Mechanisms and Vulnerabilities in Functional Neurological Disorder

Abstract

Functional neurological disorder (FND) is a disabling neuropsychiatric condition characterized by altered voluntary motor or sensory functions and cognitive symptoms. Unlike other neurological disorders, FND is not caused by structural brain damage but by disruptions across brain networks involved in agency, attention, emotion processing, sensory–motor control, and interoception. These alterations align with alterations in predictive coding, which propose that abnormal prior beliefs override sensory input, contributing to symptom generation. Early-life trauma is a significant risk factor, interacting with genetic and epigenetic vulnerabilities that influence emotional regulation, stress sensitivity, and brain connectivity. Psychiatric comorbidities are also common and may affect symptom severity and prognosis. This review synthesizes recent research to clarify the complex mechanisms underlying FND by integrating neurobiological, environmental, and psychological factors. By doing so, we aim to advance the understanding of FND pathophysiology and promote a more comprehensive conceptual framework that highlights the role of individual vulnerability.

Keywords

functional neurological disorder - mechanisms - pathophysiology - vulnerabilities

^‡ Contributed equally to the writing of this manuscript.

Publication History

Received: 29 September 2025

Accepted: 15 December 2025

Article published online:
07 January 2026

• References

• 1 Stone J, Burton C, Carson A. Recognising and explaining functional neurological disorder. BMJ 2020; 371: m3745
• 2 Espay AJ, Aybek S, Carson A. et al. Current concepts in diagnosis and treatment of functional neurological disorders. JAMA Neurol 2018; 75 (09) 1132-1141
• 3 Hallett M, Aybek S, Dworetzky BA, McWhirter L, Staab JP, Stone J. Functional neurological disorder: new subtypes and shared mechanisms. Lancet Neurol 2022; 21 (06) 537-550
• 4 Lazzari C, Nikolou-Walker E, Liu LQ, Rabottini M. Psychiatric comorbidities in functional neurological disorders and psychogenic non-epileptic seizures: a systematic review and policy recommendations for improving assessment and treatment. Neuropsychiatr Dis Treat 2024; 20: 2313-2331
• 5 World Health Association. International Classification of Diseases 11th Revision. 2025 . Accessed July 25, 2025. https://icd.who.int/browse/2025-01/mms/en#1069443471
• 6 Aybek S, Perez DL. Diagnosis and management of functional neurological disorder. BMJ 2022; 376: o64
• 7 Tinazzi M, Gandolfi M, Landi S, Leardini C. Economic costs of delayed diagnosis of functional motor disorders: preliminary results from a cohort of patients of a specialized clinic. Front Neurol 2021; 12: 786126
• 8 LaFaver K, Lang AE, Stone J. et al. Opinions and clinical practices related to diagnosing and managing functional (psychogenic) movement disorders: changes in the last decade. Eur J Neurol 2020; 27 (06) 975-984
• 9 Carle-Toulemonde G, Goutte J, Do-Quang-Cantagrel N, Mouchabac S, Joly C, Garcin B. Overall comorbidities in functional neurological disorder: a narrative review. Encephale 2023; 49 (4S): S24-S32
• 10 Morsy SK, Aybek S, Carson A. et al. The relationship between types of life events and the onset of functional neurological (conversion) disorder in adults: a systematic review and meta-analysis. Psychol Med 2022; 52 (03) 401-418
• 11 Levita L, Mayberry E, Mehmood A, Reuber M. Evaluation of LiNES: a new measure of trauma, negative affect, and relationship insecurity over the life span in persons with FND. J Neuropsychiatry Clin Neurosci 2020; 32 (01) 43-49
• 12 Edwards MJ, Yogarajah M, Stone J. Why functional neurological disorder is not feigning or malingering. Nat Rev Neurol 2023; 19 (04) 246-256
• 13 Drane DL, Fani N, Hallett M, Khalsa SS, Perez DL, Roberts NA. A framework for understanding the pathophysiology of functional neurological disorder. CNS Spectr 2020; 26 (06) 1-7
• 14 Gonzalez-Herrero B, Happé F, Nicholson TR. et al. Functional neurological disorder and autism spectrum disorder: a complex and potentially significant relationship. Brain Behav 2024; 14 (12) e70168
• 15 Sojka P, Serranová T, Khalsa SS, Perez DL, Diez I. Altered neural processing of interoception in patients with functional neurological disorder: a task-based fMRI study. J Neuropsychiatry Clin Neurosci 2025; 37 (02) 149-159
• 16 Raichle ME. The brain's default mode network. Annu Rev Neurosci 2015; 38 (01) 433-447
