Journal of neural transmission (Vienna, Austria : 1996)最新文献

{"title":"Neurofilaments support the differentiation of amyotrophic lateral sclerosis from degenerative cervical myelopathy.","authors":"Julia Goebell, Franziska Bachhuber, Jutta Karmann, Veronika Klose, Jan Kassubek, Hans-Peter Müller, Hayrettin Tumani, Albert Ludolph","doi":"10.1007/s00702-026-03277-y","DOIUrl":"10.1007/s00702-026-03277-y","url":null,"abstract":"<p><p>The differential diagnosis between degenerative cervical myelopathy (DCM) and early amyotrophic lateral sclerosis (ALS) is often clinically challenging; laboratory tests that support this distinction could be highly valuable. This study examined the concentrations of neurofilament light chain (NfL) and the phosphorylated neurofilament heavy chain (pNfH), in CSF and serum of carefully selected patients with DCM, spinal canal stenosis (SCS) and ALS, after exclusion of major neurological confounders. Patients were assigned to five groups according to MRI findings and ALS diagnosis. All patients were treated in the Department of Neurology, and were only included if a CSF or serum sample was available for retrospective measurement of neurofilaments. Z-scores were used for age-adjusted interpretation of NfL concentrations in CSF and serum. In addition, the albumin quotient (QAlb), as a marker for the integrity of the blood-CSF barrier, was investigated in the five patient groups. The levels of NfL and pNfH, including Z-score distributions, differed significantly. The groups with diagnosed ALS had elevated neurofilaments both in CSF and Serum. Comparison of neurofilament concentrations between patients with isolated spinal canal stenosis and patients with cervical myelopathy revealed no significant difference. The QAlb showed no clear correlation with elevated neurofilaments and provided limited value for differential diagnosis. In summary, we showed that NfL and pNfH in CSF and serum support the differential diagnosis of cervical SCS with and without myelopathy from ALS in carefully selected cohorts. However, since neurofilaments are not specific, they should be used in context with clinical assessment and imaging for individual diagnostic and treatment decisions.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2809-2818"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The correlates of hyperechogenicity of the substantia nigra in subjects at risk of dementia with Lewy bodies.","authors":"Kateřina Zelníčková, David Ondráček, Marek Mikulec, Jiří Mekyska, Jan Farkaš, Martin Lamoš, Irena Rektorová","doi":"10.1007/s00702-026-03171-7","DOIUrl":"10.1007/s00702-026-03171-7","url":null,"abstract":"<p><p>Substantia nigra hyperechogenicity (SN+) detected by transcranial sonography (TCS) has been proposed as a risk marker for synucleinopathies, particularly Parkinson's disease. Its role in prodromal dementia with Lewy bodies (DLB) remains insufficiently explored. To examine clinical, cognitive, genetic, EEG, and plasma biomarker differences between SN+ and normal echogenicity (SN-) individuals in a well-characterized at-risk-of-DLB cohort, with additional sex-stratified analyses. A total of 121 participants aged 55-70 years from an at-risk-of-DLB cohort underwent TCS, neurological and neuropsychological assessment, nighttime wrist actigraphy, high-density EEG, genetic testing for APOE allelic variants, and plasma biomarker analysis (NfL, GFAP, pTau181). SN status was defined using laboratory-specific cut-offs. Group differences were assessed using non-parametric statistics with relevant corrections for multiple comparisons and adjustment for age. SN+ status as compared to SN- status was associated with poorer verbal memory performance and altered visuo-constructive performance (driven mostly by males), and significant differences in distinct actigraphy-derived sleep parameters. SN+ participants showed higher plasma NfL levels (particularly in males) and a higher prevalence of DLB-specific EEG patterns (driven by females). No significant associations were observed for global cognition, motor parkinsonism, cognitive fluctuations, hallucinations, REM sleep behavior disorder, depressive symptoms, olfactory function, plasma biomarkers of degeneration, neuroinflammation, β-amyloid deposition, or APOE status. In individuals at risk of DLB, SN hyperechogenicity is linked to early markers of neurodegeneration and cholinergic dysfunction, including elevated NfL and DLB-specific EEG abnormalities, as well as selective posterior cortical cognitive impairment and sleep disturbances. The observed sex-specific effects require further investigation.