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Motor Sequence Learning and Consolidation in Unilateral De Novo Patients with Parkinson's Disease.

Dan X, King BR, Doyon J, Chan P - PLoS ONE (2015)

Bottom Line: LH-S patients demonstrated impaired learning during the initial training session and both LH-S and LH-A patients demonstrated decreased performance compared to controls during the next-day retest.Critically, the impairments in later learning stages in the LH-A patients were evident even before the appearance of traditional clinical symptoms in the tested hand.Results may be explained by the progression of disease-related alterations in relevant corticostriatal networks.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology and Neurology, Key Laboratory of Ministry of Education on Neurodegenerative Disorders, Beijing Key Laboratory on Parkinson's Disease, Xuanwu Hospital of Capital Medical University, Beijing, China.

ABSTRACT
Previous research investigating motor sequence learning (MSL) and consolidation in patients with Parkinson's disease (PD) has predominantly included heterogeneous participant samples with early and advanced disease stages; thus, little is known about the onset of potential behavioral impairments. We employed a multisession MSL paradigm to investigate whether behavioral deficits in learning and consolidation appear immediately after or prior to the detection of clinical symptoms in the tested (left) hand. Specifically, our patient sample was limited to recently diagnosed patients with pure unilateral PD. The left hand symptomatic (LH-S) patients provided an assessment of performance following the onset of clinical symptoms in the tested hand. Conversely, right hand affected (left hand asymptomatic, LH-A) patients served to investigate whether MSL impairments appear before symptoms in the tested hand. LH-S patients demonstrated impaired learning during the initial training session and both LH-S and LH-A patients demonstrated decreased performance compared to controls during the next-day retest. Critically, the impairments in later learning stages in the LH-A patients were evident even before the appearance of traditional clinical symptoms in the tested hand. Results may be explained by the progression of disease-related alterations in relevant corticostriatal networks.

No MeSH data available.


Related in: MedlinePlus

Schematic of how performance on the MSL task may reflect disease progression.All participants completed the MSL task with their non-dominant left hand. X’s denote the affected side and the size of the X represents the relative magnitude of the impairment. Squares indicate that the right (contralateral) striatum is more critical for the execution of the MSL task since the left hand was used. In the left hand symptomatic (LH-S) group, the MSL task targeted the more affected right striatum. In contrast, in the left hand asymptomatic (LH-A) group, motor deficits were limited to the right side; thus, the MSL task targeted the less affected right striatum. In the control group, the MSL task targeted the intact right striatum. Comparison of the experimental groups may represent progression of PD. Please note that this schematic is intended to depict the laterality aspect of the research approach and does not address changes within striatal subregions as a function of MSL training. These details are discussed in the main text.
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pone.0134291.g005: Schematic of how performance on the MSL task may reflect disease progression.All participants completed the MSL task with their non-dominant left hand. X’s denote the affected side and the size of the X represents the relative magnitude of the impairment. Squares indicate that the right (contralateral) striatum is more critical for the execution of the MSL task since the left hand was used. In the left hand symptomatic (LH-S) group, the MSL task targeted the more affected right striatum. In contrast, in the left hand asymptomatic (LH-A) group, motor deficits were limited to the right side; thus, the MSL task targeted the less affected right striatum. In the control group, the MSL task targeted the intact right striatum. Comparison of the experimental groups may represent progression of PD. Please note that this schematic is intended to depict the laterality aspect of the research approach and does not address changes within striatal subregions as a function of MSL training. These details are discussed in the main text.

Mentions: Bridging the results from the two groups, we propose that the pattern of results may be explained by the severity of the disease within the hemisphere-specific striatal regions that are critical for the MSL task (Fig 5). Specifically, as the onset of motor symptoms in patients with PD is predominantly asymmetric, the dopaminergic deficiency in one hemisphere is more robust than the other [50]. Thus, asking participants to complete a MSL paradigm with the symptomatic or asymptomatic hand relies on the more or less affected contralateral corticostriatal network, respectively. Thus, in the context of the current study, the LH-S patients can be conceptualized as a model for more advanced PD—relative to the LH-A patients—as the dopaminergic deficiency in the right (contralateral) striatum was presumably more marked. Conversely, the LH-A patients can be conceptualized as in earlier disease stages as the dopaminergic deficiency in the right (contralateral) striatum was presumably less severe. Accordingly, the deficits in both initial learning and extended practice in the LH-S patients may be the result of advanced disease progression in the right (contralateral) striatum. For example, and as highlighted above, striatal denervation in this group likely extends beyond the sensorimotor territories that are affected early in the disease process and into the associative regions. Conversely, the impairments that emerge later in the learning process in the LH-A patients are the result of a less advanced stage of disease, as the striatal denervation is more limited to the sensorimotor regions of the striatum. The associative regions of the contralateral striatum would then be less affected in these patients, as the LH-A patients were more similar to healthy controls early in the learning process, and the first 4 blocks of practice in particular during which rapid behavioral improvements are evident.


