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Visuomotor impairments, such as hypometria of visually guided saccades, are common in Parkinson's disease (PD). Explaining the mechanistic underpinning of such abnormal voluntary (eye) movements can provide insights into the pathophysiology of limb movement disorders in PD. We measured visually guided saccades in 20 PD patients using quantitative high-resolution oculography. The experiments source to determine whether common motor deficits in PD, such as those affecting visually-guided saccades reflect excessive inhibition of the superior colliculus or rather involvement of brainstem saccade generators. We found slowing, interruptions, and curvatures in the saccade trajectory. The curvature not only reflected the mismatch in the velocity of relatively slower vertical (compared to horizontal) saccades, but could be due to aberrant activation of the superior colliculus. The irregularities in the saccade trajectory and slowing were prominent in the vertical direction. We suggest that abnormal saccades in PD not only reflect abnormal tectal function, but also suggest abnormal oscillatory behavior in the reciprocally innervating circuit of excitatory and inhibitory burst neurons. Impaired function of excitatory and inhibitory burst neurons causing maladaptive feedback and premature activation of the superior colliculus can cause irregularity in saccade trajectory., (© 2019 Elsevier B.V. All rights reserved.)

People with Parkinson's disease (PD) show impaired decision-making when sensory and memory information must be combined. This recently identified impairment results from an inability to accumulate the proper amount of information needed to make a decision and appears to be independent of dopamine tone and reinforcement learning mechanisms. Although considerable work focuses on PD and decisions involving risk and reward, in this Opinion article we propose that the emerging findings in perceptual decision-making highlight the multisystem nature of PD, and that unraveling the neuronal circuits underlying perceptual decision-making impairment may help in understanding other cognitive impairments in people with PD. We also discuss how a decision-making framework may be extended to gain insights into mechanisms of motor impairments in PD.

Objective: Parkinson's disease (PD) hampers visual search tasks such as reading, driving, and navigation. We examined expectations from past experiences, guiding cognition and contextual priors, on visual search in PD. Methods: We compared eye movements as PD and healthy participants searched for a hidden object (target) in cluttered real‐world scenes. Results: PD participants prolonged fixation on high‐probability (high‐prior) locations for the target, consistent across expected and unexpected scenario. Such emphasis on contextual visual priors, evidenced by high fixation duration on high‐probability areas, was beneficial when the target was at the expected location but presented challenges when the target was situated in an unlikely place. Conclusion: This study contributes to understanding how PD impacts visual search behavior and cognitive processing. The findings indicate that PD alters attention allocation and visual processing by affecting the utilization of contextual visual priors. It provides insights for potential interventions targeting visuo‐cognitive deficits in PD patients. [ABSTRACT FROM AUTHOR]

Objective: Dystonias, characterized by excessive muscle contractions resulting in involuntary postures and movements, impact 3 million people globally, making them the third most common movement disorder. Often accompanied by tremors, dystonias have epidemiological links and non-motor features shared with isolated tremor, such as essential tremor. Both dystonia and tremor present with balance dysfunction and abnormal involuntary movements, potentially linked to abnormal cerebellar function. This study explores the perception of one's own linear movement, heading, particularly discrimination of heading direction, in isolated cervical dystonia, isolated tremor, and their combination. We compare such perception behavior in visual and vestibular domains, predicting that visual heading perception would be superior to vestibular heading perception. Methods: Following the focus on the perception of heading direction, we used psychophysics techniques, such as two-alternative-forced-choice task, to examine perception of direction of one's own movements as they see isolated visual star-cloud movement (visual heading perception) and en bloc body movement (vestibular heading perception). We fitted a sigmoidal psychometric function curve to determine the threshold for visual or vestibular heading perception in our participants. Results: Nineteen participants underwent a two-alternative forced-choice task in the vestibular and visual domains. Results reveal elevated vestibular heading perception thresholds in cervical dystonia with or without tremor, and isolated tremor compared to healthy controls. Vestibular heading perception threshold was comparable in cervical dystonia with tremor and isolated tremor, but it was even worse in isolated cervical dystonia. Visual heading perception, however, remained less affected all three conditions—isolated cervical dystonia, isolated tremor, and their combination. Conclusion: These findings indicate shared deficits and distinctions in the perception of linear translational heading across movement disorders, such as isolated cervical dystonia, tremor, or their combination, offering insights into their pathophysiology, particularly the involvement of cerebellum regions responsible for vestibular processing. [ABSTRACT FROM AUTHOR]

