The ethics of highly portable, cloud-based neuroimaging … Newly observed cycling neural activity pattern in the hippocampus encodes consideration of future scenarios … Kilohertz two-photon imaging of voltage dynamics in mice … Neural interface for long-lasting, high-definition recording across species … New BRAIN tool helps researchers watch neural activity in 3D …
Ethical challenges of field research using portable, cloud-based neuroimaging
Highly portable neuroimaging technologies have the potential to transform neuroimaging research. Emerging mobile technologies will allow scientists to conduct field-based research with underserved populations that have been underrepresented in neuroimaging research and may enable clinical and direct-to-consumer (DTC) applications. Researchers are already developing exciting new mobile technologies, such as portable high-field magnetic resonance imaging (MRI) and mobile positron emission tomography (PET). In contrast to conventional neuroimaging, mobile technologies will likely rely on cloud-based data processing and interpretation, enabling cheaper image acquisition and remote data capabilities. Despite these advantages, new remote features raise ethical questions surrounding data privacy, sharing, and other issues. Further, there is currently no published guidance nor defined ethical framework to address mobile neuroimaging. In this article, Drs. Michael Garwood
, and their colleagues describe several core ethical, legal, and social implications (ELSI) issues of portable, cloud-based neuroimaging and offer advice on how to address these challenges. Researchers also provide an example of how highly portable, low-cost, cloud-enabled MRI will introduce new ways in which brain data are collected, processed, stored, and shared (see diagram below). Based on a literature review and ethics analysis, the authors identified seven emerging ELSI issues: (1) informed consent; (2) data privacy; (3) ability to accurately communicate neuroimaging results to remote participants; (4) reliance on cloud-based artificial intelligence (AI) for data analysis; (5) bias of interpretive algorithms in diverse populations; (6) return of research results and incidental findings to participants; and (7) handling participant requests for access to their brain data. With this article, Drs. Garwood, Shen, and their colleagues hope to inspire more empirical research and consensus building surrounding field-based portable neuroimaging to ensure the ethical application of this powerful, new technology.
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Cycling of hippocampal neural activity underlies envisioning future scenarios
Basic cognitive processes such as planning and decision-making require envisioning future scenarios. In animals and humans, this ability is essential for satisfying daily needs, and perhaps more importantly, for survival. Recent studies have shown that place cells in the hippocampus – a brain hub important for memory and navigation – are activated by and needed for considering future events. But the activity patterns of these cells are sporadic and do not clearly relate to key features of naturalistic behaviors, such as speed and constant movement. Here, Dr. Loren Frank
and his team at the University of California, San Francisco identified a newly observed neural activity pattern associated with envisioning future scenarios by recording hippocampal activity in rats while they explored a two-armed maze. Researchers trained rats to visit the arms of a maze in a set sequence to get food rewards. As rats approached the maze juncture, just before they chose between going left or right, researchers found a new firing pattern: neural activity encoding the two possible options (two future maze paths) regularly alternated back and forth at 8 Hz, or eight times per second. Specific patterns of cycling neural activity were also linked to other elements of envisioning future options in the task, including head location and direction of travel. These cycling dynamics were identified in single cells, pairs of cells, and at the population level, and further, were both anatomically and behaviorally distinct. These results demonstrate that place cell firing represents hypothetical spatial paths, a previously unknown higher-level cognitive function of the hippocampus. Although this patten of neural firing has not yet been observed in humans, results from this study may help us better understand the neural basis of human decision-making and how this process goes awry in mental illness and neurological disease. To learn more about this work, please read the news article
published by the Howard Hughes Medical Institute.
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Ultrafast two-photon fluorescence microscope captures neural activity in vivo
Understanding how information is processed in the brain requires monitoring neural signals at high speed. Voltage imaging is currently the most direct measure of neural activity, but voltage changes at the cell membrane are difficult to capture with conventional two-photon fluorescence imaging due to their millisecond dynamics. Moreover, the current method used for voltage imaging is faster than two-photon imaging but has poor spatial resolution and is restricted to imaging the brain’s surface. By using an ultrafast two-photon fluorescence microscope powered by all-optical laser scanning, Dr. Na Ji
and her team at the University of California, Berkeley imaged neuronal activity in vivo at up to 3,000 times per second in the primary visual cortex of awake mice. Researchers created this new kilohertz imaging method by replacing one of the two-photon laser’s rotating mirrors with an optical mirror, a technique called free-space angular-chirp-enhanced display (FACED). This allowed the microscope to perform 1,000 to 3,000 two-dimensional scans of one brain layer every second, recording for the very first time millisecond changes in voltage. The new imaging method also captured slower changes in calcium and glutamate as deep as 350 microns from the brain’s surface. One advantage of this technique is that it will allow neuroscientists to monitor up to thousands of inputs a single neuron receives from other neurons in a circuit, including those that do not trigger the cell to fire. These ‘sub-threshold’ inputs contribute to important dimensions of neural activity, and now, are measurable millisecond by millisecond in single neurons. Therefore, this method may help us better understand how abnormalities in these input signals, as well as global neural circuits, underlie neurological disorders. In a separate project, Dr. Ji combined two-photon imaging with a different technique called Bessel focus scanning to generate three-dimensional images of calcium changes in neurons, up to 650 microns deep – nearly the full depth of the mouse neocortex. To learn more about these powerful new microscopy techniques, please read the UC Berkeley news release
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New electrode array for high-definition, long-term recording across species
Long-lasting, high-resolution neural interfaces that are ultra-thin and flexible are essential for mapping the brain and controlling sophisticated neuroprosthetic devices. Sampling thousands to millions of sites in the brain requires sophisticated microfabricated devices, which rely on an engineering technique called multiplexing, or combining multiple signals into one on a shared surface. Multiplexed electrode arrays, however, notoriously do not last long in the brain because they suffer from encapsulation failures – when recording devices fail due to brain tissue building up on the electrode’s surface. Dr. Jonathan Viventi
at Duke University and his collaborators at Northwestern University and New York University overcame this obstacle by building a new multiplexed electrode array, dubbed Neural Matrix, that can record neural signals in rodents and non-human primates (NHPs) long-term. The flexible, ultra-thin (~29 μm) array can maintain robust signal quality and high sampling density with little tissue damage for over one year in rodents and is projected to last at least six years in brain tissue. To achieve this longevity, researchers used specialized encapsulation strategies (i.e., applying thermally-grown silicon dioxide layers) and adjusted electrical sensing methods. Furthermore, the electrode array is scalable in coverage and resolution, and can scale to over one thousand channels. The authors also rapidly, iteratively tested kilo-scale electrode arrays in awake behaving NHPs, demonstrating the device’s translational value. In addition to introducing a new implantable array, by meticulously optimizing and iteratively testing Neural Matrix across species, Dr. Viventi and his team validate techniques for the fabrication and in vivo testing of any long-lasting, encapsulated electrode array. These results may pave the way for new flexible neural interfaces used in prosthetic and other therapeutic applications.
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NIH BRAIN Initiative tool helps researchers watch neural activity in 3D
and her colleagues at Columbia University used their ultra-fast, 3D imaging technique called SCAPE microscopy to watch for the first time how mouse olfactory epithelium reacted in real time to complex odors. For more, read the full press release.