What’s in a name?

Words used to describe patients with functional neurological symptoms suggest either that we know clearly what the mechanism is (psychogenic, psychosomatic, conversion disorder), or that we have no idea (medically unexplained). Added to this is pervasive colloquial use of terms in doctor-to-doctor communication about patients with functional neurological symptoms which betrays a considerable ambivalence as to whether there is any difference between their symptoms and feigned illness: “Are the seizures real?”,“Did you think there was a genuine weakness?”

The confident use of terms such as ‘psychogenic’ to describe patients with functional neurological symptoms suggests a misplaced confidence in dichotomising physical and psychological processes, when the neuroscientific reality is that such processes cannot be separated. Even if one believes that the psychological level is the best level on which to understand the problem of patients with functional neurological symptoms, simply declaring that the symptoms are ‘psychological’ absolutely fails to account for the mechanism of symptom production in the brain. Perhaps this is why it is easy to slip from this to also using terms such as ‘real’ or ‘genuine’, something which fits with common patient and societal perceptions1 that use of the psychogenic/psychosomatic label is similar to saying symptoms are wilfully ‘put on’.

One way forward could be to start with a simple question: what it is about the symptoms and signs presented by patients with functional symptoms that allows neurologists to make the diagnosis with such a low rate of misdiagnosis2 at long-term follow-up? It is most helpful to start to consider this question with regard to patients with functional motor symptoms, as the objective way in which the diagnosis can be made in these patients is very clear. Functional symptoms very commonly co-occur, and so there is highly likely to be generalisability from the mechanism of production of functional motor symptoms to other functional symptoms such as functional non-epileptic attacks and functional sensory disturbance.

The diagnosis of functional motor symptoms, when done correctly, is not based on the presence or absence of psychological stress or difficulty, but on positive physical signs. Thus Hoover’s sign and distractability of tremor demonstrate a key role for attention in generating symptoms: when attention is distracted movement normalises. Put simply, the dependence on attention for movement production makes such movements look voluntary. The only thing, clinically, that separates patients with such symptoms from those who are feigning symptoms is the self-report of agency: patients with functional motor symptoms describe them as involuntary and out of their control. Another important feature of functional symptoms is that they can often be shown to fit with lay beliefs about how the brain might work, rather than what is known from basic neuroanatomy and physiology. An example of this phenomenon is a tubular visual field defect, where the visual field defect is the same size close to the patient or far away, something that defies the laws of optics.

Following this logical argument, we then have three key processes, well known from decades of neuroscientific study, which are implicated in the pathophysiology of functional symptoms and which are amenable to experimental investigation: attention, belief (in the sense of prior expectations/internal models of the world) and agency.

Attention

Clinical signs in patients with functional neurological symptoms show clearly the importance of self-directed attention in the generation of symptoms: when distracted, patients are typically much less symptomatic. Conversely, it is very easy to generate new symptoms and worsen existing ones during clinical examination, most likely via enhancing self-directed attention. This phenomenon has been studied experimentally, with evidence that the duration of direct visual attention towards the body during movement (e.g.looking directly at the limb which is moving) is significantly higher in patients with functional motor symptoms than neurological disease controls.3 In patients with functional motor symptoms, movement is abnormal when explicitly cued as is motor learning in an explicit context.4,5 However, movement is normal when cued implicitly as is implicit motor learning (e.g. learning a visuo-motor transformation).5 These data fit also with the results of some of a very mixed field (in terms of patients studied and paradigms used) of functional imaging studies in functional neurological symptoms. A number of such studies (see 6 for a review) show differences in activation of prefrontal regions during attempted movement which are similar regions to those engaged when healthy people pay attention to the production of overlearned movement patterns7 (a process which in healthy people impairs movement production). The basic point here is that attention towards the mechanics of movement production and otherwise monitoring internal bodily sensations is an abnormal state, and may directly interfere with normal movement production and sensory perception. Beliefs, expectations and internal models of the world.

