Cognition and metacognition in functional motor symptoms and functional seizures: A case-control study

Cognition and metacognition in functional motor symptoms and functional seizures: A case-control study | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Cognition and metacognition in functional motor symptoms and functional seizures: A case-control study View ORCID Profile Susannah Pick , L.S. Merritt Millman , Esin Gun Gursoy , Yasmine Basamh , Jemima Uloyok-Job , Jessica Davies , Lauren Blunstone , Snigdha Bhuma , Jan Coebergh , Anthony S. David , Mark J. Edwards , Laura H. Goldstein , John Hodsoll , Mitul A. Mehta , Timothy R. Nicholson , Biba Stanton , Joel S. Winston , Matthew Hotopf , Trudie Chalder doi: https://doi.org/10.1101/2025.09.25.25336646 Susannah Pick 1 Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London , London, United Kingdom ( UK ) PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Susannah Pick For correspondence: susannah.pick{at}kcl.ac.uk L.S. Merritt Millman 1 Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London , London, United Kingdom ( UK ) PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Esin Gun Gursoy 1 Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London , London, United Kingdom ( UK ) BSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site Yasmine Basamh 1 Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London , London, United Kingdom ( UK ) MSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jemima Uloyok-Job 1 Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London , London, United Kingdom ( UK ) Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jessica Davies 1 Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London , London, United Kingdom ( UK ) BSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site Lauren Blunstone 1 Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London , London, United Kingdom ( UK ) BSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site Snigdha Bhuma 2 South London and Maudsley NHS Foundation Trust , London, UK MBBS Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jan Coebergh 3 Department of Neurology, St George’s University Hospitals NHS Foundation Trust , London, UK MBBS Find this author on Google Scholar Find this author on PubMed Search for this author on this site Anthony S. David 4 Institute of Mental Health, Division of Psychiatry, University College London , London, UK MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Mark J. Edwards 2 South London and Maudsley NHS Foundation Trust , London, UK 5 Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience , King’s College London, London, UK 6 King’s College Hospitals NHS Foundation Trust , London, UK PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Laura H. Goldstein 7 Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London , London, UK PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site John Hodsoll 8 Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology & Neuroscience , King’s College London, London, UK PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Mitul A. Mehta 9 Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King’s College London , London, United Kingdom PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Timothy R. Nicholson 2 South London and Maudsley NHS Foundation Trust , London, UK 10 Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London , London, UK PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Biba Stanton 1 Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London , London, United Kingdom ( UK ) 2 South London and Maudsley NHS Foundation Trust , London, UK 5 Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience , King’s College London, London, UK PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Joel S. Winston 5 Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience , King’s College London, London, UK 6 King’s College Hospitals NHS Foundation Trust , London, UK PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Matthew Hotopf 1 Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London , London, United Kingdom ( UK ) 2 South London and Maudsley NHS Foundation Trust , London, UK PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Trudie Chalder 1 Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London , London, United Kingdom ( UK ) 2 South London and Maudsley NHS Foundation Trust , London, UK PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abstract Full Text Info/History Metrics Data/Code Preview PDF Summary Background Cognitive symptoms are common in functional neurological disorder (FND), yet there is inconsistent evidence of impaired neurocognitive test performance in this population. We aimed to assess core cognitive functions and global metacognition in patients with functional seizures (FS) and functional motor symptoms (FMS), and to explore relationships between cognition, metacognition, and cognitive symptoms in these groups. Methods This single-centre case-control study recruited participants with FS (n=50) and FMS (n=50), in addition to age- and gender-matched healthy controls (HC, n=50), and clinical controls with depression and/or anxiety disorders (CC, n=50). The Cambridge Neuropsychological Test Automated Battery was used to assess response speed, working memory, executive functions, and social-emotional processing, with subjective confidence rated for each test. Validated measures quantified intellectual functioning, performance validity, and global cognitive symptoms. Findings Impaired performance was demonstrated in both FND groups for sustained attention (p=0.03-<0.001) and set-shifting (p=0.01-0.001), withstanding correction for response speed, education, intellectual functioning, and