Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 38 appraisals
Neuropsychologia
Number of types of synaesthesia can be predicted by structural and functional neuroimaging data.
It has been suggested that synaesthetes have a distinct neurocognitive profile with a broad variety of cognitive and behavioural differences. Recent studies have shown that people with more types (relative to fewer types) of synaesthesia are easier to classify using machine learning of questionnaires and cognitive test data. This suggests a spectrum within synaesthesia, despite synaesthesia itself being typically defined in categorical terms. This study uses the same basic approach applied to 13 brain-based biomarkers. These have previously been shown to distinguish synaesthetes from controls, but it is not known whether they explain heterogeneity amongst synaesthetes. Using machine learning methods (elastic net regression), we were able to find several biomarkers that predict above chance the number of types of synaesthesia. These include both functional MRI (the extent to which brain regions act as hubs) and structural MRI (e.g., intracortical myelination) measures. This is the first project that explores whether it's possible to predict the breadth of synaesthesia from brain-based measures.
29 July 2026
Read appraisal →Proceedings of the National Academy of Sciences of the United States of America
Active linking through narratives facilitates associative inference
In daily life, we often draw inferences about novel associations from prior experiences. This ability, associative inference, is thought to be a key process by which memory guides future behavior. Prior studies have typically instructed participants to use narratives or mental imagery to aid memory of object associations. However, these studies have not explicitly tested the role of narratives, leaving an important question: how crucial are narratives in associative inference, and what role might they play? We used a modified associative inference paradigm to answer these questions. Our design factorially combined two factors during associative encoding: use of narratives, and explicitly linking the two objects. Participants separately learned AB and BC object pairs within ABC triads using four sets of instructions: i) generate narratives to link objects together, ii) generate narratives for objects separately, iii) compare perceptual properties of two objects, and iv) describe perceptual properties of objects individually. We tested participants' ability to infer AC associations as a function of encoding strategy. Across two experiments, using narratives to actively link objects produced a robust associative memory advantage that persisted across 1-day delay and remained substantial under more stringent retrieval conditions. This benefit was not attributable to a simple linking effect or to surface-level linguistic similarity between stories. A follow-up experiment revealed that this benefit did not generalize to perceptual memory for individual objects; instead, perceptual encoding facilitated perceptual object memory. These results reveal that deep, extended encoding emphasizing either narrativity or perceptual processing can benefit different aspects of retrieval.
28 July 2026
Read appraisal →Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
The past and future of neuropsychological assessment: Back to the origins to face digital technological changes.
BACKGROUND: The procedures used for the neuropsychological assessment of patients with dementia have been undergoing significant transformations relating to technological developments and the diffusion of artificial intelligence tools. OBJECTIVES: The integration of a theoretical position and a practical approach is needed in clinical contexts so that newly available tools can enhance the fundamental principles underlying neuropsychological assessment. METHODS: Following a historical review of the various approaches to neuropsychological assessment, an analysis of the risks associated with the introduction of digital techniques, when not supervised by expert clinicians, is presented. The need to integrate new technologies in a comprehensive assessment involving clinical observation, ad-hoc tests, and other sources of information such as neuroimaging and neurophysiological data is discussed. RESULTS: The integration of new technologies with a clinical, personalised approach to the patient represents a challenge for neuropsychology that deserves ad-hoc research and discussion.
26 July 2026
Read appraisal →Medicine
Effect of physical exercise on executive function in individuals with substance use disorder: A systematic review and meta-analysis
BACKGROUND: The increasing number of individuals with substance use disorder (SUD) has a serious impact on individuals, families, and society. As a complementary therapy, physical exercise has been used in the rehabilitation of individuals with SUD. This study systematically aimed to evaluate the effect of physical exercise interventions on enhancing executive function in individuals with SUD. METHODS: Electronic databases were searched, covering the period from their inception to December 26, 2024. The Cochrane Risk of Bias Assessment Tool was utilized to assess the methodological quality of the included literature. Data were extracted from study graphs using GetData Graph Digitizer 2.26, and Stata 17.0 was also employed to conduct analysis. Grading of recommendations assessment, development and evaluation pro was utilized to evaluate the quality of evidence of outcome indicators. RESULTS: Nine studies, encompassing 752 participants, were included in the analysis. Compared with the control group, physical exercise improved inhibition (Hedges's g = 0.47, 95% CI: 0.29 to 0.65, P < .001) and working memory (Hedges's g = 0.42, 95% CI: 0.16 to 0.69, P = .002), but did not significantly affect cognitive flexibility (Hedges's g = 0.51, 95% CI: -0.22 to 1.24, P = .170). Subgroup analysis revealed that physical exercise with single time of 46 to 60 minutes (Hedges's g = 0.39, 95% CI: 0.05 to 0.73, P = .024), 5 times per week (Hedges's g = 0.45, 95% CI: 0.07 to 0.83, P = .020), duration of 8 weeks (Hedges's g = 0.46, 95% CI: 0.14 to 0.77, P = .004) may improve working memory in individuals with SUD (these subgroup findings are exploratory and should be interpreted as hypothesis-generating). CONCLUSION: Evidence from this study suggests physical exercise may enhance inhibition and working memory in individuals with SUD. However, the improvement in cognitive flexibility requires further investigation in future studies.
19 July 2026
Read appraisal →Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Creative thinking in Parkinson's disease: A systematic review and meta-analysis
INTRODUCTION: Creativity in Parkinson's disease (PD) has aroused research interest due to its neurological underpinnings, which involve brain regions crucial for creative and divergent thinking (a core-process of creative thinking), and because of some patients who displayed an increased artistic drive following dopaminergic treatment. From a cognitive point of view, creative thinking underlies several cognitive abilities, such as executive functions and memory. Therefore, a better understanding of whether it is increased (or, at least, preserved) in PD patients can provide useful insights for sustaining cognitive functioning. The aim of the present study was to investigate whether PD patients regularly assuming dopaminergic medications present higher divergent thinking skills than healthy controls. METHODS: A meta-analysis was conducted according to the PRISMA guidelines to provide a statistical synthesis of the studies. Study quality was assessed using the QUADAS -2 tool. RESULTS: Ten studies were included in the meta-analysis, which indicated the absence of significant differences between PD patients and healthy controls in tasks assessing divergent thinking (Cohen's d = -0,095 (95% CI: -0,308, 0,118)). CONCLUSIONS: Such findings support the notion that divergent thinking can be spared by the disease, maybe constituting a possible resource for patients' cognitive functioning, as it involves those cognitive abilities that can compensate impairments in PD. Clinical implications and guidance to further studies and interventions to support PD patients' cognition were discussed.
17 July 2026
Read appraisal →Journal of molecular neuroscience : MN
Scalp Acupuncture Combined with Mouse Nerve Growth Factor Acupoint Injection for Post-stroke Cognitive Impairment
Post-stroke cognitive impairment (PSCI) markedly impairs rehabilitation efficacy and quality of life. Safe and effective interventions are urgently needed. Eighty-four patients with PSCI were randomly allocated into three groups (n = 28 per group). Group A received conventional cognitive training. Group B received conventional training plus scalp acupuncture. Group C received the treatment of Group B combined with mouse nerve growth factor (mNGF) acupoint injection. All interventions lasted 4 weeks. All groups exhibited significant within-group improvements in MoCA, ADL, MBI, and FMA scores after intervention. Group C achieved the optimal cognitive efficacy: the post-treatment MoCA score was 26.7 ± 2.9 (95% CI, 25.53-27.87), significantly higher than that in Group A (21.5 ± 3.5 (95% CI, 20.22-22.78), P < 0.001) and Group B (23.8 ± 3.2)(95% CI, 22.48-25.12), P = 0.003). The ADL score in Group C was the lowest among the three groups (F = 28.963, P < 0.001), suggesting better independence. Moreover, motor function (FMA) and basic self-care ability (MBI) were also significantly improved in all groups after intervention. There were significant inter-group differences in post-treatment FMA and MBI scores (F-FMA = 29.745, P < 0.001; F-MBI = 35.872, P < 0.001). The scores increased gradually from Group A to Group C, with Group C achieving the best improvement. Conventional cognitive training improves cognitive function and daily living ability in patients with PSCI. Scalp acupuncture combined with conventional training is more effective than training alone. The triple therapy of conventional training, scalp acupuncture, and mNGF acupoint injection further enhances rehabilitation outcomes, with prominent clinical application value.
