RESUMO
Time is an omnipresent aspect of almost everything we experience internally or in the external world. The experience of time occurs through such an extensive set of contextual factors that, after decades of research, a unified understanding of its neural substrates is still elusive. In this study, following the recent best-practice guidelines, we conducted a coordinate-based meta-analysis of 95 carefully-selected neuroimaging papers of duration processing. We categorized the included papers into 14 classes of temporal features according to six categorical dimensions. Then, using the activation likelihood estimation (ALE) technique we investigated the convergent activation patterns of each class with a cluster-level family-wise error correction at p < 0.05. The regions most consistently activated across the various timing contexts were the pre-SMA and bilateral insula, consistent with an embodied theory of timing in which abstract representations of duration are rooted in sensorimotor and interoceptive experience, respectively. Moreover, class-specific patterns of activation could be roughly divided according to whether participants were timing auditory sequential stimuli, which additionally activated the dorsal striatum and SMA-proper, or visual single interval stimuli, which additionally activated the right middle frontal and inferior parietal cortices. We conclude that temporal cognition is so entangled with our everyday experience that timing stereotypically common combinations of stimulus characteristics reactivates the sensorimotor systems with which they were first experienced.
Assuntos
Mapeamento Encefálico , Imageamento por Ressonância Magnética , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Neuroimagem , Substância CinzentaRESUMO
BACKGROUND: Impaired self-awareness of cognitive deficits (ISAcog) has rarely been investigated in Parkinson's disease (PD). ISAcog is associated with poorer long-term outcome in other diseases. This study examines ISAcog in PD with and without mild cognitive impairment (PD-MCI), compared to healthy controls, and its clinical-behavioral and neuroimaging correlates. METHODS: We examined 63 PD patients and 30 age- and education-matched healthy controls. Cognitive state was examined following the Movement Disorder Society Level II criteria. ISAcog was determined by subtracting z-scores (based on controls' scores) of objective tests and subjective questionnaires. Neural correlates were assessed by structural magnetic resonance imaging (MRI) and 2-[fluorine-18]fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET) in 47 patients (43 with MRI) and 11 controls. We analyzed whole-brain glucose metabolism and cortical thickness in regions where FDG-uptake correlated with ISAcog. RESULTS: PD-MCI patients (N = 23) showed significantly more ISAcog than controls and patients without MCI (N = 40). When all patients who underwent FDG-PET were examined, metabolism in the bilateral superior medial frontal gyrus, anterior and midcingulate cortex negatively correlated with ISAcog (FWE-corrected p < 0.001). In PD-MCI, ISAcog was related to decreased metabolism in the right superior temporal lobe and insula (N = 13; FWE-corrected p = 0.023) as well as the midcingulate cortex (FWE-corrected p = 0.002). Cortical thickness was not associated with ISAcog in these regions. No significant correlations were found between ISAcog and glucose metabolism in controls and patients without MCI. CONCLUSIONS: Similar to Alzheimer's disease, the cingulate cortex seems to be relevant in ISAcog in PD. In PD-MCI patients, ISAcog might result from a disrupted network that regulates awareness of cognition and error processes.
Assuntos
Disfunção Cognitiva , Doença de Parkinson , Humanos , Giro do Cíngulo/metabolismo , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Fluordesoxiglucose F18/metabolismo , Tomografia Computadorizada por Raios X , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Cognição/fisiologia , Encéfalo , Imageamento por Ressonância Magnética/métodos , GlucoseRESUMO
Theoretical models of insomnia disorder recognise an emotional component in the maintenance of the disorder. Nonetheless, the field of emotions is vast and different processes are involved in psychological well-being. The present narrative review focusses on emotion regulation and affect dynamics, synthesising some of the most recent and relevant evidence on emotions in relation to the quality of sleep and to insomnia disorder. The literature underlines the close association between impaired sleep quality and difficulties in regulating emotions. Impaired sleep quality is also associated with reduced positive affect and increased negative affect, but little evidence supports a bi-directional association between affective states and sleep. Affect variability in relation to sleep has been less investigated. Initial evidence suggests that high variability in positive affect has a negative impact on sleep. Neurobiological and behavioural evidence indicates that insomnia disorder is associated with emotion dysregulation, negative affect, and a distinct daily profile of affective states. More research is needed on the affective experience of patients with insomnia disorder, adopting multiple sampling of affect across the day and the week. Understanding how the unfolding of emotions over time interact with sleep alterations may help to improve the tailoring and monitoring of treatments addressing disturbed emotional processes in insomnia disorder.
