Healthy brain dynamics can be understood as the emergence of a complex system far from thermodynamic equilibrium. Brain dynamics are temporally irreversible and thus establish a preferred direction in time (i.e., arrow of time). However, little is known about how the time-reversal symmetry of spontaneous brain activity is affected by Alzheimer's disease (AD). We hypothesized that the level of irreversibility would be compromised in AD, signaling a fundamental shift in the collective properties of brain activity towards equilibrium dynamics. We investigated the irreversibility from resting-state fMRI and EEG data in male and female human patients with AD and elderly healthy control subjects (HC). We quantified the level of irreversibility and, thus, proximity to non-equilibrium dynamics by comparing forward and backward timeseries through time-shifted correlations. AD was associated with a breakdown of temporal irreversibility at the global, local, and network levels and at multiple oscillatory frequency bands. At the local level, temporoparietal and frontal regions were affected by AD. The limbic, frontoparietal, default mode, and salience networks were the most compromised at the network level. The temporal reversibility was associated with cognitive decline in AD and grey matter volume in HC. The irreversibility of brain dynamics provided higher accuracy and more distinctive information than classical neurocognitive measures when differentiating AD from controls. Findings were validated using an out-of-sample cohort. Present results offer new evidence regarding pathophysiological links between the entropy generation rate of brain dynamics and the clinical presentation of AD, opening new avenues for dementia characterization at different levels.SIGNIFICANCE STATEMENT:By assessing the irreversibility of large-scale dynamics across multiple brain signals, we provide a precise signature capable of distinguishing Alzheimer's disease (AD) at the global, local, and network levels and different oscillatory regimes. Irreversibility of limbic, frontoparietal, default mode, and salience networks was the most compromised by AD in comparison to more sensory-motor networks. Moreover, the time-irreversibility properties associated with cognitive decline and atrophy outperformed and complemented classical neurocognitive markers of AD in predictive classification performance. Findings were generalized and replicated with an out-of-sample validation procedure. We provide novel multilevel evidence of reduced irreversibility in AD brain dynamics that have the potential to open new avenues for understating neurodegeneration in terms of the temporal asymmetry of brain dynamics.
IntroductionEarly detection of depression is a cost-effective way to prevent adverse outcomes on brain physiology, cognition, and health. Here we propose that loneliness and social adaptation are key factors that can anticipate depressive symptoms.MethodsWe analyzed data from two separate samples to evaluate the associations between loneliness, social adaptation, depressive symptoms, and their neural correlates.ResultsFor both samples, hierarchical regression models on self-reported data showed that loneliness and social adaptation have negative and positive effects on depressive symptoms. Moreover, social adaptation reduces the impact of loneliness on depressive symptoms. Structural connectivity analysis showed that depressive symptoms, loneliness, and social adaptation share a common neural substrate. Furthermore, functional connectivity analysis demonstrated that only social adaptation was associated with connectivity in parietal areas.DiscussionAltogether, our results suggest that loneliness is a strong risk factor for depressive symptoms while social adaptation acts as a buffer against the ill effects of loneliness. At the neuroanatomical level, loneliness and depression may affect the integrity of white matter structures known to be associated to emotion dysregulation and cognitive impairment. On the other hand, socio-adaptive processes may protect against the harmful effects of loneliness and depression. Structural and functional correlates of social adaptation could indicate a protective role through long and short-term effects, respectively. These findings may aid approaches to preserve brain health via social participation and adaptive social behavior.
Characterizing a particular neurodegenerative condition against others possible diseases remains a challenge along clinical, biomarker, and neuroscientific levels. This is the particular case of frontotemporal dementia (FTD) variants, where their specific characterization requires high levels of expertise and multidisciplinary teams to subtlety distinguish among similar physiopathological processes. Here, we used a computational approach of multimodal brain networks to address simultaneous multiclass classification of 298 subjects (one group against all others), including five FTD variants: behavioral variant FTD, corticobasal syndrome, nonfluent variant primary progressive aphasia, progressive supranuclear palsy, semantic variant primary progressive aphasia; and healthy controls. Fourteen machine learning classifiers were trained with functional and structural connectivity calculated through different methods. Due to the large number of variables, dimensionality was reduced employing statistical comparisons and progressive elimination to assess feature stability under nested cross validation. The machine learning performance was measured through the area under the receiver operating characteristic curves, reaching 0.81 on average, with a standard deviation of 0.09. Furthermore, the contributions of demographic and cognitive data were also assessed via multifeatured classifiers. An accurate simultaneous multiclass classification of each FTD variant against other variants and controls was obtained, based on the selection of an optimum set of features. The classifiers incorporating brain’s network and cognitive assessment increased performance metrics. Multimodal classifiers evidenced specific variants’ compromise, across modalities and methods through the feature importance analysis. If replicated and validated, this approach may potentially help to support clinical decision tools aimed to detect specific affectations in the context of overlapping diseases.
Social adaptation arises from the interaction between the individual and the social environment. However, little empirical evidence exists regarding the relationship between social contact and social adaptation. We propose that loneliness and social networks are key factors explaining social adaptation. Sixty-four healthy subjects with no history of psychiatric conditions participated in this study. All participants completed self-report questionnaires about loneliness, social network, and social adaptation. On a separate day, subjects underwent a resting state fMRI recording session. A hierarchical regression model on self-report data revealed that loneliness and social network were negatively and positively associated with social adaptation. Functional connectivity (FC) analysis showed that loneliness was associated with decreased FC between the fronto-amygdalar and fronto-parietal regions. In contrast, the social network was positively associated with FC between the fronto-temporo-parietal network. Finally, an integrative path model examined the combined effects of behavioral and brain predictors of social adaptation. The model revealed that social networks mediated the effects of loneliness on social adaptation. Further, loneliness-related abnormal brain FC (previously shown to be associated with difficulties in cognitive control, emotion regulation, and sociocognitive processes) emerged as the strongest predictor of poor social adaptation. Findings offer insights into the brain indicators of social adaptation and highlight the role of social networks as a buffer against the maladaptive effects of loneliness. These findings can inform interventions aimed at minimizing loneliness and promoting social adaptation and are especially relevant due to the high prevalence of loneliness around the globe. These findings also serve the study of social adaptation since they provide potential neurocognitive factors that could influence social adaptation.
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