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Peripheral inflammation and executive function among community samples across the lifespan: A systematic review and meta-analysis.

Higher levels of peripheral inflammatory markers are proposed to disrupt cognitive processes; however, the extent to which this relationship applies to executive functions, specifically, has yet to be systematically evaluated. The current meta-analysis synthesizes all available literature measuring the association between peripheral inflammation and executive functions among community individuals across the lifespan. This systematic review searched Web of Science, PubMed, and PsycINFO for published and unpublished studies, in the English language, that assessed the association between markers of peripheral inflammation and self-report and behavioral measures of executive function. In addition to methodological and demographic information, correlation/beta coefficients were extracted from included studies to quantify the association between inflammation and executive functions. This review included 58 studies, 41 of which were included in the random-effects meta-analysis (N = 255,539). Among community individuals, higher levels of CRP and IL-6 were associated with poorer executive functioning. These results did not differ when models accounted for potential confounding variables. Meta-regressions revealed that the relationship between inflammatory biomarkers and executive function did not differ as a function of age, adiposity, or percentage of the sample who identified as female. Results of the present review indicate that higher levels of specific inflammatory markers are associated with lower performance on executive function measures; however, we observed significant heterogeneity in the study design and measurement of both inflammation and executive functioning, suggesting important considerations for future research.

Humans

Effects of adjunctive memantine on executive function and global cognition in bipolar disorder (BD): A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Cognitive impairment contributes substantially to disability in bipolar disorder (BD), but effective pharmacologic options remain limited. This trial evaluated whether adjunctive memantine improves global cognition and executive function in BD. METHODS: In this double-blind, placebo-controlled randomized trial, patients with bipolar I disorder (B1D) receiving lithium and olanzapine were assigned to memantine or placebo. Memantine was titrated to 20&#xa0;mg/day over 6&#xa0;weeks. Cognitive outcomes were assessed at baseline, week 6, and week 18. Global cognition was measured with the Neurocognitive Assessment Battery (NuCog), and executive function with the Frontal Assessment Battery (FAB). Data were analyzed using generalized estimating equations and Bonferroni-adjusted post-hoc tests. RESULTS: Sixty-three participants were randomized (memantine, n&#xa0;=&#xa0;31; placebo, n&#xa0;=&#xa0;32), and all completed follow-up. Groups were comparable at baseline for demographic and clinical variables and for most cognitive measures. Both groups improved over time (P&#xa0;<&#xa0;0.001), but improvement was greater with memantine for global cognition at week 6 (MD&#xa0;=&#xa0;9.32; 95% CI, 4.84-13.81; P&#xa0;<&#xa0;0.001) and week 18 (MD&#xa0;=&#xa0;12.69; 95% CI, 8.67-16.71; P&#xa0;<&#xa0;0.001). FAB total scores favored memantine at week 18 (MD&#xa0;=&#xa0;2.68; 95% CI, 1.76-3.61; P&#xa0;<&#xa0;0.001), but not at week 6. Domain analyses showed significant benefits for NuCog attention, visuoconstructional ability, memory, and executive function, and for several FAB subscales by week 18. CONCLUSIONS: Adjunctive memantine improved global cognition and, over longer follow-up, executive function in BD. These findings support NMDA receptor modulation as a potential strategy for cognitive dysfunction in BD.

Humans

Continuous theta-burst stimulation over the right DLPFC modulates central executive network connectivity in depression: exploratory analysis of a randomized clinical trial.