Assuntos
Regulação Emocional , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/complicações , Qualidade do Sono , Emoções/fisiologia , SonoRESUMO
Existing neuroimaging studies have reported divergent structural alterations in insomnia disorder (ID). In the present study, we performed a large-scale coordinated meta-analysis by pooling structural brain measures from 1085 subjects (mean [SD] age 50.5 [13.9] years, 50.2% female, 17.4% with insomnia) across three international Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA)-Sleep cohorts. Two sites recruited patients with ID/controls: Freiburg (University of Freiburg Medical Center, Freiburg, Germany) 42/43 and KUMS (Kermanshah University of Medical Sciences, Kermanshah, Iran) 42/49, while the Study of Health in Pomerania (SHIP-Trend, University Medicine Greifswald, Greifswald, Germany) recruited population-based individuals with/without insomnia symptoms 75/662. The influence of insomnia on magnetic resonance imaging-based brain morphometry using an insomnia brain score was then assessed. Within each cohort, we used an ordinary least-squares linear regression to investigate the link between the individual regional cortical and subcortical volumes and the presence of insomnia symptoms. Then, we performed a fixed-effects meta-analysis across cohorts based on the first-level results. For the insomnia brain score, weighted logistic ridge regression was performed on one sample (Freiburg), which separated patients with ID from controls to train a model based on the segmentation measurements. Afterward, the insomnia brain scores were validated using the other two samples. The model was used to predict the log-odds of the subjects with insomnia given individual insomnia-related brain atrophy. After adjusting for multiple comparisons, we did not detect any significant associations between insomnia symptoms and cortical or subcortical volumes, nor could we identify a global insomnia-related brain atrophy pattern. Thus, we observed inconsistent brain morphology differences between individuals with and without insomnia across three independent cohorts. Further large-scale cross-sectional/longitudinal studies using both structural and functional neuroimaging are warranted to decipher the neurobiology of insomnia.
Assuntos
Distúrbios do Início e da Manutenção do Sono , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Estudos Transversais , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Sono , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , AdultoRESUMO
Ineffective use of adaptive cognitive strategies (e.g., reappraisal) to regulate emotional states is often reported in a wide variety of psychiatric disorders, suggesting a common characteristic across different diagnostic categories. However, the extent of shared neurobiological impairments is incompletely understood. This study, therefore, aimed to identify the transdiagnostic neural signature of disturbed reappraisal using the coordinate-based meta-analysis (CBMA) approach. Following the best-practice guidelines for conducting neuroimaging meta-analyses, we systematically searched PubMed, ScienceDirect, and Web of Science databases and tracked the references. Out of 1,608 identified publications, 32 whole-brain neuroimaging studies were retrieved that compared brain activation in patients with psychiatric disorders and healthy controls during a reappraisal task. Then, the reported peak coordinates of group comparisons were extracted and several activation likelihood estimation (ALE) analyses were performed at three hierarchical levels to identify the potential spatial convergence: the global level (i.e., the pooled analysis and the analyses of increased/decreased activations), the experimental-contrast level (i.e., the analyses of grouped data based on the regulation goal, stimulus valence, and instruction rule) and the disorder-group level (i.e., the analyses across the experimental-contrast level focused on increasing homogeneity of disorders). Surprisingly, none of our analyses provided significant convergent findings. This CBMA indicates a lack of transdiagnostic convergent regional abnormality related to reappraisal task, probably due to the complex nature of cognitive emotion regulation, heterogeneity of clinical populations, and/or experimental and statistical flexibility of individual studies.
