In 2004, Andre Geim and Konstantin Novoselov at the University of Manchester in England achieved a breakthrough when they isolated graphene for the first time. A flat form of carbon made up of a single layer of atoms, graphene is the thinnest known material--and one of the strongest. Hailed as a wonder material, it won Geim and Novoselov a Nobel Prize in 2010. Twenty years later, graphene is finally making its way into batteries, sensors, semiconductors, air conditioners, and even headphones. And now, it's being tested on people's brains.

This week scientists published the highest-resolution map yet of one small piece of the brain, a tissue sample one cubic millimeter in size. The resulting data set comprised 1,400 terabytes. This map is just one of many that have been in the news in recent years. So this week I thought we could walk through some of the ways researchers make these maps and how they hope to use them. Scientists have been trying to map the brain for as long as they've been studying it.

The link between chronic pain and a loss of appetite may finally be understood – in mice at least. Zhi Zhang at the University of Science and Technology of China in Hefei and his colleagues injected mice with bacteria that provoke chronic pain. Ten days later, these mice were eating less frequently and for shorter periods of time compared with control mice that had been injected with saline. When the first group of mice were later given pain medication, they ate normally, the researchers wrote in a paper published in Nature Metabolism. To better understand the neuronal activity responsible for this change in behaviour, the researchers analysed the brains of the first group of mice while the animals were in chronic pain.

Neurons make up less than half of the brain. Yet when it comes to brain mapping, they get all the limelight. It's easy to see why: as shockingly powerful mini-processors, neurons and their connections--together dubbed the connectome--hold the secret to highly efficient and flexible computation. Nestled inside the brain's wiring diagrams are the keys to consciousness, memories, and emotion. To connectomics, mapping the brain isn't just an academic exercise to better understand ourselves--it could lead to more efficient AI that thinks like us.

AI brain mapping with EEG discovered Alzheimer's brainwave and could detect preclinical Alzheimer's dementia(AD). This has been enabled by an innovative AI technology of iMediSync in brain mapping. With AI analytics and brain mapping techniques, they also serve personalized NIR-LED neuromodulation using their upcoming novel headset, iSyncWave to enhance neuronal activity. These preclinical phenomena are difficult to detect just by inspection. But Artificial Intelligence(AI) technology can do this by deep learning.

