Altered reward-related neural responses in non-manifesting carriers of the Parkinson disease related LRRK2 mutation

The LRRK2 Ashkenazi Jewish consortium

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Disturbances in reward processing occur in Parkinson’s disease (PD) however it is unclear whether these are solely drug-related. We applied an event-related fMRI gambling task to a group of non-manifesting carriers (NMC) of the G2019S mutation in the LRRK2 gene, in order to assess the reward network in an “at risk” population for future development of PD. Sixty-eight non-manifesting participants, 32 of which were non-manifesting non-carriers (NMNC), performed a gambling task which included defined intervals of anticipation and response to both reward and punishment in an fMRI setup. Behavior and cerebral activations were measured using both hypothesis driven and whole brain analysis. NMC demonstrated higher trait anxiety scores (p = 0.04) compared to NMNC. Lower activations were detected among NMC during risky anticipation in the left nucleus accumbens (NAcc) (p = 0.05) and during response to punishment in the right insula (p = 0.02), with higher activations among NMC during safe anticipation in the right insula (p = 0.02). Psycho-Physiological Interaction (PPI) analysis from the NAcc and insula revealed differential connectivity patterns. Whole brain analysis demonstrated divergent between-group activations in distributed cortical regions, bilateral caudate, left midbrain, when participants were required to press the response button upon making their next chosen move. Abnormal neural activity in both the reward and motor networks were detected in NMC indicating involvement of the ventral striatum regardless of medication use in “at risk” individuals for future development of PD.

Original languageEnglish
Pages (from-to)1009-1020
Number of pages12
JournalBrain Imaging and Behavior
Volume13
Issue number4
DOIs
StatePublished - 15 Aug 2019

Funding

FundersFunder number
Chief Scientist Department of Health, Israel
Dutch Brain Foundation
Fox Foundation for Parkinson
Israeli Science Foundation
Israeli Science Foundation Legacy Heritage Fund
Kahn Foundation Israel
Netherlands Organization for Scientific Research
Stichting International Parkinson Fonds, Hersenstichting, ZonMw
VIDI
National Institutes of Health
Michael J. Fox Foundation for Parkinson's Research
Amyotrophic Lateral Sclerosis Association
National Park Foundation
National Parkinson Foundation
Nederlandse Organisatie voor Wetenschappelijk Onderzoek016.076.352
Israel Science Foundation
Seventh Framework Programme
Israeli Centers for Research Excellence

    Keywords

    • Anticipation
    • Genomic vulnerability
    • LRRK2
    • Reward
    • fMRI

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