Assuntos
Encéfalo/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Regulação Emocional/fisiologia , Neuroimagem Funcional , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , HumanosRESUMO
PURPOSE: Alzheimer's disease (AD) and mild cognitive impairment (MCI) are characterized by both aberrant regional neural activity and disrupted inter-regional functional connectivity (FC). However, the effect of AD/MCI on the coupling between regional neural activity (measured by regional fluorodeoxyglucose imaging (rFDG)) and inter-regional FC (measured by resting-state functional magnetic resonance imaging (rs-fMRI)) is poorly understood. METHODS: We scanned 19 patients with MCI, 33 patients with AD, and 26 healthy individuals by simultaneous FDG-PET/rs-fMRI and assessed rFDG and inter-regional FC metrics (i.e., clustering coefficient and degree centrality). Next, we examined the potential moderating effect of disease status (MCI or AD) on the link between rFDG and inter-regional FC metrics using hierarchical moderated multiple regression analysis. We also tested this effect by considering interaction between disease status and inter-regional FC metrics, as well as interaction between disease status and rFDG. RESULTS: Our findings revealed that both rFDG and inter-regional FC metrics were disrupted in MCI and AD. Moreover, AD altered the relationship between rFDG and inter-regional FC metrics. In particular, we found that AD moderated the effect of inter-regional FC metrics of the caudate, parahippocampal gyrus, angular gyrus, supramarginal gyrus, frontal pole, inferior temporal gyrus, middle frontal, lateral occipital, supramarginal gyrus, precuneus, and thalamus on predicting their rFDG. On the other hand, AD moderated the effect of rFDG of the parietal operculum on predicting its inter-regional FC metric. CONCLUSION: Our findings demonstrated that AD decoupled the link between regional neural activity and functional segregation and global connectivity across particular brain regions.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de PósitronsRESUMO
A prominent finding of postmortem and molecular imaging studies on Alzheimer's disease (AD) is the accumulation of neuropathological proteins in brain regions of the default mode network (DMN). Molecular models suggest that the progression of disease proteins depends on the directionality of signaling pathways. At network level, effective connectivity (EC) reflects directionality of signaling pathways. We hypothesized a specific pattern of EC in the DMN of patients with AD, related to cognitive impairment. Metabolic connectivity mapping is a novel measure of EC identifying regions of signaling input based on neuroenergetics. We simultaneously acquired resting-state functional MRI and FDG-PET data from patients with early AD (n = 35) and healthy subjects (n = 18) on an integrated PET/MR scanner. We identified two distinct subnetworks of EC in the DMN of healthy subjects: an anterior part with bidirectional EC between hippocampus and medial prefrontal cortex and a posterior part with predominant input into medial parietal cortex. Patients had reduced input into the medial parietal system and absent input from hippocampus into medial prefrontal cortex (p < 0.05, corrected). In a multiple linear regression with unimodal imaging and EC measures (F4,25 = 5.63, p = 0.002, r2 = 0.47), we found that EC (ß = 0.45, p = 0.012) was stronger associated with cognitive deficits in patients than any of the PET and fMRI measures alone. Our approach indicates specific disruptions of EC in the DMN of patients with AD and might be suitable to test molecular theories about downstream and upstream spreading of neuropathology in AD.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Córtex Cerebral , Conectoma/métodos , Rede de Modo Padrão , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons/métodos , Idoso , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Rede de Modo Padrão/diagnóstico por imagem , Rede de Modo Padrão/metabolismo , Rede de Modo Padrão/fisiopatologia , HumanosRESUMO
Dysfunctions in bottom-up emotion processing (EP), as well as top-down emotion regulation (ER) are prominent features in pathophysiology of major depressive disorder (MDD). Nonetheless, it is not clear whether EP- and ER-related areas are regionally and/or connectively disturbed in MDD. In addition, it is yet to be known how EP- and ER-related areas are interactively linked to regulatory behavior, and whether this interaction is disrupted in MDD. In our study, regional amplitude of low frequency fluctuations (ALFF) and whole-brain functional connectivity (FC) of meta-analytic-driven EP- and ER-related areas were compared between 32 healthy controls (HC) and 20 MDD patients. Then, we aimed to investigate whether the EP-related areas can predict the ER-related areas and regulatory behavior in both groups. Finally, the brain-behavior correlations between the EP- and ER-related areas and depression severity were assessed. We found that: (a) affective areas are regionally and/or connectively disturbed in MDD; (b) EP-ER interaction seems to be disrupted in MDD; overburden of emotional reactivity in amygdala may inversely affect cognitive control processes in prefrontal cortices, which leads to diminished regulatory actions. (c) Depression severity is correlated with FC of affective areas. Our findings shed new lights on the neural underpinning of affective dysfunctions in depression.
