APBN New Site

APBN Developing Site

Substantial Nigra Damage Could Explain Sequential Memory Deficits in Parkinson’s Disease

Damage to a region in the midbrain correlates with basal ganglia dysfunction and poor sequencing performance in Parkinson’s disease.

For many of us, engaging in a conversation and scheduling our daily activities are not challenging tasks; the ability to process sequential information online comes quite naturally. In Parkinson’s disease, deficits in sequential working memory could translate into difficulties in concentrating, learning, making decisions, or remembering. This cognitive impairment is one of the most common non-motor symptoms observed in individuals with Parkinson’s that can greatly affect one’s quality of life and functional independence.

Previously, researchers have demonstrated that poor sequencing performance of individuals with Parkinson’s correlated with hyperactivation of the subthalamic nucleus and weakened functional connectivity between the subthalamic nucleus and striatum. These are components that make up the basal ganglia and are responsible for coordinating multiple aspects of cognition.

In this study, researchers from Dr. Ye Zheng’s Lab at the Institute of Neuroscience, Center for Excellence in Brain Sciences and Intelligence Technology of the Chinese Academy of Sciences, and Dr. Jin Lirong’s team from Zhongshan Hospital of the Fudan University hypothesised that the basal ganglia’s functional changes during sequential working memory correlate with the degree of substantia nigra integrity. Through their work, they were able to demonstrate that damage to the substantia nigra indeed correlates with basal ganglia dysfunction and poor sequencing performance in Parkinson’s.

To better understand the neurobiology of sequential working memory deficits in Parkinson’s disease, the team used neuromelanin-sensitive structural magnetic resonance imaging (MRI) to measure the area of substantia nigra pars compacta with high neuromelanin signals in 29 patients with Parkinson’s and 29 healthy control individuals. Neuromelanin is a dark pigment that is distinct in catecholaminergic neurons of the substantia nigra pars compacta, giving a darkened appearance in these regions of aged brains. The loss of neuromelanin of these brain regions is an indication of Parkinson’s disease.

The researchers also subjected the participants to a digit ordering task, where they were asked to remember a sequence of four digits and recall the digits in ascending order. In half of the trials, the digits appeared in ascending order, and the participants need only remember the original sequence. In the other half, the digits were randomised and the participants had to reorder the digits. Their behavioural performance and brain activity was then measured.

The team found that the substantia nigra areas with high neuromelanin signals were noticeably smaller in patients with Parkinson’s than healthy individuals, suggesting disease-related damage to the substantia nigra pars compacta.

In the digit ordering task, the striatum and globus pallidus was observed to be less active than normal, while the subthalamic nucleus was hyperactivated, and the functional connectivity between the substantia nigra and all three basal ganglia regions were found to be markedly weakened in patients with Parkinson’s than healthy individuals. On top of that, Parkinson’s patients with smaller substantia nigra displayed lower accuracy in ordering.

While anti-parkinsonian drugs like dopamine receptor agonists could modulate ordering-related subthalamic activation, it could not improve the sequencing performance of Parkinson’s patients. The results of this study suggest that basal ganglia dysfunction causes damage to the substantia nigra pars compacta, which may lead to sequential memory deficits in Parkinson’s disease. [APBN]

Source: Liu et al. (2021). Substantia Nigra Integrity Correlates with Sequential Working Memory in Parkinson’s Disease. Journal of Neuroscience, 41(29), 6304-6313.