Issues in fMRI
Encyclopedia
Functional Magnetic Resonance Imaging
Functional magnetic resonance imaging
Functional magnetic resonance imaging or functional MRI is a type of specialized MRI scan used to measure the hemodynamic response 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 neuroimaging...

, also known as ƒMRI, is a neuroimaging technique that measures the blood oxygenation, also called BOLD, that accompanies neuronal activity. The blood oxygenation level dependent fMRI has relatively high spatial resolution (of the order of a few millimetres), but lower temporal resolution (a few seconds), in comparison to other neuroimaging methods. In recent years, ƒMRI usage has increased exponentially. Functional magnetic resonance imaging is, however, hindered by some theoretical and methodological problems outlined below.

Design

When choosing a baseline condition, researchers must take into account that being “at rest” does not mean that the brain is not active at all. Moreover, certain brain processes unrelated to the research may require more neuronal activation than others. Also it has been shown that the BOLD signal cannot be infinitely increasing, therefore there will be a point where the brain cannot become any more active. If the baseline condition is too close to maximum activation, certain processes may not be represented appropriately. Another limitation on experimental design is head motion, which can lead to artificial intensity changes of the fMRI signal. This means that any experiment requiring the participant to elicit any sort of motion will leave the researcher unable to determine whether the measured BOLD signal changes are task-related or artificial “motion related” changes. Furthermore, the noise produced by the fMRI scanner has been shown to interfere with not only with acoustic activations, but also non-auditory cognitive tasks.

Block versus Event-related Design

In a block design, two or more conditions are alternated in blocks. Each block will have a duration of a certain number of fMRI scans and within each block only one condition is presented. By making the conditions differ in only the cognitive process of interest, the fMRI signal that differentiates the conditions should represent this cognitive process of interest. This is known as the subtraction paradigm.
The increase in fMRI signal in response to a stimulus is additive. This means that the amplitude of the hemodynamic response
Haemodynamic response
Haemodynamics is a medical term for the dynamic regulation of the blood flow in the brain. It is the principle on which functional magnetic resonance imaging is based....

 (HDR) increases when multiple stimuli are presented in rapid succession. When each block is alternated with a rest condition in which the HDR has enough time to return to baseline, a maximum amount of variability is introduced in the signal. As such, we conclude that block designs offer considerable statistical power There are however severe drawbacks to this method, as the signal is very sensitive to signal drift, such as head motion, especially when only a few blocks are used. Another limiting factor is a poor choice of baseline, as it may prevent meaningful conclusions from being drawn. There are also problems with many tasks lacking the ability to be repeated. Since within each block only one condition is presented, randomization
Randomization
Randomization is the process of making something random; this means:* Generating a random permutation of a sequence .* Selecting a random sample of a population ....

 of stimulus types is not possible within a block. This makes the type of stimulus within each block very predictable. As a consequence, participants may become aware of the order of the events.

Some experimental questions cannot be answered using a block design. For example, the response to an infrequently occurring stimulus appearing in a series of frequently occurring stimuli as is the focus of odd-ball experiments, using a block design is impossible. When stimuli have to be presented in blocks, it is by definition impossible to have an infrequently occurring stimulus. These kinds of experimental questions have to be addressed using an event related design. In an event related design the course of the HDR following each stimulus presentation is estimated using the averaging of a single type of stimulus through repeated measures
Repeated measures design
The repeated measures design uses the same subjects with every condition of the research, including the control. For instance, repeated measures are collected in a longitudinal study in which change over time is assessed. Other studies compare the same measure under two or more different conditions...

. This allows more real world testing, however, the statistical power of event related designs is inherently low, because the signal change in the BOLD fMRI signal following a single stimulus presentation is small.

Both block and event-related designs are based on the subtraction paradigm
Paradigm
The word paradigm has been used in science to describe distinct concepts. It comes from Greek "παράδειγμα" , "pattern, example, sample" from the verb "παραδείκνυμι" , "exhibit, represent, expose" and that from "παρά" , "beside, beyond" + "δείκνυμι" , "to show, to point out".The original Greek...

, which assumes that specific cognitive processes can be added selectively in different conditions. Any difference in blood flow (the BOLD signal) between these two conditions is then assumed to reflect the differing cognitive process. In addition, this model assumes that a cognitive process can be selectively added to a set of active cognitive processes without affecting them.

