Rev. Neurosci.

2017; aop

Ismael Conejero*, Eric Thouvenot, Mocrane Abbar, Stéphane Mouchabac,

Philippe Courtet and Emilie Olié

Neuroanatomy of conversion disorder: towards a

network approach
https://doi.org/10.1515/revneuro-2017-0041 Some findings suggest that conceptualisation of move-
Received June 18, 2017; accepted September 16, 2017 ment and motor intention is preserved in patients with
limb weakness. More studies are needed to fully under-
Abstract: The pathophysiology of conversion disorder
stand the brain alterations in conversion disorders and
is not well understood, although studies using func-
pave the way for the development of effective therapeutic
tional brain imaging in patients with motor and sensory
strategies.
symptoms are progressively increasing. We conducted a
systematic review of the literature with the aim of sum- Keywords: conversion disorder; functional neurological
marising the available data on the neuroanatomical fea- symptoms; neuroimaging; pathophysiology; psychogenic
tures of this disorder. We also propose a general model movement disorder.
of the neurobiological disturbance in motor conversion
disorder. We systematically searched articles in Medline
using the Medical Subject Headings terms ‘(conversion
disorder or hysterical motor disorder) and (neuropsychol-
Introduction
ogy or cognition) or (functional magnetic resonance imag-
Conversion disorder (CD) also called ‘functional neurologi-
ing or positron emission tomography or neuroimaging) or
cal disorder’ [Diagnostic and Statistical Manual of Mental
(genetics or polymorphisms or epigenetics) or (biomarkers
Disorders, Fifth Edition (DSM-5); American Psychiatric
or biology)’, following the Preferred Reporting Items for
Association, 2013] is a common psychiatric condition. The
Systematic Reviews and Meta-Analyses guidelines. Two
prevalence ranges from 1% to 10% in medicine or surgery
authors independently reviewed the retrieved records and
departments, and up to 30% in neurology departments
abstracts, assessed the exhaustiveness of data abstrac-
(Carson et al., 2000). CD is characterised by the presence
tion, and confirmed the quality rating. Analysis of the
of non-simulated neurological symptoms or deficits that
available literature data shows that multiple specialised
affect voluntary motor or sensory functions. This suggests
brain networks (self-agency, action monitoring, salience
that CD is a central nervous system disorder, but not caused
system, and memory suppression) influence action selec-
by a neurological injury or a general medical condition. In
tion and modulate supplementary motor area activation.
2009, Gupta and Lang revised the classification by Fahn,
and proposed that such deficits could be defined by using
*Corresponding author: Ismael Conejero, Department of Psychiatry, clinical and laboratory tests, such as electrophysiology
CHU de Nîmes, Place du Professeur Robert Debré, F-30900 Nîmes,
(Gupta and Lang, 2009). However, they omitted the contri-
France; and University of Montpellier, F-34090 Montpellier, France,
e-mail: ismael.conejero@gmail.com
bution of ‘modern’ techniques, such as functional imaging.
Eric Thouvenot: Department of Neurology, CHU de Nîmes, The functional and biological mechanisms underlying
F-30900 Nîmes, France; University of Montpellier, F-34090 CD need to be precisely determined for several reasons: (i)
Montpellier, France; and Institut de Génomique Fonctionnelle, to improve the diagnostic approach with reliable biomark-
UMR5203, Université de Montpellier, F-34295 Montpellier, France ers, (ii) to develop rational therapeutic strategies, and (iii)
Mocrane Abbar: Department of Psychiatry, CHU de Nîmes, Place du
to understand the links between the emotional and sen-
Professeur Robert Debré, F-30900 Nîmes, France
Stéphane Mouchabac: Department of Psychiatry, Assistance sory-motor systems.
Publique, Hôpitaux de Paris, Hopital Saint Antoine, F-75012 Paris, Therefore, we conducted a systematic review of the
France literature to summarise the recent brain imaging findings
Philippe Courtet and Emilie Olié: Department of Emergency on the neuroanatomical features associated with motor
Psychiatry and Post-Acute Care, Hôpital Lapeyronie, CHU
and sensitive CD. We also propose a general model to
de Montpellier, F-34295 Montpellier, France; Inserm Unit
1061 ‘Neuropsychiatry: Epidemiological and Clinical Research’,
explain CD pathophysiology and the functional networks
F-34295 Montpellier, France; and University of Montpellier, associated with each clinical dimension of this disorder
F-34090 Montpellier, France (Figure 1).

