Neurophysiologie Clinique/Clinical Neurophysiology (2014) 44, 339—342

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Functional neurological disorders: Imaging Neuro-imagerie des troubles neurologiques d’origine fonctionnelle V. Voon ∗ Department of Psychiatry, University of Cambridge, Cambridgeshire, United Kingdom Received 30 March 2014; accepted 27 July 2014 Available online 20 August 2014

KEYWORDS Functional neurological disorders; Conversion disorders; Functional neuroimaging; Motor deficit; Self-monitoring; Internal representations; Voluntariness; Arousal; Trauma

MOTS CLÉS Troubles neurologiques fonctionnels ; Conversion ; Hystérie ; Neuro-imagerie fonctionnelle ;

Summary Functional neurological disorders, also known as conversion disorder, are unexplained neurological symptoms. These symptoms are common and can be associated with significant consequences. This review covers the neuroimaging literature focusing on functional motor symptoms including motor functioning and upstream influences including self-monitoring and internal representations, voluntariness and arousal and trauma. © 2014 Published by Elsevier Masson SAS.

Résumé Les troubles neurologiques d’origine fonctionnelle, également désignés sous le terme de « troubles conversifs », rassemblent un ensemble de symptômes neurologiques qui ne trouvent aucune explication. De tels symptômes ne sont pas rares et peuvent avoir des répercussions très significatives. Cet article de revue est consacré à la neuro-imagerie des troubles

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Déficit moteur ; Autocontrôle ; Modèles internes ; Volonté ; Excitation ; Traumatisme

V. Voon neurologiques moteurs d’origine fonctionnelle et de l’influence, sur la motricité, de processus en amont tels que l’autocontrôle, les représentations internes, la volonté, l’excitation et le trauma. © 2014 Publi´ e par Elsevier Masson SAS.

Introduction Functional neurological disorders (FND) or conversion disorder are unexplained neurological symptoms. Although unexplained neurological symptoms are very common, the underlying mechanisms are poorly understood. An increasing number of studies have focused on the underlying neurophysiological mechanisms. This review will concentrate on the neuroimaging literature specifically in motor conversion disorders. Several terms will be used including conversion disorder, FND, psychogenic movement disorder (PMD), and non-epileptic seizure (NES). Amongst the diverse presentations of functional symptoms in neurology, this review focuses on motor FND, discussing motor functioning and upstream influences including self-monitoring and internal representations, voluntariness and arousal and trauma.

Motor function Motor function in FND has been the subject of studies addressing motor conceptualization or preparation [12], or inhibition of motor execution [10]. Spence et al. showed in a small PET study using joystick movement that unilateral conversion paralysis (n = 3) was associated with decreased left dorsolateral prefrontal cortex (DLPFC) activity, while the opposite was observed in feigned paralysis [12]. The authors suggest a possible impairment in higher-order internal generation or conceptualization of action. In a larger fMRI study (n = 11), Voon et al. focusing on freely chosen and cued actions in subjects with conversion motor symptoms, showed decreased supplementary motor area (SMA) activity and increased limbic (amygdala, anterior insula) activity during motor preparation compared to healthy volunteers [15]. Conversion disorder subjects had decreased functional connectivity between the DLPFC and SMA in the comparison of freely chosen vs cued voluntary movements, suggesting a possible impairment in higher-order action selection during voluntary movements. In contrast, in a within-subject study in conversion paralysis, de Lange et al. showed that cued implicit motor imagery of the affected arm is associated with opposite increase in DLPFC-SMA functional connectivity compared to the unaffected arm, thus differentiating from voluntary movements [8]. The SMA is implicated in the subjective urge and intention to move and the DLPFC in action selection and attentional processes. In contrast, several imaging studies have focused on the inhibition of motor execution. In an early classic case study of conversion paralysis, Marshall et al. showed that preparation to move was intact but that attempted movement vs preparation increased right anterior cingulate and orbitofrontal cortex activity. The authors suggest that these

findings reflect inhibition of execution by prefrontal regions [10]. An early small study of hypnotic paralysis by Halligan et al. observed similar anterior cingulate and orbitofrontal cortex activations during attempted movement [9]. Similarly, Deeley et al. using a within-subject design (n = 8) controlling for depth of hypnosis showing greater anterior cingulate and SMA activity during attempted movement in hypnotic paralysis compared to feigned paralysis but did not show abnormalities in the orbitofrontal cortex [7]. These findings suggest possible similarities between FND and hypnosis, which the authors suggest may be related to the role of the anterior cingulate in inhibitory processes but may also be implicated in action monitoring or response conflict. In a study using a motor inhibitory (go/nogo task) fMRI task comparing one patient with conversion paralysis and 30 healthy volunteers, Cojan et al. showed normal preparatory activity in motor cortices and decreased contralateral motor cortex activity during movement suggesting a primary impairment in execution [4]. Subjects with feigned paralysis engaged a voluntary motor inhibitory process (right inferior frontal cortex) during response inhibition but conversion paralysis did not, suggesting alternative mechanisms to voluntary motor response inhibition [4]. The authors thus suggest that there was no evidence for impaired intention or inhibitory processes but rather implicate the influence of internally generated thoughts influencing motor activity.