Background: Self-reported diplopia is described in up to one-third of Parkinson’s disease (PD) patients. Objective: The purpose of our study was to expand our understanding of the mechanistic underpinnings of diplopia in PD. We hypothesize that the time-based control of eye alignment and increased eye deviation under binocular viewing will be related to the fusion-initiating and fusion-maintaining component deficits of disparity-driven vergence in PD. Methods: We used high-resolution video-oculography to measure eye alignment under binocular and monocular viewing and disparity-driven vergence in 33 PD and 10 age-matched healthy participants. We computed eye deviation and time-based control of eye alignment, occurrence of conjugate saccadic eye movements, latency and gain of vergence (fusion initiation), and variance of eye position at the end of dynamic vergence (fusion maintenance). Results: We categorized PD subjects into three groups, considering their timebased control of eye alignment as compared to healthy controls in binocular viewing. Group 1 = 45% had good control and spent >80% of the time when the eyes were well-aligned, Group 2 = 26% had intermediate control and spent <80% but greater >5% of the time when the eyes were well-aligned, and Group 3 = 29% had very poor control with increased eye deviation majority of the times (<5% of the time when the eyes were well-aligned). All three groups exhibited greater eye deviation under monocular viewing than controls. PD subjects exhibited fusion-initiating and fusion-maintaining vergence deficits (prolonged latencies, reduced vergence gain, increased variance of fusion-maintaining component) with a greater probability of saccadic movements than controls. Group 2 and Group 3 subjects were more likely to exhibit failure to initiate vergence (>20%) than Group 1 (13%) and controls (0%) trials. No significant difference was found in the Unified Parkinson’s Disease Rating Scale (UPDRS—a tool to measure the severity of PD) values between the three PD groups (Group 1 = 33.69 ± 14.22, Group 2 = 38.43 ± 22.61, and Group 3 = 23.44 ± 1, p > 0.05). Conclusion: The majority of PD subjects within our cohort had binocular dysfunction with increased eye deviation under monocular viewing and disparity-driven vergence deficits. PD subjects with intermediate or poor control of eye deviation under binocular viewing had greater fusion-initiating and fusion-maintaining vergence deficits. The study highlights the importance of assessing binocular dysfunction in PD subjects independent of the severity of motor symptoms. [ABSTRACT FROM AUTHOR]

This review delves into the historical evolution and ongoing controversy surrounding the relationship between tremor and dystonia. The Dystonia Consensus Panel and the International Parkinson's and Movement Disorders Society's Tremor Taskforce have attempted to define these entities, but the complexity arises when patients have a combination of both dystonia and tremor. The term "dystonic tremor" has sparked diverse interpretations, with debates over its clinical features and the need for more objectively defined characteristics. Logistic regression analyses in a large cohort of dystonia patients identified determinants such as body region affected by dystonia, dystonia severity, age, and recruitment site, with unexpected associations emphasizing the subjectivity in detecting and classifying tremor. The study further discovered diverse prevalence of "dystonic tremor" based on different definitions, revealing substantial variability among investigators. The recently convened Dystonia-Tremor panel aimed to address these challenges by proposing a more uniform nomenclature, emphasizing precise and descriptive terms. Despite the complexity, instrumented measures, such as electromyography, temporal discrimination threshold, blink reflex, and trajectory shape analysis, seem to be useful in distinguishing between tremor and dystonia. The pathophysiology debate centers around the involvement of the cerebello-thalamo-cortical and basal ganglia-thalamo-cortical circuits. Evidence supports the role of both circuits in driving the pathophysiology of dystonic tremor, challenging the notion of a clear dichotomy. The review concludes by emphasizing the need for a nuanced understanding, highlighting the intricate interplay between tremor and dystonia, and the potential of instrumental measures in advancing diagnostic accuracy. • This minireview covers three key updates on relationship between tremor and dystonia. • Historical Complexity: Examines tremor-dystonia evolution, defining challenges over time. • Dystonic Tremor Debate: Term sparks diverse interpretations; logistic regression reveals subjectivity. • Nomenclature & Measures: Dystonia-Tremor panel proposes uniform terms; instruments aid distinction, challenging dichotomy. [ABSTRACT FROM AUTHOR]

Objectives: Parkinson's disease (PD) commonly affects visuospatial navigation causing postural instability and falls. Our overarching aim was to examine the visual and vestibular systems governing visuospatial navigation in PD. We hypothesize that PD affects vestibular and visual motion perception but to a different extent. The effects of PD on motion perception are dependent on the severity of the disease. Methods: The two‐alternative‐forced‐choice task objectively measured the motion perception during two experiments. One experiment examined the vestibular motion perception with en bloc movement of the platform. The second experiment tested the visual motion perception using an immersive virtual reality goggle. Results: We found that accuracy, threshold, and precision of vestibular perception were more impaired in advanced‐PD patients compared to those with a mild form of the disease. The parameters also correlated with the disease duration, overall axial motor impairment causing postural instability and falls, and subjective rating of the balance function. Such changes were present but less severe in visual motion perception. Conclusion: We conclude that PD affects motion perception in the visual and vestibular domains in a severity‐dependent manner. The impact of the disease in the vestibular domain is more severe compared to the visual domain. © 2020 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

