No evidence for motor recovery-related cortical connectivity changes after stroke using resting-state fMRI

It has been proposed that a form of cortical reorganization (changes in functional connectivity between brain areas) can be assessed with resting-state (rs) fMRI. Here we report a longitudinal data-set collected from 19 patients with subcortical stroke and 11 controls. Patients were imaged up to five times over one year. We found no evidence, using rs-fMRI, for post-stroke cortical connectivity changes despite substantial behavioral recovery. These results could be construed as questioning the value of resting-state imaging. Here we argue instead that they are consistent with other emerging reasons to challenge the idea of motor recovery-related cortical reorganization post-stroke when conceived of as changes in connectivity between cortical areas.

Evaluating Implementation of the Behavioral Recovery Outreach (BRO) Team: One Year of Implementation

We present evaluation results after one year of implementation by nine BRO Teams. Monthly checklists documented consistent composition across teams: a psychologist, social worker and nurse. Social workers were recognized as having a critical role in implementation, serving as a referral source and liaison between the CLC, Veteran/family, and community facility. Early implementation focused on team and program development with barriers including unprotected time for Team members. In the first year, the nine teams enrolled 70 Veterans, discharging 86% to community facilities. Characteristics of the Veterans suggest Teams are reaching the complex Veteran targeted by the model. Barriers to successful discharge include community facility inexperience/training and confidence to manage complex residents. COVID emerged as the leading barrier to outreach to internal and external partners and providing transitional support to the Veteran after discharge. We discuss the impact of these preliminary findings on future implementation and dissemination of the model.

A Transitional Care Model for Veterans With Complex Needs During COVID: The Behavioral Recovery Outreach (BRO) Team

The Veterans Health Administration’s Care for Patients with Complex Problems (CP)2 Program developed a national infrastructure to disseminate promising practice models to improve care for Veterans with complex medical, mental health, and/or neurocognitive conditions, who may also have behaviors disruptive to care. A strategic priority is improving safe and effective transitions to community care for Veterans with complex care needs, many of whom have historically been limited to VA settings as a result of behavioral concerns. The Behavioral Recovery Outreach (BRO) Team was the first model identified for national dissemination and evaluation at partner sites. Developed at VA Central Iowa, BRO is an interdisciplinary team model that identifies Veterans in long-term VA care settings with complex care needs to engage in individualized behavioral programing to manage/stabilize behaviors and safely transition them to more appropriate and less costly community settings. This symposium will describe the BRO team model, highlight the facilitators and barriers to nationally disseminating the BRO model with VA partner facilities, discuss adaptations in continuing community transitions following the COVID-19 pandemic, and describe program outcomes. The first speaker will discuss development of the BRO model and outcomes of a regional dissemination. The second speaker will present results from the program evaluation of the national dissemination. The final speaker will describe BRO Team expansion and lessons learned from the perspective of a VA partner facility. The (CP)2 Program Director will integrate findings and highlight implications for scaling and evaluating promising models for national dissemination for policy, practice, and future research.

Rolling Out Behavioral Recovery Outreach (BRO) Teams: Perspectives From an Inaugural Partner Site

The Sioux Falls VA Community Living Center (CLC) is a partner site for the Behavioral Recovery Outreach (BRO) Team dissemination. This CLC is home to over 55 Veterans requiring a variety of specialty needs such as dementia care, short-term rehabilitation, respite, hospice, and/or psychosocial needs. Many of the Veterans followed by the BRO Team on the CLC experienced frequent rehospitalizations and difficult placement in the community due to behavioral concerns. Local leadership encouraged participation in the BRO Team dissemination due to the growing need in this VA system to open access to dementia and mental health care, successfully discharge Veterans to appropriate community settings, and reduce unnecessary rehospitalizations. This presentation will discuss BRO Team development, including several factors facilitating successful BRO Team implementation (e.g., leadership support, community outreach approaches, staff partner buy-in), and identify barriers impacting successful implementation with a case example to illustrate strategies to overcome such barriers.

