Probing the functional magnetic resonance imaging response to psilocybin in functional neurological disorder (PsiFUND): study protocol

Matt Butler; Catherine Bird; Carolina Maggio; Amy Durden; Nadav Modlin; Kete Campbell-Coker; Mark Edwards; Susannah Pick; L. S.Merritt Millman; Emily Lowery; Chiranth Bhagavan; Richard Kanaan; Dawn Golder; Bridget Mildon; Mitul Mehta; James Rucker; Timothy R. Nicholson

doi:10.12688/wellcomeopenres.22543.1

Probing the functional magnetic resonance imaging response to psilocybin in functional neurological disorder (PsiFUND): study protocol

Matt Butler^*, Catherine Bird, Carolina Maggio, Amy Durden, Nadav Modlin, Kete Campbell-Coker, Mark Edwards, Susannah Pick, L. S.Merritt Millman, Emily Lowery, Chiranth Bhagavan, Richard Kanaan, Dawn Golder, Bridget Mildon, Mitul Mehta, James Rucker, Timothy R. Nicholson

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Functional neurological disorder (FND) is a common cause of neurological symptoms including paralysis, seizures, and movement disorders. It is often debilitating, is associated with high health and social care costs, and can have a poor prognosis. Functional magnetic resonance imaging (fMRI) has suggested FND is a multi-network disorder; the default mode network (DMN) may be specifically implicated. Converging evidence suggests that other variable mechanisms including dissociation, interoception, and motor agency may be differentially abnormal in people with FND. Psychedelics are currently under investigation for numerous neuropsychiatric disorders and have been shown to disrupt functional networks such as the DMN. Administering psychedelics to people with FND will help us to probe mechanistic theories of the disorder. Protocol: In this open-label neuroimaging study, we will administer 25mg oral psilocybin with psychological support to people with chronic FND (target n = 24). Participants will undergo resting-state and task-based (Libet’s clock, a measure of motor agency) fMRI sequences which will be compared in a pre-post manner. Additional mechanistic outcomes including measures of interoception (heartbeat tracking task), somatisation, illness perceptions, imaginative suggestibility, and dissociation will be collected. Data on expectancy, preparedness, and subjective experience of the psychedelic experience will also be gathered. Participants will be followed up for three months following psilocybin administration. fMRI changes in networks such as the DMN will be analysed using seed-based approaches, and additional exploratory analysis of resting-state imaging will take place. Discussion: The study will help us to probe the mechanisms thought to potentially underpin FND. As the first modern study of psychedelics in FND, it will also help us to understand whether psychedelic administration alongside psychological support might be safe and feasible in this patient population.

Original language	English
Article number	401
Journal	Wellcome Open Research
Volume	9
DOIs	https://doi.org/10.12688/wellcomeopenres.22543.1
Publication status	Published - 2024

Keywords

fMRI
functional neurological disorder
psilocybin
psychedelics

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10.12688/wellcomeopenres.22543.1

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Butler, M., Bird, C., Maggio, C., Durden, A., Modlin, N., Campbell-Coker, K., Edwards, M., Pick, S., Millman, L. S. M., Lowery, E., Bhagavan, C., Kanaan, R., Golder, D., Mildon, B., Mehta, M., Rucker, J., & Nicholson, T. R. (2024). Probing the functional magnetic resonance imaging response to psilocybin in functional neurological disorder (PsiFUND): study protocol. Wellcome Open Research, 9, Article 401. https://doi.org/10.12688/wellcomeopenres.22543.1

@article{703647966bae43edb56d453a1e8463d2,

title = "Probing the functional magnetic resonance imaging response to psilocybin in functional neurological disorder (PsiFUND): study protocol",

abstract = "Background: Functional neurological disorder (FND) is a common cause of neurological symptoms including paralysis, seizures, and movement disorders. It is often debilitating, is associated with high health and social care costs, and can have a poor prognosis. Functional magnetic resonance imaging (fMRI) has suggested FND is a multi-network disorder; the default mode network (DMN) may be specifically implicated. Converging evidence suggests that other variable mechanisms including dissociation, interoception, and motor agency may be differentially abnormal in people with FND. Psychedelics are currently under investigation for numerous neuropsychiatric disorders and have been shown to disrupt functional networks such as the DMN. Administering psychedelics to people with FND will help us to probe mechanistic theories of the disorder. Protocol: In this open-label neuroimaging study, we will administer 25mg oral psilocybin with psychological support to people with chronic FND (target n = 24). Participants will undergo resting-state and task-based (Libet{\textquoteright}s clock, a measure of motor agency) fMRI sequences which will be compared in a pre-post manner. Additional mechanistic outcomes including measures of interoception (heartbeat tracking task), somatisation, illness perceptions, imaginative suggestibility, and dissociation will be collected. Data on expectancy, preparedness, and subjective experience of the psychedelic experience will also be gathered. Participants will be followed up for three months following psilocybin administration. fMRI changes in networks such as the DMN will be analysed using seed-based approaches, and additional exploratory analysis of resting-state imaging will take place. Discussion: The study will help us to probe the mechanisms thought to potentially underpin FND. As the first modern study of psychedelics in FND, it will also help us to understand whether psychedelic administration alongside psychological support might be safe and feasible in this patient population.",