The relationship between two common movement disorders, dystonia and tremor, is controversial. Both deficits have correlates in the network that includes connections between the cerebellum and the basal ganglia. In order to assess the physiological relationship between tremor and dystonia, we measured the activity of 727 pallidal single-neurons during deep brain stimulation surgery in patients with cervical dystonia without head oscillations, cervical dystonia plus jerky oscillations, and cervical dystonia with sinusoidal oscillations. Cluster analyses of spike-train recordings allowed classification of the pallidal activity into burst, pause, and tonic. Burst neurons were more common, and number of spikes within spike and inter-burst intervals was shorter in pure dystonia and jerky oscillation groups compared to the sinusoidal oscillation group. Pause neurons were more common and irregular in pure tremor group compared to pure dystonia and jerky oscillation groups. There was bihemispheric asymmetry in spontaneous firing discharge in pure dystonia and jerky oscillation groups, but not in sinusoidal oscillation group. These results demonstrate that the physiology of pallidal neurons in patients with pure cervical dystonia is similar to those who have cervical dystonia combined with jerky oscillations, but different from those who have cervical dystonia combined with sinusoidal oscillations. These results imply distinct mechanistic underpinnings for different types of head oscillations in cervical dystonia. [ABSTRACT FROM AUTHOR]

Introduction: Saccades are rapid, yoked eye movements to direct a target over fovea. The complex circuitry of saccadic eye movements has been exhaustively described. As a result clinicians can elegantly localize the pathology if it falls on the neuraxis responsible for saccades. Traditionally saccades are studied with their quantitative characteristics such as amplitude, velocity, duration, direction, latency and accuracy. Areas covered: Amongst all subtypes, the physiology of the visually guided saccades is most extensively studied. Here we will review the basic and pertinent neuro-anatomy and physiology of visually guided saccade and then discuss common or classic disorders affecting the velocity of visually guided saccades. We will then discuss the basic mechanism for saccade slowing in these disorders. Expert commentary: Prompt appreciation of disorders of saccade velocity is critical to reach appropriate diagnosis. Disorders of midbrain, cerebellum, or basal ganglia can lead to prolonged transition time during gaze shift and decreased saccade velocity. [ABSTRACT FROM PUBLISHER]

Cervical dystonia is characterized by abnormal posturing of the head, often combined with tremor-like oscillatory head movements. The nature and source of these oscillatory head movements is controversial, so they were quantified to delineate their characteristics and develop a hypothetical model for their genesis. A magnetic search coil system was used to measure head movements in 14 subjects with cervical dystonia. Two distinct types of oscillatory head movements were detected for most subjects, even when they were not clinically evident. One type had a relatively large amplitude and jerky irregular pattern, and the other had smaller amplitude with a more regular and sinusoidal pattern. The kinematic properties of these two types of oscillatory head movements were distinct, although both were often combined in the same subject. Both had features suggestive of a defect in a central neural integrator. The combination of different types of oscillatory head movements in cervical dystonia helps to clarify some of the current debates regarding whether they should be considered as manifestations of dystonia or tremor and provides novel insights into their potential pathogenesis. © 2015 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background Several case reports and small series have indicated that tardive dystonia is responsive to globus pallidus deep brain stimulation. Whether different subtypes or distributions of tardive dystonia are associated with different outcomes remains unknown. Methods We assessed the outcomes and temporal profile of improvement of eight tardive dystonia patients who underwent globus pallidus deep brain stimulation over the past six years through record review. Due to the retrospective nature of this study, it was not blinded or placebo controlled. Results Consistent with previous studies, deep brain stimulation improved the overall the Burke–Fahn–Marsden motor scores by 85.1 ± 13.5%. The distributions with best responses in descending order were upper face, lower face, larynx/pharynx, limbs, trunk, and neck. Patients with prominent cervical dystonia demonstrated improvement in the Toronto Western Spasmodic Torticollis Rating Scale but improvements took several months. In four patients the effects of deep brain stimulation on improvement in Burke Fahn Marsden score was rapid, while in four cases there was partial rapid response of neck and trunk dystonia followed by was gradual resolution of residual symptoms over 48 months. Conclusion Our retrospective analysis shows excellent resolution of tardive dystonia after globus pallidus deep brain stimulation. We found instantaneous response, except with neck and trunk dystonia where partial recovery was followed by further resolution at slower rate. Such outcome is encouraging for using deep brain stimulation in treatment of tardive dystonia. [ABSTRACT FROM AUTHOR]

