Dopamine and eye movement control in Parkinson’s disease: deficits in corollary discharge signals?

Abstract

During motor behavior the brain has to predict the sensory consequences of movements to enable 38 accurate perception of the world. This process is assumed to rely on corollary discharge signals sent 39 through the basal ganglia and dopaminergic system, both of which malfunction in Parkinson's disease 40 (PD). We studied early-stage PD patients (N=14), and age-matched healthy control participants (N=14) 41 to examine whether PD patients reveal deficits in updating their sensory representations after eye 42 movements. The participants performed a double-saccade task where, in order to accurately fixate a 43 second target, the participant must correct for the displacement caused by the first saccade. PD 44 patients showed systematic deficits in fixating the second target, especially when they made saccades 45 towards the body side with predominant motor symptoms. Across PD patients, the impairment in 46 fixating the second target correlated with the integrity of the dopaminergic system as measured with open, but theories assume that the basal ganglia, thalamus, and the dopaminergic system contribute 59 to this process (Crutcher & DeLong, 1984;Wurtz, 2008;. The present study 60 examined this little studied hypothesis in Parkinson's disease (PD), which is a neurodegenerative 61 disease characterized by a deficiency in dopaminergic neurons which leads to malfunction of the basal 62 ganglia and thalamus (DeLong & Wichmann, 2007;Albin, et al., 1989). We examined PD patients' 63 ability to monitor their own eye movements using a double-saccade task which has been widely 64 utilized to examine internal monitoring of movements (Wurtz, 2008;Ostendorf, et al., 2010; Thakkar, 65 et al., 2015). During eye movements the image on the retina changes place, and yet we precisely 66 know the locations of objects in the world because changes in perception that are due to the eye 67 movements have been taken into account by the brain. In the double-saccade task a participant must 68 take into account the displacement caused by a first saccade to accurately perform a second saccade 69 ( Figure 1B). This is assumed to rely on corollary discharge (CD) signals that relay a copy of the motor 70 command to sensory areas ( Figure 1A) via medial thalamus (Sommer & Wurtz, 2008;Wurtz, 2008). 71 Dopaminergic deficit in PD (DeLong & Wichmann, 2007;Albin, et al., 1989) results in abnormal 72 functioning of the structures assumed to relay the CD to cortex, most importantly the thalamus. In 73 PD, the medial dorsal nucleus of the thalamus displays abnormal bursting activity which is assumed to 74 disturb the information flow to the cortex (Pifl, et al., 2012). The CD signal can be seen as a part of a 75 more general mechanism that integrates bottom-up sensory information and contextual information. 76This is clearly formalized in the predictive coding framework which assumes that the brain is movements (e.g. CD) . The two possible outcomes of CD deficits (reduced vs. 118 amplified CD relative to the motor signals) are displa...

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