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Response-optimised training improves learning of a complex motor task and closely related motor tasks.

Regular physical exercise is essential for promoting healthy aging and longevity. In older adults with varying physical and cognitive decline, optimising exercise interventions is crucial to maximise benefits. A promising approach to achieve this goal is by adjusting task demands to individual abilities in turn preventing over- or underloading their abilities. In the field of motor learning, it is currently unclear whether such an optimised training improves not only performance on the trained task but also transfers to untrained motor and cognitive tasks. We conducted a randomized, single-blinded, 6-week dynamic balance training (DBT) with healthy older adults (n = 30). Training was tailored to individual balance ability. Participants were assigned to either suboptimal (high or low difficulty) or optimal (moderate difficulty) training groups. Transfer effects were assessed via cognitive tasks (memory and executive) and motor tasks (untrained DBT variations and other balance tasks) measured pre-, mid- and post-intervention. Multivariate longitudinal statistical analysis showed higher performance gains in the optimal training group in three out of six sessions compared to the suboptimal groups, especially under testing conditions with high task demands. The optimal group also showed greater improvements in near motor transfer tasks mid- and post-intervention, while no significant differences were observed in the cognitive tasks. Within-group DBT learning positively correlated with transfer gains, highlighting the role of training response in achieving transfer. In conclusion, optimised task difficulty in balance training enhances both task-specific performance and related motor skills, supporting the use of personalised interventions to maintain function and independence in older adults.

Humans

Effects of acute resistance exercise on prefrontal oxygenation and task-switching performance: Considerations of loading strategies and blood flow restriction.

Although acute resistance exercise (RE) has been proposed to influence cognitive flexibility and underlying neural mechanisms, it remains unclear whether these effects vary across loading strategies and whether exercise-induced prefrontal hemodynamic responses translate into cognitive outcomes. The present study examined (1) prefrontal cortex (PFC) oxygenated hemoglobin (O2Hb) responses across exercise sets and conditions, (2) the effects of low-load (LL), LL with blood flow restriction (BFR), and high-load (HL) RE on task-switching performance, and (3) whether exercise-related PFC O2Hb responses were associated with pre- to post-exercise changes in task-switching performance. Thirty physically active adults completed three randomized, counterbalanced RE conditions consisting of four sets of barbell squats. LL was performed at 30% one-repetition maximum (1RM) with and without BFR, whereas HL was performed at 70% 1RM. Cognitive flexibility was assessed pre- and post-exercise using a modified Stroop task, indexed by switch-cost reaction time (RT) and accuracy. PFC O2Hb was assessed using functional near-infrared spectroscopy during exercise and expressed as changes from the resting baseline for each set (Sets 1-4). PFC O2Hb increased across sets, rising from Set 1 to Set 3 before plateauing, with no differences observed across conditions. Switch cost RT and accuracy did not improve from pre- to post-exercise, and no differences across conditions were detected. PFC O2Hb during the final set was not associated with changes in switch cost. These findings suggest that although acute RE elicits robust increases in prefrontal hemodynamic activity, such responses may not translate into acute improvements in cognitive flexibility.

Humans

Effects of Digital Mental Health Screening Alone and With the Online MINDBODYSTRONG CBT-Based Program on Burnout, Depression, Anxiety, Healthy Behaviors, and Suicidal Ideation in at-Risk Nurses at 3- and 6-Months Post-Intervention: An RCT.

