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Thursday, August 18, 2022
Dr. Brown: Functional MRIs and conduction of nerve impulses

Our brain is enormously complex and capable of great feats of imagination, creation, ingenuity and understanding the world around us. Yet our brains can be mysteriously opaque about how they go about much of their business. 

That’s not to say that we haven’t made progress – we have – by studying the absence or alteration of functions created by lesions that affect the brain, studies such as those pioneered by Penfield, who mapped the exposed brains of patients undergoing surgery for epilepsy, and the flood of functional MRI (fMRI) studies in the last two decades. Even so, the brain remains an enigma when it comes to the nature of thought, feelings, awareness and that bugaboo for physiologists and psychologists alike – consciousness.

Jack Eccles, a Nobel laureate, made the point in a lecture in the late 1980s when he repeatedly tapped the lectern with his right index finger and suggested that such movements were preceded by the firing of hundreds, if not a few thousand nerve cells, in the functionally related region of his left motor cortex.

His next slide revealed it was possible to detect electrical activity which preceded each tap of his finger by at least a tenth of a second. He went on to suggest that such localized nerve cell activity in the neocortex would be associated with local increases in oxygen consumption and blood flow. He was right.

Functional MRI was designed to detect just such activity-related changes as a means of localizing brain activity associated with a variety of tasks. Examples include localizing the increased metabolic activity associated with speech, imagining a walk along a familiar route or perhaps figuring out what goes on in the brain during mediation.

One very practical use of fMRIs is to map the brain for speech and voluntary movement to avoid injuring these regions during surgery. Positron emission tomography (PET) may be less popular than fMRI for localizing purposes but provides a sensitive way to identify deposits of amyloid and tau in the brain one or two decades before patients with Alzheimer’s disease develop their earliest symptoms. 

But beguiling as such colour images can be, they can be misleading because sometimes there’s more going on in the brain than rises to the threshold for creating those images.

There’s also the matter of scale. Functional MRI operates on a grand scale but provides little information about how the brain operates at the cellular scale. But it’s precisely at the latter scale where some of the most fundamental processes of the brain, such as conditioning, learning and memory, take place. 

The latter type of study was carried out by Eric Kandel, who won the Nobel prize for his work. He chose aplasia, a primitive sea slug because it has a small number of large, early identifiable and functionally specific nerve cells with which he was able to show how conditioning and short- and long-term memory work at the cellular level, including the genetic and biochemical underpinnings for these phenomena.

Perhaps the best examples of choosing a simple organism to study basic phenomena in nervous tissue were the classical studies of the action potential by Hodgkin and Huxley soon after the Second World War. They chose the giant axon of the squid because it was easy to see with the naked eye and large enough to easily insert one of their electrodes inside the axon.

The latter made it possible to clamp the voltage across the membrane at fixed values while they studied the associated currents that accompany the action potential. They also examined how changes to the concentrations of selected ions outside or inside the axon changed the action potential. And like Kandel’s later work, it was elegant and generalizable to far more evolved and complex nervous systems, including our own, and one more example of how biological systems that work are evolutionarily conserved. 

The giant nerve fibre of the squid has no insulating fatty sheath (myelin) wrapped about the nerve fibre as do many mammalian nerve fibres. It was left to Huxley and Stampfli to show that the “active” part of the action potential in myelinated nerve fibres was not continuously conducted as in the giant squid nerve fibre but jumped from one “active” region to the next in a string of active regions separated by intervals of 1/50th to 1/10th of a millimetre. 

Thus it greatly conserved energy and increased the conduction velocities of larger myelinated nerve fibres from a few metres per second, typical of the squid axon, to the 50 to 70 metres per second typical of large-myelinated nerve fibres in brains, spinal cords and peripheral nerves of humans.

By the way, 55 to 70 metres per second translates to 181 to 254 km/h and well over the speed limit on the QEW. Not bad for nerve fibres one-hundredth of a millimetre or less in diameter. 

McDonald, Rasminsky and Sears later showed how loss of the myelin sheath in nerve fibres could greatly slow and even block transmission in affected nerves, causing loss of sensation, paralysis and balance in multiple sclerosis and other inflammatory conditions affecting the brain, spinal cord and peripheral nerves.

These and other phenomena that govern nervous and synaptic transmission in the brain are the subject of the third virtual session in the BRAIN series on March 17. Register via the NOTL library's website.


Dr. William Brown is a professor of neurology at McMaster University and co-founder of the Infohealth series at the Niagara-on-the-Lake Public Library.