Previous studies suggest that transcranial magnetic stimulation exerts antidepressant effects and is associated with alterations in functional connectivity (FC), but the neural correlates remain unclear. This exploratory sham-controlled trial investigated the effect of continuous theta-burst stimulation (cTBS) over the right dorsolateral prefrontal cortex (DLPFC) on FC in major depressive disorder (MDD). Seventy MDD patients were randomized to receive two-week treatment of personalized cTBS or sham stimulation. Resting-state fMRI was performed at baseline and post-treatment. Ultimately, 31 patients in the active cTBS group and 28 patients in the sham group passed imaging quality control and were included in the final analysis. To identify the FC that may have been influenced by cTBS treatment, two complementary FC analyses were conducted: (1) voxel-wise degree centrality (DC) followed by seed-based FC, and (2) an individual FC analysis based on the stimulation targets. Furthermore, correlations between FC changes and clinical symptoms improvement were examined. Both groups exhibited reductions of depression scores, with greater improvement in the active group. Compared to the sham group, active cTBS showed increased DC in the precuneus and elevated FC between the precuneus (within the para-cingulate network) and the right inferior parietal lobule (IPL) and DLPFC. Further stimulation target-based analysis revealed increased FC between stimulation targets and both the precuneus and visual regions following treatment. Our findings reveal neural changes associated with cTBS over the right DLPFC in MDD, notably involving the precuneus and its connectivity with the right IPL/DLPFC, suggesting alterations within the central executive network. TRIAL REGISTRATION: chictr.org.cn; ChiCTR2300068273.

Humans

Subacute and long-term changes in cognitive functioning after administration of classic psychedelics, MDMA and ketamine: A systematic review of clinical and preclinical evidence.

Psychedelic agents induce a window of heightened neuroplasticity that extends beyond acute intoxication, during which neural circuits are more amenable to change. This period may facilitate changes in cognition relevant to the treatment of psychiatric disorders. This systematic review synthesised clinical and preclinical evidence of subacute and long-term (&#x2265;1&#x202f;day) effects of classic and non-classic psychedelics on cognition. MEDLINE, EMBASE, APA PsycInfo and Web of Science were searched to identify human and animal studies investigating psychedelics and cognition (executive function, attention, decision-making). Sixty-seven (47 clinical, 20 preclinical) articles met inclusion criteria. Psilocybin demonstrated the most consistent evidence of subacute and longer-term cognitive improvement, particularly in cognitive flexibility and attention. Ketamine showed enhancement across cognitive domains, although findings were heterogeneous. LSD and DMT showed no consistent subacute changes, while MDMA was associated with transient cognitive impairments that resolved within days. Risk of bias assessments revealed selective outcome reporting, poor reporting of missing data and inadequate methodological detail, limiting the confidence of findings. Current evidence provides preliminary support for subacute changes in cognition following administration of select psychedelic agents. Cognitive improvements were more frequently seen in psychiatric populations than healthy subjects, which may reflect a remediation of existing cognitive deficit rather than enhancement above normal functioning. Adequately powered, controlled studies with standardised reporting of cognitive outcomes are required to determine the magnitude, durability and clinical relevance of psychedelic-associated cognitive change.

Hallucinogens

Post-intervention effectiveness of a computerized personalized cognitive stimulation program adapted according to cognitive reserve in older adults without cognitive impairment in Primary Care: A randomized clinical trial.

BACKGROUND: Cognitive reserve may influence responsiveness to cognitive interventions, yet it is rarely used to tailor computerized stimulation. OBJECTIVE: To evaluate the effectiveness of a computerized cognitive stimulation program personalized according to cognitive reserve on cognition, reserve-related activities, and digital competence in community-dwelling older adults without cognitive impairment in Primary Care. METHODS: In this randomized clinical trial, 102 adults aged &#x2265;65 years with normal cognitive performance were recruited from three primary care centers in Zaragoza, Spain, and stratified by cognitive reserve level before random allocation to intervention or control. The intervention comprised digital literacy sessions followed by 8 weeks of home-based computerized cognitive stimulation tailored to participants' cognitive reserve profiles and life history. Controls received a single group-based health education session focused on maintaining everyday cognitive activity. Outcomes were assessed at baseline and post-intervention using global cognition (MEC-35), the Cognitive Reserve Questionnaire, the Mobile Device Proficiency Questionnaire-16, and domain-specific neuropsychological tests. A total of 100 participants completed the final evaluation and were included in complete-case analyses. RESULTS: Compared with controls, the intervention group showed greater adjusted post-intervention improvements in global cognition (MEC-35 between-group difference: 1.8 points) and several cognitive measures, including temporal orientation, calculation, attention, praxis, verbal fluency, processing speed, executive functions, and verbal learning. CRQ scores and digital competence also improved, with small-to-large effect sizes. CONCLUSIONS: A computerized cognitive stimulation program adapted according to cognitive reserve appears feasible in Primary Care and may improve cognition, engagement in reserve-related activities, and digital competence in older adults without cognitive impairment.

