If you are reading this article from this website right now, I would take a wild guess and suppose you might have at least some interest in how the brain works. This desire to understand more about the mind is shared by many philosophers in the last few centuries. However, they encountered some obstacles on their way. Among them, the size of the neurons (0.01-0.05 mm diameter) made it impossible to observe them prior to the invention of the microscope at the end of the 17th century, and even then, those observations could only be undertaken on post-mortem brains. Another crucial invention, which is the focus of this article, was that of the various neuro-imaging techniques that are simply necessary to observe a living brain through the skull and the different tissues surrounding it. Thus, a few techniques were proposed in the late 19s and early 20s, such as the “human circulation balance” from Angelo Mosso, which more closely resembled a medieval torture device than a brain scanner, and the pneumoencephalography, which required the cerebral spinal fluid to be replaced by air. These techniques are now outdated. Here, we will focus on the strengths and weaknesses of three more recent, important, and well-established techniques; fMRI, EEG, and PET imaging.
Functional magnetic resonance imaging or functional MRI (fMRI), not to be confused with structural MRI (simply referred to as MRI), is a painless, non-invasive neuroimaging technique that produces detailed 3D images of the anatomy of our brains and is used to measure brain activity. This activity is inferred from an indirect observation of the ratio between oxy- and deoxyhemoglobin. What does that mean? Our circulatory system is responsible for oxygenating the different cells and tissues of our body and eliminating waste products and carbon dioxide from these cells. This is done by hemoglobin, a protein in red blood cells to which oxygen and carbon dioxide can be bound and therefore transported through the body. Thus, the oxygenated blood is bound to hemoglobin and hence called oxyhemoglobin. Regarding the brain, when a particular area is active, more oxygen-rich blood is delivered. The combination of the oversized electromagnet constituting the MRI scanner and a radiofrequency current can detect the different magnetic properties between oxy- and deoxygenated blood. The signal the MRI scanner picks up is therefore called the BOLD (blood-oxygen-level-dependent) response. Simply put, fMRI makes images of brain activity based on the amount of oxygenated blood that rushes to the brain areas that are active. More details about the mechanism of this technique can be found here: fMRI - Brain Matters
FMRI is mostly used for its excellent spatial resolution. That is, it can determine very precisely which part of the brain is active (relative to others) and provide high-quality images of the brain. Therefore, it is mostly used to study the structure of the brain, assign various functions to its specific regions, but also to examine the effects of cerebrovascular accidents, trauma, or neurodegeneration on brain function, and keep track of the growth of brain tumors. On the other hand, an fMRI scan is expensive, and patients must stay still to capture clear images, which is often more difficult than it seems when it lasts for a sustained period of time, resulting sometimes in poor imaging quality. In addition, the main limitation of fMRI is that it provides a poor temporal resolution, as the blood takes some time to flow from one part of the brain to another (the BOLD response takes approximately 4 seconds, which is a very long time in the neuroscience world). This means that we can’t tell precisely when the changes observed in the brain are happening. To compensate for this, fMRI studies are often combined with EEG.
As you probably know, the brain communicates via electrical impulses, in the form of an action potential and a postsynaptic potential. Electroencephalography (EEG) is a method used to measure this electrical activity by placing electrodes with a special conducting glue on the scalp. The precise mechanism of EEG is a little bit complex and well-defined here: EEG - Brain Matters. In summary, when neurons communicate, positive and negative ions such as Na+, K+, or Cl- continually leave and enter the neurons’ membranes, which gives rise to dynamic movements of positive and negative charge throughout the brain, called dipoles. Those differences in electric charges are picked up by the electrodes and sent to a device that records and transforms the brain activity in the form of wave patterns. Those can then be analyzed and identified by specialists, who so far have classified them into five basic patterns: delta, theta, alpha, beta, and gamma waves. Each pattern is associated with different states of alertness and different functions.
Unlike fMRI, one of the biggest advantages of EEG resides in its high temporal resolution, which means its ability to record brain activity as it unfolds in real-time, at the level of milliseconds (thousandths of a second). However, EEG imaging cannot provide precise information about the origin of brain activity (low spatial resolution), nor can it reliably detect signals from subcortical structures. This is why the EEG and fMRI techniques are often combined, as they complement each other well.
As we saw previously with fMRI, neurons need oxygen to function, and measuring the changes in the magnetic properties of oxygenated vs deoxygenated blood enables us to measure changes correlated with brain activity. Positron emission tomography (PET) is a nuclear imaging technique also used to measure brain activity, by following a similar yet distinct methodological path. Neurons need oxygen, yes, but also glucose for proper operation. Precisely, the brain needs approximately 5.6mg of glucose per 100g of brain tissue per minute. Thus, the rationale underlying PET imaging is to inject a radioactive tracer into the bloodstream that will bind to glucose. Then, when certain brain areas activate, the tracer contained in the glucose will be brought there. A positron will be released from the particle and collide with an electron. This will in turn result in the creation of two photons, which will be detected by the PET scan. More details about the functioning of PET imagery can be found here: PET - Brain Matters.
One of the reasons to use a PET scan is that it can reveal which parts of your body are functioning at the cellular level with qualitative anatomic resolution. This is especially helpful for identifying and investigating cancers, infections, and how the body reacts to the diseases and their treatments. PET is also increasingly used to investigate neurotransmission. Nonetheless, PET imaging also contains some limitations. The most obvious one is that the subject must be injected with radioactive tracers. This procedure isn’t harmful if done once or twice, but becomes problematic if done more often, as the effects of radiation add up over the lifetime. Therefore you cannot scan the same individual multiple times. This is a limitation for research since you cannot conduct within-subject studies, meaning that you would compare the same individual('s brain) under different conditions. These types of studies are useful since brains tend to differ a lot between people, and the averaging or standardization process of different brains is complicated and often affects the data.
To sum up, there is no magical imaging technique enabling us to have complete access to brain structure and function on a level of milliseconds and millimeters. Different techniques permit different analyses of the brain, all containing some advantages and limitations or costs. Therefore, imaging techniques should be chosen depending on what you want to know about the brain. If the timing of brain activity is important, you should probably go for EEG, but if you are interested in where the activity takes place, fMRI or PET would be better options. Currently, scientists are working on combining multiple techniques to get the best of all worlds.
Author: Pablo de Chambrier