BACKGROUND: Burnout and mental distress among nurses are global public health epidemics that adversely affect nurse well-being and healthcare quality. Evidence-based, scalable mental health interventions are urgently needed. AIMS: To evaluate the 3- and 6-month outcomes of a randomized controlled trial (RCT) comparing a psychologically safe, digital mental health screening and referral program alone versus the same screening and referral program combined with the video-based online MINDBODYSTRONG (MBS) cognitive behavioral therapy (CBT)-based skills-building program among nurses at risk for mental distress. METHODS: 501 nurses were recruited from professional organizations and healthcare systems across the United States by email and randomized to either mental health screening and referral (standard care) or standard care plus the MBS cognitive behavioral skills-building intervention (the intervention). All study activities were conducted remotely. Follow-up surveys administered at 3- and 6-months assessed anxiety, depression, suicidal ideation, burnout, healthy lifestyle beliefs, and healthy lifestyle behaviors using valid and reliable scales. RESULTS: Compared with the screening and referral only group, participants in the intervention group had greater reductions in anxiety and depression and significantly greater increases in healthy lifestyle beliefs and behaviors at 3 and 6 months post-intervention. After controlling baseline risk, the intervention group had a lower risk of suicidal ideation than the screening and referral group at 3 months (relative risk ratio [RRR] = 0.717; 95% CI: 0.320-1.606) and 6 months (RRR = 0.329; 95% CI: 0.101-1.072). The intervention group also had a significantly lower risk of burnout at 6 months (RRR: 0.698, 95% CI: 0.528, 0.929, p = 0.012). Nurses who completed more MBS sessions had less suicidal ideation at 6 months and those who completed more MBS skills-building activities had less burnout at 3 and 6 months. LINKING ACTION TO EVIDENCE: Integrating psychologically safe mental health screening combined with the scalable online CBT-based intervention, MBS, can produce sustained improvements in burnout, mental health symptoms, including suicidality, and healthy lifestyle beliefs and behaviors among nurses experiencing mental distress.

Humans

Dissociating behavioral, neural and experiential effects of prefrontal HD-tDCS during conflict resolution.

Inconsistent evidence regarding the cognitive effects of transcranial direct current stimulation (tDCS) highlights the need for more comprehensive approaches to assess its impact. This study aimed to investigate the effects of high-definition tDCS (HD-tDCS) on conflict resolution by combining behavioral, neural, and subjective experience measures. Sixty participants were randomly assigned to anodal, cathodal, or sham HD-tDCS groups and completed a 30-min flanker task. EEG was recorded during the first and last blocks (without stimulation), while stimulation was applied during the intermediate blocks of the task. Using a multidimensional methodological approach including Drift-Diffusion Modeling (DDM), EEG spectral analysis, Lempel-Ziv complexity, and Temporal Experience Tracing (TET), we assessed the cognitive, neural, and phenomenological effects of stimulation. Behavioral results indicated no significant improvements in reaction times or accuracy across the stimulation groups. Similarly, DDM parameters showed no effect of HD-tDCS on latent cognitive processes. However, EEG data revealed a significant reduction in neural complexity in the anodal group during resting-state, suggesting a stabilization or reorganization of neural dynamics. Subjective experience analysis identified two distinct clusters of task-related feelings, though time spent in these experiential states did not differ between groups. Interestingly, sensation of stimulation was significantly higher for anodal stimulation than sham when analyzed as a single dimension. Despite null behavioral effects, this study provides important insights into the neural and subjective responses to HD-tDCS and highlights the value of integrating complementary multidimensional approaches to better characterize brain stimulation effects. These findings contribute to the ongoing debate about the efficacy of tDCS in cognitive enhancement.

Humans

Five-year outcomes in a randomised controlled trial of prolonged exposure therapy and supportive counselling for post-traumatic stress disorder in adolescents: a task-shifted intervention.

BACKGROUND: Cognitive-behavioural therapies with a trauma focus are effective in reducing posttraumatic stress disorder and other psychological distress in adolescents. Long-term follow-up data on adolescents treated for PTSD remain scarce, with few studies extending beyond 12 months after treatment completion. OBJECTIVE: To evaluate the maintenance of treatment gains in a comparative study of effectiveness of PE-A and SC up to 60 months post-treatment. METHOD: Sixty-three adolescents diagnosed with PTSD were randomly assigned to either treatment, provided by newly trained and supervised non-specialist health workers. The primary outcome measure was PTSD symptom severity, as independently assessed on the Child PTSD Symptom Scale (CPSS). We report on the 60-month post-treatment follow-up, building on post-treatment, 3-month, 6-month, 12-month and 24-month post-treatment data that have been published previously. RESULTS: Participants in both treatment groups maintained a significant reduction in PTSD symptoms up to 60-months post-treatment (F (7, 343)&#x2009;=&#x2009;2.86, p&#x2009;<&#x2009;.01). Participants receiving prolonged exposure experienced greater improvement on the CPSS at all follow-up assessment timepoints, except for the 60-month FU (p&#x2009;=&#x2009;.28; g&#x2009;=&#x2009;0.33). CONCLUSION: Adolescents with PTSD continued to maintain treatment gains up to 60-months post-treatment. These data, along with findings from the original RCT, indicate that a brief treatment protocol (averaging 9 sessions of PE-A or SC) in a LMIC, task-shifted to be delivered by nurses without prior psychotherapy experience, led to lasting improvements in PTSD and comorbid symptoms for up to five years. The sustained benefits and improved functioning over the first few years post-treatment support expanding both treatments, especially PE-A, in community settings.