psychotropic medication. Performance validity was comparable between groups. The FND groups reported reduced confidence for sustained attention performance (p<0.001) and elevated cognitive symptoms (p<0.001). Executive performance deficits correlated with reduced test-specific confidence in FS/FMS (p=0.02-<0.001). In FMS, confidence for sustained attention correlated negatively with cognitive symptoms (p=0.002). Cognitive symptoms were associated with psychological/physical symptom load, quality-of-life, and/or general functioning in FND and CC groups (p=0.04-<0.001). Interpretation Patients with FS and FMS displayed deficits in executive functioning performance, with intact metacognitive awareness, alongside significant cognitive complaints. These neurocognitive features were associated with poorer clinical status, warranting interventions targeting cognitive control and/or cognitive symptoms in everyday life. Funding This study was funded by a Medical Research Council Career Development Award granted to SP [MR/V032771/1]. This project also represents independent research part-funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. Introduction Cognitive symptoms, such as forgetfulness, distractibility, and disrupted goal-driven behaviours, are common in patients with functional neurological disorder (FND). 1 – 3 As primary symptoms in functional cognitive disorder (FCD), 3 or occurring alongside other FND presentations, 2 , 3 cognitive complaints have been associated with greater psychological symptom load and compromised quality of life. 2 , 4 – 6 Despite this, empirical evidence of cognitive deficits remains inconclusive. Intact, impaired, or superior neurocognitive test performance has been reported in FND samples compared to neurological, psychiatric, and/or healthy controls, across several relevant domains (e.g., attentional control, executive function, social-emotional processing). 2 , 3 , 5 , 7 , 8 Beyond core cognitive functions, emerging findings indicate potential differences in metacognition in FND. 3 , 9 Metacognition refers to awareness and control of one’s own cognitive processes, and adaptive use of this knowledge in goal-driven behaviours. 10 Metacognitive deficits are associated transdiagnostically with mental health symptoms and maladaptive behaviour, and may be important treatment targets across neuropsychiatric disorders. 11 ‘Global metacognition’ involves broad self-evaluations of cognitive performance in a given task/domain, whereas ‘local metacognition’ relates to momentary assessments of specific decisions or actions within a task/activity. 9 , 11 In FND, altered global metacognition has been indicated by reduced concordance between neurocognitive test performance and post-diction self-evaluations, 2 , 3 , 5 , 9 and by the presence of elevated subjective cognitive symptoms in the absence of observable performance deficits. 2 , 3 , 7 , 9 However, few high-quality experimental studies have examined local metacognition in FND, with inconsistent results. 9 These disparate findings may be due to methodological issues, such as suboptimal consideration of confounding variables (e.g., education, medication, performance validity), the wide range and variable quality of measures employed, and differing comparison groups. 2 , 5 , 8 , 9 Few studies have compared cognitive and metacognitive performance profiles in specific FND subgroups using the same measures, which could highlight shared and distinct cognitive/metacognitive features, with clinical and mechanistic relevance. Within a larger project examining aetiological factors and mechanisms in functional seizures (FS) and functional motor symptoms (FMS), 12 this study aimed to directly compare cognitive performance profiles and global metacognition in patients with a primary diagnosis of FS or FMS (not FCD). We sought to compare these groups to healthy controls without physical or mental health disorders (HC), and clinical controls (CC) with major depression and/or anxiety disorders. The objectives were to examine overall between-group differences (FS/FMS/CC/HC) and FND subgroup-specific (FS/FMS) outcome profiles in 1) executive functioning, working memory, and social-emotional processing performance, 2) test-specific post-diction confidence evaluations, and 3) global cognitive complaints. We also sought to explore within-group relationships between cognitive/metacognitive outcomes and clinical characteristics (FS/FMS/CC). Compared to HC and CC, we predicted that the FS and/or FMS groups would display: Elevated global cognitive symptoms on a validated scale 2 . Altered performance on tests of: executive functioning (i.e., diminished sustained attention, set-shifting, response inhibition), 5 , 7 , 8 working memory (poorer performance), 5 , 7 , 8 social-emotional processing (enhanced emotional bias/reduced emotion recognition), 13 Reduced (global) metacognitive confidence regarding their test performance. 9 Methods Study design and participants This single-centre, case-control study was based at King’s College London (KCL), conducted within a larger research programme. 