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2      I. Conejero et al.: Neuroanatomy of conversion disorder
A: Memory suppression
B: Action monitoring D: Selection of motor patterns
E: Self-agency
Figure 1: Proposed model.
Relationships between dysfunctional brain networks in motor conversion disorders. Memory suppression (A), action monitoring (B), sali-
ence network (C), and self-agency (E) alter selection of motor patterns (D). , Hyperactivated regions; , hypoactivated regions.
Methods
Search criteria
We systematically searched articles in Medline using the
Medical Subject Headings terms ‘(conversion disorder
or hysterical motor disorder) and (neuropsychology or
cognition) or (functional magnetic resonance imaging
or positron emission tomography or neuroimaging) or
(genetics or polymorphisms or epigenetics) or (biomark-
ers or biology)’, following the Preferred Reporting Items
for Systematic Reviews and Meta-Analyses guidelines
(Moher et  al., 2009; Shamseer et  al., 2015). Within the
reviewing team, IC and EO independently reviewed the
retrieved records and abstracts, assessed the exhaustive-
ness of data abstraction, and confirmed the quality rating.
Selection criteria
Studies were included if they met the following criteria: (i)
studies on pathophysiological aspects of CD, (ii) original
C: Salience network
articles or case reports with neuroimaging assessment,
and (iii) studies written in English. The exclusion crite-
ria were (i) studies on somatoform disorders, (ii) studies
on dissociative disorders, (iii) literature reviews, and (iv)
studies written in other languages than English (Figure 2).
Quoted neuroimaging studies are listed in the tables.
Results
Functional neuroimaging data: motor
symptoms
Motor imagery and movement tasks
Together with the production of standardised movement,
functional neuroimaging during motor imagery is a major
tool for assessing the motor system function (Table 1). It
corresponds to the mental representation of movements
that occur during the preparation phase before movement
execution. Motor imagery evaluation through specific tasks,
such as mental rotation, contributes to CD understanding.
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Records identified with the PubMed search
(n = 947)
Duplicates, editorials, conceptual texts, reviews, articles
not written in English (n = 817 items removed)
Retained records
(n = 130)
Full-text articles assessed
for eligibility
(n = 27)
Studies included in the qualitative
review (n = 82)
Figure 2: Study flow chart.
The activation of the primary motor cortex during
motor imagery and execution of movements remains
controversial in patients with motor CD. Burgmer et  al.
(2006) assessed cerebral activation in patients with con-
version hemiparesis who were asked to observe and then
reproduce a movement displayed on a screen. Compared
with controls, motor cortex was hypoactivated in patients
during the observation phase, but not during the move-
ment execution. This suggests an alteration of movement
conceptualisation. Conversely, Marshall et al. (1997) and
Cojan et al. (2009) showed adequate motor cortex activa-
tion during motor preparation in patients with hysterical
paralysis, whereas the primary motor cortex was deacti-
vated during the execution phase. Furthermore, normal
premotor activation was reported during motor imagery
in patients with functional lateralised paresis without
between-hand differences (de Lange et al., 2008). Finally,
van Beilen et al. (2011) reported increased activity of the
primary motor cortex and left anterior cingulate cortex
(ACC) and reduced activity of prefrontal areas during
movement of the affected hand. They also found decreased
I. Conejero et al.: Neuroanatomy of conversion disorder      3
Records removed (n = 103) because:
– Somatoform disorder
– No link with biological
mechanisms
– Case reports without functional
neuroimaging
Additional records identified through
other sources
(n = 55)
parietal cortex (supramarginal gyrus) activation during
motor imagery and movement execution, independently
of the side of motor deficit.
The supplementary motor area, a region adjacent
to the primary motor cortex, has been involved in motor
CD with positive symptoms (tremor and abnormal move-
ments). The supplementary motor area is considered
as a ‘supramotor’ area and plays a central role in action
selection. It controls the forces used to carry out complex
motor sequences. Voon et al. (2011) found that during an
action selection task, supplementary motor area activ-
ity decreases during the movement preparation phase
as well as the functional connectivity between the dorso-
lateral prefrontal cortex and supplementary motor area
(11 patients with CD and 11 controls). Dysfunctional top-
down control by the dorsolateral prefrontal cortex was
also observed when evaluating limb weakness by using
positron emission tomography (PET) imaging: the left dor-
solateral prefrontal cortex was hypoactivated in patients
with CD and the right dorsolateral prefrontal cortex in
feigners (Spence et al., 2000). Altogether, the dysfunction
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 Table 1: Functional neuroimaging data for motor CDs.

Study   Clinical description   Sample   Imaging   Task   Results

technique

Marshall et al. (1997)   L hemiparesis   1 Patient   PET scan   Movement preparation and   ↑ R ACC/OFC when trying to move L leg; no activation of R
execution premotor/motor cortex when trying to move L leg
Spence et al. (2000)   Limb paresis   3 Patients,   PET scan   Movement task and feigning   ↓ L DLPFC when moving the affected limb in patients vs. feigners
6 controls, paresis and controls
4 feigners
Vuilleumier et al.   Lateralised paresis   7 Patients   SPECT   Bilateral hand vibration   ↓ Activity of thalamus and basal ganglia contralateral to the
(2001) (<2 months) deficit; normalised activity with recovery
Burgmer et al. (2006)   Hemiparesis (arm and leg)   4 Patients,   fMRI   Motor imagery and   ↓ Motor cortex during movement observation in patients vs.
7 controls movement task controls
de Lange et al. (2007)  Lateralised arm paralysis   8 Patients   fMRI   Implicit motor imagery   ↑ Activity of dorso-medial and vmPFC (affected vs. unaffected
hand)
Kanaan et al. (2007)   Psychogenic non- epileptic   1 Patient   fMRI   Recall of stressful life events  ↑ Activity of R medial temporal lobe, amygdala, IFC, parietal
seizures and right-sided cortex, cingulate, and SMA in repressed vs. equally severe event;
hemiplegia ↓ activity of L primary motor cortex (idem)
Stone et al. (2007)   Lateralised paresis   4 Patients,   fMRI   Movement task   ↑ Activity of putamen/lingual gyrus/L IFC/L insula in patients vs.
4      I. Conejero et al.: Neuroanatomy of conversion disorder

4 controls feigners; ↓ activity of R OFC/middle frontal cortex in patients vs.

