Observatories of the Brain

A simple glance up at a clear night sky can show much, including the current positions of stars and planets as well as indicating where you are on Earth at that moment. If you use a telescope, even more details come into view. Quantum theory aside, viewing the universe does not prevent it from going about its regular business. Observing the real-time activities of a living brain is a very different story.

Although there are many properties of the universe that are not directly available to our eyes, there’s still an innate visibility to stars. Not so the processes of the brain — the myriad activities occurring within the skull must be rendered visible. Imaging tools such as magnetic resonance imaging (MRI) that are commonly used to do this have an obvious impact on the range of actions that a subject can do while being observed. Our brains are constantly generating electrical impulses in specific patterns that define who we are and what we do. But, these vital patterns, generated when neurons transmit electrochemical signals (called firing), are completely hidden inside our heads. Brain wave mapping with electroencephalographs (EEGs) and imaging technologies, such as fMRIs (the “f” stands for “functional”), can reveal much useful information, but the resolution is not fine enough to reveal the interaction and networks of individual neurons that hold the crucial keys to decipher the workings of the mind.

Neuroscientists routinely employ genetic methods to make individual nerve cells in specific brain regions literally light up when they are firing. The process involves genetically engineering neurons in living mice by using a special type of virus to insert additional coding instructions into the DNA. A related approach is taken in gene therapy. These modified nerve cells are now programmed to express a protein that fluoresces green when the neuron fires, thereby temporarily “lighting it up.”

Inscopix, a Palo Alto-based neuroscience company, has created a small digital microscope that attaches to the head to capture these flashes of light as they occur in thousands of individual neurons — reminiscent of stars twinkling in the night sky. The patterns of flashes are translated to familiar types of scientific plots and then analyzed. This technology is being honed by using mice, but it ushers in new ideas and applications to the human brain.

Pushkar Joshi, a neurobiology research scientist at Inscopix, describes it as decoding the patterns of optical signals and then translating them into meaningful representations of neural activity. Joshi says, “The goal of this work is to improve the human condition.” As a practical example of this, he notes, “Many neurological and psychiatric disorders have been described as 'chemical imbalances,’ but these imbalances are more a result of neural circuit activity dysfunction.” That is, many problems are primarily due to faulty wiring in the brain. That could mean that, in the future, visual representations of patterns of neuronal activity can show the root cause and potential treatment of the problem.

Joshi adds that the fact the flash-detecting devices are small and mass producible means, that in principle, “you could run experiments with 100 mice in parallel and over substantial periods of time.” That volume of comparative data can bring new insights into neuroscience, but it will also require effective measures to manage and work with the influx.

The work, Joshi says, “necessarily involves the collaboration of a highly cross-disciplinary team.” The approach requires the involvement of neuroscientists, data scientists, developers, designers, hardware engineers, software engineers, and others. This way of working will play an increasingly important role in helping to create brand new forms of visualization.

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