IntroductionOlfactory dysfunction is common in the Alzheimer’s Disease continuum, and olfaction may be altered before clinical syndrome onset. The present study aimed at investigating the functional connectivity of the olfactory cortex and its correlation with olfaction performance in a group of patients with Mild Cognitive Impairment (MCI) who subsequently converted or not converted to Alzheimer’s Disease (AD) dementia.MethodsAt baseline, 30 MCI patients were evaluated with the Sniffin’ Sticks (threshold, discrimination, and identification) to assess olfactory capacities, and they were followed up over time to identify converter and stable patients. Resting-state fMRI data acquired at baseline were analyzed to assess functional connectivity of left and right olfactory cortex. Beta values were extracted from the stable versus converter contrasts and correlated with olfactory scores.ResultsFunctional connectivity of the olfactory cortex was significantly increased with the posterior cingulate cortex, and significantly decreased with middle cingulate cortex, supplementary motor area, and left pre- and postcentral gyri, in converter compared to stable patients. Reduced negative functional connectivity between olfactory cortex and left angular gyrus emerged in converter patients, and a negative correlation was found between angular gyrus and discrimination scores.DiscussionOur findings indicate alterations of functional connectivity of the olfactory cortex in subjects with MCI at risk of conversion to AD dementia, even at the early stages of the disease. Additionally, the negative correlation between olfactory ability and the angular gyrus functional connectivity, a cerebral region known to be involved in multisensory integration processing, may be considered as a marker of disease progression.

Abstract Parkinson’s disease (PD) involves dopaminergic nigrostriatal pathways degeneration and early structural brain abnormalities, including iron accumulation in the substantia nigra (SN). Understanding how these neurodegenerative changes relate to functional network adaptations may clarify disease progression and symptom variability. We used a cross-sectional design to evaluate resting-state functional MRI, quantitative susceptibility mapping (QSM) and structural MRI measures in 38 early-stage PD patients (Hoehn&Yahr ≤2; disease duration 4.4 ± 2.3 years) and 30 age- and sex-matched healthy controls. The SN showed the earliest increase in magnetic susceptibility in PD, indicating elevated iron levels, without detectable volumetric changes. Within the PD group, higher QSM SN susceptibility was associated with increased resting-state connectivity in motor, visual, dorsal-attention, and executive-control networks. Notably, connectivity within the SN-related executive-control network cluster correlated with better executive function and visuospatial memory. These findings highlight the sensitivity of QSM in early PD and the value of multimodal imaging for characterising early functional and cognitive consequences of PD.