12 Ethical approval was granted by the North-West Greater Manchester South National Health Service (NHS) Research Ethics Committee, United Kingdom (UK, Reference: IRAS 322652). Recruitment and data collection proceeded from 11/2023 to 04/2025. Participants with FMS (n=50) or FS (n=50) were recruited from neuropsychiatry/neurology services at King’s College Hospital, South London and Maudsley, and St George’s University Hospital NHS Foundation Trusts (London, UK). Most of the FS (82%) and FMS (96%) groups self-referred to the study following adverts shared by clinicians and/or through FND Hope UK. When self-referring to the study, participants in the FND groups were asked to provide documentary evidence of an FND diagnosis from a specialist clinician. Healthy (n=50) and clinical (n=50) controls were recruited using advertisements on community webpages and participant registers. Control participants were selected to frequency-match groups for age and gender (1:1 cases/controls). An a-priori power calculation indicated that a between-group (FS/FMS/CC/HC) ANOVA/ANCOVA, used to test the primary hypotheses, would require a sample of 180 to achieve 80% power for detection of a small effect (f=0.1, p<0.05). Inclusion criteria required that participants were aged 18-65 years, fluent in English, and had normal/corrected eyesight. FND samples were required to have a confirmed DSM-5 1 diagnosis with FS or FMS as their most prominent symptom. Clinical controls met criteria for a diagnosis of major depression and/or an anxiety disorder, confirmed with a structured clinical interview (‘Materials and Measures’). We excluded candidates with active severe psychiatric disorder (i.e., severe alcohol/substance use disorder, psychosis) and neurological disease (e.g., neurodegenerative disorder, epilepsy). Other exclusion criteria were being unable to perform tasks due to significant physical/cognitive impairment, current participation in an interventional trial, lifetime diagnosis of FND (HC/CC), or the presence of concurrent FS and FMS within the previous 12 months (FND). Individuals with a primary diagnosis of FCD were ineligible. Materials and measures Clinical measures (interview, self-report questionnaires) A medical history interview was conducted at baseline (SP/LSMM/SB), including modules from the Quick Structured Clinical Interview for DSM-5 Disorders 14 (Psychosis, Alcohol/Substance Use Disorder, Affective Disorders, Anxiety Disorders). Clinical self-report questionnaires ( Supplementary Table 1 ) included validated measures of depression, generalised anxiety, psychological/somatoform dissociation, physical symptoms, health-related quality-of-life, and general functioning. 12 A study-specific scale was developed to quantify FND symptom severity/impact ( Supplementary Table 2 ). The Cognitive Failures Questionnaire ( CFQ ) 15 assessed subjective cognitive symptoms over the preceding six months, such as everyday memory and attention lapses, and disrupted action sequences. Higher scores signify poorer subjective cognitive functioning. Satisfactory psychometric properties have been demonstrated for this measure. 15 – 17 Medical Symptom Validity Test (MSVT) 18 The MSVT is a computerised test designed to examine neuropsychological test performance validity, with sound psychometric properties. 19 , 20 Performance validity indicators are Immediate and Delayed Recall scores, and immediate-delayed Consistency scores (test failure indicated by scores ≤85%). This test was included to assess task engagement/negative response biases across groups. 21 Wechsler Abbreviated Scale of Intelligence – 2nd edition (WASI-II) 22 The WASI-II two-subtest version was administered to test non-verbal and verbal intellectual abilities ( Matrix Reasoning/Vocabulary ) and to provide an estimated Full-Scale Intellectual Quotient Score (WASI-II FSIQ-2). This version has strong inter-rater reliability (.95-.99), internal consistency (0.94), and test-retest stability (.94). 22 Cambridge Neuropsychological Test Automated Battery (CANTAB) Connect 23 The CANTAB Connect platform is a modified version of the original battery, administered using a touchscreen device. Selected subtests probed motor/cognitive response times, attention, executive functioning, social-emotional cognition, and memory ( Table 1 , Supplementary Table 3 ). The original battery has strong psychometric properties in clinical and non-clinical samples, 23 , 24 although psychometric validation data for the Connect version is not currently available. View this table: View inline View popup Download powerpoint Table 1. CANTAB Connect subtests Metacognitive confidence ratings Post-diction confidence ratings were obtained immediately after every test (1=Very poor performance; 2=Poor performance; 3=Below average; 4=Average; 5=Above average; 6=Superior; 7=Very superior). Such global metacognitive assessments have been used widely in other clinical disorders. 11 Procedure The recruitment and screening process are detailed in the study protocol 12 . After obtaining written consent, the medical history interview was conducted remotely. Eligible participants were sent a link to the online questionnaires, to be completed within 48 hours of the research visit. The cognitive battery was administered in a quiet testing room, between 10am-12pm for most participants. The session commenced with the WASI-II , followed by the CANTAB battery (fixed order, Table 1 ), then the MSVT . Participants were provided with standardised instructions for each test. Abstinence from caffeine/nicotine for >2 hours before the visit was requested of all participants. Those on psychotropic medications that might alter cognition were asked to abstain for 12-24 hours, provided abstinence was unlikely to cause adverse consequences (self-report/judgement of principal investigator/research group). Participants received a £50 shopping voucher on completion of the session. Data processing and statistical analyses Data analyses were conducted in SPSS (v29, IBM, 2022) by SP and EGG independently, following a pre-registered analysis plan ( https://osf.io/grh89/ ). Assumptions were checked for each test, and if violated, suitable corrections implemented (‘Results’). We defined outliers as scores of 2.5 standard deviations (+/-) from the group mean for each variable. Analyses were rerun with outliers winsorised in sensitivity analyses. Some participants failed to complete tests due to