13 July 2026
Read appraisal →Depression and anxiety
Tree Imagery in Drawing Tests for Screening Mental Disorders: A Systematic Review and Meta-Analysis
Although tree imagery in projective drawing tests is a promising nonverbal tool for screening mental disorders, its clinical utility remains constrained by inconsistent predictor selection. To address this gap, the present systematic review and meta-analysis synthesizes the characteristics of tree imagery linked to mental disorders and evaluates their predictive efficacy. Following the PRISMA guidelines, we analyzed 42 studies involving 8552 participants from English and Chinese databases published between 1948 and 2024. The results showed that 24 specific characteristics significantly predicted mental disorders (p < 0.05), which were classified into five distinct categories: blackened out (e.g., blackened tree, odds ratio [OR] = 2.01), scribbled lines (e.g., weak lines, OR = 2.82), oddly shaped (e.g., flattened crown, OR = 3.10), no vitality (e.g., very small tree, OR = 3.93), and overly simple (e.g., simplified drawing, OR = 7.07). Furthermore, subgroup analyses indicated that features such as "blackened tree" (OR = 1.71), "no motion" (OR = 3.34), and "excessive separation" (OR = 2.77) were significantly associated with affective disorders, whereas the presence of "roots" (OR = 4.89) was uniquely associated with the thought-disorder subgroup. Ultimately, tree imagery may offer a valuable nonverbal, adjunctive approach to screening for mental disorders, offering several statistically supported indicators that may effectively complement traditional assessment tools.
13 July 2026
Read appraisal →Behavior research methods
The English spaced compound word database
Compound words combine existing words to form a new concept. Spaced compound words represent one form of compound words in which the orthographic space is preserved between the two constituent words (e.g., coffee table). While recent research has mostly focused on unspaced compound words, spaced compound words offer important insight into the cognitive processes that support lexical retrieval and comprehension. Critically, whether readers process spaced compound words as single lexical units has important implications for how these items are stored and accessed in memory. To support future research, we developed the English Spaced Compound Word Database, wherein we collected familiarity, age-of-acquisition (AoA), and semantic transparency (ST) ratings for 1,162 spaced compound words. We conducted correlational analyses to compare these ratings across words, as well as across previously collected data on compound words' constituents. These analyses revealed a strong association overall between familiarity ratings and AoA, as well as familiarity and ST. When examining the relationship between ratings and the characteristics of a compound word's constituents, we found a strong relationship between frequency, AoA, and structural simplicity (i.e., number of characters, syllables, morphemes, and lexical similarity) within all three rating tasks. These findings provide a basis for testing future theoretical models of lexical processing and reading.
12 July 2026
Read appraisal →Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Topography and functional connectivity analysis of heart surgery-associated brain lesions: a literature review
BACKGROUND: Cardiac surgery is a major therapeutic advancement but remains associated with neurological complications, including ischemic stroke and postoperative cognitive decline. Compared with stroke of other etiologies, ischemic brain injury following cardiac surgery may involve distinct vascular territories and functional networks, potentially influencing its characteristic cognitive profile. METHODS: We performed a systematic review of case reports describing ischemic brain lesions occurring after cardiac surgery in adults with available neuroimaging data. Lesions were manually traced onto a standard brain atlas and compared with ischemic stroke lesions from the ATLAS database, matched for hemispheric involvement. Lesion topography was analyzed at the arterial territory and voxel levels. Lesion network mapping was conducted using normative resting-state functional connectivity data to identify patterns of functional disconnection. Permutation-based statistical analyses were applied, with correction for multiple comparisons and lesion volume included as a covariate. RESULTS: Nineteen articles met the inclusion criteria, yielding 20 cases of post-cardiac surgery ischemic lesions. Compared with stroke controls, these lesions more frequently involved posterior arterial territories, particularly the occipital branches of the posterior cerebral arteries and posterior thalamic regions. Lesion network mapping revealed a distinct pattern of functional disconnection in the occipital lobes, posterior thalamus (including the pulvinar), and medial frontal cortex. CONCLUSIONS: Our results suggest that ischemia associated with cardiac surgery may preferentially involve posterior arterial territories and be associated with distinct patterns of functional disconnection involving the occipital lobe, the pulvinar, and the medial frontal cortex.
6 July 2026
Read appraisal →Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Limb apraxia in Parkinson's disease and atypical parkinsonian syndromes: a systematic review
BACKGROUND: Evidence regarding the clinical manifestations, disease-specific profiles and diagnostic significance of limb apraxia in Parkinson's disease and Atypical Parkinsonian Syndromes (APS) is limited. OBJECTIVES: The present systematic review aims to consolidate current knowledge on limb apraxia across neurodegenerative disorders, including Parkinson's disease (PD), corticobasal syndrome (CBS), Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA). METHODS: A systematic literature review was conducted in accordance with PRISMA guidelines. Studies were included if they enrolled ≥ 10 patients in at least one of the patient groups and ≥ 10 control subjects with quantitative data on apraxic deficits. Risk of bias assessment was assessed. RESULTS: Twenty-two studies met inclusion criteria (PD n = 11; CBS n = 10; PSP n = 7; MSA n = 3). Across PD and APS, praxis assessment primarily involved gesture imitation, pantomime, action sequencing, actual tool use and measures of fine motor coordination. CBS demonstrated the most severe/widespread apraxic impairment, affecting both meaningless and meaningful (transitive and intransitive) gestures, as well as action sequencing and fine motor control. In PD, apraxic deficits were generally milder but shared overlapping features with CBS. Direct comparative studies between PD and CBS remain scarce. PSP was characterized by less frequent and predominantly sequence-related impairments, whereas findings in MSA were heterogeneous and less pronounced. CONCLUSIONS: Limb apraxia phenotypes differ across PD, CBS, PSP and MSA and may contribute to their differential diagnosis. Future research should adopt standardized, multimodal praxis assessment protocols in larger cohorts including all major neurodegenerative parkinsonian disorders, to facilitate the direct comparison of limb apraxia across these diseases.
4 July 2026
Read appraisal →The Behavioral and brain sciences
Large language models have learned to use language.
Acknowledging that large language models have learned to use language can open doors to breakthrough language science. Achieving these breakthroughs may require abandoning some long-held ideas about how language knowledge is evaluated and reckoning with the difficult fact that we have entered a post-Turing test era.
2 July 2026
Read appraisal →The Behavioral and brain sciences
Large language models are not about natural language.
Large Language Models are useless for linguistics, as they are probabilistic models that require a vast amount of data to analyze externalized strings of words. In contrast, human language is underpinned by a mind-internal computational system that recursively generates hierarchical thought structures. The language system grows with minimal external input and can readily distinguish between real language and impossible languages.
2 July 2026
Read appraisal →Journal of Alzheimer's disease : JAD
Early diagnosis of Alzheimer's disease through handwriting analysis and deep learning: A review.