CATEGORY WINNER: CELL AND MOLECULAR BIOLOGY William E. Allen William E. Allen received his undergraduate degree from Brown University in 2012, M.Phil. in Computational Biology from the University of Cambridge in 2013, and Ph.D. in Neurosciences from Stanford University in 2019. At Stanford, he worked to develop new tools for the large-scale characterization of neural circuit structure and function, which he applied to understand the neural basis of thirst. After completing his Ph.D., William started as an independent Junior Fellow in the Society of Fellows at Harvard University, where he is developing and applying new approaches to map mammalian brain function and dysfunction over an animal's life span. [ www.sciencemag.org/content/370/6519/925.3 ][1] Charting what the pioneering neuroanatomist Santiago Ramón y Cajal called the “impenetrable jungle” of the brain ([ 1 ][2]) presents one of biology's greatest challenges. How do billions of neurons, wired through trillions of connections, work together to produce cognition and behavior? Like an orchestra, wherein many instruments played simultaneously produce a sound greater than the sum of its parts, thought and behavior emerge from communication between ensembles of molecularly distinct neurons distributed throughout vast neural circuits. Although we know much about the properties of individual genes, cells, and circuits (see the figure, panel A), a vast gap lies between the function of each brain component and an animal's behavior. Bridging this gap has proven technically and conceptually difficult. Inspired by the fact that the development of high-throughput DNA sequencing led geneticists to shift focus from individual genes to the entire genome, I wanted to develop approaches that could simultaneously link multiple levels of the brain, from molecules to neurons to brain-wide neural networks. My goal was to capture a global perspective while maintaining the high resolution and specificity necessary to understand the function of individual components at each level. This new viewpoint, I hoped, would reveal how the collective properties of the brain's building blocks give rise to behavior. During my doctoral studies at Stanford University with Karl Deisseroth and Liqun Luo, I developed new methods to map the architecture and activity of mammalian neural circuits. I applied these approaches to understand the neural basis of thirst, a fundamental regulator of behavior ([ 2 ][3]). Need-based motivational drives, such as hunger and thirst, direct animals to satisfy specific physiological imperatives important for survival ([ 3 ][4]). Despite decades of research, at the beginning of my studies it was unclear how the activity of neurons that sense these needs causes an animal to engage in specific motivated behaviors (e.g., eating or drinking) to maintain homeostasis ([ 3 ][4]). Thirst, a relatively simple yet important drive, thus seemed the perfect model system for investigating multiple levels in the brain. I first traced thirst motivational drive from cellular gene expression to a circuit mechanism. Using a new version of targeted recombination in active populations (TRAP2), a tool to genetically label neurons according to their activity, I found that neurons in the median preoptic nucleus (MnPO) of the hypothalamus became activated in thirsty mice ([ 4 ][5]) (see the figure, panel C). Single-cell RNA sequencing revealed that these neurons formed a single molecularly defined cell type. Artificial activation of these neurons caused mice to drink water within seconds, whereas their inhibition prevented mice from drinking, which suggested that these MnPO neurons were master regulators of thirst. Drinking water also gradually reduced the activity of these neurons. Finally, activation of these neurons was aversive. Together, these results suggested a surprising “drive reduction” model of thirst motivation: Genetically hard-wired thirst neurons become active when mice need hydration, which causes mice to drink water. This ability to ascribe specific functional relevance to genetically defined neurons inspired me to develop new techniques to map cells within their native tissue architecture in even greater molecular detail. To this end, I co-developed STARmap, an approach for highly multiplexed in situ RNA sequencing to measure the expression of hundreds of genes simultaneously within a brain section at the level of single mRNA molecules ([ 5 ][6]) (see the figure, panel B ). In combination with genetic markers of activity, this technique powerfully describes the molecular identity of behaviorally activated neurons and their neighbors at single-cell resolution. ![Figure][7] New large-scale, high-resolution approaches to bridging multiple levels of brain function A new approach to brain function mapping. (A) An illustration of the levels of brain function and how they are interlinked. (B to D) New approaches to bridging levels: (B) STARm ap amplicons barcoding 1020 RNA species simultaneously with single-molecule resolution in the mouse visual cortex. (C) Genetic labeling of neurons according to activity reveals thirst neurons in the median preoptic nucleus of the hypothalamus, used to identify the motivational mechanism of thirst drive. (D) Brain-wide activity map of the response of thousands of neurons across dozens of brain regions to a water-predicting sensory cue, in thirsty or sated mice, reveals widespread broadcasting of thirst state. GRAPHIC: N. DESAI/ SCIENCE FROM W. ALLEN, WANG ET AL . ([ 5 ][6]), ALLEN ET AL . ( 4 ), ALLEN ET AL . ([ 9 ][8]) Despite these insights, a question remained: How do thirst-sensitive neurons deep in the brain coordinate activity in distributed circuits spanning sensory perception, cognition, and motor output to produce motivated behavior? I found that MnPO thirst neurons projected to many brain regions potentially serving different behavioral roles ([ 4 ][5]), but the gap between individual neurons and brain-wide networks was daunting. Earlier in graduate school, I had developed several new microscopy techniques to characterize brain-wide ([ 6 ][9]) or neocortex- wide ([ 7 ][10]) activity, which revealed that global neural activity was present during even simple motivated behaviors. However, because of the mammalian brain's opacity, these approaches were limited in their ability to record fast neural activity throughout the brain at the scale required to understand thirst motivation. Fortunately, however, developments in microelectronics enabled me to construct global maps of neuronal activity with microsecond-level temporal resolution. Using advanced “Neuropixels” probes ([ 8 ][11]), thin silicon needles that can be acutely inserted into the brain to record the electrical signals of hundreds of neurons simultaneously, I developed an experimental approach to record the activity of huge neuronal ensembles across the brain and reconstruct the anatomical location of each recorded cell ([ 9 ][8]). Applying this technique, I mapped the brain-wide flow of activity through ∼24,000 single neurons during thirst-motivated behavior ([ 9 ][8]) (see the figure, panel D). My experiments revealed that this simple behavior produced an unexpectedly global coordination of activity throughout the brain. By observing how activity changed as mice drank water, as well as directly stimulating hypothalamic thirst neurons, I showed that this activity wave was dependent on the animal's motivational state. Surprisingly, the activity of a few hundred thirst neurons instantly modulated the state of the entire brain. Even more surprisingly, I found many neurons, distributed throughout the brain, that directly encoded thirst. These results suggest that even simple behaviors, such as thirst, are emergent properties of the entire brain. I hope these new approaches will at last enable us to comprehend the rules that transform distributed patterns of electrical activity in neural circuits into thoughts, emotions, and perceptions. Understanding how molecules, neurons, and networks interact to shape these rules will have a sweeping impact on our understanding of brain function in health and disease. 1. [↵][12]“Mas, por desgracia, faltábanos el arma poderosa con que descuajar la selva impenetrable de la substancia gris…” ([ 10 ][13]). 2. [↵][14]1. C. A. Zimmerman, 2. D. E. Leib, 3. Z. A. Knight , Nat. Rev. Neurosci. 18, 459 (2017). [OpenUrl][15][CrossRef][16][PubMed][17] 3. [↵][18]1. S. M. Sternson , Neuron 77, 810 (2013). [OpenUrl][19][CrossRef][20][PubMed][21][Web of Science][22] 4. [↵][23]1. W. E. Allen et al ., Science 357, 1149 (2017). [OpenUrl][24][Abstract/FREE Full Text][25] 5. [↵][26]1. X. Wang et al ., Science 361, eaat5691 (2018). [OpenUrl][27][Abstract/FREE Full Text][28] 6. [↵][29]1. L. Ye et al ., Cell 165, 1776 (2016). [OpenUrl][30][CrossRef][31][PubMed][32] 7. [↵][33]1. W. E. Allen et al ., Neuron 94, 891 (2017). [OpenUrl][34][CrossRef][35][PubMed][36] 8. [↵][37]1. J. J. Jun et al ., Nature 551, 232 (2017). [OpenUrl][38][CrossRef][39][PubMed][40] 9. [↵][41]1. W. E. Allen et al ., Science 364, eeav3932 (2019). [OpenUrl][42] 10. [↵][43]1. S. Ramón y Cajal , Recuerdos de mi vida: Historia de mi labor científica (Moya, Madrid, 1917). 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In this paper, our focus is the connection and influence of language technologies on the research in neurolinguistics. We present a review of brain imaging-based neurolinguistic studies with a focus on the natural language representations, such as word embeddings and pre-trained language models. Mutual enrichment of neurolinguistics and language technologies leads to development of brain-aware natural language representations. The importance of this research area is emphasized by medical applications.