technicalities, symptoms, or declining (‘Results’). There were no within-test missing data points because each test required all trials/elements to be completed to yield a valid score. Categorical variables were examined with Fisher’s exact/chi-squared tests. One-way Analysis of Variance (ANOVA) was used for between-group comparisons with most continuous variables. Mixed-model ANOVA was used for the CANTAB Emotion Recognition Test , with group as the between-groups factor (FMS/FS/CC/HC) and emotion (happiness, disgust, anger, fear, sadness, surprise) as the within-subjects factor. Significant main effects/interactions were examined with Bonferroni or Games-Howell post-hoc tests for ANOVA/Welch’s ANOVA. Cramer’s V, eta-squared, partial eta-squared, and omega-squared were calculated as effect sizes, as appropriate. Analysis of Covariance (ANCOVA) was applied in sensitivity analyses to examine the influence of potentially relevant confounding variables, such as performance validity, education, intellectual functioning, and psychotropic medication. Results that did not withstand sensitivity analyses were considered uninterpretable and not considered further. Exploratory Spearman’s correlations were run between variables that differed significantly between groups. Benjamini-Hochberg corrections were applied within each set of tests to control the false discovery rate (5%). Results remaining significant after correction are reported. Role of the funding source The funders of this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Results Sociodemographic and clinical characteristics of the 200 participants are presented in Table 2 ( Supplementary Tables 4 - 5 ), including common psychotropic medications and comorbid diagnoses. The groups were comparable in age, gender, and handedness. Significant overall group differences were found for self-reported education, psychotropic medication, comorbid physical/mental health diagnoses, anxiety, depression, somatoform and psychological dissociation, physical symptoms, health-related quality-of-life, and work/social functioning. These results largely reflected expected differences between HC and FS/FMS/CC groups ( https://osf.io/preprints/psyarxiv/8vtpe_v1 ). The CC and FND groups were similar in rates of physical health comorbidities (p=0.25), and anxiety/depression severity (p=0.50-0.55), but they differed significantly in education (p=0.01) and psychotropic medication use (p<0.001). View this table: View inline View popup Table 2. Sample characteristics, cognitive symptoms, performance validity, and intellectual functioning Figure 1 illustrates absolute effect sizes for the significant between-group differences in cognitive and metacognitive outcomes. Download figure Open in new tab Figure 1. Cohen’s d (effect size) for cognitive symptoms (CFQ), Motor/Reaction Time (MST/RTT), Sustained Attention (RVIP) and Set-Shifting (IEDSS) tasks Cognitive symptoms ( CFQ-Total ) were elevated in the FND and CC groups compared to HC, with scores also higher in the FND groups relative to CC ( Table 2 , Supplementary Table 6 - 7 , p=0.002-<0.001). The MSVT performance validity Pass rate was comparable between groups ( Table 2 ). On the WASI-II ( Table 2 , Supplementary Tables 8 - 9 ), mean FSIQ-2 scores were in the average range for all groups. The FS group had lower scores than CC for FSIQ-2 (p=0.005) and Vocabulary (p=0.006), whereas both FND groups displayed reduced performance on Matrix Reasoning compared to HC/CC (p=0.005-<0.001). Statistical values for CANTAB outcomes that varied consistently between groups are shown in Table 3 ( Figures 1 and 2 ). Download figure Open in new tab Figure 2. Radar plots - Motor Screening, Reaction Time, Rapid Visual Information Processing and Intra-Extra Dimensional Set-Shift subscale z-scores by group View this table: View inline View popup Table 3. CANTAB results – Motor/reaction time, sustained attention, and set-shifting Motor Screening Test (MST) Mean Motor Latency was extended in FMS compared to both HC and CC, and in FS relative to CCs (p=0.02-<0.001, Supplementary Tables 10 - 11 ). Reaction Time Test (RTT ) Mean Reaction Time and Mean Movement Time were elevated in both FND groups compared to HC/CC (p=0.01-<0.001). As extended response speed in the FND groups could unduly impair performance, MST and RTT variables were entered as covariates in sensitivity analyses for all other CANTAB outcomes. Sustained attention performance differed significantly between groups on RVIP Ability, Total Misses, Probability of Hit , and Median Response Latency ( Supplementary Tables 12 - 13 ), although the group effect on RVIP Median Response Latency did not endure sensitivity analyses ( MSVT fails, RTT Mean Reaction Time) . Both FND groups displayed inferior performance to HC and CCs on the other RVIP outcomes (p=0.03-<0.001). Set-shifting task performance deviated significantly between-groups on IEDSS Total Errors, Adjusted Errors, Pre-Extra-Dimensional Shift Errors, Total Trials Completed , and Response Latency ( Supplementary Tables 14 - 15 ). The FS and FMS groups had more Total Errors , Total Trials Completed and extended Response Latency, compared to CCs (p-values 0.01-0.001). The group effects on Adjusted Error and Pre-Extra-Dimensional Shift Errors dissipated in sensitivity analyses ( MSVT fails/education/ MST/RTT ). None of the significant group main effects and/or interactions on Spatial Span, Stop Signal, Emotion Bias, or Emotion Recognition tests remained stable in sensitivity analyses ( MSVT/ education/ FSIQ-2 /psychotropic medication/ MST/RTT , Supplementary Tables 16 - 22 ). Both FND groups expressed significantly lower post-diction confidence for sustained attention ( RVIP ) performance than HCs, and the FMS group also reported