Probabilistic normative maps of the corticospinal and cortico-reticulospinal tracts in streamline and volumetric formats.

Background: Normative maps of brain tracts are key tools for assessing the extent of tract injury and plasticity after brain lesions such as stroke. The conventional procedure for tract mapping reduces diffusion tractography streamlines to a volumetric image before warping them to a standard coordinate space. Unfortunately, this volumetric reduction discards information about tract connectivity across voxels, complicating estimation of tract injury from the resulting map.

Using a Robotic Device to Quantify the Impact of Conventional Gait Training on Ankle Proprioception After Stroke.

Ankle proprioception is important for gait control and is often impaired after stroke. It is currently unclear if conventional gait training can improve ankle proprioception. Here we used a novel robotic device, Ankle Measuring Proprioceptive Device (AMPD), to quantify key aspects of ankle proprioception before and after four weeks of gait training delivered to 24 individuals who were in the chronic phase of stroke.

The Relationship Between Stroke-Related Cognitive Impairment and Robotic Proprioceptive Assessment.

The interplay between proprioceptive and cognitive impairment following stroke is not well understood, along with the implications it may have on the design of robotic proprioception assessments. To examine the relationship between proprioceptive and cognitive impairments, we used a robotic device to measure ankle proprioception in 37 chronic stroke patients. Participants also completed the Montreal Cognitive Assessment (MoCA) and NIH stroke scale (NIHSS).

Changing genes, cells and networks to reprogram the brain after stroke.

Important advances have been made in reperfusion therapies for acute ischemic stroke. However, a majority of patients are either ineligible for or do not respond to treatments and continue to have considerable functional deficits. Stroke results in a pathological disruption of the neurovascular unit (NVU) that involves blood-brain barrier leakage, glial activation, neuronal damage and chronic inflammation, all of which create a microenvironment that hinders recovery.

Long-Term Outcomes of Vagus Nerve Stimulation Paired With Upper Extremity Rehabilitation After Stroke.

Background: Persistent upper extremity (UE) impairment is common after stroke. Durable treatment benefits for chronic ischemic stroke are needed. The purpose of this report is to determine the long-term effects of vagus nerve stimulation paired with rehabilitation on impairment, activity, and participation in people with UE impairment after ischemic stroke.

High-Dose, High-Intensity Stroke Rehabilitation: Why Aren't We Giving It?

Current doses and intensities of post-stroke rehabilitation therapy provided as “usual care” are paltry compared to the magnitudes needed to drive large behaviorally-relevant reductions in neurologic impairments. There is convergent evidence indicating that high dose, high intensity rehabilitation is effective for improving outcomes after stroke with large effect sizes compared to usual care. Here we highlight some of this evidence (focusing on studies of upper extremity motor rehabilitation) and then ask the simple question— why are we delivering high doses and intensities of rehabilitation in clinical practice? We contend that reasons for lack of implementation of high dose, high intensity rehabilitation have to do with questionable conceptual, ideological, and economic assumptions.

Gray matter morphology and pain-related disability in young adults with low back pain.

Structural neuroplasticity in the brain may contribute to the persistence of low back pain (LBP) symptoms and the disability associated with them. It is not known if structural adaptations are evident early in the lifespan in young adults with LBP. This study compared gray matter in cortical sensorimotor regions in young adults with and without persistent LBP and identified gray matter and clinical predictors of pain-related disability.

Dopaminergic Pathways in Neuroplasticity After Stroke and Vagus Nerve Stimulation.

Stroke remains a significant cause of disability worldwide. In addition to multidisciplinary rehabilitation approaches, various forms of technology, including vagus nerve stimulation, have emerged to facilitate neuroplasticity and, thereby, improve functional status after stroke. Vagus nerve stimulation was recently approved by the Food and Drug Administration, but questions remain regarding its mechanism of action.

Common Data Elements for Rehabilitation Research in Neurologic Disorders (NeuroRehab CDEs).

Objective: Common data elements (CDEs) help harmonize data collection across clinical trials and observational studies, allowing for cross-study and cross-condition comparisons. Although CDEs exist for multiple clinical conditions and diseases, this work was extended only recently to neurorehabilitation research.

Design: Subgroups of clinical neurorehabilitation investigators operationalized a domain definition, selected applicable CDEs from 23 existing National Institute of Neurological Disorders and Stroke (NINDS) CDE projects and National Institutes of Health (NIH) CDE repositories, and identified areas needing further development.

Parvalbumin interneurons regulate rehabilitation-induced functional recovery after stroke and identify a rehabilitation drug.

Motor disability is a critical impairment in stroke patients. Rehabilitation has a limited effect on recovery; but there is no medical therapy for post-stroke recovery. The biological mechanisms of rehabilitation in the brain remain unknown.

Wearable Body Sensors Integrated into a Virtual Reality Environment - A Modality for Automating the Rehabilitation of the Motor Control System.

Amidst the rising incidences of stroke and spinal cord injuries, this study introduces a Virtual Reality (VR) system integrated with wearable sensor-based motion capture technology to enhance rehabilitation and assessment of upper limb impairments. The proposed motion capture system utilizes Inertial Measurement Units (IMUs) engineered in a modular and portable fashion to best fit different rehabilitation needs of the motor control system. The wearable sensor system consists of 15 modules capable of capturing the entire human body motion, along with a pair of hand gloves including 11 miniature sensors measuring hand motion.

Evaluation of prototype multimodal resins using chromatographic separability.

