Eye Tracking in Patients with Parkinson Disease

Introduction

Many diseases of the brain cause a decline in different cognitive aspects, and Parkinson’s disease (PD) is not an exception. According to Fahn and Sulzer (2004), PD is a degenerative disease of the nerves in the basal ganglia that progressively results in the disappearance of cells in the substantia nigra that produce dopamine. People with PD are more likely to fall when executing motor tasks than simple motor tasks (Morris et al., 2001). The eyes initiate a sequence of reorientation of various body parts starting with the head, the trunk then the pelvis, and ending with the feet (Reed-Jones et al., 2009).

According to Reed-Jones et al. (2009), visual information is critical in ensuring the coordinated movement of different body parts during movement. Research on the movement of the eye in patients with PD motor control is critical in informing the training of patients to improve coordination of movement to reduce falls. This paper reviews two journal articles about the role of tracking eye movement in PD patients and highlights the limitations of eye-tracking research in PD as revealed by these articles. This paper will also evaluate whether the research has clarified the major cognitive impairment in the disease.

Constrained Eye Movement in Patients with Parkinson’s Disease

The first article that will be reviewed has been authored by Ambati et al. (2016). The research article is based on the knowledge that control of body parts orientation, called ‘steering synergy,’ in PD patients is almost concurrent and dependent on each other (Hong et al., 2009). Also, the research was informed by a hypothesis that PD patients have impaired coordination of the ad, trunk, pelvis, and legs because of malfunction of vision in guiding coordination of body segments in turning. Specifically,  research to investigate turning behavior in healthy adults shows that eye redirection starts a coordinated movement of the body leading to orientation. Reed-Jones et al., (2009) found that constraining eye movement impairs steering control and promotes en bloc turning. Furthermore, the hypothesis is that eye movements act as a feedforward mechanism for steering control and stimulate the ‘steering synergy’ that controls coordinated reorientation of the whole body (Ambati et al., 2013). Lohnes and Earhart (2011) attribute abnormalities in the turning of patients with PD to akinesia and bradykinesia (saccade deficits) that impede normal redirection of gaze necessary for coordinating the burning of body segments.

This research was founded on the assumption that characteristics of saccadic eye movements during a walking turn may provide insight into the procedure underlying turning challenges in persons with PD. The objective of the study by Ambati et al. (2016) therefore included measuring the variation in the coordination of multi-segment reorientation in patients with PD and investigating the role eye movement plays in the reorientation of the head, trunk, pelvis, and legs to turn while walking. This study expands on the previous study on the potential role of diminished eye movement on turning while standing (Lohnes & Earhart, 2011). The study investigated the effects of saccadic eye movements in making turns while walking to gain an understanding of the difficulty patients with PD encounter in turning while in motion (Ambati et al., 2016).

Methodology

The researcher used 23 participants to test their hypothesis. The sample comprised 8 PD patients, 5 healthy adults, and 9 healthy young adults. Inclusion criteria for PD participants included a diagnosis of PD by a specialist, treatment with dopaminergic drugs, and demonstration of symptoms based on the Hoehn and Yahr scale (Ambati et al., 2016). Patients with progressed disease characterized by impaired walking extended standing and motion past 15 seconds, and inability to give informed consent corresponding to a Mini-Mental State Exam (MMSE) of less than 18. The researcher obtained consent from all participants including the experimental group. Two controlled groups were used for the study, namely young adults and old adults (Ambati et al., 2016).

         3-D kinematics of the legs, pelvis, trunk, and head were captured using a special camera. The Vicon Plug-In-Gait model was used to define the whole-body marker configuration. The horizontal and vertical eye positions were recorded concurrently with the time-synced coordinated data using an ASL eye-tracking system (Ambati et al., 2016). The researchers asked the participants to keep their gaze on a specific spot in front while rotating their heads at different planes at a velocity of their choosing. Then a linear regression model (Reed-Jones et al., 2009) was used to convert raw vertical and horizontal eye to the eye-in-head reference frame.