reduced confidence on this task compared to CCs (p-values<0.001; Supplementary Tables 23 - 25 ). The groups did not differ in confidence ratings for any other test. Within-groups (FS/FMS/CC) correlations ( Supplementary Table 26 ) showed that impaired performance on the sustained attention ( RVIP ) and set-shifting ( IEDSS ) tests did not correlate significantly with global cognitive symptoms ( CFQ Total) in any group. However, performance on these tests did correlate with test-specific confidence in the FMS and/or FS samples (p=0.01-<0.001). In the FMS group, significant associations were found between performance outcomes on sustained attention ( RVIP ) and set-shifting tasks ( IEDSS, p=0.048-0.002). Cognitive symptoms ( CFQ-Total ) correlated positively with clinical features in the FND/CC samples, including anxiety (r s =0.34-0.38, p=0.02-0.008), depression (r s =0.45-0.48, p=0.001-<0.001), and psychological/somatoform dissociation (r s =0.29-0.63, p=0.04-<0.001). CFQ-Total scores were also related to physical symptoms in the FS/CC groups (r s =0.39-0.45, p=0.006-0.001), and to greater FNS severity (r s =0.34, p=0.03) and impact (r s =0.30, p=0.02) in the FMS group. CFQ-Total scores were also associated with work/social functioning in the FMS/CC groups (r s =0.39-0.50, p=0.005-<0.001), and quality-of-life in FND/CC (r s =-0.33-0.57, p=0.03-<0.001). In FMS, confidence ratings for sustained attention ( RVIP ) correlated with clinical variables, including cognitive symptoms ( CFQ-Total , r s =-0.43, p=0.002), psychological dissociation (r s =-0.36-0.59, p=0.04-<0.001), depression (r s =-0.39, p=0.005), anxiety (r s =-0.37, p=0.007), and role limitations due to physical factors (r s =-0.54, p<0.001). Discussion We examined cognitive and metacognitive functioning in patients with FMS or FS, compared to healthy and clinical controls (HC/CC). As predicted, the FND groups reported greater cognitive symptom burden, combined with localised performance impairments on tests of sustained attention and set-shifting. In contrast to our hypotheses, there were no consistent group differences in response inhibition, working memory, or social-emotional processing. In the FMS and/or FS groups, impaired performance in sustained attention and/or set-shifting was associated with reduced confidence ratings in those domains, suggesting broadly intact metacognitive accuracy. Elevated cognitive complaints in our FS and FMS samples replicated several studies, 2 , 3 , 25 , 26 showing that cognitive symptoms are a significant challenge for individuals with FND, beyond those with a primary diagnosis of FCD. As found in other populations, cognitive symptoms were related to a range of clinical features in our FS/FMS samples, but they did not correlate with performance deficits. 2 , 4 , 5 , 27 , 28 Clinical correlates of cognitive symptoms included depression, anxiety, dissociation, physical symptoms, quality-of-life, and work/social functioning, with some of these associations more prominent in our FMS sample. However, these cognitive difficulties were heightened in our FS/FMS samples compared to CCs, who were comparable in anxiety and depression severity. Together, these findings underscore the prominence and potential impact of cognitive complaints in FND and provide preliminary evidence that these symptoms may be particularly relevant in patients with FMS. Our results indicate that cognitive symptoms in FND may not be due solely to the presence of elevated anxiety and/or depression. Future research should evaluate the extent to which cognitive symptoms in FND are related to observable deficits in real-world settings, in addition to ascertaining the direction of influence between cognitive symptoms and other clinical outcomes. Importantly, patients with FMS and FS may require targeted interventions to facilitate management of cognitive symptoms and their impact in everyday life. 29 Lower intellectual functioning and extended response speed were observed in both FND groups, corresponding with some previous studies, 5 , 8 although intellectual functioning was qualitatively matched between groups, with mean scores in the average range. A minority of participants failed the performance validity test ( MSVT ), although the proportion was not significantly different between groups, consistent with other studies. 21 Nonetheless, some of our primary results failed to survive sensitivity analyses including one or more of these variables, reinforcing the importance of assessing their influence in neuropsychological studies in future. The lack of robust group differences on response inhibition, working memory, and social-emotional processing tests countered our predictions, adding to the inconsistent findings in these domains. 5 , 8 , 13 More thorough assessment of constituent processes with multiple tests may be necessary to uncover disorder-specific deficits in these functions. Performance deficits on sustained attention ( RVIP ) and set-shifting ( IEDSS ) tasks exhibited by our FS and FMS samples withstood sensitivity analyses, therefore representing compelling evidence for specific executive function difficulties. The findings relating to sustained attention align with prior accounts of attentional control impairments in FND samples. 