Motor Sequence Learning and Consolidation in Unilateral De Novo Patients with Parkinson's Disease.

Dan X, King BR, Doyon J, Chan P - PLoS ONE (2015)

Schematic of how performance on the MSL task may reflect disease progression.All participants completed the MSL task with their non-dominant left hand. X’s denote the affected side and the size of the X represents the relative magnitude of the impairment. Squares indicate that the right (contralateral) striatum is more critical for the execution of the MSL task since the left hand was used. In the left hand symptomatic (LH-S) group, the MSL task targeted the more affected right striatum. In contrast, in the left hand asymptomatic (LH-A) group, motor deficits were limited to the right side; thus, the MSL task targeted the less affected right striatum. In the control group, the MSL task targeted the intact right striatum. Comparison of the experimental groups may represent progression of PD. Please note that this schematic is intended to depict the laterality aspect of the research approach and does not address changes within striatal subregions as a function of MSL training. These details are discussed in the main text.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4519305&req=5

pone.0134291.g005: Schematic of how performance on the MSL task may reflect disease progression.All participants completed the MSL task with their non-dominant left hand. X’s denote the affected side and the size of the X represents the relative magnitude of the impairment. Squares indicate that the right (contralateral) striatum is more critical for the execution of the MSL task since the left hand was used. In the left hand symptomatic (LH-S) group, the MSL task targeted the more affected right striatum. In contrast, in the left hand asymptomatic (LH-A) group, motor deficits were limited to the right side; thus, the MSL task targeted the less affected right striatum. In the control group, the MSL task targeted the intact right striatum. Comparison of the experimental groups may represent progression of PD. Please note that this schematic is intended to depict the laterality aspect of the research approach and does not address changes within striatal subregions as a function of MSL training. These details are discussed in the main text.
Mentions: Bridging the results from the two groups, we propose that the pattern of results may be explained by the severity of the disease within the hemisphere-specific striatal regions that are critical for the MSL task (Fig 5). Specifically, as the onset of motor symptoms in patients with PD is predominantly asymmetric, the dopaminergic deficiency in one hemisphere is more robust than the other [50]. Thus, asking participants to complete a MSL paradigm with the symptomatic or asymptomatic hand relies on the more or less affected contralateral corticostriatal network, respectively. Thus, in the context of the current study, the LH-S patients can be conceptualized as a model for more advanced PD—relative to the LH-A patients—as the dopaminergic deficiency in the right (contralateral) striatum was presumably more marked. Conversely, the LH-A patients can be conceptualized as in earlier disease stages as the dopaminergic deficiency in the right (contralateral) striatum was presumably less severe. Accordingly, the deficits in both initial learning and extended practice in the LH-S patients may be the result of advanced disease progression in the right (contralateral) striatum. For example, and as highlighted above, striatal denervation in this group likely extends beyond the sensorimotor territories that are affected early in the disease process and into the associative regions. Conversely, the impairments that emerge later in the learning process in the LH-A patients are the result of a less advanced stage of disease, as the striatal denervation is more limited to the sensorimotor regions of the striatum. The associative regions of the contralateral striatum would then be less affected in these patients, as the LH-A patients were more similar to healthy controls early in the learning process, and the first 4 blocks of practice in particular during which rapid behavioral improvements are evident.

Bottom Line: LH-S patients demonstrated impaired learning during the initial training session and both LH-S and LH-A patients demonstrated decreased performance compared to controls during the next-day retest.Critically, the impairments in later learning stages in the LH-A patients were evident even before the appearance of traditional clinical symptoms in the tested hand.Results may be explained by the progression of disease-related alterations in relevant corticostriatal networks.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology and Neurology, Key Laboratory of Ministry of Education on Neurodegenerative Disorders, Beijing Key Laboratory on Parkinson's Disease, Xuanwu Hospital of Capital Medical University, Beijing, China.

ABSTRACT
Previous research investigating motor sequence learning (MSL) and consolidation in patients with Parkinson's disease (PD) has predominantly included heterogeneous participant samples with early and advanced disease stages; thus, little is known about the onset of potential behavioral impairments. We employed a multisession MSL paradigm to investigate whether behavioral deficits in learning and consolidation appear immediately after or prior to the detection of clinical symptoms in the tested (left) hand. Specifically, our patient sample was limited to recently diagnosed patients with pure unilateral PD. The left hand symptomatic (LH-S) patients provided an assessment of performance following the onset of clinical symptoms in the tested hand. Conversely, right hand affected (left hand asymptomatic, LH-A) patients served to investigate whether MSL impairments appear before symptoms in the tested hand. LH-S patients demonstrated impaired learning during the initial training session and both LH-S and LH-A patients demonstrated decreased performance compared to controls during the next-day retest. Critically, the impairments in later learning stages in the LH-A patients were evident even before the appearance of traditional clinical symptoms in the tested hand. Results may be explained by the progression of disease-related alterations in relevant corticostriatal networks.

No MeSH data available.


Related in: MedlinePlus