keywords = "fMRI, functional neurological disorder, psilocybin, psychedelics",

author = "Matt Butler and Catherine Bird and Carolina Maggio and Amy Durden and Nadav Modlin and Kete Campbell-Coker and Mark Edwards and Susannah Pick and Millman, {L. S.Merritt} and Emily Lowery and Chiranth Bhagavan and Richard Kanaan and Dawn Golder and Bridget Mildon and Mitul Mehta and James Rucker and Nicholson, {Timothy R.}",

note = "Publisher Copyright: Copyright: {\textcopyright} 2024 Butler M et al.",

year = "2024",

doi = "10.12688/wellcomeopenres.22543.1",

language = "English",

volume = "9",

journal = "Wellcome Open Research",

issn = "2398-502X",

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Butler, M , Bird, C , Maggio, C , Durden, A , Modlin, N, Campbell-Coker, K, Edwards, M , Pick, S , Millman, LSM, Lowery, E, Bhagavan, C, Kanaan, R, Golder, D, Mildon, B, Mehta, M , Rucker, J & Nicholson, TR 2024, 'Probing the functional magnetic resonance imaging response to psilocybin in functional neurological disorder (PsiFUND): study protocol', Wellcome Open Research, vol. 9, 401. https://doi.org/10.12688/wellcomeopenres.22543.1

TY - JOUR

T1 - Probing the functional magnetic resonance imaging response to psilocybin in functional neurological disorder (PsiFUND)

T2 - study protocol

AU - Butler, Matt

AU - Bird, Catherine

AU - Maggio, Carolina

AU - Durden, Amy

AU - Modlin, Nadav

AU - Campbell-Coker, Kete

AU - Edwards, Mark

AU - Pick, Susannah

AU - Millman, L. S.Merritt

AU - Lowery, Emily

AU - Bhagavan, Chiranth

AU - Kanaan, Richard

AU - Golder, Dawn

AU - Mildon, Bridget

AU - Mehta, Mitul

AU - Rucker, James

AU - Nicholson, Timothy R.

PY - 2024

Y1 - 2024

N2 - Background: Functional neurological disorder (FND) is a common cause of neurological symptoms including paralysis, seizures, and movement disorders. It is often debilitating, is associated with high health and social care costs, and can have a poor prognosis. Functional magnetic resonance imaging (fMRI) has suggested FND is a multi-network disorder; the default mode network (DMN) may be specifically implicated. Converging evidence suggests that other variable mechanisms including dissociation, interoception, and motor agency may be differentially abnormal in people with FND. Psychedelics are currently under investigation for numerous neuropsychiatric disorders and have been shown to disrupt functional networks such as the DMN. Administering psychedelics to people with FND will help us to probe mechanistic theories of the disorder. Protocol: In this open-label neuroimaging study, we will administer 25mg oral psilocybin with psychological support to people with chronic FND (target n = 24). Participants will undergo resting-state and task-based (Libet’s clock, a measure of motor agency) fMRI sequences which will be compared in a pre-post manner. Additional mechanistic outcomes including measures of interoception (heartbeat tracking task), somatisation, illness perceptions, imaginative suggestibility, and dissociation will be collected. Data on expectancy, preparedness, and subjective experience of the psychedelic experience will also be gathered. Participants will be followed up for three months following psilocybin administration. fMRI changes in networks such as the DMN will be analysed using seed-based approaches, and additional exploratory analysis of resting-state imaging will take place. Discussion: The study will help us to probe the mechanisms thought to potentially underpin FND. As the first modern study of psychedelics in FND, it will also help us to understand whether psychedelic administration alongside psychological support might be safe and feasible in this patient population.

AB - Background: Functional neurological disorder (FND) is a common cause of neurological symptoms including paralysis, seizures, and movement disorders. It is often debilitating, is associated with high health and social care costs, and can have a poor prognosis. Functional magnetic resonance imaging (fMRI) has suggested FND is a multi-network disorder; the default mode network (DMN) may be specifically implicated. Converging evidence suggests that other variable mechanisms including dissociation, interoception, and motor agency may be differentially abnormal in people with FND. Psychedelics are currently under investigation for numerous neuropsychiatric disorders and have been shown to disrupt functional networks such as the DMN. Administering psychedelics to people with FND will help us to probe mechanistic theories of the disorder. Protocol: In this open-label neuroimaging study, we will administer 25mg oral psilocybin with psychological support to people with chronic FND (target n = 24). Participants will undergo resting-state and task-based (Libet’s clock, a measure of motor agency) fMRI sequences which will be compared in a pre-post manner. Additional mechanistic outcomes including measures of interoception (heartbeat tracking task), somatisation, illness perceptions, imaginative suggestibility, and dissociation will be collected. Data on expectancy, preparedness, and subjective experience of the psychedelic experience will also be gathered. Participants will be followed up for three months following psilocybin administration. fMRI changes in networks such as the DMN will be analysed using seed-based approaches, and additional exploratory analysis of resting-state imaging will take place. Discussion: The study will help us to probe the mechanisms thought to potentially underpin FND. As the first modern study of psychedelics in FND, it will also help us to understand whether psychedelic administration alongside psychological support might be safe and feasible in this patient population.

KW - fMRI

KW - functional neurological disorder

KW - psilocybin

KW - psychedelics

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U2 - 10.12688/wellcomeopenres.22543.1

DO - 10.12688/wellcomeopenres.22543.1

M3 - Article

AN - SCOPUS:85206149077

SN - 2398-502X

VL - 9

JO - Wellcome Open Research

JF - Wellcome Open Research

M1 - 401

ER -

Probing the functional magnetic resonance imaging response to psilocybin in functional neurological disorder (PsiFUND): study protocol

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Keywords

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