Search NASA⌕ Search

SEARCH · Search NASA

Results for “neuromodulation”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Size and Structural Control of Mechanoluminescent ZnS:Mn 2+ Nanocrystals for Optogenetic Neuromodulation

Mechanoluminescent materials hold immense potential for various transformative applications, from medical imaging and diagnostics to health monitoring and wearable displays. Conventionally produced as bulk powders or microparticles, they face significant size limitations for advanced applications, particularly in biological systems and microscale devices. Here, this work presents an approach to ZnS:Mn 2+ nanocrystal synthesis that involves self-assembly and subsequent calcination. In addition to effective size control within the nanoscale, this approach promotes the formation of abundant stacking faults, significantly enhancing piezoelectric and mechanoluminescent properties by increasing trap density and reducing trap depth. Unlike mechanoluminescent materials produced using conventional methods, these nanocrystals demonstrate strong mechanoluminescence without requiring UV pre-excitation, and the light emission persists even after mechanical stress is removed. These advantageous properties make them promising candidates for optogenetic neuromodulation, as they can effectively trigger electrical signals in neurons upon ultrasound stimulation both with and without UV pre-excitation. The persistent mechanoluminescence prolongs the duration of neuronal electrical activity, providing an extended temporal window for neuromodulation compared to conventional mechanoluminescent materials. This study provides a scalable method for producing efficient mechanoluminescent nanoparticles and reveals the crucial role of particle size and defect structures in determining their mechanoluminescent behavior.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2019

Task-Based Neuromodulation Architecture for Lifelong Learning

The conventional supervised deep learning frameworks for image classification focus on finding the minimizer of an objective function. However, for a lifelong learning system, a network has to be able to dynamically learn new tasks from very few examples. In biological neural networks, it is observed that neuromodulation acts as a key factor in continual learning. In this work, we propose a dynamic learning system, ModNet, wherein a modulatory unit regulates the learning depending on the context and the internal state of the system. The modulatory unit, which consists of a group of neurons, exercises the use of neuromodulation and Hebbian plasticity mechanisms over a population of neurons instead of relying on backpropagation of error gradients. An efficient digital architecture with on-chip training and resource sharing is proposed to facilitate the efficacy of task-based processing.

brain-inspired↗
DOE OSTI2023

Implantable neuromodulation system for closed-loop stimulation and recording simultaneously at multiple brain sets

The present disclosure relates to a modular system for deep brain stimulation (DBS) and electrocorticography (ECoG). The system may have an implantable neuromodulator for generating electrical stimulation signals adapted to be applied to a desired region of a brain via an attached electrode array. An aggregator module may be used for collecting and aggregating electrical signals and transmitting the electrical signals to the neuromodulator. A control module may be used which is in communication with the aggregator module for controlling generation of the electrical signals and transmitting the electrical signals to the aggregator.

Pannu, Satinderpall S.↗
DOE OSTI2023

Development of polarization-sensitive optical coherence tomography imaging platform and metrics to quantify electrostimulation-induced peripheral nerve injury in vivo in a small animal model

Neuromodulation devices are rapidly evolving for the treatment of neurological diseases and conditions. Injury from implantation or long-term use without obvious functional losses is often only detectable through terminal histology. New technologies are needed that assess the peripheral nervous system (PNS) under normal and diseased or injured conditions. We aim to demonstrate an imaging and stimulation platform that can elucidate the biological mechanisms and impacts of neurostimulation in the PNS and apply it to the sciatic nerve to extract imaging metrics indicating electrical overstimulation. A sciatic nerve injury model in a 15-rat cohort was observed using a newly developed imaging and stimulation platform that can detect electrical overstimulation effects with polarization-sensitive optical coherence tomography. The sciatic nerve was electrically stimulated using a custom-developed nerve holder with embedded electrodes for 1 h, followed by a 1-h recovery period, delivered at above-threshold Shannon model k-values in experimental groups: sham control (SC, n = 5, 0.0 mA / 0 Hz), stimulation level 1 (SL1, n = 5, 3.4 mA / 50 Hz, and k = 2.57), and stimulation level 2 (SL2, n = 5, 6.8 mA / 100 Hz, and k = 3.17). The stimulation and imaging system successfully captured study data across the cohort. When compared to a SC after a 1-week recovery, the fascicle closest to the stimulation lead showed an average change of +4 % / – 309 % (SL1/SL2) in phase retardation and –79 % / – 148 % in optical attenuation relative to SC. Analysis of immunohistochemistry (IHC) shows a +1 % / – 36 % difference in myelin pixel counts and –13 % / + 29 % difference in axon pixel counts, and an overall increase in cell nuclei pixel count of +20 % / + 35 % . These metrics were consistent with IHC and hematoxylin/eosin tissue section analysis. The poststimulation changes observed in our study are manifestations of nerve injury and repair, specifically degeneration and angiogenesis. Optical imaging metrics quantify these processes and may help evaluate the safety and efficacy of neuromodulation devices.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Mechanisms of Action of Dorsal Root Ganglion Stimulation

