Ethical Considerations in Chronic Brain Injury.

Introduction: Chronic traumatic brain injury (cTBI) is associated with long-term cognitive, emotional, and functional impairments. It presents significant diagnostic and therapeutic challenges. Few studies have examined the effectiveness of artificial intelligence (AI) models and advanced diffusion imaging metrics to predict treatment outcomes in cTBI. This study investigated whether hybrid diffusion imaging (HYDI), a technique that employs multiple diffusion analyses, including diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), can identify imaging biomarkers predictive of treatment response. Methods: We prospectively enrolled 41 patients with cTBI who underwent HYDI scans at two timepoints. Neuropsychological outcomes were classified as favorable (clinical improvement) or unfavorable (no improvement or worsening). We assessed 6 diffusion metrics across 20 white matter regions using partial correlation analysis and 5 different AI algorithms. Outcome prediction models were trained and evaluated using k-fold cross-validation to ensure generalizability. Results: Results revealed significantly greater post-treatment changes in NODDI indices compared with DTI indices. In particular, regional changes in axonal density showed strong correlations with improvements in cognitive function. AI models incorporating both DTI and NODDI metrics showed promise for the prediction of the Mayo-Portland Adaptability Inventory, an assessment of postinjury adjustment in daily life and community reintegration. Overall, this study highlights the potential of HYDI-derived diffusion metrics, especially NODDI, as promising biomarkers for tracking microstructural changes and predicting therapeutic outcomes in cTBI. These findings support the use of advanced diffusion imaging and AI to inform treatment strategies and monitor recovery in patients with chronic brain injury.

For a significant percentage of subjects, with chronic traumatic brain injury (TBI), who report persisting cognitive impairment and functional loss, the diagnosis is often impeded by the fact that routine neuroimaging often does not reveal any abnormalities. In this paper, we used diffusion tensor imaging (DTI) to investigate the apparently normal white matter (as assessed by routine magnetic resonance imaging) in the brains of 19 subjects with sub-acute (9) and chronic (10) TBI. We also assessed memory, executive function, and visual-motor coordination in these subjects. Using a voxel-wise approach, we investigated if parameters of diffusion were significantly different between TBI subjects and 17 healthy controls (HC), who were demographically matched to the TBI group. We also investigated if changes in DTI parameters were associated with neuropsychological performance in either group. Our results indicate significantly increased mean and axial diffusivity (MD and AD, respectively) values in widespread brain locations in TBI subjects, while controlling for age, sex, and time since injury. HC performed significantly better than the TBI subjects on tests of memory and executive function, indicating the persisting functional loss in chronic TBI. We found no correlation between diffusion parameters and performance on test of executive function in either group. We found negative correlation between FA and composite memory scores, and positive correlation between RD and visuomotor coordination test scores, in various tracts in both groups. Our study suggests that changes in MD and AD can indicate persisting micro-structure abnormalities in normal-appearing white matter in the brains of subjects with chronic TBI. Our results also suggest that FA in major white matter tracts is correlated with memory in health and in disease, alike; larger and longitudinal studies are needed to discern potential differences in these correlations in the two groups.

BackgroundBrain injuries resulting from motor vehicle accidents and falls, as well as hypoxic insults and other conditions, are one of the leading causes of disability and death in the world. Current treatments are limited but include continuous rehabilitation, especially for chronic brain injury. Recent studies have demonstrated that the intravenous infusion of mesenchymal stem cells (MSCs) has therapeutic efficacy for several neurological diseases, including stroke and spinal cord injury.ObjectiveThe objective of our investigator-initiated clinical trial is to assess the safety and potential efficacy of the intravenous infusion of autoserum-expanded autologous MSCs for patients with chronic brain injury.MethodsThe (phase 2) trial will be a single-arm, open-label trial with the primary objective of confirming the safety and efficacy of autoserum-expanded autologous MSCs (STR-01; produced under good manufacturing practices) when administered to patients with chronic brain injury. The estimated number of enrolled participants is 6 to 20 patients with a modified Rankin Scale grade of 3 to 5. The assessment of safety and the proportion of cases in which the modified Rankin Scale grade improves by 1 point or more at 180 days after the injection of STR-01 will be performed after MSC infusion.ResultsWe received approval for our clinical trial from the Japanese Pharmaceuticals and Medical Devices Agency on December 12, 2017. The trial will be completed on June 11, 2023. The registration term is 5 years. The recruitment of the patients for this trial started on April 20, 2018, at Sapporo Medical University Hospital in Japan.ConclusionsOur phase 2 study will aim to address the safety and efficacy of the intravenous infusion of MSCs for patients with chronic brain injury. The use of STR-01 has been performed for patients with cerebral infarction and spinal cord injury, providing encouraging results. The potential therapeutic efficacy of the systemic administration of autoserum-expanded autologous MSCs for chronic brain injury should be evaluated, given its safety and promising results for stroke and spinal cord injury.Trial RegistrationJapan Medical Association Center for Clinical Trials JMA-IIA00333; https://tinyurl.com/nzkdfnbcInternational Registered Report Identifier (IRRID)DERR1-10.2196/37898

