Probing the Brain

Like Charcot, contemporary investigators of FND have been examining the brains of patients to find changes associated with the condition. Modern scientists, however, no longer have to wait to conduct an autopsy to peer into their subjects’ skulls. Using techniques such as fMRI, researchers have begun to reveal there are indeed differences in the brains of individuals with FND. “We're beginning to identify the dynamic lesion that Charcot was looking for,” says David Perez, a neurologist-psychiatrist at Massachusetts General Hospital.

With fMRI, researchers have identified distinct patterns of activity in brain areas such as the temporoparietal junction—associated with a sense of agency—in those with FND, compared with those asked to mimic the same symptoms. These findings help to confirm that unlike conditions such as factitious disorder (a severe form of which is known as Munchausen syndrome), in which patients deliberately act out other illnesses, symptoms in individuals with FND are out of their control.

Another significant discovery from neuroimaging is that people with FND have enhanced connectivity between the motor-control regions and two brain networks involved in emotional processing: the salience network, responsible for detecting and focusing on attention-worthy information, and the limbic network, one of the primary systems controlling emotion. In a 2010 study, for example, Hallett's group reported heightened linkages between the amygdala, a key region in the limbic system, and the supplementary motor area, which is responsible for preparing to initiate movements. Others, such as Perez, have shown hyperconnectivity between motor regions and salience network areas such as the insula and the anterior cingulate. These observations suggest that, at least in a subset of people with FND, the emotional circuitry might be hijacking the motor system, Perez explains.

Perez's team has also found that some risk factors may map onto these circuits. In a study published this year, his group reported that the magnitude of the coupling of the motor regions with the limbic and salience areas of the brain positively correlated with the degree to which patients experienced physical abuse during childhood. Perez emphasizes, however, that this will probably be relevant only to the subset of patients in whom trauma is present: in his study, a significant proportion of patients did not report any childhood physical abuse. Still, he notes that these findings point to how a risk factor such as trauma could alter brain circuits in people who develop FND.

Scientists are also investigating how factors such as stress alter brain circuits in FND. Neurologist Selma Aybek of the University of Bern says that although not all patients have a history of trauma or stress, they may possess differences in their biological stress response. Her group has found that, compared with healthy individuals, FND patients have higher levels of the stress markers cortisol and amylase and report being more stressed after taking part in a stressful task. Building on these findings, her team is using neuroimaging to examine whether there is an association between stress-related regions and agency-related regions in FND patients’ brains.

Thus, a picture of the pathophysiology of FND patients is slowly emerging. But most of this work has been conducted in patients with motor symptoms, which means that sensory symptoms such as altered vision have yet to be explored. Many of these studies also have had small sample sizes, so findings will need to be validated in larger trials, says Valerie Voon, a neuropsychiatrist at the University of Cambridge, who collaborated with Hallett on several ground-breaking projects. How these neuroimaging findings fit with the predictive-processing model also remains an open question. It is plausible, Perez notes, that many of the areas identified so far may be the circuitry through which the altered predictions arise.

A Brighter Future

In the summer after her second year of teacher's college in Scotland, a 19-year-old woman named Rachael Troup was rushed to the hospital with what appeared to be a stroke. Brain scans showed that she did not have a stroke, however, and tests for other neurological diseases came back normal. Eventually Troup was diagnosed with FND. But when she started treatment, it was excruciating. Neither her doctors nor her physiotherapists seemed to know much about how to treat her condition, and the exercises they made her do hurt more than they helped. “I was in pain constantly,” she says.

After a few months Troup decided to stop going to physiotherapy. At the time the entire right side of her body was barely functioning, and she was using a wheelchair for mobility. After being admitted to the hospital several more times for strokelike attacks, however, Troup met Stone's team and was provided with FND-tailored care. It involved a form of physiotherapy that employs techniques such as distraction to shift the spotlight of attention away from the affected limbs while engaging in exercises to help restore normal control.

