Dissociated motor learning and de-adaptation in patients with functional gait disorders.

Walking onto a stationary platform that had been previously experienced as moving generates a locomotor after-effect-the so-called 'broken escalator' phenomenon. The motor responses that occur during locomotor after-effects have been mapped theoretically using a hierarchal Bayesian model of brain function that takes into account current sensory information that is weighted according to prior contextually-relevant experiences; these in turn inform automatic motor responses. Here, we use the broken escalator phenomenon to explore motor learning in patients with functional gait disorders and probe whether abnormal postural mechanisms override ascending sensory information and conscious intention, leading to maladaptive and disabling gait abnormalities. Fourteen patients with functional gait disorders and 17 healthy control subjects walked onto a stationary sled ('Before' condition, five trials), then onto a moving sled ('Moving' condition, 10 trials) and then again onto the stationary sled ('After' condition, five trials). Subjects were warned of the change in conditions. Kinematic gait measures (trunk displacement, step timing, gait velocity), EMG responses, and subjective measures of state anxiety/instability were recorded per trial. Patients had slower gait velocities in the Before trials (P < 0.05) but were able to increase this to accommodate the moving sled, with similar learning curves to control subjects (P = 0.87). Although trunk and gait velocity locomotor after-effects were present in both groups, there was a persistence of the locomotor after-effect only in patients (P < 0.05). We observed an increase in gait velocity during After trials towards normal values in the patient group. Instability and state anxiety were greater in patients than controls (P < 0.05) only during explicit phases (Before/After) of the task. Mean 'final' gait termination EMG activity (right gastrocnemius) was greater in the patient group than controls. Despite a dysfunctional locomotor system, patients show normal adaptive learning. The process of de-adaptation, however, is prolonged in patients indicating a tendency to perpetuate learned motor programmes. The trend to normalization of gait velocity following a period of implicit motor learning has implications for gait rehabilitation potential in patients with functional gait disorders and related disorders (e.g. fear of falling).

Detecting Abnormal Eye Movements in Patients with Neurodegenerative Diseases - Current Insights.

This review delineates the ocular motor disturbances across a spectrum of neurodegenerative disorders, including Alzheimer's Disease (AD) and related disorders (ADRD), Parkinson's Disease (PD), atypical parkinsonism, and others, leveraging advancements in eye-tracking technology for enhanced diagnostic precision. We delve into the different classes of eye movements, their clinical assessment, and specific abnormalities manifesting in these diseases, highlighting the nuanced differences and shared patterns. For instance, AD and ADRD are characterized by increased saccadic latencies and instability in fixation, while PD features saccadic hypometria and mild smooth pursuit impairments. Atypical parkinsonism, notably Progressive Supranuclear Palsy (PSP) and Corticobasal Syndrome (CBS), presents with distinct ocular motor signatures such as vertical supranuclear gaze palsy and saccadic apraxia, respectively. Our review underscores the diagnostic value of eye movement analysis in differentiating between these disorders and also posits the existence of underlying common pathological mechanisms. We discuss how eye movements have potential as biomarkers for neurodegenerative diseases but also some of the existing limitations.

Reflexive and volitional saccadic eye movements and their changes in age and progressive supranuclear palsy.

BACKGROUND AND OBJECTIVES: Saccades, rapid movements of the eyes towards a visual or remembered target, are useful in understanding the healthy brain and the pathology of neurological conditions such as progressive supranuclear palsy (PSP). We set out to investigate the parameters of horizontal reflexive and volitional saccades, both visually guided and memory-guided, over a 1 min epoch in healthy individuals and PSP patients. METHODS: An experimental paradigm tested reflexive, volitional visually guided, and volitional memory-guided saccades in young healthy controls (n = 14; 20-31 years), PSP patients (n = 11; 46-75 years) and older age-matched healthy controls (n = 6; 56-71 years). The accuracy and velocity of saccades was recorded using an EyeBrain T2® video eye tracker and analyses performed using the MyEyeAnalysis® software. Two-way analysis of variance (ANOVA) was used to identify significant effects (p < 0.01) between young and older controls to investigate the effects of ageing upon saccades, and between PSP patients and age-matched controls to study the effects of PSP upon saccades. RESULTS: In both healthy individuals and PSP patients, volitional saccades are slower and less accurate than reflexive saccades. In PSP patients, accuracy is lower across all saccade types compared to age-matched controls, but velocity is lower only for reflexive saccades. Crucially, there is no change in accuracy or velocity of consecutive saccades over short (one-minute) timescales in controls or PSP patients. CONCLUSIONS: Velocity and accuracy of saccades in PSP does not decrease over one-minute timescales, contrary to that previously observed in Parkinson's Disease (PD), suggesting a potential clinical biomarker for the distinction of PSP from PD.

Ocular myasthenia gravis saccades as a measure of extraocular muscle function.

Background: It is important to understand the pathophysiology of ocular myasthenia gravis (OMG) to improve treatment. Aim: To use modern video-oculography to characterise saccadic eye movements in patients with OMG, including anti-AChR, anti-MuSK, anti-LRP4, and seronegative OMG. Methods: In total, 21 patients with OMG and five age-matched healthy control subjects underwent video-oculography. Participants performed a sequence of horizontal saccades (3 minutes each) at ±5°, ± 10°, and ±20°, followed by 3 minutes of saccades directed at randomly presented targets at ±5°, ± 10°, and ±15°. We recorded the direction, amplitude, duration, peak, and average velocity of each saccade for each task for each participant. Results: Saccadic amplitude, duration, and average velocity were all lower in OMG patients than in control subjects (p < 0.021). Saccadic amplitude and velocity decreased over time, but this decrease was similar in OMG patients and control subjects. Fixation drift and ocular disparity tended to be greater in OMG patients than in control subjects. Saccadic intrusions occurred more frequently in OMG patients than in control subjects (p < 0.001). No significant effects of time or group by time on fixation drift or ocular disparity were found. Discussion: Saccadic velocities in OMG patients differed from those in normal control subjects, which suggests that OMG affects fast-twitch fibres, although fast-twitch fibres were still able to generate "twitch" or "quiver" movements in the presence of even severe ophthalmoplegia. Slow-twitch muscle fibres involved in gaze holding were also affected, accounting for increased fixation drift following saccades. Our objective finding of increased fixation drift and a larger number of saccadic intrusions mirror our anecdotal experience of patients with OMG who report significant diplopia despite minimal ophthalmoplegia on examination. Such microsaccades may be a surrogate for compensation of a gaze-holding deficit in MG.