. The underlying mechanism of apathy implicates changes of the front-striatal circuit, but its precise alteration is unclear for apathy in healthy aged people. The aim of our study is to investigate how the frontal-striatal circuit is changed in elderly with apathy using resting-state functional MRI. Eighteen subjects with apathy (7 female, 63.7 ± 3.0 years) and eighteen subjects without apathy (10 female, 64.8 ± 3.0 years) who underwent neuropsychological assessment and MRI measurement were recruited. We compared functional connectivity with/within the striatum between the apathy and non-apathy groups. The seed-to-voxel group analysis for functional connectivity between the striatum and other brain regions showed that the connectivity was decreased between the ventral rostral putamen and the right dorsal anterior cingulate cortex/supplementary motor area in the apathy group compared to the non-apathy group while the connectivity was increased between the dorsal caudate and the left sensorimotor area. Moreover, the ROI-to-ROI analysis within the striatum indicated reduction of functional connectivity between the ventral regions and dorsal regions of the striatum in the apathy group. Our findings suggest that the changes in functional connectivity balance among different frontal-striatum circuits contribute to apathy in elderly.
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Project description:BackgroundHIV-associated neurocognitive disorder (HAND) can occur in patients without prior AIDS defining illness and can be debilitating. This study aimed to evaluate the difference in the patterns of intrinsic brain activity between patients with or without HAND for deepening our understanding of HAND.MethodsWe evaluated 24 HIV-infected individuals, 12 with previously diagnosed HAND and 12 previously diagnosed without HAND, and 11 seronegative individuals. These individuals then underwent repeat NP testing and a functional brain MRI scan. For functional MRI analysis, seed-based analysis with bilateral precuneus cortex seed was applied.ResultsAmong the 12 individuals with previously diagnosed HAND, 3 showed improvement of their neurocognitive function and 1 was excluded for worsening liver disease. Among the 12 patients who previously had normal neurocognitive function, 2 showed neurocognitive impairment. Overall, the HAND group, who had impaired cognitive function at the time of MRI scan, showed significant decrease of resting status functional connectivity between bilateral precuneus and prefrontal cortex (PFC) compared with nonHAND group, those who had normal neurocognitive function (Corrected P<0.05). The functional connectivity with the right inferior frontal operculum and right superior frontal gyrus was positively correlated with memory and learning ability.ConclusionsThis cross-sectional study found a significant difference in fMRI patterns between patients with and without HAND. Decreased functional connectivity between precuneus and PFC could be possible functional substrate for cognitive dysfunction in HIV patients, which should be characterized in a longitudinal study.
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Project description:Schizophrenia (SZ) is a severe mental disorder that arises from abnormal neurodevelopment, caused by genetic and environmental factors. SZ often involves distortions in reality perception and it is widely associated with alterations in brain connectivity. In the present work, we used Human Induced Pluripotent Stem Cells (hiPSCs)-derived neuronal cultures to study neural communicational dynamics during early development in SZ. We conducted gene and protein expression profiling, calcium imaging recordings, and applied a mathematical model to quantify the dynamism of functional connectivity (FC) in hiPSCs-derived neuronal networks. Along the neurodifferentiation process, SZ networks displayed altered gene expression of the glutamate receptor-related proteins HOMER1 and GRIN1 compared to healthy control (HC) networks, suggesting a possible tendency to develop hyperexcitability. Resting-state FC in neuronal networks derived from HC and SZ patients emerged as a dynamic phenomenon exhibiting connectivity configurations reoccurring in time (hub states). Compared to HC, SZ networks were less thorough in exploring different FC configurations, changed configurations less often, presented a reduced repertoire of hub states and spent longer uninterrupted time intervals in this less diverse universe of hubs. Our results suggest that alterations in the communicational dynamics of SZ emerging neuronal networks might contribute to the previously described brain FC anomalies in SZ patients, by compromising the ability of their neuronal networks for rapid and efficient reorganization through different activity patterns.
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Project description:Impaired connectivity is proposed to underlie pathophysiology of schizophrenia. Existing studies on functional connectivity show inconsistent results. We examined functional connectivity in a clinically homogenous sample of 34 early course schizophrenia patients compared with/to 19 healthy controls using resting state functional magnetic resonance imaging (rsfMRI). Mean duration of illness for schizophrenia patients was 4 ± 1.78 years. Following a comprehensive clinical assessment, rsfMRI data were acquired using a 3.0 T magnetic resonance imaging scanner, and analyzed using FSL version 5.01 software (FMRIB's Software Library, www.fmrib.ox.ac.uk/fsl). Compared to healthy controls, schizophrenia patients had significantly decreased functional connectivity in the left fronto-parietal network, lateral and medial visual network, motor network, default mode network and auditory network. Our data suggests significant functional hypoconnectivity in selected brain networks in early schizophrenia patients compared to controls. It is likely that the observed functional hypoconnectivity may be associated with features of schizophrenia other than those examined in this study. It is possible that hypoconnectivity is necessary but not sufficient to the clinical manifestation of schizophrenia. The examination of functional connectivity as a biomarker should be extended to a wider array of disease phenotypes to better understand its significance.
