Dataset Information

Tracking Response Dynamics of Sequential Working Memory in Patients With Mild Parkinson's Disease.

ABSTRACT: The ability to sequence thoughts and actions is impaired in Parkinson's disease (PD). In PD, a distinct error pattern has been found in the offline performance of sequential working memory. This study examined how PD's performance of sequential working memory unfolds over time using mouse tracking techniques. Non-demented patients with mild PD (N = 40) and healthy controls (N = 40) completed a computerized digit ordering task with a computer mouse. We measured response dynamics in terms of the initiation time, ordering time, movement time, and area under the movement trajectory curve. This approach allowed us to distinguish between the cognitive processes related to sequence processing before the actual movement (initiation time and ordering time) and the execution processes of the actual movement (movement time and area under the curve). PD patients showed longer initiation times, longer movement times, and more constrained movement trajectories than healthy controls. The initiation time and ordering time negatively correlated with the daily exposure to levodopa and D2/3 receptor agonists, respectively. The movement time positively correlated with the severity of motor symptoms. We demonstrated an altered temporal profile of sequential working memory in PD. Stimulating D1 and D2/3 receptors might speed up the maintenance and manipulation of sequences, respectively.

SUBMITTER: Zhang G

PROVIDER: S-EPMC7933003 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Tracking Response Dynamics of Sequential Working Memory in Patients With Mild Parkinson's Disease.

Zhang Guanyu G Ma Jinghong J Chan Piu P Ye Zheng Z

Frontiers in psychology 20210219

The ability to sequence thoughts and actions is impaired in Parkinson's disease (PD). In PD, a distinct error pattern has been found in the offline performance of sequential working memory. This study examined how PD's performance of sequential working memory unfolds over time using mouse tracking techniques. Non-demented patients with mild PD (<i>N</i> = 40) and healthy controls (<i>N</i> = 40) completed a computerized digit ordering task with a computer mouse. We measured response dynamics in ...[more]

PMID: 33679559

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Project description:Maintaining and manipulating sequences online is essential for daily activities such as scheduling a day. In Parkinson's disease (PD), sequential working memory deficits have been associated with altered regional activation and functional connectivity in the basal ganglia. This study demonstrates that the substantia nigra (SN) integrity correlated with basal ganglia function and sequencing performance in 29 patients with PD (17 women) and 29 healthy controls (HC, 18 women). In neuromelanin-sensitive structural MRI, PD patients showed smaller SN than HC. In a digit ordering task with functional MRI, participants either recalled sequential digits in the original order ('pure recall') or rearranged the digits and recalled the new sequence ('reorder & recall'). PD patients performed less accurately than HC, accompanied by the caudate and pallidal hypo-activation, subthalamic hyper-activation, and weakened functional connectivity between the bilateral SN and all three basal ganglia regions. PD patients with larger SN tended to exhibit smaller ordering-related accuracy costs ('reorder & recall' versus 'pure recall'). This effect was fully mediated by the ordering-related caudate activation. Unlike HC, the ordering-related accuracy cost correlated with the ordering-related caudate activation but not subthalamic activation in PD. Moreover, the ordering-related caudate activation correlated with the SN area but not the daily dose of D2/3 receptor agonists. In PD, the daily dose of D2/3 receptor agonists correlated with the ordering-related subthalamic activation, which was not related to the accuracy cost. The findings suggest that damage to the SN may lead to sequential working memory deficits in PD, mediated by basal ganglia dysfunction.SIGNIFICANCELiu et al. demonstrate that damage to the substantia nigra (SN) correlates with basal ganglia dysfunction and poor sequencing performance in Parkinson's disease (PD). In neuromelanin-sensitive MRI, PD showed smaller SN than healthy controls. In a digit ordering task with functional MRI, PD's lower task accuracy was accompanied by the caudate and pallidal hypo-activation, subthalamic hyper-activation, and weakened functional connectivity between the SN and basal ganglia. PD with larger SN exhibited greater ordering-related caudate activation and lower ordering-related accuracy cost when sequencing digits. PD with more daily exposure to D2/3 receptor agonists exhibited greater ordering-related subthalamic activation, which did not reduce accuracy cost. It suggests that the SN may affect sequencing performance by regulating the task-dependent caudate activation in PD.

Project description:Impairment of working memory and executive functions is already frequently observed in early stages of Parkinson's disease. Improvements in working memory performance in this cohort could potentially be achieved via working memory training. However, the specific neural mechanisms underlying different working memory processes such as maintenance as opposed to manipulation are largely under-investigated in Parkinson's disease. Moreover, the plasticity of these correlates as a function of working memory training is currently unknown in this population. Thus, the working memory subprocesses of maintenance and manipulation were assessed in 41 cognitively healthy patients with Parkinson's disease using a newly developed working memory paradigm and functional MRI. Nineteen patients were randomized to a 5-week home-based digital working memory training intervention while the remaining patients entered a control, wait list condition. Working memory task-related activation patterns and context-dependent functional connectivity, as well as the change of these neural correlates as a function of training, were assessed. While both working memory processes activated an extended frontoparietal-cerebellar network, only the manipulation of items within working memory also recruited the anterior striatum. The intervention effect on the neural correlates was small, but decreased activation in areas relevant for working memory could be observed, with activation changes correlating with behavioural change. Moreover, training seemed to result in decreased functional connectivity when pure maintenance was required, and in a reorganization of functional connectivity when items had to be manipulated. In accordance with the neural efficacy hypothesis, training resulted in overall reduced activation and reorganized functional connectivity, with a differential effect on the different working memory processes under investigation. Now, larger trials including follow-up examinations are needed to further explore the long-term effects of such interventions on a neural level and to estimate the clinical relevance to potentially delay cognitive decline in cognitively healthy patients with Parkinson's disease.

Dataset Information

Tracking Response Dynamics of Sequential Working Memory in Patients With Mild Parkinson's Disease.

Publications

Tracking Response Dynamics of Sequential Working Memory in Patients With Mild Parkinson's Disease.

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