Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 14 appraisals
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Handwritten signatures in neurological and psychiatric disorders: a systematic review with clinical and forensic implications.
BACKGROUND: Signature production represents a complex motor and cognitive behavior, highly automatized and repeated countless times throughout life. It ranks among the most durable graphic forms, often preserved even when writing processes are impaired. Studies examining signature characteristics in clinical cohorts are limited. The available evidence raises questions about its potential as a behavioral marker of neurological and psychiatric disorders. METHODS: We conducted a PRISMA-compliant systematic review up to 4th December 2025 to summarize evidence on how neurological and psychiatric conditions may affect signature features. Eligible articles on this topic were searched in Scopus, Web of Science, and PubMed databases. Sixteen papers were included, and their results were systematically described and qualitatively analyzed. RESULTS: The available literature suggests that signature production appears relatively independent of global cognitive decline, although it is sensitive to specific pathological conditions (e.g., micrographia in Parkinson's disease, increased tortuosity in cerebral small vessel disease, and alterations observed in mania, delirium, obsessive-compulsive disorder, and major depressive disorder). Alterations commonly affect kinematic parameters, as well as visuospatial and constructional features. However, no disorder-specific signature pattern emerges from current evidence, largely due to the methodological heterogeneity across studies. CONCLUSIONS: The handwritten signature holds promise as a behavioral marker of brain disorders, serving as a potentially useful, complementary - rather than a stand-alone - indicator of neurological and psychiatric conditions, which could be potentially useful in clinical settings. The implications for forensic applications remain largely theoretical and have not yet been standardized.
30 July 2026
Read appraisal →Philosophical transactions of the Royal Society of London. Series B, Biological sciences
The hippocampus as a generative model
A generative model can be defined as a model of the latent causes of sensory input that can be used to generate new data samples. By examining empirical evidence and computational theory, we propose that the hippocampus can be characterized as a generative model. The hippocampus is a brain region important for memory. Recordings of neural activity from the hippocampus have led to the view that the hippocampus represents a cognitive map by abstracting a low-dimensional representation of the external world. We extend this view to suggest the hippocampus represents the latent, unobserved causes of sensory data by virtue of the position of the hippocampus within the deep cortical hierarchy. These representations of unobserved latent causes endow the hippocampus with capacity to generate new data samples that allow exploration of future hypotheticals and provide an internally generated training signal back to the generative model. We explore how perturbations to the hippocampal generative model may explain core symptoms of neuropsychiatric disorders such as those observed in psychosis. Together, this perspective provides a unified account of hippocampal function that explains how computations performed by the hippocampus support higher-order cognition and adaptive behaviour. This article is part of the theme issue 'The role of hippocampal predictions in cognition: bridging perception and memory'.
11 July 2026
Read appraisal →Brain imaging and behavior
Associations between olfactory dysfunction and structural MRI findings in Parkinson's disease: a systematic review
Olfactory dysfunction is a common and early non-motor symptom of Parkinson's disease (PD). Structural Magnetic Resonance Imaging (MRI) studies have reported changes in olfactory-related brain regions, but findings remain inconsistent. This review synthesizes MRI evidence to clarify neuroanatomical correlates of olfactory dysfunction in PD. We performed a systematic review to find the associations between olfactory dysfunction and structural MRI findings in people with PD. A systematic search in PubMed, Scopus, and Web of Science yielded 20 eligible studies. The eligible studies involved 1,092 patients with PD. Although there were inconsistent regions of interest and types of analysis, we identified structural changes in the olfactory sulcus and bulb, cortical gray matter, hippocampus, parahippocampus, and basal ganglia that are associated with olfactory dysfunction. Olfactory dysfunction in PD is linked to structural changes in primary olfactory, limbic, and cortical regions. These MRI findings may serve as early biomarkers, but standardized, longitudinal studies are needed to confirm their diagnostic or prognostic value.