Participants were made to complete 30 successive walking tests on a 5-meter path at their own pace under a fixed and a free gaze five times for each task, namely no turn, 900 right-tu, rn and 900 left-turn at the end of the path (Ambati et al., 2016). The participants were required to first complete all the tasks successfully under a specific gaze category before switching to the other. That is, he or she was required to finish the tasks under say fixed gaze before repeating the task under a free gaze or vice versa. More than one stride to execute a turn was considered unsuccessful and warranted a repeat of the task (Ambati et al., 2016). The participants were allowed 60 seconds of rest before embarking on another trial and the time required to complete a task was not limited.

Statistical analysis involved comparing the dependent variables using a 3-by-2 randomized block factorial design between the experimental and the two control groups, and between the free and fixed visual conditions. The dependent variable consists d the start of the rotation of each segment including the eyes for the control and experimental groups and free and fixed visual conditions. The comparison was statistically analyzed using repeated measures ANOVA with modified SPSS Statistics 21. Paired t-tests were used in every experimental group to establish intersegment timing differences. Besides the segment analysis, one-way ANOVAs on turn time (TT) and lead foot distance (LFD) were performed (Ambati et al., 2016). Thus, sufficient statistical analysis was used to establish the differences between healthy and people with PD.

Results                                 

All trials were successful for all groups. The dependent variables measures for left and right turns were relatively the same.  The researchers found a significant main effect of group and condition for the timing of segment reorientation. The experimental group did not indicate significant differences in intersegment timings in the two different visual conditions. It showed that the PD group did not employ an articulated top-down coordination of different body segments involved in turning. The research also revealed that PD patients have impaired coordination between the eye and other body segments; therefore, they do not make anticipatory eye movements necessary to initiate successful turns, constituting high risks of falls during turning (Ambati et al., 2016).

Clarification of the Major Cognitive Impairment

This research has clarified a disconnect between the neurons of the superior colliculus and substantia nigra related to PD. Based on Comoli et al. (2003), this neural connection accounts for oculomotor function. This function seems to be missing in people with PD, as opposed to those without. In particular, PD sufferers have impaired saccade levels attributable to excessive firing from the basal nuclei that overwhelms the action potential from the superior colliculus (Terao et al., 2011). Consequently, the basal nuclei in people with PD cannot override the activity of the superior colliculus to facilitate voluntary anticipatory movement of the eyes essential for coordinated descending reorientation of the body segments (Ambati et al., 2016).  

Limitations of the study

This study did not investigate the ability of people with PD to make anticipatory eye movements and coordinated turning if provided visual stimulus to precede the turn (Ambati et al., 2016). This aspect of turning is crucial for understanding the neural pathway disrupted in PD patients and should inform future research.

Further, the study used a small sample which reduces the validity and reliability of the results. Specifically, the small size of the sample constitutes a significant threat to external validity (Ambati et al., 2016). Thus, further research should use more participants to prove the findings of this research. In addition, the study used the un-uniform population of participants in terms of age and time since diagnosis. These differences may confound the results of the study because of the variability of the sample. Lastly, the researchers did not control for neck rigidity, as hypertonicity reduces turning in patients with PD (Franzen et al., 2009).

Anticipation and Prediction in Eye Movement Control in PD Patients

         Helmchen et al. (2012) investigated the challenges that PD patients have in managing self-guided movements. Particularly, they investigated the ability of people with PD to anticipate and predict movement speed when a motional object vanishes from sight. In particular, the researchers studied smooth pursuit eye movement in the subjects and age-matched healthy controls by varying target blanking periods of a moving object in four different blanking states. These researchers base their studies on an understanding that visual, auditory, and tactile stimuli are essential sources of cues for locomotion aid in patients with PD (Lim et al., 2005) Expectations of the sensory and motor outcomes of a person’s movement and future motion drive self-guided movements. These authors based their research on the hypothesis that dysfunctional movement in PD patients is partly due to an impaired ability to anticipate an impending start of a visual target of preceding impending movements. The possibility of examining the predictive mechanism of movement control in the laboratory by assessing ocular behavior when displacing visual targets with predictable speed and course. In this regard, the basal ganglia are thought to provide ambiguous internal cues that are critical for the development of preparatory activity for a movement component in a sequence of motions (Georgiou, 1993). The study aimed to examine the dissociable effects in pursuit of eye movements in patients with PD.