feigners
de Lange et al.   Lateralised arm paralysis   7 Patients   fMRI   Implicit and explicit motor   ↑ Activity of dorso-medial, vmPFC and premotor cortex (M1); no
(2008)a imagery task difference between hands with explicit motor imagery
Cojan et al. (2009)   L hand paresis   1 Patient,   fMRI   Go/No Go   ↑ L OFC/ventral mPFC/PCC when preparing to move L hand; ↑
30 controls ventral mPFC/precuneus when L hand – Go; ↑ IFG when L hand
– No Go; ↓ R motor cortex when trying to move L hand
de Lange et al.   Lateralised arm paralysis   8 Patients   fMRI   Implicit motor imagery task   ↑Fc between mPFC and temporal cortex in affected vs. unaffected
(2010)a hand; ↑Fc between DLPFC and motor cortex in affected vs.
unaffected hand
Voon et al. (2010a)   Tremor, dystonia, gait   16 Patients,   fMRI   Affective face stimuli   No amygdala habituation; no difference in fearful-neutral vs.
abnormalities 16 controls happy-neutral condition; ↑ Fc between R amygdala and R SMA in
patients vs. controls
Voon et al. (2010b)   Psychogenic movement   8 Patients   fMRI   Conversion vs. mimicked   ↓ R TPJ in conversion vs. mimicked tremor; ↓ Fc between TPJ/
disorder tremor sensorimotor/limbic region
Voon et al. (2011)   Positive motor symptoms   11 Patients,   fMRI   Action selection task   ↑ R amygdala/L insula/bilateral post cingulate in patients vs.
11 controls controls; ↓ L SMA in patients vs. controls; ↓ Fc between DLPFC
and L SMA in internally vs. externally generated action

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 Table 1 (continued)

Study   Clinical description   Sample   Imaging   Task   Results

technique

van Beilen et al.   Lateralised paresis   9 Patients,   fMRI   Movement execution and   ↑ Activity of ipsilateral motor cortex during motor execution in
(2011) 21 controls motor imagery patients vs. controls; ↑ activity of ipsilateral ACC during motor
execution in patients vs. controls; ↓ activity of ipsilateral PFC
during motor execution in patients vs. controls; ↓ activity of
supramarginal gyrus during motor imagery in patients vs. controls
van der Kruijs et al.   Psychogenic non-epileptic   11 Patients,   fMRI   Resting-state imaging   ↑Fc between insula/IFC/precentral sulcus in patients vs. controls
(2012) seizures 12 controls (seed-based measure of
functional connectivity)
Aybek et al. (2014a)   Sensory-motor loss   12 Patients,   fMRI   Recall life events   ↑L DLPFC/R SMA/R TPJ and ↓ L hippocampus (escape vs. severe
13 controls condition) in patients vs. controls; no activation R IFC; ↑ Fc
between R SMA/L amygdala in patients vs. controls
van der Kruijs et al.   Psychogenic non-epileptic   21 Patients,   fMRI   Resting-state imaging   ↑ Fc in fronto-parietal/executive control/sensorimotor/default
(2014) seizures 27 controls mode networks in patients vs. controls
Saj et al. (2014)   Paraplegia   2 Patients,   fMRI   Movement task and explicit   ↑ Activity of bilateral insula in movement and motor imagery of
6 controls motor imagery affected vs. unaffected limb; ↑ activity of L ACC in motor imagery
of affected vs. unaffected limb
Aybek et al. (2015)   Sensory-motor loss   12 Patients,   fMRI   Affective face stimuli   ↑ L amygdala when negative stimuli and sensitisation of
14 controls amygdala in patients vs. controls; ↑ activity of midbrain and
superior frontal regions
Arthuis et al. (2015)   Psychogenic non- epileptic   16 Patients,   PET scan   Resting-state imaging   ↓ Activity of right parietal and bilateral ACC in patients vs.
seizures 16 controls controls; ↑ Fc between R parietal and bilateral cerebellum; ↑ Fc
between bilateral ACC and L parahippocampal gyrus
Hassa et al. (2016)   Lateralised paresis   13 Patients,   fMRI   Passive motor stimulation   ↓ Activity of mPFC in patients vs. non-feigning controls; ↑ mPFC
12 controls in patients vs. feigning controls; ↑ IFG in patients and feigning
controls vs. non-feigning controls

Fc, Functional connectivity; SMA, supplementary motor area; TPJ, temporo-parietal junction; ACC, anterior cingulate cortex; OFC, orbitofrontal cortex; IFC, inferior frontal cortex; DLPFC, dorsolat-
eral prefrontal cortex; mPFC, medial prefrontal cortex; SPECT, single-photon emission computed tomography; R, right; L, left.
a
Studies performed with the same data.

