Functional magnetic resonance imaging
Functional Magnetic Resonance Imaging (or fMRI) describes the use of MRI to measure hemodynamic signals related to neural activity in the brain or spinal cord of humans or other animals. It is one of the most recently developed forms of brain imaging.
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It has been known for over 100 years (see Sherrington) that hemodynamic activity is closely linked to neural activity. When nerve cells are active, they consume oxygen supplied by local capillaries. Approximately 4-6 seconds after a burst of neural activity, a haemodynamic response occurs and that region of the brain is infused with oxygen-rich blood.
Haemoglobin is diamagnetic when oxygenated but paramagnetic when deoxygenated. The MR signal of blood is therefore slightly different depending on the level of oxygenation, a phenomenon called the Blood Oxygenation Level Dependent (or BOLD) signal. An MR scanner can be used to detect the BOLD contrast. The precise relationship between neural signals and BOLD is under active research. As a general statement, changes in BOLD signal are well correlated with changes in blood flow, and numerous studies during the past several decades have identified a coupling between flow and metabolism; that is, the blood supply is tightly regulated in space and time to provide the nutrients for brain metabolism. However, neuroscientists have been seeking a more direct relationship between the blood supply and the neural inputs/outputs that can be related to observable electrical activity and circuit models of brain function. While current data indicate that local field potentials, an index of integrated electrical activity, form a better correlation with blood flow than the spiking action potentials that are most directly associated with neural communication, no simple measure of electrical activity to date has provided an adequate correlation with metabolism and the blood supply across a wide dynamic range. Presumably, this reflects the complex nature of metabolic processes, which form a superset with regards to electrical activity. Some recent results have suggested that the increase in CBF following neural activity is not causally related to the metablic demands of the neural activity but instead is driven by the presence of neurotrasmitter, especially glutamate.
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BOLD effects are measured using a T2 related imaging process (actually T2*), which is different from the T1 scan taken in ordinary structural MRI images (the former measures the rate of change of spin phases, while the later detects the half-life of inverted spins). T2* images can be acquired with moderately good spatial and temporal resolution; scans are usually repeated every 2-5 seconds, and the voxels in the resulting image represent cubes of tissue approximately 3 millimeters on each side. Other non-invasive functional medical imaging techniques can improve on one of these figures, but not both.
The science of applying fMRI is quite complicated and multi-disciplinary. It involves:
- A good understanding of the physics of MRI scanners.
- Statistical analysis of results. Because the signals are very subtle, correct application of statistics is essential to both "tease out" observations and avoid false-positive results.
- Psychological study design. When conducting fMRI on humans, for example, it is essential to employ carefully designed experiments which allow the precise neural effect under consideration to be separated.
- For a non-invasive scan, MRI has moderately good spatial resolution, but relatively poor temporal resolution. Increasingly, it is being combined with other data collection techniques such as EEG or MEG, which have much higher recording frequencies.
- Integration with other areas of neuroscience in order to better understand the location (and role) of the signals which fMRI is able to detect. This includes a great deal of neuroanatomy but also other sub-fields such as neurochemistry and neuropathology.
Aside from BOLD fMRI, there are other ways to probe the brain activity using MRI.
- An injected contrast agent, such as an iron oxide that has been coated by a sugar or starch to hide from the body's defense system, causes a local disturbance in the magnetic field that is measurable by the MRI scanner. The signals associated with these kinds of contrast agents are proportional to the cerebral blood volume. While this semi-invasive method presents a considerable disadvantage in terms of studying brain function in normal subjects, it enables far greater detection sensitivity than BOLD signal, which may increase the viability of fMRI in clinical populations. Other methods of investigating blood volume that do not require an injection are a subject of current research, although no alternative technique in theory can match the high sensitivity provided by injection of contrast agent.
- By magnetic labeling the proximal blood supply using "arterial spin labelling" ASL, the associated signal is proportional to the cerebral blood flow, or perfusion. This method provides more quantitative physiogical information than BOLD signal, but has less sensitivity for detecting task-induced changes in local brain function.
Magnetic resonance spectroscopic imaging (MRS) is another, NMR-based process for assessing function within the living brain. MRS takes advantage of the fact that protons (H) residing in differing chemical environments depending upon the molecule they inhabit (H2O vs. protein, for example) possess slightly different resonant properties. For a given volume of brain (typically > 1 cubic cm), the distribution of these H resonances can be displayed as a spectrum. The area under the peak for each resonance provides a quantitative measure of the relative abundance of that compound. The largest peak is composed of H2O. However, there are also discernable peaks for choline, creatine, n-acetylaspartate (NAA) and lactate. Fortuitously, NAA is mostly inactive within the neuron, serving as a precursor to glutamate and as storage for acetyl groups (to be used in fatty acid synthesis) -- but its relative levels are a reasonable approximation of neuronal integrity and functional status. Brain diseases (schizophrenia, strokes, certain tumors, multiple sclerosis) can be characterized by the regional alteration in NAA levels when compared to healthy subjects. Creatine is used a relative control value since its levels remain fairly constant, while choline and lactate levels have been used to evaluate brain tumors.
diffusion tensor imaging (DTI) is a related use of MR to measure anatomical connectivity between areas. Although it is not strictly a functional imaging technique, because it does not measure dynamic changes in brain function, the measures of inter-area connectivity it provides are complementary to images of cortical function provided by BOLD fMRI. As protons are directed along certain axes in the brain (for example, as water flowing down a neuronal axon within a bundle of nerve fibers in cerebral white matter), this directionality can be measured. Connectivity between brain regions may be inferable from diffusion images, and illnesses that disrupt the normal organization or integrity of cerebral white matter (such as multiple sclerosis) have a quantitative impact on DTI measures.
Scanning in Practice
Subjects in a fMRI are asked to lie still, and usually restrained with soft pads to prevent small motions from disturbing measurements. It is possible to correct for some amount of motion with postprocessing of the data, but significant motion can easily render these attempts futile. Motion becomes a considerable problem when scanning subject populations that are not physically or emotionally equipped for even short MRI sessions (e.g., Alzheimer's dementia or schizophrenia).
Is fMRI worthwhile?
Since its inception, fMRI has been strongly critised. Some people go so far as to suggest that fMRI is just a modern-day phrenology and is destined to fail (after using up large sums of public money) because it's fundamentally uninformative. There are two main critisims often levelled at fMRI:
- The theoretical models used to explain the brain activations are so poorly specifies that they are very rarely falsifiable (a central tenet from the philosophy of science). Hence, some argue, fMRI is not really a "science". The counter argument would be that a well designed and honest fMRI study does provide evidence to falsify a prior theory.
- fMRI only asks "where" activations take place. Some psychologists take issue with this because they prefer models which explain "how" psychological mechanisms function. The counter-argument to this critisism would be that knowing "where" a cognitive function is located is vitally important - neuropsychology, invasive manipulation of brain function and functional imaging have given us some understanding of what each brain area does and it's useful to compare fMRI results to these prior hypotheses.