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It Is All in Their Head
Functional MRI identifies Neural Abnormalities in Patients with Functional Movement Disorders

ARTICLE IN BRIEF

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FUNCTIONAL MAGNETIC RESONANCE IMAGES show decreased functional connectivity in FMD patients between the right temporo-parietal junction and the (A) bilateral supplementary motor area (arrow); (B) right precentral gyrus (arrow); (C) right postcentral gyrus (arrow); (D) right insula (arrow); and (E) cerebellar vermis (arrow).

Researchers reported finding an abnormal signal — decreased functional connectivity between the right temporo-parietal junction and bilateral sensorimotor regions — in the functional magnetic resonance imaging scans of patients with FMDs taken during a resting state compared with that of healthy controls.

A brain region that governs self-agency — the knowledge that an individual has control over his or her own movement — is impaired in patients with functional movement disorders (FMDs), according to a report published in the July 6 online edition of Neurology.

The researchers found an abnormal signal — decreased functional connectivity between the right temporo-parietal junction (TPJ) and bilateral sensorimotor regions — in the functional magnetic resonance imaging (fMRI) scans of patients with FMDs taken during a resting state compared with that of healthy controls.

“This resting-state fMRI analysis provides important evidence supporting organic abnormalities in functional connectivity in patients with FMD,” the study authors wrote. “This is particularly relevant given the persistent false belief among many neurologists that functional neurological symptoms are commonly feigned, and that many patients are malingering.”

The scientists believe that the deficits in this brain region impair self-agency, and that contributes to the patient's belief that the abnormal movements are not under their control.

The concept of self-agency stems from research that shows that the brain is always monitoring whether “an action's consequences occur as predicted,” the study authors wrote. The right TPJ works to compare a person's internal prediction with feedback from the actual action.

The study authors, led by Carine W. Maurer, MD, PhD, a senior clinical fellow in the Human Motor Control Section of the medical neurology branch at the National Institute of Neurological Disorders and Stroke (NINDS), decided to look for abnormalities in functional connectivity of the TPJ after their previous task-oriented studies identified an abnormal signal in this region.

STUDY METHODS, FINDINGS

The scientists recruited 35 patients with clinically diagnosed FMD who are part of an ongoing study to better understand the disorder, and compared their resting-state scans with those of 35 age- and sex-matched healthy controls. The participants were screened for psychiatric diagnoses using a structured clinical interview, including the Beck Depression Inventory and Childhood Trauma Questionnaire.

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DR. MARK HALLETT believes that the primary abnormality is probably elsewhere in the brain but it ends up affecting the right temporo-parietal junction. “There is too little connectivity from this region to other places in the brain, particularly the motor cortex and the cerebellum, both of which are involved with triggering movement.”

The patients with FMDs reported a range of involuntary movements: 74 percent reported tremor, and 63 percent, jerking movements. They also reported abnormal gait and/or balance (63 percent), abnormal speech (46 percent), abnormal posturing/dystonia (43 percent), and paresis (31 percent.)

The researchers suspect that the TPJ abnormality makes it difficult to integrate the feed-forward system — thinking about carrying out a movement — and the feedback system, given decreased communication to regions of the brain that control movement, such as the right sensorimotor cortex, cerebellar vermis, bilateral supplementary motor area, and right insula.

In other words, the patients' brains do not register that they are planning and carrying out a particular movement, explained Mark Hallett, MD, FAAN, chief of the NINDS Human Motor Control Section and co-author of the study.

“FMD falls into a category of somatic disorders,” Dr. Hallett said. “Presumably, psychiatric factors initiate a change in the brain that leads to somatic symptoms. The pathophysiology is not understood, and we have a lot to learn.”

Dr. Hallett believes that the primary abnormality is probably elsewhere in the brain but it ends up affecting the right TPJ. “There is too little connectivity from this region to other places in the brain, particularly the motor cortex and the cerebellum, both of which are involved with triggering movement.”

How might the finding help in designing a treatment? Dr. Hallett said that if people realize that the actions are voluntary, the faulty brain signal might normalize “and create a sense of self-agency.”

“Exploring the changes to the self-agency network before and after successful treatment regimens, such as those advocating greater accountability and reinforcement of normal motor patterns, might shed further light on this question,” the study authors wrote.

EXPERTS WEIGH IN

“The findings provide a model for better understanding FMDs, which have been previously challenging based on the heterogeneity of disease,” said Elizabeth A. Coon, MD, senior associate consultant and assistant professor of neurology at the Mayo Clinic in Rochester, MN, who was not involved with the study.

