Effects of subthalamic nucleus deep brain stimulation and l-dopa on blinking in Parkinson's disease

https://doi.org/10.1016/j.expneurol.2012.02.004Get rights and content

Abstract

In this study we asked whether subthalamic nucleus deep brain stimulation (STN-DBS) alone, or in combination with l-dopa, modifies voluntary, spontaneous and reflex blinking in patients with Parkinson's disease (PD). Sixteen PD patients who underwent STN-DBS were studied in four experimental conditions: without STN-DBS and without l-dopa, STN-DBS alone, l-dopa alone and STN-DBS plus l-dopa. The results were compared with those obtained in 15 healthy controls. Voluntary blinking was assessed by asking participants to blink as fast as possible; spontaneous blinking was recorded during two 60 s rest periods; reflex blinking was evoked by electrical stimulation of the supraorbital nerve. Blinking were recorded and analysed with the SMART motion system. STN-DBS increased the peak velocity and amplitude for both the closing and opening voluntary blink phases, but prolonged the inter-phase pause duration. l-dopa had no effects on voluntary blinking but reversed the increased inter-phase pause duration seen during STN-DBS. Spontaneous blink rate increased after either STN-DBS or l-dopa. Reflex blinking kinematics were not modified by STN-DBS or l-dopa. The STN-DBS effects on voluntary blinking kinematics and spontaneous blinking rate may occur as results of changes of cortico-basal ganglia activity. The prolonged pause duration of voluntary blinking indicates that STN-DBS has detrimental effects on the cranial region. These results also shed light on the pathophysiology of eyelids opening apraxia following STN-DBS.

Highlights

► STN-DBS modifies voluntary and spontaneous blinking but not reflex blinking. ► The STN-DBS effects on voluntary blinking may be detrimental. ► The STN-DBS effects on blinking reflect changes of cortico-basal ganglia activity. ► Our results shed lights on the eyelids opening apraxia following STN-DBS.

Introduction

Blinking is a stereotyped motor act consisting of a closing and opening phase resulting from the antagonistic activation of the orbicularis oculi and levator palpebrae superioris muscles, respectively, with an inter-phase pause in between (Agostino et al., 2008a, Bologna et al., 2009, Malbouisson et al., 2010). Blinking may be performed voluntarily, spontaneously or reflexively (VanderWerf et al., 2003). The neurophysiological assessment of different types of blinking is a valuable tool to explore the function of various neuroanatomical substrates, such as the brainstem structures and suprasegmental control systems (Agostino et al., 2008a, Bologna et al., 2009, Esteban et al., 2004, Morcuende et al., 2002).

Voluntary, spontaneous and reflex blinking has been all reported to be abnormal in Parkinson's disease (PD). Patients were found to have a normal amplitude and peak velocity for both the closing and opening voluntary blinking phase (Agostino et al., 2008a, Korosec et al., 2006), though with a prolonged inter-phase pause duration, which tended to decrease after dopaminergic administration (Agostino et al., 2008a). The spontaneous blink rate and its kinematics variables have been found to be abnormally reduced (Agostino et al., 2008a, Deuschl and Goddemeier, 1998, Kaneko and Sakamoto, 2001, Karson, 1983, Karson et al., 1982, Karson et al., 1984) and believed to strictly reflect the abnormally reduced central dopaminergic tone that characterizes PD (Agostino et al., 2008a, Karson, 1983, Taylor et al., 1999). Finally, studies of reflex blinking induced by electrical stimulation of the supraorbital nerve have demonstrated an enhanced brainstem excitability (Agostino et al., 2008a, Kimura, 1973, Peshori et al., 2001) resulting from the dysfunction of the inhibitory influences exerted by the basal ganglia on brainstem structures (Basso and Evinger, 1996, Basso et al., 1993, Basso et al., 1996).

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established surgical technique for the treatment of PD (Bronstein et al., 2011, Deuschl et al., 2006, Krack et al., 2003, Limousin et al., 1995, Weaver et al., 2009). While several studies have assessed the effects of STN-DBS on motor function of the arms (Agostino et al., 2008b, Agostino et al., 2008c, Brown et al., 1999, Dafotakis et al., 2008, Potter-Nerger et al., 2009, Vaillancourt et al., 2004, Wenzelburger et al., 2003) the influence exerted by the STN-DBS in the cranial district has been only partially investigated. Both motor responses of muscles supplied by cranial nerves (Costa et al., 2007) and pre-pulse inhibition of the blink reflex have been recorded in patients with PD by means of stimuli delivered by electrodes implanted in the STN (Costa et al., 2006).

To our knowledge, no study has yet addressed whether STN–DBS modifies voluntary, spontaneous and reflex blinking in PD. This study would increase our knowledge of the influence exerted by STN-DBS on the cranial region and provide further insights on the pathophysiology of blinking abnormalities in PD, including the phenomenon of the eyelid opening apraxia following STN-DBS surgery (Fasano et al., 2010, Tozlovanu et al., 2001, Umemura et al., 2008, Weiss et al., 2010).

For these purposes, we investigated the effects of STN-DBS on the kinematics of voluntary, spontaneous and reflex blinking in PD patients. In order to compare the effects of STN-DBS to those of l-dopa (Agostino et al., 2008a) each patient was studied in four different treatment conditions: without STN-DBS and without l-dopa, STN-DBS alone, l-dopa alone and STN-DBS plus l-dopa. Data were also compared with those from age-matched healthy controls.

Section snippets

Participants

The study was performed on 16 PD patients who had previously received bilateral STN-DBS (4 females; mean age ± 1 SEM: 63.44 ± 1.70; Table 1). Fifteen age-matched healthy subjects (6 females; mean age ± 1 SEM: 65.53 ± 1.84) served as a control group.

The diagnosis of PD was made according to the criteria of the UK Parkinson's Disease Society Brain Bank (Hughes et al., 1992). Targeting of the STN and implantation of the electrodes were performed according to currently used methods (Hamani et al., 2006,

Results

None of the participants experienced any adverse effects during or after the experiments. No significant differences were found in age and gender distributions between patients and healthy controls. As expected, STN-DBS, l-dopa and STN-DBS + l-dopa reduced the UPDRS-III score with respect to the STN-DBS OFF/l-dopa OFF condition in PD patients (− 38.63%, − 25.14% and − 49.85%, respectively; all P < 0.01; Table 1).

Discussion

In the present study, we found that STN-DBS modifies, to varying degrees, voluntary blinking and the spontaneous blink rate, without changing reflex blinking. STN-DBS increased the peak velocity and amplitude of both the closing and opening voluntary blinking phases and prolonged the inter-phase pause duration. In DBS patients l-dopa reversed the increased inter-phase pause duration on voluntary blinking, seen during STN-DBS (namely STN-DBS ON/l-dopa OFF condition) and increased the spontaneous

Conclusions

In the present study we have demonstrated for the first time that STN-DBS modifies voluntary blinking and the spontaneous blinking rate in PD. The evidence that STN-DBS, differently from voluntary blinking, did not affect the kinematic variables of spontaneous blinking suggest that the control systems for these two types of blinking only partially overlap. The prolonged inter-phase pause duration we observed after STN-DBS supports the notion that STN-DBS may also have some detrimental effects

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