Abstract Background Depression is common and costly. First-line antidepressants are ineffective for many and have little impact against cognitive deficits. Stimulating 5-HT4 receptors (5-HT4R) rapidly improves learning and has antidepressant-like effects in rodents 1,2. The highly-selective 5-HT4R agonist, prucalopride (licensed for constipation), had a facilitatory effect on behavioural learning/memory in healthy humans after a single 3 and 6 days' treatment 4,5. Neurally, it also increased hippocampal activity 4 and reduced activation within the default mode network 5, findings supported at a network level by resting state analyses 6. Aims & Objectives Here, we present results from 2 further translational studies, examining 5-HT4R agonists in the context of mental illness. In study 1, we hypothesised that 5-HT4R agonism in participants with un-medicated depression would also increase hippocampal activation during a memory encoding task. In study 2, using a live electronic health record database, we investigated whether a prescription of prucalopride for constipation compared to alternative anti-constipation agents would reduce the future risk of depression. Method For study 1, 57 right-handed un-medicated depressed patients were randomised to a 5-HT4R agonist PF-04995274 (15mg) or placebo in a double-blind design. 53 participants received a 3T scan and fMRI memory task eliciting hippocampal activation 7 on day 6-9. Emotionally-neutral “familiar” pictures were viewed before the scan, and again in the scanner with similar “novel” images. Imaging data were analysed with FSL and corrected for multiple comparisons/sex/perfusion/grey matter. Study 2 was an emulated target trial using anonymised routinely collected data from TriNetX Analytics. We included adults without prior mental illness who received either a prescription of prucalopride (primary cohort) or linaclotide/lubiprostone (comparator cohorts). Cohorts were matched for 118 covariates capturing sociodemographics, comorbidities, and concurrent medications. The primary outcome was a first diagnosis of depressive disorder (ICD-10 F32) within two years of prescription date. Results 5-HT4 versus placebo participants had significantly lower HAM-D scores after study 1 [HAM-D 17: F(1,56)=7.6; p<0.01]. In hippocampal analyses, while processing scenes, the 5-HT4 group had significantly increased activity to novel compared to familiar images, particularly in the left hemisphere [condition*hemisphere*group: F(1,49)=3.56, p=0.04, ηρ2=0.08); novel vs familiar (i) prucalopride L (p=0.035) &R hemisphere (p=0.050); (ii) placebo L (p=0.789) &R hemisphere (p=0.053)]. In study 2, treatment with prucalopride was associated with reduced incidence of depression compared to both lubiprostone [HR 0.84, 95% CI 0.73-0.96, p=0.01, n=7101) and linaclotide (HR 0.85, 95% CI 0.75-0.97, p=0.016, n=6460]. Secondary analyses indicated robustness and specificity of the results. Discussion & Conclusion In participants with un-medicated depression, the 5-HT4R agonist PF-04995274 increased hippocampal activation during a memory task; a replication of previous results in healthy volunteers using another 5-HT4R agonist. The pharmaco-epidemiological findings also suggest 5-HT4R agonists may be novel agents in the prevention of depression. Results from both studies are consistent with preclinical evidence establishing a key role for 5-HT4Rs in mood disorders and cognitive deficits. References 1) Lucas G, Rymar VV, Du J, et al. Serotonin(4) (5-HT(4)) receptor agonists are putative antidepressants with a rapid onset of action. Neuron 2007; 55(5): 712-25. 2) Murphy SE, de Cates AN, Gillespie AL, et al. Translating the promise of 5HT4 receptor agonists for the treatment of depression. Psychol Med 2021; 51(7): 1111-20. 3) Murphy S, Wright L, Browning M, Cowen P, Harmer C. A role for 5-HT4 receptors in human learning and memory. Psychol Med 2020; 50(16): 2722-30. 4)de Cates AN, Wright LC, Martens MAG, et al. Deja-vu? Neural and behavioural effects of the 5-HT4 receptor agonist, prucalopride, in a hippocampal-dependent memory task. Trans Psychiatry 2021; 11: 497. 5) de Cates AN, Martens MAG, Wright LC, et al. The effect of the 5-HT4 agonist, prucalopride, on an fMRI faces task in the healthy human brain. Frontiers in Psychiatry 2022; 13(859123). 6) de Cates AN, Martens MAG, Wright LC, et al. 5-HT4 receptor agonist effects on functional connectivity in the human brain; Implications for pro-cognitive action. Biol Psychiatry Cogn Neurosci Neuroimaging 2023. 7) Filippini N, MacIntosh BJ, Hough MG, et al. Distinct patterns of brain activity in young carriers of the APOE-epsilon4 allele. Proc Natl Acad Sci U S A 2009; 106(17): 7209-14.

AIM:Crohn's disease (CD) is associated with psychological disorders and insecure attachment styles, potentially reflecting the long-lasting disease effect. Although functional magnetic resonance imaging (fMRI) studies revealed differences in CD patients relative to HC, the brain properties underlying the attachment dimensions in CD remain scarcely investigated. We carried out an fMRI study to investigate the neural substrate of the attachment dimensions in CD patients and healthy controls (HCs). MATERIALS AND METHOD:Nineteen CD patients and 18 HC were included in this study. All participants filled out the Attachment Style Questionnaire (ASQ) widely used to evaluate the dimensions of the attachment style and underwent an MRI protocol including structural and functional scans. RESULTS:The ASQ scores were similar between groups. Concerning the resting fMRI data, we identified two opposite trajectories for the association between two ASQ subscales reflecting attachment insecurity and the default mode network (DMN) connectivity between the two study groups. For the HC, higher scores at the ASQ were associated with reduced DMN connectivity, whereas in CD patients were related to increased DMN connectivity. The significant clusters were located in the superior frontal gyrus, posterior cingulate, and orbito-frontal regions. CONCLUSION:DMN is involved in higher mental functions including self-consciousness and affective processes. In CD patients, the DMN modifications associated with attachment insecurity might reflect dysfunctional monitoring of the self and the significant relationships potentially involved in the development of psychological stress and decreased mentalization. Our study strengthens the notion that the attachment dimensions should be considered in the treatment of IBD and encourages novel psychotherapeutic approaches based on mentalization.