The dorsal root ganglion (DRG) serves as a pivotal site for managing chronic pain through dorsal root ganglion stimulation (DRG-S). In recent years, the DRG-S has emerged as an attractive modality in the armamentarium of neuromodulation therapy due to its accessibility and efficacy in alleviating chronic pain refractory to conventional treatments. Despite its therapeutic advantages, the precise mechanisms underlying DRG-S-induced analgesia remain elusive, attributed in part to the diverse sensory neuron population within the DRG and its modulation of both peripheral and central sensory processing pathways. Emerging evidence suggests that DRG-S may alleviate pain by several mechanisms, including the reduction of nociceptive signals at the T-junction of sensory neurons, modulation of pain gating pathways within the dorsal horn, and regulation of neuronal excitability within the DRG itself. However, elucidating the full extent of DRG-S mechanisms necessitates further exploration, particularly regarding its supraspinal effects and its interactions with cognitive and affective networks. Understanding these mechanisms is crucial for optimizing neurostimulation technologies and improving clinical outcomes of DRG-S for chronic pain management. This review provides a comprehensive overview of the DRG anatomy, mechanisms of action of the DRG-S, and its significance in neuromodulation therapy for chronic pain.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

A novel statistical methodology for quantifying the spatial arrangements of axons in peripheral nerves

A thorough understanding of the neuroanatomy of peripheral nerves is required for a better insight into their function and the development of neuromodulation tools and strategies. In biophysical modeling, it is commonly assumed that the complex spatial arrangement of myelinated and unmyelinated axons in peripheral nerves is random, however, in reality the axonal organization is inhomogeneous and anisotropic. Present quantitative neuroanatomy methods analyze peripheral nerves in terms of the number of axons and the morphometric characteristics of the axons, such as area and diameter. In this study, we employed spatial statistics and point process models to describe the spatial arrangement of axons and Sinkhorn distances to compute the similarities between these arrangements (in terms of first- and second-order statistics) in various vagus and pelvic nerve cross-sections. We utilized high-resolution transmission electron microscopy (TEM) images that have been segmented using a custom-built high-throughput deep learning system based on a highly modified U-Net architecture. Our findings show a novel and innovative approach to quantifying similarities between spatial point patterns using metrics derived from the solution to the optimal transport problem. We also present a generalizable pipeline for quantitative analysis of peripheral nerve architecture. Our data demonstrate differences between male- and female-originating samples and similarities between the pelvic and abdominal vagus nerves.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Percutaneous Neurolysis for Pain Management in Oncological Patients

Cancer pain is most commonly classified as nociceptive (somatic or visceral) or neuropathic. Different types of pain or pain syndromes are present in all phases of cancer (early and metastatic) and are inadequately treated in 56% to 82.3% of patients. Percutaneous neurolysis and neuromodulation are feasible and reproducible, efficient (70–80% success rate) and safe (≈ 0.5% mean complication rate) palliative therapies for pain reduction in oncologic patients with refractory pain. Percutaneous neurolysis can be performed either by injection of a chemical agent (phenol or alcohol) or by application of continuous radiofrequency or cryoablation. During chemical neurolysis nerve damage is achieved by means of Wallerian degeneration. A thorough knowledge of neural anatomy and pain transmission pathways is fundamental to appropriate patient and technique selection. Imaging guidance and strict asepsis are prerequisites. The purpose of this article is to describe the basic concepts of percutaneous neurolysis in oncologic patients. Controversies concerning techniques and products will be addressed. Finally, the necessity for an individually tailored approach for the selection of the different techniques and targets will be emphasized.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