5 , 7 , 8 , 26 Our observation of weaker performance on the set-shifting task ( IEDSS ) in the FND groups differed to two previous studies that used the same task, 2 , 30 although the pattern of deficits suggested overall rule-learning difficulties during the task, rather than set-shifting performance specifically. Effect sizes were large for sustained attention performance in this sample, whereas they were small-medium for set-shifting, demonstrating that differences in the former domain might be more clinically meaningful. Impaired attentional control might represent a valuable neurocognitive marker in FS and FMS, characterised by diminished maintenance of attentional focus, together with difficulties in learning implicit rules and/or voluntarily switching from a particular cognitive set. However, given that test performance in these domains did not correlate meaningfully with clinical outcomes (e.g., FND, cognitive, psychological, and physical symptoms, quality-of-life, work/social functioning), the relevance of these differences to FND should be scrutinised in greater detail. Investigators may also examine executive function performance in FS/FMS relative to patients with FCD, to identify possible shared and distinctive profiles and mechanisms in these subgroups. Participants with FS and FMS expressed markedly reduced confidence on the sustained attention task, mirroring the performance deficit displayed on this measure. Actual performance and confidence ratings on the set-shifting task ( IEDSS ) were correlated within both FND groups, but not in CCs, indicating that the FND groups were aware of their difficulties to some extent. These results imply intact global metacognition in these domains in FS/FMS, contrary to our hypothesis and some prior findings, 3 , 5 , 7 , 9 although more work is needed to establish this with greater certainty. Confidence for sustained attention test performance, but not actual performance on that test, correlated significantly with global cognitive symptoms in the FMS group, replicating our pilot findings. 2 Lower confidence for sustained attention performance was also associated with other adverse clinical characteristics in the FMS group. Therefore, reduced confidence in attentional control might be relevant to increased subjective cognitive symptoms and/or other clinical outcomes in FMS, beyond the degree of actual performance deficits displayed. Further investigations should clarify the direction of effects between these variables, whilst also seeking to replicate these findings with additional neurocognitive tests. The major strength of this study was the direct comparison of two common FND subgroups using the same test battery, with a sample size providing adequate statistical power to detect small effects. Inclusion of HC and CC groups provided insights into cognitive features in FND that were distinct from the general population, whilst controlling for elevated psychological distress. We employed a range of measures to comprehensively assess cognitive performance, along with two measures of global metacognition (subjective symptoms, post-diction appraisals), in addition to a test of performance validity. Our groups were comparable on most relevant background characteristics (e.g., age, gender, handedness), and we accounted for any pertinent group differences within our analyses (e.g., education, response speed, psychotropic medications). Examining potential relationships between cognitive variables and other clinical features allowed us to explore the clinical significance of neurocognitive differences in our FS/FMS/CC samples. Some limitations of this study should be considered. Whilst we controlled statistically for the influence of education, psychotropic medications, and other confounds, there may have been residual effects on our results. A minority of our FND/CC samples reported diagnoses of attention-deficit hyperactivity disorder, which may have affected attentional performance. The use of a retrospective self-report questionnaire to assess cognitive symptoms may have resulted in recall biases. The CANTAB Connect battery lacks psychometric validation, established clinical cut-off scores, and has limited ecological validity. Performance-controlled experimental assessment of local metacognitive accuracy would complement measures of global metacognition in future studies. 9 In conclusion, our findings provide robust evidence of performance deficits in sustained attention and set-shifting in FS and FMS, with seemingly intact global metacognitive awareness of these impairments, accompanied by elevated cognitive complaints in daily life. Poorer subjective cognitive functioning is associated with greater physical/psychological symptom burden, decreased work/social functioning, and worse quality-of-life, in patients with FND and/or common psychological symptoms (anxiety/depression). Neuropsychological rehabilitation approaches might hold promise for some patients with FMS and FS, specifically targeting cognitive control and associated self-appraisals in everyday activities, and facilitating self-management of subjective cognitive symptoms and their impact. Data Availability The anonymised dataset will be made available in response to reasonable requests, on a case-by-case basis. Completion of a Data Sharing Agreement will be required, facilitated by the Kings College London Data Management team. Supplementary Materials View this table: View inline View popup Supplementary Table 1. Clinical self-report questionnaire details View this table: View inline View popup Download powerpoint Supplementary Table 2. Functional Neurological Symptoms Questionnaire (Pick et al., 2024) Please look at the symptoms in the table below and tell us whether you have experienced these functional neurological symptoms in the past week.LIf you mark yes to indicate that the symptom was present in the past week, please complete the additional columns to tell us how frequent the symptoms were, how severe (intense) they were, and how much impact they had on you. When rating the average severity of symptoms, please choose a number from 1 to 7, where 1=Symptom not present; 2=Minimal; 3=Mild; 4=Moderate; 5=Moderately severe; 6=Severe; 7=Very severe. When rating the impact of