10 July 2026
Read appraisal →Psychological medicine
Sorting the mind: cognitive enhancement through transcutaneous auricular vagus nerve stimulation: a systematic review and meta-analysis
Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive technique engaging vagal afferents that may enhance cognition, but results vary across domains and samples. Following PRISMA, seven databases (inception-October 2025) plus registries and gray literature were searched. Random-effects meta-analyses (REML; Hedges' g) were complemented by Bayesian hierarchical models and sensitivity analyses. Fifty-three studies were included; 30 contributed quantitative data (>1,500 participants). taVNS was associated with improved cognitive performance overall (g = 0.41, 95% CI: 0.30-0.53; I2 = 51.4%). Effects were moderate for executive functions (g = 0.46, 95% CI: 0.27-0.65; I2 = 9.5%) and cognitive flexibility/learning (g = 0.53, 95% CI: 0.32-0.75; I2 = 52.9%), and small for working memory/attention (g = 0.19, 95% CI: 0.04-0.33; I2 = 14.9%). Social cognition/emotion regulation showed larger but imprecise effects (k = 3; g = 0.80, 95% CI: 0.07-1.52; I2 = 82.1%). Clinical samples benefited similarly (k = 7; g = 0.55, 95% CI: 0.31-0.79; I2 = 29.5%), with no difference from healthy cohorts (β = -0.001, p = .994). High-intensity protocols (>1.0 mA) yielded larger effects; mode, duration, and site were not moderators. Bayesian models supported effects (P [μ > 0] ≥ 0.93). taVNS is associated with statistically significant improvements in cognitive performance, strongest for executive control and adaptive learning. We propose a Vagal Neurocognitive Integration Model linking LC-NE arousal modulation to prefrontal control. Future diagnosis-specific, adequately powered trials with multimodal neuroimaging should refine mechanisms and dose-response.
25 June 2026
Read appraisal →Current psychiatry reports
The Digital Mirror: Clinical Potentials and Relational Risks of Generative AI in Mental Health Interventions
PURPOSE OF REVIEW: This review explores the rapidly evolving integration of Generative Artificial Intelligence (GenAI) in mental health care. It aims to evaluate current applications in assessment, treatment planning, and psychotherapeutic interventions, while critically examining the clinical risks, ethical dilemmas, and the future potential of GenAI as an adjunctive tool rather than a replacement for human-delivered therapy. RECENT FINDINGS: Recent studies indicate that AI models can effectively assist in diagnostic reasoning, biomarker identification via EEG, and the prediction of symptom trajectories from session transcripts. Randomized controlled trials (RCTs) suggest that GenAI chatbots significantly reduce anxiety and depressive symptoms in the short term, particularly in settings with limited access to clinicians. However, human-led therapy remains superior in fostering deep emotional engagement and clinical impact. Significant risks identified include the potential for GenAI to foster dependency, reinforce maladaptive schemas or delusional ideation through "sycophantic" mirroring, and raise complex ethical-legal challenges regarding the reporting of criminal disclosures. AI represents a transformative adjunctive layer in mental health, offering scalable support for assessment, training, and between-session monitoring. While technological advances in personalization, multimodality, and immersive virtual reality enhance its clinical utility, GenAI lacks the authentic relational depth and"calibrated mismatches" essential for autonomy and transformative change. Future integration must prioritize a human-centered, blended approach, where GenAI is strictly supervised by clinicians within a robust ethical and regulatory framework to preserve the essential heart of the therapeutic connection. Research priorities, interim clinical safeguards, and recommendations for navigating the gap between current evidence and real-world adoption need to be defined and implemented.
19 June 2026
Read appraisal →Brain research bulletin
Neural substrates of apathy in Parkinson's disease: A systematic review of structural and functional neuroimaging studies
BACKGROUND: Apathy is a frequent and disabling non-motor symptom in Parkinson's disease (PD), characterized by diminished motivation, reduced goal-directed behavior, and emotional indifference. Growing evidence suggests that apathy in PD represents a distinct neuropsychiatric syndrome that may coexist with depression and global cognitive impairment, while also showing partially dissociable clinical and neural correlates. OBJECTIVE: This systematic review aimed to investigate the neural substrates of apathy in PD by synthesizing evidence from structural and functional neuroimaging studies. METHODS: Following PRISMA guidelines, we searched PubMed, Embase, Web of Science, and Scopus for studies assessing apathy in PD through neuroimaging techniques, including structural MRI, resting-state functional MRI, diffusion tensor imaging, PET/SPECT molecular imaging, and connectivity analyses. Apathy severity was evaluated using validated clinical scales, and findings were compared between PD population with and without apathy, as well as healthy controls. RESULTS: Across 16 heterogeneous studies, recurrent findings implicated structural, functional, and molecular alterations within fronto-striatal-limbic networks. However, differences in apathy measures and neuroimaging modalities limit direct comparability across studies and do not support a single unified imaging signature of apathy in PD. Apathetic PD subjects consistently exhibited reduced gray matter volume and altered spontaneous activity in the dorsolateral, inferior frontal gyri, anterior cingulate cortex (ACC), and nucleus accumbens, alongside disrupted functional and structural connectivity in fronto-limbic tracts. These alterations were significantly correlated with apathy severity and, in several studies, remained detectable after accounting for depressive symptoms or global cognitive status. Furthermore, the available findings suggest that apathy in PD may involve heterogeneous neurobiological mechanisms, including variable involvement of frontal, striatal, and limbic circuits; however, current evidence remains insufficient to support firm transmitter-based subtyping or treatment stratification. CONCLUSIONS: Current evidence suggests that apathy in PD involves partially dissociable neural correlates across prefrontal, striatal, and limbic systems. However, methodological heterogeneity across studies limits strong generalization, and future harmonized longitudinal studies are needed to clarify which findings are robust and clinically meaningful.