Hi reddit! In honor of the Super Bowl yesterday, we have assembled a panel of clinicians and researchers who specialize in the study of traumatic brain injury (often referred to as concussions). TBI is of growing interest to researchers, especially with questions surrounding the effects of chronic (repeated) injuries. Recent autopsies of deceased professional football players have found evidence of chronic traumatic encephalopathy, a neurodegenerative disease thought to be caused by chronic TBI. TBI is also a problem in other groups as well. Military members are often at risk of TBI– between 2000 and 2012, there were over 310,000 reported TBIs in active duty military serving in Middle Eastern combat theaters. Likewise, in the general population, children and older adults experience the highest rates of TBI (according to recent data from the Centers for Disease Control). If you have ever had questions about head injury, or some of the long-term outcomes of head injury, now is the time to ask! The panel we have assembled represent expertise in pediatric, sports-related, military-related, and chronic brain injury. Our panel includes: Dr. Robert Stern (u/RobertAStern) - I am a Professor of Neurology, Neurosurgery, and Anatomy & Neurobiology at Boston University (BU) School of Medicine, where I am also Director of the Clinical Core of the BU Alzheimer’s Disease Center. My primary area of research is chronic traumatic encephalopathy (CTE) and the long-term effects of repetitive head impacts in athletes. I am Co-Founder and Director of Clinical Research for the BU CTE Center, and I am proud to be the lead investigator of the DIAGNOSE CTE Research Project, a $16 million, 7-year grant (funded by the National Institutes of Health) for a multi-center, longitudinal study to develop methods of diagnosing CTE during life as well as examining potential risk factors of the disease. I have published over 160 peer-reviewed journal articles, as well as two new textbooks, including Sports Neurology. As a clinical neuropsychologist, I have also developed several commonly used cognitive, including the Neuropsychological Assessment Battery (NAB). Dr. Keith Yeates (u/KeithYeates) - Keith Yeates: I am a pediatric neuropsychologist by training. I hold the Ronald and Irene Ward Chair in Pediatric Brain Injury and am Professor and Head of the Department of Psychology at the University of Calgary in Alberta, Canada. I head the University’s Integrated Concussion Research Program. I have been doing clinical and research work on TBI in children for about 30 years. Dr. Elisabeth Wilde (u/LisaWildePhD) - I am an Associate Professor in the Department of Neurology at the University of Utah and an Associate Professor in the Departments of Physical Medicine and Rehabilitation, Neurology and Radiology at Baylor College of Medicine. I also hold an appointment as a Health Research Scientist in the US Veterans Affairs Health System (VA Salt Lake City Healthcare System). My research interests include the use of advanced forms of neuroimaging to enhance diagnosis and prognosis, monitor recovery and neurodegeneration, evaluate the efficacy of therapeutic intervention, and elucidate aspects of neuroplasticity in traumatic brain injury. As a clinical neuropsychologist, I have an interest in brain-behavior relationships involving cognitive, neurological, and functional outcome and clinical trials in traumatic brain injury and associated comorbidities. For the last 20 years, I have worked with patients with traumatic brain injury and concussion across a spectrum of age, severity, and acuity, with particular interests in children and adolescents, athletes, and Veteran and Active Duty Service Members with concussion or traumatic brain injury. I have participated in over 40 federally-funded clinical projects in TBI, and authored over 120 peer-reviewed publications. I am currently the Director of the Neuroimaging Core for the Department of Defense and Veterans Affairs co-funded Chronic Effects of Neurotrauma Consortium (CENC) Neuroimaging Core and has been actively involved in the International Common Data Elements (CDE) initiative and co-leads the Enhancing Neuroimaging Genetics Meta-analysis (ENIGMA) Working Group for TBI. Dr. Vicki Anderson (u/VickiAndersonPhD) - I am a clinical neuropsychologist at the University of Melbourne and Royal Children’s Hospital, Australia. My work spans clinical practice, research and teaching, with my focus being on children with acquired brain injury and their families. In particular, I am interested in the impact of environment and family on socio-emotional recovery, and on developing parent-based psychosocial interventions to optimise child recovery. Dr. Chris Giza (u/grizwon) - I graduated from Dartmouth College, received my M.D. from West Virginia University and completed my training in Neurology at UCLA. Then I worked on the Yosemite Search and Rescue team before joining the UCLA Brain Injury Research Center in 1998. I served on the California State Athletic Commission from 2005-2015, and traveled to Afghanistan in 2011 as a civilian advisor to the Department of Defense. I founded and direct the UCLA Steve Tisch BrainSPORT program, and serve as Medical Director for the Operation MEND-Wounded Warrior Project mild TBI program. I co-authored concussion / mild TBI guidelines for the American Academy of Neurology, Centers for Disease Control and the Concussion in Sport Group (Berlin guidelines), and have been a clinical consultant for the NFL, NHL/NHLPA, NBA, MLB and Major League Soccer. I am a Professor of Pediatric Neurology and Neurosurgery at the David Geffen School of Medicine and UCLA Mattel Children’s Hospital.

