Altered Saccades, Pupil, and Blink Responses in Functional Motor Disorder: Insight into Neurobiological Mechanisms

BackgroundFunctional motor disorder (FMD) is a common and disabling condition with incompletely understood pathophysiology. Eye-tracking offers a method to objectively examine cognitive and motor control processes and their underlying neural pathways. We aimed to quantify saccade, blink and pupil responses in FMD and healthy controls performing an interleaved pro-/anti-saccade task, and to investigate the relationships between oculomotor measures and motor and non-motor symptom severity. MethodsWe conducted video-based eye-tracking in 104 patients with clinically definite FMD and 115 age- and sex-matched healthy controls performing the saccade task. Patients completed questionnaires on depressive, pain-related, dissociative, non-motor somatic symptoms. Clinician-rated motor severity and centrally acting medication was recorded in FMD patients. ResultsCompared to controls, FMD patients showed increased anti-saccade error rates (p < 0.001), anticipatory saccades (p [&le;] 0.003), altered blink distribution (p < 0.001), and reduced pupil dilation velocity (p < 0.001). However, reduced pupil dilation velocity was not significant in subsample of unmedicated patients. Higher anti-saccade error rates were significantly associated with depressive symptoms, pain severity, dissociative symptoms, non-motor somatic symptom burden, and motor severity (all p < 0.05). ConclusionsWe hypothesize that the altered saccade and blink responses result from altered processing in the frontal cortex and basal ganglia which provide critical input to brainstem oculomotor control areas in FMD. These results support neurobiological models proposing altered predictive and attentional processing underlying FMD. Association between oculomotor measures and symptom severity suggests that specific cognitive abnormalities may play a role in the pathophysiology of these symptoms in FMD. WHAT IS ALREADY KNOWN ON THIS TOPICFMD is increasingly interpreted through predictive coding models suggesting abnormalities in predictions about motor and sensory states driven by abnormally focused attention. Yet the underlying neurobiology remains poorly defined. Empirical studies directly probing basic predictive processes in FMD are scarce, and implicit cognitive-motor interactions, particularly those involving motor learning and adaptation, have been insufficiently explored. WHAT THIS STUDY ADDSOnly two previous studies have used eye-tracking in FMD, focusing mainly on diagnostic saccadic markers. Using time-series analyses of saccadic, blink, and pupillary data, we show abnormalities in inhibitory control, predictive processing, and implicit learning. Due to strong homology between human and primate neurophysiology and neuroimaging findings in oculomotor control, the findings can be linked to dysfunction within cortico-basal ganglia circuits. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYOculomotor abnormalities correlated with motor and non-motor symptom severity, indicating mechanistic relevance. The findings provide empirical support for predictive coding accounts and point to involvement of subcortical structures including projections from the frontal cortex to the basal ganglia. This highlights the value of studying cortico-basal ganglia circuits with implications for treatment and of developing oculomotor measures as potential biomarkers in FMD.