Structural network topology associated with naming improvements following intensive aphasia therapy in post-stroke aphasia.

A stroke can disrupt the finely tuned language network resulting in aphasia, a language impairment. Though many stroke survivors with aphasia recover within the first 6 months, a significant proportion have lasting deficits. The factors contributing to optimal treatment response remain unclear. Some evidence suggests that increased modularity or fragmentation of brain networks may underlie post-stroke aphasia severity and the extent of recovery. We examined associations between network organization and aphasia recovery in sixteen chronic stroke survivors with non-fluent aphasia following 35 h of Multi-Modality Aphasia Therapy over 10 days and 20 healthy controls who underwent imaging at a single timepoint. Using diffusion-weighted scans obtained before and after treatment, we constructed whole-brain structural connectomes representing the number of probabilistic streamlines between brain regions. Graph theory metrics were quantified for each connectome using the Brain Connectivity Toolbox. Correlations were examined between graph metrics and speech performance measured using the Boston Naming Test (BNT) at pre-, post- and 3-months post-intervention. Compared to controls, participants with stroke demonstrated higher whole-brain modularity at pre-treatment. Modularity did not differ between pre- and post-treatment. In individuals who responded to therapy, higher pre-treatment modularity was associated with worse performance on the BNT. Moreover, higher pre-treatment participation coefficients (i.e., how well a region is connected outside its own module) for the left IFG, planum temporale, and posterior temporal gyri were associated with greater improvements at post-treatment. These results suggest that pre-treatment network topology may impact therapeutic gains, highlighting the influence of network organization on post-stroke aphasia recovery.

Clinical, Neuroimaging and Robotic Measures Predict Long-Term Proprioceptive Impairments following Stroke.

Proprioceptive impairments occur in ~50% of stroke survivors, with 20-40% still impaired six months post-stroke. Early identification of those likely to have persistent impairments is key to personalizing rehabilitation strategies and reducing long-term proprioceptive impairments. In this study, clinical, neuroimaging and robotic measures were used to predict proprioceptive impairments at six months post-stroke on a robotic assessment of proprioception. Clinical assessments, neuroimaging, and a robotic arm position matching (APM) task were performed for 133 stroke participants two weeks post-stroke (12.4 ± 8.4 days). The APM task was also performed six months post-stroke (191.2 ± 18.0 days). Robotics allow more precise measurements of proprioception than clinical assessments. Consequently, an overall APM Task Score was used as ground truth to classify proprioceptive impairments at six months post-stroke. Other APM performance parameters from the two-week assessment were used as predictive features. Clinical assessments included the Thumb Localisation Test (TLT), Behavioural Inattention Test (BIT), Functional Independence Measure (FIM) and demographic information (age, sex and affected arm). Logistic regression classifiers were trained to predict proprioceptive impairments at six months post-stroke using data collected two weeks post-stroke. Models containing robotic features, either alone or in conjunction with clinical and neuroimaging features, had a greater area under the curve (AUC) and lower Akaike Information Criterion (AIC) than models which only contained clinical or neuroimaging features. All models performed similarly with regard to accuracy and F1-score (>70% accuracy). Robotic features were also among the most important when all features were combined into a single model. Predicting long-term proprioceptive impairments, using data collected as early as two weeks post-stroke, is feasible. Identifying those at risk of long-term impairments is an important step towards improving proprioceptive rehabilitation after a stroke.

Directional and general impairments in initiating motor responses after stroke.

Visuospatial neglect is a disorder characterized by an impairment of attention, most commonly to the left side of space in individuals with stroke or injury to the right hemisphere. Clinical diagnosis is largely based on performance on pen and paper examinations that are unable to accurately measure the speed of processing environmental stimuli-important for interacting in our dynamic world. Numerous studies of impairment after visuospatial neglect demonstrate delayed reaction times when reaching to the left. However, little is known of the visuospatial impairment in other spatial directions and, further, the influence of the arm being assessed. In this study, we quantify the ability of a large cohort of 204 healthy control participants (females = 102) and 265 individuals with stroke (right hemisphere damage = 162, left hemisphere damage = 103; mean age 62) to generate goal-directed reaches. Participants used both their contralesional and ipsilesional arms to perform a centre-out visually guided reaching task in the horizontal plane. We found that the range of visuospatial impairment can vary dramatically across individuals with some individuals displaying reaction time impairments restricted to a relatively small portion of the workspace, whereas others displayed reaction time impairments in all spatial directions. Reaction time impairments were observed in individuals with right or left hemisphere lesions (48% and 30%, respectively). Directional impairments commonly rotated clockwise when reaching with the left versus the right arms. Impairment in all spatial directions was more prevalent in right than left hemisphere lesions (32% and 12%, respectively). Behavioral Inattention Test scores significantly correlated (r = -0.49, P < 0.005) with reaction time impairments but a large portion of individuals not identified as having visuospatial neglect on the Behavioral Inattention Test still displayed reaction time impairments (35%). MRI and CT scans identified distinct white matter and cortical regions of damage for individuals with directional (insula, inferior frontal-occipital fasciculus and inferior longitudinal fasciculus) and general (superior and middle temporal gyri) visuospatial impairment. This study highlights the prevalence and diversity of visuospatial impairments that can occur following stroke.

