Substantia Nigra Integrity Correlates With Sequential Working Memory In Parkinson’s Disease

The storage and processing of sequential information is essential for daily activities.For example,we need to plan daily schedules in advance according to the order and importance of events.In Parkinson’s disease(PD),the impairment of the patient’s sequential working memory function is related to the activation of altered regional activation and changes in functional connectivity.In this study,we demonstrated that the integrity of the substantia nigra(SN)correlated with basal ganglia function and sequencing performance.We recruited 29 PD patients(17 female)and 29 healthy controls(HC,18 female)for this research.We used neuromelanin-sensitive structural MRI to assess the integrity of SN.We found that PD patients have a smaller SN area than HC.We combined the digit ordering task and functional MRI(f MRI)to evaluate the ability of HC and PD to maintain and manipulate sequence information,requiring the subjects to recall in ascending order.In one task type,the participant needs to recall the numbers that have been arranged in order("pure recall");in the other task type,the participant needs to remember and adjust the random order,and then recall the order from small to large("reorder & recall").We found that compared with HC,PD patients showed lower task accuracy,while brain activity showed hypo-activation of the caudate nucleus and globus pallidus(GP),accompanied by the subthalamic hyper-activation,and weakened functional connectivity between the bilateral SN and basal ganglia regions.PD patients with a larger SN area tended to exhibit smaller ordering-related accuracy costs("reorder &recall" versus "pure recall").This effect is mediated by the ordering-related activities of the caudate activation.Different from HC,the ordering-related accuracy costs related with the activation of the caudate but not subthalamic activation in PD.Moreover,the ordering-related activation of the caudate correlated with the SN area but not the daily dose of D2/3 receptor agonist.In PD,the daily dose of D2/3 receptor agonists correlated with the ordering-related activation of subthalamic,but not with the behavioral accuracy cost.These findings indicate that damage to SN may lead to sequential working memory deficits in PD,which is mediated by altered basal ganglia functions.