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I. Conejero et al.: Neuroanatomy of conversion disorder      5
6      I. Conejero et al.: Neuroanatomy of conversion disorder
of the supplementary motor area and dorsolateral prefron-
tal cortex suggests that patients with CD cannot properly
control the selection of neural patterns related to action.
The left ACC and insula, which are involved in body
representation (Haggard et al., 2013) and are part of sali-
ency and monitoring networks, could also play a role in
motor imagery. Mental rotation of the affected leg has been
associated with activation of the left ACC in patients with
acute conversion paraplegia (Saj et  al., 2014). Moreover,
bilateral insular cortex activation is increased during
motor imagery and movement of the legs compared with
the arms. Stone et al. (2007) evaluated patients and healthy
feigners, and showed an increased activation of the left
insula, bilateral putamen, and lingual gyri only in patients
when moving the affected but not the unaffected limb.
Besides the dysfunction of the left ACC and insula
related to motor weakness, positive motor symptoms were
associated with altered activation of brain regions that
support self-agency. Voon et  al. (2010b) showed hypo-
activation of the temporo-parietal junction (TPJ) and a
decreased functional connectivity between the TPJ, limbic
cortex, and sensorimotor cortex in conversion compared
with mimicked (voluntary) tremor in eight patients. Brain
regions that support action self-monitoring are activated
in patients with CD during mental rotation tasks (also
called implicit motor imagery tasks). Participants are
asked to judge on the laterality of a pivoting hand dis-
played on a screen and mentally rotate their own corre-
sponding hand for this purpose (Parsons, 1987). A study
on eight patients showed hyperactivation of the ventro-
medial prefrontal cortex (vmPFC) and superior temporal
cortex when considering the affected hand (de Lange
et  al., 2007). Similarly, vmPFC activity increases when
patients with CD are asked to imagine their own hand
moving (explicit motor imagery task) (de Lange et  al.,
2008). Thus, CD may be associated with greater monitor-
ing of self-initiated actions (i.e. self-monitoring), related
to vmPFC overactivation. Other studies highlighted the
possible involvement of self-monitoring also during move-
ment execution. Cojan et  al. (2009) reported increased
activation of the vmPFC, posterior cingulate cortex, and
precuneus, as well as increased functional connectivity
between these brain regions, which belong to the default
mode network, and the primary motor cortex (Cojan et al.,
2009), although these regions should be deactivated
during movement (Damoiseaux et al., 2006). Hassa et al.
(2016) assessed the activation of the medial prefrontal
cortex (mPFC) during passive movements of the affected
hand in patients with CD compared with healthy con-
trols (assessed in feigning and non-feigning condition).
Compared with non-feigners, mPFC was less activated
in patients, but activation remained higher than during
feigning. Such mPFC mid-level activation could explain
the disturbance of self-monitoring in CD (Hassa et  al.,
2016). Finally, the evaluation of eight patients with lat-
eralised conversion paresis using motor imagery of the
affected hand (de Lange et  al., 2010) suggested that the
dorsolateral prefrontal cortex is strongly connected with
the motor system and may mediate the vmPFC influence
on the motor area. Altogether, these results underline the
involvement of altered self-monitoring and default mode
network deactivation in CD.
Resting-state brain imaging
Resting-state functional neuroimaging studies have been
conducted in patients with psychogenic non-epileptic
seizures (PNES), which are a motor subtype of CD accord-
ing to DSM-5 (American Psychiatric Association, 2013).
A resting-state neuroimaging study in 21 patients with
PNES and 27  healthy controls showed increased func-
tional connectivity within the fronto-parietal network
and default mode network, positively associated with the
level of dissociation (van der Kruijs et  al., 2014). Func-
tional connectivity between the insula, inferior frontal
gyrus, and precentral regions was also positively cor-
related with the dissociation scores in patients with CD
(van der Kruijs et al., 2012). This tendency to dissociation
in CD could affect the executive control and promote the
direct influence of emotion on motor execution. Moreo-
ver, dysregulation of brain regions involved in emotion
processing has been emphasised. PET hypometabolism
within both ACC regions and increased functional con-
nectivity between both ACC regions and the left para-
hippocampal gyrus have been observed in patients
with PNES at rest, compared with controls (Arthuis
et  al., 2015). Thus, dysregulated emotional states could
bypass the executive control and induce abnormal move-
ments by directly influencing motor planning regions.
Conversely, organic epilepsy has been associated with
decreased functional default mode network connectivity
(Luo et al., 2011; Song et al., 2011).
Affective and sensory tasks
Results of imaging studies that investigated emotional
processing in CD underline the role of the amygdala in
saliency detection, thus allowing individuals to focus
their cognitive resources towards the most relevant
subset of available sensory data. Aybek et  al. (2015)
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showed increased activation of the left amygdala in
patients with motor CD (n = 12) when viewing negative
(fearful and sad) faces, compared with 14  healthy con-
trols (Aybek et  al., 2015). Conversely, greater activation
of the right amygdala was reported in patients with CD
when viewing happy but not fearful faces, and increased
functional connectivity between the right amygdala
and the supplementary motor area (Voon et al., 2010a).
The lack of habituation of the right amygdala to salient
stimuli in this study could reflect the patients’ inability
to adapt and shift attentional resources towards the rel-
evant emotional situation. The amygdala might interact
with voluntary motor actions through the supplementary
motor area, which is involved in the automatic inhibi-
tion of primed actions and flexible volitional behaviour
(Sumner et al., 2007). This hypothesis was supported by
Sagaspe et al. (2011), who reported a modulation of brain
regions involved in motor control (supplementary motor
area) by the amygdala under the influence of emotional
cues, when healthy subjects performed a stop-signal
task (Sagaspe et al., 2011).
Other brain regions involved in the behavioural
response to danger show overactivation in patients with
motor CD. Hyperactivation of the midbrain and periaque-
ductal grey matter (PAG) was reported in patients com-
pared with healthy controls (Aybek et al., 2015). The PAG is
a major site for processing fear and anxiety, and supports
the primitive freezing response (i.e. arrest of somatomotor
activity related to danger).
Moreover, memory of past threatening life events
could be altered and affect CD pathogenesis. A study
evaluated the neural correlates of recall of threatening life
events considered as potential CD triggers (Aybek et  al.,
2014b) by assessing the ‘escape condition’, which corre-
sponds to the recall of stressors that can be avoided by
developing the illness, and the ‘severe condition’, which
corresponds to the recall of non-escapable life events.
Compared with healthy controls, patients with CD pre-
sented higher activation of the left dorsolateral prefron-
tal cortex and lower activation of the hippocampus and
parahippocampal gyrus during the escape condition than
