scholarly journals Loss of diffuse noxious inhibitory control after traumatic brain injury in rats: A chronic issue

2020 ◽  
Vol 333 ◽  
pp. 113428
Author(s):  
Karen-Amanda Irvine ◽  
Peyman Sahbaie ◽  
Adam R. Ferguson ◽  
J. David Clark
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inhibitory Control ◽  
Diffuse Noxious Inhibitory Control

CGRP monoclonal antibody prevents the loss of diffuse noxious inhibitory controls (DNIC) in a mouse model of post-traumatic headache

Cephalalgia ◽  
2021 ◽  
pp. 033310242098168
Author(s):  
Caroline M Kopruszinski ◽  
Joelle M Turnes ◽  
Juliana Swiokla ◽  
Troy J Weinstein ◽  
Todd J Schwedt ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inhibitory Control ◽  
Mild Traumatic Brain Injury ◽  
Pain Modulation ◽  
Diffuse Noxious Inhibitory Controls ◽  
Diffuse Noxious Inhibitory Control ◽  
Cutaneous Allodynia ◽  
Calcitonin Gene ◽  
Post Traumatic

Aim Determine the role of calcitonin-gene related peptide in promoting post-traumatic headache and dysregulation of central pain modulation induced by mild traumatic brain injury in mice. Methods Mild traumatic brain injury was induced in lightly anesthetized male C57BL/6J mice by a weight drop onto a closed and unfixed skull, which allowed free head rotation after the impact. We first determined possible alterations in the diffuse noxious inhibitory controls, a measure of net descending pain inhibition called conditioned pain modulation in humans at day 2 following mild traumatic brain injury. Diffuse noxious inhibitory control was assessed as the latency to a thermally induced tail-flick that served as the test stimulus in the presence of right forepaw capsaicin injection that provided the conditioning stimulus. Post-traumatic headache-like behaviors were assessed by the development of cutaneous allodynia in the periorbital and hindpaw regions after mild traumatic brain injury. We then determined if intraperitoneal fremanezumab, an anti-calcitonin-gene related peptide monoclonal antibody or vehicle administered 2 h after sham or mild traumatic brain injury induction could alter cutaneous allodynia or diffuse noxious inhibitory control responses on day 2 post mild traumatic brain injury. Results In naïve and sham mice, capsaicin injection into the forepaw elevated the latency to tail-flick, reflecting the antinociceptive diffuse noxious inhibitory control response. Periorbital and hindpaw cutaneous allodynia, as well as a loss of diffuse noxious inhibitory control, was observed in mice 2 days after mild traumatic brain injury. Systemic treatment with fremanezumab blocked mild traumatic brain injury-induced cutaneous allodynia and prevented the loss of diffuse noxious inhibitory controls in mice subjected to a mild traumatic brain injury. Interpretation Sequestration of calcitonin-gene related peptide in the initial stages following mild traumatic brain injury blocked the acute allodynia that may reflect mild traumatic brain injury-related post-traumatic headache and, additionally, prevented the loss of net descending inhibition within central pain modulation pathways. As loss of conditioned pain modulation has been linked to multiple persistent pain conditions, dysregulation of descending modulatory pathways may contribute to the persistence of post-traumatic headache. Additionally, evaluation of the conditioned pain modulation/diffuse noxious inhibitory controls response may serve as a biomarker of vulnerability for chronic/persistent pain. These findings suggest that early anti-calcitonin-gene related peptide intervention has the potential to be effective both for the treatment of mild traumatic brain injury-induced post-traumatic headache, as well as inhibiting mechanisms that may promote post-traumatic headache persistence.

scholarly journals Executive Function Training in Chronic Traumatic Brain Injury Patients: Study Protocol

2019 ◽  
Author(s):  
Daniel Krawczyk ◽  
Kihwan Han ◽  
David Martinez ◽  
Jelena Rakic ◽  
Matthew Kmiecik ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Working Memory ◽  
Executive Function ◽  
Brain Injury ◽  
Executive Functions ◽  
Inhibitory Control ◽  
Cognitive Rehabilitation ◽  
Daily Life ◽  
Chronic Phase ◽  
Post Injury

Abstract Background: Some individuals who sustain traumatic brain injuries (TBIs) continue to experience significant cognitive impairments chronically (months-to-years post-injury). Many tests of executive function are insensitive to these executive function impairments, as such impairments may only appear during complex daily life conditions. Daily life often requires us to divide our attention and focus on abstract goals. In the current study, we compare the effects of two one-month electronic cognitive rehabilitation programs for individuals with chronic TBI. The active program (Expedition: Strategic Advantage) focuses on improving goal-directed executive functions including working memory, planning, long-term memory, and inhibitory control by challenging participants to accomplish life-like cognitive simulations. The challenge level of the simulations increase in accordance with participant achievement. The control intervention (Expedition: Informational Advantage) is identical to the active; however, the cognitive demand level is capped preventing participants from advancing beyond a set level. We will evaluate these interventions with a military veteran TBI population. Methods: One hundred individuals will be enrolled in this double-blinded clinical trial (all participants and testers are blinded to condition). Each individual will be randomly assigned to one of two interventions. The primary anticipated outcomes are improvement of daily life cognitive function skills and daily life functions. These are measured by a daily life performance task, which tests cognitive skills, and a survey that evaluates daily life functions. Secondary outcomes are also predicted to include improvements in working memory, attention, planning, and inhibitory control as measured by a neuropsychological test battery. Lastly, neuroimaging measures will be used to evaluate changes in brain networks supporting cognition pre-intervention and post-intervention. Discussion: We will test whether electronically delivered cognitive rehabilitation aimed at improving daily life functional skills will provide cognitive and daily life functional improvements for individuals in the chronic phase of TBI recovery (greater than three months post-injury). We aim to better understand the cognitive processes involved in recovery and the characteristics of individuals most likely to benefit. This study will also address the potential to observe generalizability, or transfer, from a software-based cognitive training tool toward daily life improvement. Trial Registration: ClinicalTrials.gov Identifier: NCT03704116 (retrospectively registered) https://clinicaltrials.gov/ct2/show/NCT03704116?term=tbi+krawczyk&rank=1 Keywords: Cognitive rehabilitation, traumatic brain injury, executive functions, daily life functions, memory, attention, planning. Support: Joint Warfighter Program; U. S. Dept. of Defense W81XWH-16-1-0053

