Novel approaches to the investigation of psychobiological mechanisms in functional neurological disorder

Functional (dissociative) neurological symptom disorder (FND) is defined by distressing and disabling physical symptoms (e.g., seizures, tremor, paralysis) that are not caused by a known neurological injury or illness. People with FND have difficulties in daily functioning (e.g., work, relationships) and reduced life satisfaction. FND is also associated with stigma and barriers to accessing treatment, partly because the causes of FND are not well understood and patients often 'fall through the gaps' between physical and mental health services. It is crucial that FND is better understood scientifically, so that treatment options and outcomes improve rapidly.

People with FND report higher rates of trauma and stressful life events, challenging personal relationships and a range of mental health symptoms (e.g., depression, anxiety), compared to the general population (Brown & Reuber, 2016; Ludwig et al., 2019; Pick et al., 2016; 2017). Studies have shown that people with FND experience difficulties in recognising and regulating emotions, potentially having stronger physical reactions to stressors, yet often being unaware of this (Pick et al., 2016; 2017; 2018; 2019). However, it is not well understood how these psychological factors contribute to FND symptoms, nor how they relate to subtle abnormalities reported in some brain scan studies. More research is needed to explore the relevance of these psychological factors, and how they relate to symptoms and other biological features in FND.

On the basis of research evidence, I recently proposed that stronger emotional reactions could trigger or worsen FND symptoms, because of a greater physical 'fight or flight' response ('autonomic arousal') (Pick et al., 2019). This could be due to abnormalities in communication between emotional brain systems and brain areas involved in other important functions, such as movement, sensation and self/body awareness (e.g., knowledge of one's own bodily or emotional states). My findings have recently suggested that a psychological process called 'dissociation' might directly trigger FND symptoms (Pick et al., 2017; 2020). Dissociation broadly refers to a disconnection between different aspects of a person's experience (e.g., feeling detached from one's emotions or the outside world, feeling in less control over one's body) and often occurs in response to stressful experiences and strong emotional reactions. Dissociation could therefore potentially explain the connection between emotional abnormalities and FND symptoms.

The primary aim of the proposed research is to investigate factors that trigger or worsen FND symptoms, with a focus on emotional responses, autonomic arousal and dissociation. A second aim is to assess whether these processes are linked to differences in brain functioning. Patients with different types of FND (i.e., seizures or movement symptoms) will be included and compared to people with common mental health symptoms (depression) and people with no significant mental or physical health disorders, to examine potential similarities and differences to these groups. A variety of relevant features will be measured, including participants' subjective 'in-the-moment' experiences (emotions, dissociation), physical measures of arousal (e.g., heart rate), and FND symptoms. Some measures will be taken in both laboratory and real-life settings, to assess whether findings are consistent. Brain structure and functioning will also be assessed in a scanner.

The results of the research will provide more information about the interaction between biological and psychological factors in FND and will have considerable implications for improving or developing new treatments, which are much needed. It is hoped that the research will provide a basis for a more integrated approach to studying and treating this complex disorder, combining both physical and mental health perspectives.

Functional (dissociative) neurological disorder is a neuropsychiatric disorder defined by the presence of motor, sensory and/or seizure symptoms that are not caused by neuropathology (DSM-5; ICD-11). The mechanisms underlying FND symptoms are poorly understood. Psychological risk factors (e.g., trauma, emotional dysregulation), comorbidities (e.g., dissociative, affective disorders) and distress are common, yet the ways in which these factors contribute to FND symptoms is unclear.

The aim of this research is to investigate further the psychobiological mechanisms underlying FND with robust, innovative methods. I recently proposed that aberrant emotional processing of salient stimuli results in elevated autonomic arousal, thereby triggering or exacerbating FND symptoms (Pick et al., 2019). I have also proposed a key role for dissociation (Pick et al., 2017; 2020), which potentially mediates the relationship between abnormal emotional responses and FND symptoms. Hyperactivity in limbic regions (e.g., amygdala) and abnormal interactions between limbic neurocircuits and those involved in awareness of self/body (e.g., insula, anterior cingulate), executive (e.g., dorsolateral prefrontal cortex) and motor control (e.g., supplementary motor area) are predicted (Pick et al., 2019).

Laboratory-based experimental tasks, neuroimaging and remote measurement technology (RMT) will be used to rigorously test these hypotheses. Patients with FND (seizure or motor) will be compared to clinical and healthy control groups. Experimental tasks and functional neuroimaging will probe subjective and physiological responses to affective stimuli, alongside measuring the impact on FND symptoms. RMT will allow real-time capture of affectively salient triggers, autonomic arousal, dissociation and FND symptoms in daily life. The results will have considerable translational value and will inform the further development of integrative explanatory models.