Astrocytes in the mouse visual cortex reliably respond to visual stimulation

Highlights: • We performed dual-color in vivo two-photon Ca{sup 2+} imaging of neurons and astrocytes. • α1-adrenoblocker prazosin substantially reduced global astrocytic activities. • Astrocytes showed weak but reliable visual responses in the awake mouse visual cortex. • Astrocytic visual responses were delayed by 5 s relative to the neuronal ones. Astrocytes are known to contact with a great number of synapses and may integrate sensory inputs. In the ferret primary visual cortex, astrocytes respond to a visual stimulus with a delay of several seconds with respect to the surrounding neurons. However, in the mouse visual cortex, it remains unclear whether astrocytes respond to visual stimulations. In this study, using dual-color simultaneous in vivo two-photon calcium imaging of neurons and astrocytes in the awake mouse visual cortex, we examined the visual response of astrocytes and their precise response timing relative to the surrounding neurons. Neurons reliably responded to visual stimulations, whereas astrocytes often showed neuromodulator-mediated global activities, which largely masked small visual responses. Administration of the selective α1-adrenergic receptor antagonist prazosin substantially reduced such global astrocytic activities without affecting the neuronal visual responses. In the presence of prazosin, astrocytes showed weak but consistent visual responses mostly at their somata. Cross-correlation analysis estimated that the astrocytic visual responses were delayed by approximately 5 seconds relative to the surrounding neuronal responses. In conclusion, our research demonstrated that astrocytes in the primary visual cortex of awake mice responded to visual stimuli with a delay of several seconds relative to the surrounding neurons, which may indicate the existence of a common mechanism of neuron–astrocyte communication across species.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

A Copper-Binding Peptide with Therapeutic Potential against Alzheimer′s Disease: From the Blood–Brain Barrier to Metal Competition

Alzheimer’s disease (AD) is the most common form of dementia worldwide. AD brains are characterized by the accumulation of amyloid-β peptides (Aβ) that bind Cu 2+ and have been associated with several neurotoxic mechanisms. Although the use of copper chelators to prevent the formation of Cu 2+ -Aβ complexes has been proposed as a therapeutic strategy, recent studies show that copper is an important neuromodulator that is essential for a neuroprotective mechanism mediated by Cu 2+ binding to the cellular prion protein (PrPC). Therefore, in addition to metal selectivity and blood–brain barrier (BBB) permeability, an emerging challenge for copper chelators is to prevent the formation of neurotoxic Cu 2+ -Aβ species without perturbing the neuroprotective Cu 2+ -PrPC interaction. Previously, we reported the design of a tetrapeptide (TP) that withdraws Cu 2+ from Aβ(1–16) and impacts the Cu 2+ -induced aggregation of Aβ(1–40). In this study, we improved the drug-like properties of TP in a BBB model, evaluated the metal selectivity of the optimized peptide (TP*), and tested its effect on Cu 2+ coordination to PrPC and proteins involved in copper trafficking, such as copper transporter 1 and albumin. Our results show that changing the stereochemistry of the first residue prevents TP degradation in the BBB model and coadministration of TP with a peptide that increases BBB permeability allows its passage through the BBB model. TP* is highly selective toward Cu 2+ in the presence of Zn 2+ ions, transfers Cu 2+ to copper-trafficking proteins, and forms a ternary TP*-Cu 2+ -PrP species that does not perturb the physiological conformation of PrP and displays only a minor impact in the neuroprotective Cu 2+ -dependent interaction of PrPC with the N-methyl-d-aspartate receptor. Overall, these results show that TP* displays desirable features for a copper chelator with therapeutic potential against AD. Moreover, this is the first study that explores the effect of a Cu 2+ chelator with therapeutic potential for AD on Cu 2+ coordination to PrPC (an emerging key player in AD pathology), integrating recent knowledge about metalloproteins involved in AD with the design of copper chelators against AD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Mapping the Morphology of DNA on Carbon Nanotubes in Solution Using X-ray Scattering Interferometry