Predictive coding mechanisms facilitate detection and perceptual recognition, thereby influencing recognition judgements, and, broadly, perceptual decision-making. The anterior insula (AI) has been shown to be involved in reaching a decision about discrimination and recognition, as well as to coordinate brain circuits related to reward-based learning. Yet, experimental studies in the context of recognition and decision-making, targeting this area and based on formal trial-by-trial predictive coding computational quantities, are sparse. The present study goes beyond previous investigations and provides a predictive coding computational account of the role of the AI in recognition-related decision-making, by leveraging Zaragoza-Jimenez et al. (2023) open fMRI dataset (17 female, 10 male participants) and computational modeling, characterized by a combination of view-independent familiarity learning and contextual learning. Using model-based fMRI, we show that, in the context a two-option forced-choice identity recognition task, the AI engages in feature-level (i.e., view-independent familiarity) updating and error signaling processes and context-level familiarity updating to reach a recognition judgment. Our findings highlight that an important functional property of the AI is to update the level of familiarity of a given stimulus while also adapting to task-relevant, contextual information. Ultimately, these expectations, combined with input visual signals through reciprocally interconnected feedback and feedforward processes, facilitate recognition judgments, thereby guiding perceptual decision-making.

Obesity is a significant global public health concern with over 1 billion people worldwide suffering from obesity. It is a major risk factor for several health conditions, so understanding the causes is crucial. With regard to the psychological state, depression plays a key role as it increases the risk of weight gain by 58%, with a reciprocal relationship where obesity can also lead to depression due to societal stigma and chronic health-related issues. Attachment theory provides insight into the psychological underpinnings of obesity, suggesting that insecure attachment can lead to maladaptive coping strategies such as emotional eating. This study aims to explore attachment style and related variables (ie, obesity-related well-being, perceived stress, and eating behaviour) as predictors of obesity, with the potential to inform targeted prevention and intervention programmes. A cross-sectional design was used. Ninety-two female patients with overweight or obesity participated in the study. Multiple regression analyses showed that three factors of attachment style were significant predictors of depression. Particularly, confidence and relationships as secondary were negative predictors (low score on attachment high score on depression), whereas need for approval was a positive predictor (high score on attachment high score on depression). Finally, high score on well-being was associated with high score on obesity (a positive predictor). This study shows that psychological traits, such as attachment style, are fundamental in predicting depression in patients with obesity. The results intend to pave the way to develop clinical intervention to prevent and reduce the impact of depression in patients with obesity.

Introduction. Obesity is a complex condition associated not only with physical health risks but also with social discrimination and a reduced quality of life (QoL). Psychological factors, including attachment styles, may play a role in emotional regulation and eating behaviors. According to attachment theory, insecure attachment is linked to difficulties in managing emotions and an increased likelihood of engaging in dysfunctional eating patterns. This study aimed to investigate the relationship between past and present attachment styles, binge-eating behaviors, and QoL scores in individuals with overweight or obesity (BMI ≥ 25 kg/m2) compared to those with a BMI in the normal weight range (18.5–24.9 kg/m2). Methods. A cross-sectional study evaluated 96 women with overweight/obesity and 96 women with normal weight. Psychological measures included the Parental Bonding Instrument (PBI), the Attachment Style Questionnaire (ASQ), the Binge Eating Scale (BES), and the Obesity-Related Well-being questionnaire (ORWELL 97). Data analysis included between-group comparisons of attachment dimensions and hierarchical regression to examine associations with the QoL score. Results. Participants with overweight/obesity showed less secure attachment (U = 5508, p = 0.019) and more avoidant attachment styles (U = 3825, p = 0.042) compared to participants with normal weight. Conversely, no significant differences were observed in PBI scores. Regression analysis revealed that attachment anxiety (B = 0.83, p = 0.009) and binge-eating behaviors (B = 0.57, p = 0.003) were significantly associated with a lower QoL. Conclusions. Obesity is associated with avoidant attachment in adulthood, but no differences were found in parental attachment when compared to individuals with normal body weight. Anxious attachment in individuals with obesity is strongly linked to reduced QoL, underlying the role played by attachment-related factors in the psychosocial challenges individuals often have to face.

