Elsevier

Neurobiology of Aging

Volume 34, Issue 10, October 2013, Pages 2277-2286
Neurobiology of Aging

Regular article
Age-related changes of blood-oxygen-level–dependent signal dynamics during optokinetic stimulation

https://doi.org/10.1016/j.neurobiolaging.2013.03.031Get rights and content

Abstract

The present study aimed to reveal the effects of age on the temporal profile of the positive blood-oxygen-level–dependent response (PBR) during low-velocity optokinetic nystagmus (OKN) in healthy subjects. We were specifically interested in comparing these effects with the effects of age on the PBR elicited by pure visual and motor tasks. Therefore, we conducted 2 additional control experiments: a checkerboard experiment (visual stimulation) and a finger-tapping (motor task) experiment. Whereas the oculomotor performance of the subjects remained unaltered, the temporal profile of the PBR changed significantly with increasing age in visual and oculomotor areas. None of the control experiments revealed significant age-related PBR changes. Thus, this study demonstrates that the PBR changes during OKN occur before any changes in the oculomotor performance can be detected. These effects of age are specific for the OKN task and probably reflect both changes in the neurovascular coupling and changes in the neural processing during OKN.

Introduction

Optokinetic nystagmus (OKN) is an important oculomotor reflex that stabilizes the image on the retina during motion of the visual field, thereby enabling proper object recognition and control of self-motion. Behavioral studies have shown that OKN progressively deteriorates with increasing age. Investigating the age-related changes of the blood-oxygen-level–dependent (BOLD) signal correlated to OKN would offer new insights into the effects of age on the cortical function associated with this reflexive sensorimotor task.

OKN consists of slow tracking eye movements and fast resetting saccades. The visual information is carried from the retina, through the optic nerve, to the lateral geniculate body, from where ascending cortical and descending brain stem pathways originate. Previous animal and human studies have shown that the occipital cortex, the adjacent visual-motion areas medial temporal/medial superior temporal cortex ([MT/MST complex]), the frontal eye field (FEF), the supplementary eye field (SEF), the parietal eye field (PEF), the cerebellum, and the brain stem are involved in processing of OKN (for review on anatomic and neurophysiological studies, see Büttner and Büttner-Ennever, 2006, and for imaging studies, see Bense et al., 2006; Della-Justina et al., 2008; Dieterich et al., 1998, 2003; Kikuchi et al., 2009; Konen et al., 2005).

Behavioral studies have shown an age-related decrease in the OKN slow-phase velocity and gain when stimulus velocities above 40°/s were applied. Simons and Büttner (1985) found that the maximal OKN slow-phase velocity closely followed stimulus velocity up to 40–50°/s and then progressively decreased with increasing age. Baloh et al. (1993) found a rapid decrease in OKN gain (defined as the ratio of OKN slow-phase velocity and stimulus velocity) in subjects above 75 years when higher stimulus velocities were applied, whereas during low-stimulus velocities the gain reached one. A significant age-related decline of OKN gain was also found in the study of Kerber et al. (2006) when stimulus velocity of 60°/s was used. Furthermore, Kato et al. (1994) found a significant dynamic decrease in OKN slow-phase velocity when a linearly increasing stimulus velocity of more than 40°/s was applied and no significant age-related change when a constant stimulus velocity of up to 60°/s was used. Thus, the OKN slow-phase velocity and gain remain unaffected by age during stimulation with lower velocities but decrease significantly when higher stimulus velocities are applied.

Question arises whether the cortical activity pattern associated with OKN behaves in a similar manner or whether changes in this pattern can be detected before a decrement in the OKN performance. Indeed, with a “hand-grip” task, Ward and Frackowiak (2003) found an age-related increase in the amplitude of the BOLD response before any changes in the performance could be detected. As this study addressed solely age-related changes during a motor task, it remains to be further investigated whether the same behavior of the BOLD signal would be detected in other tasks, the performance of which is maintained despite an increasing age.

Regarding the effects of age on the BOLD signal elicited by pure visual, pure motor, or nonreflexive oculomotor tasks, the available studies showed inconsistent results. Raemaekers et al. (2006) investigated the effects of age on the BOLD signal during nonreflexive ocumlomotor tasks (prosaccades and antisaccades) and found a moderate decrease in the performance of the subjects accompanied by an age-related shift in the spatial pattern of the BOLD signal and an overall decrease of its amplitude. Studies, on the other hand, using pure motor or pure visual tasks showed no changes in the BOLD signal amplitude but changes in its latency and duration with increasing age (Huettel et al., 2001; Richter and Richter, 2003; Taoka et al., 1998). As these studies did not compare the effects of age among different tasks in the same subjects, it remains unclear whether the observed changes in the BOLD signal are because of global changes in the brain structure, vasculature, and function or dependent on task-specific factors.

The first aim in the present study was to investigate the effects of age on the BOLD response during a preserved oculomotor performance. We, therefore, applied a stimulus velocity of 15°/s to keep a stable OKN through the entire age range. Specific imaging measures were the dynamics of the positive BOLD response (PBR) as revealed by the parameter estimates of the canonical hemodynamic response function (HRF), the temporal derivative, and the dispersion derivative. The second aim was to test whether the changes of the PBR dynamics are specific for the OKN task or reflect general aging effects found in pure visual or motor tasks. For this purpose, checkerboard stimulation was used as sensory control task and self-paced finger tapping as a motor control task. This experimental paradigm should allow investigating how the BOLD signal, as a correlate of neural activity, changes with increasing age when reflexive sensorimotor tasks are performed. Furthermore, it should contribute to the question whether the brain behaves differently with increasing age during performance of pure sensory, motor, or sensorimotor tasks.

Section snippets

Subjects

Sixty-eight right-handed healthy subjects, evenly distributed between 20 and 80 years, were examined. Because of poor data quality (see Section 2.5.2), 23 subjects had to be excluded from the analysis. Consequently, 45 subjects (19 men and 26 women), evenly distributed between 20 and 76 years (47.6 ± 17.9 years), were included in the study. All subjects were free of neurologic, psychiatric, and cerebrovascular disorders and received no medication known to affect the neural function. A

Video-oculography data

Analysis of the eye-movement recordings showed that the applied visual stimulation elicited OKN and that all subjects included in the analysis were able to accurately perform the task. The mean OKN gain for the whole group was 0.7 ± 0.2 (range from 0.1 to 1.2), the mean frequency of resetting saccades was 2.9 ± 0.5 Hz (range from 0.9 to 4.1), and the mean amplitude of saccades was 3.2° ± 0.9° (range from 1.7 to 5.7). The OKN slow-phase velocity test revealed mean maximal OKN slow-phase velocity

Discussion

The major findings of this study were as follows: (1) during OKN, the β2 decreased and the β3 increased significantly with increasing age despite an unaltered oculomotor performance; (2) there was no significant correlation between the PBR (β1) and age during OKN performance; and (3) no significant age-related changes were observed in the control experiments of pure visual and pure motor tasks. Thus, the age-related changes in the temporal shape of the PBR were specific for the reflexive

Disclosure statement

The authors state that there are no actual or potential conflicts of interest.

The study was conducted in accordance with the World Medical Association WMA declaration of Helsinki and approved by the local Ethics Committee of the Ludwig-Maximilians University of Munich. All subjects gave their informed written consent.

Acknowledgements

This study was supported by the German Research Foundation (DFG-GRK 1091 “Orientation and Motion in Space”) and by the Hertie Foundation. The authors thank the Department of Neuroradiology, University Clinic of Munich, for the technical support and Dr Ing. Thomas Eggert for the help with the statistical analysis.

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