• 17 van der Kruijs SJM, Jagannathan SR, Bodde NMG. et al. Resting-state networks and dissociation in psychogenic non-epileptic seizures. J Psychiatr Res 2014; 54: 126-133
• 18 Seeley WW. The salience network: a neural system for perceiving and responding to homeostatic demands. J Neurosci 2019; 39 (50) 9878-9882
• 19 Perez DL, Matin N, Barsky A. et al. Cingulo-insular structural alterations associated with psychogenic symptoms, childhood abuse and PTSD in functional neurological disorders. J Neurol Neurosurg Psychiatry 2017; 88 (06) 491-497
• 20 Aybek S, Nicholson TR, Zelaya F. et al. Neural correlates of recall of life events in conversion disorder. JAMA Psychiatry 2014; 71 (01) 52-60
• 21 Baizabal-Carvallo JF, Hallett M, Jankovic J. Pathogenesis and pathophysiology of functional (psychogenic) movement disorders. Neurobiol Dis 2019; 127: 32-44
• 22 Rai S, Foster S, Griffiths KR, Breukelaar IA, Kozlowska K, Korgaonkar MS. Altered resting-state neural networks in children and adolescents with functional neurological disorder. Neuroimage Clin 2022; 35: 103110
• 23 Nahab FB, Kundu P, Maurer C, Shen Q, Hallett M. Impaired sense of agency in functional movement disorders: an fMRI study. PLoS One 2017; 12 (04) e0172502
• 24 Salomon R, Kannape OA, Debarba HG. et al. Agency deficits in a human genetic model of schizophrenia: insights from 22q11DS patients. Schizophr Bull 2022; 48 (02) 495-504
• 25 Baek K, Doñamayor N, Morris LS. et al. Impaired awareness of motor intention in functional neurological disorder: implications for voluntary and functional movement. Psychol Med 2017; 47 (09) 1624-1636
• 26 Kranick SM, Moore JW, Yusuf N. et al. Action-effect binding is decreased in motor conversion disorder: implications for sense of agency. Mov Disord 2013; 28 (08) 1110-1116
• 27 Pareés I, Brown H, Nuruki A. et al. Loss of sensory attenuation in patients with functional (psychogenic) movement disorders. Brain 2014; 137 (Pt 11): 2916-2921
• 28 Neafsey EJ. Conscious intention and human action: Review of the rise and fall of the readiness potential and Libet's clock. Conscious Cogn 2021; 94: 103171
• 29 Edwards MJ, Moretto G, Schwingenschuh P, Katschnig P, Bhatia KP, Haggard P. Abnormal sense of intention preceding voluntary movement in patients with psychogenic tremor. Neuropsychologia 2011; 49 (09) 2791-2793
• 30 Jungilligens J, Wellmer J, Schlegel U, Kessler H, Axmacher N, Popkirov S. Impaired emotional and behavioural awareness and control in patients with dissociative seizures. Psychol Med 2020; 50 (16) 2731-2739
• 31 Blakemore SJ, Wolpert DM, Frith CD. Central cancellation of self-produced tickle sensation. Nat Neurosci 1998; 1 (07) 635-640
• 32 Demartini B, Ricciardi L, Crucianelli L, Fotopoulou A, Edwards MJ. Sense of body ownership in patients affected by functional motor symptoms (conversion disorder). Conscious Cogn 2016; 39: 70-76
• 33 Nisticò V, Conte F, Rossetti I. et al. Exploring specific alterations at the explicit and perceptual levels in sense of ownership, agency, and body schema in functional motor disorder: a pilot comparative study with irritable bowel syndrome. Cortex 2025; 184: 106-119
• 34 van Beilen M, de Jong BM, Gieteling EW, Renken R, Leenders KL. Abnormal parietal function in conversion paresis. PLoS One 2011; 6 (10) e25918
• 35 Voon V, Gallea C, Hattori N, Bruno M, Ekanayake V, Hallett M. The involuntary nature of conversion disorder. Neurology 2010; 74 (03) 223-228
• 36 Maurer CW, LaFaver K, Ameli R, Epstein SA, Hallett M, Horovitz SG. Impaired self-agency in functional movement disorders: a resting-state fMRI study. Neurology 2016; 87 (06) 564-570
• 37 Hallett M. Volitional control of movement: the physiology of free will. Clin Neurophysiol 2007; 118 (06) 1179-1192
• 38 Edwards MJ, Adams RA, Brown H, Pareés I, Friston KJ. A Bayesian account of 'hysteria'. Brain 2012; 135 (Pt 11): 3495-3512
• 39 Nielsen G, Buszewicz M, Stevenson F. et al. Randomised feasibility study of physiotherapy for patients with functional motor symptoms. J Neurol Neurosurg Psychiatry 2017; 88 (06) 484-490
• 40 Věchetová G, Nikolai T, Slovák M. et al. Attention impairment in motor functional neurological disorders: a neuropsychological study. J Neurol 2022; 269 (11) 5981-5990
• 41 Huys AML, Bhatia KP, Edwards MJ, Haggard P. The flip side of distractibility—executive dysfunction in functional movement disorders. Front Neurol 2020; 11: 969
• 42 Huys AML, Haggard P, Bhatia KP, Edwards MJ. Misdirected attentional focus in functional tremor. Brain 2021; 144 (11) 3436-3450