Introduction Generalized dystonia, both primary and secondary forms, and axial dystonias such as tardive dystonia, and idiopathic cervical dystonia are responsive to globus pallidus interna (GPi) DBS. There is a paucity of investigations probing the impact of DBS on adult-onset axial dystonia. We assessed the efficacy of GPi DBS in four patients with rare adult-onset axial dystonia. Methods Primary outcome measure was improvement in the motor component of the Burke-Fahn-Marsden (BFM) rating scale. Secondary outcome measures were quality of life as determined by the SF-36 questionnaire, time to achieve best possible benefit and DBS parameters that accounted for the best response. In patients with prominent concomitant cervical dystonia we also used the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Results GPi DBS improved BFM scores by 87.63 ± 11.46%. Improvement in total severity scale of TWSTRS was 71.5 ± 12.7%. Quality of life also remarkably improved as evidenced by 109.38 ± 82.97 and 7.05 ± 21.48% percent change in psychometrically-based physical component summary (PCS), and a mental component summary (MCS) score respectively. Conclusions GPi DBS is a very effective treatment for adult-onset axial dystonia. Considering its refractoriness to medical therapy and significant impact on quality of life DBS should be considered for this disorder. [ABSTRACT FROM AUTHOR]

Ataxia-telangiectasia is known for cerebellar degeneration, but clinical descriptions of abnormal tone, posture, and movements suggest involvement of the network between cerebellum and basal ganglia. We quantitatively assessed the nature of upper-limb movement disorders in ataxia-telangiectasia. We used a three-axis accelerometer to assess the natural history and severity of abnormal upper-limb movements in 80 ataxia-telangiectasia and 19 healthy subjects. Recordings were made during goal-directed movements of upper limb (kinetic task), while arms were outstretched (postural task), and at rest. Almost all ataxia-telangiectasia subjects (79/80) had abnormal involuntary movements, such as rhythmic oscillations (tremor), slow drifts (dystonia or athetosis), and isolated rapid movements (dystonic jerks or myoclonus). All patients with involuntary movements had both kinetic and postural tremor, while 48 (61%) also had resting tremor. The tremor was present in transient episodes lasting several seconds during two-minute recording sessions of all three conditions. Percent time during which episodic tremor was present was greater for postural and kinetic tasks compared to rest. Resting tremor had higher frequency but smaller amplitude than postural and kinetic tremor. Rapid non-rhythmic movements were minimal during rest, but were triggered during sustained arm postures and goal directed arm movements suggesting they are best considered a form of dystonic jerks or action myoclonus. Advancing age did not correlate with the severity of involuntary limb movements. Abnormal upper-limb movements in ataxia-telangiectasia feature classic cerebellar impairment, but also suggest involvement of the network between the cerebellum and basal ganglia. [ABSTRACT FROM AUTHOR]

Dystonia and tremor frequently co-occur. In some cases, they have shared biological mechanisms, while in others dystonia and tremor are two comorbid conditions. The term "dystonic tremor" is used to describe tremor in those who have dystonia. Two mutually exclusive definitions of "dystonic tremor" were proposed. According to one definition, dystonic tremor is the tremor in the dystonic body part. An alternate definition of dystonic tremor entails irregular and jerky oscillations that have saw tooth appearance with or without overt dystonia. This paper outlines the differences in two definitions of dystonic tremor and identifies their limitations. Given the diverse views defining "dystonic tremor", this paper will use the term "tremor in dystonia". In addition, we will outline different ways to separate the subtypes of tremor in dystonia. Then we will discuss pathophysiological mechanisms derived from the objective measures and single neuron physiology analyses of tremor in dystonia. This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh. • Relationship between frequently co-occurring tremor and dystonia is controversial. • Physiological studies have suggested obvious differences between tremor and dystonia. • Here we review controversy, clinical features, and pathophysiology of tremor in dystonia. [ABSTRACT FROM AUTHOR]