Humans

Game changer? Cognitive-motor effects of VR exergaming compared to video-based training.

BACKGROUND/OBJECTIVE: Virtual reality (VR) exergaming enhances several cognitive domains through multisensory engagement. Acute cognitive benefits of VR are established, but evidence for direct comparisons with non-immersive controls is limited. This study aimed to determine whether VR exercise provides additional cognitive and cognitive-motor benefits beyond a matched non-immersive active stick-fight video (SFV) intervention, and whether effects persist after training. METHODS: In this randomized quasi-experimental study, N&#x2009;=&#x2009;55 healthy adults (VR: n&#x2009;=&#x2009;30; SFV: n&#x2009;=&#x2009;25; 25.5&#x2009;&#xb1;&#x2009;7.1&#x2009;years; 41.8% female) completed an 8-week program (2&#x2009;&#xd7;&#x2009;30&#x2009;min/week), of VR or SFV matched in movement patterns, frequency, intensity and duration. Measurements included reaction time (RT), Stroop Test (versions 1-3), Letter Cancellation Test (LCT), Trail Making Test (TMT), Trail Walking Test (TWT) and Fitts task (difficulty level 1-4). Data were analyzed using mixed-design ANOVAs. RESULTS: Improvements were observed in Stroop reading (F(1,53) = 14.84, p < .001, &#x3b7;2 = 0.219), Stroop inhibition (F(1,53) = 10.99, p = .002, &#x3b7;2 = 0.172), and LCT (F(1,53) = 4.57, p = .037, &#x3b7;2 = 0.079). A time&#x2009;&#xd7;&#x2009;group interaction was found for TMT (F(1,53) = 6.55, p = .031, &#x3b7;2 = 0.110), indicating greater changes following VR training. Both groups improved cognitive-motor performance (TWT: F(1,25) = 55.32, p < .001, &#x3b7;2 = 0.689; Fitts3: F(1,53) = 44.97, p < .001, &#x3b7;2 = 0.459), with greater gains for VR in Fitts3 (p = .006). CONCLUSION(S): Eight weeks of VR and SFV enhanced cognitive and cognitive-motor performance. VR provided domain-specific advantages in executive function, but these effects were not uniformly persistent. SFV sustained more improvements in real-world-relevant cognitive-motor tasks.

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

Brain network alterations underlying cue reactivity and craving in abstinent methamphetamine users: a systematic review of functional MRI findings.

BACKGROUND: Methamphetamine use disorder (MUD) is marked by intense craving and high relapse risk, often triggered by drug-related cues. Functional magnetic resonance imaging (fMRI) provides key insight into the neural basis of this cue reactivity, implicating large-scale brain networks for reward, motivation, and control. Yet, findings remain inconsistent across studies due to differences in task design, abstinence duration, and participant characteristics. OBJECTIVE: This systematic review synthesises evidence on how abstinence influences brain network alterations underlying cue reactivity and craving in methamphetamine users, integrating task-based and resting-state fMRI findings within leading neurobiological models of addiction. METHODS: A systematic search of PubMed, Scopus, Web of Science, and Ovid was conducted up to August 10, 2025, following PRISMA 2020 guidelines. Eligible fMRI studies examined cue reactivity or craving in abstinent methamphetamine users. Data were extracted on activation, connectivity, and brain-behaviour associations, and synthesised narratively. RESULTS: Task-based studies revealed heightened activation across reward, salience, and control networks during cue exposure, which diminished as parietal and executive control systems re-engaged with longer abstinence. Resting-state findings showed disrupted intrinsic connectivity among default mode, salience, and frontoparietal networks, reflecting persistent imbalances linked to craving and use severity. CONCLUSION: fMRI evidence shows that MUD is marked by network-level disruption linking reward, salience, and control systems. Task-based findings reveal strong cue reactivity in reward circuits, while resting-state data show persistent imbalance among default mode and control networks. With abstinence, partial restoration of network integrity emerges, highlighting both vulnerability and opportunities for targeted, recovery-based interventions.