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders worldwide, requiring early identification for timely intervention and to slow disease progression. However, existing diagnostic approaches, while effective at later stages, remain limited in detecting early-stage AD. Handwriting analysis has recently emerged as a non-invasive, cost-effective, and ecologically valid digital behavioral biomarker that reflects neurocognitive impairment. This review examines the role of handwriting as a neurocognitive marker for AD, focusing on integrating deep learning methodologies to enhance early diagnostic accuracy. It also elucidates the neurocognitive mechanisms linking handwriting behavior and AD, addressing current methodological and translational challenges. We performed a PRISMA-informed structured literature search and narrative synthesis of handwriting- and drawing-based studies for detecting AD/mild cognitive impairment (MCI), including offline handwriting images and online pen-stroke kinematics captured by digital devices. Task paradigms, data dimensions, preprocessing pipelines, modeling strategies (traditional machine learning and deep learning), evaluation practices, and translational considerations were summarized, and studies were organized by detection purpose and analytic approach. Our findings show that handwriting-based models generally discriminate AD/MCI from healthy controls with accuracy exceeding 80%, while deep learning models (e.g., convolutional neural network and multimodal Transformer fusion) approach 90% in structured tasks like clock drawing and figure copying. Online kinematic markers (e.g., reduced velocity, prolonged in-air time, increased pausing, and pressure instability) recur across studies, and multimodal integration with speech, gait, or facial signals can further improve sensitivity and ecological validity, although most studies are small and single-center.
2 July 2026
Read appraisal →Behavioural brain research
Sex differences in the use of spatial strategies in humans: An updated systematic review of the last decade.
Although sex differences in spatial cognition have been widely studied, the extent to which men and women differ in their use of egocentric and allocentric spatial strategies remains unclear. This systematic review summarizes findings from 21 studies published between 2014 and 2024 that examined sex differences in spatial strategy use throughout development, adulthood, and aging. Studies were identified through searches of Scopus, Web of Science, PubMed, and PsycINFO, in accordance with PRISMA guidelines. Eligible articles examined egocentric and allocentric spatial strategies in humans and reported results by sex. Results demonstrated male advantages in allocentric strategy, as observed in thirteen studies involving children, young adults, and older adults. Men also outperformed women in several navigation outcomes, including target retrieval, route efficiency, and directional accuracy. Evidence for a female advantage in egocentric strategies was limited and inconsistent. Seven studies reported no sex differences, particularly those using small-scale, familiar, or less immersive tasks. This suggests that methodological factors and task demands strongly influence the observed effects. Age also influenced outcomes. Male advantages in allocentric strategies emerged in early childhood. Older women showed relatively preserved egocentric abilities, but greater decline in allocentric tasks. Men showed stronger hippocampal-parietal connectivity supporting allocentric processing, while women exhibited enhanced fronto-temporal connectivity. Hormonal studies highlight the context-dependent effects of testosterone and estrogen. These findings indicate that sex differences in spatial strategies are highly sensitive to task complexity, environmental familiarity, cognitive load, and individual factors. These findings emphasize the necessity of integrative models that consider developmental, neurobiological, and sociocultural contributors.
25 June 2026
Read appraisal →Journal of mathematical biology
Spiking neural models for decision-making tasks with learning.
In cognition, response times and choices in decision-making tasks are commonly modeled using Drift Diffusion Models (DDMs), which describe the accumulation of evidence for a decision as a stochastic process, specifically a Brownian motion, with the drift rate reflecting the strength of the evidence. In the same vein, the Poisson counter model describes the accumulation of evidence as discrete events whose counts over time are modeled as Poisson processes. This model has a spiking neurons interpretation as these processes are used to model neuronal activities. However, these models lack a learning mechanism and are limited to tasks where participants have prior knowledge of the categories. To bridge the gap between cognitive and biological models, we propose a biologically plausible Spiking Neural Network (SNN) model for decision-making that incorporates a learning mechanism and whose neurons activities are modeled by a multivariate Hawkes process. First, we show a coupling result between the DDM and the Poisson counter model, establishing that these two models provide similar categorizations and reaction times and that the DDM can be approximated by spiking Poisson neurons. To go further, we show that a particular DDM with correlated noise can be derived from a Hawkes network of spiking neurons governed by a local learning rule. In addition, we designed an online categorization task to evaluate the model predictions. This work provides a significant step toward integrating biologically relevant neural mechanisms into cognitive models, fostering a deeper understanding of the relationship between neural activity and behavior.
14 June 2026
Read appraisal →Behavioural brain research
Function-specific repetitive transcranial magnetic stimulation enhances motor strategy adaptation when combined with motor practice.
Effective motor strategy adaptation is essential for both high-performance sports and neurorehabilitation. Repetitive transcranial magnetic stimulation (rTMS) can modulate brain function; however, its efficacy may depend on the specificity of the stimulation targets. This study investigated whether function-specific rTMS, guided by fMRI-defined activation during motor imagery, enhances motor strategy adaptation. Forty-six healthy adults were randomized into three groups: function-specific rTMS, hotspot rTMS, and a no-stimulation control. All participants received identical motor imagery and physical practice in the backward glide shot put. Kinematic and resting-state functional magnetic resonance imaging (rs-fMRI) data were collected before and after the 7-day intervention, and functional connectivity (FC) was analyzed. Results showed that function-specific rTMS led to significantly greater improvements in trunk angle during the glide phase, a critical biomechanical parameter. FC between the right inferior frontal gyrus (IFG) and primary sensorimotor cortex increased significantly in this group and was positively correlated with kinematic improvements. These findings demonstrate that rTMS targeting task-relevant brain regions enhances motor strategy adaptation via mechanisms involving FC associated with motor performance, highlighting its potential for optimizing motor learning in both athletic and clinical populations.
7 June 2026
Read appraisal →Lancet (London, England)
Comparison of [18F]flortaucipir and [18F]MK6240 for the detection of tau pathology in Alzheimer's disease (HEAD): a multicentre, prospective, cross-sectional, within-participant study
BACKGROUND: Tau PET imaging has emerged as a critical biomarker for Alzheimer's disease, informing diagnosis, staging, and therapeutic selection. We investigated whether PET tracer selection alters tau detection. METHODS: We conducted a prospective, multicentre, non-randomised, within-participant comparison of [18F]flortaucipir (Tauvid), currently used in clinical settings in the USA and Europe, and [18F]MK6240, an investigational tau PET tracer. Participants were recruited from eight north American sites and underwent tau PET, amyloid-β (Aβ) PET, and detailed cognitive assessments. Tau PET with both agents was acquired within a 45-day window. Coprimary outcomes were the discriminative accuracy for Alzheimer's disease-related cognitive impairment and the frequency of tau positivity in early medial temporal lobe (MTL) and late neocortical regions. The study is registered with ClinicalTrials.gov, NCT05361382. FINDINGS: Between March 2, 2022, and Aug 27, 2025, 775 individuals were enrolled, with 682 completing all procedures (373 [55%] female, 309 [45%] male; 38 [6%] aged 19-27 years, 214 [31%] aged 50-65 years, and 430 [63%] aged 65-89 years). 32 (5%) participants identified as Hispanic or Latino. 637 (93%) identified as White, 24 (4%) as Black or African American, 16 (2%) as Asian, and five (1%) as other. In addition, 49 (7%) individuals were identified as being from a rural area. [18F]MK6240 showed greater accuracy than [18F]flortaucipir in distinguishing Alzheimer's disease from non-Alzheimer's disease impairment (area under the curve 0·93, 95% CI 0·89-0·95 vs 0·86, 0·75-0·91; p<0·0001). Among the older adults, tau positivity status was concordant in 560 (87%) for MTL and 603 (94%) for neocortical regions. In cognitively unimpaired participants, [18F]MK6240 identified twice as many MTL-positive cases as [18F]flortaucipir (n=54 [15%] vs n=23 [6%]). Prevalence ratio in Aβ-positive was 2·43 (95% CI 1·50-3·94; p=0·0003), identifying 23 additional cases per 100. Among discordant cases, 75 (89%) were [18F]MK6240-positive only and had higher Aβ burden (p<0·0001), APOEε4 frequency (p<0·0001), and cognitive impairment (p=0·0043) than those negative on both tracers. Neocortical tau positivity was more frequent with [18F]MK6240 than with [18F]flortaucipir in cognitively impaired individuals (80 [28%] vs 46 [16%]). Prevalence ratio in Aβ-positive was 1·74 (95% CI 1·32-2·29; p<0·0001), identifying 15 additional mild cognitive impairment and 21 dementia cases per 100. INTERPRETATION: Tau PET tracer selection influences the frequency of detection of tau pathology across the ageing and Alzheimer's disease spectrum. Compared with [18F]flortaucipir, [18F]MK6240 identified more individuals with tau pathology in cognitively unimpaired and cognitively impaired individuals, with direct implications for patient stratification in clinical trials and more precise guidance for therapeutic decision-making. FUNDING: National Institute on Aging.
