Delay Discounting of Reward and Caudate Nucleus Volume in Individuals with α-Synuclein Gene Duplication before and after the Development of Parkinson’s Disease

Abstract

Background/Aims: α-Synuclein (SNCA) may be a key factor in dopaminergic neurotransmission, reward processing, and neurodegeneration in Parkinson’s disease (PD). We investigated delay discounting of reward and caudate volume in SNCA gene duplication carriers before and after the development of PD. Methods: Participants were 7 presymptomatic SNCA duplication carriers who later developed PD (follow-up period: 5.4 years) and 10 matched non-carrier controls. At the follow-up assessment, patients received levodopa (<smlcap>l</smlcap>-DOPA) therapy. Delay discounting of reward was assessed with the Kirby discounting questionnaire. We measured the volume of the caudate nucleus and cerebral cortex using structural MRI and FreeSurfer software. Results: In the presymptomatic stage, carriers showed similar delay discounting and caudate volume to that of non-carrier controls. However, after the development of PD, we observed a significant elevation in delay discounting (impulsive decisions) and reduced caudate volume. There was no cortical atrophy. Conclusion: Impaired reward-related decision making and caudate volume loss are not detectable in the presymptomatic stage in SNCA duplication carriers. These behavioral and neuroanatomical alterations are observed after the development of clinical symptoms when there is extensive neurodegeneration. Study limitations include a small sample size as well as the potential confounding effect of general cognitive decline.

Functional connectivity mapping of regions associated with self‐ and other‐processing

“…Amemori and Graybiel [] postulate, therefore, that the pACC, in interaction with the striatum, may thus be necessary in “interrelating cognitive and emotional processing to modulate behavior by affecting evaluation of aversive outcome” [Amemori and Graybiel, ; p. 784]. Hence, the self‐seed is selectively associated with reward and value assessment and representation, likely due to its functional connectivity with the striatum [Nakamura et al, ; Szamosi et al, ], which we observed across both MACM and RS.…”

“…784]. Hence, the self-seed is selectively associated with reward and value assessment and representation, likely due to its functional connectivity with the striatum [Nakamura et al, 2012;Szamosi et al, 2013], which we observed across both MACM and RS.…”

Cognitive changes in prodromal Parkinson's disease: A review

“…Four studies analyzed cognition in carriers of the SNCA gene, and global cognition was assessed in all of them. One of the studies, which included 6 SNCA carriers, found global cognition to be reduced, whereas patients in the other 3 did not show global cognitive decline . A “dysexecutive syndrome” in 3 of the 6 carriers and episodic memory impairment in 1 carrier were also found, although the small sample size limited the significance of this finding…”

The role of the dorsal striatum in choice impulsivity

“…One study reported that choice impulsivity was correlated with higher GM density in the putamen, but a lack of comparable studies impeded generalization of this finding. Meanwhile, choice impulsivity was associated with smaller GM volume in the caudate/putamen, but later reports indicated that choice impulsivity is associated with larger GM volume in the caudate/putamen . Tschernegg and colleagues addressed this discrepancy by arguing that, compared with the study by Cho and colleagues, their study included more items to score in the delay‐discounting task, and they averaged discounting scores recorded over repeated sessions to obtain a more stable measure.…”