March 23, 2012

Looking Inside a Damaged Brain

(Ivanhoe Newswire)-- Why do we see distinct patterns of brain damage linked to diseases such as Alzheimer's? Questions like this baffled researchers for years.

Until recently models for predicting regional neurodegeneration in humans has remained a mystery. Having an answer to this information is useful because it can predict memory decline in patients and help find solutions to treat their needs.

Variations of dementias involve specific parts of the brain, and previous theories state that neurodegenerative diseases target specific networks of neurons that are linked by connectivity rather than spatial proximity. Furthermore, this neurodegenerative process is thought to involve the accumulation of abnormal toxic proteins and possibly even the spread of these proteins between neurons, which my travel from neuron to neuron through their synaptic connections.

One study, led by Drs. Juan Zhou and William Seeley, from the University of California, San Francisco, addressed this theory. "We were interested in whether knowing the healthy brain's functional "wiring diagram" would help us predict specific patterns of neurodegeneration seen in patients," Dr. Seeley was quoted as saying. "For each illness we studied, specific regions emerged as critical network 'epicenters,' and functional connectivity to these epicenters predicted each region's vulnerability. The findings best fit a model wherein disease spreads from neuron to neuron along network connections that link brain structures."

Another study, led by Dr. Ashish Raj from Weill Medical College of Cornell University, researchers modeled this same kind of "transneuronal" disease transmission by mathematically analyzing structural connectivity networks gathered from healthy brain MRIs. Their model predicted spatially distinct "eigenmodes," tightly connected sub networks in the brain, which demonstrated traditional patterns of damage seen in dementia.

"Our findings provide the first plausible explanation of why various dementias appear to selectively target distinct regions of the brain–as a simple mechanical consequence of transneuronal spread within the brain networks. This also suggests that all dementias, previously considered to be pathologically distinct, might share a common progression mechanism," Dr. Raj was quoted as saying. "Importantly, this model of disease progression may be useful clinically for prediction of future cognitive decline in patients, based on their current MRI scans. Knowledge of what the future holds would allow patients to make informed choices regarding their lifestyle and therapeutic interventions."

SOURCE: Neuron, March 2012.