Two connectivity gradients discovered in the substantia nigra, one linked to aging and motor function and the other to memory and mood
Two connectivity gradients discovered in the substantia nigra, one linked to aging and motor function and the other to memory and mood
On September 8, Molecular Psychiatry published a study of the substantia nigra, a small midbrain region involved in motor control. Using data from over a thousand participants across four independent datasets, the authors identified two stable gradients: smooth, continuous shifts in how different subregions of the substantia nigra connect to the rest of the brain.
The substantia nigra is most commonly associated with Parkinson's disease: the loss of its dopamine-producing neurons disrupts movement. However, its different subregions also participate in networks involved in memory, emotion, and decision-making. The authors examined how these connectivity profiles are distributed across the entire structure, from one subregion to the next.
To do this, they used resting-state functional MRI: while a person lies still in the scanner, the instrument records correlated signal fluctuations across different brain regions. For each small subregion of the substantia nigra, the researchers compared its pattern of correlated activity with the rest of the brain. The gradual shift in connectivity profiles from one neighboring subregion to the next forms a gradient, a smooth transition within a single structure.
The map was first constructed in 618 healthy individuals aged 18 to 88, then validated in a separate group of 184 young participants scanned at higher resolution. Both samples reproduced the same two principal gradients. The first, running from the medial to the lateral aspect of the structure, correlated with age, reaction time, motor learning, and planning ability. In the clinical datasets, this gradient differed between groups classified by the results of cerebrospinal fluid seed amplification assay (SAA), which tests whether alpha-synuclein protein forms aggregates.
The second gradient ran from the posterior to the anterior portion. In the healthy aging sample, it was associated with memory, cognitive flexibility, anxiety, and depression. In groups with Parkinson's disease and with mild cognitive impairment linked to Alzheimer's disease, it correlated with measures of memory, mood, and psychiatric symptoms.
This map makes it possible to frame a more precise next question: how the different connectivity patterns of the substantia nigra change over time within a single individual, and which clinical manifestations accompany each of them.