Adverse childhood experiences in adults with chronic traumatic brain injury: Support for a life course approach to brain injury rehabilitation

BackgroundA traumatic brain injury (TBI) event is a devastating injury to the brain that may result in heightened inflammation, neurodegeneration, and subsequent cognitive and mood deficits. TBI victims with co-morbidities such as heart disease, diabetes, or obesity may be more vulnerable to the secondary brain injury that follows the initial insult. Compared to lean individuals, obese subjects tend to have worse clinical outcomes and higher mortality rates after trauma.MethodsTo elucidate whether obesity predisposes individuals to worse outcomes after TBI, we subjected adult lean and obese male/female mice to a mild TBI. The injury was administered using a controlled skull impact (CSI) device. Lean or obese 6-month-old C57 BL/6 mice were subjected once to a mild TBI. Additionally, at day 30 after injury, both the lean and obese mice were tested for increased anxiety using the open field test.ResultsAt day 30 after TBI, compared to the lean mice, we found heightened microglial (MG) activation in the cerebral cortex, corpus callosum, and hypothalamus. Another compelling finding was that, compared to the non-injured obese male control mice, the obese TBI mice had a decrease in the rate of weight gain and serum corticosterone levels at day 30 after injury. Additionally, the injured obese mice displayed higher levels of anxiety as determined by a significant decrease in time spent in the non-peripheral zones in the open field test. In contrast to the obese males, the obese female mice did not exhibit increases in the number of active MG in the brain, changes in weight gain/corticosterone levels, or increased anxiety at day 30 after TBI.ConclusionsThe data presented here suggests that obese mice have worse outcomes compared to lean mice after mild TBI. Also, the obese males have worse outcomes than the injured female mice. This data may explain the sequela of chronic secondary brain injury in obese adults after a single mild TBI. Also, this report may help shape how the overweight/obese populations are monitored over the days and months following a TBI.

High-Level Mobility in Chronic Traumatic Brain Injury and Its Relationship With Clinical Variables and Magnetic Resonance Imaging Findings in the Acute Phase