Humans

AI-driven snapshot hyperspectral imaging for on-line sorting systems in food industry: From real-time sensing to intelligent decision-making.

High-throughput food sorting requires rapid, non-destructive detection of external defects, foreign materials, and internal quality attributes in heterogeneous food matrices. Conventional scanning hyperspectral imaging may suffer from motion-induced spatial-spectral mismatches, whereas snapshot hyperspectral imaging (S-HSI) captures spectral images within a single integration time. However, its advantage is limited by trade-offs in resolution, signal-to-noise ratio (SNR), reconstruction uncertainty, and calibration stability, which are further amplified by variable tissue structure, surface reflection, moisture, and fat distribution in foods. This review critically examines artificial intelligence (AI)-driven S-HSI for on-line food sorting within a sensing-representation-decision-execution framework. Compact architectures are compared according to their physical constraints, food-sorting suitability, and ability to support mapping between spectral responses and physicochemical quality attributes. AI strategies are reviewed for spectral reconstruction, image restoration, spatial-spectral representation, band selection, uncertainty-aware decision-making, and edge implementation. AI can partially compensate for snapshot-specific limitations, but current evidence remains largely limited to laboratory or prototype studies. Future work should link system performance to food safety and quality outcomes by reporting throughput, decision latency, calibration drift, missed-detection risk, false-rejection cost, and closed-loop sorting success.

Hyperspectral Imaging

The impact of supernormal lung function on mortality risk in adults with and without sleep-disordered breathing.

BACKGROUND: In the general population, supernormal lung function is associated with a lower risk of all-cause mortality. RESEARCH QUESTION: It remains unclear whether sleep-disordered breathing (SDB) affects this relationship. METHODS: This cohort analysis included 4,839 adults. Lung function was categorised as supernormal (FEV1&#x2009;>&#x2009;ULN), normal (LLN&#x2009;&#x2264;&#x2009;FEV1&#x2009;&#x2264;&#x2009;ULN), and below normal (FEV1&#x2009;<&#x2009;LLN). SDB severity was classified using apnoea-hypopnoea index categories: no SDB (<5 events/hour), mild SDB (5-<15 events/hour), moderate SDB (15-<30 events/hour), and severe SDB (&#x2265;30 events/hour). The association between lung function and all-cause mortality was assessed using Cox proportional hazards models with subgroup analyses according to SDB severity and formal testing for interaction. Analyses were repeated using FVC-defined lung function groups as an alternative definition of supernormal lung function. RESULTS: Among the included participants, 4,068 (84.1%) had normal lung function, 369 (7.6%) had supernormal lung function, and 402 (8.3%) had below normal lung function. During 52 421.5 person-years of follow-up (median 11.72&#x2009;years; IQR, 10.46-12.56), 1,188 deaths occurred. Compared with the normal lung function group, the supernormal lung function group had a lower prevalence of baseline hypertension and cardiovascular disease. The association between lung function and all-cause mortality varied across SDB severity strata (P for interaction&#x2009;=&#x2009;0.034). A lower mortality risk associated with supernormal lung function was observed in participants without SDB (HR: 0.24, 95% CI: 0.06-0.97), whereas this association was not statistically significant in the mild, moderate, or severe SDB strata. Below normal lung function was generally associated with an increased all-cause mortality risk. Sensitivity analyses using FVC-defined lung function groups yielded broadly consistent findings. CONCLUSION: Supernormal lung function was associated with lower all-cause mortality primarily among individuals without SDB. These findings underscore the importance of considering SDB severity when assessing the health implications of lung function.

Humans

Repetitive transcranial magnetic stimulation in functional motor disorders: A systematic review of effects and targets.

