A framework for understanding the pathophysiology of functional neurological disorder

Abstract

The symptoms of functional neurological disorder (FND) are a product of its pathophysiology. The pathophysiology of FND is reflective of dysfunction within and across different brain circuits that, in turn, affects specific constructs. In this perspective article, we briefly review five constructs that are affected in FND: emotion processing (including salience), agency, attention, interoception, and predictive processing/inference. Examples of underlying neural circuits include salience, multimodal integration, and attention networks. The symptoms of each patient can be described as a combination of dysfunction in several of these networks and related processes. While we have gained a considerable understanding of FND, there is more work to be done, including determining how pathophysiological abnormalities arise as a consequence of etiologic biopsychosocial factors. To facilitate advances in this underserved and important area, we propose a pathophysiology-focused research agenda to engage government-sponsored funding agencies and foundations.

Keywords: agency; attention; conversion disorder; emotion; interoception; psychogenic.

Figure 1:

A) Illustration of the relationship between symptoms, constructs and neural circuits underlying functional neurological disorder (FND). Symptoms can be understood as mapping onto alterations of different constructs, which are generated by neural circuit abnormalities. B) Examples of how different symptoms or observable manifestations of FND can be understood as arising from one or a combination of specific abnormal constructs. For example, paroxysmal movements can be perceived as involuntary by an individual with FND due to a dysfunction of the construct of agency, which is driven by abnormalities of a TPJ-based circuit. TPJ indicates temporo-parietal junction.

Figure 2:

Abnormalities of several constructs (and their associated neural circuits) can interact in different ways to produce symptoms and observable signs of functional neurological disorder.

Figure 3:

Display of brain circuits (and related constructs) that are emerging as important in the pathophysiology of functional neurological disorder (FND). As depicted, FND is a multi-network disorder involving abnormalities within and across brain circuits implicated in self-agency, emotion processing, attention, homeostatic balance, interoception, multimodal integration, and cognitive/motor control among other functions. Circuits are described by their related dysfunction in the pathophysiology of FND. It should also be noted that several areas cut across multiple networks; for example, the dorsal anterior insula is most strongly interconnected with the dorsal anterior cingulate cortex (dACC), while the posterior insula receives afferent projections from the lamina I spinothalamocortical pathway and somatosensory cortices. Similarly, the amygdala is part of both the salience and limbic networks. Prefrontal brain regions are interconnected with striatal-thalamic areas (not shown), and these pathways should also be factored into the neural circuitry of FND. TPJ indicates temporoparietal junction; FEF, frontal eye fields; dlPFC, dorsolateral prefrontal cortex; pgACC, perigenual anterior cingulate cortex; sgACC, subgenual anterior cingulate cortex; OFC, orbitofrontal cortex; SMA, supplementary motor area; AMY, amygdala; HYP, hypothalamus; PAG, periaqueductal gray.