the severe condition. They also showed increased sup-
plementary motor area and TPJ activation. Event recall
in the escape condition is associated with dysregulation
of brain regions that control the emotional load (activa-
tion of the dorsolateral prefrontal cortex and deactivation
of hippocampal regions), motor planning (supplemen-
tary motor area activation), and sensory integration (TPJ
hyperactivation).
Moreover, in a 37-year-old woman with motor CD, the
recollection of stressful life events that precipitated the
I. Conejero et al.: Neuroanatomy of conversion disorder      7
symptoms, but not of other adverse or neutral events,
during neuroimaging was associated with hyperac-
tivation of the right amygdala and frontal lobe and
with hypoactivation of the motor cortex (Kanaan et al.,
2007). This suggests an association between recall of
clinically relevant stressors and activation of emotional
regions (limbic system) in motor CD. Impaired top-
down control of emotional arousal by the dorsolateral
prefrontal cortex occurs simultaneously with altered
motor activation.
Sensory tasks have been used to explore somatosen-
sory networks in patients with motor CD. The only pro-
spective study on CD was conducted by Vuilleumier et al.
(2001), who performed single-photon emission computed
tomography imaging in seven patients with unilateral
motor deficit during passive sensory stimulation at the
beginning of the symptoms and 2–4  months after recov-
ery. During the symptomatic phase but not after recovery,
stimulation was associated with decreased activation of
the contralateral thalamus, caudate, and putamen. There-
fore, deactivation of basal ganglia might be a key factor in
CD pathogenesis and was suggested to be associated with
poor recovery.
Altogether, the evaluation of emotion processing and
affective response in patients with CD highlights the role
of the amygdala and other limbic structures, such as the
dorsolateral prefrontal cortex and hippocampus, in CD
pathophysiology. These structures exert a behavioural
influence through supplementary motor area dysregu-
lation. Moreover, primitive protective mechanisms (the
freeze response) could play a role in conversion symptom
development.
Functional neuroimaging and sensory CDs
Besides motor CD, several neuroimaging studies have
been conducted to better understand the pathophysiol-
ogy of unexplained sensory loss (Table 2). In healthy
controls, vibrotactile stimulation triggers the activation
of the primary sensory and motor cortices, basal ganglia,
and thalamus (Seitz and Roland, 1992). Conversely, in a
functional magnetic resonance imaging (fMRI) study on
three patients with lateralised sensory loss, vibrotactile
stimulation of the numb limb failed to activate the con-
tralateral primary somatosensory (S1) area, whereas bilat-
eral stimulation activated both right and left S1 regions
(Ghaffar et  al., 2006). However, in the study by Vuille-
umier et al. (2001), bilateral vibrotactile stimulation was
not associated with decreased activation of the contralat-
eral S1 region, but rather with decreased activity of the
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8      I. Conejero et al.: Neuroanatomy of conversion disorder
Table 2: Functional neuroimaging data for sensory CDs.
Study   Clinical description   Sample  
Mailis-Gagnon et al.   Non-dermatomal   4 Patients   fMRI
(2003) sensory deficit
Werring et al. (2004)   Medically unexplained   5 Patients,   fMRI
visual loss 7 controls
Ghaffar et al. (2006)   Lateralised sensory   3 Patients   fMRI
loss
Becker et al. (2013)   Medically unexplained   1 Patient  
visual loss
Burke et al. (2014)   Lateralised sensory   10 Patients   fMRI
loss
thalamus and basal ganglia. Burke et al. (2014) reported
an increased activation of the right TPJ, bilateral dorso-
lateral prefrontal cortex, right orbitofrontal cortex, right
caudate, and left angular gyrus during stimulation of the
affected compared with the unaffected body part. Using
noxious and non-noxious stimuli, Mailis-Gagnon et  al.
(2003) showed activation of the rostral ACC and deacti-
vation of the S1 and S2 regions with unperceived but not
with perceived stimuli.
Brain activation related to unexplained visual loss
has also been studied. Patients showed lower activation
of the primary visual cortex and increased activation of
the left inferior frontal cortex, insula, striatum, posterior
cingulate cortex, and bilateral thalami during visual stim-
ulation (Werring et al., 2004). Furthermore, the evaluation
of a single patient with conversion blindness using fMRI
in symptomatic condition relative to the asymptomatic
state showed a hypoactivation of the occipital cortex
and a hyperactivation of emotion processing regions (the
angular gyrus bilaterally, the left medial frontal gyrus,
and the left ACC) in response to complex visual stimuli
(Becker et  al., 2013). However, cortex response to basic
visual stimuli was unaltered in this case.
Altogether, studies that assessed the neural corre-
lates of sensory CD suggest that activation of primary
sensory regions is not affected. However, as observed in
motor CD, limbic regions might play a role in the genesis
of conversion symptoms. The inferior frontal cortex, dor-
solateral prefrontal cortex, insula, and cingulate cortex
are involved in emotion processing and could modulate
Imaging   Protocol   Results
technique
  Noxious and non-   ↑ ACC in perceived vs. unperceived
noxious stimuli stimuli; ↓ S1, S2, posterior parietal
and frontal cortices, thalamus
  8-Hz visual   ↑ Activity of L IFC, insula, striatum,
stimulation bilateral thalami, L PCC in patients
vs. controls; ↓ activity of visual cortex
  Vibrotactile   ↓ Activity of contralateral S1 upon
stimulation anaesthetic limb stimulation
fMRI   fMRI during   ↑ Angular of gyrus bilaterally, left
symptomatic and medial frontal gyrus, and left ACC
asymptomatic states in symptomatic vs. asymptomatic
state; ↓ activity of visual cortex in
symptomatic vs. asymptomatic state
  Vibrotactile   ↑ Activity of R insula, ACC, TPJ, OFC,
stimulation caudate bilateral, DLPFC, L angular
gyrus (anaesthetic vs. contralateral
region)
the integration of sensory inputs, leading to clinical
sensory loss.
Structural neuroimaging and CD
In patients with lateralised motor conversion symptoms,
the volumes of the caudate nucleus (both sides) and of
the right (Atmaca et al., 2006) and left thalamus (Nichol-
son et al., 2014) are reduced compared with healthy con-
trols (Table 3). The thalamus nuclei, which are part of the
basal ganglia, modulate the motor signals and receive
motor afferent projections that go to the motor cortex
(Biane et al., 2016; Bickford, 2016; He et al., 2016). They
are closely linked to the supplementary motor area (Sakai
et al., 2002), and are involved in cortical and subcortical
loops to control movement engagement (Middleton and
Strick, 2000; Atmaca et al., 2006). Besides the alteration
of subcortical structures involved in controlling on-going
movements, other studies have highlighted modifications
in the volume of grey matter in the primary motor cortex.
Aybek et al. (2014a) reported increased cortical thickness
of the right and left premotor cortex in patients with CD
compared with healthy controls (Aybek et al., 2014a). Con-
versely, reduced cortical thickness of the right motor brain
regions was found in patients with PNES (Labate et  al.,
2012).
In addition to the altered cortical structure, decreased
pituitary gland volume was observed in patients with
PNES compared with healthy controls (Atmaca et  al.,
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 I. Conejero et al.: Neuroanatomy of conversion disorder      9