31 May 2026
Read appraisal →Behavioural brain research
Efficacy of repetitive transcranial magnetic stimulation at different frequencies for post-stroke cognitive impairment: A network meta-analysis
PURPOSE: Post-stroke cognitive impairment (PSCI) affects nearly half of stroke survivors, necessitating effective interventions. This Bayesian network meta-analysis evaluated the efficacy of various repetitive transcranial magnetic stimulation (rTMS) protocols for PSCI. METHODS: We systematically searched PubMed, Cochrane Library, and Chinese databases up to December, 2025, including 37 randomized controlled trials (2543 patients) comparing rTMS protocols with different frequencies (low/high) and sites (left/right). Outcomes were measured using the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and Modified Barthel Index (MBI). RESULTS: Results indicated that high-frequency left dorsolateral prefrontal cortex stimulation (HFL-rTMS) most effectively improved MoCA scores (MD=3.38, SUCRA=87.6%), high-frequency right-sided stimulation (HFR-rTMS) ranked highest for MMSE improvement (MD=2.93, SUCRA=79.7%), and high-frequency bilateral stimulation (HFB-rTMS) yielded the greatest MBI enhancement (MD=13.47, SUCRA=89.6%). CONCLUSIONS: High-frequency rTMS demonstrated superior efficacy in cognitive and functional recovery. HFL-rTMS, HFR-rTMS, and HFB-rTMS are recommended as optimal interventions for MoCA, MMSE, and MBI outcomes, respectively. Further studies are warranted to validate stimulation parameters and expand multicenter evidence for clinical application.
30 May 2026
Read appraisal →Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Exercise effects on cognitive function and molecular markers in post-stroke patients with cognitive impairment: a systematic review and meta-analysis
INTRODUCTION: Exercise may improve cognitive function in stroke survivors. However, no study has yet examined the most effective exercise modalities and associated changes in biomarkers. This study aims to investigate the effects of different exercise types on cognitive function and biomarker trends, providing evidence-based guidance for early rehabilitation interventions. METHODS: Data from randomized controlled trials were collected from January 1, 2000, to March 6, 2025, using medical subject headings combined with free-text terms from PubMed, Cochrane Library, Embase, Wanfang, CNKI, CSTJ, and the China Medical Information Database. The Cochrane Risk of Bias Tool was used to assess the quality of the studies. Review Manager version 5.4.1 was employed to conduct all statistical syntheses. RESULTS: The forty-four original studies involving 4,450 patients with PSCI(Post-stroke cognitive impairment) were analyzed. Subgroup analysis by exercise intervention type revealed larger effect sizes when combining aerobic exercise with other task-based interventions(cognitive-motor dual-tasking and functional motor training) [SMD = 1.18, 95% CI (0.68, 1.68)]. Patients also showed improvements in motor function [MD = 13.98, 95% CI (10.06, 17.89)] and activities of daily living [MD = 16.78, 95% CI (12.97, 20.58)]. Concerning molecular biomarkers, serum levels of brain-derived neurotrophic factor (BDNF), glutathione (GSH), and neuron-specific enolase (NSE) increased significantly, whereas interleukin-6 (IL-6) levels decreased notably in PSCI patients following exercise therapy. CONCLUSION: Structured exercise effectively improves cognitive recovery, motor skills, and daily functioning in patients with PSCI. These clinical gains are accompanied by favorable peripheral biomarker modulations, characterized by significantly increased serum BDNF and GSH, as well as markedly decreased IL-6 levels.
28 May 2026
Read appraisal →Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
How can social cognition be improved in neurological patients? a systematic review.
BACKGROUND: The neural network underlying social cognition (SC) may be vulnerable to different types of lesions, but also amenable to recovery through interventions that stimulate brain plasticity. This review assessed current non-pharmacological interventions (NPIs) and their effects on SC in neurological patients. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Randomized controlled studies, cohort studies, cross-sectional studies, case series, case reports, and literature reviews were included if they reported a precise description of the NPI in subjects older than 6 years, with brain or cerebellar lesion. RESULTS: Among 5.077 screened articles, 17 fulfilled the eligibility criteria. These articles provided 19 face-to-face, online or hybrid methods, involving 344 patients with multiple sclerosis, stroke, Parkinson disease, cerebellar ataxia, traumatic brain injuries or mixed acquired brain injuries. The methods were applied in observational and randomized study designs using group or individual settings, involving SC, general cognition, and relational aspects. These NPIs, classifiable into training, rehabilitation or combined interventions, improved SC in patients with various diagnosis and age. CONCLUSIONS: Results show that NPIs for SC in neurological patients is being addressed with insightful methods and study designs with improvement possibility in children and adults suffering different pathologies. This is not sufficient for thorough consensus but can trigger a range of broader high-quality and interdisciplinary clinical and research applications.
27 May 2026
Read appraisal →The journal of trauma and acute care surgery
Cognitive dysfunction after polytrauma in the absence of traumatic brain injury: A systematic review of incidence.
BACKGROUND: Polytrauma patients frequently experience long-term health impacts, including cognitive impairments. While traumatic brain injury (TBI) is a recognized nonmodifiable cause, polytrauma patients are likely to face cognitive challenges potentially linked to systemic inflammation and multiple surgical interventions even in the absence of TBI. This review aims to describe the incidence and identify factors associated with cognitive dysfunction in adult multiple injury patients without Frank TBI. METHODS: A systematic search was conducted across MEDLINE, CINAHL, EMBASE, and Scopus databases on August 17, 2023, to identify studies reporting on cognitive dysfunction in adults with polytrauma, excluding brain injuries. The Critical Appraisal Skills Programme checklists guided study appraisal, and findings were narratively synthesized. RESULTS: From 2719 articles identified (including one through citation searching), 47 were fully screened, yielding 10 cohort studies for inclusion. The reported incidence of cognitive dysfunction among multiple injury patients without TBI varied widely, from 0% to 60%, with a majority (eight out of ten studies) noting incidences of 30% or higher. No consensus was found for a relationship of other studied factors with cognitive dysfunction. Injury Severity Score was found to not be associated with cognitive dysfunction in selected studies which analyzed this factor. CONCLUSION: This review suggests a high prevalence of cognitive dysfunction in multiple injury patients without TBI. The evidence base is limited by heterogeneity of the inclusion criteria, and the cognitive outcome measures. IMPLICATIONS OF KEY FINDINGS: Multiple injury is associated with long term cognitive dysfunction even without primary brain injury. This aspect of the disease of multiple injury needs further characterization to identify predictors and potential preventive and therapeutic interventions. Standardized reporting is also required to be able to monitor incidence and prevalence. ( J Trauma Acute Care Surg . 2026;100: 973-981. Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.). LEVEL OF EVIDENCE: Systematic Review; Level II.