The idea that beliefs about ourselves and our health can alter perceptual experience and movement is not new: this is the basis of placebo effects and hypnotic suggestion. However, the combination of prescient work by 18th and 19th century scientists Thomas Bayes and Herman Helmholtz and modern cognitive neuroscience has moved ‘beliefs’ (in the sense of predictions or expectations about the world) to the centre of an idea of how the brain works. In these models, the brain is an inference machine, constantly making predictions about expected sensory data and comparing it with actual sensory data received from the environment.8 Via interactions of this sort at multiple reciprocally connected levels, a percept arises which combines varying contributions of actual sensory data and expectations about that data. Importantly, this mix is not fixed and depends on the weighting of expectations over sensory data: this is why perception is so malleable depending on context. This same process is proposed to account for movement too and therefore provides a potentially neurobiologically sound foundation to build a neurobiological model of functional neurological symptoms. In one study relevant to this, patients with functional and organic tremor were asked to wear a ‘tremor watch’ which recorded tremor constantly.9 They were in parallel asked to fill in a diary reporting how much of the day they felt they were affected by tremor. Both groups of patients over-estimated the amount of the day they experienced tremor (i.e.perception was more in line with expectations than sensory data), but those with functional tremor did this to a significantly greater extent than patients with organic tremor: on average they had only 30 minutes of tremor a day while reporting tremor 80-90% of the time. As the nature of the study was made explicitly clear to participants, malingering seems an unlikely explanation. An alternative explanation is that whenever attention was turned towards the limb in patients with functional tremor, tremor was generated, and that expectations/predictions relating to the presence of constant tremor was so strong that it overwhelmed any sensory feedback that should have indicated absence of tremor during periods when attention was diverted. In a more abstract study of belief formation under conditions of uncertainty, patients with PMD demonstrated a ‘jumping to conclusions’ style of decision making.10 This decision-making pattern, making a decision on the basis of limited evidence, has previously been reported in patients with delusions, and makes a potentially interesting link between functional symptoms and perceptual distortions that occur in neuropsychiatric illness.

Agency

Agency relates to the subjective sense that a movement (for example) was self-generated and did not just ‘happen’. Patients with functional tremor scanned during their habitual tremor and periods when they deliberately mimicked their tremor were found to have reduced temporoparietal junction (TPJ) activity during their habitual tremor.11 The TPJ is a key node in the network that is thought to mediate comparison between sensory data from the body and expectations/predictions about that data. The hypoactivity found in patients was interpreted as reflecting the lack of an appropriate sensory prediction signal that one would usually associate with voluntary movement,and hence could explain why functional movement symptoms, while looking voluntarily generated, are not experienced as such by patients. This is in keeping with a subsequent behavioural study showing a lack of the normal feeling of intention to move before a voluntary movement in patients with psychogenic tremor.12

Putting it together

So where does this leave us in our understanding of the mechanism of functional neurological symptoms? A number of proposed models13-15 highlight the aetiological importance of the natural flexibility that exists in the brain regarding the way that sensory information about the state of the body and expectations/predictions about these data are integrated to produce our perceptual experience and action. The crucial first step in the production of functional symptoms is therefore proposed to be the instigation of an abnormal belief/expectancy relating to the symptom(s). This suggestion is at the heart of a number of proposed models for the generation of functional symptoms.13-15 It is of note that the instigation of this belief/expectation could arise from a number of different factors (which could be different in different people) including emotionally traumatic events, but also physical triggering events (injury, organic illness) that are commonly reported around onset and panic responses associated with such events (also commonly reported) which could serve to increase the salience of the novel sensory data coming from the physical event. The second step required for symptom generation is simply the activation of this ‘rogue representation’13/ ‘previously mapped conversion motor representation’14 / ‘abnormal intermediate level prior’.15 Here there may well be a role for abnormal limbic system activation,16 and also for self-directed attention. The last step in the model is that activation of the ‘rogue representation’13 is not accompanied by the normal neural ‘baggage’ that accompanies voluntary movement or normal sensory experience, and hence it is misattributed by the patient as being a symptom and out of their control.

From mechanism to treatment… and clinical responsibility

Much of the debate about aetiology of functional neurological symptoms focuses on factors such as childhood or recent emotional trauma, anxiety, depression and personality disorder, and hence these factors are often considered of prime (perhaps sole) importance in treatment. Maybe this is why neurological practice is commonly to make the diagnosis of ‘no neurological disease’ and hand the patient back to primary care or on to mental health services. Epidemiological research suggests, however, that while such ‘psychological’ factors are present at higher rates in patients with functional neurological symptoms than the general population, that many, perhaps even the majority of patients are unaffected.17 The discussion of mechanism above does not rule out a role, perhaps a very important one for such factors, but it is within a much richer aetiological context that is likely to be different for different people. In some patients, a simple biological understanding of how symptoms are being generated and physical and/or cognitive intervention directly informed by this understanding is the most effective form of treatment.18 If there are continuing underlying psychological issues that may increase the chance of relapse of symptoms then direct treatment of these is likely to be important too. In patients with severe symptoms, these processes may need to be carried out in parallel as part of multidisciplinary specialist rehabilitation. However, for many patients, focusing on the ‘how’ rather than the ‘why’ of symptoms is more productive, more important, and ultimately more relevant for recovery than an exhaustive trawl through previous life events. In the end this is just about truly applying an individually flexible biopsychosocial model of care. Importantly, this implies that it is the neurologist who is the key person in diagnosis, explanation and coordination of treatment. Patients with functional neurological symptoms deserve a neurologist-led and properly supported service that is flexible to their differing needs regarding treatment. This is what we expect for our patients with neurological disease and we should expect no less for our patients with functional symptoms.

References

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