Resolving to map the brain: resolution, resolution, resolution

-April 16, 2013

Just less than six months after being proposed in this very space, the executive branch of the US government has seen the light. The BRAIN  (brain research through advancing innovative neurotechnologies) initiative injects $100M into the NIH (National Institutes of Health), DARPA (Defense Advanced Research Projects Agency), and the NSF (National Science Foundation) earmarked to kick start a project more challenging than the human genome project.

Mapping the brain amounts to isolating and monitoring every neuron in the brain—any brain. Neurons are the brain cells that do the nervous systems’ heavy lifting: from thought to metabolic monitoring. You have about 10 trillion neurons in your head and each averages 10,000 connections – a huge number of possible permutations. They consist of a central structure that includes a nucleus and the usual wetware of cell biology along with what makes them fantastic: axons, dendrites, and synapses. The cell body is the transmitter, the axon the output channel, synapse the receiver and dendrite the reception channel.

Figure 1: Diagram of a neuron (Copyright & Courtesy National Institutes of Health)

Electrical signals of about 100 mV peak-to-peak, called action potentials, propagate from the cell body along axons through chemically driven alternating polarization-depolarizations—think of an axon as a long string of tiny repeaters—eventually connecting to the dendrite of another neuron through a synapse. The synapse is like the chemical version of a variable threshold logic gate.

Current brain scanning technology includes: CT (computed tomography) scans, PET (positron emission tomography) scans, and fMRI (functional nuclear magnetic resonance imaging).

CT scans project X-rays through the head at different angles. The resulting set of 2D images are processed into a 3D tomograph of the brain.

PET scans begin with an injection of a positron emitting radioactive substance. As the substance courses through the blood, it emits positrons which are easy to detect. The result is a blood flow map of brain metabolism, in particular, neurotransmitter activity at synapses.

The colorful images you’ve seen in the news, called “brainbows” or even “brain porn,” are produced by fMRI scanners based on nuclear magnetic resonance. Superconducting magnets generate multi-Tesla fields that alternate at the resonant radio frequencies of hydrogen nuclei, a.k.a., protons. The rotating protons radiate their own RF signals which are detected and projected back to their source. The result is an image of the hydrogen distribution, in particular, water, which provides a map of brain activity.

Figure 2: A brainbow (Copyright & Courtesy National Institutes of Health)

High X-ray dose CT scans have the best resolution, just over 0.1 mm but are static pictures, PET scans come in second 1 mm, and the photogenic fMRI is third at 2-3 mm and both can produce movies. Unfortunately, neurons are comparatively tiny. The central cell body is about 0.03 mm across. While axon length varies from millimeters to feet, dendrites are rarely longer than a millimeter. The problem, from an imaging perspective, is that axons and dendrites are close-packed in the brain and have diameters of about 0.001 mm.

The challenge for the brain project is to develop noninvasive imaging technology, like fMRI, that is capable of submicron resolution in three dimensions and able to record dynamic, moving images.

Development of the technology will not be done by biologists and neuroscientists. Just as existing imagers were developed by teams of engineers and physicists in physics laboratories, so will the BRAIN imager. Once the data start rolling in, the myriad signals and the incredible number of correlating signals will be analyzed by physicists, mathematicians, electrical engineers, chemists, and, yes, biologists, at least those who took probability and statistics.

The obvious application of BRAIN imaging will be diagnostic tools for a vast array of brain diseases from Alzheimer’s to Wilson’s disease. But that’s obvious, here’s where it gets interesting:

Once the data is in hand, the shouting will begin.

While existing lie detector technology, e.g., polygraph tests, are no better than a coin flip, a BRAIN imager can easily distinguish whether a statement is sincere or not for the simple reason that we use separate brain components to tell lies than to tell truths.

The very essence of free will, already discarded in most neuroscience circles, will come under study and have immediate impact on how society operates. Can a mass murderer be blamed for his/her errant behavior? We’ll see.

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