23 May 2026
Read appraisal →Neurosurgical review
Short-and long-term responsiveness of deep brain stimulation on motor and cognitive outcomes in GBA vs. Non-GBA parkinson's disease: a systematic review and meta-analysis of observational studies
Deep brain stimulation (DBS) is an established therapy for motor complications in Parkinson's disease (PD). Patients carrying glucocerebrosidase (GBA) mutations exhibit distinct disease trajectories, raising questions regarding potential differences in clinical outcomes following DBS compared with non-carriers. To evaluate short- and long-term motor, medication, and cognitive outcomes following DBS in patients with GBA-PD compared with non-GBA PD. We conducted a systematic review and meta-analysis of studies reporting clinical outcomes in PD patients with and without GBA mutations who underwent DBS and had a minimum follow-up of one year. Random-effects inverse variance models were applied, with subgroup analyses according to GBA status. DBS was associated with significant improvements in motor function in the off-medication state and sustained reductions in levodopa equivalent daily dose in both GBA carriers and non-carriers, with no significant between-group differences. Cognitive performance declined over long-term follow-up in both groups. At five years, greater cognitive decline, assessed using the Mattis Dementia Rating Scale, was observed among GBA-PD mutation carriers compared with non-carriers. Motor improvement and medication reduction following DBS were comparable between PD patients with and without GBA mutations. Over long-term follow-up, greater cognitive decline was observed among GBA-PD carriers.
21 May 2026
Read appraisal →Journal of neurology, neurosurgery, and psychiatry
Comparison of neuropsychological side effects between contemporary radiofrequency ablative neurosurgery for psychiatric disorders and conventional neurosurgical procedures: systematic review and meta-analysis
BACKGROUND: Psychiatric disorders are increasingly contributing to global disability. Despite advances in conservative management, the prevalence of treatment-resistant cases remains high. Meanwhile, neurosurgery for psychiatric disorders (NPD) remains underused, largely due to strict regulations and historical concerns, particularly those related to neuropsychological side effects (NPSE). OBJECTIVE: To address this issue, we conducted a systematic review with meta-analysis to compare NPSE associated with radiofrequency ablative NPD to those observed in neuro-oncological, neurovascular and epilepsy surgeries. METHODS: PubMed, Embase and LILACS databases were searched in April 2024 for articles published in English/Spanish from 1990 to 2022, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: A total of 48 articles with 2678 participants were included. The frequency of transient and permanent NPSE in the NPD group ranged from 0.94% to 11.50% and 0.94% to 2.03%, respectively, comparable to the other surgical groups (epilepsy: 0.31-11.70%; vascular: 0.52-22.90%; oncology: 0.94-17.60% for transient NPSE; epilepsy: 0.31-12%; vascular: 0.40-1.96% and oncology: 0.84-1.48% for permanent NPSE). Regarding permanent NPSE, arguably the most critical consideration, the NPD group showed better outcomes in memory, language and social cognition than the epilepsy group, but worse outcomes in executive and perceptual-motor functions. Compared with the vascular group, the NPD group had better executive function but worse complex attention. Finally, the NPD group had fewer permanent deficits than the oncology group in executive function, complex attention and perceptual-motor domains, although language performance was lower. CONCLUSIONS: Contemporary NPD apparently carries a similar risk of NPSE as other conventional neurosurgical procedures, challenging misconceptions and this unjustified barrier to its broader use.
16 May 2026
Read appraisal →Journal of neurology
The effects of computerized cognitive training on cognitive function in patients with mild cognitive impairment: a systematic review and meta-analysis
BACKGROUND: We sought to quantify the effects of computerized cognitive training (CCT) on patients with mild cognitive impairment (MCI), to inform the development of clinical non-pharmacological intervention strategies. METHODS: We searched PubMed, Cochrane Library, Embase, and Web of Science databases from 2007 to February 2026 for randomized controlled trials (RCTs) of CCT in patients with MCI. Outcomes including global cognition, specific cognitive domains, psychosocial functioning, and activities of daily living were analyzed separately by stata 18 and Review Manager 5.4. RESULTS: We included 30 studies and 2056 participants. Our meta-analysis revealed that, compared with control conditions, CCT led to a significant moderate improvement in overall cognitive function, standardized mean difference (SMD) = 0.62, 95% confidence interval (CI) = 0.43-0.81; I2 = 73%. Subgroup analysis showed that intervention characteristics-including session duration, training device, total intervention length, weekly frequency, sample size, and assessment tools-yielded similar improvements in global cognition, with no statistically significant differences between subgroups. These findings indicate that the cognitive benefits of CCT are consistent and robust. CONCLUSION: This systematic review and meta-analysis shows CCT significantly improves global cognitive function in MCI patients, with stable benefits across subgroups. Despite clear overall effects, high heterogeneity, varying training protocols and assessment tools exist. Further large, long-term RCTs are needed to clarify CCT's long-term effects and support its standardized clinical application. TRIAL REGISTRATION: PROSPERO International prospective register of systematic reviews CRD420261328762; https://www.crd.york.ac.uk/PROSPERO/view/CRD420261328762 .
15 May 2026
Read appraisal →Fluids and barriers of the CNS
Cognitive assessment methods and outcomes following shunt surgery in idiopathic normal pressure hydrocephalus (iNPH): a systematic review and meta-analysis
INTRODUCTION: Core cognitive deficits in iNPH include slowed information processing, psychomotor slowing and executive dysfunction. However, cognitive outcomes following shunt surgery are not well understood. This review synthesised evidence on cognitive assessment methods and outcomes following shunt surgery in iNPH. METHODS: PubMed, Scopus, PsycINFO and Web of Science were searched for peer-reviewed studies including adults with iNPH who underwent shunt surgery and had within-subject cognitive evaluations pre- and post-operatively. Key data were extracted and study quality was assessed. Random-effects meta-analyses were performed on pooled baseline and post-shunt difference scores for frequently reported cognitive tests with comparable outcome data. RESULTS: Of 1,876 records, 195 met the inclusion criteria, comprising 11,445 patients. Cognitive evaluation methods ranged from subjective reports and NPH grading scales to brief screening tools and comprehensive test batteries. Over 193 distinct tests were reported and 54.4% of studies did not formally assess any core iNPH cognitive deficits. Post-shunt improvement rates, follow-up times and criteria for defining improvement varied widely. Eighty-five studies contributed data to meta-analyses of ten outcomes. Pooled estimates indicated post-shunt cognitive improvement, with Trail Making Test-A, Grooved Pegboard-Dominant and Trail Making Test-B showing changes exceeding thresholds for clinically significant improvement. CONCLUSIONS: Cognitive assessment in iNPH is highly heterogeneous and frequently omits core domains, limiting detection of treatment effects. When domain-relevant cognitive measures are used, shunt surgery is associated with statistically and clinically significant cognitive improvement. These findings highlight the need for standardised iNPH-appropriate cognitive evaluation tools with validated criteria for detecting clinically meaningful change and have direct implications for clinical assessment, interpretation of shunt response and the selection of cognitive endpoints in future interventional studies.
