Limits...
The disturbance of gaze in progressive supranuclear palsy: implications for pathogenesis.

Chen AL, Riley DE, King SA, Joshi AC, Serra A, Liao K, Cohen ML, Otero-Millan J, Martinez-Conde S, Strupp M, Leigh RJ - Front Neurol (2010)

Bottom Line: These vertical and vergence eye movements habitually work in concert to enable visuomotor skills that are important during locomotion with the hands free.Taken with the prominent early feature of falls, these findings suggest that PSP tauopathy impairs a recently evolved neural system concerned with bipedal locomotion in an erect posture and frequent gaze shifts between the distant environment and proximate hands.This approach provides a conceptual framework that can be used to address the nosological challenge posed by overlapping clinical and neuropathological features of neurodegenerative tauopathies.

View Article: PubMed Central - PubMed

Affiliation: Veterans Affairs Medical Center, University Hospitals Case Medical Center Cleveland, OH, USA.

ABSTRACT
Progressive supranuclear palsy (PSP) is a disease of later life that is currently regarded as a form of neurodegenerative tauopathy. Disturbance of gaze is a cardinal clinical feature of PSP that often helps clinicians to establish the diagnosis. Since the neurobiology of gaze control is now well understood, it is possible to use eye movements as investigational tools to understand aspects of the pathogenesis of PSP. In this review, we summarize each disorder of gaze control that occurs in PSP, drawing on our studies of 50 patients, and on reports from other laboratories that have measured the disturbances of eye movements. When these gaze disorders are approached by considering each functional class of eye movements and its neurobiological basis, a distinct pattern of eye movement deficits emerges that provides insight into the pathogenesis of PSP. Although some aspects of all forms of eye movements are affected in PSP, the predominant defects concern vertical saccades (slow and hypometric, both up and down), impaired vergence, and inability to modulate the linear vestibulo-ocular reflex appropriately for viewing distance. These vertical and vergence eye movements habitually work in concert to enable visuomotor skills that are important during locomotion with the hands free. Taken with the prominent early feature of falls, these findings suggest that PSP tauopathy impairs a recently evolved neural system concerned with bipedal locomotion in an erect posture and frequent gaze shifts between the distant environment and proximate hands. This approach provides a conceptual framework that can be used to address the nosological challenge posed by overlapping clinical and neuropathological features of neurodegenerative tauopathies.

No MeSH data available.


Related in: MedlinePlus

Comparison of vertical smooth pursuit (A,B) and ocular following responses (C,D) of a normal subject and a PSP patient. Both sets of responses were evoked as subjects viewed vertically-moving sine-wave gratings on a monitor subtending 50° × 37.5°. For pursuit, the stimulus was sinusoidal motion of a 0.27 cycles per degree grating over the range of temporal frequencies shown. For OFR, the stimulus was ramp motion for 200 ms of a 0.17 cycles per degree grating. At lower frequencies of motion, both the normal subject (A) and the PSP patient (B) showed smooth tracking with some predictive properties (arrows); at high frequencies, the PSP (B) showed substantial decrease in the size of the pursuit movements compared with the control subject. Both upward (C) and downward (D) grating motion induced similar-sized OFR from the control subject (blue line) and PSP patient (red line), although the latency to onset was larger in the patient. See Joshi et al. (2010) for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3008928&req=5

Figure 7: Comparison of vertical smooth pursuit (A,B) and ocular following responses (C,D) of a normal subject and a PSP patient. Both sets of responses were evoked as subjects viewed vertically-moving sine-wave gratings on a monitor subtending 50° × 37.5°. For pursuit, the stimulus was sinusoidal motion of a 0.27 cycles per degree grating over the range of temporal frequencies shown. For OFR, the stimulus was ramp motion for 200 ms of a 0.17 cycles per degree grating. At lower frequencies of motion, both the normal subject (A) and the PSP patient (B) showed smooth tracking with some predictive properties (arrows); at high frequencies, the PSP (B) showed substantial decrease in the size of the pursuit movements compared with the control subject. Both upward (C) and downward (D) grating motion induced similar-sized OFR from the control subject (blue line) and PSP patient (red line), although the latency to onset was larger in the patient. See Joshi et al. (2010) for details.

Mentions: Motion of images across the retina (retinal slip) serves as the primary stimulus to a range of smooth ocular tracking, including the ocular following response (OFR), optokinetic nystagmus, and smooth pursuit (Table 1; Miles, 1998). The OFR is a pre-attentive, short-latency visual tracking mechanism that can be induced by sudden motion of a sinusoidal grating on a computer screen (in our laboratory, subtending 37.5° high × 50° wide; Gellman et al., 1990; Sheliga et al., 2005; Joshi et al., 2009). The OFR can even be tested in PSP patients, who cannot focus their visual attention (or fovea) on the stimulus. Typically, OFR are small, and variable between subjects, but show consistent dependence on the direction and spatial frequency of the stimulus (Gellman et al., 1990; Sheliga et al., 2005). The current consensus is that the OFR represents an early, low-level response of the visual system to a moving stimulus (Sheliga et al., 2005; Joshi et al., 2009). The OFR is preserved in patients with PSP (Figure 7C), and shows a similar dependence on the spatial frequency of the stimulus to that shown by normal subjects (Joshi et al., 2010). One difference from control subjects is that responses occur at an increased latency in PSP patients (Figures 7C,D).