Single-walled carbon nanotubes (SWCNTs) with adsorbed single-stranded DNA (ssDNA) are applied as sensors to investigate biological systems, with potential applications ranging from clinical diagnostics to agricultural biotechnology. Unique ssDNA sequences render SWCNTs selectively responsive to target analytes such as (GT)n-SWCNTs recognizing the neuromodulator, dopamine. It remains unclear how the ssDNA conformation on the SWCNT surface contributes to functionality, as observations have been limited to computational models or experiments under dehydrated conditions that differ substantially from the aqueous biological environments in which the nanosensors are applied. We demonstrate a direct mode of measuring in-solution ssDNA geometries on SWCNTs via X-ray scattering interferometry (XSI), which leverages the interference pattern produced by AuNP tags conjugated to ssDNA on the SWCNT surface. We employ XSI to quantify distinct surface-adsorbed morphologies for two (GT) n ssDNA oligomer lengths (n = 6, 15) that are used on SWCNTs in the context of dopamine sensing and measure the ssDNA conformational changes as a function of ionic strength and during dopamine interaction. Here, we show that the shorter oligomer, (GT) 6 , adopts a more periodically ordered ring structure along the SWCNT axis (inter-ssDNA distance of 8.6 ± 0.3 nm), compared to the longer (GT) 15 oligomer (most probable 5'-to-5' distance of 14.3 ± 1.1 nm). During molecular recognition, XSI reveals that dopamine elicits simultaneous axial elongation and radial constriction of adsorbed ssDNA on the SWCNT surface. Our approach using XSI to probe solution-phase morphologies of polymer-functionalized SWCNTs can be applied to yield insights into sensing mechanisms and inform future design strategies for nanoparticle-based sensors.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Structure and mechanism of human vesicular polyamine transporter

Polyamines play essential roles in gene expression and modulate neuronal transmission in mammals. Vesicular polyamine transporters (VPAT) from the SLC18 family exploit the transmembrane H + gradient to translocate polyamines into secretory vesicles, enabling the quantal release of polyamine neuromodulators and underpinning learning and memory formation. Here, we report the cryo-electron microscopy structures of human VPAT in complex with spermine, spermidine, H + , or tetrabenazine, elucidating discrete lumen-facing states of the antiporter and pivotal interactions between VPAT and its substrate or inhibitor. Leveraging structure-inspired mutagenesis studies and protein structure prediction, we deduce an unforeseen mechanism whereby the polyamine and H + compete for multiple acidic protein residues both directly and indirectly, and rationalize how the antidopaminergic therapeutic tetrabenazine impedes vesicular transport of polyamines. This study unravels the mechanism of an H + -coupled polyamine antiporter, reveals mechanistic diversity between VPAT and other SLC18 antiporters, and raises new prospects for combating human disorders of polyamine homeostasis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Synapse-specific catecholaminergic modulation of neuronal glutamate release

Norepinephrine in vertebrates and its invertebrate analog, octopamine, regulate the activity of neural circuits. We find that, when hungry,Drosophilalarvae switch activity in type II octopaminergic motor neurons (MNs) to high-frequency bursts, which coincide with locomotion-driving bursts in type I glutamatergic MNs that converge on the same muscles. Optical quantal analysis across hundreds of synapses simultaneously reveals that octopamine potentiates glutamate release by tonic type Ib MNs, but not phasic type Is MNs, and occurs via the G q -coupled octopamine receptor (OAMB). OAMB is more abundant in type Ib terminals and acts through diacylglycerol and its target Unc13A, a key component of the glutamate release machinery. Potentiation varies significantly—by up to 1,000%—across synapses of a single Ib axon, with synaptic Unc13A levels determining both release probability and potentiation. We propose that a dual molecular mechanism—an upstream neuromodulator receptor and a downstream transmitter release controller—fine-tunes catecholaminergic modulation so that strong tonic synapses exhibit large potentiation, while weaker tonic and all phasic synapses maintain consistency, yielding a sophisticated regulation of locomotor behavior.

Science & Technology - Other Topics↗
DOE OSTI2021

Molecular mechanisms of metabotropic GABA B receptor function

Metabotropic γ-aminobutyric acid G protein–coupled receptors (GABA B ) represent one of the two main types of inhibitory neurotransmitter receptors in the brain. These receptors act both pre- and postsynaptically by modulating the transmission of neuronal signals and are involved in a range of neurological diseases, from alcohol addiction to epilepsy. A series of recent cryo-EM studies revealed critical details of the activation mechanism of GABA B . Structures are now available for the receptor bound to ligands with different modes of action, including antagonists, agonists, and positive allosteric modulators, and captured in different conformational states from the inactive apo to the fully active state bound to a G protein. These discoveries provide comprehensive insights into the activation of the GABA B receptor, which not only broaden our understanding of its structure, pharmacology, and physiological effects but also will ultimately facilitate the discovery of new therapeutic drugs and neuromodulators.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Topological supramolecular network enabled high-conductivity, stretchable organic bioelectronics

