Isabel Pareés

A Bayesian account of ‘hysteria’

This article provides a neurobiological account of symptoms that have been called ‘hysterical’, ‘psychogenic’ or ‘medically unexplained’, which we will call functional motor and sensory symptoms. We use a neurobiologically informed model of hierarchical Bayesian inference in the brain to explain functional motor and sensory symptoms in terms of perception and action arising from inference based on prior beliefs and sensory information. This explanation exploits the key balance between prior beliefs and sensory evidence that is mediated by (body focused) attention, symptom expectations, physical and emotional experiences and beliefs about illness. Crucially, this furnishes an explanation at three different levels: (i) underlying neuromodulatory (synaptic) mechanisms; (ii) cognitive and experiential processes (attention and attribution of agency); and (iii) formal computations that underlie perceptual inference (representation of uncertainty or precision). Our explanation involves primary and secondary failures of inference; the primary failure is the (autonomous) emergence of a percept or belief that is held with undue certainty (precision) following top-down attentional modulation of synaptic gain. This belief can constitute a sensory percept (or its absence) or induce movement (or its absence). The secondary failure of inference is when the ensuing percept (and any somatosensory consequences) is falsely inferred to be a symptom to explain why its content was not predicted by the source of attentional modulation. This account accommodates several fundamental observations about functional motor and sensory symptoms, including: (i) their induction and maintenance by attention; (ii) their modification by expectation, prior experience and cultural beliefs and (iii) their involuntary and symptomatic nature.

Active inference, sensory attenuation and illusions

Active inference provides a simple and neurobiologically plausible account of how action and perception are coupled in producing (Bayes) optimal behaviour. This can be seen most easily as minimising prediction error: we can either change our predictions to explain sensory input through perception. Alternatively, we can actively change sensory input to fulfil our predictions. In active inference, this action is mediated by classical reflex arcs that minimise proprioceptive prediction error created by descending proprioceptive predictions. However, this creates a conflict between action and perception; in that, self-generated movements require predictions to override the sensory evidence that one is not actually moving. However, ignoring sensory evidence means that externally generated sensations will not be perceived. Conversely, attending to (proprioceptive and somatosensory) sensations enables the detection of externally generated events but precludes generation of actions. This conflict can be resolved by attenuating the precision of sensory evidence during movement or, equivalently, attending away from the consequences of self-made acts. We propose that this Bayes optimal withdrawal of precise sensory evidence during movement is the cause of psychophysical sensory attenuation. Furthermore, it explains the force-matching illusion and reproduces empirical results almost exactly. Finally, if attenuation is removed, the force-matching illusion disappears and false (delusional) inferences about agency emerge. This is important, given the negative correlation between sensory attenuation and delusional beliefs in normal subjects—and the reduction in the magnitude of the illusion in schizophrenia. Active inference therefore links the neuromodulatory optimisation of precision to sensory attenuation and illusory phenomena during the attribution of agency in normal subjects. It also provides a functional account of deficits in syndromes characterised by false inference and impaired movement—like schizophrenia and Parkinsonism—syndromes that implicate abnormal modulatory neurotransmission.

Believing is perceiving: mismatch between self-report and actigraphy in psychogenic tremor

We assessed the duration and severity of tremor in a real-life ambulatory setting in patients with psychogenic and organic tremor by actigraphy, and compared this with self-reports of tremor over the same period. Ten participants with psychogenic tremor and eight with organic tremor, diagnosed using standardized clinical criteria, were studied. In an explicit design, participants were asked to wear a small actigraph capable of continuously monitoring tremor duration and intensity for 5 days while keeping a diary of their estimates of tremor duration during the same period. Eight patients with psychogenic tremor and all patients with organic tremor completed the study. Psychogenic patients reported significantly more of the waking day with tremor compared with patients with organic tremor (83.5 ± 14.0% of the waking day versus 58.0 ± 19.0% of the waking day; P < 0.01), despite having almost no tremor recorded by actigraphy (3.9 ± 3.7% of the waking day versus 24.8 ± 7.7% of the waking day; P = 0.001). Patients with organic tremor reported 28% more tremor than actigraphy recordings, whereas patients with psychogenic tremor reported 65% more tremor than actigraphy. These data demonstrate that patients with psychogenic tremor fail to accurately perceive that they do not have tremor most of the day. The explicit study design we employed does not support the hypothesis that these patients are malingering. We discuss how these data can be understood within models of active inference in the brain to provide a neurobiological framework for understanding the mechanism of psychogenic tremor.

