Larger dlPFC and vmPFC grey matter volumes are associated with high adherence to the Mediterranean diet: A cross-sectional study in older adults.

Dietary self-control is associated with inter-individual differences in neuroanatomy. Yet, whether such inter-individual differences are also associated with healthier dietary patterns is yet to be determined. In this cross-sectional study, a total of 100 northern Portuguese older community-dwellers were assessed with regards to i) the adherence to a healthy dietary eating pattern - the Mediterranean diet (MedDiet), and ii) grey matter density (GMD) of brain regions associated with valuation and dietary self-regulation, the ventromedial (vmPFC) and dorsolateral prefrontal cortex (dlPFC), through voxel-based morphometry. Healthy food choices were ascertained through the Mediterranean Diet Adherence Screener (MEDAS) where higher scores indicated greater adherence to the MedDiet. Voxel-based morphometry showed that greater grey matter density in the dlPFC and vmPFC associated with a higher adherence to the MedDiet. These results replicate previous links between dietary decision-making measured under laboratory conditions and the neuroanatomy of the brain's valuation and self-control system. Importantly, they shed new light on the potential relevance of inter-individual differences in the neuroanatomy of these two brain regions for adhering to healthier dietary patterns in everyday life.

Anticipatory cues in emotional processing shift the activation of a combined salience sensorimotor functional network in drug-naïve depressed patients.

BACKGROUND: Major depressive disorder is characterized by a large-scale brain network dysfunction, contributing to impairments in cognitive and affective functioning. Core regions of default mode, limbic and salience networks are also impaired in emotional processing and anticipation. This study aimed to explore default mode, salience, and limbic networks modulation during the processing of emotional stimuli with and without anticipatory cues in depression, and further investigate how these networks were functionally coupled with the rest of the brain. METHODS: Twenty-one drug-naïve depressed patients and 15 matched controls were included in the study. All participants completed a psychological assessment and the affective pictures paradigm during an fMRI acquisition. Group independent component analysis and psychophysiological interactions analyses were performed. RESULTS: A significant interaction between Cue, Valence and Group was found for the salience/sensorimotor network. When processing uncued emotional stimuli, patients showed increased activation of this network for negative vs. neutral pictures, whereas when anticipatory cues were displayed previously to the picture presentation, they invert this pattern of activation (hyperactivating the salience/sensorimotor network for positive vs. neutral pictures). Patients showed increased functional connectivity between the salience/sensorimotor network and the left amygdala as well as the right inferior parietal lobule compared to controls when processing uncued negative pictures. LIMITATIONS: The sample size was modest, and the salience/sensorimotor network included regions not typically identified as part of salience network. Thus, this study should be replicated to further interpret the results. CONCLUSIONS: Anticipatory cues shift the pattern of activation of the salience/sensorimotor network in drug-naïve depressed patients.

Perceived stress modulates the activity between the amygdala and the cortex.

The significant link between stress and psychiatric disorders has prompted research on stress's impact on the brain. Interestingly, previous studies on healthy subjects have demonstrated an association between perceived stress and amygdala volume, although the mechanisms by which perceived stress can affect brain function remain unknown. To better understand what this association entails at a functional level, herein, we explore the association of perceived stress, measured by the PSS10 questionnaire, with disseminated functional connectivity between brain areas. Using resting-state fMRI from 252 healthy subjects spanning a broad age range, we performed both a seed-based amygdala connectivity analysis (static connectivity, with spatial resolution but no temporal definition) and a whole-brain data-driven approach to detect altered patterns of phase interactions between brain areas (dynamic connectivity with spatiotemporal information). Results show that increased perceived stress is directly associated with increased amygdala connectivity with frontal cortical regions, which is driven by a reduced occurrence of an activity pattern where the signals in the amygdala and the hippocampus evolve in opposite directions with respect to the rest of the brain. Overall, these results not only reinforce the pathological effect of in-phase synchronicity between subcortical and cortical brain areas but also demonstrate the protective effect of counterbalanced (i.e., phase-shifted) activity between brain subsystems, which are otherwise missed with correlation-based functional connectivity analysis.

Association of amygdala size with stress perception: Findings of a transversal study across the lifespan.

