The Brainy Scientist

This week's "The Scientist" contains several relevant articles for neurotechnology.

Here are the highlights:

1. Numbers on the Brain breaks down the public and private funding initiatives supporting the $60B neuroscience/pharmacology market.

2. Cutting Neurons Down to Size details the latest research into how and why connections among neurons go through a process of self-pruning in early child development. Neuroscientists have known about neural pruning for decades, where synaptic density peaks from ages 1 to 2, declines until age 16, and then levels off. Experts predict that sorting out how pruning works might eventually help in understanding epilepsy, neurodegenerative diseases, mental retardation, autism, and schizophrenia.

3. fMRI The Perfect Imperfect Instrument covers how most investigators rely on the fMRI method that uses a blood oxygenation level-dependent (BOLD) contrast. The signal arises from changes in magnetic characteristics of blood related to differences in the relative amounts of oxygenated and deoxygenated hemoglobin. Though many researchers correlate blood flow to neural activity, the connection hasn't been solidly determined.

4. Caution: Brain Working further deconstructs fMRI. This has important implications for cognitive related experiments that depend on fMRI. fMRI suffers from poor temporal resolution which means it is impossible to segregate the different stages of how during conversions words and their meaning are differentiated. For this reason, language experts like Peter Hagoort use fMRI in combination with electroencephalography (EEG) and magnetoencephalography (MEG) in his efforts to identify those stages.

5. It's Neuron's Time describes how scientists are taking the first stabs at answering at least one part of the question, how the brain perceives time. A recent University of Washington study was the first to document how neurons in primates track time from one instant to the next. Timing is a subject of increasing interest, because it's important in learning. Learning skilled movements, for instance, involves internalizing their sequences and timing.

The Take Away: All these articles show that we are suffering from a brain imaging bottleneck.

Peter Hagoort's quote sums it up nicely, "Many neuroscientists dream of a "more perfect" instrument, one that will combine the spatial sensitivity of fMRI with the millisecond temporal acuity of EEG or MEG, but it is difficult to predict what such an already rapidly changing technology will look like in 10 or 20 years."

That timing seems just about right to me.

2003 Nobel Prize in Medicine

Recognizing the importance of brain imaging technologies, the Nobel Assembly has awarded the 2003 Nobel in Medicine to American Paul Lauterbur and Britain's Peter Mansfield for their discoveries on magnetic resonance imaging (MRI), a painless diagnostic method used by doctors to look inside the bodies of millions of patients every year.

Update: 22,000 MRI's are in use worldwide, and more than 60 million scans had been performed.  More.

Dividing Dyslexics for Their Own Good

Using fMRI brain scanners, Yale scientists report in the NYTimes that two types of brain problems cause dyslexia. This new information should lead to more effective treatment for both types. The two types are divided into those whose dyslexia is, either:

• Predominately genetic: these individuals had gaps in the neural circuitry that the normal readers used for the basic processing of sound and language, but had learned to enlist other parts of the brain to compensate for the difficulty. They still read slowly but can comprehend what they read.
  
• Environmentally influenced: these individuals had their brain system for processing sound and language intact, but they seemed to rely more on memory than on the linguistic centers of the brain for understanding what they were reading. These students had remained persistently poor readers, scoring poorly on speed as well as comprehension.

As I've written previously, neurotechnology will continue to define mental disorders more accurately as we understand how the brain operates at increasingly refined scales. Dyslexia is just the latest example. What's next?

Charting Your Neurome

San Diego-based Neurome is racing to chart the brain's neural circuitry in the hope of creating breakthroughs treatments for mental illnesses.

"All this information about the function of the brain has to somehow be stored in a database that is standardized and can accurately depict the molecular, cellular and circuitry patterns of brain activity so that researchers can look at it and determine what's normal and what's not, section by section, circuit by circuit. And that is the function that Neurome intends to provide to drug discovery companies, said Dr. Floyd Bloom, Neurome's chairman and one of its founders.

Neurome scientists have improved the technology so that now it takes about 35 minutes to collect the volume of data it previously took about seven hours to record, Bloom said.

They are trying to measure and record how over time the disease affects the connection and communication, or electrical charges, between the neurons and cells in the brain." (more)

Backed up by an all-star team and $13m in funding, Neurome is initially focused on Alzheimer's disease.  Although I expect valuable results from their work, they will have to solve the animal mental health model problem at some point, as human neural circuitry doesn't correlate precisely with mice neural circuitry.

The Human Brain Project

This year's annual Human Brain Project meeting will be held in Bethesda, Maryland, May 12-13.  Because understanding brain function requires the integration of information from the level of the gene to the level of behavior, neuroinformatics is the primary area of focus for the National Institute of Mental Health who sponsors most of government grants in this area. This meeting always has a few outstanding presentations.

Lastest Brain Imaging Breakthroughs

Developing safe and effective neurotechnology will depend on continued advances in biochips and brain imaging technologies.  This week's Science reports good progress on the imaging front: (article links require subscription).

• Single Neuron Imaging: Using a combination of genetic engineering techniques and optical imaging techniques, neuroscientists at several universities are now able to observe synapse development in live rats.  Still in it's infancy, this technique will be an important one to follow, as it will have significant implications for understanding how the brain learns.
  
• Brain Imaging Archives Are Catching On: Standardized databases of brain images (especially fMRI data) are igniting neuroinformatics, making possible the analysis of different brain phenomena across thousands of subjects instead of just a few.  Moreover, it is leading to standardized formats and descriptions that are searchable and fantastic process,  Free examples at: BRAID, FMRIDC, MITRE. (see these!)
  
• Visualizing Signals Moving Through Cells: The development of fluorescent sensors and improved microscopic imaging techniques it is now becoming possible to investigate how signals propagate through living cells.  Although a far cry from being able to do this for neurons, this approach does show promise.

Brain science still has a long way to go but these efforts show that we are making headway on many fronts.

The Brain Imaging Bottleneck

Current brain imaging technologies constrain our ability to understand how the brain functions. To develop next-generation cogniceuticals we will need to move beyond today's three brain imaging technologies to the level of neuron and intra-neuron scanning.

fMRI's (functional magnetic resonance imaging) have a resolution limit of about a cubic millimeter, this volume can still contain tens of thousands of neurons. PET (positron emission tomography) scans are more accurate in determining where in the brain neurons are being activated but have poor temporal resolution, while EEG's (electro-encephalogram) are more accurate in precisely timing events, they are unable to track important biochemical attributes.

Update 5/20: Current brain imaging still provides only a crude snapshot of brain activity.  Neural processes are thought to occur on a 0.1 millimeter scale in 100 milliseconds (msec), but the spatial and temporal resolution of a typical scanner is only 3 millimeters and about two seconds.