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Novel Platform Reveals Insights into Control of Brain Network

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Researchers at the University of North Carolina (UNC) School of Medicine combined fiber photometry with functional magnetic resonance imaging (fMRI) to examine the dynamic activity of brain regions related to the brain’s default mode network (DMN). With the help of Stanford University scientists — and advanced computational modeling — the researchers obtained results that could provide a more informed model for translational studies.

The fMRI-compatible, four-channel, spectrally resolved, optical fiber photometry recording system used for the research is based on a platform used by the team in previous studies. Fiber photometry, an imaging technique that the researchers used to capture population-level calcium activity from specific cell types within a brain region or functional network in order to study neural circuits, relies on the expression of genetically encoded calcium indicators. These indicators can be targeted to specific cells.

The recently developed technique involves the surgical implantation of fiber optics into the brains of living animals. The benefits to researchers are that optical fibers are simpler to implant, less invasive, and less expensive than other calcium-based methods. There is also less weight and stress on the animal compared to an approach that would use miniscopes. Fiber photometry also allows for imaging of multiple interacting brain regions and integration with other neuroscience techniques.
Researchers at the UNC School of Medicine combined fiber photometry with fMRI to examine the dynamic activity of brain regions related to the brain’s DMN (shown via graphical representation). Experimental results showed that activation of the brain’s anterior insular cortex is associated with the suppression of the DMN. Courtesy of the Shih Lab/UNC School of Medicine.
Researchers at the UNC School of Medicine combined fiber photometry with fMRI to examine the dynamic activity of brain regions related to the brain’s DMN (shown via graphical representation). Experimental results showed that activation of the brain’s anterior insular cortex is associated with the suppression of the DMN. Courtesy of the Shih Lab/UNC School of Medicine.
The animal model used by the researchers is one in which putative DMN-related brain regions have been identified, the researchers said. According to researcher Tzu-Hao Harry Chao, they used a rodent model, where genetically encoded calcium sensors were expressed in neurons.

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“This allowed us to record neuronal activity in multiple DMN-related brain regions by detecting changes in fluorescence via optical fibers without interfering with the measurement of fMRI signals,” he said.

The experiment on the transgenic rat models revealed that activation of the brain’s anterior insular cortex is associated with the suppression of the DMN. The researchers further found that salient oddball stimuli suppressed the DMN and enhanced neuronal activity in the anterior insular cortex, and that the anterior insular cortex causally inhibited a prominent DMN node.

In collaboration with Stanford University, the researchers used a variety of computational approaches to identify the brain states and information flow during the changes in neuronal activity.

“This is important neuronal evidence highlighting the role of the anterior insular cortex in controlling DMN activity,” professor Ian Shih said. Alzheimer’s, ADHD, and mood disorders have been linked to the DMN. However, the neurophysiological basis of the DMN — a large-scale network in the brain that is active when a person is not focused on the outside world — is not yet fully understood.

Neuroscientists are growing more interested in these large-scale neuronal networks as they learn that certain cognitive tasks depend on “functionally connected” brain regions. The findings of the UNC team help clarify the neurophysiological foundations of the rodent DMN.

“This could help design network-based treatment regimens for many neurological and neuropsychiatric disorders,” Shih said.

The research was published in Science Advances (www.science.org/doi/10.1126/sciadv.ade5732).

Published: February 2023
Glossary
fiber photometry
An optical recording technique that uses light source(s), a beamsplitting cube, light detector(s) and an optical fiber chronically implanted in animal brain to deliver excitation light to neurons tagged with a fluorescent calcium indicator(s) and to collect their overall calcium activity-induced fluorescence. The measured changes in fluorescence intensity are related to the underlying neuronal activity.
photometry
Photometry is the branch of science that deals with the measurement of light, particularly in terms of its intensity and the way the human eye perceives it. It involves the quantification of visible light and its characteristics, such as brightness and color. Photometric measurements often consider the spectral sensitivity of the human eye to different wavelengths of light and use standardized units to express light intensity. In astronomy, photometry is used to study the brightness of...
optical fiber
Optical fiber is a thin, flexible, transparent strand or filament made of glass or plastic used for transmitting light signals over long distances with minimal loss of signal quality. It serves as a medium for conveying information in the form of light pulses, typically in the realm of telecommunications, networking, and data transmission. The core of an optical fiber is the central region through which light travels. It is surrounded by a cladding layer that has a lower refractive index than...
BiophotonicsbrainImagingSensors & DetectorsmedicalAmericasResearch & TechnologyeducationFiber PhotometryphotometryUNCUniversity of North Carolina - Chapel Hilldiseasefunctional magnetic resonance imagingfMRIneurological disordersbrain activityoptical fiberfiber opticsneurophotonicsBioScan

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