Daily routines are getting increasingly stressful. Interestingly, associations between stress perception and amygdala volume, a brain region implicated in emotional behaviour, have been observed in both younger and older adults. Life stress, on the other hand, has become pervasive and is no longer restricted to a specific age group or life stage. As a result, it is vital to consider stress as a continuum across the lifespan. In this study, we investigated the relationship between perceived stress and amygdala size in 272 healthy participants with a broad age range. Participants were submitted to a structural magnetic resonance imaging (MRI) to extract amygdala volume, and the Perceived Stress Scale (PSS) scores were used as the independent variable in volumetric regressions. We found that perceived stress is positively associated with the right amygdala volume throughout life.

The Association of Metabolic Dysfunction and Mood Across Lifespan Interacts With the Default Mode Network Functional Connectivity.

Background: Numerous studies suggest a relationship between depression and metabolic syndrome, which is likely influenced by age. Interestingly, functional imaging analysis has shown an association between functional connectivity in the default mode network (DMN-FC) and components of metabolic syndrome, which is explored in this study. Methods: From a larger longitudinal cohort study on healthy aging, 943 individuals were extensively characterized for mood and cognition. Among these, 120 individuals who were selected for displaying extreme cognitive performance within the normal range (good and poor performers) were further studied. Here, in a cross-sectional design, using confirmatory factor analysis (CFA), the association between metabolic dysfunction and depressive mood as a function of age and its relationship with DMN-FC was studied. Results: Metabolic dysfunction was modeled as a second-order latent variable using CFA. First-order latent variables were obesity, glucose dysmetabolism, lipids imbalance, and blood pressure. Using multiple linear regression models, this study observed that metabolic dysfunction, glucose dysmetabolism, and lipids imbalance were linearly associated with depressive mood, and the association with obesity was U-shaped. The association of metabolic dysfunction, obesity, and glucose dysmetabolism with depressive mood is positive for the younger individuals in our sample and vanishes with aging. The FC of the right superior temporal gyrus with the DMN correlated with both obesity and depressive mood. In participants with higher obesity scores, FC increased with higher GDS scores, while in those with lower GDS scores, FC decreased. Age and blood pressure were associated with a more complex pattern of association between FC of the right supramarginal gyrus and GDS score. Conclusion: The association of metabolic dysfunction with depressive mood is influenced by age and relates with differential patterns of DMN-FC. The combination of the effects of age, mood, and metabolic dysfunction is likely to explain the heterogeneity of DMN-FC, which deserves further investigation with larger and longitudinal studies.

White Matter Microstructure Alterations Associated With Paroxetine Treatment Response in Major Depression.

More than one-third of depressive patients do not achieve remission after the first antidepressant treatment. The "watch and wait" approach used to find the most effective antidepressant leads to an increased personal, social, and economic burden in society. In order to overcome this challenge, there has been a focus on studying neural biomarkers associated with antidepressant response. Diffusion tensor imaging measures have shown a promising role as predictors of antidepressant response by pointing to pretreatment differences in the white matter microstructural integrity between future responders and non-responders to different pharmacotherapies. Therefore, the aim of the present study was to explore whether response to paroxetine treatment was associated with differences in the white matter microstructure at baseline. Twenty drug-naive patients diagnosed with major depressive disorder followed a 6- to 12-week treatment with paroxetine. All patients completed magnetic resonance brain imaging and a clinical assessment at baseline and 6-12 weeks after treatment. Whole-brain tract-based spatial statistics was used to explore differences in white matter microstructural properties estimated from diffusion magnetic resonance imaging. Voxel-wise statistical analysis revealed a significant increase in fractional anisotropy and a decrease in radial diffusivity in forceps minor and superior longitudinal fasciculus in responders compared to non-responders. Thus, alterations in white matter integrity, specifically in forceps minor and the superior longitudinal fasciculus, are associated with paroxetine treatment response. These findings pave the way for personalized treatment strategies in major depression.

Assessing Impulsivity in Humans and Rodents: Taking the Translational Road.