15 May 2026
Read appraisal →Experimental brain research
Subthalamic nucleus deep brain stimulation and associations with attention and processing speed in Parkinson's disease
Although subthalamic nucleus deep brain stimulation (STN DBS) is an effective treatment for the motor symptoms of Parkinson's disease (PD), its effects on cognitive functions are controversial. This cross-sectional study aimed to compare attention and processing speed in PD patients with STN-DBS and those receiving medical therapy, using a multimodal assessment combining P300 event-related potentials and neuropsychological tests. The study included 20 PD patients who underwent STN DBS and 17 PD patients who were followed with medical treatment. Demographic and clinical data for all patients were recorded. Cognitive functions were assessed using the P300 potential, the Stroop test (ST), and the Serial Digit Learning Test (SDLT). P300 potential latency and amplitude values, as well as neuropsychometric test results, were statistically compared between the two groups. P300 latency was shorter in the DBS-treated group than in the non-DBS group (p = 0.004). Performance times on Part III of the ST were shorter in the DBS-treated group (p = 0.03). In addition, a higher proportion of patients in the DBS-treated group performed normally on Part I of the ST compared to the non-DBS group (p = 0.03). There was no significant difference between the two groups in SDLT results. Shorter P300 latency and subtle differences in ST performance suggest a potential association between STN-DBS and the cognitive domains of attention and processing speed. Combining neuropsychological and electrophysiological assessments could provide a more comprehensive evaluation, and future large-scale, longitudinal studies are needed to clarify domain-specific cognitive effects.
14 May 2026
Read appraisal →Psychological medicine
Cognitive effects of intravenous Ketamine in treatment-resistant depression: A systematic review
Intravenous (IV) low-dose ketamine has emerged as a promising treatment for patients with treatment-resistant depression (TRD). However, its impact on cognitive functioning remains unclear. This systematic review examines the cognitive and executive effects of IV ketamine in TRD, focusing on their relationship to depressive and suicidal outcomes. A systematic search of Cochrane, MEDLINE, Embase, and PsycINFO databases was conducted up to May 15, 2025, using the terms depression, cognition, and ketamine. This review was conducted in accordance with the PRISMA guidelines, and the protocol was registered in PROSPERO (ID: 1160487). Risk of bias was evaluated using the Cochrane RoB 2 tool for randomized trials and the ROBINS-I tool for non-randomized studies. Twenty-one studies, comprising approximately 900-1,180 participants with TRD, assessed cognitive domains of processing speed, working memory, attention, verbal and visual memory, cognitive flexibility, and executive control. Procognitive effects were frequently observed in processing speed and working memory, while attention results were preserved or modestly improved, and verbal and visual memory results were heterogeneous. Executive control, particularly inhibitory performance on Stroop paradigms, improved in several trials. Two studies directly examined cognition as it relates to suicidal behaviors. No cognitive deterioration was reported. Subanesthetic IV ketamine appears to preserve and enhance specific cognitive functions in TRD, notably across processing speed, working memory, and executive control. These procognitive effects, particularly in executive control, may mediate ketamine's antisuicidal action. Standardized longitudinal studies are warranted to clarify their durability and clinical significance.
12 May 2026
Read appraisal →BMJ open
Multimodal personalised executive function intervention (E-Fit) for school-aged children with complex congenital heart disease in Switzerland: a randomised controlled feasibility study
OBJECTIVE: To explore the feasibility of a novel multimodal executive function intervention in school-aged children with complex congenital heart disease (cCHD). DESIGN: Single-centre, single-blinded, randomised-controlled 8-week multimodal personalised executive function intervention (E-Fit) study. Outcomes were measured throughout the intervention, post-intervention (T1) and at 4-month follow-up (T2). SETTING: Tertiary care centre between May 2022 and May 2024. PARTICIPANTS: Children 10 to 12 years (M=11.0, SD=0.9) with cCHD without a genetic diagnosis with infant open-heart surgery and reported difficulties (T-scores ≥60) on any of the summary scales of the parent- or teacher-reported Behavior Rating Inventory for Executive Function (BRIEF). INTERVENTIONS: Children with cCHD were randomly assigned to one of two groups: the intervention or the control group. The 8-week intervention was multimodal including three modalities: (1) computerised executive function (EF) training 3×20 min/week with CogniFit; (2) a weekly, remote standardised 1:1 individual EF strategy coaching; (3) analogue games played at convenience. The control group completed activity logs. FEASIBILITY MEASURES: Acceptability: Acceptance and Feasibility Scale (AFS) and coach-rated engagement during coaching sessions. Demand: Number of completed computerised training, strategy coaching and analogue game sessions. IMPLEMENTATION: E-Fit Fidelity Measurement System, assessing adherence to core components. Practicality: Retention rate. Integration: AFS integration items. Exploratory efficacy: BRIEF, neuropsychological EF testing and psychosocial variables at baseline, post-intervention (8 weeks) and at 4-month follow-up. RESULTS: We recruited 42 participants (Nfemale=20). Acceptability: The intervention was acceptable, with moderate observed engagement. Demand: median number of computerised training sessions completed was 16 of 24 sessions (67%, (IQR; 6 to 19)), all children attended all scheduled coaching sessions, analogue games were played in total a median of 9 times (IQR 4 to 14). IMPLEMENTATION: Coaching sessions could be implemented by the coaches as intended. Practicality: Overall retention rate was 90%. Integration: E-Fit was well integrable into the home setting. Exploratory efficacy favoured the intervention group with improvements in the parent-rated Behavioral Regulation Index of the BRIEF (adjusted Hedge's (gA1) = -0.408 to -0.903) and in social responsiveness (gA1 = -0.427 to -0.521) at T1 and at T2. CONCLUSIONS: E-Fit is a feasible intervention suggesting EF and social responsiveness improvements in children with cCHD. Motivational strategies to improve adherence to computerised training should be refined before a full-scale efficacy trial. TRIAL REGISTRATION NUMBER: NCT05198583.
12 May 2026
Read appraisal →Behavioral and brain functions : BBF
Neuropeptide S modulation of learning and memory: a systematic review
BACKGROUND: In the last two decades, Neuropeptide S (NPS) has been identified as a key bioactive peptide in the mammalian brain, influencing fear, anxiety, wakefulness, reward, and learning. While some reviews have addressed its role in reward-seeking and anxiety, few have addressed its particular role in learning and memory. The neuropeptide S receptor 1 is highly expressed in key areas for learning processing, such as the hippocampus, cortex, thalamus, and amygdala. This review aims to examine evidence from human and animal studies that focused on the NPS system's role in modulating learning and memory. A special focus is given to experiments addressing the impact of NPS on associative learning leading to addiction and in fear conditioning, pointing to its potential therapeutic value in associated pathologies. MAIN BODY: An advanced search was conducted using the databases PubMed, Google Scholar, Web of Science, and Scopus, focusing on memory and Neuropeptide S. The reviewed data suggest that NPS modulation occurs at all memory phases, including acquisition, consolidation, and retrieval, and in extinction learning, whether motivated by appetitive or aversive stimuli. The summarized evidence shows that the NPS system interferes with working and short-term memory, mitigates learning impairments, enhances spatial and object memory consolidation, supports fear extinction learning and inhibitory avoidance consolidation, and reinstates drug-seeking behaviors. The NPS system closely interacts with key neuromodulators, including orexinergic, dopaminergic, and noradrenergic systems, in influencing memory. CONCLUSION: The Neuropeptide S system emerges as a critical modulator of memory processes. The NPS signaling may preferentially influence learning that involves emotionally or motivationally relevant stimuli. This highlights the NPS system's potential as a target for therapeutic interventions for particular memory impairments.
11 May 2026
Read appraisal →Neuropsychologia
Sparsity and memory constraints interact with training sequence to bias learning of associative maps.