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2429-2442"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unrevealing the sequence of dysphagia progression in ALS: an event-based, FEES-driven staging approach.","authors":"Giammarco Milella, Maria Luisa Fiorella, Vittorio Velucci, Diletta Sciancalepore, Fedele Luisi, Angela Fraddosio, Eustachio D'Errico, Antonella Muroni, Giovanni Defazio","doi":"10.1007/s00702-025-03069-w","DOIUrl":"10.1007/s00702-025-03069-w","url":null,"abstract":"<p><p>Dysphagia drives morbidity and mortality in amyotrophic lateral sclerosis (ALS), yet staging systems treat it as a binary milestone and do not capture its trajectory. Reports diverge on the earliest abnormality, with some citing cohesive-bolus inefficiency and others thin-liquid impairment. Furthermore, how these findings relate to patient-perceived dysphagia remains unclear. In a prospective cohort, 78 incident ALS patients underwent one or more fiberoptic endoscopic evaluations of swallowing (FEES), yielding 108 assessments. Pharyngeal residue for four consistencies was rated with a validated scale. An event-based model (EBM) inferred the temporal order of abnormalities and defined a five-stage, FEES-based dysphagia staging system (DSS). Construct, convergent, discriminant, and prognostic validity were tested against established measures; responsiveness was assessed in patients with longitudinal FEES. The EBM identified a consistent sequence of swallowing impairment: solids, semisolids, liquids, saliva. Patient-perceived dysphagia occurred in 38% of DSS 1-2 evaluations versus 100% of DSS 3-4. The DSS showed construct validity by distinguishing bulbar- from spinal-onset ALS and convergent validity with the ALSFRS-R bulbar subscore and LMN bulbar score. Discriminant validity was supported by weak, non-significant associations with spinal/respiratory measures. Agreement with King's staging was moderate, and all King's stage IV patients mapped to DSS stages 3-4. The DSS was responsive to change (Stuart-Maxwell χ² = 11.034; p = 0.026). The EBM reconciles prior discrepancies: pathophysiology begins with solids, whereas symptom recognition typically coincides with liquid-phase residue. The FEES-based DSS is reproducible and clinically meaningful for tracking bulbar involvement and identifying higher-risk patients.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2317-2327"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment stability comparison among different ADD-ON therapies in fluctuating Parkinson's disease patients: the role of clinical and demographic factors.","authors":"Domiziana Rinaldi, Silvia Galli, Gabriele Imbalzano, Serena Budicin, Edoardo Bianchini, Lanfranco De Carolis, Claudia Ledda, Pierre Pacilio, Maurizio Zibetti, Marika Alborghetti, Francesco Ernesto Pontieri, Carlo Alberto Artusi, Leonardo Lopiano","doi":"10.1007/s00702-026-03164-6","DOIUrl":"10.1007/s00702-026-03164-6","url":null,"abstract":"<p><strong>Introduction: </strong>Motor fluctuations represent a major challenge in Parkinson's disease (PD) management. To address them, ADD-ON therapies with monoamine oxidase type B (MAO-B) and catechol-O-methyl transferase (COMT) inhibitors are used to enhance and prolong dopaminergic effects of levodopa, thereby improving motor fluctuations. Despite widespread use, real-life comparative data remain limited.</p><p><strong>Methods: </strong>We performed a retrospective, longitudinal study including PD patients referred to two Italian tertiary movement disorder centers. Patients with motor fluctuations requiring ADD-ON therapy (selegiline [SL], rasagiline [RS], safinamide [SF], or opicapone [OP]) and ≥ 12 months of follow-up were included. The primary outcome was treatment stability, defined as months without significant therapy modifications or ADD-ON discontinuation. Secondary outcomes included levodopa dosage changes, initiation of other antiparkinsonian therapies, and ADD-ON discontinuation rates. Cox regression models and Kaplan-Meier survival analyses evaluated the influence of ADD-ON type and clinical-demographic variables on treatment stability.</p><p><strong>Results: </strong>We analyzed 169 patients (SL = 20; RS = 26; SF = 78; OP = 45). Groups differed in age at ADD-ON initiation (p = 0.020; RS > OP), disease duration (p = 0.002; OP > RS and SF), and baseline levodopa equivalent daily dose (p = 0.003; SF and OP > RS). No significant differences in treatment stability were found between groups (p = 0.29). SF group showed higher levodopa increases (p = 0.02) and initiation of new therapies (p = 0.02). ADD-ON discontinuation occurred in 23.1% of patients, mainly due to AEs (16.6%). Cox regression showed no significant predictors of treatment stability.</p><p><strong>Conclusions: </strong>All ADD-ON therapies showed comparable treatment stability and tolerability. No statistically significant sex-related differences were observed, although a trend toward more frequent therapy modifications was found in female patients.