Impulsivity is a multidimensional construct encompassing domains of behavioral inhibition as well as of decision making. It is often adaptive and associated with fast responses, being in that sense physiological. However, abnormal manifestations of impulsive behavior can be observed in contexts of drug abuse and attention-deficit/hyperactivity disorder (ADHD), among others. A number of tools have therefore been devised to assess the different facets of impulsivity in both normal and pathological contexts. In this narrative review, we systematize behavioral and self-reported measures of impulsivity and critically discuss their constructs and limitations, establishing a parallel between assessments in humans and rodents. The first rely on paradigms that are typically designed to assess a specific dimension of impulsivity, within either impulsive action (inability to suppress a prepotent action) or impulsive choice, which implies a decision that weighs the costs and benefits of the options. On the other hand, self-reported measures are performed through questionnaires, allowing assessment of impulsivity dimensions that would be difficult to mimic in an experimental setting (e.g., positive/negative urgency and lack of premeditation) and which are therefore difficult (if not impossible) to measure in rodents.

Amygdala size varies with stress perception.

Stress is inevitably linked to life. It has many and complex facets. Notably, perception of stressful stimuli is an important factor when mounting stress responses and measuring its impact. Indeed, moved by the increasing number of stress-triggered pathologies, several groups drew on advanced neuroimaging techniques to explore stress effects on the brain. From that, several regions and circuits have been linked to stress, and a comprehensive integration of the distinct findings applied to common individuals is being pursued, but with conflicting results. Herein, we performed a volumetric regression analysis using participants' perceived stress as a variable of interest. Data shows that increased levels of perceived stress positively associate with the right amygdala and anterior hippocampal volumes.

Signatures of white-matter microstructure degradation during aging and its association with cognitive status.

Previous studies have shown an association between cognitive decline and white matter integrity in aging. This led to the formulation of a "disconnection hypothesis" in the aging-brain, which states that the disruption in cortical network communication may explain the cognitive decline during aging. Although some longitudinal studies have already investigated the changes occurring in white matter microstructure, most focused on specific white matter tracts. Our study aims to characterize the longitudinal whole-brain signatures of white matter microstructural change during aging. Furthermore, we assessed the relationship between distinct longitudinal alterations in white matter integrity and cognition. White matter microstructural properties were estimated from diffusion magnetic resonance imaging, and cognitive status characterized from extensive neurocognitive testing. The same individuals were evaluated at two timepoints, with a mean interval time of 52.8 months (SD = 7.24) between first and last assessment. Our results show that age is associated with a decline in cognitive performance and a degradation in white matter integrity. Additionally, significant associations were found between diffusion measures and different cognitive dimensions (memory, executive function and general cognition). Overall, these results suggest that age-related cognitive decline is related to white matter alterations, and thus give support to the "disconnected hypothesis" of the aging brain.

A Wake-up Call for Burnout in Portuguese Physicians During the COVID-19 Outbreak: National Survey Study.

BACKGROUND: The COVID-19 outbreak has imposed physical and psychological pressure on health care professionals, including frontline physicians. Hence, evaluating the mental health status of physicians during the current pandemic is important to define future preventive guidelines among health care stakeholders. OBJECTIVE: In this study, we intended to study alterations in the mental health status of Portuguese physicians working at the frontline during the COVID-19 pandemic and potential sociodemographic factors influencing their mental health status. METHODS: A nationwide survey was conducted during May 4-25, 2020, to infer differences in mental health status (depression, anxiety, stress, and obsessive compulsive symptoms) between Portuguese physicians working at the frontline during the COVID-19 pandemic and other nonfrontline physicians. A representative sample of 420 participants stratified by age, sex, and the geographic region was analyzed (200 frontline and 220 nonfrontline participants). Moreover, we explored the influence of several sociodemographic factors on mental health variables including age, sex, living conditions, and household composition. RESULTS: Our results show that being female (ß=1.1; t=2.5; P=.01) and working at the frontline (ß=1.4; t=2.9; P=.004) are potential risk factors for stress. In contrast, having a house with green space was a potentially beneficial factor for stress (ß=-1.5; t=-2.5; P=.01) and anxiety (ß=-1.1; t=-2.4; P=.02). CONCLUSIONS: It is important to apply protective mental health measures for physicians to avoid the long-term effects of stress, such as burnout.

Iron Status is Associated with Mood, Cognition, and Functional Ability in Older Adults: A Cross-Sectional Study.

