Date: June 2023
Prepared by SIC Member: Kirsten Zeuner, MD
Authors: Anne Weissbach, MD; Isabel Pareés, MD; and Carine W. Maurer, MD, PhD
Editor: Lorraine Kalia, MD, PhD
Is there evidence for abnormal sense of agency in patients with functional movement disorders?
There are several studies in patients with FMD suggesting a disturbed sense of agency and providing us with information why patients experience their symptoms as involuntary2. Multiple aspects need to be considered when analyzing the causes of defective agency of movements in patients with FMD. On the one hand, it probably results from a combination of defective attentional focus (towards motor symptoms and internal body processes), emotional dysregulation, and abnormal expectation (prior beliefs), which alter physiological action execution and its awareness. Moreover, abnormalities in sensorimotor integration processes need to be considered and are described in the answers to the questions below.
One of the most intriguing aspects of FMD is why a movement, which appears to be voluntary in nature (because it can be altered by distraction) and is probably generated by the same brain networks involved in voluntary motor control, is experienced as involuntary. Where do patients lose voluntariness for a particular action? Over the past fifteen years a significant neuroscientific research effort has been made and several functional neuroimaging and neurophysiology studies have contributed to our knowledge surrounding the lack of agency for movement in these patients. In a relevant study using fMRI, Voon et al3 found a relative reduction in activation of the right temporoparietal junction, an area associated with the sense of agency, in patients with functional tremor while they were tremoring compared to when they were voluntarily producing tremor. Selective dysfunction of the sense of agency neural network was also demonstrated by Nahab et al4 in a subsequent fMRI study using a virtual-reality movement paradigm that could modulate the sense of agency. We also tried to understand more about the lack of voluntariness in patients with FMD by assessing the phenomenon of sensory attenuation5 which is considered to be an implicit measure of the sense of agency, as discussed below.
As mentioned by Dr. Pareés, individuals with FMD experience their abnormal movements as involuntary. Yet these movements can be impacted by distraction or entrainment in a similar manner to voluntary movements. Work from clinical neurophysiology studies also indicates functional movements can be preceded by cortical potentials identical to those that characterize self-paced voluntary movements6. However, while functional movements may use a similar final motor pathway as voluntary movements, patients lack a sense of control for these abnormal movements; this lack of sense of control is referred to as an impairment in self-agency.
There is growing evidence contributing to our knowledge about self-agency in patients with FMD from both functional neuroimaging studies as well as implicit behavioral measures. The action-effect binding paradigm is an implicit behavioral task involving the subjective temporal binding of an action to its effect; this task has been used to quantify sense of self-agency. In individuals with FMD, there is a reduction in this action-effect binding, even for normal voluntary movements7. As noted above, the right temporoparietal junction (TPJ)/inferior parietal lobule plays a key role in self-agency, and indeed several functional neuroimaging studies have demonstrated abnormalities in this region in individuals with FMD. In addition to the studies Dr. Pareés mentioned above3, 4, we also demonstrated that individuals with FMD exhibit altered connectivity from the right TPJ in a resting state fMRI study; this altered connectivity was seen between the right TPJ and regions implicated in emotional processing as well as sensorimotor processing8. Another fMRI study by Baek et al9 using a Libet’s clock paradigm in the scanner showed that the patients with FMD had not only delayed awareness of their intention to move but that their intention to move was associated with reduced activity in the right TPJ/inferior parietal region. Loss of sensory attenuation, as described below, also provides additional evidence for abnormal sense of self-agency in FMD.
Sensory attenuation has been found to be abnormal in patients with functional movement disorders. What are the mechanisms and the clinical implications for patients?