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2387-2394"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodegenerative diseases and environmental risk factors: an overview of the available scientific evidence.","authors":"Giuseppe Stipa, Carlo Colosimo, Nicola Vanacore","doi":"10.1007/s00702-026-03202-3","DOIUrl":"10.1007/s00702-026-03202-3","url":null,"abstract":"<p><p>Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are among the most well-known and prevalent neurodegenerative disorders. These diseases result from an interaction between the environment and genetically predisposed individuals. This review examines the evidence available in the literature underlying this multifaceted interaction, focusing on various chemical substances such as metals, fertilizers, and herbicides, as well as toxic agents of microbiological origin, including cyanobacteria and their neurotoxins. In addition, the pathways through which toxic substances can enter the human body are discussed, such as air and water, which may lead to absorption through the lungs, the gastrointestinal tract, the skin, and mucosae. The routes by which neurotoxic substances gain access to the human body may help explain the increased risk of developing neurodegenerative diseases observed in sports played on soil and grass surfaces, such as soccer, American football, and golf.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2055-2067"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148348557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative efficacy and safety of botulinum neurotoxin type A in blepharospasm and hemifacial spasm: a systematic review and Bayesian network meta-analysis.","authors":"Zsófia Kühn, Rabán Scheibl, Peter Schnider","doi":"10.1007/s00702-026-03210-3","DOIUrl":"10.1007/s00702-026-03210-3","url":null,"abstract":"<p><p>While botulinum neurotoxin type A (BoNT-A) has demonstrated efficacy in the treatment of blepharospasm and hemifacial spasm, comparative efficacy and safety of different BoNT-A formulations remain uncertain. We conducted a systematic review and network meta-analysis with random-effects Bayesian models of randomized controlled trials comparing BoNT-A preparations with each other or with placebo. Separate networks were constructed for duration of clinical effect, analyzed as mean differences (MD), and ptosis, analyzed as odds ratios (ORs). The network included 13 randomized controlled trials with 870 participants contributing to duration outcomes and 964 participants to ptosis outcomes. All BoNT-A preparations demonstrated a significantly longer duration of clinical effect compared with placebo in a combined blepharospasm and hemifacial spasm population. No clinically meaningful differences in duration were observed between active preparations. AbobotulinumtoxinA (Abo/BoNT-A), onabotulinumtoxinA (Ona/BoNT-A), incobotulinumtoxinA (Inco/BoNT-A) and lanbotulinumtoxinA (Lan/BoNT-A) were associated with significantly higher odds of ptosis compared with placebo. Abo/BoNT-A, which was generally administered at higher dose ratios in the included studies, showed higher odds of ptosis than Ona/BoNT-A, although estimates were imprecise with wide credible intervals. In the dose-level network, higher-dose BoNT-A was associated with a greater risk of ptosis than lower-dose BoNT-A. The available evidence suggests that BoNT-A formulations have comparable efficacy in the combined blepharospasm and hemifacial spasm population. Differences in ptosis risk may reflect differences in dosing strategies rather than intrinsic differences between BoNT-A formulations. The review protocol was registered in PROSPERO (CRD420261299121).</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2577-2587"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148274519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of amantadine in the treatment of fatigue in multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials.","authors":"Ahmed Mostafa Amin, Muataz Kashbour, Ahmed Fawzy Alsokery, Ahmed Nady, Mohamed Wagdy, Ahmed ElSayed Awadallah, Ahmed Reda Aboyadak, Mostafa Meshref","doi":"10.1007/s00702-026-03213-0","DOIUrl":"10.1007/s00702-026-03213-0","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic inflammatory condition that leads to the gradual loss of myelin in the central nervous system. Approximately half of MS patients experience fatigue that hinders daily activities and impairs quality of life. We aimed to assess the efficacy and safety of amantadine in the treatment of fatigue in MS. In accordance with PRISMA guidelines, we conducted a comprehensive search across four electronic databases. We retrieved the relevant