symptoms, please choose a number from 1 to 7, where 1=No impact at all; 2=Minimal impact; 3=Mild impact; 4=Moderate impact; 5=Moderately severe impact; 6=Severe impact; 7=Very severe impact. View this table: View inline View popup Supplementary Table 3. CANTAB Connect outcome variables View this table: View inline View popup Supplementary Table 4. Sample characteristics: Sociodemographic and clinical variables View this table: View inline View popup Supplementary Table 5. Clinical self-report measure statistics View this table: View inline View popup Download powerpoint Supplementary Table 6. Cognitive Failures Questionnaire sensitivity analyses View this table: View inline View popup Download powerpoint Supplementary Table 7. Cognitive Failures Questionnaire Bonferroni post-hoc tests View this table: View inline View popup Download powerpoint Supplementary Table 8. WASI-II post-hoc tests View this table: View inline View popup Download powerpoint Supplementary Table 9. WASI-II sensitivity analyses View this table: View inline View popup Supplementary Table 10. Motor Screening and Reaction Time Test sensitivity analyses View this table: View inline View popup Download powerpoint Supplementary Table 11. Motor screening and reaction time Games-Howell post-hoc tests View this table: View inline View popup Supplementary Table 12. Rapid Visual Information Processing sensitivity analyses View this table: View inline View popup Download powerpoint Supplementary Table 13. Rapid Visual Information Processing Bonferroni post-hoc tests View this table: View inline View popup Supplementary Table 14. Intra-Extra Dimensional Set-Shift sensitivity analyses View this table: View inline View popup Download powerpoint Supplementary Table 15. Intra-Extra Dimensional Set Shift post-hoc tests View this table: View inline View popup Download powerpoint Supplementary Table 16. Spatial Span Test uncorrected results View this table: View inline View popup Supplementary Table 17. Spatial Span Test sensitivity analyses View this table: View inline View popup Download powerpoint Supplementary Table 18. Stop Signal Task uncorrected results View this table: View inline View popup Download powerpoint Supplementary Table 19. Stop Signal Task sensitivity analyses View this table: View inline View popup Supplementary Table 20. Emotional bias and recognition tasks uncorrected results View this table: View inline View popup Supplementary Table 21. Emotional Bias Task sensitivity analyses View this table: View inline View popup Supplementary Table 22. Emotion Recognition Test sensitivity analyses View this table: View inline View popup Download powerpoint Supplementary Table 23. Metacognitive performance ratings View this table: View inline View popup Download powerpoint Supplementary Table 24. RVIP performance ratings sensitivity analyses View this table: View inline View popup Download powerpoint Supplementary Table 25. RVIP performance ratings post-hoc tests View this table: View inline View popup Supplementary Table 26. Significant within-group correlations Acknowledgements We are grateful to all participants and the FND Patient and Carer Advisory Panel who oversaw the study. With thanks to FND Hope UK, clinicians and administrative staff at King’s College Hospital, South London and Maudsley, and St George’s University Hospital NHS Foundation Trusts (including Dr Simon Harrison, Dr Albert Joseph, Dr Sotiris Posporelis, Dr Norman Poole, Dr Tim Segal), and the RADAR-MDD team, for contributions to recruitment and screening. We thank NIHR BioResource volunteers for their participation, and gratefully acknowledge NIHR BioResource centres, NHS Trusts and staff for their contribution. Thanks also to the research assistants who assisted in some testing sessions (Chrystel-Jazz Campbell, Akshaana Manoharan). Footnotes CRediT statement: Conceptualisation – SP., Methodology – SP, MH, TC, ASD, MJE, LHG, MAM, TRN, BS, JSW., Validation – SP, EGG. Formal analysis – SP, EGG., Investigation (data collection/recruitment) – LSMM, SP, YB, JUJ, JD, LB, SB, JC, BS. Resources – SP, TC, MH., Data curation (data processing/preparation) – LSMM, EGG, SP., Writing (original draft) – SP (introduction, methods, results, discussion, supplementary materials), EGG (results/supplementary materials)., Writing (review/editing) – TC, JC, ASD, MJE, LHG, JH, MH, MAM, LSMM, BS, JSW. Visualisation - SP., Supervision – SP, TC, MH, ASD, MJE, LHG, MAM, TRN, BS, JSW., Project administration – SP, LSMM. Funding acquisition – SP, MH, TC. Declarations of interest: None. Funding: The study was funded by a Medical Research Council Career Development Award to SP [MR/V032771/1]. This paper represents independent research part-funded by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Data sharing: The anonymised dataset will be made available in response to reasonable requests, on a case-by-case basis. Completion of a Data Sharing Agreement will be required, facilitated by the King’s College London Data Management team. References 1. ↵ American Psychiatric Association . Diagnostic and statistical manual of mental disorders (5th ed.) ; 2013 . 