Self-monitoring Neural regions involved in self-monitoring, or the default mode network, have been implicated in conversion disorder. De Lange et al. showed that implicitly induced motor imagery of the affected hand recruited the ventromedial prefrontal cortex (VMPFC) and superior temporal cortices in an fMRI study of conversion paralysis as compared to the unaffected hand, suggesting heightened self-monitoring [8]. Similarly, in a SPECT study, Czarnecki et al. showed that conversion tremor subjects had decreased VMPFC rCBF during a tremor-inducing motor task, which were not observed in essential tremor [5]. Using the go/nogo task, Cojan et al. further showed in the patient with conversion paralysis, greater functional connectivity between the VMPFC, precuneus and posterior cingulate cortex with right M1, suggesting a role for internal self-related representations in influencing motor activity [4]. Similarly, Cojan et al. studied hypnotic paralysis using a similar go/nogo task [4], showing similarities in precuneus activity and functional connectivity between the precuneus and motor cortex [3] with no evidence of impairments in motor intention or inhibition. The authors propose that suggestion in both hypnosis and conversion

Functional neurological disorders: Imaging disorder might act through self-monitoring processes to allow internal representations to guide behavior.

Involuntariness Conversion motor positive symptoms are experienced as involuntary, or out-of-the-person’s control, a process known as impaired self-agency. This experience of involuntariness was indirectly addressed by Voon et al., who compared conversion tremor with voluntary mimicked tremor in a within-subject design (n = 8), showing decreased right temporoparietal junction (TPJ) activity [16]. Lower functional connectivity was observed between the right TPJ and regions involved in sensory feedback (sensorimotor cortices and cerebellar vermis) and limbic regions (ventral anterior cingulate and ventral striatum) in conversion vs voluntary tremor [16]. Motor control is believed to follow a feedforward model, in which self-generated movements are accompanied by a sensory prediction of the motor outcome, which is compared to the actual sensory outcome for online adjustment of motor control. The movement prediction usually matches the sensory outcome, giving rise to a sense of self-agency whereas a mismatch may give rise to a loss of self-agency. The right TPJ has been proposed to act as a comparator of internal predictions with actual external events underlying processes such as agency, theory of mind and attention [6]. Since sensory feedback appeared to be intact, the decrease in TPJ activity was proposed to represent an abnormality in internal prediction, leading to a mismatch of prediction and outcome, decreased TPJ comparator activity and the experience that the movement was not under the subject’s control.

Arousal and trauma The influence of arousal was assessed by Voon et al. in motor conversion disorder subjects (n = 16) showing greater amygdala activity to arousing positive and negative facial stimuli compared to healthy volunteers [14]. Arousing stimuli were also associated with greater amygdala-SMA functional connectivity in conversion disorder subjects. However, not all studies have replicated these findings. Van der Kruijs et al. using positive outdoor images and with a Stroop task studying PNES subjects (n = 11) did not show any differences compared to healthy controls [13]. Using a vocalization task in a single within-subject case of mutism, Bryant and Das showed, after speech recovery but not during mutism, greater functional connectivity between inferior frontal gyrus activity and anterior cingulate activity and lower connectivity with amygdala [2]. Aybek et al. compared stressful life events in motor CD (n = 12) with healthy controls (n = 13) focusing on Escape (defined as the threat and extent to which illness might allow escape from the consequences) compared to Severity (equally threatening control events) [1]. The Escape events were associated with longer reaction times and were subjectively less upsetting than severe events. In the contrast of Escape—Severe, CD patients had greater left DLPFC and decreased left hippocampal activity along with increased right SMA and temporoparietal junction activity. These findings were suggested to support the Freudian

341 concept of repression with greater DLPFC activity with memory repression and lower hippocampal activity with a subjective decrease in the experience of the memory but with a ‘conversion’ of symptoms with greater SMA activity. CD patients had lower right inferior frontal cortex activity for both Escape and Severe events suggesting a role for cognitive control. Greater functional connectivity between amygdala and SMA for both Escape and Severe events were consistent with previous findings of greater limbic-motor interaction [14].

Striatal activity Aberrant striatal activity has been shown in studies on conversion paralysis and dystonia, which may provide an anatomical link between the amygdala and SMA allowing motor and limbic interactions. Using SPECT with a passive vibration task, Vuilleumier et al. showed that patients with unilateral sensorimotor loss (n = 7) had decreased contralateral thalamic and basal ganglia activity with caudate hypoactivity predicting poor recovery [17]. Schrag et al. compared paced ankle movements, fixed posture and rest using PET in patients with unilateral psychogenic dystonia (n = 6) and organic dystonia (DYT1; n = 5) and healthy volunteers (n = 6) [11]. Psychogenic dystonia was associated with greater basal ganglia and decreased primary motor cortical blood flow compared to healthy volunteers and organic dystonia across all tasks. Greater right DLPFC activation was observed in both psychogenic and organic dystonia during movement compared to rest. The authors suggest that whereas abnormal prefrontal activity may be common to both organic and psychogenic disorders, abnormal basal ganglia activity may be specific to psychogenic dystonia. Differences in the direction of basal ganglia activity may be a function of the symptom presentation (paralysis vs dystonia) or task (passive vibration vs movement).

Conclusion Imaging studies in motor FND implicate possible influences of self-monitoring or internal representations along with processes related to arousal and trauma that may interfere with motor functioning. Further imaging studies are indicated including addressing the role of expectations and attention.

Disclosure of interest The author declares that she has no conflicts of interest concerning this article.

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Functional neurological disorders: imaging.

Functional neurological disorders, also known as conversion disorder, are unexplained neurological symptoms. These symptoms are common and can be asso...
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