scholarly journals Lasting deficit in inhibitory control with mild traumatic brain injury

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Benjamin Xu ◽  
Marco Sandrini ◽  
Sarah Levy ◽  
Rita Volochayev ◽  
Oluwole Awosika ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inhibitory Control ◽  
Mild Traumatic Brain Injury

scholarly journals The Effects of Pediatric Traumatic Brain Injury on Verbal and Visual-Spatial Working Memory

2011 ◽  
Vol 18 (1) ◽  
pp. 29-38 ◽  
Author(s):  
Stephanie Gorman ◽  
Marcia A. Barnes ◽  
Paul R. Swank ◽  
Mary Prasad ◽  
Linda Ewing-Cobbs
Keyword(s):  
Traumatic Brain Injury ◽  
Working Memory ◽  
Brain Injury ◽  
Inhibitory Control ◽  
Dual Task ◽  
Spatial Working Memory ◽  
Pediatric Traumatic Brain Injury ◽  
Visual Spatial ◽  
Intrusion Errors ◽  
Visual Spatial Working Memory

AbstractThe purpose of this study was to investigate the effects of pediatric traumatic brain injury (TBI) on verbal and visual-spatial working memory (WM). WM tasks examined memory span through recall of the last item of a series of stimuli. Additionally, both verbal and visual-spatial tests had a dual-task condition assessing the effect of increasing demands on the central executive (CE). Inhibitory control processes in verbal WM were examined through intrusion errors. The TBI group (n= 73) performed more poorly on verbal and visual-spatial WM tasks than orthopedic-injured children (n= 30) and non-injured children (n= 40). All groups performed more poorly on the dual-task conditions, reflecting an effect of increasing CE load. This effect was not greater for the TBI group. There were no group differences in intrusion errors on the verbal WM task, suggesting that problems in WM experienced by children with TBI were not primarily due to difficulties in inhibitory control. Finally, injury-related characteristics, namely days to follow commands, accounted for significant variance in WM performance, after controlling for relevant demographic variables. Findings suggest that WM impairments in TBI are general rather than modality-specific and that severity indices measured over time are better predictors of WM performance than those taken at a single time point. (JINS, 2012,18, 29–38)

scholarly journals Cognitive decline and mortality in a community-based sample of homeless and precariously housed adults: 9-year prospective study

BJPsych Open ◽  
2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Kristina M. Gicas ◽  
Andrea A. Jones ◽  
Allen E. Thornton ◽  
Anna Petersson ◽  
Emily Livingston ◽  
...  
Keyword(s):  
Risk Factors ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Alcohol Dependence ◽  
Inhibitory Control ◽  
Verbal Learning ◽  
Study Entry ◽  
Community Based ◽  
Cognitive Ageing ◽  
Risk Of Mortality

Background Homeless and precariously housed individuals experience a high burden of comorbid illnesses, and excess mortality. Cross-sectional studies report a high rate of cognitive impairment. Long-term trajectories have not been well investigated in this group. Aims To longitudinally assess risks for premature and/or accelerated cognitive ageing, and the relationship with early mortality in homeless and precariously housed people. Method This is a 9-year community-based study of 375 homeless and precariously housed individuals from Vancouver, Canada. Annual cognitive testing assessed verbal learning and memory, and inhibitory control. Linear mixed-effects models examined associations between clinical risk factors (traumatic brain injury, psychotic disorders, viral exposure, alcohol dependence) and cognitive change over 9 years. Cox regression models examined the association between cognition and mortality. Results Traumatic brain injury and alcohol dependence were associated with decline in verbal memory. Inhibitory control declined, independent of risk factors and to a greater extent in those who died during the study. Better inhibitory control was associated with a 6.6% lower risk of mortality at study entry, with a 0.3% greater effect for each year of life. For each one-point increase in the Charlson Comorbidity Index score at study entry, the risk of mortality was 9.9% higher, and was consistent across age. Adjusting for comorbidities, inhibitory control remained a significant predictor of mortality. Conclusions Findings raise the possibility of a premature onset, and accelerated trajectory, of cognitive ageing in this group of homeless and precariously housed people. Traumatic brain injury, alcohol dependence and cognition could be treatment priorities.

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