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Project description:Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder caused by absence of dystrophin protein. Dystrophin is expressed in muscle, but also in the brain. Difficulties with attention/inhibition, working memory and information processing are well described in DMD patients but their origin is poorly understood. The default mode network (DMN) is one of the networks involved in these processes. Therefore we aimed to assess DMN connectivity in DMD patients compared to matched controls, to better understand the cognitive profile in DMD. T1-weighted and resting state functional MRI scans were acquired from 33 DMD and 24 male age-matched controls at two clinical sites. Scans were analysed using FMRIB Software Library (FSL). Differences in the DMN were assessed using FSL RANDOMISE, with age as covariate and threshold-free cluster enhancement including multiple comparison correction. Post-hoc analyses were performed on the visual network, executive control network and fronto-parietal network with the same methods. In DMD patients, the level of connectivity was higher in areas within the control DMN (hyperconnectivity) and significant connectivity was found in areas outside the control DMN. No hypoconnectivity was found and no differences in the visual network, executive control network and fronto-parietal network. We showed differences both within and in areas outside the DMN in DMD. The specificity of our findings to the DMN can help provide a better understanding of the attention/inhibition, working memory and information processing difficulties in DMD.
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Project description:ImportancePostoperative neurocognitive disorders (PNDs) after surgical procedures are common and may be associated with increased health care expenditures.ObjectiveTo quantify the economic burden associated with a PND diagnosis in 1 year following surgical treatment among older patients in the United States.Design, setting, and participantsThis retrospective cohort study used claims data from the Bundled Payments for Care Improvement Advanced Model from 4285 hospitals that submitted Medicare Fee-for-service (FFS) claims between January 2013 and December 2016. All Medicare patients aged 65 years or older who underwent an inpatient hospital admission associated with a surgical procedure, did not experience a PND before index admission, and were not undergoing dialysis or concurrently enrolled in Medicaid were included. Data were analyzed from October 2019 and May 2020.ExposuresPND, defined as an International Classification of Diseases, Ninth or Tenth Revision, diagnosis of delirium, mild cognitive impairment, or dementia within 1 year of discharge from the index surgical admission.Main outcomes and measuresThe primary outcome was total inflation-adjusted Medicare postacute care payments within 1 year after the index surgical procedure.ResultsA total of 2 380 473 patients (mean [SD] age, 75.36 (7.31) years; 1 336 736 [56.1%] women) who underwent surgical procedures were included, of whom 44 974 patients (1.9%) were diagnosed with a PND. Among all patients, most were White (2 142 157 patients [90.0%]), presenting for orthopedic surgery (1 523 782 patients [64.0%]) in urban medical centers (2 179 893 patients [91.6%]) that were private nonprofits (1 798 749 patients [75.6%]). Patients with a PND, compared with those without a PND, experienced a significantly longer hospital length of stay (mean [SD], 5.91 [6.01] days vs 4.29 [4.18] days; P < .001), were less likely to be discharged home (9947 patients [22.1%] vs 914 925 patients [39.2%]; P < .001), and had a higher incidence of mortality at 1 year after treatment (4580 patients [10.2%] vs 103 767 patients [4.4%]; P < .001). After adjusting for patient and hospital characteristics, the presence of a PND within 1 year of the index procedure was associated with an increase of $17 275 (95% CI, $17 058-$17 491) in cost in the 1-year postadmission period (P < .001).Conclusions and relevanceThe findings of this cohort study suggest that among older Medicare patients undergoing surgical treatment, a diagnosis of a PND was associated with an increase in health care costs for up to 1 year following the surgical procedure. Given the magnitude of this cost burden, PNDs represent an appealing target for risk mitigation and improvement in value-based health care.
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Project description:IntroductionBrain structural injury and metabolic deficits in the hippocampus and caudate nuclei may contribute to cognitive and emotional deficits found in obstructive sleep apnea (OSA) patients. If such contributions exist, resting-state interactions of these subcortical sites with cortical areas mediating affective symptoms and cognition should be disturbed. Our aim was to examine resting-state functional connectivity (FC) of the hippocampus and caudate to other brain areas in OSA relative to control subjects, and to relate these changes to mood and neuropsychological scores.MethodsWe acquired resting-state functional magnetic resonance imaging (fMRI) data from 70 OSA and 89 healthy controls using a 3.0-Tesla magnetic resonance imaging scanner, and assessed psychological and behavioral functions, as well as sleep issues. After standard fMRI data preprocessing, FC maps were generated for bilateral hippocampi and caudate nuclei, and compared between groups (ANCOVA; covariates, age and gender).ResultsObstructive sleep apnea subjects showed significantly higher levels of anxiety and depressive symptoms over healthy controls. In OSA subjects, the hippocampus showed disrupted FC with the thalamus, para-hippocampal gyrus, medial and superior temporal gyrus, insula, and posterior cingulate cortex. Left and right caudate nuclei showed impaired FC with the bilateral inferior frontal gyrus and right angular gyrus. In addition, altered limbic-striatal-cortical FC in OSA showed relationships with behavioral and neuropsychological variables.ConclusionsThe compromised hippocampal-cortical FC in OSA may underlie depression and anxious mood levels in OSA, while impaired caudate-cortical FC may indicate deficits in reward processing and cognition. These findings provide insights into the neural mechanisms underlying the comorbidity of mood and cognitive deficits in OSA.