The representation of memory in the brain is one of the unresolved questions in neuroscience. A key feature of learning and memory is the process of neuroplasticity--the ability of the brain to remodel structurally and functionally as a result of cognitive experience. Although the neurobiological basis of this process (that is, synaptic plasticity) is well established, the system level dynamics of neuroplasticity are still unclear. Recently, diffusion-weighted magnetic resonance imaging (DW-MRI), which can be carried out noninvasively in humans, provided a new approach to explore neuroplasticity. One of the parameters extracted from DW-MRI is mean diffusivity (MD) of water molecules, which is a biomarker of tissue microstructure (1).

When you repair electronics, you frequently test individual parts to see how they affect the whole. Why not try that with the brain? Stanford is doing just that. It developed a technique that fires specific kinds of neurons to map the brain and identify problems caused by Parkinson's and other diseases. The approach first uses optogenetics to make neurons activate in response to light, and follows up with a functional MRI scan to look for the increased blood flow that indicates activity in other brain regions.

Functional neuroimaging can measure the brain?s response to an external stimulus. It is used to perform brain mapping: identifying from these observations the brain regions involved. This problem can be cast into a linear supervised learning task where the neuroimaging data are used as predictors for the stimulus. Brain mapping is then seen as a support recovery problem. On functional MRI (fMRI) data, this problem is particularly challenging as i) the number of samples is small due to limited acquisition time and ii) the variables are strongly correlated. We propose to overcome these difficulties using sparse regression models over new variables obtained by clustering of the original variables. The use of randomization techniques, e.g. bootstrap samples, and clustering of the variables improves the recovery properties of sparse methods. We demonstrate the benefit of our approach on an extensive simulation study as well as two fMRI datasets.