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Brain 2010: 133; 1295–1299
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BRAIN
A JOURNAL OF NEUROLOGY
SCIENTIFIC COMMENTARIES
Conversion disorder: understanding the
pathogenic links between emotion and motor
systems in the brain
When neurology and psychiatry moved apart from each other
around the turn of the 20th century, casualties included the
many patients with unexplained neurological disorders. Many
labels have been applied to these patients. Some are descriptive
(functional disorders, medically unexplained symptoms), while
others refer to a presumed aetiology (psychogenic, hysteria,
non-organic) or putative mechanism (dissociative or conversion
disorder). Whatever is the label, for some physicians these patients
are among the most interesting and challenging in the clinic. For
others they are frustrating, using much time and resources for an
often disappointing outcome.
Whether you are an enthusiast or nihilist, it is clear that that
neither neurology nor psychiatry alone have succeeded in sufficiently advancing our neurobiological understanding or management of these disorders. The slow progress is in stark contrast to
the scale of the problem. Medically unexplained neurological
symptoms account for 30% of referred neurology out-patients
(Carson et al., 2000; Stone et al., 2009). Conversion disorder
alone, explicitly associated with psychological stressors at the
outset, accounts for 5% of referrals and is a stable, accurate
diagnosis (Perkin, 1989; Stone et al., 2005, 2009).
Psychogenic movement disorders are common in neurological
practice, including tremor, dystonia, gait change and paralysis.
Diagnostic criteria emphasize clinical observations such as inconsistency, distractibility and false neurological signs (Fahn and
Williams, 1988). These can be both sensitive and specific, at
least in the context of a movement disorder clinic (Shill and
Gerber, 2006). Physiological criteria have also been developed,
such as coherence of tremor oscillations distinguishing psychogenic
from organic syndromes (McAuley and Rothwell, 2004). The emphasis in this ‘neurological’ approach is on the physical examination, supplemented by physiological tests. The psychological
aspects of the disease take second place, e.g. requiring ‘obvious’
but not specified psychiatric or emotional disturbance (Fahn and
Williams, 1988; Shill and Gerber, 2006).
In contrast, the ‘psychiatric’ approach emphasizes features of
the clinical interview, including psychological factors at outset
and inferences of intent. This is not ideal as a diagnostic ‘gold
standard’ for developing a biological science of conversion disorder
but the Diagnostic and Statistical Manual of Mental Disorders
(DSM-IV) at least provides strict diagnostic criteria. The diagnosis
requires the temporal association of psychological factors with the
neurological symptoms (Criterion B: note that in the current revision of DSM, the aetiological relevance of the psychological factors has been downgraded from causal to association only). A
further condition (Criterion C) is the lack of wilful simulation of
symptoms (otherwise indicative of malingering, factitious disorders
or ‘Munchausen syndrome’) but this is difficult to substantiate.
The neurological approach to psychogenic movement disorders
and the psychiatric approach to conversion movement disorder are
therefore both problematic. Many patients move between neurological and psychiatric services, but a unified formulation may not
emerge, contributing to an unsatisfactory outcome. Importantly,
we lack mechanisms to explain the neurological manifestation of
the conversion disorder, even when likely psychological aetiological factors are established. An objective, explanatory framework for
conversion disorder is clearly required, one that brings together
both psychological and physiological phenomena.
Against this troubled background, in the current issue, Voon
et al. (p 1526) use functional magnetic resonance imaging to
study conversion movement disorders. The combination of psychiatrists and neurologists among the research team is important,
and not just for the credibility of this particular study. It also signifies a trend towards a common understanding of conversion
disorder, which is important for developing effective neuropsychiatric management strategies.
Voon et al. are not the first to use neuroimaging methods to
study conversion disorder or psychogenic movement disorders [see
Nowak and Fink (2009) for a review of ‘psychogenic paralysis’].