Humans

Beyond multidimensionality: a systematic review of recurrent frailty archetypes in community-dwelling older adults.

BACKGROUND: Frailty is a clinically heterogeneous geriatric syndrome commonly summarised using physical or multidomain severity scores. Whether person-centred analyses identify recurring within-frailty configurations has not been systematically examined in community-dwelling older adults. METHODS: We searched PubMed, Embase, MEDLINE, and CINAHL (January 2000-November 2025) for cross-sectional studies using latent class, latent profile, or analogous clustering methods to derive frailty subgroups. Quality was assessed using the AHRQ checklist and a purpose-built appraisal of person-centred model reporting. Study-derived classes were mapped in duplicate to a structured archetype framework developed through comparison of class-defining features across studies. RESULTS: Fourteen reports representing 12 independent datasets from eight countries were included. Six configurations were identified: minimally impaired reference, mobility-physical, nutritional-metabolic, cognitive-predominant, combined cognitive-physical, and psychosocial/mood-predominant. Convergence was measurement-dependent. The reference and mobility-physical configurations recurred across physical-only and multidomain indicator sets, while the combined cognitive-physical configuration appeared across several multidomain frameworks but required cognition to be measured. The remaining configurations emerged only when their defining domains were included. Evidence of prognostic value beyond aggregate frailty severity came from one deficit-index study. Collapsing shared-provenance reports and excluding the boundary-eligible study did not alter recurrence; excluding the Croatian dataset left five configurations recurrent, with the cognitive-predominant configuration supported by one independent dataset. CONCLUSIONS: Person-centred analyses identify recurring within-frailty configurations, but their apparent stability is partly measurement-dependent. A five-configuration core persisted after exclusion of the Croatian dataset, whereas the cognitive-predominant configuration remained weakly replicated. Harmonised indicators and rigorous external validation are needed before clinical application.

Humans

Chronic postsurgical pain: risk assessment and mitigation.

PURPOSE OF THE REVIEW: Chronic postsurgical pain (CPSP) and persistent postoperative opioid use (PPOU) are two of the most common complications of a number of surgical interventions, which can cause significant personal and economic negative consequences. This review outlines known and potential risk factors for CPSP and PPOU and approaches to reduce these risk factors. RECENT FINDINGS: Modifiable risk factors for developing CPSP include psychological distress, preoperative pain intensity, and perioperative opioid exposure. Although less studied, psychological comorbidities are also risk factors for PPOU. Evidence-based mitigation strategies include psychological interventions and perioperative opioid sparing. SUMMARY: A number of perioperative risk factors for developing CPSP and PPOU have been identified, and anesthesiologists should be cognizant of these risk factors and potential risk mitigation strategies. Additional prospective studies are needed to further develop easily adoptable, evidence-based interventions to reduce the incidence of CPSP and PPOU.

Humans

Utility of hearing aid use on neurocognitive functions and auditory processing: A systematic review.

PURPOSE: Hearing loss not only affects the peripheral auditory system but also leads to changes in central auditory pathways and neurocognitive skills. The use of hearing aids has shown potential benefits in mitigating the adverse effects of hearing loss. Earlier literature showed various studies assessing the impact of hearing aid use on cognitive functions and auditory processing, a comprehensive review of the existing literature is warranted. Existing literature showed heterogeneous outcomes among studies investigated the effect of Hearing aid use in combating the adverse effects of hearing loss on neurocognitive functions and auditory processing. METHOD: Databases including PubMed, SciELO, Cochrane Library, PsycINFO, Web of Science, and Index Copernicus were searched (2005-2025) using English keywords on hearing aid effects on neurocognition and auditory processing in individuals with hearing loss. Studies on effect of hearing aid use on neurocognition and auditory processing were included, while those involving cochlear implant users or other neurological disorders unrelated to hearing loss were excluded. Titles, authors and publication years were examined, and duplicates were removed. RESULTS: Total of 61 research papers were found on specific area and were included in the present review. Findings of these 61 articles have been analysed and are reported in this article. The outcome of the present study showed usefulness of hearing aid use on neurocognitive functions and auditory processing. CONCLUSION: The present literature review emphasized the importance of early rehabilitation through hearing aid use to alleviate the adverse effects of hearing loss on neurocognitive function and auditory processing.