Assuntos
Sintomas Afetivos/fisiopatologia , Tonsila do Cerebelo/fisiopatologia , Córtex Cerebral/fisiopatologia , Conectoma/métodos , Transtorno Depressivo Maior/fisiopatologia , Regulação Emocional/fisiologia , Adulto , Sintomas Afetivos/diagnóstico por imagem , Sintomas Afetivos/etiologia , Tonsila do Cerebelo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
Involvement of the default mode network (DMN) in cognitive symptoms of Parkinson's disease (PD) has been reported by resting-state functional MRI (rsfMRI) studies. However, the relation to metabolic measures obtained by [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) is largely unknown. We applied multimodal resting-state network analysis to clarify the association between intrinsic metabolic and functional connectivity abnormalities within the DMN and their significance for cognitive symptoms in PD. PD patients were classified into normal cognition (n = 36) and mild cognitive impairment (MCI; n = 12). The DMN was identified by applying an independent component analysis to FDG-PET and rsfMRI data of a matched subset (16 controls and 16 PD patients) of the total cohort. Besides metabolic activity, metabolic and functional connectivity within the DMN were compared between the patients' groups and healthy controls (n = 16). Glucose metabolism was significantly reduced in all DMN nodes in both patient groups compared to controls, with the lowest uptake in PD-MCI (p < .05). Increased metabolic and functional connectivity along fronto-parietal connections was identified in PD-MCI patients compared to controls and unimpaired patients. Functional connectivity negatively correlated with cognitive composite z-scores in patients (r = -.43, p = .005). The current study clarifies the commonalities of metabolic and hemodynamic measures of brain network activity and their individual significance for cognitive symptoms in PD, highlighting the added value of multimodal resting-state network approaches for identifying prospective biomarkers.
Assuntos
Córtex Cerebral , Disfunção Cognitiva , Conectoma , Rede de Modo Padrão , Doença de Parkinson , Idoso , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Rede de Modo Padrão/diagnóstico por imagem , Rede de Modo Padrão/metabolismo , Rede de Modo Padrão/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Tomografia por Emissão de PósitronsRESUMO
PURPOSE: Tau pathology progression in Alzheimer's disease (AD) is explained through the network degeneration hypothesis and the neuropathological Braak stages; however, the compatibility of these models remains unclear. METHODS: We utilized [18F]AV-1451 tau-PET scans of 39 subjects with AD and 39 sex-matched amyloid-negative healthy controls (HC) in the ADNI (Alzheimer's Disease Neuroimaging Initiative) dataset. The peak cluster of tau-tracer uptake was identified in each Braak stage of neuropathological tau deposition and used to create a seed-based functional connectivity network (FCN) using 198 HC subjects, to identify healthy networks unaffected by neurodegeneration. RESULTS: Voxel-wise tau deposition was both significantly higher inside relative to outside FCNs and correlated significantly and positively with levels of healthy functional connectivity. Within many isolated Braak stages and regions, the correlation between tau and intrinsic functional connectivity was significantly stronger than it was across the whole brain. In this way, each peak cluster of tau was related to multiple Braak stages traditionally associated with both earlier and later stages of disease. CONCLUSION: We show specificity of healthy FCN topography for AD-pathological tau as well as positive voxel-by-voxel correlations between pathological tau and healthy functional connectivity. We propose a model of "up- and downstream" functional tau progression, suggesting that tau pathology evolves along functional connectivity networks not only "downstream" (i.e., along the expected sequence of the established Braak stages) but also in part "upstream" or "retrograde" (i.e., against the expected sequence of the established Braak stages), with pathology in earlier Braak stages intensified by its functional relationship to later disease stages.
