The Disturbance of Gaze in Progressive Supranuclear Palsy: Implications for Pathogenesis

Chen, Athena L.; Riley, David E.; King, Susan A.; Joshi, Anand C.; Serra, Alessandro; Liao, Ke; Cohen, Mark L.; Otero‐Millan, Jorge; Martínez-Conde, Susana; Strupp, Michael; Leigh, R. John

doi:10.3389/fneur.2010.00147

Cited by 110 publications

(105 citation statements)

References 98 publications

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“…The video-oculography and ABV analysis confirmed that reduced peak eye velocities are the hallmark of PSP and they are tightly correlated with midbrain atrophy where the excitatory burst neurons responsible for vertical saccades are located [28]. Degeneration of midbrain gaze centers including the mesencephalic reticular formation apparently causes progressive slowing of vertical saccades and may lead to vertical gaze palsy [1].…”

Section: Discussionmentioning

confidence: 99%

Patterns of Eye Movement Impairment Correlate with Regional Brain Atrophy in Neurodegenerative Parkinsonism

Vintonyak

Gorges²,

Müller³

et al. 2017

Neurodegener Dis

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Background: One common feature of neurodegenerative parkinsonism including Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP) is altered eye movement control. Characteristic regional structural atrophy patterns in MRI can be observed in PD, MSA, and PSP. Objective: To investigate the association between eye movement disturbances and regional brain atrophy in patients with PD, MSA, and PSP. Methods: High-resolution 3-dimensional T1-weighted MRI images and video-oculographic recordings (EyeLink®) were obtained from 39 PD, 32 PSP, and 18 MSA patients and 24 matched healthy control subjects. Automatic regional volumetric assessment was performed using atlas-based volumetry (ABV). Results: The prevalence of saccadic intrusions as a measure of inhibitory control was significantly increased in PD patients compared to controls (p < 0.001) and negatively correlated with whole brain volume, cerebral brain volume, and occipital lobe volume (p = 0.0057, p = 0.0049, and p = 0.0059, respectively; all p values are false discovery rate corrected). In MSA, smooth pursuit was disturbed by characteristic “catch-up” saccades (p < 0.001) and it was significantly correlated with cerebellar volume (p = 0.004) and pontine volume (p < 0.001). The hallmark of PSP was pathologically slowed vertical peak eye velocities (p < 0.001); the lower the peak eye velocity, the more marked midbrain atrophy (p = 0.007). Conclusions: Foci of regional atrophy correlated with disease-specific eye movement alterations in all investigated parkinsonian syndromes. Oculomotor impairment in PD, predominantly the result of executive dysfunction, was linked to cerebral atrophy. Impairment in the corresponding oculomotor pathways was associated with atrophy of pontocerebellar oculomotor structures in MSA and midbrain atrophy in PSP.

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Section: Discussionmentioning

confidence: 99%

Patterns of Eye Movement Impairment Correlate with Regional Brain Atrophy in Neurodegenerative Parkinsonism

Vintonyak

Gorges²,

Müller³

et al. 2017

Neurodegener Dis

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“…61 Decreases in saccade velocity and gain account for the most characteristic PSP ocular motor deficits, and have been demonstrated to be highly specific findings that allow differentiation of autopsy-confirmed PSP from other disorders. 26 Profound changes in saccade velocity and gain over the course of one year have been demonstrated in two autopsy confirmed cases of PSP.…”

Section: Biomarkers (Table 1)mentioning

confidence: 99%

“…26 Profound changes in saccade velocity and gain over the course of one year have been demonstrated in two autopsy confirmed cases of PSP. 61 Retinal optical coherence tomography (OCT) may also be a promising biomarker for PSP, but it remains in an early stage of investigation. 62 …”