16 June 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 →Neurosurgical review
Deep brain stimulation for freezing of gait in Parkinson's disease: An updated systematic review, meta-analysis, and a single-center clinical experience.
Freezing of gait is a disabling and treatment-resistant manifestation of Parkinson's disease (PD). The effectiveness of deep brain stimulation (DBS) for freezing of gait remains inconsistent across stimulation targets, frequencies, and medication states. We conducted a systematic review and meta-analysis following PRISMA guidelines to examine how DBS affects freezing of gait in patients with PD. We searched Medline, Scopus, Web of Science, and Cochrane up to September 28, 2025. For synthesis, we combined mean differences and 95% confidence intervals for the Freezing of Gait Questionnaire (FOG-Q) and the Unified Parkinson's Disease Rating Scale (UPDRS) part III across different medication and stimulation settings to calculate the final effect size. Thirty-one studies with 905 patients were included. Of these, 21 provided FOG-Q data, and all reported UPDRS-III results. DBS led to a modest decrease in FOG-Q scores (mean difference [MD] = - 2.99; 95% CI = - 5.69 to - 0.29). The biggest improvement in FOG was seen when stimulation was used while patients were off medication (Med-OFF/Stim-OFF vs. Med-OFF/Stim-ON: MD - 5.88; 95% CI - 9.28 to - 2.47). Stimulation during the medication-ON state had smaller effects (Med-ON/Stim-OFF vs. Med-ON/Stim-ON: MD - 2.65; 95% CI - 4.99 to - 0.32), and there was no significant benefit when comparing Med-ON/Stim-OFF to Med-OFF/Stim-ON (MD - 0.70; 95% CI - 3.88 to 2.48). UPDRS-III scores improved substantially in the medication-OFF state with stimulation (MD - 14.35; 95% CI - 17.39 to - 11.32). High-frequency stimulation targeting the subthalamic nucleus provided more consistent benefits, yet substantial variation persisted across studies. The results of our small cohort showed significant improvement in FOG-Q and UPDRS-III (P values = 0.034, 0.022, respectively). DBS improves freezing of gait primarily in the medication-OFF state, with greater effects observed using high-frequency stimulation and subthalamic nucleus targets. Significant heterogeneity and limited data for alternative targets warrant cautious interpretation and further controlled studies.
13 May 2026
Read appraisal →AJNR. American journal of neuroradiology
Hippocampal Subfield Susceptibility Alterations in Mild Cognitive Impairment Revealed by 7T MRI
BACKGROUND AND PURPOSE: Hippocampal magnetic susceptibility alterations may serve as early neurodegenerative biomarkers of Alzheimer disease (AD), but subfield-level evidence in mild cognitive impairment (MCI) remains limited. This study uses submillimeter high-resolution quantitative susceptibility mapping (QSM) to investigate hippocampal subfield susceptibility changes in MCI. MATERIALS AND METHODS: Thirteen individuals with MCI and 13 cognitively normal controls (NC) underwent 7T MRI scans including MP2RAGE and multiecho gradient echo imaging (for QSM). The visibility of hippocampal strata radiatum, lacunosum, and moleculare (SRLM) was assessed using a visual rating scale. Hippocampal subfields (Cornu Ammonis 1 [CA1], CA2, CA3, dentate gyrus [DG], and subiculums) were segmented, and magnetic susceptibility values (χ) were extracted for each subfield. The susceptibility difference between the DG and other subfields was also calculated. Associations between subfield susceptibility measures and cognitive performance were then assessed. RESULTS: Qualitative analysis revealed a distinct hyperintense curved pattern in the hippocampus on the 7T QSM image, corresponding to the SRLM. In NC, this pattern was clearly visible exhibiting consistently delineated boundaries, while it appeared blurred or absent in most subjects with MCI. The visual rating results showed that NC had significantly higher scores than subjects with MCI (Hedgesg = 1.43, 95% confidence interval) [95% CI, 0.60-2.35; P = .003], with most NC rating 3-4 and most subjects with MCI rating 1-2. Quantitative analysis of hippocampal subfield susceptibility revealed significantly elevated susceptibility [χ] in the left DG in those with MCI compared with NC (Hedgeg = 0.88, 95% CI, 0.10-1.72; P = .03), leading to reduced susceptibility contrast between the SRLM and adjacent CA1-CA3 or DG. Furthermore, regional differences of susceptibility between key subfields (left CA1 versus DG and subiculum versus DG) were significantly reduced in MCI, reflecting a loss of subfield contrast. These quantitative changes were significantly associated with lower cognitive performance, even when controlling for age. CONCLUSIONS: 7T QSM reveals susceptibility changes in hippocampal substructures in individuals with MCI, providing a potential early biomarker for AD.