Physical precipitating factors in functional movement disorders

BACKGROUND A traditional explanation for functional (psychogenic) neurological symptoms, including functional movement disorders (FMD), is that psychological stressors lead to unconsciously produced physical symptoms. However, psychological stressors can be identified in only a proportion of patients. Patients commonly reported a physical event at onset of functional symptoms. In this study, we aim to systematically describe physical events and surrounding circumstances which occur at the onset of FMD and discuss their potential role in generation of functional symptoms. METHODS We recruited 50 consecutive patients from a specialized functional movement disorders clinic. Semi-structured interviews provided a retrospective account of the circumstances in the 3 months prior to onset of the FMD. Questionnaires to assess mood disturbance and life events were also completed. RESULTS Eleven males and 39 females were recruited. Forty (80%) patients reported a physical event shortly preceding the onset of the FMD. The FMD occurred after an injury in 11 patients and after an infection in 9. Neurological disorders (n=8), pain (n=4), drug reactions (n=3), surgery (n=3) and vasovagal syncope (n=2) also preceded the onset of the functional motor symptom. 38% of patients fulfilled criteria for a panic attack in association with the physical event. CONCLUSIONS In our cohort, physical events precede the onset of functional symptoms in most patients with FMD. Although historically neglected in favour of pure psychological explanation, they may play an important role in symptoms development by providing initial sensory data, which along with psychological factors such as panic, might drive subsequent FMD.

Secondary and primary dystonia: pathophysiological differences

Primary dystonia is thought to be a disorder of the basal ganglia because the symptoms resemble those of patients who have anatomical lesions in the same regions of the brain (secondary dystonia). However, these two groups of patients respond differently to therapy suggesting differences in pathophysiological mechanisms. Pathophysiological deficits in primary dystonia are well characterized and include reduced inhibition at many levels of the motor system and increased plasticity, while emerging evidence suggests additional cerebellar deficits. We compared electrophysiological features of primary and secondary dystonia, using transcranial magnetic stimulation of motor cortex and eye blink classical conditioning paradigm, to test whether dystonia symptoms share the same underlying mechanism. Eleven patients with hemidystonia caused by basal ganglia or thalamic lesions were tested over both hemispheres, corresponding to affected and non-affected side and compared with 10 patients with primary segmental dystonia with arm involvement and 10 healthy participants of similar age. We measured resting motor threshold, active motor threshold, input/output curve, short interval intracortical inhibition and cortical silent period. Plasticity was probed using an excitatory paired associative stimulation protocol. In secondary dystonia cerebellar-dependent conditioning was measured using delayed eye blink classical conditioning paradigm and results were compared with the data of patients with primary dystonia obtained previously. We found no difference in motor thresholds, input/output curves or cortical silent period between patients with secondary and primary dystonia or healthy controls. In secondary dystonia short interval intracortical inhibition was reduced on the affected side, whereas it was normal on the non-affected side. Patients with secondary dystonia had a normal response to the plasticity protocol on both the affected and non-affected side and normal eye blink classical conditioning that was not different from healthy participants. In contrast, patients with primary dystonia showed increased cortical plasticity and reduced eye blink classical conditioning. Normal motor cortex plasticity in secondary dystonia demonstrates that abnormally enhanced cortical plasticity is not required for clinical expression of dystonia, and normal eye blink conditioning suggests an absence of functional cerebellar involvement in this form of dystonia. Reduced short interval intracortical inhibition on the side of the lesion may result from abnormal basal ganglia output or may be a consequence of maintaining an abnormal dystonic posture. Dystonia appears to be a motor symptom that can reflect different pathophysiological states triggered by a variety of insults.

Neurobiology of functional (psychogenic) movement disorders.

Purpose of review This review explores recent developments in understanding the neurobiological mechanism of functional (psychogenic) movement disorders (FMDs). This is particularly relevant given the resurgence of academic and clinical interest in patients with functional neurological symptoms and the clear shift in diagnostic and treatment approaches away from a pure psychological model of functional symptoms. Recent findings Recent research findings implicate three key processes in the neurobiology of FMD (and by extension other functional neurological symptoms): abnormal attentional focus, abnormal beliefs and expectations, and abnormalities in sense of agency. These three processes have been combined in recent neurobiological models of FMD in which abnormal predictions related to movement are triggered by self-focused attention, and the resulting movement is generated without the normal sense of agency that accompanies voluntary movement. Summary New understanding of the neurobiology of FMD forms an important part of reappraising the way that patients with FMD (and other functional disorders) are characterized and treated. It also provides a testable framework for further exploring the pathophysiology of these common causes of ill health.

