Functional MRI Will Enable Non-Invasive Visualization of brain Cortical Columns


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The issue of the scientific journal Nature Neuroscience (24.1.00) includes two articles describing scientific findings based on functional MRI (fMRI) and optical imaging technology, that may considerably advance the field of brain research as well treatment of neurological disorders. The accomplishment is the result of parallel research efforts made by scientists from Minnesota University USA, and the Weizmann Institute of Science.

Brain researchers throughout the world aspire to accurately map nerve cell clusters in action --'conversing' with their peers in the form of electrical impulses, while processing sensory information or performing cognitive functions.

Each cluster, containing thousands of nerve cells performing a given processing task, is called a 'cortical column.' Cortical columns are the 'microprocessors' of the brain. Brain researchers maintain that the ability to obtain an exact mapping of the cortical column is critical to understanding how the human brain can perform its remarkable functions. Yet, until now they have been unable to do so directly, and have had to rely on several indirect methods such as Positron-Emission-Tomography (PET), optical imaging and fMRI.

Brain-Vein Mapping

These methods are based on the more than 100 years old discovery made by Lord Sherrington of a connection between the brain's electrical activity and changes in blood circulation. For example, PET is based on injecting a radioactive substance into the blood stream and mapping the locational alterations in blood flow in response to electrical activity in the brain. Using fMRI, scientists track changes in the levels of oxygen bound to hemoglobin in the blood stream, resulting from hemoglobin supplying oxygen to active nerve cells. fMRI is entirely non-invasive, hence its advantage over PET, which relies on the injection of radioactive tracers. Therefore, fMRI may be used to explore the same brain for many years, thereby potentially enabling researchers to track and map memory traces, aging processes, or functional recovery from trauma or stroke.

Until recently, the level of mapping accuracy rendered by these techniques was fairly limited: they could map an active area in the human brain at an accuracy level of 1-3mm (fMRI) or 3-7mm (PET), and thus were unable to map the brain's basic processing units - the 0.5mm wide 'microprocessors.'

Mapping Brain microprocessors

In the last 15 years, Prof. Amiram Grinvald of the Weizmann Institute's Neurobiology Department has developed a novel optical imaging brain-mapping approach based on tracking color changes in the blood supplying oxygen to the active microprocessors. Using this technology, Grinvald was able to identify the exact time and place in which nerve cells consume oxygen from the blood-dense microcirculation system. The high resolution achieved by optical imaging permitted him to fully map individual cortical columns - the brain's 'microprocessors.' These included visual system microprocessors related to shape, color, and motion perception. Optical imaging also laid the foundation for the development of functional MRI, which is more suitable for non-invasive human brain research and clinical applications. Initially, scientists hoped that using fMRI would enable brain mapping at the same level of accuracy achieved by the optical imaging technology. Indeed, both methods detect a considerable 'activity crest' that appears roughly 6 seconds after the onset of electrical activity. Unfortunately, the fMRI systems could not detect the 'initial dip,' a negative signal that appearsearlier, which is clearly visible by optical imaging systems.

'Initial Dips' and 'Activity Crests'

This is where things stood until recently. Two months ago, however, Ivo Vanzetta and Amiram Grinvald of the Weizmann Institute of Science, published a paper in Science in which they proposed how the fMRI system's resolution could be greatly enhanced. A team of scientists from Minnesota University, led by Prof. Kamil Ugurbil, has adopted this 'recipe.' First, they found the missing 'initial dip' with fMRI, thus showing that the two techniques can monitor the same vascular events provided the fMRI is done in a strong magnetic field. (Just like with optical imaging, the 'initial dip' provides a much smaller signal relative to the delayed 'activity crest.' Therefore, naturally, fMRI researchers had previously used the greater 'activity crest' to map the exact location of electrical activity.)

However, Dae-Shik Kim, Timothy Duong, and Seong-Gi Kim from the Minnesota group report today in Nature Neuroscience that this 'activity crest' cannot be used to monitor the precise location of electrical activity with fMRI. The major finding of their report is that the exact location of 'firing' indeed corresponds to the location of the 'initial dip.' Utilization of this small signal enabled the first exact mapping of 'orientation columns' -- the microprocessors responsible for shape perception in early processing areas of the visual cortex.

The current Nature Neuroscience contains a News and Views article written by Amiram Grinvald, Hamutal Slovin and Ivo Vanzetta of the Weizmann Institute, in which they discuss the accomplishment achieved by the Minnesota team, and provide new data from optical imaging. Taken together, these articles suggest that by focusing on the 'initial dip,' fMRI will enable non-invasive mapping of cortical columns in human brain research as well.

Scientists believe that the pivotal improvement in MRI accuracy will greatly advance scientific research aimed at better understanding the fundamental mechanisms underlying human perception and higher cognitive functions. Additionally, it may have valuable significance in improving the capacity for early diagnosis and perhaps prevention of diverse mental disorders.

Prof. Grinvald, who holds the Helen and Norman Asher Professorial Chair in Brain Research, is head of the Murray H. and Meyer Grodetsky Center for Research of Higher Brain Functions and of the Wolfson Center for Applied Scientific Research in Functional Brain Imaging at the Weizmann Institute.
This study was supported by the German Israeli Foundation for Scientific Research and Development, the Horace W. Goldsmith Foundation, of New York and Ms. Margaret Enoch of New York.

The Weizmann Institute of Science is a major center of scientific research and graduate study located in Rehovot, Israel. Its 2,500 scientists, students and support staff are engaged in more than 1,000 research projects across the spectrum of contemporary science