However, previous studies often used motor tasks that are close to
the functional deficit. For example, in studies of conversion/psychogenic paralysis, participants have been asked to try to move
the affected limb, imagine moving the paralysed limb or feign
immobility of the ‘good’ limb (Marshall et al., 1997; Halligan
et al., 2000; Spence et al., 2000; Ward et al., 2003; de Lange
et al., 2007). These studies indicate abnormalities outside the core
motor network, including the prefrontal cortex and anterior cingulate cortex. The results support the hypothesis of abnormal
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| Brain 2010: 133; 1295–1299
inhibition of motor systems by limbic regions (Marshall et al.,
1997; Halligan et al., 2000; Spence et al., 2000; Ward et al.,
2003) or impairments of motor conceptualization (Burgmer
et al., 2006; de Lange et al., 2007). However, imaging abnormalities identified from tasks that are based directly on the motor
deficits can be confounded by differences in motor performance
and sensory feedback (the latter studied directly by Vuilleumier
et al., 2001). In addition, the interactions between limbic and
motor areas are inferred, but have not been shown directly in
the previous studies.
A different strategy has been taken by Voon et al. They study
patients using a task that they can perform normally, and one that
is at first sight unrelated to the motor deficit: a gender discrimination task with face pictures. By manipulating the emotional expression of the faces, irrelevant to the task at hand, they are able
to study a robust neurocognitive system for emotion processing
and arousal, including the amygdala. This choice of task is very
important, given the emotional events that may contribute to the
initiation or maintenance of conversion disorder.
A second interesting aspect of this study is the inclusion of a
diverse patient population with tremor, gait disorder, dystonia or
mixed syndromes. This contrasts with smaller series (median n = 4)
of closely matched patients in previous neuroimaging studies
(Marshall et al., 1997; Halligan et al., 2000; Spence et al.,
2000; Ward et al., 2003; de Lange et al., 2007). Whereas clinical
heterogeneity can reduce sensitivity to the neural correlates of
individual phenotypes, it also means that results reflect the communalities, not differences, of conversion movement disorders. It is
all the more interesting, therefore, that common abnormalities are
seen in the amygdala and its interaction with the supplementary
motor area. This provides direct support for a model of conversion
disorder based on abnormal limbic–motor interactions.
Is it sufficient to identify neural correlates of chronic conversion
movement disorder? Several issues arise here. First, one must acknowledge that, in isolation, physiological correlations do not provide the cause or mechanisms of disease. However, they do support
a change in the direction of research, striving for a neurobiological
model. This should not discard the importance of psychological or
psychodynamic factors, but they must lie within an evidence-based
functional and causal (mechanistic) neuroanatomical model.
Second, the search for a neural signature of conversion disorder
implicitly challenges the historical ‘non-organic’ model. This problem is not unique to conversion disorder, but applies to other major
psychiatric syndromes including depression or schizophrenia.
The observed neural correlates of conversion disorder might also
be due to late epiphenomena or comorbidities in chronically disabled patients, e.g. depression. In the study by Voon et al., the
patients do not meet diagnostic criteria for major affective or
psychotic disorders or substance misuse. However, they do have
significantly higher rates of depression and anxiety symptoms than
controls. In separate studies, depression, remitted depression or
elevated depressive symptoms without depression have been
shown to influence the activity of the amygdala (Drevets, 2000)
and its response to salient stimuli (Taylor Tavares et al., 2008;
Beesdo et al., 2009). Voon et al. argue cogently that their findings
are independent of depressive or anxiety symptoms. However,
they rely partly on a lack of significant correlation between
Scientific Commentaries
depression scores and amygdala activity (possible risk of type II
error) and partly on interpretation of left versus right differences
(possible risk of false lateralization arising in thresholded images).
Nonetheless, the depression scores in their patients may have been
elevated by somatic symptoms, a common feature of conversion
disorder, rather than mood disturbance per se.