Repetitive transcranial magnetic stimulation (rTMS) combined with multi-modality aphasia therapy for chronic post-stroke non-fluent aphasia: A pilot randomized sham-controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) shows promise in improving speech production in post-stroke aphasia. Limited evidence suggests pairing rTMS with speech therapy may result in greater improvements. Twenty stroke survivors (>6 months post-stroke) were randomized to receive either sham rTMS plus multi-modality aphasia therapy (M-MAT) or rTMS plus M-MAT. For the first time, we demonstrate that rTMS combined with M-MAT is feasible, with zero adverse events and minimal attrition. Both groups improved significantly over time on all speech and language outcomes. However, improvements did not differ between rTMS or sham. We found that rTMS and sham groups differed in lesion location, which may explain speech and language outcomes as well as unique patterns of BOLD signal change within each group. We offer practical considerations for future studies and conclude that while combination therapy of rTMS plus M-MAT in chronic post-stroke aphasia is safe and feasible, personalized intervention may be necessary.

Beyond the Dorsal Column Medial Lemniscus in Proprioception and Stroke: A White Matter Investigation.

Proprioceptive deficits are common following stroke, yet the white matter involved in proprioception is poorly understood. Evidence suggests that multiple cortical regions are involved in proprioception, each connected by major white matter tracts, namely: Superior Longitudinal Fasciculus (branches I, II and III), Arcuate Fasciculus and Middle Longitudinal Fasciculus (SLF I, SLF II, SLF III, AF and MdLF respectively). However, direct evidence on the involvement of these tracts in proprioception is lacking. Diffusion imaging was used to investigate the proprioceptive role of the SLF I, SLF II, SLF III, AF and MdLF in 26 participants with stroke, and seven control participants without stroke. Proprioception was assessed using a robotic Arm Position Matching (APM) task, performed in a Kinarm Exoskeleton robotic device. Lesions impacting each tract resulted in worse APM task performance. Lower Fractional Anisotropy (FA) was also associated with poorer APM task performance for the SLF II, III, AF and MdLF. Finally, connectivity data surrounding the cortical regions connected by each tract accurately predicted APM task impairments post-stroke. This study highlights the importance of major cortico-cortical white matter tracts, particularly the SLF III and AF, for accurate proprioception after stroke. It advances our understanding of the white matter tracts responsible for proprioception.

Functional magnetic resonance imaging study of working memory several years after pediatric concussion.

PRIMARY OBJECTIVE: The neurophysiological effects of pediatric concussion several years after injury remain inadequately characterized. The objective of this study was to determine if a history of concussion was associated with BOLD response differences during an n-back working memory task in youth. RESEARCH DESIGN: Observational, cross-sectional. METHODS AND PROCEDURES: Participants include 52 children and adolescents (M = 15.1 years, 95%CI = 14.4-15.8, range = 9-19) with past concussion (n = 33) or orthopedic injury (OI; n = 19). Mean time since injury was 2.5 years (95%CI = 2.0-3.0). Measures included postconcussion symptom ratings, neuropsychological testing, and blood-oxygen-dependent-level (BOLD) functional magnetic resonance imaging (fMRI) during an n-back working memory task. MAIN OUTCOMES AND RESULTS: Groups did not differ on accuracy or speed during the three n-back conditions. They also did not differ in BOLD signal change for the 1- vs. 0-back or 2- vs. 0-back contrasts (controlling for task performance). CONCLUSIONS: This study does not support group differences in BOLD response during an n-back working memory task in youth who are on average 2.5 years post-concussion. The findings are encouraging from the perspective of understanding recovery after pediatric concussion.

Microstructure of the Corpus Callosum Long after Pediatric Concussion.

OBJECTIVE: The long-term effects of pediatric concussion on white matter microstructure are poorly understood. This study investigated long-term changes in white matter diffusion properties of the corpus callosum in youth several years after concussion. METHODS: Participants were 8-19 years old with a history of concussion (n = 36) or orthopedic injury (OI) (n = 21). Mean time since injury for the sample was 2.6 years (SD = 1.6). Participants underwent diffusion magnetic resonance imaging, completed cognitive testing, and rated their post-concussion symptoms. Measures of diffusivity (fractional anisotropy, mean, axial, and radial diffusivity) were extracted from white matter tracts in the genu, body, and splenium regions of the corpus callosum. The genu and splenium tracts were further subdivided into 21 equally spaced regions along the tract and diffusion values were extracted from each of these smaller regions. RESULTS: White matter tracts in the genu, body, and splenium did not differ in diffusivity properties between youth with a history of concussion and those with a history of OI. No significant group differences were found in subdivisions of the genu and splenium after correcting for multiple comparisons. Diffusion metrics did not significantly correlate with symptom reports or cognitive performance. CONCLUSIONS: These findings suggest that at approximately 2.5 years post-injury, youth with prior concussion do not have differences in their corpus callosum microstructure compared to youth with OI. Although these results are promising from the perspective of long-term recovery, further research utilizing longitudinal study designs is needed to confirm the long-term effects of pediatric concussion on white matter microstructure.

