Functional neurological disorder mega-analysis
Year: 2022
Type: preprint
Abstract: Functional neurological disorder (FND), also known as conversion disorder, is characterised by a loss of voluntary control over parts of the nervous system (Espay et al., 2018). Examples of FND subtypes include paralysis, dystonia, seizures, and sensory abnormalities. Despite being the second most common disorder in neurology outpatient clinics (A. Carson & Lehn, 2016; Stone et al., 2010) and causing similar physical disability to multiple sclerosis and Parkinson’s disease (Alan Carson et al., 2011), FND has been relatively neglected by research. Current treatment options are limited, and many patients have severe long-term symptoms despite best-available treatment (Nicholson et al., 2020). There is a pressing need for better understanding of the neurobiology of the disorder (Perez et al., 2021). FND patients have shown increased connectivity in brain regions which comprise the default mode network (DMN), such as the posterior cingulate cortex (Cojan et al., 2009; de Lange et al., 2007, 2008, 2010), and the medial prefrontal cortex (Marapin et al., 2020). The increased DMN connectivity in patients with FND may be a correlate of abnormal predictions (otherwise known as over-weighted priors) about the body, for example that one cannot move one’s limb (Edwards et al., 2012). Patients with FND have also shown heightened limbic-motor cortex connectivity (Baizabal-Carvallo et al., 2019) and temporo-parietal junction (TPJ) aberrations (Marapin et al., 2020). Evidence from structural neuroimaging is heterogenous, although morphometric alterations have been seen in limbic and frontal cortices (Begue et al., 2019). There are some studies (albeit not always replicated) which have shown increased amygdala volumes in mixed FND cohorts, consistent with the idea that FND is a threat-related disorder (Maurer et al., 2018; Perez et al., 2017). Leading neurobiological theories of FND symptom generation have implicated regions associated with limbic-motor and limbic-frontal cortical connectivity, such as the cingulate cortex, orbitofrontal cortex, and insula (Pick et al., 2018). Patients with functional weakness have also been shown to have reduced left thalamic volume (unrelated to the laterality of symptoms) (Atmaca et al., 2006; Nicholson et al., 2014), which fits with structural imaging of patients with amputated limbs – conditions linked by loss of use of a limb - who also show reduction in thalamic volumes (Draganski et al., 2006). Structural neuroimaging in other causes of limb weakness with peripheral causes – namely motor neurone disease – have shown decreased grey matter volume in the motor cortex (Devine et al., 2015). A mega-analysis of all available structural neuroimaging data would (i) allow determination of morphometric alterations with increased statistical power clarifying inconsistencies in the literature (ii) allow grouping of participants my presentation phenomenology (iii) allow the inclusion of potential confounding factors (e.g. mood symptoms) in the analysis and (iv) allow the exploration of correlations with clinical features (e.g. frequency of seizures). 5-HT2A receptors are found throughout the cortex, especially so in high-level associative cortices (such as the DMN). It is thought that 5-HT2A receptors are upregulated in response to stress and may enhance plasticity and learning in response to stressors (Murnane, 2019), a hypothesis which is supported by data from mouse models of stress (Murnane, 2019). Although childhood adversity has been removed as a qualifier for the diagnosis of FND in the Diagnostic and Statistical Manual 5 (DSM-V), many patients do have a history of past or current stressors (Keynejad et al., 2019), indicating a possibility of increased cortical 5-HT2A receptor expression in this patient population.
Source: OSF Preprints (OSF Preprints)
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W6925243518