randomized controlled trials (RCTs) comparing the efficacy and safety of amantadine versus placebo for the treatment of fatigue in MS. Ten RCTS were included with a total of 1210 patients. Patients treated with amantadine had a significant improvement in fatigue compared to the placebo, according to the Fatigue Severity Scale (FSS) and self-reported treatment response (MD = - 0.53, p < 0.001), (RR = 1.73, p < 0.001), respectively. While there is no significant difference in the Modified Fatigue Impact Scale (MFIS) (P = 0.40) between the two groups. Amantadine also improved walking speed as measured by Timed 25-foot Walk (MD = 0.18, p = 0.03). Regarding safety, there were no significant differences between groups in the overall risk of treatment-emergent adverse events (TEAEs) (p = 0.07). However, amantadine was associated with a higher risk of discontinuation related to TEAE (p < 0.001), constipation (p = 0.04), hallucinations (p = 0.05), and mouth dryness (p < 0.001). Amantadine was associated with modest improvements in fatigue and mobility outcomes; however, the overall clinical benefit is offset by an increased risk of adverse events, notably any TEAE leading to study drug discontinuation, any drug-related TEAE, constipation, hallucinations, and mouth dryness.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2083-2101"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148431922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The BDNF-mediated association between NGAL and cognitive function in drug-naïve schizophrenia.","authors":"Zhenning Feng, Xue Li, Xiaoshan Zhai, Yuying Qiu, Xiaoxiao Sun, Qiao Su, Ying Xu, Fuyou Bi, Meijuan Li, Jie Li","doi":"10.1007/s00702-026-03275-0","DOIUrl":"10.1007/s00702-026-03275-0","url":null,"abstract":"<p><p>Previous studies have observed a correlation between plasma gelatinase-associated lipocalin (NGAL) levels and cognitive function in drug-naïve patients with schizophrenia (DNS), but the mechanism is unclear. Basic research suggests that the neuroprotective effect of NGAL may be related to the regulation of growth factors. So, we hypothesized that growth factors such as brain-derived neurotrophic factor (BDNF) mediated the effect between NGAL and cognitive function in DNS. This study recruited 137 DNS patients and divided the patients into severe cognitive impairment group (SCI-DNS, n = 58) and non-SCI group (non-SCI-DNS, n = 79) according to the MATRICS Consensus Cognitive Battery (MCCB), with SCI defined as MCCB composite T-score < 25. Sociodemographic characteristics, cognitive function, psychotic symptoms and peripheral blood samples were collected from all participants. Plasma levels of NGAL, BDNF, epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) were measured using enzyme-linked immunosorbent assay (ELISA). (1) SCI was observed in 42.3% of DNS. (2) Plasma levels of NGAL, BDNF, and EGF were significantly lower in the SCI-DNS group compared with the non-SCI-DNS group. (3) Plasma NGAL exhibited significant positive correlations with all three growth factors (BDNF, EGF, VEGF). (4) Plasma NGAL, BDNF, and EGF levels were positively associated with cognitive function. (5) Plasma BDNF demonstrated a significant mediating effect in the relationship between plasma NGAL and cognitive function. In patients with DNS, those with SCI exhibited lower plasma levels of NGAL, BDNF and EGF. Notably, a significant BDNF-mediated pathway was identified in the association between NGAL and cognitive function.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2787-2798"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149077185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the relationship between interoception and mental body representation in Parkinson's disease.","authors":"Alfonsina D'Iorio, Chiara Alves, Francesca Pisano, Giovanni Luca Di Benedetto, Mariachiara Gaita, Carmine Vitale, Marianna Amboni, Simona Raimo, Liana Palermo, Gabriella Santangelo","doi":"10.1007/s00702-026-03194-0","DOIUrl":"10.1007/s00702-026-03194-0","url":null,"abstract":"<p><p>Interoception refers to the process through which the nervous system detects, interprets, and integrates internal bodily signals, forming a dynamic representation of the body's internal state at both conscious and unconscious levels. It is commonly conceptualized along three dimensions: interoceptive accuracy, interoceptive awareness and interoceptive sensitivity. Mental body representation (MBR) is a multifaceted cognitive construct encompassing structural, spatial, lexical, and semantic components of the body. A widely accepted taxonomy distinguishes between two types of MBR: action-oriented representations and non-action-oriented representations. To date, only a few studies have examined interoception