Visualizing the Connectome

ORIGINAL: Discover

By Neuroskeptic

May 12, 2013 4:49 am 

Last year, I blogged about a new and very pretty way of displaying the data about the human ‘connectome’ – the wiring between different parts of the brain. 

But there are many beautiful ways of visualizing the brain’s connections, as neuroscientists Daniel Margulies and colleagues of Leipzig discuss in a colourful paper showcasing these techniques. 

Here, for example, are two ways of showing the brain’s white matter tracts, as studied with diffusion tensor imaging (DTI): 

Another striking image is this one, a representation of the brain’s functional connectivity – the degree to which activation in each part of the brain is correlated with activity in every other part. 

The functional connectome is inherently difficult to visualize in 2D (or even 3D), but in this ingenious display, the brain’s surface is shown covered with hundreds of little brains, each one a colour-coded map of the connectivity from that particular point: 

The Margulies paper is about more than just pretty pictures, though. The authors also discuss the scientific questions and theoretical tensions that surround the choice of one visualization over another: 

Scientific figure and illustrations are – to paraphrase Tufte – where seeing turns into showing. The capacity of these images to influence our interpretation of data and to direct the questions of the scientific community make visualizations worthy of careful consideration during their production… 

If we present a figure that clarifies the scientific content, but does so by creating a distortion of brain space, is that bad practice? What if the caption and methods explicitly stated that the contents of the figure were not to be taken literally? To what degree should a visualization be allowed to stand alone? 

In my view, the study of connections has been dominated by images, more than any other branch of neuroscience. It’s rarely easy to say where ‘method’ or ‘analysis’ ends and ‘visualization’ begins. 

This is not a bad thing – connectivity is spatial, by definition, and to understand space is to visualize it. But it does mean that in the connectome, there is always a danger of valuing aesthetics over accuracy, beauty above brains. 

Margulies DS, Böttger J, Watanabe A, & Gorgolewski KJ (2013). Visualizing the Human Connectome. NeuroImage PMID: 23660027

CATEGORIZED UNDER: fMRI, media, methods, papers, select, top-posts, Uncategorized

Flashing fish brains filmed in action

ORIGINAL: Nature

Monya Baker

18 March 2013 

Fast imaging in larval zebrafish produces first neuron-level vertebrate brain-activity map.

It looks like an oddly shaped campfire, but it is activity of individual neurons across a larval fish brain. It is the first time that researchers have been able to image an entire vertebrate brain at the level of single cells.

At first glance, it looks like an oddly shaped campfire: smoky grey shapes light up with red sparks and flashes. But the video actually represents a different sort of crackle — the activity of individual neurons across a larval fish brain. It is the first time that researchers have been able to image an entire vertebrate brain at the level of single cells. 

“We see the big picture without losing resolution,” says Phillipp Keller, a microscopist at the Howard Hughes Medical Institute's Janelia Farm Research Campus in Ashburn, Virginia, who developed the system with Janelia neurobiologist Misha Ahrens. The researchers are able to record activity across the whole fish brain almost every second, detecting 80% of its 100,000 neurons. (The rest lie in hard-to-access areas, such as between the eyes; their activity is visible but cannot be pinned down to single cells.) The work is published today in Nature Methods1. 

“It’s phenomenal,” says Rafael Yuste, a neuroscientist at Columbia University in New York. “It is a bright star now in the literature, suggesting that it is not crazy to map every neuron in the brain of an animal.” Yuste has been leading the call for a big biology project2 that would do just that in the human brain, which contains about 85,000 times more neurons than the zebrafish brain. 

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The resolution offered by the zebrafish study will enable researchers to understand how different regions of the brain work together, says Ahrens. With conventional techniques, imaging even 2,000 neurons at once is difficult, so researchers must pick and choose which to look at, and extrapolate. Now, he says, “you don't need to guess what is happening — you can see it”. 

The increased imaging power could, for example, help to explain how the brain coordinates movement, consolidates learning or processes sights and smells. “It allows a much better view of the dynamics throughout the brain during different behaviours and during learning paradigms,” says Joseph Fetcho, a neurobiologist at Cornell University in Ithaca, New York. 