11 May 2026
Read appraisal →Behavioural brain research
Targeting the prefrontal-supplementary motor network with online and offline tDCS to modulate disgust: A single-blind and sham-controlled study
In certain individuals, disgust experience is abnormally high. This heightened sensitivity serves as a cognitive component that can lead to dysfunction in neural circuits related to emotion processing and psychological disorders such as contamination-based obsessive-compulsive disorder. In this single-blind study, 36 individuals with high disgust sensitivity were randomly assigned to three groups: online, offline, and sham. The online group received intensified and repetitive transcranial direct current stimulation (tDCS) while performing a disgust image watching task, whereas the offline and sham groups performed the task at two time points: immediately before (pre-test) and immediately after (post-test) the stimulation session. The offline group received active tDCS, whereas the sham group received placebo tDCS to control for the interval duration. Anodal and cathodal stimulation was applied to the left dorsolateral prefrontal cortex (l-DLPFC; F3) and pre-supplementary motor area (pre-SMA; FC2), respectively. The intervention consisted of 10 sessions of tDCS (2 sessions per day) over 5 days, with a stimulation intensity of 2 mA for 20 min and a 20-minute interval between sessions. The results showed a significant decrease in disgust experience in the online group compared to the offline group, while there was no significant difference between the online and sham groups. Although these findings suggest potential effects of tDCS combined with a task, further studies are necessary to confirm its efficacy.
1 May 2026
Read appraisal →Reviews in the neurosciences
Microstructural alterations of the amygdala in neurodegenerative and neuroinflammatory disorders: insights from diffusion tensor imaging
Diffusion tensor imaging (DTI) is a valuable method for evaluating microstructural changes in the amygdala associated with neurodegenerative and neuroinflammatory disorders. This systematic review examines amygdala microstructural alterations in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), and multiple sclerosis (MS) using DTI metrics. Following PRISMA 2020 guidelines, we searched PubMed, Scopus, and Web of Science databases through August 2025, identifying 4,442 records. After screening and eligibility assessment, 13 studies were included, comprising 1,412 patients and 1,146 healthy controls. Due to sample heterogeneity and lack of standardized effect size measures, meta-analysis was not performed. Across disorders, elevated mean diffusivity (MD) emerged as the most consistent finding, present in 100 % of AD patients and observed in all examined conditions. Reduced fractional anisotropy (FA) was the second most frequent alteration, with 36.6 % of AD patients showing decreased FA. In MS, increased radial diffusivity (RD) was prominent, while longitudinal DLB studies revealed progressive free water (FW) increases. These DTI-based microstructural changes often preceded volumetric atrophy and correlated with clinical severity. Our findings demonstrate that DTI metrics, particularly MD and FA, serve as sensitive markers of amygdala pathology across neurodegenerative diseases and may facilitate early diagnosis, disease monitoring, and differential diagnosis of these conditions.
26 Apr 2026
Read appraisal →PloS one
The journey to diagnosis and care of functional neurological disorder (FND).
PURPOSE: Functional neurological disorder (FND) is a common condition, associated with high disability and healthcare costs, and poor treatment access. This qualitative study aimed to explore participants' experiences of being diagnosed with functional neurological disorder (FND), accessing treatment, and navigating life after diagnosis. Participants were drawn from a randomised feasibility study of eye movement desensitisation and reprocessing therapy for people with FND (MODIFI, Trial Registration: NCT05455450 (www.clinicaltrials.gov)). METHODS: Reflexive thematic analysis was used to analyse the data from eighteen semi-structured interviews with participants diagnosed with FND. RESULTS: Six main themes were identified: (1) the process of seeking a diagnosis and initial relief from the physical struggles, (2) receiving a diagnosis of FND, (3) treatment for FND, (4) the burden of FND in day-to-day life, (5) the need to assert agency and return to normal, and (6) hopes for the future. CONCLUSION: The findings emphasize the need for personalised and compassionate care for individuals suffering from FND, underpinned by increased service provision within the healthcare system.