Table 3: Structural neuroimaging studies.

Study   Clinic   Participants   Imaging technique   Results

Atmaca et al.   Lateralised motor CD   12 Patients,   MRI   Decreased volume of bilateral caudate and
(2006) 12 controls lentiform nucleus, R thalamus
Labate et al.   Psychogenic non-epileptic   20 Patients,   MRI (voxel-based   Atrophy of R motor and premotor cortex
(2012) seizures 40 controls morphometry and (volume and thickness)
cortical thickness)
Nicholson et al.   Conversion motor deficits   15 Patients,   MRI   Decreased volume of L thalamus
(2014) 31 controls
Aybek et al.   Conversion motor deficits   15 Patients,   MRI (voxel-based   Increased cortical thickness of bilateral
(2014a) 25 controls morphometry and premotor cortex
cortical thickness)
Atmaca et al.   Motor symptoms and   20 Patients,   MRI   Decreased pituitary gland volume
(2015) pseudo-epileptic seizures 20 controls

2015). These findings may reflect a dysfunctional hypo-
thalamus-pituitary-adrenal axis and dysregulated stress
response related to CD.
prefrontal cortex could also play a role in suppression
of memories that could be involved in CD pathogenesis.
Hence, in patients with CD, recalling traumatic life events
increases dorsolateral prefrontal cortex activity together
with inhibition of hippocampal regions.

Discussion
General pathophysiological model
CD is characterised by functional and structural abnor-
malities of several regions: vmPFC, precuneus, amygdala,
ACC, supplementary motor area, dorsolateral prefrontal
cortex, and TPJ. These brain structures form networks that
are involved in CD pathophysiology and exert an influence
on primary motor and sensory areas. Considering brain
‘networks’ allows the development of new approaches in
brain disorder research. Indeed, CD can be considered as
a ‘global’ brain disease, and each dysfunctional network
may be linked to a cognitive dimension of this pathology.
Moreover, dysfunctional brain networks constitute new
therapeutic targets, for example when applying magnetic
or electric stimulation (Schönfeldt-Lecuona et al., 2016).
Regions involved in self-focused attention and action
monitoring (vmPFC, precuneus) show abnormal activa-
tion in CD. Moreover, dysfunction of the salience network
(amygdala, insula, and ACC) leads to inadequate alloca-
tion of cognitive resources to environmental stimuli and
is related to supplementary motor area and dorsolateral
prefrontal cortex alterations. These regions are involved in
action selection and its impairment could explain motor
symptoms.
In parallel, the dorsolateral prefrontal cortex, together
with the TPJ and angular gyrus, is involved in self-agency
and control over action. These three brain regions are
hypoactivated in patients with CD. The dorsolateral
Self-monitoring
Action monitoring may be defined as the capacity to eval-
uate the outcome of our actions and detect subsequent
errors (Bonini et  al., 2014). Increased action monitor-
ing and heightened self-referential processes have been
related to CD. For instance, with closed eyes, postural
instability is higher in patients with CD than in healthy
controls, whereas cognitive distraction (solving an atten-
tion-demanding task) leads to greater postural stability in
patients than in controls (Stins et al., 2015). Hence, self-
monitoring and cognitive control strongly influence pos-
tural balance in patients with motor CD, to the detriment
of more efficient and automatised control systems.
Brain structures involved in action monitoring show
altered activation in CD. Overactivation of vmPFC and ACC
occurs during motor imagery and mental rotation tasks.
The vmPFC is implicated in information processing about
environment and internal body states. It projects towards
limbic structures (nucleus accumbens, hypothalamus,
amygdala, and PAG) and receives information from the
orbitofrontal cortex (Ongür and Price, 2000) and insula
(Liang et al., 2015). This region can be considered as a sen-
sorimotor link and is involved in self-monitoring or deci-
sion making. More broadly, the mPFC is involved in action
monitoring and in the adaptive control of behaviours
(Saunders et al., 2017). Laubach et al. (2015) have found
a link between enhanced theta oscillations in mPFC and
adaptive control during reaction time tasks. The mPFC