Several conditions are risk factors for iron deficiency (ID), some of which are highly prevalent in older individuals. Despite the amount of evidence pointing for a role of ID in cognition, mood and physical functional ability, the research addressing these associations in older individuals is still scarce. In the present study, 162 older community-dwelling individuals (29.53% classified as ID) were enrolled in a cross-sectional analysis and characterized regarding cognition, mood, functional ability, general nutritional intake and iron status. Assessment of iron status was performed using several blood biomarkers. Storage and erythropoiesis dimensions were positively associated with memory, along with an interaction (moderator effect) between iron storage and nutritional status. A more depressed mood was negatively associated with (iron) transport, transport saturation and erythropoiesis dimensions, and functional tiredness was positively associated with the erythropoiesis dimension. These observations indicate that lower iron status is associated with depressive mood, functional tiredness and poorer memory ability, with the latter moderated by nutritional status. These findings suggest that using iron as a continuous variable may be useful in finding associations with iron homeostasis, eventually missed when iron levels are considered within the usual classification groups.

Higher Adherence to the Mediterranean Diet Is Associated With Preserved White Matter Integrity and Altered Structural Connectivity.

The Mediterranean diet (MedDiet) has been associated with cognitive performance. Yet, controlled trials have yielded contradictory results. To tackle this controversy, a comprehensive multimodal analysis of the association of the MedDiet with cognitive performance and brain structure in normative aging is still necessary. Here, community dwellers ≥50 years from a cohort study on normative aging (n = 76) underwent a (i) magnetic resonance imaging session with two acquisitions: structural and diffusion-weighted imaging (DWI); (ii) neuropsychological battery of tests focusing on memory and executive functioning; and (iii) dietary assessment through the Mediterranean Diet Assessment Screener (MEDAS, score range: 0-14, scores ≥10 indicate high adherence to the Mediterranean diet) 18 months prior to the brain imaging and neuropsychological assessment. We found that high adherence to the MedDiet (MEDAS ≥10) was associated with higher values of fractional anisotropy and lower diffusivity values in the brain white matter. Similarly, high adherence to the MedDiet was associated with higher structural connectivity between left hemisphere brain regions. Specifically, the amygdala, lingual, olfactory, middle occipital gyrus, and calcarine areas. No association was found between high adherence to the MedDiet and total brain volumes or hypointensities. Higher adherence to the MedDiet was positively associated with executive functioning scores. These results suggest that high adherence to the MedDiet positively associates with brain health, specifically with executive function scores and white matter integrity of bundles related to the processing and integration of taste, reward, and decision making. These findings seem to support the view that the MedDiet should be part of recommendations to promote a healthy brain.

Modality-specific overlaps in brain structure and function in obsessive-compulsive disorder: Multimodal meta-analysis of case-control MRI studies.

Neuroimaging research has shown that patients with obsessive-compulsive disorder (OCD) may present brain structural and functional alterations, but the results across imaging modalities and task paradigms are difficult to reconcile. Are the same brain systems that are structurally different in OCD patients also involved in executive function and emotional processing? To answer this, we conducted separate meta-analyses of voxel-based morphometry studies, executive function functional magnetic resonance imaging (fMRI) studies, and emotional processing fMRI studies. Next, with a multimodal approach (conjunction analysis), we identified the common alterations across meta-analyses. Patients presented increased gray matter volume and hyperactivation in the putamen, but the putamen subregions affected differed depending on the psychological process. Left posterior/dorsal putamen showed hyperactivation during executive processing tasks, while predominantly right anterior/ventral putamen showed hyperactivation during emotional processing tasks. Interestingly, age was significantly associated with increased right putamen volume. Finally, the left dorsolateral prefrontal cortex was hyperactive in both functional domains. Our findings highlight task-specific correlates of brain structure and function in OCD and help integrate a growing literature.

Altered response to risky decisions and reward in patients with obsessive­compulsive disorder

Background: Patients with obsessive­compulsive disorder (OCD) employ ritualistic behaviours to reduce or even neutralize the anxiety provoked by their obsessions. The presence of excessive rumination and indecision has motivated the view of OCD as a disorder of decision-making. Most studies have focused on the "cold," cognitive aspects of decision-making. This study expands current understanding of OCD by characterizing the abnormalities associated with affective, or "hot" decision-making. Methods: We performed a functional MRI study in a sample of 34 patients with OCD and 33 sex- and age-matched healthy controls, during which participants made 2-choice gambles taking varying levels of risk. Results: During risky decisions, patients showed significantly reduced task-related activation in the posterior cingulum, lingual gyrus and anterior cingulate cortex. We identified significant group × risk interactions in the calcarine cortex, precuneus, amygdala and anterior cingulate cortex. During the outcome phase, patients with OCD showed stronger activation of the orbitofrontal cortex, anterior cingulate cortex and putamen in response to unexpected losses. Limitations: The group of patients not receiving medication was very small (n = 5), which precluded us from assessing the effect of medication on risk-taking behaviour in these patients. Conclusion: Obsessive­compulsive disorder is associated with abnormal brain activity patterns during risky decision-making in a set of brain regions that have been consistently implicated in the processing of reward prediction errors. Alterations in affective "hot" processes implicated in decision-making may contribute to increased indecisiveness and intolerance to uncertainty in patients with OCD.

