The Basal Ganglia Under The Magnet (by P. Beukema)

A blog post on the article In vivo characterization of the connectivity and subcomponents of the human globus pallidus

If you wanted to understand how traffic flows in a busy city like New York, you would probably start with a map of the city’s streets. But a map alone would not get you very far. You would probably also want to know how big the streets are and how fast traffic moves on particular streets. Understanding how information is processed in the brain is a bit like building this detailed map. You might start with how information moves around by examining which parts are connected to others. Then you would examine how big or robust these pathways are.

One area of the brain where we only have a relatively coarse map is the basal ganglia. The basal ganglia refers to a group of four interconnected deep brain structures that collectively (among other functions) facilitate movement. A better map of the circuitry in the basal ganglia is highly desirable, because certain diseases are associated with damage to the pathways between these basal ganglia regions. For example, Huntington’s disease and Parkinson’s disease, two debilitating neurological disorders with profound motor deficits result, in part, from a breakdown in the pathways within the basal ganglia. For reasons that are not fully understood, these connections are highly susceptible to damage and because they are important for motor control, this damage can result in substantial motor deficits.

Clinically, it is difficult to see the pathways within the basal ganglia with neuroimaging techniques, like the ever popular MRI, because many of the fiber bundles that make up key parts of this circuit are very small and buried within areas of dense cell bodies. Specifically, many of these fibers are nestled within a set of nuclei that are known collectively as the globus pallidus, or just the pallidum for short. This means that it is difficult to distinguish the physical connections themselves (called white matter) that run through the pallidum from the other more cellular parts of the pallidum (called gray matter).

However, in a recent paper published in the journal NeuroImage, we show that it is now possible to detect signatures of these pathways using a non-invasive brain imaging tool called diffusion MRI. By measuring the movement of water molecules, diffusion MRI provides a map of the physical connections in the brain, comprised of long fibers known as axons. Using this tool, we were able to indirectly visualize the major pathways that course within the globus pallidus in two large samples of healthy subjects and found that the diffusion MRI signal was shaped in a way that is consistent with that of the underlying connections. Importantly, we found that these results were consistent across two unique datasets and are thus robust to brain images acquired with different technical specifications.

While using these careful reconstructions of the diffusion MRI signal, we showed how it is possible to detect these small but important fiber connections in the living human brain, but we also found that, using statistical analysis on the diffusion imaging signal, we could separate the two components that make up the pallidum, called the internal and external globus pallidus. This means that by looking at the general patterns of water movement in the brain, we can automatically distinguish one small brain region from the next… at least within the basal ganglia.

These intriguing findings tell us that, with diffusion MRI, it is possible to detect two unique aspects of these critical pathways in the brain. First we can detect signatures of the fiber bundles running through deep brain nuclei. Second we can localize different segments of these nuclei. Both of these findings suggest that the diffusion signal might serve as a marker of the collective health of key basal ganglia pathways and potentially be used to track the progression of diseases like Parkinson’s or Huntington’s disease.

This work, of course, raises more questions than it answers. One question is whether or not this technique is sensitive enough to be used as the foundation for a novel in vivo biomarker of the health of these pathways in disease. Another question is whether the strength at which information flows between these pathways is predictive of differences in behavior, like how fast you can learn to play the piano, or ride a bike. These questions will, of course, pave the foundation for many future projects in the CoAx lab.

Stay tuned.

Source Paper: “In vivo characterization of the connectivity and subcomponents of the human globus pallidus.” P Beukema, FC Yeh, T. Verstynen NeuroImage 120(15), 382–393 (2015). (pdf)

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