Humans

Does impulsivity predict treatment outcomes in PTSD with borderline personality disorder features? Results from a randomized clinical trial.

BACKGROUND: Trauma-focused psychotherapies are first-line treatments for posttraumatic stress disorder (PTSD). However, a substantial proportion of clients do not respond adequately or drop out of therapy prematurely. This has sparked interest in identifying individual-level predictors of treatment outcomes, including improvement in PTSD severity and dropout. Impulsivity may be a predictor because it may interfere with key therapeutic processes, such as cognitive restructuring and emotional processing. Consequently, we present a hypothesis-driven secondary analysis of a 15-month randomized clinical trial comparing Dialectical Behavior Therapy for PTSD (DBT-PTSD) and Cognitive Processing Therapy (CPT) in women with childhood abuse-related PTSD and borderline personality disorder features to test whether impulsivity, assessed at baseline, predicts PTSD improvement and dropout. We further explore whether the dimensions of impulsivity (non-planning, attentional impulsivity, and motor impulsivity) differentially affect the outcomes in DBT-PTSD vs. CPT. METHODS: A total of 193 cis women with PTSD related to childhood abuse and borderline personality disorder features were assessed using the Clinician-Administered PTSD Scale (CAPS) and the Barratt Impulsiveness Scale (BIS-10). Separate probit models and general linear models were applied to predict dropout and pre-to-post changes in PTSD severity (&#x394;CAPS) from total impulsivity and subscale scores, i.e. non-planning, attentional and motor impulsivity. RESULTS: Overall, dropout rates were higher for participants with higher baseline impulsivity scores (p&#x202f;=&#x202f;0.049), particularly for those with higher non-planning impulsivity (p&#x202f;=&#x202f;0.012). In participants randomized to CPT improvement in PTSD symptom severity (&#x394;CAPS) was negatively related to baseline total impulsivity (p&#x202f;=&#x202f;0.021). In participants randomized to DBT-PTSD this relation was not significant. CONCLUSIONS: The results suggest that impulsivity may predict treatment outcomes. Specifically, patients with elevated impulsivity may be less likely to respond adequately to CPT. If replicated, these findings have implications for personalization of treatment.

Humans

Sex differences in sleep and alcohol consumption outcomes following a digital insomnia intervention.

BACKGROUND: Poor sleep is a well-established risk factor for heavy drinking, and evidence suggests that sleep could serve as a potential treatment target for reducing alcohol consumption. The relationship between poor sleep and problematic drinking appears to be stronger among females, but no studies to date have assessed sex differences in alcohol consumption following insomnia treatment. Here, we combine the samples from two clinical trials to investigate sex differences in the effects of a digital cognitive behavioral therapy for insomnia (Sleep Healthy Using the Internet; SHUTi) on sleep and alcohol outcomes. METHODS: 184 heavy drinking individuals with insomnia (weekly binge episodes: 4/5&#x2009;+ drinks in one sitting for females/males; AUDIT score >7; ISI score >14) were randomly assigned to either the SHUTi program (n&#x2009;=&#x2009;102) or an active control program (n&#x2009;=&#x2009;82). Participants completed self-report assessments at baseline, immediately following the 9-week intervention period, and at 3 and 6-months post-intervention. RESULTS: Linear mixed effects models showed that SHUTi effects over time were stronger among females than males for improved sleep outcomes and reduced frequency of total and heavy drinking days (ps &#x2264; 0.038). Follow-up comparisons of within-group effect sizes revealed consistently larger reductions in alcohol consumption among SHUTi females (Cohen's d range = 0.92-2.23) than SHUTi males (Cohen's d range = 0.65-1.95). CONCLUSIONS: Findings suggest that SHUTi may be more efficacious in improving sleep and reducing drinking among females with insomnia compared to males. These results could have important implications for sex-specific prevention and treatment efforts for heavy drinking individuals with insomnia.

Humans

A systematic review and meta-analysis of visuospatial attentional deficits in Parkinson's patients.