Population-based studies have shown that the intake of Angiotensin-II receptor blockers (ARBs), commonly used to treat high blood pressure, is associated with reduced post-traumatic stress disorder (PTSD) symptoms. However, the underlying neural mechanisms remain unclear. While PTSD development is characterized by maladaptive processing within brain networks associated with fear processing and memory formation during trauma exposure, there is increasing evidence that such aberrations manifest in altered resting state functional connectivity (rsFC) of brain regions in these networks.In this double-blind placebo-controlled study in 45 healthy volunteers with high trait-anxiety, we investigated whether the ARB losartan would affect rsFC in prominent seeds of the fear and memory network, counteracting effects seen in PTSD.Seed selection was informed by established rsFC aberrations seen in PTSD and consisted of the hippocampus and the parahippocampal gyrus (memory network), as well the amygdala and insula (fear network).Our results showed that a single dose of the ARB losartan decreased rsFC in the memory network from modulatory structures in the frontal cortex: losartan decreased rsFC (i) between the hippocampus and the inferior frontal gyrus involved in threat processing and memory intrusion development, and (ii) between the parahippocampal gyrus and the dorsolateral prefrontal cortex involved in top-down control. There were no drug effects on the fear network seeds. These findings may imply that ARB preserves adaptive memory function during trauma.

Background/Objectives: Olfactory decline is common in normal aging and frequent in neurodegenerative diseases such as Alzheimer’s disease (AD). Therefore, it has been suggested as a marker for the Mild Cognitive Impairment (MCI) progression to AD. Although suggested, the relationship between olfactory deficits and cerebral atrophy in MCI conversion to AD is still debated. This study aims at investigating the olfaction-related morphological and behavioural alterations in MCI in order to understand whether they can predict the progression to AD. Methods: Twenty-seven MCI patients and thirty-five healthy controls (HCs) took part in the study, with follow-up showing conversion to AD in thirteen patients (converter-MCI, cMCI). The Burgarth Sniffin’ Sticks Tests (threshold—TT, discrimination—DT, identification—IT) assessed the olfactory capacities. The Voxel-Based Morphometry (VBM) analysis investigated the atrophic patterns. Results: The Receiving Operating Characteristics analyses demonstrated that DT and IT could distinguish HC from MCI (DT Area Under Curve—AUC = 0.8; IT AUC = 0.8), as well as cMCI from sMCI (stable) patients (DT AUC = 0.7; IT AUC = 0.6), similarly to memory and executive functions tests. Olfactory performance positively correlated with memory tests in sMCI (all rhos ≥ 0.8, all ps < 0.01), whereas it positively correlated with executive functions in cMCI (all rhos ≥ 0.6, all ps < 0.05). VBM results revealed distinct atrophic patterns in cMCI, especially in the olfactory cortex, that were already present at the MCI diagnosis, before AD conversion. A larger volume of the olfactory cortex was associated with better memory and executive functions. Conclusions: Quantitative olfactory and morphological patterns represent non-invasive, predictive biomarkers of the MCI progression to AD; thus, their assessments at MCI onset allows earlier interventions for MCI patients.

Obesity is a global health concern, and it is thought to accelerate the normal ageing process. Obesity has also been linked to neurodegenerative processes, possibly as a manifestation of accelerated brain-ageing. In this cross-sectional study we combined multimodal neuroimaging data and machine learning techniques to assess the discrepancy between brain-based predicted age and chronological age, known as brain age delta, in obese participants and in normal-weighted individuals using a tight matching for age, gender and education across groups. Data were taken from the publicly available dataset 'The Cambridge Centre for Ageing and Neuroscience (Cam-CAN)' covering the adult lifespan (18-90 years old). Overall, brain age delta was greater in obese individuals for grey matter (GM) and functional connectivity (intra- and inter-network connectivity) measures. When considering the age-range, the difference between groups peaked in mid-age (40-60 years old) for GM, while for intra-network connectivity it was more marked in late age (60-90 years old). Overall, our results provide evidence to the hypothesis that obesity accelerates the brain ageing process, with the earliest effect already evident in the 40-60 age range. Earlier intervention on obesity might contribute to maintain a healthy brain potentially reducing the risk of developing late-life brain-related pathologies.