OBJECTIVE: To evaluate the effectiveness, safety, and potential mechanistic implications of repetitive transcranial magnetic stimulation (rTMS) in adults with functional motor disorders (FMD), focusing on possible phenotype-specific responses and stimulation protocols. METHODS: Seven databases were searched from inception to July 2026. Randomised and non-randomised interventional studies were included. Risk of bias and evidence certainty were assessed using PEDro, RoB 2, JBI tools, and GRADE. Because of substantial clinical and methodological heterogeneity, findings were synthesised qualitatively. RESULTS: Fourteen studies were included. The primary motor cortex was targeted in 11 studies. Functional tremor showed the most consistent evidence with inhibitory stimulation: one small sham-controlled trial found a significant group-by-time effect on tremor severity (p&#xa0;=&#xa0;0.007), while an uncontrolled prospective series reported 40&#xa0;% reduction in postural tremor amplitude (p&#xa0;=&#xa0;0.05). Evidence for functional weakness was conflicting: excitatory M1 stimulation increased objective strength by 25&#xa0;% versus 10&#xa0;% with sham (p&#xa0;=&#xa0;0.004), whereas the largest inhibitory sham-controlled trial found no benefit (p&#xa0;=&#xa0;0.80). No severe adverse events were reported, but safety reporting was incomplete. GRADE certainty was moderate for tremor and very low for all other outcomes. CONCLUSIONS: Current evidence is insufficient to establish the efficacy of rTMS in FMD or to recommend phenotype-specific protocols. Preliminary findings support further investigation of inhibitory stimulation for functional tremor, whereas evidence for excitatory stimulation in functional weakness remains uncertain. SIGNIFICANCE: The possible interaction between phenotype and stimulation direction is hypothesis-generating. rTMS should currently be considered an experimental, context-sensitive adjunct within multidisciplinary care, pending adequately powered phenotype-stratified sham-controlled trials. Prospero Registration Number: CRD420251250969.

Humans

Sustained cognitive and functional effects of pro-cognitive interventions for bipolar disorder: A systematic review of randomised controlled trials.

A substantial proportion of individuals with bipolar disorder (BD) experience considerable cognitive deficits. Existing systematic reviews have evaluated the efficacy of pro-cognitive interventions in BD, but have not established whether any cognitive benefits translate into functional improvements, with evidence for sustained functional effects remaining limited. A systematic search was conducted on MEDLINE, EMBASE, PsycINFO and Cochrane Library from inception until 21 May 2026. Eligible studies were randomised controlled trials (RCTs) in BD reporting cognitive or functional outcomes at three or more months following a pro-cognitive intervention, or examining the translation of cognitive benefits into improvements in functional outcomes at any timepoint. Seven unique RCTs plus three secondary analyses of these trials (n&#xa0;=&#xa0;615) met the inclusion criteria. Approximately 13% (7/55) of RCTs identified in the search of pro-cognitive interventions in adult BD assessed cognitive or functional outcomes at least 3&#xa0;months after treatment end. Of the seven unique RCTs, most evaluated cognitive remediation (CR; k&#xa0;=&#xa0;4). The average follow-up length was 4&#xa0;months (range: 3-6&#xa0;months). Three of the four RCTs examining CR reported cognitive benefits at 3 to 6&#xa0;months, whereas only one CR RCT found consistent functional effects at 3&#xa0;months. Evidence on the translation of cognitive benefits to functional improvements is scarce and inconsistent. Most trials examining pro-cognitive interventions do not examine whether potential benefits are sustained or whether they translate into improvements in real-world functioning. CR appears to be a promising intervention for achieving durable cognitive gains in BD, although evidence for sustained effects of other interventions is limited.

Humans

Probiotic-derived extracellular vesicles as food-based nanocarriers: Mechanisms, functional applications, and future perspectives in food systems.