Parkinson's disease (PD) is a neurodegenerative condition primarily characterized by motor deficits, yet cognitive impairments are increasingly recognized. While deficits in executive functioning are well documented even in the absence of cognitive decline, evidence of attentional deficits in PD remains inconsistent, and the role of motor symptom lateralization is unclear. In this systematic review and meta-analysis, we examined visual attention in right-handed, cognitively unimpaired idiopathic PD patients, focusing on the canonical attentional domains (sustained, selective, divided) and processes (alerting, endogenous and exogenous orienting, reorienting), as well as visuospatial bias. Four databases were searched for studies comparing PD patients with healthy controls. Meta-analytic estimates were derived using Hedges' g within random-effects models, and studies that could not be quantitatively integrated were summarized narratively. In addition, studies directly comparing patients with left- and right-predominant motor symptoms (LPD vs. RPD) were reviewed qualitatively. Across 51 studies, PD patients exhibited deficits in sustained, selective, and divided attention. Among attentional processes, only exogenous orienting was impaired, whereas alerting, endogenous orienting, and reorienting were preserved. Findings from the few studies examining visuospatial bias indicated small, context-dependent shifts in spatial attention rather than a consistent directional bias. These findings indicate that PD patients show visual-attentional impairments, particularly under high-demand conditions, while basic alertness and voluntary orienting appear preserved. Exogenous orienting deficits and subtle rightward spatial tendencies in LPD suggest disruption of right-hemisphere attentional networks. These results have implications for early cognitive assessment, rehabilitation strategies, and understanding the neural bases of attentional dysfunction in PD.

Humans

Does future-oriented imagery rescripting increase willingness to carry out a social anxiety-related behavioral experiment? An extended replication.

BACKGROUND AND OBJECTIVES: Mental images of threat are common in social anxiety disorder and could impede exposure to fear-relevant situations. Landkroon et al. (2022) found that imagery rescripting of anticipated future threat, compared to no-task, increases willingness of non-clinical individuals to conduct a social anxiety-related behavioral experiment. The aim of this two-day preregistered extended replication study was to examine whether the effects persist beyond the intervention session by scheduling the behavioral experiment 1-7 days after the intervention. METHODS: On Day 1, 60 pre-screened participants were asked to design a behavioral experiment to test an idiosyncratic negative belief about a feared social situation. They were then randomly assigned to imagery rescripting (focused on their worst feared outcome of the behavioral experiment) or no-task. Participants' willingness to do the behavioral experiment and their threat beliefs was measured. On Day 2, they were asked to carry out the behavioral experiment. RESULTS: The imagery rescripting group, compared to the control group, did not show increased willingness or compliance to do the behavioral experiment on Day 1 or 2. Furthermore, the imagery rescripting did not lead to greater reductions in threat beliefs on either day. LIMITATIONS: The quality of the imagery rescripting intervention was not assessed, and given the brief nature of the intervention, any effects may have dissipated before participants decided whether to carry out the behavioral experiment. CONCLUSIONS: There was no evidence that imagery rescripting leads to changes in willingness or compliance to do a fear-relevant behavioral experiment. More research is needed to examine interventions that can enhance exposure in socially anxious people.

Humans

Nondominant Hand Training in Laparoscopy for Surgical Interns: Feasibility and Impact.

OBJECTIVE: Laparoscopy requires bimanual proficiency, yet early trainees demonstrate underdeveloped nondominant hand (NDH) performance. Although deliberate practice of NDH skill contributes to overall performance, NDH training is rarely incorporated into residency simulation curricula and has not been formally evaluated in surgical trainees. We assessed feasibility and impact of integrating structured NDH training with established laparoscopic curriculum for surgery interns. DESIGN: Prospective, single-institution randomized pilot study. Interns were assigned the standard 4-week curriculum of laparoscopic dominant hand and bimanual tasks (Control) or completed assigned NDH tasks in addition to the standard curriculum (Intervention). Feasibility was determined by assigned task completion, daily standard and NDH-specific self-reported practice time, and improvement in bimanual task performance. Performance was video recorded weekly and assessed by blinded evaluators using MISTELS and GOALS scoring. Cognitive workload during laparoscopic tasks was measured via NASA-TLX. Exploratory analyses were conducted within a Bayesian framework. SETTING: A single academic institution with a surgical simulation training program. PARTICIPANTS: General surgery interns on their 4-week simulation rotation. RESULTS: Eleven general surgery interns (6 intervention, 5 controls; all right-hand dominant) completed the study with 100% task completion and practice log compliance. Both groups improved in bimanual performance and perceived cognitive load. Reduction in cognitive workload during bimanual task performance was greater in the NDH group. Time spent on NDH practice over 4 weeks was associated with improved bimanual performance, independent of time spent on standard curriculum tasks. CONCLUSIONS: Structured NDH training is feasible to implement within an existing curriculum and reduces perceived cognitive workload during bimanual laparoscopic tasks. NDH practice demonstrates a beneficial dose-response relationship with performance, supporting its integration into early laparoscopic training.

