Imaging studies of functional neurologic disorders.

Brain imaging techniques provide unprecedented opportunities to study the neural mechanisms underlying functional neurologic disorder (FND, or conversion disorder), which have long remained a mystery and clinical challenge for physicians, as they arise with no apparent underlying organic disease. One of the first questions addressed by imaging studies concerned whether motor conversion deficits (e.g., hysteric paralysis) represent a form of (perhaps unconscious) simulation, a mere absence of voluntary movement, or more specific disturbances in motor control (such as abnormal inhibition). Converging evidence from several studies using different techniques and paradigms has now demonstrated distinctive brain activation patterns associated with functional deficits, unlike those seen in actors simulating similar deficits. Thus, patients with motor FND show consistent hypoactivation of both cortical and subcortical motor pathways, with frequent increases in other brain areas within the limbic system, but no recruitment of prefrontal regions usually associated with voluntary motor inhibition. Other studies point to a dysfunction in sensorimotor integration and agency - related to parietal dysfunction - and abnormal motor planning related to supplementary motor area and prefrontal areas. These findings not only suggest that functional symptoms reflect a genuine brain dysfunction, but also give new insights into how they are produced. However, fewer studies attempted to understand why these symptoms are produced and linked to potential psychologic or emotional risk/triggering factors. Results from such studies point towards abnormal limbic regulation with heightened emotional arousal and amygdalar activity, potentially related to engagement of defense systems and stereotyped motor behaviors, mediated by medial prefrontal cortex and subcortical structures, including the periaqueductal gray area and basal ganglia. In addition, across different symptom domains, several studies reported abnormal recruitment of ventromedial prefrontal cortex (vmPFC), a region known to regulate emotion appraisal, memory retrieval, and self-reflective representations. The vmPFC might provide important modulatory signals to both cortical and subcortical sensorimotor, visual, and even memory circuits, promoting maladaptive self-protective behaviors based on personal affective appraisals of particular events. A better understanding of such a role of vmPFC in FND may help link how and why these symptoms are produced. Further research is also needed to determine brain activation patterns associated with FND across different types of deficits and different evolution stages (e.g., acute vs. chronic vs. recovered).