OBJECTIVE:People who have survived stroke may have motor and cognitive impairments. High dose of motor rehabilitation was found to provide clinically relevant improvement to upper limb (UL) motor function. Besides, mounting evidence suggests that clinical, neural, and neurophysiological features are associated with spontaneous recovery. However, the association between these features and rehabilitation-induced, rather than spontaneous, recovery has never been fully investigated. The objective was to explore the association between rehabilitation dose and UL motor outcome after stroke, as well as to identify which variables can be considered potential candidate predictors of motor recovery. METHODS:People who survived stroke were assessed before and after a period of rehabilitation using motor, cognitive, neuroanatomical, and neurophysiological measures. We investigated the association between dose of rehabilitation and UL response (ie, Fugl-Meyer Assessment for upper extremity [FMA-UE]), using ordinary least squares regression as the primary analysis. To obtain unbiased estimates, adjusting covariates were selected using a directed acyclic graph. RESULTS:Baseline FMA-UE was the only factor associated with motor recovery (b = 0.99; 95% CI = 0.83 to 1.15 points). Attention emerged as a confounder of the association between rehabilitation and final FMA-UE (b = 5.5; 95% CI = -0.8 to 11.9 points), influencing both rehabilitation and UL response. CONCLUSION:Preserved attention in people who have survived stroke might lead to greater UL motor recovery, albeit estimates have high levels of variability. Moreover, the increase in the dose of rehabilitation can lead to 5.5 points improvement on the FMA-UE, a nonsignificant but potentially meaningful finding. The approach described here discloses a new framework for investigating the effect of rehabilitation treatment as a potential driver of recovery. IMPACT:Attentional resources could play a key role in UL motor recovery. There is a potential association between amount of UL recovery and dose of rehabilitation delivered, needing further exploration. Preserved attention and rehabilitation dose are candidate predictors of UL motor recovery.

The choice of control conditions can significantly influence the outcomes of functional MRI (fMRI) studies. Moreover, especially in language experiments, the sensory modality (auditory, visual) of stimuli might have an influence on experimental results. In this study we leverage a repository dataset (Mother of Unification Studies; MOUS), to systematically investigate the influence of control condition and stimulation modality on fMRI results during sentence processing. Here, we explored fMRI data of 187 subjects that underwent sentence comprehension with either auditory or visual task presentation (reading or listening). Sentences were either complex, including a relative clause, or simple, not including a relative clause. Control conditions were randomly scrambled words as constructed out of the latter sentence conditions. While auditory stimulation resulted in strong activation changes in the bilateral auditory cortices, visual stimulation revealed stronger activation changes in the anterior temporal lobe if compared to simple and complex words, but not simple sentences. A direct comparison between the auditory and visual modality revealed stronger involvement of the primary auditory cortices for auditory stimulation and left inferior frontal gyrus for visual stimulation over all four conditions (complex sentences, simple sentences, complex words, simple words). The results of this study suggest that stimulation modality and control condition strongly influence sentence processing fMRI results. Future fMRI studies should bear this in mind for study planning.