Loss of sensory attenuation in patients with functional (psychogenic) movement disorders

Functional movement disorders require attention to manifest yet patients report the abnormal movement to be out of their control. In this study we explore the phenomenon of sensory attenuation, a measure of the sense of agency for movement, in this group of patients by using a force matching task. Fourteen patients and 14 healthy control subjects were presented with forces varying from 1 to 3 N on the index finger of their left hand. Participants were required to match these forces; either by pressing directly on their own finger or by operating a robot that pressed on their finger. As expected, we found that healthy control subjects consistently overestimated the force required when pressing directly on their own finger than when operating a robot. However, patients did not, indicating a significant loss of sensory attenuation in this group of patients. These data are important because they demonstrate that a fundamental component of normal voluntary movement is impaired in patients with functional movement disorders. The loss of sensory attenuation has been correlated with the loss of sense of agency, and may help to explain why patients report that they do not experience the abnormal movement as voluntary.

Failure of explicit movement control in patients with functional motor symptoms

Functional neurological symptoms are one of the most common conditions observed in neurological practice, but understanding of their underlying neurobiology is poor. Historic psychological models, based on the concept of conversion of emotional trauma into physical symptoms, have not been implemented neurobiologically, and are not generally supported by epidemiological studies. In contrast, there are robust clinical procedures that positively distinguish between organic and functional motor signs that rely primarily on distracting attention away from movement or accessing it covertly. We aimed to investigate the neurobiological principles underpinning these techniques and implications for understanding functional symptoms. We assessed 11 patients with functional motor symptoms and 11 healthy controls in three experimental set‐ups, where voluntary movements were made either with full explicit control or could additionally be influenced automatically by factors of which participants were much less aware (one‐back reaching, visuomotor transformation, and precued reaction time with variable predictive value of the precue). Patients specifically failed in those tasks where preplanning of movement could occur and under conditions of increasing certainty regarding the movement to be performed. However, they implicitly learned to adapt to a visuomotor transformation as well as healthy controls. We propose that when the movement to be performed can be preplanned or is highly predicted, patients with functional motor symptoms shift to an explicit attentive mode of processing that impairs kinematics of movement control, but movement becomes normal when such processes cannot be employed (e.g., during unexpected movement or implicit motor adaptation).

Movement Disorders in Adult Patients With Classical Galactosemia

Classical galactosemia is an autosomal recessive inborn error of metabolism leading to toxic accumulation of galactose and derived metabolites. It presents with acute systemic complications in the newborn. Galactose restriction resolves these symptoms, but long‐term complications, such as premature ovarian failure and neurological problems including motor dysfunction, may occur despite adequate treatment. The objective of the current study was to determine the frequency and phenotype of motor problems in adult patients with classical galactosemia. In this cross‐sectional study, adult patients with a biochemically confirmed diagnosis of galactosemia attending our clinic were assessed with an interview and neurological examination and their notes retrospectively reviewed. Patients were classified according to the presence/absence of motor dysfunction on examination. Patients with motor dysfunction were further categorized according to the presence/absence of reported motor symptoms. Forty‐seven patients were included. Thirty‐one patients showed evidence of motor dysfunction including: tremor (23 patients), dystonia (23 patients), cerebellar signs (6 patients), and pyramidal signs (4 patients). Tremor and dystonia were often combined (16 patients). Thirteen patients reported motor symptoms, with 8 describing progressive worsening. Symptomatic treatment was effective in 4 of 5 patients. Nonmotor neurological features (cognitive, psychiatric, and speech disorders) and premature ovarian failure were more frequent in patients with motor dysfunction. Motor dysfunction is a common complication of classical galactosemia, with tremor and dystonia the most frequent findings. Up to one third of patients report motor symptoms and may benefit from appropriate treatment. Progressive worsening is not uncommon and may suggest ongoing brain damage in a subset of patients.

‘Jumping to conclusions’ bias in functional movement disorders

Background Patients with functional neurological disorders often report adverse physical events close to the onset of functional symptoms. However, the mechanism via which a triggering event may set off a functional condition is lacking. One possibility is that patients make abnormal inferences about novel information provided by physical triggering events. In this study, the authors aimed to specifically investigate whether patients with functional movement disorders have abnormalities in probabilistic reasoning. Methods The authors used a well-studied probabilistic reasoning paradigm, ‘the bead task’, in 18 patients with functional movement disorders and 18 healthy agematched controls. The authors assessed the number of beads that participants needed to reach a decision and changes in the certainty of their decisions when confronted with confirmatory or contradictory evidence. Findings Patients with functional movement disorders requested on average significantly fewer beads before reaching a decision than controls (3 vs 6 beads). When confronted with potentially disconfirmatory evidence, patients showed a significantly greater reduction in confidence in their estimates than controls. 40% of patients reached a decision after one or two beads whereas no controls showed this bias. Interpretation Patients with functional movement disorders requested less information to form a decision and were more likely to change their probability estimates in the direction suggested by the new evidence. These findings may have relevance to the manner with which patients with functional neurological disorders process novel sensory data occurring during physical triggering events commonly reported at onset of symptoms.