Cognitive maps support inference and planning by representing associations between experiences encoded in memory. These map-like representations are thought to carry information not only about directly observed links but also about longer paths. The ability to make judgments based on multi-step associations varies with one's experience in an environment and with changes in memory abilities across the lifespan. However, it remains unclear exactly how representations of associative structure are influenced by learning curricula and memory constraints. Prior studies have suggested a tradeoff: memory representations can either be more integrated to improve inference, or more separated to recall distinct direct associations. Whether overlapping associations are experienced nearby in time (interleaved) or spaced apart (blocked) can bias memory representations toward integration or separation. However, key recent findings about how blocked versus interleaved experience bias integration or separation have been inconsistent. Here, we introduce a computational framework that helps reconcile these apparent discrepancies. Using neural network simulations of three separate memory-guided inference tasks, we show that variations in memory capacity and the sparsity of neural codes interact with learning sequence to shape network representations. Specifically, blocked learning promotes integration when memory capacity is low, while interleaved learning promotes integration when memory capacity is high. Integration is especially likely to result from representations formed when neural codes are both sparse and distributed. These results offer a principled computational account of how flexible, map-like representations can arise from experience and suggest avenues for individualized memory interventions to improve inference, generalization, and planning.
10 May 2026
Read appraisal →International journal of psychophysiology : official journal of the International Organization of Psychophysiology
Task-evoked brain network dynamics underlying cognitive control using source-localized EEG and machine learning
OBJECTIVE: Functional connectivity (FC) coordinates brain activity during cognitive tasks, yet the influence of demographic variables and health factors on task-related dynamic FC remains underexplored. We examined FC within and between seven core brain networks: Default Mode (DMN), Ventral Attention (VAN), Somatomotor (SMN), Dorsal Attention (DAN), Frontoparietal (FPN), Visual (VIN), and Limbic (LIN) during a modified Eriksen flanker task. We aimed to identify distinct network configurations linked to varying cognitive control demands and assess the influence of demographic and health factors. METHODS: Secondary analyses of source-localized EEG data from 255 adults (mean age 38.97 ± 11.65 years; BMI 30.21 ± 9.29 kg/m2) were conducted. A hidden Markov model extracted spatiotemporal dynamics, quantifying within- and between-network correlations. Extreme Gradient Boosting with recursive feature elimination identified connectivity metrics predicting reaction time (RT) of high performers (>80% accuracy). Regression models assessed effects of age, sex, BMI, and income on task-related FC. RESULTS: Classification accurately predicted RT in both congruent (AUC = 0.81) and incongruent (AUC = 0.86) trials. Key FC features included VAN-LIN, VIN-VAN, and SMN-DAN for congruent trials; SMN-DMN, LIN-FPN, and VIN-DAN for incongruent trials. Age was linked to reduced FC, while higher BMI showed modest positive FC associations in LIN-FPN and VIN-DAN. Sex and income were not significant predictors of RT or FC. CONCLUSIONS: These findings reveal the relevance of specific dynamic network interactions in cognitive control and highlight the need to consider age and BMI as contributors to brain connectivity during task performance.
4 May 2026
Read appraisal →Psychological medicine
Characterizing executive dysfunctions in patients with schizo-obsessive comorbidity: comparing schizophrenia with obsessive-compulsive disorder
BACKGROUND: The term 'schizo-obsessive comorbidity (SOC)' is used to describe the presence of obsessive-compulsive symptoms or obsessive-compulsive disorder (OCD) in patients with schizophrenia (SOC). Recent studies have found overlapped executive dysfunctions in SCZ and OCD implicating shared pathophysiology. However, specific deficits in the components of executive function (EF) in patients with SOC remains unclear. METHODS: We recruited 37 patients with SOC, 68 patients with SCZ, 70 patients with OCD, and 59 healthy controls (HCs). All participants completed a battery of measures for EF components, namely initiation, sustained attention, online updating, switching, disinhibition, and planning. Apart from traditional group-mean analysis, we applied machine learning approaches to identify the unique patterns of EF among different clinical groups. RESULTS: The results showed that the three clinical groups could be distinguished from HCs. The feature importance analysis showed that, to classify clinical groups from HC, online updating was the core feature of SCZ patients, whereas disinhibition and online updating jointly determine classification between OCD patients and HC. In differentiating SOC from HC, online updating, planning, and disinhibition collectively served as key features. Machine learning algorithms classified SOC and OCD with acceptable performance but classified SOC and SCZ with lower performance. CONCLUSIONS: Deficits of EF are shared features among patients with SOC, SCZ, and OCD. However, the specific components of executive dysfunction in these clinical groups appeared distinct.
2 May 2026
Read appraisal →Neurology
Association of MRI-Visible Perivascular Spaces With Longitudinal Cognitive Decline Over a Decade
BACKGROUND AND OBJECTIVES: Cerebral small vessel disease (SVD) is the most common vascular contributor to dementia. SVD markers often coexist, contributing to difficulty assessing their independent contributions to cognitive domains. MRI-visible perivascular spaces (PVSs) are an emerging SVD marker visualized by MRI. We previously showed that basal ganglia PVSs cross-sectionally contribute to worse cognition, independent of other SVD markers. To further characterize the clinical relevance of PVS, we studied its role as a unique SVD marker of longitudinal cognitive decline. METHODS: Participants without stroke or dementia were included in the Vanderbilt Memory and Aging Project, a longitudinal observational cohort study based in Nashville, TN. Participants completed 3T MRI at study entry to measure SVD burden (PVS volume fraction, white matter hyperintensities volume, lacune counts, and cerebral microbleeds counts). PVS volumes were segmented using a deep learning algorithm. Participants underwent comprehensive serial neuropsychological testing over an 11-year follow-up period (mean follow-up = 4.9 ± 3.1 years). Each SVD marker was related to longitudinal neuropsychological performances using a linear mixed-effects model adjusting for age, sex, race/ethnicity, education, baseline cognitive status, apolipoprotein E-ε4 presence, Framingham Stroke Risk Profile, and intracranial volume. Head-to-head comparisons simultaneously tested multiple statistically significant SVD markers. RESULTS: Among participants (n = 750, age 68 ± 9 years, 52% female), higher basal ganglia PVS burden at baseline was associated with worse longitudinal performances in Boston Naming Test (β = -29.63; 95% CI -56.66 to -2.60), Animal Naming (β = -33.09; 95% CI -65.66 to -0.51), Wechsler Adult Intelligence Scale IV Coding (β = -86.36; 95% CI -150.9 to -21.82), executive function composite (β = -9.51; 95% CI -14.33 to -4.68), Hooper Visual Organization Test (β = -26.06; 95% CI -50.53 to -1.59), and episodic memory composite (β = -7.05; 95% CI -11.9 to -2.21). In head-to-head comparisons, basal ganglia PVS remained independent associations with executive function composite (β = -7.47; 95% CI -12.84 to -2.10) and Hooper Visual Organization Test (β = -22.11; 95% CI -42.38 to -1.85). DISCUSSION: Basal ganglia PVS burden independently contributes to worse longitudinal executive function and visuospatial skills independent of other SVD markers, highlighting PVS as an emerging marker of domain-specific cognitive decline in aging. Although causation cannot be established, findings further support PVS as a vascular contributor to deep brain structure damage underlying cognitive decline over time.
