wellelabbackground.png

Publications

Vagus nerve stimulation drives selective circuit modulation through cholinergic reinforcement

Spencer Bowles, Jordan Hickman, Xiaoyu Peng, W. Ryan Williamson, Rongchen Huang, Kayden Washington, Dane Donegan, Cristin G. Welle

Vagus nerve stimulation (VNS) is a neuromodulation therapy for a broad and expanding set of neurologic conditions. However, the mechanism through which VNS influences central nervous system circuitry is not well described, limiting therapeutic optimization. . .

Closed-loop automated reaching apparatus (CLARA) for interrogating motor systems.

Bowles S, Williamson WR, Nettles D, Hickman J, Welle CG.

Closed-loop neuromodulation technology is a rapidly expanding category of therapeutics for a broad range of indications. Development of these innovative neurological devices requires high-throughput systems for closed-loop stimulation of model organisms, while monitoring physiological signals and complex, naturalistic behaviors. . .

Development and characterization of a chronic implant mouse model for vagus nerve stimulation.

Mughrabi IT, Hickman J, Jayaprakash N, Papadoyannis ES, Abbas A, Chang YC, Lee S, Datta-Chaudhuri T, Chang EH, Zanos TP, Froemke RC, Welle CG*, Al-Abed Y, Zanos S

Vagus nerve stimulation (VNS) suppresses inflammation and autoimmune diseases in preclinical and clinical studies. The underlying molecular, neurological, and anatomical mechanisms have been well characterized using acute electrophysiological stimulation of the vagus. . .

Motor Learning Promotes Remyelination via New and Surviving Oligodendrocytes.

Bacmeister CM, Barr HJ, McClain CR, Thorton MA, Nettles D, Welle CG, Hughes EG

Oligodendrocyte loss in neurological disease leaves axons vulnerable to damage and degeneration, and activity-dependent myelination may represent an endogenous mechanism to improve remyelination following injury. Here we report that, while learning a forelimb reach task transiently suppresses oligodendrogenesis, it subsequently increases oligodendrocyte precursor cell differentiation . . .

Longitudinal neural and vascular structural dynamics produced by chronic microelectrode implantation.

Welle CG, Gao Y, Ye M, Lozzi A, Boretsky A, Abliz E, Hammer DX

Implanted microelectrode arrays sense local neuronal activity, signals which are used as control commands for brain computer interface (BCI) technology. Patients with tetraplegia have used BCI technology to achieve an extraordinary degree of interaction with their local environment. However . . .

Innovations in electrical stimulation harness neural plasticity to restore motor function.

Peng XP, Hickman JL, Bowles SG, Donegan DC, Welle CG

Novel technology and stimulation paradigms allow for closed-loop implementation of neurostimulation systems with unprecedented spatiotemporal precision. In turn, precise, closed-loop neurostimulation appears to preferentially drive neural plasticity in motor networks, promoting neural repair. Recent clinical studies demonstrate that electrical stimulation . . .

Phantom-based evaluation of near-infrared intracranial hematoma detector performance.

Wang J, Chen Y, Welle CG, Pfefer T, Lin J

Near-infrared spectroscopy (NIRS) is emerging as a rapid, low-cost approach for point-of-care triage of hematomas resulting from traumatic brain injury. However, there remains a lack of standardized test methods for benchtop performance assessment of these devices and incomplete understanding of relevant light–tissue interactions. . .

Characterizing longitudinal changes in impedance spectra of in-vivo peripheral nerve electrodes.

Stratka MM, Schafer B, Vasudevan S, Welle CG, Reith L

Near-infrared spectroscopy (NIRS) is emerging as a rapid, low-cost approach for point-of-care triage of hematomas resulting from traumatic brain injury. However, there remains a lack of standardized test methods for benchtop performance assessment of these devices and incomplete understanding of relevant light–tissue interactions. . .

Advancing Science – how bias holds us back.

Asplund M and Welle CG

As scientists and engineers, we must recognize the overwhelming evidence that we each harbor bias that influences our professional decisions. Yet, solving today’s increasingly complex public health challenges requires diverse perspectives from multidisciplinary teams. . .

New Light on Gamma Oscillations.

Welle CG, Contreras D

Two papers in this issue of Neuron by Saleem et al. (2017) and Storchi et al. (2017) show that increases in background light intensity trigger proportional increases in narrowband gamma oscillations with a peak at 60 Hz in retina, lateral geniculate, and primary visual cortex of the mouse visual system. . .

Epidermal electrode technology for detecting ultrasonic perturbation of sensory brain activity.

Huang S, Fisher JAN, Ye M, Kim Y, Ma R, Nabili M, Krauthamer V, Myers M, Coleman TP, Welle CG

We found that cortical SSEPs recorded by flexible epidermal sensors were stimulus frequency dependent. Immediately following controlled, focal ultrasound perturbation, the sensors detected significant SSEP modulation, which consisted of dynamic amplitude decreases and altered stimulus-frequency dependence. These modifications were also . . .

Alterations in neurovascular coupling as noninvasive biomarkers for acute traumatic brain injury.