The moderator effect of age in the association between mood and adiposity in the elderly is specific for the subcutaneous adipose compartment: An MRI study.

The positive association between obesity and depressive mood in young- and middle-age individuals is a phenomenon with major clinical implications in public health. Interestingly, the trend of this association in older individuals is not clear, given the conflicting results of multiple studies. Since aging is accompanied by changes in body fat distribution, we questioned whether age is a modulator of such association. This study explores the role of age in the association between mood and general (body mass index [BMI]) and abdominal adiposity (waist circumference [WC]) in older adults characterizing the different abdominal adipose tissue compartments (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT]) with magnetic resonance imaging (MRI) techniques. METHODS: One hundred twenty aged community-dwelling individuals (≥50 y of age) were assessed regarding depressive mood (Geriatric Depression Scale) and adiposity (BMI and WC). From these, 96 were assessed for SAT and VAT using MRI. RESULTS: Using multiple linear regression models, depressive mood was positively associated with BMI, WC, and VAT. Age was a significant moderator of the association between depressive mood and BMI, WC, and SAT: positive in younger participants and null or negative in older participants. On the other hand, higher VAT was significantly associated with a more depressive mood, independently of age. CONCLUSIONS: This study identifies age as a relevant moderator in the association between depressive mood and adiposity in the elderlies. Furthermore, the body fat compartment analysis revealed that the effect of age is specific for the SAT, suggesting its protective role in depressive mood.

Relationship between obsessive compulsive disorder and cortisol: Systematic review and meta-analysis.

Altered stress response and consequent elevated levels of circulating glucocorticoids have been found in neuropsychiatric disorders such as depression or anxiety disorders and proposed to also play a role in the pathophysiology of obsessive-compulsive disorder (OCD). Despite the observation that stressful events may precede the disease onset or even exacerbate its symptoms, studies in this field do not always report consistent results regarding the cortisol profile of OCD patients. As such, a systematic review and meta-analysis was developed to clarify this issue. This systematic review and meta-analysis was elaborated according to the PRISMA method. The analytical procedures were implemented using Metafor package in R software. Nineteen studies were included in the systematic review and 18 were included in the meta-analysis. The meta-analytic results demonstrated that OCD patients had significantly higher cortisol levels compared to controls (d = 0.76, SE = 0.146, p < 0.001). For studies using the average of multiple assessments, the standardized coefficient was significantly higher when compared to studies focusing on single measurements. Both the systematic review and meta-analysis suggest that cortisol levels are significantly higher in OCD patients than healthy individuals.

The resting-brain of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is one of the most debilitating psychiatric conditions, having a dramatic impact on patients' daily living. In this work, we aimed to explore resting-state functional connectivity in OCD patients, using an independent component analysis. Eighty individuals (40 patients and 40 healthy controls) performed a resting state fMRI protocol. OCD patients displayed reduced functional connectivity (FC) in visual and sensorimotor networks. In addition, patients displayed decreased FC between sensory networks and increased FC between default-mode and cerebellar networks.

Brain functional connectivity is altered in patients with Takotsubo Syndrome.

Takotsubo syndrome (TTS) is an acute, reversible cardiomyopathy. The central autonomic nervous system (ANS) is believed to play a role in this disease. The aim of the present study was to investigate the patterns of brain functional connectivity in a sample of patients who had experienced a previous episode of TTS. Brain functional connectivity, both at rest and in response to the stressful stimulus of topical cold stimulation, was explored using functional magnetic resonance imaging (fMRI), network-based statistics (NBS) and graph theory analysis (GTA) in a population consisting of eight patients with a previous episode of TTS and eight sex- and age-matched controls. At rest, a network characterized by increased connectivity in the TTS group compared to controls and comprising elements of the central ANS was identified. GTA revealed increased local efficiency, clustering and strength in regions of the bilateral hippocampus in subjects with a previous episode of TTS. When stressed by local exposure to cold, the TTS group differed significantly from both a pre-stress baseline interval and from the control group, showing increased connectivity in a network that included the left amygdala and the right insula. Based on the results, patients with TTS display a reorganization of cortical and subcortical networks, including areas associated with the emotional response and autonomic regulation. The findings tend to support the hypothesis that a deregulation of autonomic control at the central level plays a significant role in this syndrome.