For FND patients, shifting focus away from affected limbs is often a crucial part of physiotherapy because, as Edwards's predictive-processing model suggests, attention is critical to the generation of symptoms. With attention deployed elsewhere, the brain's abnormal expectations about movement are unable to take hold. Stone and his colleagues are part of an ongoing U.K.-wide, randomized controlled clinical trial testing this type of specialized physiotherapy for functional motor disorders (a subset of FND affecting movement). In addition to retraining movement, the treatment includes educating patients about how such symptoms could arise and the physical and psychological factors that may underlie it.

To expand the tool kit of interventions for FND, researchers are also testing other alternatives. Another large clinical trial with more than 300 patients assessed the efficacy of cognitive-behavioral therapy (CBT)—a type of goal-oriented intervention focused on changing disruptive patterns of thinking or behavior—for functional seizures. The findings, published in June in Lancet Psychiatry, suggest that CBT may not reduce seizure frequency in all patients.

At King's College London, neuropsychiatrist Tim Nicholson and his team are examining a noninvasive method of exciting the brain known as transcranial magnetic stimulation (TMS) as a potential intervention for FND. His group recently completed a feasibility study, and the results were promising enough to initiate a larger pilot clinical trial. There are competing explanations for why TMS might work. It induces a brief muscle twitch that could kickstart the relearning of movement; stimulating brain areas altered in FND might help restore function, or it may have a placebo effect. LaFaver's group at Northwestern is examining the use of meditation and mindfulness practice, which, according to LaFaver, patients have anecdotally reported as helpful for maintaining the benefits of treatment.

Psychological treatments such as CBT currently remain among the first-line interventions for people with FND, according to Perez. There is a pressing need for a range of effective treatments, however: the prognosis remains poor. It is still relatively uncommon for FND patients to completely regain function, and relapses occur often. According to a 2014 meta-analysis of 24 studies, on average 40 percent of patients reported similar or worsened symptoms seven years after their initial diagnosis. On top of that, patients still experience high levels of stigma and have trouble accessing treatment, LaFaver says. “I still think we have a long way to go.”

Fortunately, the situation is changing. As researchers’ interest in FND surged over the past decade, so did the number of FND clinics around the world. Patients are speaking up as well. In 2012, for example, the international charity FND Hope was established with the aim of raising awareness and empowering patients.

Still, debates linger—and are reflected in an ongoing tussle over the name of the illness. In what fraction of patients are psychological factors present, for example? Do symptoms primarily arise through conversion of stressors, or are other explanations also necessary? One meta-analysis found that reports of stressors in FND patients vary between 23 and 86 percent in different studies. W. Curt LaFrance, Jr., a neurologist-psychiatrist at Brown University, says that it takes more time to identify such stressors than some doctors can devote to an individual patient—which may account for this enormous spread. In his clinic and in the scientific literature, he has consistently seen evidence of psychological stressors having converted into physical symptoms, and, accordingly, he supports use of the term “conversion disorder.” Partially reflecting such views, the older name remained when FND was added to the DSM-5, but the need to identify psychological factors for a diagnosis was dropped. That excision also remains contentious.

One thing is clear, however: because the condition lies at the crossroads of neurology and psychiatry, insights from both fields will be necessary to solve the puzzle. This blurring of the line between mental and physical illness is a growing trend. Scientists now understand, for example, that stress—a psychological factor—can predispose people to Alzheimer's disease and that inflammation—a physical factor—may give rise to depression. In addition, traditional neurological diseases such as epilepsy and stroke are often associated with mood and behavioral disturbances. “The brain doesn't separate into neurology and psychiatry,” Perez says. “We need a new science of brain and mind that really encapsulates that brain health equals mental health and physical health.”

Over the past few years McNiven has frequently used a wheelchair because of her FND. But with the help of both physiotherapy and psychotherapy, she has started to recover. Her symptoms are not gone—she still experiences a lack of sensation in her legs, altered vision, and pain—and some days are worse than others. “I constantly feel like I'm fighting against my body,” McNiven says. But she hopes to make a full recovery. “You've got to keep that positive attitude to keep fighting through it. There's always hope you can get there with this condition.”