• 43 Sojka P, Bareš M, Kašpárek T, Světlák M. Processing of emotion in functional neurological disorder. Front Psychiatry 2018; 9: 479
• 44 Demartini B, Petrochilos P, Ricciardi L, Price G, Edwards MJ, Joyce E. The role of alexithymia in the development of functional motor symptoms (conversion disorder). J Neurol Neurosurg Psychiatry 2014; 85 (10) 1132-1137
• 45 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 (06) 704-711
• 46 Koreki A, Garfkinel SN, Mula M. et al. Trait and state interoceptive abnormalities are associated with dissociation and seizure frequency in patients with functional seizures. Epilepsia 2020; 61 (06) 1156-1165
• 47 Millman LSM, Short E, Stanton B. et al. Interoception in functional motor symptoms and functional seizures: preliminary evidence of intact accuracy alongside reduced insight and altered sensibility. Behav Res Ther 2023; 168: 104379
• 48 Pick S, Rojas-Aguiluz M, Butler M, Mulrenan H, Nicholson TR, Goldstein LH. Dissociation and interoception in functional neurological disorder. Cogn Neuropsychiatry 2020; 25 (04) 294-311
• 49 Williams B, Ospina JP, Jalilianhasanpour R, Fricchione GL, Perez DL. Fearful attachment linked to childhood abuse, alexithymia, and depression in motor functional neurological disorders. J Neuropsychiatry Clin Neurosci 2019; 31 (01) 65-69
• 50 Zamariola G, Maurage P, Luminet O, Corneille O. Interoceptive accuracy scores from the heartbeat counting task are problematic: evidence from simple bivariate correlations. Biol Psychol 2018; 137: 12-17
• 51 Desmedt O, Luminet O, Corneille O. The heartbeat counting task largely involves non-interoceptive processes: evidence from both the original and an adapted counting task. Biol Psychol 2018; 138: 185-188
• 52 Stoffel N, Sojka P, Gninenko N. et al. Respiratory sensitivity is reduced in functional neurological disorder and associated with higher somatoform dissociation. Brain Commun 2025; 7 (04) fcaf283
• 53 Aspell JE, Heydrich L, Marillier G, Lavanchy T, Herbelin B, Blanke O. Turning body and self inside out: visualized heartbeats alter bodily self-consciousness and tactile perception. Psychol Sci 2013; 24 (12) 2445-2453
• 54 Heydrich L, Aspell JE, Marillier G, Lavanchy T, Herbelin B, Blanke O. Cardio-visual full body illusion alters bodily self-consciousness and tactile processing in somatosensory cortex. Sci Rep 2018; 8 (01) 9230
• 55 Sadnicka A, Daum C, Meppelink AM, Manohar S, Edwards M. Reduced drift rate: a biomarker of impaired information processing in functional movement disorders. Brain 2020; 143 (02) 674-683
• 56 Fiorio M, Braga M, Marotta A. et al. Functional neurological disorder and placebo and nocebo effects: shared mechanisms. Nat Rev Neurol 2022; 18 (10) 624-635
• 57 Hanzlíková Z, Kofler M, Slovák M. et al. Prepulse inhibition of the blink reflex is abnormal in functional movement disorders. Mov Disord 2019; 34 (07) 1022-1030
• 58 Diez I, Larson AG, Nakhate V. et al. Early-life trauma endophenotypes and brain circuit-gene expression relationships in functional neurological (conversion) disorder. Mol Psychiatry 2021; 26 (08) 3817-3828
• 59 Grimble N, Scarfo J, Katherveloo J, Ganci M, Ball M, Suleyman E. The relationship between interoceptive emotional awareness, neuroticism, and depression, anxiety, and stress. PLoS One 2024; 19 (04) e0299835
• 60 Hallett M. Functional neurologic disorder, lésion dynamique: 2024 Wartenberg lecture. Neurology 2024; 103 (11) e210051
• 61 Spagnolo PA, Johnson K, Hodgkinson C, Goldman D, Hallett M. Methylome changes associated with functional movement/conversion disorder: influence of biological sex and childhood abuse exposure. Prog Neuropsychopharmacol Biol Psychiatry 2023; 125: 110756
• 62 Weber S, Stoffel N, Rey Álvarez LT. et al. Increased prevalence of oxytocin receptor gene variant in functional neurological disorder: a preliminary case-control study. J Neuropsychiatry Clin Neurosci 2025; ;appineuropsych20250031
• 63 Apazoglou K, Adouan W, Aubry JM, Dayer A, Aybek S. Increased methylation of the oxytocin receptor gene in motor functional neurological disorder: a preliminary study. J Neurol Neurosurg Psychiatry 2018; 89 (05) 552-554
• 64 Weber S, Stoffel N, Ansede-Bermejo J. et al. Salivary oxytocin and amygdalar alterations in functional neurological disorders. Brain Commun 2024; 7 (01) fcae455
• 65 Tamilson B, Poole N, Agrawal N. The co-occurrence of functional neurological disorder and autism spectrum disorder: a systematic literature review and meta-analysis. Cogn Neuropsychiatry 2024; 29 (06) 358-385