This paper employs a previously developed high-throughput parallel batch adsorption screen with sequential salt step increases to rapidly investigate a set of prototype multimodal anion- (MMA) and cation-exchange (MMC) resins. Experiments were carried out using a model protein library with varying charge and hydrophobic characteristics at several pH conditions. Partition coefficients were calculated from the batch chromatograms and fed into a column (linear salt gradient) simulator to determine peak first moments (elution salt concentration).

Coupling high-throughput and modeling approaches to streamline early-stage process development for biologics.

Platforms have long been implemented for downstream process development of monoclonal antibodies (mAbs) to streamline development and reduce timelines. These platforms are also increasingly being used for other complex biologics modalities. While development has traditionally been conducted at the lab bench scale in a sequential manner, automated miniaturized and parallelized approaches like RoboColumns and resin plates have also been implemented for chromatographic screening.

Larger perivascular space volume fraction is associated with worse post-stroke sensorimotor outcomes: An ENIGMA analysis.

Background: Perivascular Spaces (PVS) are a marker of cerebral small vessel disease (CSVD) that are visible on brain imaging. Larger PVS has been associated with poor quality of life and cognitive impairment post-stroke. However, the association between PVS and post-stroke sensorimotor outcomes has not been investigated.

Greater lesion damage is bidirectionally related with accelerated brain aging after stroke.

Regional neuron loss following stroke can result in remote brain changes due to diaschisis and secondary brain atrophy. Whole brain changes post-stroke can be captured by the predicted brain age difference (brain-PAD), a neuroimaging-derived biomarker of global brain health previously associated with poorer chronic stroke outcomes. We hypothesized that greater lesion damage would be longitudinally associated with worsening brain-PAD during subacute stroke, and conversely, that poorer baseline brain-PAD would be associated with enlarged lesion damage.

Association that Neuroimaging and Clinical Measures Have with Change in Arm Impairment in a Phase 3 Stroke Recovery Trial.

Objective: Vagus nerve stimulation (VNS) paired with rehabilitation therapy improved motor status compared to rehabilitation alone in the phase III VNS-REHAB stroke trial, but treatment response was variable and not associated with any clinical measures acquired at baseline, such as age or side of paresis. We hypothesized that neuroimaging measures would be associated with treatment-related gains, examining performance of regional injury measures versus global brain health measures in parallel with clinical measures.

Methods: Baseline magnetic resonance imaging (MRI) scans in the VNS-REHAB trial were used to derive regional injury measures (extent of injury to corticospinal tract, the primary regional measure; plus extent of injury to precentral gyrus and postcentral gyrus; lesion volume; and lesion topography) and global brain health measures (degree of white matter hyperintensities, the primary global brain measure; plus volumes of cerebrospinal fluid, cortical gray matter, white matter, each thalamus, and total brain).

Development and Evaluation of a Real-Time Phase-Triggered Stimulation Algorithm for the CorTec Brain Interchange.

With the development and characterization of biomarkers that may reflect neural network state as well as a patient's clinical deficits, there is growing interest in more complex stimulation designs. While current implantable neuromodulation systems offer pathways to expand the design and application of adaptive stimulation paradigms, technological drawbacks of these systems limit adaptive neuromodulation exploration. In this paper, we discuss the implementation of a phase-triggered stimulation paradigm using a research platform composed of an investigational system known as the CorTec Brain Interchange (CorTec GmbH, Freiburg, Germany), and an open-source software tool known as OMNI-BIC.

In silico mediated workflow for rapid development of downstream processing: Orthogonal product-related impurity removal for a Fc-containing therapeutic.

Therapeutic formats derived from the monoclonal antibody structure have been gaining significant traction in the biopharmaceutical market. Being structurally similar to mAbs, most Fc-containing therapeutics exhibit product-related impurities in the form of aggregates, charge variants, fragments, and glycoforms, which are inherently challenging to remove. In this work, we developed a workflow that employed rapid resin screening in conjunction with an in silico tool to identify and rank orthogonally selective processes for the removal of product-related impurities from a Fc-containing therapeutic product.

Mesenchymal Stromal Cell Implants for Chronic Motor Deficits After Traumatic Brain Injury: Post Hoc Analysis of a Randomized Trial.

Background And Objectives: Traumatic brain injury (TBI) is frequently characterized by chronic motor deficits. Therefore, this clinical trial assessed whether intracranial implantation of allogeneic modified mesenchymal stromal (SB623) cells can improve chronic motor deficits after TBI.

Methods: Post hoc analysis of the double-blind, randomized, prospective, surgical sham-controlled, phase 2, STEMTRA clinical trial (June 2016 and March 2019) with 48 weeks of follow-up was conducted.

Altered brain function during movement programming is linked with motor deficits after stroke: a high temporal resolution study.

Introduction: Stroke leads to motor deficits, requiring rehabilitation therapy that targets mechanisms underlying movement generation. Cortical activity during the planning and execution of motor tasks can be studied using EEG, particularly via the Event Related Desynchronization (ERD). ERD is altered by stroke in a manner that varies with extent of motor deficits.

EEG Provides Insights Into Motor Control and Neuroplasticity During Stroke Recovery.

In many branches of medicine, treatment is guided by measuring its effects on underlying physiology. In this regard, the efficacy of rehabilitation/recovery therapies could be enhanced if their administration was guided by measurements that directly capture treatment effects on neural function. Measures of brain function via EEG may be useful toward this goal and have advantages such as ease of bedside acquisition, safety, and low cost.