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To show these blood flow changes were related to functional brain activity, they changed the composition of the air breathed by rats, and scanned them while monitoring brain activity with EEG. However, this method is not popular in human fMRI, because of the inconvenience of the contrast agent injection, and because the agent stays in the blood only for a short time. Three studies in were the first to explore using the BOLD contrast in humans.

Kenneth Kwong and colleagues, using both gradient-echo and inversion recovery Echo Planar Imaging EPI sequence at a magnetic field strength of 1.

Functional Magnetic Resonance Imaging Processing | Xingfeng Li | Springer

Ogawa and others conducted a similar study using a higher field 4. Bandettini and colleagues used EPI at 1. The magnetic fields, pulse sequences and procedures and techniques used by these early studies are still used in current-day fMRI studies. But today researchers typically collect data from more slices using stronger magnetic gradients , and preprocess and analyze data using statistical techniques.

Principles of fMRI Part 1, Module 13: Pre-processing I

The brain does not store glucose, its primary source of energy. When neurons become active, getting them back to their original state of polarization requires actively pumping ions across the neuronal cell membranes, in both directions. The energy for those ion pumps is mainly produced from glucose. More blood flows in to transport more glucose, also bringing in more oxygen in the form of oxygenated hemoglobin molecules in red blood cells. This is from both a higher rate of blood flow and an expansion of blood vessels. Usually the brought-in oxygen is more than the oxygen consumed in burning glucose it is not yet settled whether most glucose consumption is oxidative , and this causes a net decrease in deoxygenated hemoglobin dHb in that brain area's blood vessels.

This changes the magnetic property of the blood, making it interfere less with the magnetization and its eventual decay induced by the MRI process. The cerebral blood flow CBF corresponds to the consumed glucose differently in different brain regions. Initial results show there is more inflow than consumption of glucose in regions such as the amygdala , basal ganglia , thalamus and cingulate cortex , all of which are recruited for fast responses.

In regions that are more deliberative, such as the lateral frontal and lateral parietal lobes, it seems that incoming flow is less than consumption. This affects BOLD sensitivity. Hemoglobin differs in how it responds to magnetic fields, depending on whether it has a bound oxygen molecule.

Magnetic Resonance, Functional (fMRI) - Brain

The dHb molecule is more attracted to magnetic fields. This effect increases with the square of the strength of the magnetic field. The fMRI signal hence needs both a strong magnetic field 1. The physiological blood-flow response largely decides the temporal sensitivity, that is how accurately we can measure when neurons are active, in BOLD fMRI.

The basic time resolution parameter sampling time is designated TR; the TR dictates how often a particular brain slice is excited and allowed to lose its magnetization. For fMRI specifically, the hemodynamic response lasts over 10 seconds, rising multiplicatively that is, as a proportion of current value , peaking at 4 to 6 seconds, and then falling multiplicatively. Changes in the blood-flow system, the vascular system, integrate responses to neuronal activity over time.

Because this response is a smooth continuous function, sampling with ever-faster TRs does not help; it just gives more points on the response curve obtainable by simple linear interpolation anyway. Experimental paradigms such as staggering when a stimulus is presented at various trials can improve temporal resolution, but reduces the number of effective data points obtained. It lags the neuronal events triggering it by a couple of seconds, since it takes a while for the vascular system to respond to the brain's need for glucose.

If the neurons keep firing, say from a continuous stimulus, the peak spreads to a flat plateau while the neurons stay active. After activity stops, the BOLD signal falls below the original level, the baseline, a phenomenon called the undershoot. Over time the signal recovers to the baseline. There is some evidence that continuous metabolic requirements in a brain region contribute to the undershoot.


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This glutamate affects nearby supporting cells, astrocytes , causing a change in calcium ion concentration. This, in turn, releases nitric oxide at the contact point of astrocytes and intermediate-sized blood vessels, the arterioles. Nitric oxide is a vasodilator causing arterioles to expand and draw in more blood. A single voxel 's response signal over time is called its timecourse. Typically, the unwanted signal, called the noise, from the scanner, random brain activity and similar elements is as big as the signal itself.