25 Apr 2026
Read appraisal →Medicine
Effect of parecoxib on postoperative anxiety and cognitive function after pancreaticoduodenectomy: A clinical trial
BACKGROUND: After pancreaticoduodenectomy, perioperative neurocognitive disorders (PND) are a common complication. Parecoxib, a selective cyclooxygenase-2 inhibitor, is used for its analgesic and antiinflammatory effects, but its impact on postoperative anxiety and cognitive function is not clear. METHODS: The patients undergoing laparoscopic pancreaticoduodenectomy at the Second Hospital of Hebei Medical University were enrolled in the study from November 1, 2020 to September 30, 2022 in this randomized controlled trial. Patients were randomly divided into Group P who received 20 mg of parecoxib intravenously 10 minutes before anesthesia and at the end of surgery and Group C who received an equal volume of normal saline at the same times. Primary outcomes included the effect of parecoxib on anxiety, cognitive impairment, and postoperative intestinal function recovery, with the incidence of PND calculated using the Z-value method. Secondary outcomes included pain control, length of hospital stay, postoperative recovery, complication rates, and analgesic use. RESULTS: 80 patients were enrolled and randomly divided into 2 groups of 40 equally: there were no significant differences in postoperative flatus passage, defecation time, hospital stay, or complication rates (P > .05). In terms of postoperative anxiety, the experimental group had significantly lower State Anxiety Inventory scores at 24 hours postoperatively (T2) (P < .05). Cognitive function, measured by Montreal Cognitive Assessment scores, did not show significant differences; however, cognitive decline was less pronounced in the experimental group. PND rates were 5% (2/40) in the experimental group versus 12.5% (5/40) in the control group, suggesting a possible clinical tendency toward reduced incidence, although the difference did not reach statistical significance. The rates of PND at 24 hours (T2) and 7 days (T3) postoperatively were 10% (4/40) and 5% (2/40) for the experimental group, compared to 15% (6/40) and 12.5% (5/40) for the control group using the Z-value method, Although the between-group differences did not reach statistical significance, a lower incidence was observed in the parecoxib group, suggesting a possible clinical tendency. CONCLUSION: Parecoxib, when used with pancreaticoduodenectomy, alleviates postoperative anxiety and neurocognitive disorders without affecting postoperative intestinal function recovery or increasing the incidence of postoperative complications.
19 Apr 2026
Read appraisal →Journal of neurology
Systematic review of movement disorders mislabeled as functional: when incongruence misleads
BACKGROUND: Misdiagnosis of functional movement disorders (FMD) remains a concern for clinicians. We sought to review the phenomenology and clinical features associated with FMD misdiagnosis. METHODS: We conducted a systematic review of case reports, case series, and observational studies of adults diagnosed with FMD and subsequently reclassified as having another neurological or medical condition. PubMed was searched from inception to September 13, 2025, focusing on reported features of inconsistency, incongruence with known diseases, and low-validity features. Isolated (iMD) and mixed (mMD) movement disorders were analyzed separately. RESULTS: Forty-two included studies comprised 150 patients, of which 73 cases underwent detailed analysis. Gait disturbance (35%) and dystonia (27.5%) were the most common iMD phenomenologies (n = 40), while jerks and rigidity (24%) were the most common mMD phenomenology (n = 33). Incongruence with known diseases (50.7%), psychological factors (34.2%), and symptom variability (31.5%) were the main factors associated with misdiagnosis. Application of incongruence alone was associated with the highest rate of FMD misdiagnosis, similar to that of applying neither incongruence nor inconsistency (49% in both cases). Conversely, reliance on inconsistency alone was least associated with an FMD misdiagnosis (13.7%). Misdiagnoses of iMD were more likely in the absence of documented inconsistency (OR 3.94, 95% CI 1.32-12.82). CONCLUSIONS: FMD misdiagnoses, particularly of gait disorders and dystonia, were most commonly associated with the application of incongruence as diagnostic criterion. The lowest rate of FMD misdiagnosis was associated with ascertaining at least two positive neurological signs of inconsistency.
9 Apr 2026
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