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Project description:BackgroundChronic unilateral vestibulopathy (CUVP) is often accompanied by dizziness and postural instability, which restrict patients' daily activities. It is important to understand central compensation mechanisms underlying these symptoms in patients with CUVP by evaluating their brain functional status.PurposeTo analyze the changes in resting-state intranetwork and internetwork functional connectivity (FC) and explore the state of central vestibular compensation in patients with CUVP.Study typeRetrospective.PopulationEighteen patients with right-sided CUVP and 18 age- and sex-matched healthy controls.Field strength/sequenceA 3.0 T, three-dimensional magnetization-prepared rapid gradient-echo (MP-RAGE) and resting-state echo-planar imaging (EPI) functional MRI sequences.AssessmentFC alterations were explored using independent component analysis (ICA). Twelve independent components were identified via ICA. Dizziness Handicap Inventory (DHI) score for all patients was determined.Statistical testsTwo-sample t test, family-wise error (FWE) correction, Pearson correlation coefficient (r). A P value <0.05 was considered statistically significant.ResultsCompared with healthy controls, patients with CUVP showed significantly decreased FC in the right middle occipital gyrus within the lateral visual network, and significantly increased FC in the right supplementary motor area within the sensorimotor network. The FC was decreased between the medial visual and auditory networks, the right frontoparietal and posterior default networks, as well as the sensorimotor and auditory networks. There was a significant negative correlation between the FC changes in the visual, auditory networks and the DHI score in patients with CUVP (r = -0.583).Data conclusionCompared to healthy controls, the FC was significantly decreased in the right visual cortex and significantly enhanced in the right sensorimotor network in patients with CUVP. Patients with CUVP showed decreased FC between multiple whole-brain networks, suggesting that abnormal integration of multisensory information may be involved in the occurrence of chronic dizziness and instability in patients with CUVP.Level of evidence4 TECHNICAL EFFICACY: Stage 2.
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Project description:BackgroundNeuroimaging studies have identified aberrant activity patterns in multiple brain regions in functional dyspepsia (FD) patients. However, due to the differences in study design, these previous findings are inconsistent, and the underlying neuropathological characteristics of FD remain unclear.MethodsEight databases were systematically searched for literature from inception to October 2022 with the keywords "Functional dyspepsia" and "Neuroimaging." Thereafter, the anisotropic effect size signed the differential mapping (AES-SDM) approach that was applied to meta-analyze the aberrant brain activity pattern of FD patients.ResultsA total of 11 articles with 260 FD patients and 202 healthy controls (HCs) were included. The AES-SDM meta-analysis demonstrated that FD patients manifested increased activity in the bilateral insula, left anterior cingulate gyrus, bilateral thalamus, right precentral gyrus, left supplementary motor area, right putamen, and left rectus gyrus and decreased functional activity in the right cerebellum compared to the HCs. Sensitivity analysis showed that all these above regions were highly reproducible, and no significant publication bias was detected.ConclusionThe current study demonstrated that FD patients had significantly abnormal activity patterns in several brain regions involved in visceral sensation perception, pain modulation, and emotion regulation, which provided an integrated insight into the neuropathological characteristics of FD.
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Project description:This study aimed to explore the role of the default mode network (DMN) and salience network (SN) in the assessment of pathophysiology of generalized anxiety disorder (GAD) through analyzing the characteristics of internal function connectivity (FC) and to investigate the relationship of FC with Hamilton anxiety (HAMA) scale scores in untreated GAD patients during a resting-state functional magnetic resonance imaging (rs-fMRI). Rs-fMRI and HAMA scale scoring were performed in 51 GAD patients (31 GAD patients with liver stagnation transforming into fire type and 20 GAD patients with stagnation of liver-Qi syndrome type) and 20 healthy controls. Spearman correlation analysis was performed to assess the association between HAMA scores and abnormal brain FC. Compared with healthy controls, the FC of the right medial prefrontal gyrus of the DMN and the right superior temporal gyrus of the SN increased significantly in the GAD patients (P < 0.001). However, the FC of the left middle frontal gyrus and bilateral medial superior frontal gyrus of the SN reduced significantly in the GAD patients with stagnation of liver-Qi syndrome type as compared with healthy controls and GAD patients with liver stagnation transforming into fire type (P < 0.001). There was no relationship between abnormal brain FC and HAMA scores. In conclusion, the FC of the DMN and SN may be abnormal in the GAD patients at the resting state. The aberrant FC of some crucial brain regions of these networks may contribute to the pathophysiology of GAD.
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