Laparoscopy

Innovation-related perception as a key driver of alternative protein acceptance: evidence from an early-stage model for cultivated meat and algae-/microalgae-based alternative protein products in Italy.

Alternative proteins are increasingly considered part of the transition toward more sustainable food systems, yet their diffusion depends critically on consumer acceptance. This study investigates the early-stage acceptance of two alternative protein categories in Italy-cultivated meat and algae-/microalgae-based alternative protein products. Focusing on the first three phases of acceptance, the analysis examines how innovation-related perception (IRP) shapes consumer perceived value (CPV), consumer perceived risk (CPR), and subsequent affective (AFF), cognitive (COG), and conative (CON) responses. Data were collected through an online survey administered to 238 Italian respondents and analysed using partial least squares structural equation modelling (PLS-SEM). The results show that IRP is the main upstream driver of early-stage acceptance in both product domains: more favourable perceptions strongly increase perceived value and reduce perceived risk. In turn, CPV exerts a much stronger influence than CPR on both affective and cognitive attitudes. A tentative cross-model comparison suggests only a descriptive variation in the final transition toward conative acceptance: affective and cognitive responses were both significant in the two models, with a relatively larger affective coefficient for cultivated meat and more balanced coefficients for algae-/microalgae-based products. Overall, the findings support a process-based interpretation of alternative protein acceptance and highlight the central role of innovation-related perception in shaping early consumer responses. These results provide relevant implications for communication strategies, product positioning, and policy actions aimed at improving the acceptability of alternative proteins in food cultures characterised by strong culinary traditions.

Italy

Functional neuroimaging subtypes of obsessive-compulsive disorder: A systematic review and meta-analysis.

Obsessive-compulsive disorder (OCD) exhibits substantial clinical heterogeneity that may reflect underlying neurobiological diversity. Neuroimaging-based subtyping may advance precision psychiatry by identifying biologically distinct subgroups with differential treatment responses. This study systematically synthesized evidence from functional neuroimaging subtyping studies in OCD to identify reproducible neurobiological subtypes, characterize their clinical profiles, and establish a consensus-based classification framework. We reviewed 40 original studies employing machine learning, clustering, normative modeling, or classification approaches, encompassing approximately 8,150 patients. Consensus clustering identified three reproducible neurobiological subtypes. The Limbic-Hyperactive subtype, comprising approximately 40% of patients, exhibited amygdala and insula hyperconnectivity, elevated anxiety levels, predominant contamination and washing symptoms, and favorable response to cognitive-behavioral therapy. The Fronto-Striatal-Hypoconnected subtype, comprising approximately 35% of patients, demonstrated reduced orbitofrontal-striatal connectivity, cognitive inflexibility, predominant checking and ordering symptoms, and a favorable response to selective serotonin reuptake inhibitors. The Global-Disrupted subtype, comprising approximately 25% of patients, exhibited widespread connectivity disruption, greater symptom severity, and poor treatment response. Support vector machine classification achieved 81.5% accuracy for subtype assignment, though classification of OCD versus healthy controls showed limited generalizability in multisite settings (AUC 0.567-0.673). These findings support a neuroimaging-based framework for personalized treatment selection but require prospective validation.

Humans

Does high fructose consumption trigger microglia activation and neuroinflammation? A systematic review.

