functional MRI
Opening the doors of perception

The working of the brain has always fascinated people. Yet it is only in the past decade, with the advent of functional MRI, that major inroads have been made in understanding this intriguing organ. Callan Emery reports.

The brain has intrigued anatomical investigators and scientific researchers since the earliest days of the study of human anatomy. There are many questions asked of the brain. How does the brain function? How does it control the body’s movements? How does it affect the sense of smell, touch and hearing? How does it affect speech? Does it hold memory? How does it control cognition and determine behaviour? These are key questions, which have baffled researchers for centuries and, to a certain extent continues to do so, even though some remarkable discoveries and insights have been made in the course of the past century with the aid of modern technology and rigorous scientific endeavour.

These technological advances in the past century have, in a sense, opened up the brain and provided never-before-seen images of this mysterious bundle of neuronal matter and this, in turn, has sparked a renewed vigour in the scientific community to research and investigate the functioning of the brain.

The electroencephalogram (EEG), x-rays, ultrasound, Computed Tomography (CT), Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI), among others, have all played a big role in the renewed interest in the working of the brain. However, EEG and MRI specifically are now being used widely in neuroscience as they are non-invasive and don’t rely on harmful radiation such as x-rays, CT and PET.

Electroencephalogram

The first major advance in understanding the workings of the brain came about when Russian physiologist, Vladimir Vladimirovich Pravdich-Neminsky published the first electroencephalogram in 1912. He had used it to read electrical activity in the brain of a dog. However, it wasn’t until 1920 when German physiologist Hans Berger began studying electrical activity in the human brain with the EEG, that the device became more widely recognised as an instrument that could be used to begin to decipher the workings of the brain. Berger is credited with giving the EEG its name.

Since then, the EEG procedure has found application in many areas of neuroscience and clinical diagnosis. For example some theories to explain sleep are based on EEG patterns recorded during sleep sessions. And, most recently, the device has even found commercial application as a ‘mind-controlled device for video games’ by a company called Emotiv Systems.

However, although the EEG has greatly improved our understanding of the functioning of the brain, it does have limitations. Although it provides good temporal specificity it has poor anatomical or spatial specificity – a field of investigation much better suited to magnetic resonance imaging.

MRI was first used in medical research in the 1970s, but it is really only since the 1990s that researchers – particularly Seiji Ogawa and Ken Kwong – realised that they can use MRI to map changes in brain haemodynamics and that these changes correspond to changes in neural activity in the brain. This in turn has extended traditional anatomical imaging of the brain to include maps of brain function and to a new field of MRI called functional MRI, or fMRI.

fMRI

fMRI has lead to some remarkable findings and is currently enhancing our understanding of the brain’s role in cognition and behaviour more profoundly and more rapidly than at any other time in the history of neurological endeavour.

This technology is resulting in a rapidly growing body of research literature documenting a wide range of localised and quite specific functions of the brain. Brain mapping, as it is called, is greatly improving our knowledge of, for example, the processing areas in the visual cortex, the speech and language-related areas of the brain, the areas of the brain that are active during epileptic seizures, how memories are formed, pain, emotion and learning, to name few.

fMRI is also being applied in clinical settings for presurgical planning.

So how does fMRI work? When nerve cells are active they consume oxygen carried by hemoglobin in red blood cells from local capillaries. The local response to this oxygen utilisation is an increase in blood flow to regions of increased neural activity. This, in turn, leads to local changes in the relative concentration of oxyhemoglobin and deoxyhemoglobin. Hemoglobin is diamagnetic when oxygenated but paramagnetic when deoxygenated. The magnetic resonance (MR) signal of blood is therefore slightly different depending on the level of oxygenation. These differential signals can be detected with MR as blood-oxygenlevel dependent (BOLD) contrast.

An MRI scanner can detect changes in BOLD contrast which can then be assessed. These changes can be both positive or negative depending upon the relative changes in both cerebral blood flow (CBF) and oxygen consumption. Increases in CBF that outstrip changes in oxygen consumption will lead to increased BOLD signal, conversely decreases in CBF that outstrip changes in oxygen consumption will cause decreased BOLD signal intensity.

As with conventional MRI, the subject is placed in the MR scanner and their brain is scanned. An fMRI experiment usually lasts between 15 minutes and 2 hours. Depending on the purpose of study, subjects may view movies, hear sounds, smell odors, perform cognitive tasks such as memorisation or imagination and so on. BOLD effects are measured using the acquisition of three dimensional images. Images are usually taken every 1–4 seconds, and the voxels (volumetric pixels) in the resulting image typically represent cubes of tissue about 2–4 millimetres. The resultant image is a 3-D brain activation map which shows which regions of the brain are involved in a particular mental process.

The ultimate goal of fMRI data analysis is to detect correlations between brain activation and the task the subject performs during the scan.

Speaking to Middle East Health, fMRI expert Frank Hoogenraad, PhD, chairman of the Neuro segment at Philips Medical Systems’ MR Clinical Science section, explained that in principle even low field strength [1.5 Tesla] MR can produce fMRI results.