The Behavioral Recovery Outreach (BRO) Team: A Transitional Care Model for Veterans With Complex Care Needs

In 2012, VA Central Iowa developed a novel program known as the Behavioral Recovery Outreach (BRO) Team to address unmet needs of our aging Veteran population with complex medical, psychological, neurocognitive and behavioral concerns. BRO Teams provide evidence-informed treatments in inpatient VA settings, and transitional care/support post-discharge to ensure successful placement and stability in the community. We will discuss how implementation science informed the expansion of this model from a local pilot to a nationally disseminated program. We will explore the challenges of ensuring program fidelity while fostering innovation and adaptation. Given the challenges of national dissemination, we will highlight the predicted and unforeseen aspects of program evaluation and policy implications. Finally, we will discuss the impacts of the COVID-19 pandemic on delivery of care methods and community-based interactions, as well as how this program has improved the lives and quality of care for this high-risk Veteran population.

Common and unique structural plasticity after left and right hemisphere stroke

Strokes to the left and right hemisphere lead to distinctive behavioral profiles. Are left and right hemisphere strokes (LHS and RHS) associated with distinct or common poststroke neuroplasticity patterns? Understanding this issue would reveal hemispheric neuroplasticity mechanisms in response to brain damage. To this end, we investigated poststroke structural changes (2 weeks to 3 months post-onset) using longitudinal MRI data from 69 LHS and 55 RHS patients and 31 demographic-matched healthy control participants. Both LHS and RHS groups showed statistically common plasticity independent of the lesioned hemisphere, including 1) gray matter (GM) expansion in the ipsilesional and contralesional precuneus, and contralesional superior frontal gyrus; 2) GM shrinkage in the ipsilesional medial orbital frontal gyrus and middle cingulate cortex. On the other hand, only RHS patients had significant GM expansion in the ipsilesional medial superior and orbital frontal cortex. Importantly, these common and unique GM changes post-stroke largely overlapped with highly-connected cortical hub regions in healthy individuals. Moreover, they correlated with behavioral recovery, indicating that post-stroke GM volumetric changes in cortical hubs reflect compensatory rather than maladaptive mechanisms. These results highlight the importance of structural neuroplasticity in hub regions of the cortex, along with the hemispheric specificity, for stroke recovery.

Trophoblast glycoprotein is a marker for efficient sorting of ventral mesencephalic dopaminergic precursors derived from human pluripotent stem cells

Successful cell therapy for Parkinson’s disease (PD) requires large numbers of homogeneous ventral mesencephalic dopaminergic (vmDA) precursors. Enrichment of vmDA precursors via cell sorting is required to ensure high safety and efficacy of the cell therapy. Here, using LMX1A-eGFP knock-in reporter human embryonic stem cells, we discovered a novel surface antigen, trophoblast glycoprotein (TPBG), which was preferentially expressed in vmDA precursors. TPBG-targeted cell sorting enriched FOXA2+LMX1A+ vmDA precursors and helped attain efficient behavioral recovery of rodent PD models with increased numbers of TH+, NURR1+, and PITX3+ vmDA neurons in the grafts. Additionally, fewer proliferating cells were detected in TPBG+ cell-derived grafts than in TPBG− cell-derived grafts. Our approach is an efficient way to obtain enriched bona fide vmDA precursors, which could open a new avenue for effective PD treatment.

The Atr-Chek1 pathway inhibits axon regeneration in response to Piezo-dependent mechanosensation

Atr is a serine/threonine kinase, known to sense single-stranded DNA breaks and activate the DNA damage checkpoint by phosphorylating Chek1, which inhibits Cdc25, causing cell cycle arrest. This pathway has not been implicated in neuroregeneration. We show that in Drosophila sensory neurons removing Atr or Chek1, or overexpressing Cdc25 promotes regeneration, whereas Atr or Chek1 overexpression, or Cdc25 knockdown impedes regeneration. Inhibiting the Atr-associated checkpoint complex in neurons promotes regeneration and improves synapse/behavioral recovery after CNS injury. Independent of DNA damage, Atr responds to the mechanical stimulus elicited during regeneration, via the mechanosensitive ion channel Piezo and its downstream NO signaling. Sensory neuron-specific knockout of Atr in adult mice, or pharmacological inhibition of Atr-Chek1 in mammalian neurons in vitro and in flies in vivo enhances regeneration. Our findings reveal the Piezo-Atr-Chek1-Cdc25 axis as an evolutionarily conserved inhibitory mechanism for regeneration, and identify potential therapeutic targets for treating nervous system trauma.