Anatomic and non-anatomic reconstruction improves post-operative outcomes in chronic acromio-clavicular instability: a systematic review.

PURPOSE: To systematize the surgical outcomes of anatomic and non-anatomic reconstruction in patients with chronic acromio-clavicular joint (ACJ) instability and determine which technique is superior. METHODS: This review was conducted according to the PRISMA guidelines. PubMed and Cochrane Library databases were searched up to April 30th, 2018 for original articles that assessed the outcomes of one or more surgical techniques of anatomic and non-anatomic reconstruction in patients with chronic ACJ instability. The Methodological Index for Non-randomized Studies (MINORS) was used to assess study quality. Pre-to-post meta-analysis was performed for both anatomic and non-anatomic reconstructions. RESULTS: Twenty-eight studies were included comprising 799 patients (mean age of 36.6 years old and 84% males) with a mean follow-up of 34.6 months (range 13 to 74). Surgical techniques included anatomic (tendinous or synthetic grafts/constructs) and non-anatomic reconstruction (Weaver-Dunn or Modified Weaver-Dunn, conjoined tendon transfer, or temporary hook plate). There were significant pre-to-post improvements on the constant score with an average improvement ranging from 11.1 to 50.7 (p < 0.01). Average failure rate was 7.6% (7.5% for anatomic and 8.5% for non-anatomic reconstruction). Non-comparative studies had a mean MINORS score of 9 points (out of 16) and comparative studies 17 (out of 24) with excellent interrater agreement (k = 0.910). CONCLUSION: Both anatomic and non-anatomic ACJ reconstructions provide significant post-operative improvements, but definitive conclusions on optimal technique remain elusive. Notwithstanding, comparative studies support the use of anatomic ACJ reconstruction which should be preferably used. However, until superiority is demonstrated by robust studies, surgeons should supplement their decision-making with experience and patient preference. LEVEL OF EVIDENCE: IV.

Poor Sleep Quality Associates With Decreased Functional and Structural Brain Connectivity in Normative Aging: A MRI Multimodal Approach.

Sleep is a ubiquitous phenomenon, essential to the organism homeostasis. Notwithstanding, there has been an increasing concern with its disruption, not only within the context of pathological conditions, such as neurologic and psychiatric diseases, but also in health. In fact, sleep complaints are becoming particularly common, especially in middle-aged and older adults, which may suggest an underlying susceptibility to sleep quality loss and/or its consequences. Thus, a whole-brain modeling approach to study the shifts in the system can cast broader light on sleep quality mechanisms and its associated morbidities. Following this line, we sought to determine the association between the standard self-reported measure of sleep quality, the Pittsburgh Sleep Quality Index (PSQI) and brain correlates in a normative aging cohort. To this purpose, 86 participants (age range 52-87 years) provided information regarding sociodemographic parameters, subjective sleep quality and associated psychological variables. A multimodal magnetic resonance imaging (MRI) approach was used, with whole-brain functional and structural connectomes being derived from resting-state functional connectivity (FC) and probabilistic white matter tractography (structural connectivity, SC). Brain regional volumes and white matter properties associations were also explored. Results show that poor sleep quality was associated with a decrease in FC and SC of distinct networks, overlapping in right superior temporal pole, left middle temporal and left inferior occipital regions. Age displayed important associations with volumetric changes in the cerebellum cortex and white matter, thalamus, hippocampus, right putamen, left supramarginal and left lingual regions. Overall, results suggest that not only the PSQI global score may act as a proxy of changes in FC/SC in middle-aged and older individuals, but also that the age-related regional volumetric changes may be associated to an adjustment of brain connectivity. These findings may also represent a step further in the comprehension of the role of sleep disturbance in disease, since the networks found share regions that have been shown to be affected in pathologies, such as depression and Alzheimer's disease.