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10      I. Conejero et al.: Neuroanatomy of conversion disorder
works as a performance and error monitoring system. Its
activation is associated with reward anticipation and the
need for performance adjustment (Ridderinkhof et  al.,
2004). The ACC is part of the mPFC and is involved in
monitoring the outcome of on-going actions (Warren
et  al., 2015). In CD, enhanced ACC activity assessed by
event-related potentials recording is associated with
increased self-monitoring (Roelofs et al., 2006). The mPFC
provides information about the need to adapt or to shift
the on-going behaviour, and it engages control processes
in the dorsolateral prefrontal cortex (involved in action
selection).
Like the vmPFC, the precuneus is part of the default
mode network and shows abnormal activation during
movement execution in patients with CD (Knyazeva et al.,
2011). These regions are involved in information process-
ing about the self (Raichle, 2015) and are deactivated
during a specific task in controls (Goldberg et al., 2006).
Dysregulation of frontal and parietal regions belonging to
the default mode network has been highlighted at rest in
patients with PNES (Knyazeva et al., 2011). More sponta-
neous activity of the precuneus is linked to hippocampal
activation and is modulated by memory recollection in
healthy controls (Vincent et al., 2006). Hence, the precu-
neus and hippocampus form a network that takes charge
of episodic memory and diurnal experience (Shannon
et al., 2013). During movement execution, lack of default
mode network deactivation may reflect an interaction
between memorised events, self-referential processes,
and motor activity. In parallel, independent component
analysis revealed reduction in functional connectivity
within parts of the default-mode network (posterior cin-
gulate cortex and vmPFC) and a reduced connectivity of
right motor cortex with other motor regions in patients
with CD compared with healthy controls (Vuilleumier and
Cojan, 2011). These networks are differentially modulated
in patients and in simulators.
Sense of agency
Sense of agency refers to the self-attribution of a given
behaviour. Self-agency is considered to be a retrospec-
tive judgment emerging from the comparison of internal
models of actions, ‘forward models’ (Blakemore et  al.,
1998), with sensory feedback (Voon et al., 2010b). It was
studied in patients with motor CD by using action-effect
binding paradigms as a measure of agency (Kranick et al.,
2013). Patients were asked to judge the time of their vol-
untary action (key pressing) and of its effect (tone). Nor-
mally, the decrease of the subjective time span between
action and effect is associated with the feeling of self-
initiated action (Libet et  al., 1983; Haggard et  al., 2002).
Patients with CD showed reduced subjective binding
between action and specific effect compared with healthy
controls. These results suggest a lack of self-agency and
impaired sense of control in patients with CD. Indeed,
several brain regions that support self-agency are func-
tionally altered in CD. First, the TPJ is hypoactivated. This
region could play a role in balancing internal predictions
and sensory feedbacks. The TPJ and inferior parietal lobe
overlap and are involved in self-representation (Ruby and
Decety, 2001). These regions are activated when compar-
ing the third-person and first-person perspective taking
during motor imagery.
Second, impaired dorsolateral prefrontal cortex acti-
vation could affect self-agency in patients with conver-
sion symptoms. The dorsolateral prefrontal cortex shows
tight connectivity with parietal regions (angular gyrus)
(Chambon et al., 2013), and its role in the sense of agency
was confirmed by transcranial direct current stimulation
studies (Khalighinejad et  al., 2016). The role of the dor-
solateral prefrontal cortex in sense of agency is related
to action selection and occurs when choosing between
voluntary action patterns (Chambon et al., 2013). Hence,
dysfunctional action selection related to dorsolateral
prefrontal cortex hypofunction and decreased action
monitoring by TPJ could explain impaired self-agency in
patients with CD.
Moreover, abnormal precuneus activation during
motor preparation could also be related to a disturbed
sense of control over an action or to altered perspective
taking (Ruby and Decety, 2001).
Salience system and action selection
Abnormal functioning of the salience system could con-
tribute to CD pathogenesis. The amygdala, insula, and
cingulate cortex are involved in arousal and evaluation of
self-relevant stimuli (Vogt et  al., 2006; Craig, 2009; Hry-
bouski et al., 2016). In patients with CD, salience system
hyperactivation occurs concomitantly with decreased
supplementary motor area activity (Voon et al., 2011), and
increased functional connectivity between the amygdala
and supplementary motor area was reported (Voon et al.,
2010a). Hence, the hyperactive salience system could
affect action selection and motor initiation through altera-
tion of supplementary motor area activity.
The dorsolateral prefrontal cortex also plays a role in
action selection (Rowe et al., 2000) and provides selection
of representations within working memory, thus allowing
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accurate planning of the behavioural response. Together,
the hyperactive salience system, impaired action selec-
tion, and top-down motor control by the dorsolateral pre-
frontal cortex could generate CD motor symptoms.
Memory suppression
Memory suppression was first described by Freud (Breuer
et al., 2000) and could affect patients with CD. However,
its role remains controversial. In patients with CD, recall of
escapable events was associated with cerebral activation
patterns similar to those involved in memory suppression.
Experimental memory suppression of previous learned
words is associated with increased dorsolateral prefrontal
cortex and ACC activation and reduced hippocampus
activation in healthy volunteers (Anderson et al., 2004).
A neuroimaging study of direct suppression revealed the
modulatory influence of the dorsolateral prefrontal cortex
over the hippocampus (Benoit and Anderson, 2012).