A third important aspect of the study by Voon et al. is their
analysis of the connectivity of the amygdala. It has previously
been proposed that conversion disorder arises from abnormal
interactions between limbic and motor regions. To test hypotheses
of interacting neural systems calls for formal analyses of network
connectivity, but this has been lacking in previous studies. Voon
et al. use two methods to study connectivity. The first is psychophysiological interactions (Friston et al., 1997), revealing that patients viewing salient stimuli have abnormal connectivity between
the amygdala and the supplementary motor area. The second
method, Granger Causality Modelling (Roebroeck et al., 2009),
is used to identify the directionality of this effect: amygdala activity is predictive of future changes in the supplementary motor
area, but not vice versa. Future studies will no doubt refine task
designs and analysis options to include more realistic biophysical
models with anatomically defined networks (Friston, 2009). As a
first step, however, the concordance between connectivity methods and their immediate relevance to the predicted limbic–motor
interactions is impressive.
There remain many unanswered questions. For example, firstly,
why do even common and mild mood disorders or stressors lead to
bizarre and disabling conversion disorders/psychogenic movement
disorders? Secondary gain, or exposure to neurological illness in
personal or professional life, may be relevant (Shill and Gerber,
2006), but they lack objective measures and are prone to recollection bias. Secondly, what determines the nature of the neurological
deficit—tremor, paralysis, blindness, sensory loss? Here, at least the
approach taken by Voon et al. provides clear testable hypotheses
regarding interactions between amygdala and visual or sensory
cortex in other syndromes. Thirdly, why do patients experience
a sense of loss of control over their movements? This speaks
to the broader neuroscience of volition (Haggard, 2008) and
disturbed sense of ‘agency’ in neurological disorders (Moore
et al., 2009).
Answers to these questions will require further long-term integration of psychiatry and neurology during training, in the clinic
and in the laboratory. With its high prevalence and disability, conversion disorder clearly requires higher priority for research, into
both basic mechanisms and effective therapies. In the meantime,
be inspired by the work of Voon et al., whose results are a significant step towards understanding the neurobiological basis of
conversion disorder and developing better therapies.
James B. Rowe
Department of Clinical Neurosciences,
University of Cambridge,
Cambridge, UK
E-mail: [email protected]
doi:10.1093/brain/awq096
Scientific Commentaries
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Are we getting to grips with Alzheimer’s disease
at last?
Recent statistics from the Alzheimer Research Trust suggest that in
the UK alone 820 000 people are affected by dementia with a cost
to the economy of £23 billion/year. Similar figures apply to all
developed countries and most others are catching up rapidly.
With increasing life expectancy, age-related dementia is seen globally as an urgent public health priority.
Histological examination of the brain is still regarded as the gold
standard for diagnosis of the specific disease process underlying
dementia, the commonest cause of which is Alzheimer’s disease.
The main features of Alzheimer’s disease are extracellular accumulation of amyloid b-protein (Ab) in the form of plaques and in
blood vessel walls as cerebral amyloid angiopathy; intraneuronal
accumulation of tau protein forming tangles in neuronal cell
bodies as well as in neuronal processes situated close to plaques
(dystrophic neurites) and elsewhere (neuropil threads); activation
of microglia and astrocytes; and neuronal and synaptic loss.
However, histological assessment of the disease has several limitations including, almost by definition, observations made at only
one time point in the disease, usually the end-stage of a neurodegenerative process that has been developing over many years.
This means that using post-mortem neuropathology, we have little
or no notion of the dynamics of the pathological processes
involved, how they are interrelated in terms of cause and effect,
and which feature, if any, best correlates with, or causes, the
cognitive dysfunction.
The principal hypothesis for the pathogenesis of Alzheimer’s
disease for two decades or more has been built around amyloid,
and known as the Ab cascade hypothesis, which states that Ab,
either in the form of extracellular amyloid plaques or in soluble or
oligomeric forms, has the key role in initiation of the disease. A
powerful way to test the Ab hypothesis is to modify this aspect of
the pathophysiology and observe any effects on other aspects of
the pathology and on brain function.
In this issue of Brain, Serrano-Pozo and colleagues (page 1312)
have studied the effects of Ab immunization on neuronal and tau
pathology in Alzheimer’s disease. Active immunization with