Traumatic brain injury as a chronic disease: insights from the United States Traumatic Brain Injury Model Systems Research Program.

Traumatic brain injury (TBI) is a global health priority, associated with substantial burden. Historically conceptualised as an injury event with finite recovery, TBI is now recognised as a chronic condition that can affect multiple domains of health and function, some of which might deteriorate over time. Many people who have had a TBI remain moderately to severely disabled at 5 years, are rehospitalised up to 10 years post-injury, and have a reduced lifespan relative to the general population. Understanding TBI as a chronic disease process can be highly informative for optimising care, which has traditionally focused on acute care. Chronic brain injury care models must be informed by a holistic understanding of long-term outcomes and the factors that can affect how care needs evolve over time. The United States Traumatic Brain Injury Model Systems of Care follows up individuals with moderate-to-severe TBI for over 30 years, allowing characterisation of the chronic (2-30 years or more post injury) functional, cognitive, behavioural, and social sequelae experienced by individuals who have had a moderate-to-severe TBI and the implications for their health and quality of life. Older age, social determinants of health, and lower acute functional status are associated with post-recovery deterioration, while younger age and greater functional independence are associated with risky health behaviours, including substance misuse and re-injury. Systematically collected data on long-term outcomes across multiple domains of health and function are needed worldwide to inform the development of models for chronic disease management, including the proactive surveillance of commonly experienced health and functional challenges.

Abnormal thalamic functional connectivity correlates with cardiorespiratory fitness and physical activity in progressive multiple sclerosis.

BACKGROUND: Altered thalamic volumes and resting state (RS) functional connectivity (FC) might be associated with physical activity (PA) and cardiorespiratory fitness (CRF) in people with progressive multiple sclerosis (PMS). OBJECTIVES: To assess thalamic structural and functional alterations and investigate their correlations with PA/CRF levels in people with PMS. METHODS: Seven-day accelerometry and cardiopulmonary exercise testing were used to assess PA/CRF levels in 91 persons with PMS. They underwent 3.0 T structural and RS fMRI acquisition with 37 age/sex-matched healthy controls (HC). Between-group comparisons of MRI measures and their correlations with PA/CRF variables were assessed. RESULTS: PMS people had lower volumes compared to HC (all p < 0.001). At corrected threshold, PMS showed decreased intra- and inter-thalamic RS FC, and increased RS FC between the thalamus and the hippocampus, bilaterally. At uncorrected threshold, decreased thalamic RS FC with caudate nucleus, cerebellum and anterior cingulate cortex (ACC), as well as increased thalamic RS FC with occipital regions, were also detected. Lower CRF, measured as peak oxygen consumption (VO2peak), correlated with lower white matter volume (r = 0.31, p = 0.03). Moreover, lower levels of light PA correlated with increased thalamic RS FC with the right hippocampus (r = - 0.3, p = 0.05). DISCUSSION: People with PMS showed widespread brain atrophy, as well as pronounced intra-thalamic and thalamo-hippocampal RS FC abnormalities. White matter atrophy correlated with CRF, while increased thalamo-hippocampal RS FC was associated to worse PA levels. Thalamic RS FC might be used to monitor physical impairment and efficacy of rehabilitative and disease-modifying treatments in future studies.

Task-Based and Resting-State Cortical Functional Differences After Spinal Cord Injury: A Pilot Functional Near-Infrared Spectroscopy Study.

Brain reorganization following spinal cord injury (SCI) has been well-established using animal and human studies. Yet, much is unknown regarding functional recovery and adverse secondary outcomes after SCI. Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique that offers methodological flexibility in a real-world setting. We used fNIRS to examine the cortical functional differences between 12 males with thoracolumbar SCI (46.41 ± 11.09 years of age) and 12 healthy males (47.61 ± 11.94 years of age) during resting state and task conditions-bilateral finger tapping (FT), mental imagery of bilateral FT with action observation (FTI+AO), and bilateral ankle tapping (AT). We found an overall decrease in hemodynamic response of the SCI group during all three task conditions. Task modulated functional connectivity (FC) computed using beta series correlation technique was compared using independent sample t-tests at α = 0.05. Connectivity between the right mediolateral sensorimotor network (SMN) and the right medial SMN was reduced during the FT task in SCI. A mixed analysis of variance revealed that the FC within the right mediolateral SMN was reduced during FT but preserved during FTI+AO (i.e., comparable to controls) in the SCI group. Lower FC of these regions was associated with longer injury durations. Additionally, we found a general decrease in resting state FC of the SCI group, specifically in the Slow-3 frequency range (0.073 to 0.1 Hz). These results, though preliminary, are consistent with past studies and highlight the potential of fNIRS in SCI and rehabilitative research.

Improving mental health in Multiple Sclerosis with an interpersonal emotion regulation intervention: A prospective, randomized controlled trial.