“This also validates what our patients are telling us. Now, when our patients with FMDs are told that ‘it is all in their head,’ [we can tell them] it's true. There is really a physiologic underpinning to their disorder.”

“Functional movement disorders are heterogeneous, in that no two patients present with similar background and history, and the abnormal movements may be highly variable,” she said. However, there are certainly characteristics shared amongst patients with this disorder.

“Patients are told that their movements are psychiatric, due to stress or previous abuse and often, that is not the case for patients so they seek additional opinions or become frustrated. This approach also rarely leads to a therapeutic course, and all of this is difficult for patients,” Dr. Coon said.

The Mayo Clinic offers an intensive motor reprogramming outpatient treatment program that typically lasts five days. The treatment involves physical therapy and rehabilitation, but psychiatrists and psychologists are also involved. The main focus is on relearning the correct motor pattern. “The results are really astounding, and through intensive physical therapy and occupational therapy sessions, patients show remarkable improvement that can be sustained.”

Janis M. Miyasaki, MD, professor of neurology and director of the movement disorders program at the University of Alberta, coauthored with Peggy J. Planetta, PhD, a scientist in the department of applied physiology and kinesiology at the University of Florida, an editorial accompanying the study in the same issue of Neurology. In an interview with Neurology Today Dr. Miyasaki said that it is still not clear what comes first: the brain changes or the behavior that drives the brain change. “It is the classic chicken-and-egg scenario. Still, the study confirms that patients don't have a sense that they have control over these movements. This is potentially a target for our interventions,” she said.

“Instead of trying to get rid of the movements, we may be able to increase their feeling of self-agency,” Dr. Miyasaki said. “The biggest challenge is for neurologists to keep in mind that this may be the thousandth patient you have seen with FMD, but for the patient in front of you this is the first experience. Empathy is critical.”

Howard I. Hurtig, MD, the Elliott professor of neurology, emeritus and former chief of neurology and co-director of the Parkinson Disease and Movement Disorders Center at the Perelman School of Medicine at the University of Pennsylvania, agreed with the need for showing empathy. “These patients must know that they are being taken seriously and that the health care practitioner is committed to seeing them through the duration of their illness.”

“The authors interpret their finding of an abnormal fMRI neural network centered in the temporo-parietal region as evidence in a group of patients, compared with healthy controls, that FMD is not psychogenic but physiologic,” Dr. Hurtig continued. “This is not a new idea, but the results of their innovative research reinforce the notion that FMD is an identifiable disruption of the brain's normal neural circuitry, notwithstanding the conclusion that it is unclear how this finding explains the clinical heterogeneity of the broad spectrum of the involuntary movements seen in patients with FMD.”

He added: “This doesn't mean that fMRI will be immediately usefuI as a diagnostic test for the individual patient. Other researchers must reproduce these results before the principal finding can be considered more definitive.”

EXPERTS: ON ABNORMAL SIGNALS IN IMAGES OF PATIENTS WITH FUNCTIONAL MOVEMENT DISORDERS

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DR. ELIZABETH A. COON: “The findings provide a model for better understanding FMDs, which have been previously challenging based on the heterogeneity of disease. This also validates what our patients are telling us. Now, when our patients with FMDs are told that ‘it is all in their head,’ [we can tell them] its true. There is really a physiologic underpinning to their disorder.”

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DR. JANIS M. MIYASAKI said that it is still not clear what comes first: the brain changes or the behavior that drives the brain change. “It is the classic chicken-and-egg scenario. Still, the study confirms that patients dont have a sense that they have control over these movements. This is potentially a target for our interventions.”

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DR. HOWARD I. HURTIG: That FMDs are not psychogenic “is not a new idea, but the results of their innovative research reinforce the notion that FMD is an identifiable disruption of the brains normal neural circuitry, notwithstanding the conclusion that it is unclear how this finding explains the clinical heterogeneity of the broad spectrum of the involuntary movements seen in patients with FMD.”

LINK UP FOR MORE INFORMATION:

• Maurer CW, LaFaver K, Ameli R, et al. Impaired self-agency in functional movement disorders: A resting-state fMRI study http://www.neurology.org/content/early/2016/07/06/WNL.0000000000002940.short. Neurology 2016; Epub 2016 Jul 6.
    • Planetta PJ, Miyasaki JM. New insights into the neural basis of functional movement disorders http://www.neurology.org/content/early/2016/07/06/WNL.0000000000002957.short. Neurology 2016; Epub 2016 Jul 6.