Probiotic-derived extracellular vesicles (PDEVs) are a promising type of postbiotic nanoparticle derived by fermentation of probiotics, and have gained growing interest as a potential application in food science and nutrition. These are lipid bilayer vesicles of nanoscale, which are naturally released by probiotic cells and contain a wide variety of bioactive molecules, such as proteins, nucleic acids, and metabolites. Moreover, PDEVs are highly stable, biocompatible, and can be easily engineered to have surfaces with high functionality, which makes them good candidates in functional engineering. In contrast to traditional live probiotics, PDEVs overcome the difficulties of preserving microbial viability during processing and storage, thus providing superior safety, stability, and predictable biological performance. This is a systematic review of the various functions of PDEVs in food systems. We conclude on the processes through which PDEVs control intestinal barrier integrity, alter gut microbiota composition, and alter host immune responses, and their potential to enhance gut health when added to functional foods. In addition to their health-promoting effects, PDEVs have shown significant potential as natural antimicrobial agents to preserve food and as effective nanocarriers of hydrophobic bioactive compounds, including fucoxanthin, to improve their stability, bioavailability, and targeted delivery. Moreover, PDEVs can be used as new regulators of microbial fermentation. However, it should be noted that a lot of the evidence that is available is still preliminary and the effectiveness of these applications in real food-processing and storage conditions has not been fully proven. Although they have potential, there are a number of challenges that still hinder the widespread use of PDEVs in the food industry. These involve the creation of scalable and cost-effective production processes, batch-to-batch consistency, vesicle stability in a variety of food matrices, and regulatory and safety considerations. Other emerging engineering approaches, such as surface functionalization and cargo loading, are also discussed in this review and could further increase the specificity, functionality, and application versatility of PDEVs in food systems. Moving forward, the incorporation of PDEVs into the next generation functional foods, novel food preservation methods, and customized nutrition plans should be prioritized in future studies. Further developments in these fields can make PDEVs useful platforms at the interface of food microbiology, nanotechnology, and human health.

Probiotics

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

Short-term psychodynamic psychotherapy for functional neurological disorder: A pilot randomized controlled trial.

BACKGROUND: Evidence-based psychotherapeutic treatments for Functional Neurological Disorder (FND) remain limited. This pilot trial evaluated the preliminary efficacy of Short-term Psychodynamic Psychotherapy (STPP) plus Standard Medical Care (SMC) compared with SMC alone in reducing FND symptom frequency. METHODS: Adults with FND were randomized (1:1) to receive either SMC alone or 12 weekly sessions of STPP plus SMC. The primary outcome was symptom frequency (days with symptoms in the last 4 weeks) assessed at the end of treatment (3 months) and at 6-month follow-up. Secondary outcomes included treatment response (&#x2265;50% reduction in symptom frequency) and scores on the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). RESULTS: Of 91 randomized patients (mean age 38.2 years, 75.8% female), 81.3% completed follow-up. Intention-to-treat analysis using Linear Mixed Models showed that STPP plus SMC significantly reduced symptom frequency compared with SMC alone (estimated mean difference -5.72 [95% CI -8.68 to -2.77]; Cohen's d = 0.77; p&#x202f;<&#x202f;0.001).Treatment response was achieved by 65.8% in the intervention group versus 16.7% in controls (OR 8.21 [95% CI 2.79-24.19]; p&#x202f;<&#x202f;0.001; NNT 2.0).Significant improvements were also observed for depression (HAM-D: estimated mean difference -10.80; d = 1.45), anxiety (HAM-A: -7.94; d = 1.06), and disability (WHODAS 2.0: -5.77; d = 0.74), all p&#x202f;<&#x202f;0.001. CONCLUSIONS: STPP was associated with clinically meaningful improvements in FND symptom frequency and all secondary outcomes, with large effect sizes and high treatment response rates. These findings support the preliminary efficacy of STPP for FND and justify larger, multicenter confirmatory trials.

Humans

A single session of high-definition transcranial direct current stimulation does not modulate effects of knee two-point discrimination training or sensorimotor function in healthy adults: Double-blind randomised controlled trial.

