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.

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.

Investigating the neuroanatomy underlying proprioception using a stroke model.

Neuroanatomical investigations have associated cortical areas, beyond Primary Somatosensory Cortex (S1), with impaired proprioception. Cortical regions have included temporoparietal (TP) regions (supramarginal gyrus, superior temporal gyrus, Heschl's gyrus) and insula. Previous approaches have struggled to account for concurrent damage across multiple brain regions. Here, we used a targeted lesion analysis approach to examine the impact of specific combinations of cortical and sub-cortical lesions and quantified the prevalence of proprioceptive impairments when different regions are damaged or spared. Seventy-seven individuals with stroke (49 male; 28 female) were identified meeting prespecified lesion criteria based on MRI/CT imaging: 1) TP lesions without S1, 2) TP lesions with S1, 3) isolated S1 lesions, 4) isolated insula lesions, and 5) lesions not impacting these regions (other regions group). Initially, participants meeting these criteria (1-4) were grouped together into right or left lesion groups and compared to each other, and the other regions group (5), on a robotic Arm Position Matching (APM) task and a Kinesthesia (KIN) task. We then examined the behaviour of individuals that met each specific criteria (groups 1-5). Proprioceptive impairments were more prevalent following right hemisphere lesions than left hemisphere lesions. The extent of damage to TP regions correlated with performance on both robotic tasks. Even without concurrent S1 lesions, TP and insular lesions were associated with impairments on the APM and KIN tasks. Finally, lesions not impacting these regions were much less likely to result in impairments. This study highlights the critical importance of TP and insular regions for accurate proprioception. SIGNIFICANCE STATEMENT: This work advances our understanding of the neuroanatomy of human proprioception. We validate the importance of regions, beyond the dorsal column medial lemniscal pathway and S1, for proprioception. Further, we provide additional evidence of the importance of the right hemisphere for human proprioception. Improved knowledge on the neuroanatomy of proprioception is crucial for advancing therapeutic approaches which target individuals with proprioceptive impairments following neurological injury or with neurological disorders.