Interestingly, patients with CD show a similar activation
pattern (increased dorsolateral prefrontal cortex and
decreased hippocampus activation) when recalling in the
escape condition (Aybek et al., 2014b). However, a recent
neuropsychological study using directed forgetting task
failed to report the implication of memory suppression
mechanisms in CD pathophysiology (Brown et al., 2014).
Primary motor cortex
Dysregulations of the primary motor cortex have been
reported in CD, but they vary depending on the type of
paradigm/task and depending on the timing of evaluation.
A study suggested a defect in movement conceptualisation
and preparation (Burgmer et  al., 2006); however, other
works showed primary motor cortex deactivation only
during the actual movement, and normal activation during
motor imagery (Marshall et al., 1997; Cojan et al., 2009).
Altered movement conceptualisation could be
explained by reduced movement capacities. Moreover,
questions about volition could be raised in patients with
motor CD. The activation of primary motor regions during
movement preparation reported by two studies argues
towards a preserved will to perform movement. Indeed,
although voluntary action is supported by many other
brain regions (e.g. the parietal premotor circuit, frontopo-
lar cortex, and supplementary motor area) (Ludwig et al.,
2015), these brain networks converge towards the primary
motor area M1 (Haggard, 2008). Hence, if this region is
activated when patients prepare to move, the intention
I. Conejero et al.: Neuroanatomy of conversion disorder      11
to execute actions is probably preserved. The existence of
markers of preserved volition in patients with CD could
allow refuting the hypothesis that they are feigning.
Finally, increased activation of the primary motor cortex
could represent a compensatory phenomenon in patients
with limb weakness.
Limitations and perspectives
Although CD is well defined and diagnosis is made using
validated DSM-5 criteria, patients often show heterogene-
ous symptoms with positive (tremor, PNES) and negative
symptoms (motor weakness), as well as various deficit
durations from acute to chronic. This leads to difficulties
in generalising the neuroimaging results. Therefore, it
is crucial to develop objective tools to evaluate CD clini-
cal symptoms to allow the comparison of patient groups
and symptom follow-up. Moreover, different experimen-
tal paradigms have been used to assess brain activation,
and patients with CD were compared to healthy con-
trols, feigners, or within themselves. This huge variety of
experimental protocols and control groups may explain
the observed inconsistent findings. For instance, primary
motor cortex activation differs depending on whether it
occurs during the movement preparation or execution
phase, or during motor imagery. Within-patients compari-
son (for instance, between the affected and non-affected
side) is a way to address these issues because it takes into
account individual symptom fluctuations and variations
in task realisation.
Another limitation is the small clinical sample
(between 1 and 21 patients) of the selected studies. CD is
a rare pathological condition and insufficient statistical
power could explain some of the negative results.
Conclusion
Our systematic review of the current literature about CD
neuroanatomical correlates provides a framework to
better understand the specific mechanisms of this pathol-
ogy. It was first described as a functional brain disorder by
Charcot (1825–1893) originating from a ‘dynamic lesion’.
The functional mechanisms of conversion symptoms have
been confirmed with recent functional neuroimaging tech-
niques, including PET and fMRI. CD clinical features result
from abnormal interactions between emotional regions
and the motor and sensory systems. The concomitant
dysfunction of the following brain regions characterises
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12      I. Conejero et al.: Neuroanatomy of conversion disorder
motor conversion symptoms: (i) salience network (amyg-
dala, insula, and cingulate cortices) that is connected
with motor regions through supplementary motor area,
(ii) prefrontal regions involved in behavioural control, (iii)
vmPFC regions that support self-monitoring and informa-
tion processing about internal body states and environ-
ment, and (iv) self-agency network and regions involved
in memory suppression. We hypothesise that these dys-
functional brain networks alter the selection of motor pat-
terns through the influence of the supplementary motor
area and the dorsolateral prefrontal cortex (Figure 1).
Both brain regions (supplementary motor area and dor-
solateral prefrontal cortex) are critical ‘hubs’ connecting
affective networks with brain regions underpinning motor
function. In parallel, the dysregulation of brain networks
related to processing of emotional information affects the
integration of complex sensory inputs and may lead to
functional sensory loss.
Although similar brain regions are involved in both
positive (abnormal movements) and negative (motor weak-
ness) motor symptoms, differences may concern the nature
of the functional alterations (i.e. increased or decreased
activity). For instance, supplementary motor area activa-
tion is reduced in patients with tremor, dystonia, and other
abnormal movements, whereas it is increased in patients
with paresis and paralysis. Patients with sensory disor-
ders show impairment of specific primary sensory cortex
regions, but also increased activation of limbic regions
(insula, cingulate cortex, or inferior frontal cortex).
Altogether, these findings support the hypothesis of
a specific alteration in emotion processing that triggers a
large variety of symptoms through dysregulation of spe-
cific sensory or motor systems.
More studies on CD pathophysiology are needed to
identify and validate biomarkers related to the functional
neurological symptoms, to open the way to a positive
diagnosis and develop different therapeutic approaches.
Conflict of interest statement: The authors declare no
conflicts of interest.
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14      I. Conejero et al.: Neuroanatomy of conversion disorder
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