This systematic review evaluated the effects of fructose intake on neuroinflammatory markers in rodent models. The search terms Fructose AND neuroinflammation OR Neurodegeneration OR chemokines OR interleukins OR microglia OR behaviour OR memory OR cognition were used in Google Scholar, Scopus and Web of Science. Thirteen animal studies investigating fructose-induced neuroinflammation that matched the eligibility criteria were included in the study. Across the studies, 16 inflammatory markers were identified and significantly altered following exposure to fructose. The findings consistently demonstrated elevated expression of pro-inflammatory cytokines, TNF-&#x3b1;, IL-6, and IL-1&#x3b2;, following fructose administration. Fructose consumption also dysregulated MCP-1, fractalkine, and CX3CR1 levels, thereby promoting inflammatory signalling and microglial activation. Furthermore, fructose exposure significantly increased IBA-1 and CD11b, indicating sustained neuroimmune activation. Alterations in important inflammatory pathways involving TLR4, NLRP3, NF-&#x3ba;B, MyD88, iNOS, and cyclooxygenases (COX-1 and COX-2) were also observed. In contrast, expression of the anti-inflammatory regulator peroxisome proliferator-activated receptor gamma (PPAR&#x3b3;) was reduced after fructose treatment. Overall, the findings suggest that chronic fructose consumption induces neuroinflammation through multiple inflammatory and immune-related mechanisms in the brain. These effects appear to be dose- and duration-dependent and may contribute significantly to neurodegeneration and cognitive impairment.

Microglia

The effect of olfactory training and odor exposure on visual selective attention.

Olfactory training (OT) is a well-established, non-invasive intervention that improves olfactory function by repeated, structured exposure to odorants. Beyond sensory outcomes, it also influences multiple aspects of cognition. Yet, its influence on attention, a fundamental process underlying many cognitive domains, remains unclear. This study examined the impact of a 12-week OT program on visual selective attentional performance and the effect of on-task odor exposure. Ninety-four healthy participants were initially included, and randomized into OT or placebo groups. Participants completed the d2 Test of Attention simultaneously with and without odor exposure in a randomized sequence at baseline, post-training, and a follow-up four weeks after stopping the training. The d2 test measures commission errors, omission errors, and concentration performance. Ninety-three participants (OT=51, placebo=42) completed baseline measurement, 74 (OT=39, placebo=35) returned for post-training session, and 57 participants (OT=29, placebo=28) returned for the follow-up appointment. Results showed that OT did not significantly improve d2 test performance. In the primary model, on-task PEA exposure reduced commission errors compared to the odorless condition, suggesting a possible transient effect of olfactory input on the inhibitory control in the context of the d2 attentional test. This effect, however, was no longer significant once the follow-up data were included and should be regarded as preliminary. Overall, these findings raise the possibility of a distinction between relatively long-term OT and short-term odor exposure: while OT did not improve visual selective attention, brief on-task odor exposure may transiently enhance inhibitory control during attentional tasks, a possibility that remains to be confirmed.

Humans

Lipid metabolism is a key central, systemic and gut microbial feature of the decline in rat hippocampal function during middle age.

Middle age is emerging as a turning point in brain ageing, prognostic of future cognitive health and amenable to intervention. Metabolic and proteomic differences during this period are not yet fully understood and may potentially influence functions of the hippocampus, a brain area that regulates memory and anxiety. While the gut microbiota is implicated in brain ageing, the relationship between the gut microbiota, the metabolic state, and hippocampal proteome in middle age has not been investigated. We hypothesise that peripheral metabolic or protein features are associated with hippocampal vulnerability in middle age. Therefore, young adult and middle-aged rats were assessed for behavioural, proteomic, metabolic, and gut microbiota differences. Proteomic profiling of the hippocampus revealed differential expression of proteins indicative of altered synaptic signalling. Concurrently, adult hippocampal neurogenesis was decreased in middle age. Hippocampal microglia exhibited a lipid rich, inflammatory phenotype in middle age which correlated with poorer memory performance. CSF and serum proteomic and metabolomic analyses identified dysregulated lipid-related pathways potentially contributing to hippocampal vulnerability in middle age. Furthermore, 16S rRNA sequencing revealed reduced abundance of bacteria involved in lipid metabolism regulation. However, faecal microbiota transfer from young to middle aged rats was not sufficient to robustly improve hippocampus-dependent spatial memory. Together, these findings highlight dysfunctional lipid metabolism as a key feature of middle age that may contribute to decline in hippocampal function. Given that the scope for intervention is limited during older age, targeting biomarkers involved in metabolic and lipid homeostasis may be pivotal for the development of pharmacological or lifestyle-based interventions during middle age which could ultimately delay future cognitive ageing.

Animals