BACKGROUND: Over a third of people with Multiple Sclerosis (PwMS) struggle with poor mental health, which exacerbates physical symptoms and complicates clinical treatment. To address this, we tested the efficacy of an interpersonal emotion regulation intervention: this intervention seeks to improve mental health by teaching participants to use emotion regulation strategies which leverage social support (e.g., reaching out to others for comfort when experiencing a stressful event). METHOD: Nineteen PwMS completed this prospective, blinded randomized controlled trial (intervention n = 10; control n = 9). Intervention participants met with an interventionist over six weeks to discuss their emotional challenges and develop goals to use interpersonal emotion regulation strategies. Participants in the control condition met with the interventionist on the same schedule but their emotion regulation strategies were only measured and not manipulated. Pre-registered primary outcomes were self-reported depression, stress, and quality of life (QoL). The pre-registered secondary outcome was self-reported social support. RESULTS: Intervention participants' depression scores improved from time 1 to time 2 (mean difference=3.60, 95% CI [0.44-6.76]), yet remained unchanged for the control group (mean difference=-1.67, 95% CI [-5.00-1.67], overall interaction, F(1,17)=5.84, p=.027, ηp2=.256). The remaining primary (stress and QoL) and secondary (social support) outcomes did not show a significant effect of the intervention (stress: p=.601, ηp2=.016; QoL: p=.179, ηp2=.104; social support: p=.140, ηp2=.124). CONCLUSION: Interpersonal emotion regulation is beneficial in improving depression in PwMS. Consequently, these strategies can be implemented in conjunction with existing mental health treatments in a holistic approach to improving well-being.

Brain activation patterns associated with paragraph learning in persons with multiple sclerosis: The MEMREHAB trial.

The modified Story Memory Technique (mSMT) is a memory rehabilitation program that combines training in visualization and context formation to improve learning and memory. Previous studies have shown improvement in learning and memory in individuals with multiple sclerosis (MS) after undergoing the mSMT, including changes in brain activity related to working memory and word encoding. The current study examined changes in brain activity in 16 individuals diagnosed with MS (n treatment = 6; n placebo control = 10) when they were presented with to-be-remembered information within a meaningful context (i.e. a paragraph) from before to after mSMT treatment. We expected treatment-related changes in brain activation in the language network (LAN), default mode network (DMN), and executive control network (ECN). Consistent with this prediction, fMRI results revealed reduced brain activation in the LAN, DMN and ECN after completing the mSMT treatment in the context of paragraph learning. While no significant behavioral changes were observed, a marginally significant improvement with a large effect size was noted between baseline and follow-up performance on the Rivermead Behavioral Memory Test in persons who completed treatment. Results are discussed in terms of the impact of imagery training on patterns of cerebral activation when learning words presented within a context.

Efficacy of the Spanish modified Story Memory Technique in Mexicans with multiple sclerosis: A pilot randomized controlled trial.

BACKGROUND: Memory impairments commonly afflict individuals with MS. While evidence-based cognitive rehabilitation treatments are available in English, the lack of such interventions in Spanish is an important barrier to care for Hispanics with MS. There is class I evidence that the modified Story Memory Technique (mSMT) improves learning in English. This intervention has been translated and adapted into Spanish. OBJECTIVE: To examine the preliminary efficacy of the Spanish mSMT to improve learning in Mexicans with MS. METHODS: Twenty individuals with relapsing-remitting MS were randomized to treatment (n = 10) or placebo control (n = 10) groups. The Spanish mSMT is a 10-session intervention that teaches imagery and context to facilitate learning. The control condition was matched to the treatment condition in treatment duration, and stimulus content and presentation. Participants completed baseline and post-treatment neuropsychological assessments. RESULTS: Individuals who received the Spanish mSMT showed significant improvements in learning and life satisfaction relative to the control group. Also observed were a near-moderate effect size on perceived memory complaints and a moderate-to-large effect size on the family's perception of the patient's competency. CONCLUSIONS: The Spanish mSMT showed preliminary efficacy in improving learning deficits in Mexicans with MS, and such improvements may extend to other domains.

An RCT to Treat Learning Impairment in Traumatic Brain Injury: The TBI-MEM Trial.