Assuntos
Doença de Alzheimer , Proteínas tau , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Humanos , Neuroimagem , Tomografia por Emissão de Pósitrons , Proteínas tau/metabolismoRESUMO
Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.
Assuntos
Encéfalo , Encéfalo/diagnóstico por imagem , Humanos , Neuroimagem , Tamanho da Amostra , Privação do SonoRESUMO
The spreading hypothesis of neurodegeneration assumes an expansion of neural pathologies along existing neural pathways. Multimodal neuroimaging studies have demonstrated distinct topographic patterns of cerebral pathologies in neurodegeneration. For Parkinson's disease the hypothesis so far rests largely on histopathological evidence of α-synuclein spreading in a characteristic pattern and progressive nigrostriatal dopamine depletion. Functional consequences of nigrostriatal dysfunction on cortical activity remain to be elucidated. Our goal was to investigate multimodal imaging correlates of degenerative processes in Parkinson's disease by assessing dopamine depletion and its potential effect on striatocortical connectivity networks and cortical metabolism in relation to parkinsonian symptoms. We combined 18F-DOPA-PET, 18F-fluorodeoxyglucose (FDG)-PET and resting state functional MRI to multimodally characterize network alterations in Parkinson's disease. Forty-two patients with mild-to-moderate stage Parkinson's disease and 14 age-matched healthy control subjects underwent a multimodal imaging protocol and comprehensive clinical examination. A voxel-wise group comparison of 18F-DOPA uptake identified the exact location and extent of putaminal dopamine depletion in patients. Resulting clusters were defined as seeds for a seed-to-voxel functional connectivity analysis. 18F-FDG metabolism was compared between groups at a whole-brain level and uptake values were extracted from regions with reduced putaminal connectivity. To unravel associations between dopaminergic activity, striatocortical connectivity, glucose metabolism and symptom severity, correlations between normalized uptake values, seed-to-cluster ß-values and clinical parameters were tested while controlling for age and dopaminergic medication. Aside from cortical hypometabolism, 18F-FDG-PET data for the first time revealed a hypometabolic midbrain cluster in patients with Parkinson's disease that comprised caudal parts of the bilateral substantia nigra pars compacta. Putaminal dopamine synthesis capacity was significantly reduced in the bilateral posterior putamen and correlated with ipsilateral nigral 18F-FDG uptake. Resting state functional MRI data indicated significantly reduced functional connectivity between the dopamine depleted putaminal seed and cortical areas primarily belonging to the sensorimotor network in patients with Parkinson's disease. In the inferior parietal cortex, hypoconnectivity in patients was significantly correlated with lower metabolism (left P = 0.021, right P = 0.018). Of note, unilateral network alterations quantified with different modalities corresponded with contralateral motor impairments. In conclusion, our results support the hypothesis that degeneration of nigrostriatal fibres functionally impairs distinct striatocortical connections, disturbing the efficient interplay between motor processing areas and impairing motor control in patients with Parkinson's disease. The present study is the first to reveal trimodal evidence for network-dependent degeneration in Parkinson's disease by outlining the impact of functional nigrostriatal pathway impairment on striatocortical functional connectivity networks and cortical metabolism.
