Abstract
In order to understand the influence of two dopaminergic signalling pathways, TaqIA rs1800497 (influencing striatal D2 receptor density) and Ser9Gly rs6280 (influencing the striatal D3 dopamine-binding affinity), on saccade generation and psychiatric comorbidities in Parkinson’s disease, this study aimed to investigate the association of saccadic performance in hypomanic or impulsive behaviour in parkinsonian patients; besides we questioned whether variants of D2 (A1+/A1−) and D3 (B1+/B1−) receptor polymorphism influence saccadic parameters differently, and if clinical parameters or brain connectivity changes modulate this association in the nigro-caudatal and nigro-collicular tract. Initially, patients and controls were compared regarding saccadic performance and differed in the parameter duration in memory-guided saccades (MGS) and visually guided saccades (VGS) trials (p < 0.0001) and in the MGS trial (p < 0.03). We were able to find associations between hypomanic behaviour (HPS) and saccade parameters (duration, latency, gain and amplitude) for both conditions [MGS (p = 0.036); VGS (p = 0.033)], but not for impulsive behaviour. For the A1 variant duration was significantly associated with HPS [VGS (p = 0.024); MGS (p = 0.033)]. In patients with the B1 variant, HPS scores were more consistently associated with duration [VGS (p = 0.005); MGS (p = 0.015), latency [VGS (p = 0.022)]] and amplitude [MGS (p = 0.006); VGS (p = 0.005)]. The mediation analysis only revealed a significant indirect effect for amplitude in the MGS modality for the variable UPDRS-ON (p < 0.05). All other clinical scales and brain connectivity parameters were not associated with behavioural traits. Collectively, our findings stress the role of striatal D2 and D3 signalling mechanisms in saccade generation and suggest that saccadic performance is associated with the clinical psychiatric state in Parkinson’s disease.
Highlights
Changes in saccadic performance are strongly associated with dopaminergic modulation of the reward system, as shown in the human species[1] and in the monkey.[2,3,4,5] Diverse anatomical regions participate in the control of saccades subsuming cortical as well as subcortical regions [e.g., substantia nigra (SN), superior colliculus (SC) and caudate nucleus (CD)], the brainstem and the cerebellum [for overview in the human species and the monkey see Leigh and Kennard6]
We scrutinised the (I) association of impulsive and hypomanic traits relating to saccadic performance in Parkinson’s disease (PD) and (II)
We scrutinised the association of impulsive and hypomanic traits relating to saccadic performance in PD; all key results are summarised in Table 1 and raw gaze positions of the three patients and one control are visualised in Figs. 1 and 2
Summary
Changes in saccadic performance are strongly associated with dopaminergic modulation of the reward system, as shown in the human species[1] and in the monkey.[2,3,4,5] Diverse anatomical regions participate in the control of saccades subsuming cortical (e.g., the dorsolateral prefrontal cortex and the frontal eye field) as well as subcortical regions [e.g., substantia nigra (SN), superior colliculus (SC) and caudate nucleus (CD)], the brainstem and the cerebellum [for overview in the human species and the monkey see Leigh and Kennard6]. In the last step we (3) conducted a mediation analysis, to question, if clinical parameters or brain connectivity have a relevant influence on the association of saccadic performance onto hypomanic or impulsive. Multiple regression analysis was consecutively performed including MGS [R = 0.55; F (4; 28) = 3.0; p = 0.036] or VGS [R = 0.55; F (4; 28) = 3.0; p = 0.033]; both analyses revealed a significant association of HPS measured by the HPS questionnaire (relating to an association with schizotypy, obsessive compulsivity and emotional instability) by the four saccade parameters (see Supplementary Fig. 2); no significance was found for the impulsivity scale (BIS-11).
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