Full-brain studies use larger voxels, while those that focus on specific regions of interest typically use smaller sizes. Smaller voxels contain fewer neurons on average, incorporate less blood flow, and hence have less signal than larger voxels. Smaller voxels imply longer scanning times, since scanning time directly rises with the number of voxels per slice and the number of slices. This can lead both to discomfort for the subject inside the scanner and to loss of the magnetization signal.

A voxel typically contains a few million neurons and tens of billions of synapses , with the actual number depending on voxel size and the area of the brain being imaged. The vascular arterial system supplying fresh blood branches into smaller and smaller vessels as it enters the brain surface and within-brain regions, culminating in a connected capillary bed within the brain.


This can be achieved either by using strong static magnetic fields or by using spin-echo pulse sequences. Temporal resolution is the smallest time period of neural activity reliably separated out by fMRI. One element deciding this is the sampling time, the TR. Temporal resolution can be improved by staggering stimulus presentation across trials.

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When a person performs two tasks simultaneously or in overlapping fashion, the BOLD response is expected to add linearly. This is a fundamental assumption of many fMRI studies that is based on the principle that continuously differentiable systems can be expected to behave linearly when perturbations are small; they are linear to first order.

Linear addition means the only operation allowed on the individual responses before they are combined added together is a separate scaling of each. Since scaling is just multiplication by a constant number, this means an event that evokes, say, twice the neural response as another, can be modeled as the first event presented twice simultaneously. The HDR for the doubled-event is then just double that of the single event. To the extent that the behavior is linear, the time course of the BOLD response to an arbitrary stimulus can be modeled by convolution of that stimulus with the impulse BOLD response.

Accurate time course modeling is important in estimating the BOLD response magnitude [32] [33].. Their result showed that when visual contrast of the image was increased, the HDR shape stayed the same but its amplitude increased proportionally. With some exceptions, responses to longer stimuli could also be inferred by adding together the responses for multiple shorter stimuli summing to the same longer duration. In , Dale and Buckner tested whether individual events, rather than blocks of some duration, also summed the same way, and found they did.


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The refractory effect can be used in a way similar to habituation to see what features of a stimulus a person discriminates as new. Researchers have checked the BOLD signal against both signals from implanted electrodes mostly in monkeys and signals of field potentials that is the electric or magnetic field from the brain's activity, measured outside the skull from EEG and MEG. The local field potential, which includes both post-neuron-synaptic activity and internal neuron processing, better predicts the BOLD signal.

In humans, electrodes can be implanted only in patients who need surgery as treatment, but evidence suggests a similar relationship at least for the auditory cortex and the primary visual cortex. Some regions just a few millimeters in size, such as the lateral geniculate nucleus LGN of the thalamus, which relays visual inputs from the retina to the visual cortex, have been shown to generate the BOLD signal correctly when presented with visual input. Nearby regions such as the pulvinar nucleus were not stimulated for this task, indicating millimeter resolution for the spatial extent of the BOLD response, at least in thalamic nuclei.



This is expected to be due to increased efficiency in performing the task. However, the BOLD response can often be compared across subjects for the same brain region and the same task. More recent characterization of the BOLD signal has used optogenetic techniques in rodents to precisely control neuronal firing while simultaneously monitoring the BOLD response using high field magnets a technique sometimes referred to as "optofMRI".


Clinicians also use fMRI to anatomically map the brain and detect the effects of tumors, stroke, head and brain injury, or diseases such as Alzheimer's , and developmental disabilities such as Autism etc.. Clinical use of fMRI still lags behind research use. Tumors and lesions can change the blood flow in ways not related to neural activity, masking the neural HDR. Drugs such as antihistamines and even caffeine can affect HDR. Using head restraints or bite bars may injure epileptics who have a seizure inside the scanner; bite bars may also discomfort those with dental prostheses.



Pharmacological fMRI, assaying brain activity after drugs are administered, can be used to check how much a drug penetrates the blood—brain barrier and dose vs effect information of the medication. Research is primarily performed in non-human primates such as the rhesus macaque. These studies can be used both to check or predict human results and to validate the fMRI technique itself. But the studies are difficult because it is hard to motivate an animal to stay still and typical inducements such as juice trigger head movement while the animal swallows it.