Assuntos
Córtex Cerebral/fisiopatologia , Corpo Estriado/fisiopatologia , Doença de Parkinson/fisiopatologia , Substância Negra/fisiopatologia , Idoso , Estudos de Casos e Controles , Córtex Cerebral/metabolismo , Corpo Estriado/metabolismo , Di-Hidroxifenilalanina/análogos & derivados , Di-Hidroxifenilalanina/metabolismo , Dopamina/metabolismo , Feminino , Fluordesoxiglucose F18/metabolismo , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Vias Neurais/fisiopatologia , Doença de Parkinson/metabolismo , Tomografia por Emissão de Pósitrons , Putamen/fisiopatologia , Substância Negra/metabolismoRESUMO
Alzheimer's disease (AD) and sleep-disordered breathing (SDB) are prevalent conditions with a rising burden. It is suggested that SDB may contribute to cognitive decline and advanced aging. Here, we assessed the link between self-reported SDB and gray matter volume in patients with AD, mild cognitive impairment (MCI) and healthy controls (HCs). We further investigated whether SDB was associated with advanced brain aging. We included a total of 330 participants, divided based on self-reported history of SDB, and matched across diagnoses for age, sex and presence of the Apolipoprotein E4 allele, from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Gray-matter volume was measured using voxel-wise morphometry and group differences in terms of SDB, cognitive status, and their interaction were assessed. Further, using an age-prediction model fitted on gray-matter data of external datasets, we predicted study participants' age from their structural images. Cognitive decline and advanced age were associated with lower gray matter volume in various regions, particularly in the bilateral temporal lobes. Brains age was well predicted from the morphological data in HCs and, as expected, elevated in MCI and particularly in AD subjects. However, there was neither a significant difference between regional gray matter volume in any diagnostic group related to the SDB status, nor in SDB-by-cognitive status interaction. Moreover, we found no difference in estimated chronological age gap related to SDB, or by-cognitive status interaction. Contrary to our hypothesis, we were not able to find a general or a diagnostic-dependent association of SDB with either gray-matter volumetric or brain aging.
Assuntos
Doença de Alzheimer/patologia , Disfunção Cognitiva/patologia , Substância Cinzenta/patologia , Neuroimagem , Síndromes da Apneia do Sono/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Síndromes da Apneia do Sono/diagnóstico por imagem , Máquina de Vetores de SuporteRESUMO
PURPOSE OF REVIEW: Previous research has struggled with identifying clear-cut, objective counterparts to subjective distress in insomnia. Approaching this discrepancy with a focus on hyperarousal and dysfunctional affective processes, studies examining brain structures and neural networks involved in affect and arousal are reviewed and conclusions for an updated understanding of insomnia are drawn. RECENT FINDINGS: Recent studies found that amygdala reactivity, morphometry and adaptation in insomnia are altered, indicating that processing of negative stimuli is intensified and more lasting. Also, patients with insomnia show aberrant connectivity in the default mode network (DMN) and the salience network (SN), which is associated with subjective sleep disturbances, hyperarousal, maladaptive emotion regulation and disturbed integration of emotional states. The limbic circuit is assumed to play a crucial role in enhanced recall of negative experiences. There is reason to consider insomnia as a disorder of affect and arousal. Dysregulation of the limbic circuit might perpetuate impaired connectivity in the DMN and the SN. However, the interplay between the networks is yet to be researched.
Assuntos
Distúrbios do Início e da Manutenção do Sono , Nível de Alerta , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Neuroimagem , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagemRESUMO
Over the past decades, neuroimaging has become widely used to investigate structural and functional brain abnormality in neuropsychiatric disorders. The results of individual neuroimaging studies, however, are frequently inconsistent due to small and heterogeneous samples, analytical flexibility, and publication bias toward positive findings. To consolidate the emergent findings toward clinically useful insight, meta-analyses have been developed to integrate the results of studies and identify areas that are consistently involved in pathophysiology of particular neuropsychiatric disorders. However, it should be considered that the results of meta-analyses could also be divergent due to heterogeneity in search strategy, selection criteria, imaging modalities, behavioral tasks, number of experiments, data organization methods, and statistical analysis with different multiple comparison thresholds. Following an introduction to the problem and the concepts of quantitative summaries of neuroimaging findings, we propose practical recommendations for clinicians and researchers for conducting transparent and methodologically sound neuroimaging meta-analyses. This should help to consolidate the search for convergent regional brain abnormality in neuropsychiatric disorders.