However, Hoogenraad said that as the magnetic field strength increases researchers got a clearer image of activity in the cortex – the key area of focus – as there was a decrease in intravascular effects on the image. “At 1.5 Tesla the image is dominated by vascular components, while 3T is much better, providing a clearer image of the cortex. “At 7 Tesla the intravascular effect is totally gone, while the extravascular effects remain; we thus get a better localised cortex activation, and can have a much clearer idea of what is happening.”

Neuroscience

Hoogenraad said, although clinical use of fMRI is not very widespread, “there are many centres using fMRI for neurological research – brain mapping. The key ones being the Wellcome Trust research facilities in London, Oxford University, and Johns Hopkins, UCLA and Vanderbilt in the United States.”

fMRI is now widely used by psychologists, Hoogenraad said, adding that it is one of the first real tools that enables them to look inside the brain.

He explained that in the few places where it finds clinical application, it is being used for presurgical planning “to highlight which areas of the brain should be avoided during surgery such as language (broca/wernicke) regions, motor, pre-motor, supplementary- motor areas and sensory cortices”.

It has been well documented that fMRI now provides highly accurate and precise functional and structural information for neurosurgery and has in a number of instances been used in the surgical treatment of brain tumours located near active areas of the brain.“Neuroscience is developing fast.

For example, Alzheimer patients are being followed with so-called ‘resting-state fMRI’ to see which ‘networks of activity’ are active, and how these change according to medical treatment,” Hoogenraad pointed out. “In some studies patients suffering from depression are monitored to see how certain training modifies activity in the thalamus so that treatment can be adapted.”

“Resting state fMRI I think is one of the biggest discoveries with fMRI without paradigms. “In these cases patients do not perform a specific paradigm [task] but simply “lie still” in the scanner. However, their brain remains active and timepatterns of activity will correlate when it concerns brain activity between different parts of the brain. As such, these networks can be detected (with a slightly time-consuming analysis). This is especially useful in patients with Alzheimer’s, who cannot remember given tasks.”

One of the criticisms that has been levelled at fMRI in the past is that it focuses only on certain regions of the brain and not on the connectivity between these regions, which the critics say is the key to understanding mental processes.

However, Hoogenraad said this is not entirely the case as fMRI combined with fibertractography based on Diffusion Tensor Imaging (DTI) “provides a good deal of information on physical connections; which may (or rather should) match functional connectivity”.

DTI uses MR to measure anatomical connectivity between areas of the brain. It is not strictly a functional imaging technique because it does not measure dynamic changes in brain function, but rather the measures of inter-area connectivity it provides are complementary to images of cortical function provided by BOLD fMRI.

“All-in-all there should be a logic framework between the two methods (fMRI and DTI) and this is heavily researched at the moment. Already different pathways (and thus understanding) of the language systems have been exposed (work by Catani).

“These methods are also being used to find causes or early detectors in dyslexia, as it may correlate to limited connectivity between left and right hemispheres,” said Hoogenraad. The future role of fMRI is enormous and extremely wide ranging. At United States-based Colombia University’s fMRI unit, for example, researchers are studying the possibility of using fMRI in chronic pain management.

According to the unit’s website their studies “indicate that the cortical representation of sympathetically maintained pain involves specific and identifiable cortical activity, as well as does the relief of that pain achieved by a peripheral nerve block procedure. Continuing investigations will extend these findings to other pain treatments to determine the extent to which this finding can be generalised to other pain relief mechanisms.

“These preliminary studies suggest a wide range of other approaches using fMRI to investigate cortical representations of specific pain types, and therefore, new specific therapy options.”

Hoogenraad said he believed the frontiers of fMRI neuroscience lay in very high field work with very high spatial resolution; as well as trying to understand the individual brain “Much brain mapping work reflects group studies, and although these provide great insights in the general pathways, it does not say much about the individual patients,” he said.

He added that there was a lot of room for improvement in the analysis of data “especially how to discern physiological from real noise”. And where is it leading to? “Hopefully it will provide clear patterns of how systems in the brain work.” “I think a combination of fMRI/DTI will become the presurgical standard – with lots of automated analysis and viewing. The brainmapping community will simply keep on going,” predicted Hoogenraad.

Websites worth visiting: www.brainmapping.org – the place to start. Brain mapping community news, science, information and fMRI web links.http://brainmaps.org – an interactive zoomable highresolution digital brain atlas.


Decade of the Mind research call

World-renowned scientists convene at George Mason University in the United States in May to call for a 10- year intellectual revolution – the "decade of the mind". The proceedings made the case for a US$4 billion public research initiative dedicated to reaching the next level of understanding the human brain -- the yetto- be-discovered inner workings of the mind. The symposium also outlined the dramatic implications the decade will have on the global economy and healthcare.

"We are at the 'tipping point' of making enormous advances in public health, particularly in managing diseases that affect the mind, such as Alzheimer's disease, Parkinson's disease, autism and schizophrenia," said Jim Olds, director of Mason's Krasnow Institute for Advanced Study.

"A 10-year focus to bring the enormous promise of brain research will launch an intellectual revolution here and throughout the world, with lasting impacts on society," said Olds.

"The economic impact of the ‘Decade of the Mind’ will be felt in all levels of society," said Olds. "By translating our knowledge of the human mind to building more intelligent machines and computer applications, we can improve the welfare of millions of people worldwide." For more information about the Decade of the Mind visit: http://krasnow.gmu.edu/decade

                                  
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