Although in vivo exposure therapy is highly effective in the treatment of specific phobias, only a minority of patients seeks therapy. Exposure to virtual objects has been shown to be better tolerated, equally efficacious, but the technology has not been made widely accessible yet. We developed an augmented reality (AR) application (app) to reduce fear of spiders and performed a randomized controlled trial comparing the effects of our app (six 30-min sessions at home over a two-week period) with no intervention. Primary outcome was subjective fear, measured by a Subjective Units of Distress Scale (SUDS) in a Behavioural Approach Test (BAT) in a real-life spider situation at six weeks follow-up. Between Oct 7, 2019, and Dec 6, 2019, 66 individuals were enrolled and randomized. The intervention led to significantly lower subjective fear in the BAT compared to the control group (intervention group, baseline: 7.12 [SD 2.03] follow-up: 5.03 [SD 2.19] vs. control group, baseline: 7.06 [SD 2.34], follow-up 6.24 [SD 2.21]; adjusted group difference -1.24, 95 % CI -2.17 to -0.31; Cohen’s d = 0.57, p = 0.010). The repeated use of the AR app reduces subjective fear in a real-life spider situation, providing a low-threshold and low-cost treatment for fear of spiders.
The lack of satisfactory treatment for persistent pain profoundly impairs the quality of life for many patients. Stimulation of brainstem pain control systems can trigger powerful analgesia, but their complex network organization frequently prevents separation of analgesia from side effects. To overcome this long-standing challenge, we developed a biocompatible gelatin-embedded cluster of ultrathin microelectrodes that enables fine-tuned, high-definition three-dimensional stimulation in periaqueductal gray/dorsal raphe nucleus in awake rats. Analgesia was assessed from both motor reactions and intracortical signals, corresponding to pain-related signals in humans. We could select an individual-specific subset of microelectrodes in each animal that reliably provided strong pain inhibition during normal and hyperalgesia conditions, without noticeable behavioral side effects. Gait, spontaneous cortical activity at rest, and cortical tactile responses were minimally affected, indicating a highly selective action. In conclusion, our developed biocompatible microelectrode cluster and stimulation paradigm reliably enabled powerful, fine-tuned, and selective analgesia without noticeable side effects.
Nature controls the assembly of complex architectures through self-limiting processes; however, few artificial strategies to mimic these processes have been reported to date. Here we demonstrate a system comprising two types of nanocrystal (NC), where the self-limiting assembly of one NC component controls the aggregation of the other. Our strategy uses semiconducting InP/ZnS core–shell NCs (3 nm) as effective assembly modulators and functional nanoparticle surfactants in cucurbit[n]uril-triggered aggregation of AuNCs (5–60 nm), allowing the rapid formation (within seconds) of colloidally stable hybrid aggregates. The resultant assemblies efficiently harvest light within the semiconductor substructures, inducing out-of-equilibrium electron transfer processes, which can now be simultaneously monitored through the incorporated surface-enhanced Raman spectroscopy–active plasmonic compartments. Spatial confinement of electron mediators (for example, methyl viologen (MV2+)) within the hybrids enables the direct observation of photogenerated radical species as well as molecular recognition in real time, providing experimental evidence for the formation of elusive σ–(MV+)2 dimeric species. This approach paves the way for widespread use of analogous hybrids for the long-term real-time tracking of interfacial charge transfer processes, such as the light-driven generation of radicals and catalysis with operando spectroscopies under irreversible conditions.
In 2013 the European Union (EU) embarked on one of its three largest-ever targeted technology R&D programs, a 10-year, €1 billion ($1.18 billion) program called the Graphene Flagship, with the aim of creating applications and markets for the two-dimensional material and establishing Europe at the forefront of the technology. Ultimately, its impact and whether it has been worth the public spending and effort won’t be known for years to come. “Over the past seven years, the Graphene Flagship has successfully brought graphene out of the lab, creating a fruitful European industrial ecosystem that develops applications of graphene and layered materials,” says the flagship’s 2020 annual report. “Today, our industrial family includes over 100 companies working together with the Graphene Flagship’s academic partners in fields ranging from the automotive and aviation industries to electronics, energy, composites and biomedicine.”
Radiological examination of the brain is a critical determinant of stroke care pathways. Accessible neuroimaging is essential to detect the presence of intracerebral hemorrhage (ICH). Conventional magnetic resonance imaging (MRI) operates at high magnetic field strength (1.5–3 T), which requires an access-controlled environment, rendering MRI often inaccessible. We demonstrate the use of a low-field MRI (0.064 T) for ICH evaluation. Patients were imaged using conventional neuroimaging (non-contrast computerized tomography (CT) or 1.5/3 T MRI) and portable MRI (pMRI) at Yale New Haven Hospital from July 2018 to November 2020. Two board-certified neuroradiologists evaluated a total of 144 pMRI examinations (56 ICH, 48 acute ischemic stroke, 40 healthy controls) and one ICH imaging core lab researcher reviewed the cases of disagreement. Raters correctly detected ICH in 45 of 56 cases (80.4% sensitivity, 95%CI: [0.68–0.90]). Blood-negative cases were correctly identified in 85 of 88 cases (96.6% specificity, 95%CI: [0.90–0.99]). Manually segmented hematoma volumes and ABC/2 estimated volumes on pMRI correlate with conventional imaging volumes (ICC = 0.955, p = 1.69e-30 and ICC = 0.875, p = 1.66e-8, respectively). Hematoma volumes measured on pMRI correlate with NIH stroke scale (NIHSS) and clinical outcome (mRS) at discharge for manual and ABC/2 volumes. Low-field pMRI may be useful in bringing advanced MRI technology to resource-limited settings.