BackgroundCognitive impairment associated with mild-to-moderate chronic traumatic brain injury (TBI) presents substantial challenges for which the functionality of the brain glymphatic system is a key area of interest. This study aimed to explore the functionality of the brain glymphatic system in patients with chronic cognitive impairment following mild-to-moderate TBI using diffusion tensor image analysis along the perivascular space (DTI-ALPS).MethodsThis was a prospective cross-sectional study. A total of 56 patients with mild-to-moderate chronic TBI at the Radiology Outpatient Clinic of the First Affiliated Hospital of Hainan Medical University were enrolled in the study between January 2021 and July 2022. Additionally, 20 healthy control (HC) subjects were recruited from the Health Screening Center during the same period as the HC group. Relevant clinical data for all the participants were collected, and cognitive assessments were conducted using cognitive scales. The TBI patients were categorized into the traumatic brain injury cognitive impairment (TBI-CI) and traumatic brain injury cognitively normal (TBI-CN) groups based on their of the Chinese Version of the Montreal Cognitive Assessment-Basic (MoCA-BC) scores. Each group comprised 20 subjects. All three groups of participants underwent diffusion tensor imaging (DTI). The DTI data were processed and analyzed using the MRIcron and FMRIB Software Library (FSL) toolboxes, and the analysis along the perivascular space (ALPS) index was calculated. Differences in the ALPS index among the three groups were examined by an analysis of covariance, adjusted for age and gender. A corrected receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic performance of the ALPS index in identifying patients with traumatic chronic cognitive impairment.ResultsCompared with the HC group, both the mild-to-moderate TBI patients with and without cognitive impairment had a decreased ALPS index (HC vs. TBI-CI: 1.629 vs. 1.302, P<0.001; HC vs. TBI-CN: 1.629 vs. 1.523, P=0.003). Moreover, the decrease in the ALPS index was more significant in the mild-to-moderate TBI patients with cognitive impairment (TBI-CN vs. TBI-CI: 1.523 vs. 1.302, P<0.001). The adjusted ROC curve analysis revealed that the area under the curve (AUC) of the ALPS index for diagnosing traumatic chronic cognitive impairment was 0.983 [95% confidence interval (CI): 0.953–1, P<0.001], with a sensitivity of 90% and specificity of 95%.ConclusionsCognitive impairment in patients with mild-to-moderate chronic TBI may be associated with impairment of the glymphatic system. Additionally, the ALPS index may serve as a potential predictor of the disease. Our findings provide some novel insights into the pathophysiological mechanisms underlying cognitive impairment in mild-to-moderate chronic TBI.

Primary objective: To determine if individuals with brain injury can modify heart rate variability (HRV) through biofeedback and, if so, enhance its pattern to improve emotional regulation and problem-solving ability.Design: A quasi-experimental design with repeated measures was employed. Thirteen individuals aged 23–63 years with severe brain injury (13–40 years post-onset) participating in a community-based programme were enrolled.Main outcomes: Response-to-treatment was measured with HRV indices, Behavior Rating Inventory of Executive Function (BRIEF-A-Informant) and attention/problem-solving tests.Results: At post-treatment, HRV indices (Low Frequency/High Frequency [LF/HF] and coherence ratio) increased significantly. Increased LF/HF values during the second-half of a 10-minute session were associated with higher attention scores. Participants who scored better (by scoring lower) in informant ratings at pre-treatment had highest HRV scores at post-treatment. Accordingly, at post-treatment, families’ ratings of participants’ emotional control correlated with HRV indices; staffs’ ratings of participants’ working memory correlated with participants’ HRV indices. Self-ratings of the BRIEF-A Task Monitoring scale at post-treatment correlated with family ratings at pre-treatment and post-treatment.Conclusions: Results demonstrate an association between regulation of emotions/cognition and HRV training. Individuals with severe, chronic brain injury can modify HRV through biofeedback. Future research should evaluate the efficacy of this approach for modifying behavioural problems.

Huanglian-Jie-Du-Tang (HJDT) is a traditional Chinese herbal formula which is widely used clinically. In this study, we investigated the effects of an aqueous (HJDTaq) and an ethanolic (HJDTet) extract of HJDT on chronic brain injury after focal cerebral ischemia in mice. The ischemia was induced by occlusion of the right middle cerebral artery for 30 min. HJDTaq (4 g/kg) and HJDTet (200, 400, 800 mg/kg) were orally administered for 21 d from day 7 before ischemia to day 14 after ischemia. The survival rate decreased to less than 50% at 35 d after ischemia. HJDTet at 400 mg/kg increased the survival rate. HJDTaq (4 g/kg) and HJDTet (400, 800 mg/kg) significantly attenuated the neurological dysfunction, brain atrophy and infarct volume after ischemia. There were few cells positive for CD31, hypoxia-inducible-factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and Flk-1 in the sham control. After ischemia, the number increased. HJDTaq (4 g/kg) and HJDTet (400 or 800 mg/kg) further increased the numbers of CD31, HIF-1α, VEGF and Flk-1-positive cells in the ischemic hemisphere. We conclude that HJDTaq and HJDTet have neuroprotective effects on chronic brain injury after focal cerebral ischemia and lead to accelerated angiogenesis by HIF-1α-regulated VEGF signaling.