Baseline versus Activity Conditions

The brain is never completely at rest. It never stops functioning and firing neuronal signals, as well as using oxygen as long as the person in question is alive. In fact, in Stark and Squire’s, 2001 study When zero is not zero: The problem of ambiguous baseline conditions in fMRI, activity in the medial temporal lobe (as well as in other brain regions) was substantially higher during rest than during several alternative baseline conditions. The effect of this elevated activity during rest was to reduce, eliminate, or even reverse the sign of the activity during task conditions relevant to memory functions. These results demonstrate that periods of rest are associated with significant cognitive activity and are therefore not an optimal baseline for cognition tasks. In order to discern baseline and activation conditions it is necessary to interpret a lot of information. This includes situations as simple as breathing. Periodic blocks may result in identical data of other variance in the data if the person breathes at a regular rate of 1 breath/5sec, and the blocks occur every 10s, thus impairing the data.

Other Factors

Neuroimaging methods such as ƒMRI do not have very good external validity. The study is conducted in a small, narrow, noisy tube, in which you are not supposed to move. It is so sensitive to movement, that even breathing must be taken into account. It is also noisy enough to require ear-defenders to be worn in an attempt to maintain patient comfort and prevent ear damage. Also, just as no two people’s brains’ are exactly alike, everyone perceives the experience of undergoing an ƒMRI study differently. Some people might feel claustrophobic
Claustrophobia
Claustrophobia is the fear of having no escape and being closed in small spaces or rooms...

, nervous, excited, or physically taxed by the novel environment. It is also important to note that in Alexiou, Zamenopoulos and Johnson’s study on neural design, some participants had to substitute their glasses with plastic ones for use inside the magnetic field, which after a while made them feel uncomfortable and distracted. This condition and these factors do not qualify to be inferred to as a general, everyday life situation.

Reverse Inference

Neuroimaging methods such as fMRI offer a measure of the activation of certain brain areas in response to cognitive tasks engaged in during the scanning process. Data obtained during this time allow cognitive neuroscientists to gain information regarding the role of particular brain regions in cognitive function. However, an issue arises when certain brain regions are alleged by researchers to identify the activation of previously labeled cognitive processes. Poldrack clearly describes this issue:
The usual kind of inference that is drawn from neuroimaging data is of the form ‘if cognitive process X is engaged, then brain area Z is active.’ Perusal of the discussion sections of a few fMRI articles will quickly reveal, however, an epidemic of reasoning taking the following form:
(1) In the present study, when task comparison A was presented, brain area Z was active.
(2) In other studies, when cognitive process X was putatively engaged, then brain area Z was active.
(3) Thus, the activity of area Z in the present study demonstrates engagement of cognitive process X by task comparison A.
This is a ‘reverse inference’, in that it reasons backwards from the presence of brain activation to the engagement of a particular cognitive function.

Reverse inference demonstrates the logical fallacy of affirming what you just found, although this logic could be supported by instances where a certain outcome is generated solely by a specific occurrence. With regard to the brain and brain function it is seldom that a particular brain region is activated solely by one cognitive process. Some suggestions to improve the legitimacy of reverse inference have included both, increasing the selectivity of response in the brain region of interest, and increasing the prior probability
Bayes' theorem
In probability theory and applications, Bayes' theorem relates the conditional probabilities P and P. It is commonly used in science and engineering. The theorem is named for Thomas Bayes ....

 of the cognitive process in question. However, Poldrack suggests that reverse inference should be used merely as a guide to direct further inquiry rather than a direct means to interpret results.

Forward Inference

Forward inference is a data driven method that uses patterns of brain activation to distinguish between competing cognitive theories. It shares characteristics with cognitive psychology’s dissociation logic and philosophy’s forward chaining
Forward chaining
Forward chaining is one of the two main methods of reasoning when using inference rules and can be described logically as repeated application of modus ponens. Forward chaining is a popular implementation strategy for expert systems, business and production rule systems...

. For example, Henson discusses forward inference’s contribution to the “single process theory vs. dual process theory” debate with regard to recognition memory
Recognition memory
Recognition memory is a subcategory of declarative memory Essentially, recognition memory is the ability to recognize previously encountered events, objects, or people...

. Forward inference supports the dual process theory by demonstrating that there are two qualitatively different brain activation patterns when distinguishing between “remember vs. know judgments
Remember versus know judgements
There is evidence suggesting that different processes are involved in remembering something versus knowing whether it is familiar or not. It appears that "remembering" and "knowing" represent relatively different characteristics of memory as well as reflect different ways of using memory.To...

”. Although forward inference is typically enlisted in cognitive neuroscience research, it too has its downfalls. The main issue with forward inference is that it is a correlational method. Therefore one cannot be completely confident that brain regions activated during cognitive process are completely necessary for that execution of those processes. In fact, there are many known cases that demonstrate just that. For example, the hippocampus has been shown to be activated during classical conditioning, however lesion studies have demonstrated that classical conditioning can occur without the hippocampus. That being said, it has been suggested that like reverse inference, forward inference should be used with caution and supplemented with other methods of inquiry.
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