Motor imagery offers an excellent opportunity as a stimulus-free paradigm for brain–machine interfaces. Conventional electroencephalography (EEG) for motor imagery requires a hair cap with multiple wired electrodes and messy gels, causing motion artifacts. Here, a wireless scalp electronic system with virtual reality for real-time, continuous classification of motor imagery brain signals is introduced. This low-profile, portable system integrates imperceptible microneedle electrodes and soft wireless circuits. Virtual reality addresses subject variance in detectable EEG response to motor imagery by providing clear, consistent visuals and instant biofeedback. The wearable soft system offers advantageous contact surface area and reduced electrode impedance density, resulting in significantly enhanced EEG signals and classification accuracy. The combination with convolutional neural network-machine learning provides a real-time, continuous motor imagery-based brain–machine interface. With four human subjects, the scalp electronic system offers a high classification accuracy (93.22 ± 1.33% for four classes), allowing wireless, real-time control of a virtual reality game.
Multichannel electrophysiological sensors and stimulators—particularly those used to study the nervous system—are usually based on monolithic microelectrode arrays. However, the architecture of such arrays limits flexibility in electrode placement and scaling to a large number of nodes, especially across non-contiguous locations. Here we report wirelessly networked and powered electronic microchips that can autonomously perform neural sensing and electrical microstimulation. The microchips, which we term neurograins, have an ~1 GHz electromagnetic transcutaneous link to an external telecom hub, providing bidirectional communication and control at the individual device level. To illustrate the potential of the approach, we show that 48 neurograins can be individually addressed on a rat cortical surface and used for the acute recording of neural activity. Theoretical calculations and experimental measurements show that the link configuration could potentially be scaled to 770 neurograins using a customized time-division multiple access protocol.
Highlights •Extrasynaptic levels of dopamine in mouse cortex exhibit spontaneous impulses •Impulses are broadly distributed in amplitude and time, with a rate of about 0.01/s •Feedback was used to train mice to volitionally control their spontaneous impulses •Mice learned to reliably modulate dopamine impulses in order to receive a reward Summary In their pioneering study on dopamine release, Romo and Schultz speculated “...that the amount of dopamine released by unmodulated spontaneous impulse activity exerts a tonic, permissive influence on neuronal processes more actively engaged in preparation of self-initiated movements....”1 Motivated by the suggestion of “spontaneous impulses,” as well as by the “ramp up” of dopaminergic neuronal activity that occurs when rodents navigate to a reward,2, 3, 4, 5 we asked two questions. First, are there spontaneous impulses of dopamine that are released in cortex? Using cell-based optical sensors of extrasynaptic dopamine, [DA]ex,6 we found that spontaneous dopamine impulses in cortex of naive mice occur at a rate of ∼0.01 per second. Next, can mice be trained to change the amplitude and/or timing of dopamine events triggered by internal brain dynamics, much as they can change the amplitude and timing of dopamine impulses based on an external cue?7, 8, 9 Using a reinforcement learning paradigm based solely on rewards that were gated by feedback from real-time measurements of [DA]ex, we found that mice can volitionally modulate their spontaneous [DA]ex. In particular, by only the second session of daily, hour-long training, mice increased the rate of impulses of [DA]ex, increased the amplitude of the impulses, and increased their tonic level of [DA]ex for a reward. Critically, mice learned to reliably elicit [DA]ex impulses prior to receiving a reward. These effects reversed when the reward was removed. We posit that spontaneous dopamine impulses may serve as a salient cognitive event in behavioral planning.
Importance: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood. Objective: To identify pathological CT features associated with adverse outcomes after mTBI. Design, Setting, and Participants: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021. Exposures: Acute nonpenetrating head trauma. Main Outcomes and Measures: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores
Over the last decade, nanoneedle-based systems have demonstrated to be extremely useful in cell biology. They can be used as nanotools for drug delivery, biosensing or biomolecular recognition inside cells; or they can be employed to select and sort in parallel a large number of living cells. When using these nanoprobes, the most important requirement is to minimize the cell damage, reducing the forces and indentation lengths needed to penetrate the cell membrane. This is normally achieved by reducing the diameter of the nanoneedles. However, several studies have shown that nanoneedles with a flat tip display lower penetration forces and indentation lengths. In this work, we have tested different nanoneedle shapes and diameters to reduce the force and the indentation length needed to penetrate the cell membrane, demonstrating that ultra-thin and sharp nanoprobes can further reduce them, consequently minimizing the cell damage.