Section: Biomarkers (Table 1)mentioning

confidence: 99%

Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

Boxer

Golbe

et al. 2017

The Lancet Neurology

351

393

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Progressive supranuclear palsy (PSP), once simply considered a common cause of atypical parkinsonism is now recognized as a spectrum of motor and behavioral syndromes associated with a specific four repeat (4R) tau neuropathology at autopsy. There are currently no effective treatments for PSP, but because PSP is strongly linked biochemically and genetically to tau protein abnormalities, there is a growing interest in pursuing clinical trials of new tau-directed therapies for this disorder. Such new tau therapies are envisioned to have disease-modifying effects by reducing brain levels of toxic forms of tau or compensating for loss of tau function. To be most effective, these treatments will need to be initiated at early stages of disease. New research criteria that recognize early forms of PSP and operationalize diagnosis of the full spectrum of clinical phenotypes have recently been published. These criteria and new clinical trial designs have benefited from rapid advances in MRI, physiological and fluid biomarker development for PSP. As tau pathology is also central to Alzheimer’s disease and chronic traumatic encephalopathy, it is believed that a successful tau therapeutic for PSP would inform the treatment of other neurodegenerative diseases.

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“…In that case, it might be baseless to distinguish between fixational and exploratory behaviors. Recent studies have identified abnormal dynamics of saccades and microsaccades as potential diagnostic markers of neurological disease (14)(15)(16); thus, the frame of reference proposed here may have important clinical implications concerning the role of the affected brain centers in the patients' oculomotor behavior.…”

mentioning

confidence: 95%

An oculomotor continuum from exploration to fixation

Otero‐Millan

Macknik

Langston

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

109

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During visual exploration, saccadic eye movements scan the scene for objects of interest. During attempted fixation, the eyes are relatively still but often produce microsaccades. Saccadic rates during exploration are higher than those of microsaccades during fixation, reinforcing the classic view that exploration and fixation are two distinct oculomotor behaviors. An alternative model is that fixation and exploration are not dichotomous, but are instead two extremes of a functional continuum. Here, we measured the eye movements of human observers as they either fixed their gaze on a small spot or scanned natural scenes of varying sizes. As scene size diminished, so did saccade rates, until they were continuous with microsaccadic rates during fixation. Other saccadic properties varied as function of image size as well, forming a continuum with microsaccadic parameters during fixation. This saccadic continuum extended to nonrestrictive, ecological viewing conditions that allowed all types of saccades and fixation positions. Eye movement simulations moreover showed that a single model of oculomotor behavior can explain the saccadic continuum from exploration to fixation, for images of all sizes. These findings challenge the view that exploration and fixation are dichotomous, suggesting instead that visual fixation is functionally equivalent to visual exploration on a spatially focused scale.free-viewing | fixational eye movements | miniature eye movements | fixational saccades | natural images C lassic and current vision studies distinguish between visual exploration, characterized by the alternation of saccades and brief fixation periods, and attempted visual fixation, where subjects maintain relative gaze stability despite continuous but minute fixational eye movements (i.e., microsaccades, slow drift, and oculomotor tremor) (1-7). The theoretical separation between exploratory gaze shifts and attempted fixation dates back to the discovery of fixational eye movements in the early 1900s (2-4), and remains central to contemporary discourse in visual, cognitive, and oculomotor research (8). However, mounting evidence in support of a common generator for both exploratory saccades and fixational microsaccades (refs. 9-12 but see ref. 13) brings into question whether such a dichotomy is justified. Instead, it may be that saccades and microsaccades form an oculomotor continuum along the entire spectrum of exploratory scales, with classical exploratory saccades at one end and classical fixational microsaccades at the other end. In that case, it might be baseless to distinguish between fixational and exploratory behaviors. Recent studies have identified abnormal dynamics of saccades and microsaccades as potential diagnostic markers of neurological disease (14-16); thus, the frame of reference proposed here may have important clinical implications concerning the role of the affected brain centers in the patients' oculomotor behavior.To establish such a framework, one must first reconcile any known discrepancy between the ...

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The Disturbance of Gaze in Progressive Supranuclear Palsy: Implications for Pathogenesis

Cited by 110 publications

References 98 publications

Patterns of Eye Movement Impairment Correlate with Regional Brain Atrophy in Neurodegenerative Parkinsonism

Patterns of Eye Movement Impairment Correlate with Regional Brain Atrophy in Neurodegenerative Parkinsonism

Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

An oculomotor continuum from exploration to fixation

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