This study aimed to investigate the effects of enriched environment (EE) on promoting angiogenesis and neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI) brain injury. HI brain damage was induced in seven day-old CD-1® mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min). At six weeks of age, the mice were randomly assigned to either EE or standard cages (SC) for two months. Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. In order to identify angiogenic growth factors regulated by EE, an array-based multiplex ELISA assay was used to measure the expression in frontal cortex, striatum, and cerebellum. Among the growth factors, the expression of fibroblast growth factor-2 (FGF-2) was confirmed using western blotting. Platelet endothelial cell adhesion molecule-1 (PECAM-1) and α-smooth muscle actin (α-SMA) were also evaluated using immunohistochemistry. As a result, mice exposed to EE showed significant improvements in rotarod and ladder walking performances compared to SC controls. The level of FGF-2 was significantly higher in the frontal cortex of EE mice at 8 weeks after treatment in multiplex ELISA and western blot. On the other hand, FGF-2 in the striatum significantly increased at 2 weeks after exposure to EE earlier than in the frontal cortex. Expression of activin A was similarly upregulated as FGF-2 expression pattern. Particularly, all animals treated with FGF-2 neutralizing antibody abolished the beneficial effect of EE on motor performance relative to mice not given anti-FGF-2. Immunohistochemistry showed that densities of α-SMA+ and PECAM-1+ cells in frontal cortex, striatum, and hippocampus were significantly increased following EE, suggesting the histological findings exhibit a similar pattern to the upregulation of FGF-2 in the brain. In conclusion, EE enhances endogenous angiogenesis and neurobehavioral functions mediated by upregulation of FGF-2 in chronic hypoxic-ischemic brain injury.

Impaired attention is one of the most common, debilitating, and persistent consequences of traumatic brain injury (TBI), which impacts overall cognitive and executive functions in these patients. Previous neuroimaging studies, trying to understand the neural mechanism underlying attention impairment post TBI, have highlighted the role of prefrontal white matter tracts in attentional functioning in mild TBI (mTBI). Goal-Oriented Attentional Self-Regulation (GOALS) is a cognitive rehabilitation training program that targets executive control functions in participants by applying mindfulness-based attention regulation and goal management strategies. GOALS training has been demonstrated to improve attention and executive functioning in patients with chronic TBI. However, its impact on microstructural integrity of attention-associated prefrontal white matter tracts is still unclear. Here, using diffusion magnetic resonance imaging in a pilot randomized controlled trial, we investigated the effect of GOALS training on prefrontal white matter microstructure in 19 U.S. military veterans with chronic mTBI, compared with a matched control group of 14 veterans with chronic mTBI who received standard of care brain health education. We also tested for an association between microstructural white matter changes and sustained attention ability in these patients pre- and post-GOALS training. Our results show significantly better white matter microstructural integrity in left and right anterior corona radiata (ACR) in the GOALS group compared with the control group post-training. Moreover, we found a significant correlation between sustained attention ability of GOALS training participants and white matter integrity of their right ACR pre- and post-training. Finally, our findings indicated that the improved white matter integrity of the ACR in GOALS training participants was the result of increased neurite density and decreased fiber orientation dispersion within this tract.