ObjectiveFrailty has emerged as prevalent condition in ageing. While frailty has been assessed through physical and functional criteria, recent studies have explored the link between cognitive decline and frailty, which remains complex and warrants further investigation. Our aims were to compare differences at the brain level between robust and frail older people without dementia and to explore possible associations between brain measures and cognitive performance assessed with neuropsychological tests.MethodsUsing data from the "CAM-Cam" project that recruited a community dwelling population, we identified robust and frail participants based on the Rockwood Frailty index. Magnetic Resonance Imaging was performed to probe the interplay between physical frailty and cognitive health. The main aims were: (i) to identify differences in cognitive performance using the Cattell Culture Fair test and the Tip of the Tongue test and (ii) to assess voxel-wise group-related effects, using a general linear model design to investigate potential differences between our two study groups ("frail" and "robust").ResultsOur findings revealed significantly smaller grey matter volume in frail individuals, primarily localized in cerebellar areas and in the right supramarginal gyrus. Diffusion magnetic resonance imaging scans showed diminished axial diffusivity values in frail participants, particularly in the corticospinal tract. Resting-state functional MRI showed increased functional connectivity values within the Default Mode Network (DMN) in frail individuals, relative to the robust group in parietal and cerebellar portions of the DMN. Moreover, we observed significant correlations between cognitive score and brain measures for our study groups.ConclusionsThe associations between cognitive test scores and anatomical and functional patterns in the brain highlight the complex interconnections between physical and cognitive aspects of frailty. This study brings novel insights into the early neurobiological markers associated with physical frailty in a cognitively healthy population.

INTRODUCTION:Crohn's disease (CD) is a chronic inflammatory condition associated with psychological stress and anxiety. Functional magnetic resonance imaging (fMRI) studies have shown differences in brain function between patients with CD and healthy controls (HC). This study aimed to compare the neural correlates of anxiety inindividuals with CD relative to HC, using resting-state fMRI data. METHODS:Participants filled in the State-Trait Anxiety Inventory (STAI), a validated tool for measuring anxiety, and underwent an MRI acquisition, including both structural and functional sequences, to identify brain regions associated with anxiety scores. RESULTS:Seventeen patients with CD and eighteen HC matched for age, education, and sex participated in the study. No significant group differences emerged in the STAI scores. However, resting-state fMRI analysis revealed distinct patterns of functional connectivity associated with anxiety scores for the two study groups. Among CD group, greater STAI scores correlated with increased functional connectivity, whereas, in HC, they correlated with decreased functional connectivity. Significant clusters were found in brain regions belonging to specific resting-state networks (RSNs): (a) Posterior Cingulate Cortex (PCC, within the Default Mode Network), (b) left Middle Frontal Gyrus (within the Left Fronto-Parietal Network), and (c) PCC and right Superior Temporal Gyrus (within the Dorsal Attention Network). CONCLUSION:The differential association between functional connectivity and STAI scores observed for CD and HC participants was located in areas within self-referential (Default Mode Network) and cognitive (Left Fronto-Parietal Network and Dorsal Attention Network) RSNs. Our findings suggest that maladaptive/dysfunctional processing of negative emotions and visceral sensitivity may occur in patients with CD.

Recent studies have shown a growing interest in the so-called “aperiodic” component of the EEG power spectrum, which describes the overall trend of the whole spectrum with a linear or exponential function. In the field of brain aging, this aperiodic component is associated both with age-related changes and performance on cognitive tasks. This study aims to elucidate the potential role of education in moderating the relationship between resting-state EEG features (including aperiodic component) and cognitive performance in aging. N = 179 healthy participants of the “Leipzig Study for Mind–Body-Emotion Interactions” (LEMON) dataset were divided into three groups based on age and education. Older adults exhibited lower exponent, offset (i.e. measures of aperiodic component), and Individual Alpha Peak Frequency (IAPF) as compared to younger adults. Moreover, visual attention and working memory were differently associated with the aperiodic component depending on education: in older adults with high education, higher exponent predicted slower processing speed and less working memory capacity, while an opposite trend was found in those with low education. While further investigation is needed, this study shows the potential modulatory role of education in the relationship between the aperiodic component of the EEG power spectrum and aging cognition.

The ageing process is associated with reduced emotional recognition (ER) performance. The ER ability is an essential part of non-verbal communication, and its role is crucial for proper social functioning. Here, using the 'Cambridge Centre for Ageing and Neuroscience cohort sample', we investigated when ER, measured using a facial emotion recognition test, begins to consistently decrease along the lifespan. Moreover, using structural and functional MRI data, we identified the neural correlates associated with ER maintenance in the age groups showing early signs of ER decline (N = 283; age range: 58-89 years). The ER performance was positively correlated with greater volume in the superior parietal lobule, higher white matter integrity in the corpus callosum and greater functional connectivity in the mid-cingulate area. Our results suggest that higher ER accuracy in older people is associated with preserved gray and white matter volumes in cognitive or interconnecting areas, subserving brain regions directly involved in emotional processing.