Methodology

The sample comprised 15 patients with PD after 5 candidates were excluded from the study after they showed vascular central nervous system lesions. Other participants were 19 healthy individuals who served as controls. The experimental group, PD patients, were on medications that did not affect the movement of the eye (Helmchen et al., 2012).

The participants performed 4 pursuit ramp tasks with each stimulus starting at an eccentric horizontal position before displacement to the side. The target was either pure ramp paradigm, or blanked at various intervals, constituting early onset blanking, mid-ramp blanking, and short ramp blanking. The mid-ramp paradigm tested the capacity to maintain the pursuit of eye speed; the short-ramp paradigm did not have a target reappearance to allow pure decay of eye velocity after the first ramp (Helmchen et al., 2012). The speed discrepancy between mid-ramp blanking and the short ramp was used to establish the predictive component of responses of smooth pursuit ramps. On the other hand, early-onset blanking reflected anticipation before target onset, whereas short ramp captured pure predictive behavior following target blanking. The subjects were made to perform other tasks including prosaccade and antisaccade tasks and smooth pursuit tasks that oscillate (Helmchen et al., 2012).  

Results

The experimental group differed from the controls demonstrating the lower initial speed of eye drift before target onset and extended latency of acceleration in the blanking paradigm. This outcome indicates a possibility of anticipating imminent motions (Helmchen et al., 2012). On the other hand, the PD patients predicted target velocity after the disappearance of the target once they began pursuit of a target. However, the experimental group showed reduced pursuit velocity for oscillating as well as ramp target presentation devoid of the blanking condition. Triangular and sinusoidal stimuli offered the highest level of predictability of the target. Moreover, participants pursued a ramp target that moved at a constant speed with the target being illuminated intermittently when it passed the central position (Helmchen et al., 2012). The study showed that the ability of the PD patients to anticipate target onset was impaired, but the capacity to pursue moving objects that disappeared temporarily was not.

Clarification of Cognitive Impairment

The study revealed that residual pursuit of velocity concerns another element of the extra-retinal pursuit possibly associated with a separate velocity-storage mechanism (Barnes & Collins, 2008). It also substantiated the theory that an internal representation of the world controls the movement and expectation of the motor and sensory consequences of future motions. Such predictive theorization of future events influences the control of movements (Helmchen, et al., 2012). Thus, it is easier to maintain relevant routines devoid of sensory stimuli.

The basal ganglia functions as a presenter of cues for the creation of anticipatory activity for a specific motion in a set of repetitive movements. The basal ganglia act as an initiator of an imminent action in light of the anticipation or prediction (Gurvich et al., 2007). Deficits in anticipatory pursuit and movement initiation thus reflect a functional impairment at the basal ganglia or pre-motor cortical areas characteristic of progressed PD (Ambati et al., 2016). This cognitive impairment means that persons with PD use external stimuli to guide their movements. Thus, they must rely on prediction to sustain control of their movements because spatial memory and motion imagery are preserved in PD sufferers.

         Importantly, the pars reticulate of the substantia nigra play in pursuit of target objects (Basso, Pokorny & Liu, 2005). Specifically, the control of frontostriatal and nigrostriatal neurons has been partially implicated in the abnormal pursuit of target objects in PD patients (Lewis et al., 2003). 

Conclusion

The findings of the first article suggest that the tendency of people with PD to fix their gaze on a specific spot during walking and turning is the main reason for their high risk of falling. Thus, improving the quality of life of such paints should integrate training eye movements and coordination patterns of the relevant body segments. The second article provides insight into the contribution of anticipation and prediction capacity in the successful navigation of patients with PD from one point to another. The article concluded that deficient anticipation and prediction ability accounts for abnormal initiation and termination of gait. However, the main limitations of these studies relate to the small sample size used, which reduces the external validity and generalization of the findings to the general patient with PD population.