Sensory attenuation is a physiological phenomenon in which the perceived intensity of a self-induced force is reduced compared to an externally generated force10. It has been investigated by a force matching paradigm, which revealed significantly reduced sensory attenuation in patients with FMD5. Whereas healthy controls consistently overestimate the force required to match a pre-defined force applied to their finger when using their contralateral finger, this was not the case in patients who were, in fact, more accurate in their estimation5. In a similar vein, FMD patients showed a loss of a physiological reduction of the amplitude of sensory evoked potentials (e. g., N20 and N30) at the onset of self-generated movements, as present in healthy controls, also resembling abnormal sensory attenuation11. The latter is probably the electrophysiological correlate of the psychophysiological reduction in intensity of self-generated sensory stimuli examined by the force matching paradigm5. The experience of sensory attenuation is important for perceiving movements as self-generated and, as a corollary, a loss of sensory attenuation is associated with a loss of agency for movement12, as described above. Potential clinical implications are summarized in the section below.
As Dr Weissbach has already mentioned, sensory attenuation is a phenomenon whereby the intensity of sensation produced by self-generated movement is reduced. A common example of this is the observation that while one cannot tickle oneself, one can be tickled by another person. Sensory attenuation contributes to label a movement as self-generated. After reading previous literature about impaired sensory attenuation in patients with schizophrenia and delusions of control, we designed a study to assess sensory attenuation in patients with FMD by using similar methods (a force matching paradigm)5. We found that patients have a loss of sensory attenuation as compared with healthy controls. Patients were extremely accurate in their force estimation performance when they directly applied the force, in contrast to controls who consistently overestimated the target force. These results have several implications. They imply that malingering is not an explanation for all these patients and instead, they display abnormalities in the mechanisms implicated in the experience of oneself as the agent controlling one´s own movements (additionally, one would not expect malingers to be extremely precise in a task). These results also have implications in terms of therapy, as one of the main goals in psychotherapy and physical therapy should be to restore the sense of agency and to gain control of the abnormal movement. One of the questions that remains unsolved is why abnormal sense of agency is restricted to a particular movement or action. Further research is needed to enlighten our understanding of this intriguing aspect.
As noted above, a self-generated touch is typically associated with a reduction in the intensity of perceived sensory experience as compared to an externally generated touch, a phenomenon referred to as sensory attenuation. This phenomenon is important in defining movements as self-generated, and a loss of sensory attenuation can be correlated with a loss of self-agency. Sensory attenuation can be quantified using sensory evoked potentials (SEPs), and prior studies have found a reduction in this sensory attenuation in patients with FMD11. Above, Dr. Pareés has described the force matching paradigm which also demonstrated this loss of sensory attenuation in FMD patients5. This loss of sensory attenuation, in addition to reflecting impaired self-agency, may be viewed as being consistent with an increase in body-focused attention in individuals with FMD. Therapy targeting this altered attention can be beneficial for treatment of FMD. Physical and occupational therapy guidelines reinforce the importance of minimizing self-focused attention towards patient’s abnormal movements and encouraging automatically generated movements13, 14.
Although functional movement disorders patients have a motor disorder, abnormal sensory processing has been discussed. What are the mechanisms and does an overweighting of the feedforward message in functional movement disorders play a role?
Patients with FMD show an impairment in different sensory modalities of temporal discrimination, which suggests that they might even suffer from sensory processing alterations. In a previous study, FMD patients exhibited not only elevated tactile temporal discrimination thresholds but also revealed a reduced drift rate in a decision-making model taking accuracy and response time into account, suggesting that sensory processing is defective15. In the predictive coding framework proposed for functional neurological disorders16, this can be interpreted in a way that bottom-up sensory information tends to be down-regulated in favor of top-down predictions (prior beliefs, feedforward information), reducing the quality of sensory information (feedback information) available to the patients during the above mentioned decision-making task15. This was also shown in a study investigating belief formation under conditions of uncertainty by using a visual probabilistic reasoning task17. Patients with FMD requested less visual information and relied more on newly presented (and even dis-confirmatory data) before making a definite decision, i.e., showed a tendency for “jumping to conclusions” by favoring the formation of abnormal interference over the actually presented sensory data17. This may result in incorrect updating of cognitive control resources, which guide the formation of expectations on future sensory data to accomplish response selection and also alter the sense of agency as mentioned in the above sections. These aspects have direct clinical implication. Psychoeducation may enable patients to update/correct their prior belief, i.e., feedforward information, thus, restoring the balance between feedforward and feedback information. In a similar vein, physiotherapy and cognitive attentional training may guide patients to refocus their attention on body parts/motor actions/external processes which are unaffected. Thereby patients can experience that they can reduce/control their symptoms, strengthening their physiological agency of movements.