Evaluating anxiety and depression symptoms in children and adolescents with prior mild traumatic brain injury: Agreement between methods and respondents.

Psychological functioning can be adversely impacted after a mild traumatic brain injury (mTBI) and may be a potential target for intervention. Despite the use of symptom ratings or structured diagnostic interview to assess long-term anxiety and depression symptoms in children and adolescents post-injury, no known studies have considered the agreement between different assessment methods and between respondents. The objectives of this study were to investigate the agreement between symptom ratings and structured diagnostic interview and between children and parents' symptom reporting. Participants (N = 33; 9-18 years old) were recruited from the Emergency Department and assessed on average 22.8 months (SD = 5.6) after their mTBI. Anxiety and depression symptoms were evaluated via subscales of a questionnaire (Behavior Assessment System for Children) and parts of a computerized structured diagnostic interview (generalized anxiety disorder and major depressive episode; Diagnostic Interview Schedule for Children - C-DISC-IV) administered individually to children and their parents. Results showed that the inter-method agreement to identify high levels of anxiety and depression was moderate to perfect in children while it was lower in parents. Although a similar percentage of participants with elevated anxiety or depression were identified by both children and parents, the agreement between youth and parents was variable, ranging from poor to good for anxiety and poor to moderate for depression. These results highlight the importance of collecting youth and parents' reports of anxiety and depression symptoms and considering potential discrepancies between informants' answers.

Cerebral blood flow in children and adolescents several years after concussion.

OBJECTIVES: The long-term effects of concussion in youth remain poorly understood. The objective of this study was to determine the association between history of concussion and cerebral blood flow (CBF) in youth. METHODS: A total of 53 children and adolescents with a history of concussion (n = 37) or orthopaedic injury (OI; n = 16) were considered. Measures included pseudo-continuous arterial spin labelling magnetic resonance imaging to quantify CBF, post-concussion symptoms, psychological symptoms, and cognitive testing. RESULTS: Participants (mean age: 14.4 years, 95% CI = 13.8-15.4, range = 8-19) were on average 2.7 years (95% CI = 2.2-3.1) post-injury. Youth with a history of concussion had higher parent-reported physical, cognitive, anxiety, and depression symptoms than children with OI, but the groups did not differ on self-reported symptoms (post-concussive or psychological) or cognitive testing. Global CBF did not differ between groups. Regional CBF analyses suggested that youth with a history of concussion had hypoperfusion in posterior and inferior regions and hyperperfusion in anterior/frontal/temporal regions as compared to those with OI. However, neither global nor regional CBF were significantly associated with demographics, pre-injury functioning, number of concussions, time since injury, post-concussive symptoms, psychological symptoms, or cognitive abilities. CONCLUSIONS: Youth with a history of concussion demonstrate differences in regional CBF (not global CBF), but without clear clinical expression.

Test or Rest? Computerized Cognitive Testing in the Emergency Department after Pediatric Mild Traumatic Brain Injury Does Not Delay Symptom Recovery.

Rest is commonly prescribed following a mild traumatic brain injury (mTBI). There is concern that cognitive exertion by an acutely or sub-acutely injured brain may negatively alter outcome. The objective of this study was to determine if computerized cognitive testing in the emergency department alters symptom outcome from mTBI. Participants included 77 youth with mTBI who underwent computerized cognitive testing (mean age, 13.6; 95% confidence interval [CI] = 13.0-14.2) and were matched to 77 youth with mTBI who did not participate in cognitive testing (mean age, 13.5; 95% CI = 12.9-14.0). Participants who underwent cognitive testing did not differ from those who did not undergo acute cognitive testing on mean symptom ratings or the proportion who were not recovered at 7-10 days, 1 month, 2 months, or 3 months. There also was no difference in symptom outcome for those who underwent a shortened (four subtests, mean time = 16 min) or full-length (seven subtests, mean time = 28 min) version of the computerized test. Brief cognitive exertion using a computerized cognitive assessment after mTBI in youth does not result in worse symptoms at these follow-up periods, does not prolong symptom recovery, should not be considered contraindicated to recovery, and could be considered as another tool to aid in the management of these injuries. Further research with different samples is warranted.