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Cerebral pathological and compensatory mechanisms in the premotor phase of leucine-rich repeat kinase 2 parkinsonism.
Brain. 2012 Dec; 135(Pt 12):3687-98.B

Abstract

Compensatory cerebral mechanisms can delay motor symptom onset in Parkinson's disease. We aim to characterize these compensatory mechanisms and early disease-related changes by quantifying movement-related cerebral function in subjects at significantly increased risk of developing Parkinson's disease, namely carriers of a leucine-rich repeat kinase 2-G2019S mutation associated with dominantly inherited parkinsonism. Functional magnetic resonance imaging was used to examine cerebral activity evoked during internal selection of motor representations, a core motor deficit in clinically overt Parkinson's disease. Thirty-nine healthy first-degree relatives of Ashkenazi Jewish patients with Parkinson's disease, who carry the leucine-rich repeat kinase 2-G2019S mutation, participated in this study. Twenty-one carriers of the leucine-rich repeat kinase 2-G2019S mutation and 18 non-carriers of this mutation were engaged in a motor imagery task (laterality judgements of left or right hands) known to be sensitive to motor control parameters. Behavioural performance of both groups was matched. Mutation carriers and non-carriers were equally sensitive to the extent and biomechanical constraints of the imagined movements in relation to the current posture of the participants' hands. Cerebral activity differed between groups, such that leucine-rich repeat kinase 2-G2019S carriers had reduced imagery-related activity in the right caudate nucleus and increased activity in the right dorsal premotor cortex. More severe striatal impairment was associated with stronger effective connectivity between the right dorsal premotor cortex and the right extrastriate body area. These findings suggest that altered movement-related activity in the caudate nuclei of leucine-rich repeat kinase 2-G2019S carriers might remain behaviourally latent by virtue of cortical compensatory mechanisms involving long-range connectivity between the dorsal premotor cortex and posterior sensory regions. These functional cerebral changes open the possibility to use a prospective study to test their relevance as early markers of Parkinson's disease.

Authors+Show Affiliations

Department of Neurology (935), Radboud University Nijmegen Medical Centre, PO Box 9 101, 6500 HB Nijmegen, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23250886

Citation

van Nuenen, Bart F L., et al. "Cerebral Pathological and Compensatory Mechanisms in the Premotor Phase of Leucine-rich Repeat Kinase 2 Parkinsonism." Brain : a Journal of Neurology, vol. 135, no. Pt 12, 2012, pp. 3687-98.
van Nuenen BF, Helmich RC, Ferraye M, et al. Cerebral pathological and compensatory mechanisms in the premotor phase of leucine-rich repeat kinase 2 parkinsonism. Brain. 2012;135(Pt 12):3687-98.
van Nuenen, B. F., Helmich, R. C., Ferraye, M., Thaler, A., Hendler, T., Orr-Urtreger, A., Mirelman, A., Bressman, S., Marder, K. S., Giladi, N., van de Warrenburg, B. P., Bloem, B. R., & Toni, I. (2012). Cerebral pathological and compensatory mechanisms in the premotor phase of leucine-rich repeat kinase 2 parkinsonism. Brain : a Journal of Neurology, 135(Pt 12), 3687-98. https://doi.org/10.1093/brain/aws288
van Nuenen BF, et al. Cerebral Pathological and Compensatory Mechanisms in the Premotor Phase of Leucine-rich Repeat Kinase 2 Parkinsonism. Brain. 2012;135(Pt 12):3687-98. PubMed PMID: 23250886.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cerebral pathological and compensatory mechanisms in the premotor phase of leucine-rich repeat kinase 2 parkinsonism. AU - van Nuenen,Bart F L, AU - Helmich,Rick C, AU - Ferraye,Murielle, AU - Thaler,Avner, AU - Hendler,Talma, AU - Orr-Urtreger,Avi, AU - Mirelman,Anat, AU - Bressman,Susan, AU - Marder,Karen S, AU - Giladi,Nir, AU - van de Warrenburg,Bart P C, AU - Bloem,Bastiaan R, AU - Toni,Ivan, AU - ,, PY - 2012/12/20/entrez PY - 2012/12/20/pubmed PY - 2013/2/16/medline SP - 3687 EP - 98 JF - Brain : a journal of neurology JO - Brain VL - 135 IS - Pt 12 N2 - Compensatory cerebral mechanisms can delay motor symptom onset in Parkinson's disease. We aim to characterize these compensatory mechanisms and early disease-related changes by quantifying movement-related cerebral function in subjects at significantly increased risk of developing Parkinson's disease, namely carriers of a leucine-rich repeat kinase 2-G2019S mutation associated with dominantly inherited parkinsonism. Functional magnetic resonance imaging was used to examine cerebral activity evoked during internal selection of motor representations, a core motor deficit in clinically overt Parkinson's disease. Thirty-nine healthy first-degree relatives of Ashkenazi Jewish patients with Parkinson's disease, who carry the leucine-rich repeat kinase 2-G2019S mutation, participated in this study. Twenty-one carriers of the leucine-rich repeat kinase 2-G2019S mutation and 18 non-carriers of this mutation were engaged in a motor imagery task (laterality judgements of left or right hands) known to be sensitive to motor control parameters. Behavioural performance of both groups was matched. Mutation carriers and non-carriers were equally sensitive to the extent and biomechanical constraints of the imagined movements in relation to the current posture of the participants' hands. Cerebral activity differed between groups, such that leucine-rich repeat kinase 2-G2019S carriers had reduced imagery-related activity in the right caudate nucleus and increased activity in the right dorsal premotor cortex. More severe striatal impairment was associated with stronger effective connectivity between the right dorsal premotor cortex and the right extrastriate body area. These findings suggest that altered movement-related activity in the caudate nuclei of leucine-rich repeat kinase 2-G2019S carriers might remain behaviourally latent by virtue of cortical compensatory mechanisms involving long-range connectivity between the dorsal premotor cortex and posterior sensory regions. These functional cerebral changes open the possibility to use a prospective study to test their relevance as early markers of Parkinson's disease. SN - 1460-2156 UR - https://www.unboundmedicine.com/medline/citation/23250886/Cerebral_pathological_and_compensatory_mechanisms_in_the_premotor_phase_of_leucine_rich_repeat_kinase_2_parkinsonism_ L2 - https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/aws288 DB - PRIME DP - Unbound Medicine ER -