Sensory processing difficulties in patients with functional neurological symptoms have been recently highlighted but remain poorly characterized. Preliminary evidence has shown sensory processing difficulties as measured by a self-report scale, which evaluates behavioral responses to everyday sensory experiences18. A tendency toward low registration (failing to detect stimuli that others notice), sensory sensitivity, and sensory avoiding has been found, suggesting that some sensory experiences in patients with functional symptoms differ from those in the general population. Apart from evidence that sensory attenuation is impaired in patients with FMD, lower interoceptive accuracy19 and elevated temporal discrimination threshold have been reported20. More recently, an enlightening study using a randomized and automated version of the temporal discrimination task, where both response accuracy and reaction time were recorded15, confirmed elevated temporal discrimination thresholds in patients. After modelling data by using the drift diffusion model, they found a significant reduction in drift rate, which implies an impairment in the quality of the information that drives decision processes. They suggested that abnormal allocation of attention, which is typically observed in patients with FMD, may impair the quality of sensory information available and be, at least partially, the cause of abnormal sensory processing. An additional explanation, as Dr Weissbach has already mentioned, which is based on current models of brain functioning (active inference), is that abnormal “top-down” predictions from the cortex overwhelm ”bottom-up” sensory inputs, reducing the quality of sensory information available during a decision-making task.
Carine MaurerDrs. Weissbach and Pareés have already noted many of the studies describing the abnormal sensory processing in FMD patients. Important work by Pareés and colleagues, mentioned by Dr. Weissbach above, is relevant to how we conceptualize the processing of novel sensory data in patients with FMD. In their study17, Pareés and colleagues demonstrated that individuals with FMD form a decision with less sensory information, and are more likely to change their decision when confronted with new sensory evidence.
The active inference model considers the brain as a structure with information flowing from the “bottom-up” (i.e. sensory information) and the “top-down” (i.e. from the cortex). Our model for understanding FMD within this framework posits that in FMD patients “bottom-up” sensory information is down-weighted while “top-down” predictions (“priors”) are weighted more strongly 16. The work by Pareés and colleagues on “jumping to conclusions”, as well as the abnormalities in sensory processing my colleagues have described above, are consistent with this model. The comparison between “bottom-up” (sensory feedback) and “top-down” (feedforward) signals impacts sense of self-agency. Psychotherapies such as cognitive behavioral therapy (CBT), may be used to target cognitive distortions such as “jumping to conclusions”, thereby rebalancing feedforward with feedback signals, and restoring a sense of self-agency in individuals with FMD.
Functional movements may use a similar final motor pathway as voluntary movements. However, patients lack a sense of control for these abnormal movements that is referred to as an impairment in self-agency and has been confirmed in several neurophysiological and imaging studies. Most likely impaired self-agency is associated with reduced activation of the right temporoparietal junction.
Apart from a lack of agency, patients with FMD have a loss of sensory attenuation, a physiological phenomenon describing a decrease of perceived intensity of a self-induced force compared to an externally generated force. Sensory attenuation contributes to label a movement as self-generated and can be correlated with a loss of self-agency. Its impairment has been demonstrated in two studies, the first one using a force matching paradigm5 and the second one showing a loss of a physiological amplitude reduction of sensory evoked potentials (e. g., N20 and N30) at the onset of self-generated movements11. Both phenomena, the loss of sensory attenuation, in addition to impaired self-agency, probably contribute to the increase in body-focused attention in our patients.
Sensory processing dysfunction is an additional mechanism likely involved in FMD. Pathophysiological models suggest an abnormal allocation of attention that may impair the quality of sensory information available. As a result, abnormal ”top-down” predictions from the cortex may dominate “bottom-up” sensory inputs, reducing the quality of sensory information available during a decision-making task. Consequently, individuals with FMD form a decision with less sensory information and are more likely to change it when confronted with new sensory evidence. The pathophysiological phenomena elucidated above have great impact on possible treatment strategies.
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