Assuntos
Encéfalo/diagnóstico por imagem , Transtornos Mentais/diagnóstico por imagem , Metanálise como Assunto , Neuroimagem , Projetos de Pesquisa , HumanosRESUMO
Evidence shows the possible link between insomnia and perinatal depressive symptoms. In order to find a convergent quantitative answer, we collected data via the search of Medline, EMBASE and reference tracking, which included nine studies (a total sample of 1,922 women). An aggregate effect size estimate (correlation coefficient) was generated using the comprehensive meta-analysis software. For the meta-analytic procedure, a random effects model was set a priori. Moderating factors, including study design, method of assessment of depression, geographical origin of data, publication year, mean age, % married, breastfeeding rate, quality and type of data, % primiparous and history of depression, were examined via categorical or univariate mixed-effects (method of moments) meta-regression methods. Heterogeneity and publication bias were examined using standard meta-analytic approaches. We found a significant, medium-size relationship between insomnia and perinatal depressive symptoms (point estimate, 0.366; 95% confidence interval [CI], 0.205-0.508; p < 0.001; n = 9) and this was significantly heterogeneous (Q, 118.77; df, 8; p < 0.001; I2 , 93.26%). The effect size estimate was significant for studies reporting no history of depression (point estimate, 0.364; 95% CI, 0.035-0.622; p < 0.05; n = 5) and for study design. With meta-regression, no moderating factor (age, marriage rate, breastfeeding rate, pregnancy history or publication year) significantly mediated the effect size estimate. The depression assessment scale used, but not other categorical variables, explained the magnitude of heterogeneity. We found that insomnia during the perinatal period is associated with depressive symptoms, which warrants screening pregnant mothers for insomnia and depression.
Assuntos
Transtorno Depressivo/etiologia , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/psicologia , Adulto , Feminino , Humanos , Mães , Gravidez , Adulto JovemRESUMO
Over the last decade, synchronized resting-state fluctuations of blood oxygenation level-dependent (BOLD) signals between remote brain areas [so-called BOLD resting-state functional connectivity (rs-FC)] have gained enormous relevance in systems and clinical neuroscience. However, the neural underpinnings of rs-FC are still incompletely understood. Using simultaneous positron emission tomography/magnetic resonance imaging we here directly investigated the relationship between rs-FC and local neuronal activity in humans. Computational models suggest a mechanistic link between the dynamics of local neuronal activity and the functional coupling among distributed brain regions. Therefore, we hypothesized that the local activity (LA) of a region at rest determines its rs-FC. To test this hypothesis, we simultaneously measured both LA (glucose metabolism) and rs-FC (via synchronized BOLD fluctuations) during conditions of eyes closed or eyes open. During eyes open, LA increased in the visual system, and the salience network (i.e., cingulate and insular cortices) and the pattern of elevated LA coincided almost exactly with the spatial pattern of increased rs-FC. Specifically, the voxelwise regional profile of LA in these areas strongly correlated with the regional pattern of rs-FC among the same regions (e.g., LA in primary visual cortex accounts for â¼ 50%, and LA in anterior cingulate accounts for â¼ 20% of rs-FC with the visual system). These data provide the first direct evidence in humans that local neuronal activity determines BOLD FC at rest. Beyond its relevance for the neuronal basis of coherent BOLD signal fluctuations, our procedure may translate into clinical research particularly to investigate potentially aberrant links between local dynamics and remote functional coupling in patients with neuropsychiatric disorders.
Assuntos
Mapeamento Encefálico , Encéfalo , Fluordesoxiglucose F18/metabolismo , Vias Neurais/fisiologia , Descanso , Adulto , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Tomografia por Emissão de PósitronsRESUMO
In major depressive disorder, depressive episodes reoccur in â¼60% of cases; however, neural mechanisms of depressive relapse are poorly understood. Depressive episodes are characterized by aberrant topology of the brain's intrinsic functional connectivity network, and the number of episodes is one of the most important predictors for depressive relapse. In this study we hypothesized that specific changes of the topology of intrinsic connectivity interact with the course of episodes in recurrent depressive disorder. To address this hypothesis, we investigated which changes of connectivity topology are associated with the number of episodes in patients, independently of current symptoms and disease duration. Fifty subjects were recruited including 25 depressive patients (two to 10 episodes) and 25 gender- and age-matched control subjects. Resting-state functional magnetic resonance imaging, Harvard-Oxford brain atlas, wavelet-transformation of atlas-shaped regional time-series, and their pairwise Pearson's correlation were used to define individual connectivity matrices. Matrices were analysed by graph-based methods, resulting in outcome measures that were used as surrogates of intrinsic network topology. Topological scores were subsequently compared across groups, and, for patients only, related with the number of depressive episodes and current symptoms by partial correlation analysis. Concerning the whole brain connectivity network of patients, small-world topology was preserved but global efficiency was reduced and global betweenness-centrality increased. Aberrant nodal efficiency and centrality of regional connectivity was found in the dorsal striatum, inferior frontal and orbitofrontal cortex as well as in the occipital and somatosensory cortex. Inferior frontal changes were associated with current symptoms, whereas aberrant right putamen network topology was associated with the number of episodes. Results were controlled for effects of total grey matter volume, medication, and total disease duration. This finding provides first evidence that in major depressive disorder aberrant topology of the right putamen's intrinsic connectivity pattern is associated with the course of depressive episodes, independently of current symptoms, medication status and disease duration. Data suggest that the reorganization of striatal connectivity may interact with the course of episodes in depression thereby contributing to depressive relapse risk.