Intrinsically stretchable bioelectronic devices based on soft and conducting organic materials have been regarded as the ideal interface for seamless and biocompatible integration with the human body. A remaining challenge is to combine high mechanical robustness with good electrical conduction, especially when patterned at small feature sizes. We develop a molecular engineering strategy based on a topological supramolecular network, which allows for the decoupling of competing effects from multiple molecular building blocks to meet complex requirements. We obtained simultaneously high conductivity and crack-onset strain in a physiological environment, with direct photopatternability down to the cellular scale. We further collected stable electromyography signals on soft and malleable octopus and performed localized neuromodulation down to single-nucleus precision for controlling organ-specific activities through the delicate brainstem.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Human perception of ionizing radiation

Here, in this work, we address the question of whether humans can perceive ionizing radiation. We conducted a thorough review of the clinical and experimental literature related to ionizing radiation, with a focus on its acute effects. Specifically, we examined the three domains of X-ray perception found in animals (abdominal, olfactory, and retinal), which led us to instances of ionizing radiation-induced hearing and taste sensory phenomena in humans thus suggesting that humans can perceive X-rays across various sensory modalities via multiple mechanisms. We also analyzed literature to understand the mechanisms associated with reported symptoms, this led us to the concept of radiomodulation, an understudied modulatory effect of sub-ablative ionizing radiation doses on neurons. Based on this review of the literature we propose the hypothesis that a significant radiomodulation mechanism is the formation of reactive oxygen species from radiolysis which activates immune and sensory signal transduction mechanisms specifically related to the redox activity in TRP and K+ channels. Additionally, we find evidence to support the previous claims of perception stemming from Cherenkov radiation and ozone production which are perceived using canonical sensory modalities. Finally, for we provide a concise summary of the applications of ionizing radiation in clinical imaging and therapy, as well as prospects for future developments of radiation technologies for biomedical and fundamental research.

Ionizing radiation↗
DOE OSTI2021

Wireless Optogenetic Modulation of Cortical Neurons Enabled by Radioluminescent Nanoparticles

While offering high precision control of neural circuits, optogenetics is hampered by the necessity to implant fiber-optic waveguides in order to deliver photons to genetically engineered light-gated neurons in the brain. Unlike laser light, X-rays freely pass biological barriers. In this work, we show that radioluminescent Gd 2 (WO 4 ) 3 :Eu nanoparticles, which absorb an external X-rays energy and then down-converter it into optical photons with wavelengths of ~610 nm, can be used for the transcranial stimulation of cortical neurons expressing red-shifted, ~590-630 nm, channelrhodopsin ReaChR, thereby promoting optogenetic neural control to the practical implementation of minimally-invasive wireless deep brain stimulation.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Sex Differences in Vagus Nerve Stimulation Effects on Rat Cardiovascular and Immune Systems

Background: Investigations into the benefits of vagus nerve stimulation (VNS) through pre-clinical and clinical research have led to promising findings for treating several disorders. Despite proven effectiveness of VNS on conditions such as epilepsy and depression, understanding of off-target effects and contributing factors such as sex differences can be beneficial to optimize therapy design. New Methods: In this article, we assessed longitudinal effects of VNS on cardiovascular and immune systems, and studied potential sex differences using a rat model of longterm VNS. Rats were implanted with cuff electrodes around the left cervical vagus nerve for VNS, and wireless physiological monitoring devices for continuous monitoring of cardiovascular system using electrocardiogram (ECG) signals. ECG morphology and heart rate variability (HRV) features were extracted to assess cardiovascular changes resulting from VNS in short-term and long-term timescales. We also assessed VNS effects on expression of inflammatory cytokines in blood during the course of the experiment. Statistical analysis was performed to compare results between Treatment and Sham groups, and between male and female animals from Treatment and Sham groups. Results: Considerable differences between male and female rats in cardiovascular effects of VNS were observed in multiple cardiovascular features. However, the effects seemed to be transient with approximately 1-h recovery after VNS. While short-term cardiovascular effects were mainly observed in male rats, females in general showed more significant long-term effects even after VNS stopped. We did not observe notable changes or sex differences in systemic cytokine levels resulting from VNS. Comparison With Existing Methods: Compared to existing methods, our study design incorporated wireless physiological monitoring and systemic blood cytokine level analysis, along with long-term VNS experiments in unanesthetized rats to study sex differences. Conclusion: The contribution of sex differences for long-term VNS off-target effects on cardiovascular and immune systems was assessed using awake behaving rats. Although VNS did not change the concentration of inflammatory biomarkers in systemic circulation for male and female rats, we observed significant differences in cardiovascular effects of VNS characterized using ECG morphology and HRV analyses.

59 BASIC BIOLOGICAL SCIENCES↗