28 Apr 2026
Read appraisal →Journal of neurology
Iron accumulation in multiple sclerosis and implications for cognitive and clinical progression: a systematic review of advanced neuroimaging studies
BACKGROUND AND AIMS: Iron-related alterations are frequently implicated in multiple sclerosis (MS) neurodegeneration, but its relationship with clinical symptoms and cognitive impairment remains unclear. We systematically reviewed evidence linking iron-sensitive susceptibility-based magnetic resonance imaging (MRI) metrics to cognitive outcomes, in order to evaluate their potential role as diagnostic and prognostic biomarkers of cognitive decline in MS. MATERIALS AND METHODS: A systematic review was conducted using the PRISMA guidelines. 600 studies were identified by searching PubMed, Scopus, Web of Science, and Embase in October 2025. After screening, 12 studies fulfilled the eligibility criteria and were included. RESULTS: Two main patterns emerged: (i) higher basal ganglia susceptibility/iron-related metrics are consistently linked to worse cognitive performance, particularly information processing speed and executive control; and (ii) thalamic findings are more variable in direction and clinical meaning, with susceptibility often capturing a mixed signal that overlaps with thalamic atrophy. CONCLUSIONS: Iron-sensitive quantitative MRI captures clinically relevant deep gray matter (DGM) pathology associated with cognitive impairment in MS, with basal ganglia measures showing the strongest linkage with cognitive and clinical outcomes. Future studies should include harmonized methodology and a longitudinal component.
19 Apr 2026
Read appraisal →Journal of rehabilitation medicine
Does aerobic exercise affect memory, attention, working memory, and fatigue after acquired brain injury? A single-blinded, randomized controlled pilot study.
OBJECTIVE: To explore potential effects of aerobic exercise on cognitive function, fatigue, and neuroplasticity after stroke or traumatic brain injury. DESIGN: A randomized controlled pilot study. SUBJECTS/PATIENTS: Twelve participants, 10 men and 2 women aged 16-65 years diagnosed with acquired brain injury (moderate to severe stroke or traumatic brain injury), enrolled in an outpatient rehabilitation programme at least 3 months post-injury. METHODS: The intervention group (n = 6) participated in 30 min of aerobic exercise 3-4 times/week for 8 weeks during their outpatient rehabilitation. The control group (n = 6) received routine physical therapy. In addition, both groups received rehabilitation according to their rehabilitation plan. Neuropsychological and endurance testing was performed before and after the intervention and at a 3-month follow-up. Functional magnetic resonance imaging was performed before and after the intervention. RESULTS: Preliminary findings show no significant difference between the groups regarding cognitive variables, fatigue, or neuroplasticity. However, working memory/executive demanding processing speed, measured with the Paced Auditory Serial Addition Test, improved significantly (p = 0.042) in the aerobic exercise group and there were trends of improvements on several other executive tests in the aerobic exercise group. Automatic visual search speed improved in the control group (p = 0.027). CONCLUSION: The question of whether aerobic exercise promotes cognition and fatigue after brain injury remains unanswered. This randomized controlled pilot study and its preliminary findings indicate greater improvements in executive processing speed in the aerobic exercise group, while more automatized attention speed improved more in the control group. The experiences from this study might facilitate the design of future studies on this intriguing topic. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT07429526.
17 Apr 2026
Read appraisal →Brain : a journal of neurology
Multimodal multicentre investigation of diagnostic and prognostic markers in disorders of consciousness
Severely brain-injured patients may enter a spectrum of conditions collectively known as disorders of consciousness. This spectrum includes clinical conditions such as unresponsive wakefulness syndrome or minimally conscious state, where the behavioural assessment of consciousness can often be deceptive. To bridge this dissociation, neuroimaging techniques are employed to identify the residual brain functions. Each neuroimaging modality imperfectly captures distinct aspects of brain preservation-functional, anatomical, or both. In this study, we adopt a comprehensive approach by integrating the neurophysiology and neuroimaging modalities available from the standard and advanced clinical assessments through interpretable machine learning. The electrophysiological modalities included high-density EEG (resting state and task), whereas neuroimaging modalities included anatomical and resting-state functional MRI, diffusion MRI and 18F-fluorodeoxyglucose PET. Our investigation reveals that specific modalities, such as functional assessments, provide comprehensive insights into the currently evaluated state of consciousness, the diagnosis of the patients. Conversely, structural modalities offer valuable information about the patient's evolution within the consciousness spectrum. We validate the proposed analysis with data coming from other centres with different acquisition parameters. Importantly, we demonstrate that model performance improves with an increase in the number of modalities. We observe a higher inter-modality disagreement for minimally conscious state patients and those patients who improve. Lastly, we observe a difference in feature importances between diagnosis and prognosis, with an interaction between modality and anatomical structures: some subcortical markers tend to contribute more to prognosis, while other cortical markers are more informative for diagnosis. This integrative multimodal and machine learning methodology presents a promising avenue for a more nuanced understanding of disorders of consciousness, contributing to enhanced diagnostic precision, prognostic capabilities and the personalization of rehabilitative strategies in clinical practice.
9 Apr 2026
Read appraisal →Archives of endocrinology and metabolism
Cushing's syndrome: a systematic review of psychiatric and cognitive symptoms in case studies
OBJECTIVE: Cushing's syndrome, characterized by chronic hypercortisolism, is associated with various health risks, including psychiatric symptoms and cognitive impairments. This systematic review of case studies aimed to map and categorize these symptoms. MATERIALS AND METHODS: We hypothesized that a broader range of psychiatric and cognitive manifestations would be observed beyond anxiety, depression, and memory impairment. The review followed PRISMA guidelines and was preregistered in PROSPERO (CRD42024433186). We conducted searches in PsycINFO, Embase, PubMed, and Scopus, identifying 273 potentially relevant studies. After screening, 66 studies were included, comprising 74 cases (81% female; mean age 35.7 years, range 13-81). RESULTS: revealed that 93% of cases presented psychiatric complaints, including depression (39.2%), psychosis/schizophrenic symptoms (35.1%), suicidal ideation/attempts (20.3%), anxiety (17.5%), panic attacks (2.7%), and post-traumatic stress disorder (1.4%). Cognitive complaints were reported in 32% of cases, primarily as general cognitive complaints (18.9%), memory impairment (9.5%), and attentional deficits (5.4%). An overlap of psychiatric and cognitive symptoms was observed in 26% of cases. CONCLUSION: This review underscores the clinical relevance of symptoms such as mania, psychosis, and suicidal behavior in Cushing's syndrome, which are often underreported. Individualized clinical assessment informed by these case studies is crucial for comprehensive management that extends beyond the typical focus on depression and memory. Moreover, greater awareness of the full spectrum of neuropsychiatric manifestations in hypercortisolism is needed.
8 Apr 2026
Read appraisal →Neuroscience
Effects of single/dual-target transcranial alternating current stimulation on working memory in healthy individuals
This study compared the effects of single- and dual-target high-definition transcranial alternating current stimulation(tACS) on working memory and explored the associated neural mechanisms using functional near-infrared spectroscopy(fNIRS). In a randomized, single-blind, sham-controlled design, 45 healthy participants received either dual-target stimulation, single-target stimulation, or sham stimulation, before and after which working memory performance was performed using n-back tasks with simultaneous fNIRS recording. Behavioral results showed that dual-target stimulation improved working memory performance, particularly under higher cognitive load, and yielded a greater proportion of responders when compared with sham stimulation, whereas single-target stimulation induced relatively limited effects. fNIRS findings indicated that dual-target stimulation modulated task-related cortical activation in prefrontal and temporal regions and enhanced both intra- and inter-hemispheric functional connectivity. Moreover, improvements in task accuracy were associated with strengthened functional connectivity within the frontoparietal and default mode networks. These findings suggest that dual-target tACS may be a promising strategy for enhancing working memory and highlight the importance of network-level modulation in cognitive enhancement.
6 Apr 2026
Read appraisal →