Conversion disorder is characterized in the Diagnostic and Statistical Manual of Mental Disorders, Version IV, 1994
by neurological signs and symptoms such as movements, seizures or sensory symptoms unrelated to an underlying neurological or medical disorder. Unexplained neurological symptoms are common and reported in 30% of general neurology clinics (Carson et al.
) and are the cause of prominent disability (Carson et al.
), yet the mechanisms are very poorly understood.
Functional imaging studies have focused on conversion paralysis or the absence of movement. The main hypotheses to explain conversion paralysis include either impairments in the generation of motor intention (Spence et al.
; Roelofs et al.
; Burgmer et al.
) or that motor intention is intact but execution is disrupted (Marshall et al.
; Cojan et al.
). Furthermore, impairments in self-monitoring (de Lange et al.
; Cojan et al.
), limbic processing or higher order regulation (Tiihonen et al.
; Marshall et al.
) have been proposed to inhibit motor execution (reviewed in Nowak and Fink, 2009
). In this study, we focused on conversion disorder with positive motor symptoms such as tremor, dystonia, chorea, tics and gait disorders rather than conversion paralysis. We hypothesize that there may be mechanistic differences between conversion disorders resulting in the absence or presence of movement. For instance, the generation of positive conversion motor symptoms may be characterized by abnormalities in the conversion motor representation possibly through implicit learning processes, or implicate abnormal action selection processes such as excessive facilitation or impaired inhibition. Whether the abnormalities of conversion motor symptoms versus conversion paralysis may implicate a different process (e.g. abnormal action selection at the level of initiation rather than inhibition of motor execution), and hence a different neural network, is not known. Although motor network abnormalities may possibly differ, we further hypothesize that similar to that of conversion paralysis, upstream inputs such as emotion, arousal or hyperactive self-monitoring may also play a role in interfering with these processes. In this study, we focus on these upstream inputs of emotion or arousal and its role in the pathophysiology of conversion disorder with positive motor symptoms.
Several lines of evidence suggest a relationship between conversion disorder and psychological issues. For instance, patients with conversion disorder have a high frequency of comorbid depressive and anxiety symptoms (Bowman and Markand, 1996
; Sar et al.
) and conversion disorder symptom severity is associated with more frequent early and later adverse life events (Bowman, 1993
; Roelofs et al.
). In an early paper, Lader and Sartorius (1968
) demonstrated that patients with mixed active conversion disorder symptoms failed to habituate skin conductance to repeated auditory stimuli compared with control patients with anxiety and to healthy volunteers (Lader and Sartorius, 1968
). The patients with conversion disorder also had higher baseline arousal levels as measured by the rate of spontaneous fluctuation in skin resistance as compared with the control patients with ‘anxiety’ and healthy volunteers. As the failure to habituate has been inversely correlated with high arousal level, other authors (Horvath et al.
) have suggested that the Lader and Sartorius (1968
) findings may be related to the demonstrated high arousal levels. Horvath et al.
) extended these findings in patients with remitted mixed conversion disorder symptoms compared with control subjects with ‘free floating anxiety’ emphasizing a failure to habituate in skin conductance response to repeated acoustic stimuli with normal baseline responses (Horvath et al.
). The authors suggest the findings may reflect either greater arousal or a failure to inhibit the orienting response to a familiar stimulus, which may be a risk factor for the development of conversion disorders. More recently, patients with non-epileptic seizures have been shown to have higher basal cortisol levels compared with healthy volunteers, which is a marker of stress levels, unrelated to seizure frequency, physical activity or acute psychological stress (Bakvis et al.
, in press). Patients with non-epileptic seizures also have greater vigilant attentional bias towards threat stimuli (angry faces) in a masked emotional Stroop task, a bias that positively correlates with baseline cortisol levels (Bakvis et al.
). Both the baseline cortisol levels and increased threat vigilance were more likely in patients with a history of sexual abuse (Bakvis et al.
, in press). Patients with non-epileptic seizure also have reduced heart rate variability and increased threat vigilance compared with healthy volunteers (Bakvis et al.
). Finally, patients with psychogenic movement disorder, another form of conversion disorder characterized by abnormal movements, were demonstrated to have greater startle response to both positive and negative affective stimuli compared with healthy volunteers linking arousal to a reflexive motor response (Seignourel et al.
). In summary, patients with conversion disorder mixed symptoms appear to be associated with greater arousal during the illness state (e.g. galvanic skin response, baseline cortisol, reduced heart rate variability, greater threat vigilance, greater startle response to arousing stimuli). The extent of previous exposure to childhood sexual abuse may also modulate measures including the baseline cortisol levels and threat vigilance (Roelofs and Spinhoven, 2007
Preliminary data from neuroimaging studies provide information on possible networks engaging limbic and motor regions that may be involved in conversion paralysis. Studies demonstrate the engagement of regions in the limbic-motor interface to attempted or imagined movement (ventromedial prefrontal cortex) and non-noxious brush stimuli (caudate/putamen) in conversion paralysis. These regions have been suggested as potential nodal points for emotional stimuli to influence motor mechanisms (Marshall et al.
; Vuilleumier et al.
; de Lange et al.
). Furthermore, a patient with conversion paralysis was demonstrated to have greater amygdala activity and lower motor cortex activity to recall of a personal emotionally distressing event (Kanaan et al.
). Finally, a comparison of one patient with conversion paralysis and 30 healthy volunteers showed greater functional connectivity between the right motor cortex and posterior cingulate during a go/no-go task, leading the authors to suggest that internal monitoring of memories or emotional states may play a role in interfering with motor execution (Cojan et al.
The literature suggests a potential role between arousal and conversion disorder that may play a role in modulating motor networks, resulting in the abnormal conversion motor symptom. We sought to investigate the relationship between affect or arousal and conversion disorder with positive motor symptoms (herein referred to as motor conversion disorder) by investigating amygdala activity in association with viewing affective stimuli in a large patient sample size. We use an affective task that has been extensively investigated in healthy volunteers and patients with psychiatric disorders. Healthy volunteers have been well-documented to have greater amygdala activity to both negative and positive emotional stimuli relative to neutral stimuli along with greater activity to negative relative to positive stimuli (Breiter et al.
; Morris et al.
; Costafreda et al.
). We hypothesized that motor conversion disorder would be associated with greater amygdala activity to both positive and negative affective stimuli.