Light, camera, activity 

The imaging system relies on a genetically engineered zebrafish (Danio rerio). The fish's neurons make a protein that fluoresces in response to fluctuations in the concentration of calcium ions, which occur when nerve cells fire. A microscope sends sheets of light rather than a conventional beam through the fish's brain, and a detector captures the signals like a viewer watching a cinema screen. The system records activity from the full brain every 1.3 seconds. 

Ahrens, Keller and others have previously used light-sheet microscopy to image developing embryos over days3; for the latest study, they modified light detectors and other aspects of the system to increase the rate of imaging tenfold. In a series of hour-long experiments, each of which generated 1 terabyte (1 million megabytes) of data, the researchers were able to see populations of neurons in distinct regions that correlated to their activity (see video above). 

The technique does have its limitations. For one thing, it works best in zebrafish embryos, which are transparent. Ahrens and Keller think that it could work in intact mammal brains, but it would require surgery and would cover only a small fraction of the brain. 

Another limitation is that neither the protein sensor nor the imaging system yet works fast enough to distinguish whether a neuron has fired once or several times in quick succession. But Fetcho says that it is fast enough to start to understand how activity flows through the brain. “No one is anywhere in the ball park of this for any other animal model.” 

Nature doi:10.1038/nature.2013.12621 

References

Ahrens, M. B. & Keller, P. J. Nature Meth. http://dx.doi.org/10.1038/NMETH.2434 (2013). Show context

Alivasatos, A. P. et al. Science 339, 1284–1285 (2013). 

Article

PubMed Show context

Tomer, R., Khairy, K., Amat, F. & Keller, P. J. Nature Meth. 9, 755–763 (2012). 

Article

ChemPort Show context

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29 November 2011

Location of the mind remains a mystery

ORIGINAL: New Scientist

by Douglas Heaven

22 August 2012 

Where does the mind reside? It's a question that's occupied the best brains for thousands of years. Now, a patient who is self-aware – despite lacking three regions of the brain thought to be essential for self-awareness – demonstrates that the mind remains as elusive as ever.

The finding suggests that mental functions might not be tied to fixed brain regions. Instead, the mind might be more like a virtual machine running on distributed computers, with brain resources allocated in a flexible manner, says David Rudrauf at the University of Iowa in Iowa City, who led the study of the patient.

Recent advances in functional neuroimaging – a technique that measures brain activity in the hope of finding correlations between mental functions and specific regions of the brain – have led to a wealth of studies that map particular functions onto regions.

Previous neuroimaging studies had suggested that three regions – 

• the insular cortex, 
• anterior cingulated cortex and 
• medial prefrontal cortex 

– are critical for self-awareness. But for Rudrauf the question wasn't settled.

So when his team heard about patient R, who had lost brain tissue including the chunks of the three 'self-awareness' regions following a viral infection, they immediately thought he could help set the record straight.

Not a zombie

According to the models based on neuroimaging, says Rudrauf, "patients with no insula should be like zombies".

But patient R displays a strong concept of selfhood. Rudrauf's team confirmed this by checking whether he could recognise himself in photographs and by performing the tickle test – based on the observation that you can't tickle yourself. They concluded that many aspects of R's self-awareness remained unaffected. "Having interacted with him it was clear from the get go that there was no way that [the theories based on neuroimaging] could be true," says Rudrauf.

However, R does have severe amnesia, which prevents him from learning new information, and he struggles with social interaction.

Self-awareness and other high-level cognitive functions probably do not relate to the brain in a simple way, says Rudrauf. "They involve layers of abstraction and mechanisms that cannot be explained by standard functional-neuroanatomy." He suggests that there are fundamental mechanisms yet to be discovered. "We would all like simple answers to complicated questions, and we tend to oversimplify our conceptions about the brain and the mind," he says.

Linda Clare, a psychologist at Bangor University, UK, is also not surprised by the finding. "Awareness has many manifestations," she says. "It's not just a matter of a few brain cells."

Journal reference: PLoS ONE, DOI:10.1371/journal.pone.0038413