It is also expensive to maintain a colony of larger animals such as the macaque. The goal of fMRI data analysis is to detect correlations between brain activation and a task the subject performs during the scan. It also aims to discover correlations with the specific cognitive states, such as memory and recognition, induced in the subject. This means that a series of processing steps must be performed on the acquired images before the actual statistical search for task-related activation can begin.







This consists of an array of voxel intensity values, one value per voxel in the scan. The voxels are arranged one after the other, unfolding the three-dimensional structure into a single line. The first part of that analysis is preprocessing. The first step in preprocessing is conventionally slice timing correction. The MR scanner acquires different slices within a single brain volume at different times, and hence the slices represent brain activity at different timepoints.







While this is conceptually similar to motion correction, the changes required are more complex than just translation and rotation, and hence optimization even more likely to depend on the first transformations in the chain that is checked. Temporal filtering is the removal of frequencies of no interest from the signal.







Then, appropriate study participants can be recruited. Before the scan, subjects must first be screened for MRI safety, and any participants with MRI counter-indications, like the presence of a cardiac pacemaking device, must be excluded. Next, the nature of the experiment and the functional task directions should be reviewed, as subject performance is critical for robust results. In the scanner room, hearing protection should be provided before placing the head coil with padding around the head to reduce motion. The stimulus presentation equipment also needs to be set up.

Goggle or projector systems are often used for visual presentation, but other types of stimulus delivery equipment exist. Once the subject is comfortable, the scanner bed is sent into the magnet bore. Then, the imaging sequences are set up, including a high-resolution anatomical scan to reregister to the functional scans.

The subject should be reminded of the task instructions, and the functional acquisition needs to be synchronized with the start of the task paradigm. This is critical, as the task timing needs to be matched with image acquisition timing for accurate BOLD measurements. The subject should be monitored during the scan, and additional functional runs performed if necessary. Finally, the subject is helped out of the scanner and off the scanner bed.

The specific image processing method and software package used will vary depending on the experiment. In this video, we will go over common BOLD task based processing methods. First, fMR data should be pre-processed to remove image artifacts and prepare it for statistical analysis. This involves slice time correction and motion correction, as well as co-registration to the anatomical image.

For group studies, normalization to a standard template space is often performed as well, so the brain areas and spatial coordinates can be compared across subjects. Once data is prepped, statistical analysis is performed to locate regions with significant MR signal correlated with the stimulus or cognitive function that was tested. The general linear model is typically used to analyze task-based experiments. This model assumes that a BOLD signal was obtained that matches the expected hemodynamic response function, and convolves this function with the stimulus design.

Further analysis can be performed as needed. Although these are seemingly basic functions, there is still much to be learned about these and many other cognitive processes. In addition, fMRI can be used to investigate brain function in diseased brain states and psychological disorders. There are many active areas of research such as anxiety disorders, posttraumatic stress disorder, autism, and dementia.

There are also resting state fMRI analysis techniques that can be used to investigate functional connectivity, such as independent component analysis and cross correlation analysis. Thanks for watching, good luck with your experiments, and remember that MRI safety always comes first! A subscription to J o VE is required to view this content. You will only be able to see the first 20 seconds. To learn more about our GDPR policies click here.

If you want more info regarding data storage, please contact gdpr jove. This is a sample clip. To watch the full video start a free trial today! Add to Favorites Embed Share. Summary Functional magnetic resonance imaging fMRI is a non-invasive neuroimaging technique used to investigate human brain function and cognition in both healthy individuals and populations with abnormal brain states. Already have an Account? Glimcher 3,4,5. Kana 1 , Donna L. Murdaugh 1 , Lauren E. Libero 1 , Mark R. Pennick 1 , Heather M. Wadsworth 1 , Rishi Deshpande 1 , Christi P.

Zatorre 1. General Laboratory Techniques. Introduction to Fluorescence Microscopy. Introduction to Light Microscopy. An Introduction to Neuroanatomy. An Introduction to Behavioral Neuroscience. An Introduction to Neurophysiology.