(1) Background: Traumatic brain injury (TBI) is caused from rapid head acceleration/deceleration, focal blows, blasts, penetrating forces, and/or shearing forces, whereas hypoxic-anoxic injury (HAI) is caused through oxygen deprivation events, including strangulation. Most service-seeking domestic violence (DV) survivors have prior mechanistic exposures that can lead to both injuries. At the time of our study, some evidence existed about the exposure to both injuries over the course of a survivor's lifetime from abuse sources, yet little was known about their co-occurrence to the same survivor within the same episode of physical intimate partner violence (IPV). To better understand the lived experience of service-seeking DV survivors and the context in which partner-inflicted brain injury (PIBI) is sustained, we sought to understand intentional brain injury (BI) exposures that may need to be addressed and accommodated in services. Our aims were to 1. characterize the lifetime co-occurrence of strangulation and intentional head trauma exposures from all abuse sources to the same survivor and within select physical episodes of IPV and 2. establish the lifetime prevalence of PIBI. (2) Methods: Survivors seeking DV services in the state of Ohio in the United States of America (U.S.) completed interview-administered surveys in 2019 (n = 47). Community-based participatory action approaches guided all aspects of the study development, implementation, and interpretation. (3) Results: The sample was primarily women. Over 40% reported having Medicaid, the government-provided health insurance for the poor. Half had less than a postsecondary education. Over 80% of participants presented to DV services with both intentional head trauma and strangulation exposures across their lifetime from intimate partners and other abuse sources (i.e., child abuse, family violence, peer violence, sexual assault, etc.), though not always experienced at the same time. Nearly 50% reported an experience of concurrent head trauma and strangulation in either the first or last physical IPV episode. Following a partner's attack, just over 60% reported ever having blacked out or lost consciousness-44% experienced a loss of consciousness (LOC) more than once-indicating a conservative estimate of a probable brain injury by an intimate partner. Over 80% of service-seeking DV survivors reported either a LOC or two or more alterations in consciousness (AICs) following an IPV attack and were classified as ever having a partner-inflicted brain injury. (4) Conclusions: Most service-seeking IPV survivors experience repetitive and concurrent exposures to abusive strangulation and head trauma through the life course and by intimate partners within the same violent event resulting in brain injury. We propose the use of the term partner-inflicted brain injury (PIBI) to describe the physiological disruption of normal brain functions caused by intentional, often concurrent and repeated, traumatic and hypoxic neurologic insults by an intimate partner within the context of ongoing psychological trauma, coercive control, and often past abuse exposures that could also result in chronic brain injury. We discuss CARE (Connect, Acknowledge, Respond, Evaluate), a brain-injury-aware enhancement to service delivery. CARE improved trauma-informed practices at organizations serving DV survivors because staff felt knowledgeable to address and accommodate brain injuries. Survivor behavior was then interpreted by staff as a "can't" not a "won't", and social and functional supports were offered.

Dizziness and imbalance are common symptoms during the acute phase of traumatic brain injury (TBI). However, there is evidence to suggest that these symptoms persist into the chronic phase of injury. Few prospective studies have examined the frequency and type of dizziness and imbalance in adults with chronic moderate-severe TBI. The aim of this preliminary analysis was to investigate the prevalence of these symptoms in adults with chronic moderate-severe TBI. Twenty-four adults with chronic moderate-severe TBI and a group of 19 age-, sex-, and education-matched noninjured comparison participants were recruited. Self-reported dizziness and imbalance were measured using a modified version of a standard case history form. Significant associations between group (TBI group or noninjured comparison [NC] participants) and self-reports of dizziness, imbalance, and related symptoms (endorsed "yes" or "no") were explored. The TBI group most reported lightheadedness (75%), vertigo (38%), and imbalance and/or falling (46%). The most common related symptom reported by the TBI group was headache (63%) and nausea (46%). Significant associations revealed that the TBI group responded "yes" in higher percentages than the NC group across all categories (dizziness, imbalance, and related symptoms). There were no statistically significant relationships among dizziness, imbalance, or headache symptoms within the TBI group. These preliminary findings suggest that dizziness and imbalance are prevalent in adults with chronic moderate-severe TBI. Persistent vertiginous symptoms may point to an underlying vestibular impairment. However, further research is needed to characterize vestibular function in chronic moderate-severe TBI.

Primary objective: The purpose of this study was to evaluate the effects of an errorless training approach, Spaced Retrieval (SR) training delivered over the telephone, on the reported everyday memory problems of adults with chronic traumatic brain injury (TBI).Research design: The study was a randomized controlled clinical trial.Methods: Thirty-eight participants received either SR training or didactic strategy instruction (SI). Participants in both groups identified three memory-related goals and were paired to receive the same total telephone contact time. The main outcome measures were frequency of reported memory problems and perceived quality of life.Results: Participants in the SR group reported significantly more treatment goal mastery/strategy use than those in the SI group, immediately and at 1-month post-training. Caregivers reported similarly significant between-groups differences in everyday use of treatment behaviours at 1 month. Both groups reported some generalized strategy use to other non-targeted behaviours and decreased frequency of reported memory problems, but there were no significant between-groups differences in participant or caregiver reports of generalized strategy use or reported memory problems at either time-point. There was no change in perceived quality of life in either group.Conclusions: SR treatment delivered by phone produced significantly more treatment goal mastery/strategy use and maintenance than SI; however, both treatments improved reported everyday memory functioning for persons with TBI, without significant group differences on measures of generalized strategy use or perceived quality of life.