OBJECTIVE: To examine the efficacy of the modified Story Memory Technique (mSMT) to improve learning (ie, acquisition) and memory in participants with TBI. The mSMT is a behavioral intervention that teaches context and imagery to facilitate learning within 10 sessions over 5 weeks. METHODS: A total of 69 participants with moderate-severe Traumatic Brain Injury (TBI), 35 in the treatment group and 34 in the placebo control group, completed this double-blind, placebo-controlled randomized clinical trial. A baseline neuropsychological assessment was administered, including questionnaires assessing everyday memory. Repeat assessments were conducted immediately posttreatment and 6 months following treatment. Participants in the treatment group were randomly assigned to a booster session or a non-booster session group after completion of treatment with the mSMT to examine the efficacy of monthly booster sessions in facilitating the treatment effect over time. RESULTS: The treatment group demonstrated significant improvement on a prose memory task relative to the placebo group posttreatment (η(2) = 0.064 medium effect). Similar results were noted on objective measures of everyday memory, specifically prospective memory (Cohen's w = 0.43, medium effect), and family report of disinhibition in daily life (η(2) = 0.046, medium effect). CONCLUSION: The mSMT is effective for improving learning and memory in TBI. CLASSIFICATION OF EVIDENCE: Based on widely accepted classification systems for treatment study design, this study provides class I evidence that the mSMT behavioral intervention improves both objective memory and everyday memory in persons with TBI over 5 weeks. Thus, this study extends the evidence for efficacy of the treatment protocol to a sample of persons with TBI.

Individual Differences in Working Memory Capacity Predicts Responsiveness to Memory Rehabilitation After Traumatic Brain Injury.

OBJECTIVE: To explore how individual differences affect rehabilitation outcomes by specifically investigating whether working memory capacity (WMC) can be used as a cognitive marker to identify who will and will not improve from memory rehabilitation. DESIGN: Post hoc analysis of a randomized controlled clinical trial designed to treat learning and memory impairment after traumatic brain injury (TBI): 2 × 2 between-subjects quasiexperimental design (2 [group: treatment vs control] × 2 [WMC: high vs low]). SETTING: Nonprofit medical rehabilitation research center. PARTICIPANTS: Participants (N=65) with moderate to severe TBI with pre- and posttreatment data. INTERVENTIONS: The treatment group completed 10 cognitive rehabilitation sessions in which subjects were taught a memory strategy focusing on learning to use context and imagery to remember information. The placebo control group engaged in active therapy sessions that did not involve learning the memory strategy. MAIN OUTCOME MEASURE: Long-term memory percent retention change scores for an unorganized list of words from the California Verbal Learning Test-II. RESULTS: Group and WMC interacted (P=.008, ηp(2)=.12). High WMC participants showed a benefit from treatment compared with low WMC participants. Individual differences in WMC accounted for 45% of the variance in whether participants with TBI in the treatment group benefited from applying the compensatory treatment strategy to learn unorganized information. CONCLUSIONS: Individuals with higher WMC showed a significantly greater rehabilitation benefit when applying the compensatory strategy to learn unorganized information. WMC is a useful cognitive marker for identifying participants with TBI who respond to memory rehabilitation with the modified Story Memory Technique.

An RCT to treat learning impairment in multiple sclerosis: The MEMREHAB trial.

OBJECTIVE: To examine the efficacy of the modified Story Memory Technique (mSMT), a 10-session behavioral intervention teaching context and imagery to facilitate learning, to improve learning and memory abilities in persons with multiple sclerosis (MS). METHODS: This double-blind, placebo-controlled, randomized clinical trial included 86 participants with clinically definite MS, 41 in the treatment group and 45 in the placebo control group. Participants completed a baseline neuropsychological assessment, including questionnaires assessing everyday memory, a repeat assessment immediately posttreatment, and a long-term follow-up assessment 6 months after treatment. After completion of the treatment phase, persons in the treatment group were assigned to a booster session or a non-booster session group to examine the efficacy of monthly booster sessions in facilitating the treatment effect over time. RESULTS: The treatment group showed a significantly improved learning slope relative to the placebo group posttreatment. Similar results were noted on objective measures of everyday memory, general contentment, and family report of apathy and executive dysfunction. Long-term follow-up data showed that posttreatment improvement in the treatment group continued to be noted on the list learning and self-report measures. The provision of booster sessions demonstrated little benefit. CONCLUSION: The mSMT is effective for improving learning and memory in MS. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that the mSMT behavioral intervention improves both objective memory and everyday memory in patients with MS over 5 weeks, with treatment effects lasting over a 6-month period.

Deciphering components of impaired working memory in multiple sclerosis.

OBJECTIVE: To identify working memory (WM) impairment by examining components of auditory working memory with the same sample of individuals with multiple sclerosis (MS). BACKGROUND: Although individuals with MS have consistently demonstrated WM impairments, the specific components involved (i.e., central executive versus storage/maintenance) remain unclear. METHOD: Individuals with MS with and without cognitive impairment and healthy controls were administered a task primarily assessing storage and rehearsal/maintenance (auditory n-back) and a task with a significant central executive component (Paced Auditory Serial Addition Task). RESULTS: Results indicate when the phonological loop is minimally challenged, maintenance of information is generally efficient. However, the addition of a central executive component to processing appears to be the key factor in differentiating individuals with MS with cognitive impairment from those without cognitive impairment and healthy controls. CONCLUSIONS: Results indicated that the primary WM impairment in MS is within the central executive rather than the phonological loop.