Aging is associated with changes in the oscillatory -periodic-brain activity in the alpha band (8-12 Hz), as measured with resting-state EEG (rsEEG); it is characterized by a significantly lower alpha frequency and power. Aging influences the aperiodic component of the power spectrum: at a higher age the slope flattens, which is related with lower cognitive efficiency. It is not known whether education, a cognitive reserve proxy recognized for its modulatory role on cognition, influences such relationship. N=179 healthy participants of the LEMON dataset (Babayan et al., 2019) were grouped based on age and education: young adults with high education and older adults with high and low education. Eyes-closed rsEEG power spectrum was parametrized at the occipital level. Lower IAPF, exponent, and offset in older adults were shown, compared to younger adults. Visual attention and working memory were differently predicted by the aperiodic component across education: in older adults with high education, higher exponent predicted slower processing speed and less working memory capacity, with an opposite trend in those with lower education. Further investigation is needed; the study shows the potential modulatory role of education in the relationship between the aperiodic component of the EEG power spectrum and aging cognition.

ObjectivesIn healthy aging, the way people cope differently with cognitive and neural decline is influenced by exposure to cognitively enriching life-experiences. Education is one of them, so that in general, the higher the education, the better the expected cognitive performance in aging. At the neural level, it is not clear yet how education can differentiate resting state functional connectivity profiles and their cognitive underpinnings. Thus, with this study, we aimed to investigate whether the variable education allowed for a finer description of age-related differences in cognition and resting state FC. MethodsWe analyzed in 197 healthy individuals (137 young adults aged 20-35 and 60 older adults aged 55-80 from the publicly available LEMON database), a pool of cognitive and neural variables, derived from magnetic resonance imaging, in relation to education. Firstly, we assessed age-related differences, by comparing young and older adults. Then, we investigated the possible role of education in outlining such differences, by splitting the group of older adults based on their education. ResultsIn terms of cognitive performance, older adults with higher education and young adults were comparable in language and executive functions. Interestingly, they had a wider vocabulary compared to young adults and older adults with lower education. Concerning functional connectivity, the results showed significant age- and education-related differences within three networks: the Visual-Medial, the Dorsal Attentional, and the Default Mode network (DMN). For the DMN, we also found a relationship with memory performance, which strengthen the evidence that this network has a specific role in linking cognitive maintenance and FC at rest in healthy aging. DiscussionOur study revealed that education contributes to differentiating cognitive and neural profiles in healthy older adults. Also, the DMN could be a key network in this context, as it may reflect some compensatory mechanisms relative to memory capacities in older adults with higher education.

Emotion regulation (ER) is the process by which individuals can modulate the intensity of their emotional experience and it plays a crucial role in daily life. So far, behavioral analyses seem to suggest that ER ability remains stable throughout the lifespan. However, imaging studies evaluating the neural correlates of ER performance during the aging process have shown mixed results. In this study, we used the "Cambridge Centre for Ageing and Neuroscience cohort sample" to investigate: (1) ER behavioral performance and (2) the differential association between brain measures (based on both structural and functional connectivity data) and ER performance, in a group of younger/middle-aged participants (N = 159; age range: 18y < x < 58y) relative to a group of older healthy subjects (N = 136; age range: 58y < =x < 89y). Whereas we found no group-related differences either in ER behavioral data or the association between ER performance and structural data, we did observe that ER performance was differentially correlated in our two study groups to functional connectivity measures in the fronto-insular-temporal network, which has been shown to be involved in emotional processing. Group-related differences were specifically localized in a cluster of voxels within the anterior cingulate areas which revealed a reverse pattern between our study groups: in younger/middle-aged participants better ER performance was associated with increase connectivity, whereas among older participants better ER performance was related to reduced connectivity. Based on our results, we suggest that a de-differentiation mechanism, known to affect the frontal lobes brain activity and connectivity in older subjects, might explain our findings.