Abstract Dystonia is the third most common movement disorder affecting three million people worldwide. Cervical dystonia is the most common form of dystonia. Despite common prevalence the pathophysiology of cervical dystonia is unclear. Traditional view is that basal ganglia is involved in pathophysiology of cervical dystonia, while contemporary theories suggested the role of cerebellum and proprioception in the pathophysiology of cervical dystonia. It was recently proposed that the cervical dystonia is due to malfunctioning of the head neural integrator – the neuron network that normally converts head velocity to position. Most importantly the neural integrator model was inclusive of traditional proposal emphasizing the role of basal ganglia while also accommodating the contemporary view suggesting the involvement of cerebellum and proprioception. It was hypothesized that the head neural integrator malfunction is the result of impairment in cerebellar, basal ganglia, or proprioceptive feedback that converge onto the integrator. The concept of converging input from the basal ganglia, cerebellum, and proprioception to the network participating in head neural integrator explains that abnormality originating anywhere in the network can lead to the identical motor deficits – drifts followed by rapid corrective movements – a signature of neural integrator dysfunction. We tested this hypothesis in an experiment examining simultaneously recorded globus pallidal single-unit activity, synchronized neural activity (local field potential), and electromyography (EMG) measured from the neck muscles during the standard-of-care deep brain stimulation surgery in 12 cervical dystonia patients (24 hemispheres). Physiological data were collected spontaneously or during voluntary shoulder shrug activating the contralateral trapezius muscle. The activity of pallidal neurons during shoulder shrug exponentially decayed with time constants that were comparable to one measured from the pretectal neural integrator and the trapezius electromyography. These results show that evidence of abnormal neural integration is also seen in globus pallidum, and that latter is connected with the neural integrator. Pretectal single neuron responses consistently preceded the muscle activity; while the globus pallidum internus response always lagged behind the muscle activity. Globus pallidum externa had equal proportion of lag and lead neurons. These results suggest globus pallidum receive feedback from the muscles or the efference copy from the integrator or the other source of the feedback. There was bi-hemispheric asymmetry in the pallidal single-unit activity and local field potentials. The asymmetry correlated with degree of lateral head turning in cervical dystonia patients. These results suggest that bihemispheric asymmetry in the feedback leads to asymmetric dysfunction in the neural integrator causing head turning. Highlights • Integrative network of brainstem, cerebellum, and basal ganglia can cause dystonia. • Integration is changing dynamic signal to steady-state discharge. • Discharge property of the basal ganglia output reflect abnormal neural integration. • Basal ganglia abnormality is secondary, due to impaired network feedback. [ABSTRACT FROM AUTHOR]

The aim of this paper is to find the differences in the physiology of the pallidal neurons in DYT1 and non-DYT1 dystonia. We performed microelectrode recording of the single unit activity in both segments of the globus pallidus during stereotactic implantation of electrodes for deep brain stimulation (DBS). We found a reduced firing rate, reduced burst rate, and increased pause index in both pallidal segments in DYT1. Also, in DYT1 the activity in both pallidal segments was similar, but not so in non-DYT1. The results suggest a common pathological focus for both pallidal segments, located in the striatum. We also speculate that strong striatal influence on GPi and GPe overrides other input sources to the pallidal nuclei causing similarity in neuronal activity. We found significant differences in neuronal activity between DYT1 and non-DYT1 neurons. Our findings shed light on the pathophysiology of DYT-1 dystonia which can be very different from non-DYT1 dystonia and have other efficient treatment tactics. [Display omitted] • In globus pallidus in DYT1 neurons was observed decreased firing and burst rate and shift towards pause pattern. • Similar changes in DYT1 neurons show a common for globus pallidus segments pathological focus, which can be the striatum. • The similarity between both globus pallidus segments can be caused by strong striatal influence, overriding other inputs. [ABSTRACT FROM AUTHOR]

Ocular oscillations often have critical role in diagnostic algorithm of neurodegenerative disorders. Nystagmus, if present in parkinsonian syndrome, suggests cerebellar involvement that is typical of multiple system atrophy. We found vertical jerky oscillations of the eyes during oculographic assessments using head-fixed corneal curvature trackers in six patients with progressive supranuclear palsy. The oscillations were eliminated by adequate head stabilization of the patients. Although this phenomenon gave the initial impression of "downbeat nystagmus", the oscillations were phase locked and frequency matched with subtle jerky head oscillations. We interpreted such jerky eye oscillations as "pseudonystagmus" representing the vestibulo-ocular reflex in response to involuntary subtle jerky head oscillations in our patients. This study further emphasizes the importance of head stabilization during instrumented or clinical assessment of gaze holding. • Ocular oscillations play an important role in diagnosing neurodegenerative disorders. • Oculography showed vertical jerky eye oscillations in progressive supranuclear palsy. • The oscillations were frequency matched with subtle jerky head oscillations. • They were the vestibulo-ocular reflex in response to jerky head oscillations. [ABSTRACT FROM AUTHOR]