and MBR in Parkinson's disease (PD), often yielding inconsistent findings, and no study has directly investigated the relationship between these two domains in this clinical population. This study therefore aims to (1) further characterize interoceptive and MBR profiles in PD and (2) explore their potential association. Twenty-seven patients with PD and twenty-four healthy controls completed a neuropsychological battery assessing global cognitive functioning, interoceptive abilities, MBR, and depressive and apathetic symptoms. Mann-Whitney analyses revealed significantly poorer MBR performance in patients compared with healthy controls. Spearman correlations showed significant associations between action-oriented MBR and global cognitive functioning as measured by the Parkinson's Disease Cognitive Rating Scale (PD-CRS). Regression analyses further demonstrated that PD-CRS performance significantly predicted action-oriented MBR abilities. These findings indicate a characteristic difficulty among individuals with PD in mentally representing body features. Moreover, results suggest that both cortical and subcortical cognitive functions contribute to supporting action-oriented MBR.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2547-2556"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148177498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive reappraisal training as an intervention in patients with functional movement disorders: a placebo-controlled EEG pilot study.","authors":"Melanie Suette, Petra Schwingenschuh, Daniela Kern, Birgit Ludwig, Lukas Gattermeyer-Kell, Mariella Kögl, Maria Zangl, Corinna M Perchtold-Stefan","doi":"10.1007/s00702-025-03028-5","DOIUrl":"10.1007/s00702-025-03028-5","url":null,"abstract":"<p><p>Functional movement disorders (FMD) are common and disabling neurological conditions characterized by impaired voluntary motor control in the absence of structural disease. Accumulating evidence suggests that emotion regulation deficits contribute to the pathophysiology of FMD. This randomized, placebo-controlled pilot study investigated the clinical and neural effects of a digital cognitive reappraisal training program in patients with FMD, targeting emotion regulation as a potential therapeutic mechanism. Twenty adult patients diagnosed with clinically definite FMD (mean age = 50.7 years, 11 females) were randomly assigned in a 1:1 ratio to either an intervention group practicing cognitive reappraisal (n = 11) or an active control group completing reflection exercises (n = 9). Both groups underwent 14 brief, app-based training sessions over four weeks. Clinical outcomes were assessed before and after the intervention using standardized measures of mood, motor function, and overall illness severity. Simultaneously, brain activity at rest and during a standardized reappraisal task was recorded via electroencephalography, focusing on prefrontal alpha asymmetry as a neural marker of reappraisal engagement. Compared to the control group, the intervention group showed significantly greater improvements in mood (Mdiff = 0.542, p = .010), motor function (Mdiff = 0.542, p = .033), and overall illness severity (Mdiff = 0.528, p = .040). Both groups improved over time in mood (p = .030), tremor severity (p = .014), and subjectively rated motor function (p = .022), suggesting non-specific benefits of structured emotional self-reflection. Crucially, electroencephalography data revealed a significant post-training increase in right-lateralized frontopolar resting-state activity in the intervention group (Mdiff = 13.29, p = .026), aligning with prior evidence linking right prefrontal activity to successful reappraisal. Although task-related EEG activity did not differ significantly between groups, a statistical trend (p = .115, d = 1.14) suggests increased right frontal activity during reappraisal generation in the intervention group. Reappraisal training performance correlated with EEG changes and with the frequent use of the distancing strategy \"relativizing,\" implicating right prefrontal involvement in specific cognitive control processes. These findings provide preliminary evidence that cognitive reappraisal training delivered via mobile app is feasible and may enhance both clinical outcomes and prefrontal brain function in FMD. Future studies with larger samples are needed to confirm these effects and better understand the neural mechanisms of digital interventions for emotion regulation in functional neurological disorders.</p>","PeriodicalId":520679,"journal":{"name":"Journal of neural transmission (Vienna, Austria : 1996)","volume":" ","pages":"2853-2865"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146042404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}