BACKGROUND: Benefits of sensory-training interventions on sensorimotor outcomes are inconsistent, and it is unclear whether transcranial direct current stimulation (tDCS) can enhance proprioception, which is fundamental to neuromuscular control. Existing evidence is dominated by upper-limb studies, so transferability to the knee is unclear. This study investigated whether a single session of anodal high-definition (HD)-tDCS, alone or combined with brief two-point discrimination (TPD) training, enhances knee sensorimotor function and performance in healthy adults. METHODS: In a double-blind randomised-controlled trial, 57 healthy participants received (1) 20-min, 1&#xa0;mA anodal HD-tDCS over the knee primary somatosensory (S1) map or sham stimulation, and (2) 15-min knee TPD training or no training. Knee somatosensory, sensorimotor, and functional performance measures were assessed pre- and immediately post-intervention. Three-way mixed-design ANOVAs, equivalence testing (smallest effect size of interest &#x3b7;2&#xa0;=&#xa0;0.02), Bayes factors, and linear mixed-effects models quantified effects. RESULTS: HD-tDCS, TPD training, and their sequential combination had no effect on any outcome measure (p&#xa0;&#x2265;&#xa0;0.05; &#x3b7;2&#xa0;&#x2264;&#xa0;0.015). Confidence intervals spanned equivalence bounds, and equivalence testing results were non-significant (p&#xa0;&#x2265;&#xa0;0.05). Bayes factors (<0.33) showed moderate evidence for the null (no effect). Mixed-effects modelling attributed &#x2264;8% of total variance to intervention fixed effects, with the remainder captured by participant-level random effects. CONCLUSION: A single 20-minute session of 1&#xa0;mA HD-tDCS, with or without brief TPD training, does not acutely modify knee somatosensory, sensorimotor, or functional performance in healthy adults. Existing evidence at the hand may not translate to the lower limb. Future work should investigate higher-dose, multi-session, task-concurrent, or network-targeted strategies in clinical populations.

Humans

Extended Long-Term Effects of Cognitive and Aerobic Training on Cognitive Function in Patients With Stress-Related Exhaustion Disorder: A 4.5-Year Follow-Up of a Randomized Controlled Trial.

Stress-related conditions like clinical burnout and exhaustion disorder (ED) are associated with enduring cognitive problems. We have previously demonstrated that the addition of computerised cognitive training (CCT) and aerobic training (AT) to a multimodal rehabilitation programme (MMR) yielded greater improvements in cognitive function compared to MMR alone in patients with ED. These effects were maintained at the 1-year follow-up for CCT, but not for AT. Building on these findings, the present study examined the extended long-term effects of CCT and AT on cognitive function, psychological health, and work ability, 4.5&#xa0;years after the interventions. Participants were recruited from a stress-rehabilitation clinic and 56 of the initial 132 participants returned for the 4.5-year follow-up. Assessments were conducted before (T1), immediately after (T2), 1-year after (T3) and 4.5-years after (T4) the interventions. Mixed model analyses assessed changes in the intervention groups relative to the control group from T1 to T4, with follow-up comparisons examining within-group stability of outcomes between T3 to T4. The primary outcome was cognitive performance on a global cognitive score. Secondary outcomes included domain-specific cognitive functioning, self-reported cognitive function, psychological health (burnout, depression, anxiety, and fatigue), and work ability. The analysis revealed sustained long-term effects on the global cognitive score, a trained updating task and episodic memory in the CCT group, with stable performance between one- and 4.5-year follow-up. The addition of AT did not yield any extended long-term effects on cognitive performance. Both groups showed extended long-term improvements in self-reported memory problems, although findings were mixed. Extended long-term improvements were observed on burnout for both groups, with additional effects on anxiety and work ability in the AT group. Notably, these effects were not present at the 1-year follow-up and are more plausibly explained by selective attrition rather than a delayed intervention effect. In conclusion, the result indicates that cognitive interventions such as CCT can have lasting positive effects on cognitive function in patients with ED, whereas the long-term psychological effects should be interpreted with caution. TRIAL REGISTRATION: ClinicalTrials.gov: NCT0073772.

Adult