Jang H, Huang S, Hammer DX, Wang L, Ye M, Welle CG

Following acute traumatic brain injury (TBI), timely transport to a hospital can significantly improve the prognosis for recovery. There is, however, a dearth of quantitative biomarkers for brain injury that can be rapidly acquired and interpreted in active, field environments in which TBIs are frequently incurred. We explored potential functional indicators for TBI that can. . .

Rodent model for assessing the long term safety and performance of peripheral nerve recording electrodes.

Vasudevan S, Patel K, Welle CG

In the US alone, there are approximately 185 000 cases of limb amputation annually, which can reduce the quality of life for those individuals. Current prosthesis technology could be improved by access to signals from the nervous system for intuitive prosthesis control. After amputation, residual peripheral nerves continue to convey motor signals and electrical stimulation of these nerves can elicit sensory percepts. However, current . . .

Acute insertion effects of penetrating cortical microelectrodes imaged with quantitative optical coherence angiography.

Hammer DX, Lozzi A, Boretsky A, Welle CG

The vascular response during cortical microelectrode insertion was measured with amplitude decorrelation-based quantitative optical coherence angiography (OCA). Four different shank-style microelectrode configurations were inserted in murine motor cortex beneath a surgically implanted window in discrete steps while OCA images were collected and processed for angiography and flowmetry. Quantitative measurements included . . .

Real-Time Detection and Monitoring of Acute Brain Injury Utilizing Evoked Electroencephalographic Potentials

Fisher JAN, Huang S, Ye M, Nabili M, Wilent B, Myers M, Krauthamer V and Welle CG

Rapid detection and diagnosis of a traumatic brain injury (TBI) can significantly improve the prognosis for recovery. Helmet-mounted sensors that detect impact severity based on measurements of acceleration or pressure show promise for aiding triage and transport decisions in active . . .

Brain-Computer Interface Devices for Patients with Paralysis and Amputation: A Meeting Report.

Bowsher K, et al. (33 authors, Bowsher K and Welle CG, co-corresponding authors)

The Food and Drug Administration's (FDA) Center for Devices and Radiological Health (CDRH) believes it is important to help stakeholders (eg, manufacturers, health-care professionals, patients, patient advocates, academia, and other government agencies . . .

Tissue damage thresholds during therapeutic electrical stimulation.

Cogan SF, Ludwig KA, Welle CG, Takmakov P

For macroelectrodes, the potential for tissue damage is often assessed by comparing the intensity of stimulation, characterized by the charge density and charge per phase of a stimulus pulse, with a damage threshold identified through histological evidence from in vivo experiments as described by the Shannon equation. While the Shannon equation has proved useful in assessing the likely …

Spontaneous and sensory-driven gamma oscillations engage distinct cortical circuitry.

Welle CG, Contreras D

16 Gamma oscillations are a robust component of sensory responses but are also part of the 17 background spontaneous activity of the brain. To determine whether the properties of gamma 18 oscillations in cortex are specific to their mechanism of generation, we compared in mouse 19 visual cortex in vivo, the laminar geometry and single neuron rhythmicity of oscillations 20 produced during sensory representation with those . . .

Image quality metrics for optical coherence angiography

Lozzi A, Agrawal A, Boretsky A, Welle CG, Hammer DX

We characterized image quality in optical coherence angiography (OCA) en face planes of mouse cortical capillary network in terms of signal-to-noise ratio (SNR) and Weber contrast (W_c) through a novel mask-based segmentation method. . .

Rapid evaluation of the durability of cortical neural implants using accelerated aging with reactive oxygen species.

Takmakov P, Ruda K, Phillips SK, Isayeva IS, Krauthamer V, Welle CG

A challenge for implementing high bandwidth cortical brain–machine interface devices in patients is the limited functional lifespan of implanted recording electrodes. Development of implant technology currently requires extensive non-clinical testing to demonstrate device performance. . .

Longitudinal vascular dynamics following cranial window and electrode implantation measured with speckle variance optical coherence angiography.

Hammer DX, Lozzi A, Abliz E, Greenbaum N, Agrawal A, Krauthamer V, Welle CG

Speckle variance optical coherence angiography (OCA) was used to characterize the vascular tissue response from craniotomy, window implantation, and electrode insertion in mouse motor cortex. We observed initial vasodilation ~40% greater than original diameter 2-3 days post-surgery (dps). After 4 weeks, dilation subsided in large vessels (>50 µm diameter) but persisted in smaller vessels (25-50 µm diameter). Neovascularization began 8-12 dps and vessel migration continued throughout the study. Vasodilation and . . .

FDA Regulation of Invasive Neural Recording Electrodes.

Welle CG, Krauthamer V

The US Food and Drug Administration (FDA) is charged with assuring the safety and effectiveness of medical devices. Before any medical device can be brought to market, it must comply with all federal regulations regarding FDA processes for clearance or approval. Navigating the FDA regulatory process may seem like a daunting task to the innovator of a novel medical device who has little experience with the FDA regulatory process or device commercialization. . . .

Full list of publications can be found here