Assuntos
Mapeamento Encefálico/métodos , Corpo Estriado/patologia , Transtorno Depressivo Maior/patologia , Rede Nervosa/patologia , Adulto , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/patologia , Fatores de TempoRESUMO
BACKGROUND: The hippocampus (HP) is part of the default mode network (DMN), and both are key targets of Alzheimer's disease (AD). Because of widespread network degeneration, it has been suggested that increasing HP disconnection from the DMN may lead to progressive disinhibition of intra-HP synchronized activity. METHODS: To analyze HP local (i.e., within HP) and global (i.e., within DMN) intrinsic functional connectivity (local/global intrinsic functional connectivity [iFC]), healthy controls and patients with mild cognitive impairment and AD dementia were assessed by spatial high and normal resolution resting-state functional magnetic resonance imaging. RESULTS: Although patients' parietal local-iFC was reduced and positively correlated with reduced global-iFC within the DMN, HP local connectivity was progressively increased and negatively correlated with HP decreased global connectivity. Increased intra-HP connectivity was associated with impaired memory. CONCLUSION: Our result demonstrates a link between increased local and reduced global hippocampal connectivity in AD. Increased intra-HP synchrony may contribute to distinct symptoms such as memory impairment or more speculatively epileptic seizure.
Assuntos
Doença de Alzheimer/patologia , Hipocampo/patologia , Rede Nervosa/patologia , Vias Neurais/patologia , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Feminino , Hipocampo/irrigação sanguínea , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/irrigação sanguínea , Vias Neurais/irrigação sanguínea , Exame Neurológico , Oxigênio/sangue , Escalas de Graduação PsiquiátricaRESUMO
STUDY OBJECTIVES: Insomnia symptoms are prevalent along the trajectory of Alzheimer's disease (AD), but the neurobiological underpinning of their interaction is poorly understood. Here, we assessed structural and functional brain measures within and between the default mode network (DMN), salience network (SN), and central executive network (CEN). METHODS: We selected 320 subjects from the ADNI database and divided by their diagnosis: cognitively normal (CN), Mild Cognitive Impairment (MCI), and AD, with and without self-reported insomnia symptoms. We measured the gray matter volume (GMV), structural covariance (SC), degrees centrality (DC), and functional connectivity (FC), testing the effect and interaction of insomnia symptoms and diagnosis on each index. Subsequently, we performed a within-group linear regression across each network and ROI. Finally, we correlated observed abnormalities with changes in cognitive and affective scores. RESULTS: Insomnia symptoms were associated with FC alterations across all groups. The AD group also demonstrated an interaction between insomnia and diagnosis. Within-group analyses revealed that in CN and MCI, insomnia symptoms were characterised by within-network hyperconnectivity, while in AD, within- and between-network hypoconnectivity was ubiquitous. SC and GMV alterations were non-significant in the presence of insomnia symptoms, and DC indices only showed network-level alterations in the CEN of AD individuals. Abnormal FC within and between DMN and CEN hubs was additionally associated with reduced cognitive function across all groups, and increased depressive symptoms in AD. CONCLUSIONS: We conclude that patients with clinical AD present with a unique pattern of insomnia-related functional alterations, highlighting the profound interaction between both conditions.