References

Ambati, V.N.P., Murray, N.G., Saucedo, F., Powell, D.W., & Reed-Jones, R.J. (2013). Constraining eye movement when redirecting walking trajectories alters turning control in healthy young adults. Exp Brain Res, 226, 549-556.

Ambati, P. V., Saucedo, F., Murray, N.G., Powell, D.W., & Reed-Jones, R.J. (2016). Constraining eye movement in individuals with Parkinson’s disease during walking turns. Exp Brain Res, 234, 2957-2965.

Barnes, G.R., & Collins, C.J. (2008). Internally generated smooth eye movement: its dynamic characteristics and role in randomized and predictable
Pursuit. Prog Brain Res, 171, 441–449.

Basso, M.A., Pokorny, J.J., & Liu, P. (2005). Activity of substantia nigra pars reticulata neurons during smooth pursuit eye movements in monkeys. Eur J Neurosci, 22, 448-464.

Comoli, E., Coizet, V., Boyes, J. et al (2003). A direct projection from the superior colliculus to substantia nigra for detecting salient visual events. Nat Neurosci., 6, 974-980.

Gurvich, C., Georgiou-Karistianis, N., Fitzgerald, P.B., Millist, L., & White, O.B. (2007). Inhibitory control and spatial working memory in Parkinson’s
Disease. Mov Disord, 22, 1444-1450.

Fahn, S., & Sulzer, D. (2004) Neurodegeneration and neuroprotection in Parkinson’s disease. NeuroRx., 1, 139-154

Franzen, E., Paquette, C., Gurfnkel, V.S., Cordo, P.J., Nutt, J.G., & Horak, F.B. (2009) Reduced performance in balance, walking, and turning tasks is associated with increased neck tone in Parkinson’s disease. Exp Neurol., 219, 430–438

Georgiou, N., Iansek, R., Bradshaw, J.L., Phillips, J.G., Mattingley, J.B., & Bradshaw, J.A. (1993). An evaluation of the role of internal cues in the pathogenesis of parkinsonian hypokinesia. Brain, 116, 1575-1587.

Helmchen, C., Pohlmann, J., Trillenberg, P., Lencer, R., Graf, J., & Sprenger, A. (2012). Role of anticipation and prediction in smooth pursuit eye movement control in Parkinson’s disease. Movement Disorders, 27 (8), 1012-1018.

Hong, M., Perlmutter, J.S., & Earhart, G.M. (2009) A kinematic and electromyographic analysis of turning in people with Parkinson’s disease. Neurorehabil Neural Repair., 23, 166-176.

Lim, I., van Wegen, E., de Goede, C., et al. (2005). Effects of external rhythmical cueing on gait in patients with Parkinson’s disease: a systematic review. Clin Rehabil , 19, 695–713.

Lewis, S.J., Dove, A., Robbins, T.W., Barker, R.A., & Owen, A.M. (2003). Cognitive impairments in early Parkinson’s disease are accompanied by reductions in activity in frontostriatal neural circuitry. J Neurosci, 23, 6351–6356.

Lohnes, C.A., & Earhart, G.M. (2011). Saccadic eye movements are related to turning performance in Parkinson’s disease. J Parkinsons Dis., 1, 109-118.

Reed-Jones, R., Reed-Jones, J., Vallis, L.A., & Hollands, M. (2009). The effects of constraining eye movements on visually evoked steering responses during walking in a virtual environment. Exp Brain Res., 197, 357-367.

Terao, Y., Fukuda, H., Yugeta, A., et al (2011) Initiation and inhibitory control of saccades with the progression of Parkinson’s disease—changes in three major drives converging on the superior colliculus. Neuropsychologia, 49, 1794–1806.