The disturbance of gaze in progressive supranuclear palsy: implications for pathogenesis.

Chen AL, Riley DE, King SA, Joshi AC, Serra A, Liao K, Cohen ML, Otero-Millan J, Martinez-Conde S, Strupp M, Leigh RJ - Front Neurol (2010)

Comparison of vertical smooth pursuit (A,B) and ocular following responses (C,D) of a normal subject and a PSP patient. Both sets of responses were evoked as subjects viewed vertically-moving sine-wave gratings on a monitor subtending 50° × 37.5°. For pursuit, the stimulus was sinusoidal motion of a 0.27 cycles per degree grating over the range of temporal frequencies shown. For OFR, the stimulus was ramp motion for 200 ms of a 0.17 cycles per degree grating. At lower frequencies of motion, both the normal subject (A) and the PSP patient (B) showed smooth tracking with some predictive properties (arrows); at high frequencies, the PSP (B) showed substantial decrease in the size of the pursuit movements compared with the control subject. Both upward (C) and downward (D) grating motion induced similar-sized OFR from the control subject (blue line) and PSP patient (red line), although the latency to onset was larger in the patient. See Joshi et al. (2010) for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3008928&req=5

Figure 7: Comparison of vertical smooth pursuit (A,B) and ocular following responses (C,D) of a normal subject and a PSP patient. Both sets of responses were evoked as subjects viewed vertically-moving sine-wave gratings on a monitor subtending 50° × 37.5°. For pursuit, the stimulus was sinusoidal motion of a 0.27 cycles per degree grating over the range of temporal frequencies shown. For OFR, the stimulus was ramp motion for 200 ms of a 0.17 cycles per degree grating. At lower frequencies of motion, both the normal subject (A) and the PSP patient (B) showed smooth tracking with some predictive properties (arrows); at high frequencies, the PSP (B) showed substantial decrease in the size of the pursuit movements compared with the control subject. Both upward (C) and downward (D) grating motion induced similar-sized OFR from the control subject (blue line) and PSP patient (red line), although the latency to onset was larger in the patient. See Joshi et al. (2010) for details.
Mentions: Motion of images across the retina (retinal slip) serves as the primary stimulus to a range of smooth ocular tracking, including the ocular following response (OFR), optokinetic nystagmus, and smooth pursuit (Table 1; Miles, 1998). The OFR is a pre-attentive, short-latency visual tracking mechanism that can be induced by sudden motion of a sinusoidal grating on a computer screen (in our laboratory, subtending 37.5° high × 50° wide; Gellman et al., 1990; Sheliga et al., 2005; Joshi et al., 2009). The OFR can even be tested in PSP patients, who cannot focus their visual attention (or fovea) on the stimulus. Typically, OFR are small, and variable between subjects, but show consistent dependence on the direction and spatial frequency of the stimulus (Gellman et al., 1990; Sheliga et al., 2005). The current consensus is that the OFR represents an early, low-level response of the visual system to a moving stimulus (Sheliga et al., 2005; Joshi et al., 2009). The OFR is preserved in patients with PSP (Figure 7C), and shows a similar dependence on the spatial frequency of the stimulus to that shown by normal subjects (Joshi et al., 2010). One difference from control subjects is that responses occur at an increased latency in PSP patients (Figures 7C,D).

Bottom Line: These vertical and vergence eye movements habitually work in concert to enable visuomotor skills that are important during locomotion with the hands free.Taken with the prominent early feature of falls, these findings suggest that PSP tauopathy impairs a recently evolved neural system concerned with bipedal locomotion in an erect posture and frequent gaze shifts between the distant environment and proximate hands.This approach provides a conceptual framework that can be used to address the nosological challenge posed by overlapping clinical and neuropathological features of neurodegenerative tauopathies.

View Article: PubMed Central - PubMed

Affiliation: Veterans Affairs Medical Center, University Hospitals Case Medical Center Cleveland, OH, USA.

ABSTRACT
Progressive supranuclear palsy (PSP) is a disease of later life that is currently regarded as a form of neurodegenerative tauopathy. Disturbance of gaze is a cardinal clinical feature of PSP that often helps clinicians to establish the diagnosis. Since the neurobiology of gaze control is now well understood, it is possible to use eye movements as investigational tools to understand aspects of the pathogenesis of PSP. In this review, we summarize each disorder of gaze control that occurs in PSP, drawing on our studies of 50 patients, and on reports from other laboratories that have measured the disturbances of eye movements. When these gaze disorders are approached by considering each functional class of eye movements and its neurobiological basis, a distinct pattern of eye movement deficits emerges that provides insight into the pathogenesis of PSP. Although some aspects of all forms of eye movements are affected in PSP, the predominant defects concern vertical saccades (slow and hypometric, both up and down), impaired vergence, and inability to modulate the linear vestibulo-ocular reflex appropriately for viewing distance. These vertical and vergence eye movements habitually work in concert to enable visuomotor skills that are important during locomotion with the hands free. Taken with the prominent early feature of falls, these findings suggest that PSP tauopathy impairs a recently evolved neural system concerned with bipedal locomotion in an erect posture and frequent gaze shifts between the distant environment and proximate hands. This approach provides a conceptual framework that can be used to address the nosological challenge posed by overlapping clinical and neuropathological features of neurodegenerative tauopathies.

No MeSH data available.


Related in: MedlinePlus