2. ↵ Pick S , Millman LSM , Sun Y , et al. Objective and subjective neurocognitive functioning in functional motor symptoms and functional seizures: preliminary findings . J Clin Exp Neuropsychol 2023 ; 45 ( 10 ): 970 – 87 . OpenUrl PubMed 3. ↵ Teodoro T , Edwards MJ , Isaacs JD . A unifying theory for cognitive abnormalities in functional neurological disorders, fibromyalgia and chronic fatigue syndrome: systematic review . J Neurol Neurosurg Psychiatry 2018 ; 89 ( 12 ): 1308 – 19 . OpenUrl Abstract / FREE Full Text 4. ↵ Forejtova Z , Serranova T , Sieger T , et al. The complex syndrome of functional neurological disorder . Psychol Med 2023 ; 53 ( 7 ): 3157 – 67 . OpenUrl CrossRef PubMed 5. ↵ Millman LSM , Williams IA , Jungilligens J , Pick S . Neurocognitive performance in functional neurological disorder: A systematic review and meta-analysis . Eur J Neurol 2025 ; 32 ( 1 ): e16386 . OpenUrl PubMed 6. ↵ Vechetova G , Slovak M , Kemlink D , et al. The impact of non-motor symptoms on the health-related quality of life in patients with functional movement disorders . J Psychosom Res 2018 ; 115 : 32 – 7 . OpenUrl CrossRef PubMed 7. ↵ Alluri PR , Solit J , Leveroni CL , et al. Cognitive Complaints in Motor Functional Neurological (Conversion) Disorders: A Focused Review and Clinical Perspective . Cogn Behav Neurol 2020 ; 33 ( 2 ): 77 – 89 . OpenUrl PubMed 8. ↵ Van Patten R , Austin TA , Cotton E , et al. Cognitive performance in functional seizures compared with epilepsy and healthy controls: a systematic review and meta analysis . Lancet Psychiatry 2024 ; 11 ( 7 ): 516 – 25 . OpenUrl PubMed 9. ↵ Sadnicka A , Strudwick AM , Grogan JP , Manohar S , Nielsen G . Going ‘meta’: a systematic review of metacognition and functional neurological disorder . Brain Commun 2025 ; 7 ( 1 ): fcaf014 . OpenUrl 10. ↵ Fleming SM . Metacognition and Confidence: A Review and Synthesis . Annu Rev Psychol 2024 ; 75 : 241 – 68 . OpenUrl CrossRef PubMed 11. ↵ Seow TXF , Rouault M , Gillan CM , Fleming SM . How Local and Global Metacognition Shape Mental Health . Biol Psychiatry 2021 ; 90 ( 7 ): 436 – 46 . OpenUrl CrossRef PubMed 12. ↵ Pick S , David AS , Edwards MJ , et al. Investigating psychobiological causes and mechanisms in functional seizures and functional motor symptoms: Study protocol . PLoS One 2024 ; 19 ( 6 ): e0305015 . OpenUrl PubMed 13. ↵ Pick S , Goldstein LH , Perez DL , Nicholson TR . Emotional processing in functional neurological disorder: a review, biopsychosocial model and research agenda . J Neurol Neurosurg Psychiatry 2019 ; 90 ( 6 ): 704 – 11 . OpenUrl Abstract / FREE Full Text 14. ↵ First MB , First MB . QuickSCID-5: quick structured clinical interview for DSM-5 disorders . Washington, DC : American Psychiatric Association Publishing ; 2021 . 15. ↵ Broadbent DE , Cooper PF , FitzGerald P , Parkes KR . The Cognitive Failures Questionnaire (CFQ) and its correlates . Br J Clin Psychol 1982 ; 21 ( 1 ): 1 – 16 . OpenUrl CrossRef PubMed Web of Science 16. Bridger RS , Johnsen SA , Brasher K . Psychometric properties of the Cognitive Failures Questionnaire . Ergonomics 2013 ; 56 ( 10 ): 1515 – 24 . OpenUrl CrossRef PubMed Web of Science 17. ↵ Wallace JC , Kass SJ , Stanny CJ . The cognitive failures questionnaire revisited: dimensions and correlates . J Gen Psychol 2002 ; 129 ( 3 ): 238 – 56 . OpenUrl CrossRef PubMed Web of Science 18. ↵ Green P . Medical Symptom Validity Test for Windows: User’s manual and program .. 2005 . 19. ↵ Green P , Flaro L . Results From Three Performance Validity Tests in Children With Intellectual Disability . Appl Neuropsychol Child 2016 ; 5 ( 1 ): 25 – 34 . OpenUrl PubMed 20. ↵ Green P , Montijo J , Brockhaus R . High specificity of the Word Memory Test and Medical Symptom Validity Test in groups with severe verbal memory impairment . Appl Neuropsychol 2011 ; 18 ( 2 ): 86 – 94 . OpenUrl CrossRef PubMed 21. ↵ McWhirter L , Ritchie CW , Stone J , Carson A . Performance validity test failure in clinical populations-a systematic review . J Neurol Neurosurg Psychiatry 2020 ; 91 ( 9 ): 945 – 52 . OpenUrl Abstract / FREE Full Text 22. ↵ Wechsler D. Wechsler Abbreviated Scale of Intelligence (2nd ed.). Pearson, Inc .; 2011 . 23. ↵ Robbins TW , James M , Owen AM , Sahakian BJ , McInnes L , Rabbitt P . Cambridge Neuropsychological Test Automated Battery (CANTAB): a factor analytic study of a large sample of normal elderly volunteers . Dementia 1994 ; 5 ( 5 ): 266 – 81 . OpenUrl CrossRef PubMed Web of Science 24. ↵ Robbins TW , James M , Owen AM , et al. A study of performance on tests from the CANTAB battery sensitive to frontal lobe dysfunction in a large sample of normal volunteers: implications for theories of executive functioning and cognitive aging. Cambridge Neuropsychological Test Automated Battery . J Int Neuropsychol Soc 1998 ; 4 ( 5 ): 474 – 90 . OpenUrl CrossRef PubMed Web of Science 25. ↵ Heintz CE , van Tricht MJ , van der Salm SM , et al. Neuropsychological profile of psychogenic jerky movement disorders: importance of evaluating non-credible cognitive performance and psychopathology . J Neurol Neurosurg Psychiatry 2013 ; 84 ( 8 ): 862 – 7 . OpenUrl Abstract / FREE Full Text 26. ↵ Vechetova G , Nikolai T , Slovak M , et al. Attention impairment in motor functional neurological disorders: a neuropsychological study . J Neurol 2022 ; 269 ( 11 ): 5981 – 90 . OpenUrl PubMed 27. ↵ Van Patten R , Mulhauser K , Austin TA , et al. The association between subjective and objective cognitive functioning from a transdiagnostic perspective: An umbrella review and meta-analysis . Clin Psychol Rev 2025 ; 121 : 102648 . 28. ↵ Goodman ZT , Timpano KR , Llabre MM , Bainter SA . Revisiting the factor structure and construct validity of the Cognitive Failures Questionnaire . Psychol Assess 2022 ; 34 ( 7 ): 671 – 83 . OpenUrl PubMed 29. ↵ Poole N , Cope S , Vanzan S , et al. Randomised controlled feasibility trial of online group acceptance and commitment therapy for functional cognitive disorder . BJPsych Open 2025 ; 11 ( 3 ): e91 . OpenUrl 30. ↵ O’Brien FM , Fortune GM , Dicker P , et al. Psychiatric and neuropsychological profiles of people with psychogenic nonepileptic seizures . Epilepsy Behav 2015 ; 43 : 39 – 45 . OpenUrl PubMed View the discussion thread. Back to top Previous Next Posted September 27, 2025. Download PDF Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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