Predicting Language Function Post-Stroke: A Model-Based Structural Connectivity Approach.

BACKGROUND: The prediction of post-stroke language function is essential for the development of individualized treatment plans based on the personal recovery potential of aphasic stroke patients. OBJECTIVE: To establish a framework for integrating information on connectivity disruption of the language network based on routinely collected clinical magnetic resonance (MR) images into Random Forest modeling to predict post-stroke language function. METHODS: Language function was assessed in 76 stroke patients from the Non-Invasive Repeated Therapeutic Stimulation for Aphasia Recovery trial, using the Token Test (TT), Boston Naming Test (BNT), and Semantic Verbal Fluency (sVF) Test as primary outcome measures. Individual infarct masks were superimposed onto a diffusion tensor imaging tractogram reference set to calculate Change in Connectivity scores of language-relevant gray matter regions as estimates of structural connectivity disruption. Multivariable Random Forest models were derived to predict language function. RESULTS: Random Forest models explained moderate to high amount of variance at baseline and follow-up for the TT (62.7% and 76.2%), BNT (47.0% and 84.3%), and sVF (52.2% and 61.1%). Initial language function and non-verbal cognitive ability were the most important variables to predict language function. Connectivity disruption explained additional variance, resulting in a prediction error increase of up to 12.8% with variable omission. Left middle temporal gyrus (12.8%) and supramarginal gyrus (9.8%) were identified as among the most important network nodes. CONCLUSION: Connectivity disruption of the language network adds predictive value beyond lesion volume, initial language function, and non-verbal cognitive ability. Obtaining information on connectivity disruption based on routine clinical MR images constitutes a significant advancement toward practical clinical application.

Predicting Individual Treatment Response to rTMS for Motor Recovery After Stroke: A Review and the CanStim Perspective.

Background: Rehabilitation is critical for reducing stroke-related disability and improving quality-of-life post-stroke. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique used as stand-alone or adjunct treatment to physiotherapy, may be of benefit for motor recovery in subgroups of stroke patients. The Canadian Platform for Trials in Non-Invasive Brain Stimulation (CanStim) seeks to advance the use of these techniques to improve post-stroke recovery through clinical trials and pre-clinical studies using standardized research protocols. Here, we review existing clinical trials for demographic, clinical, and neurobiological factors which may predict treatment response to identify knowledge gaps which need to be addressed before implementing these parameters for patient stratification in clinical trial protocols. Objective: To provide a review of clinical rTMS trials of stroke recovery identifying factors associated with rTMS response in stroke patients with motor deficits and develop research perspectives for pre-clinical and clinical studies. Methods: A literature search was performed in PubMed, using the Boolean search terms stroke AND repetitive transcranial magnetic stimulation OR rTMS AND motor for studies investigating the use of rTMS for motor recovery in stroke patients at any recovery phase. A total of 1,676 articles were screened by two blinded raters, with 26 papers identified for inclusion in this review. Results: Multiple possible factors associated with rTMS response were identified, including stroke location, cortical thickness, brain-derived neurotrophic factor (BDNF) genotype, initial stroke severity, and several imaging and clinical factors associated with a relatively preserved functional motor network of the ipsilesional hemisphere. Age, sex, and time post-stroke were generally not related to rTMS response. Factors associated with greater response were identified in studies of both excitatory ipsilesional and inhibitory contralesional rTMS. Heterogeneous study designs and contradictory data exemplify the need for greater protocol standardization and high-quality controlled trials. Conclusion: Clinical, brain structural and neurobiological factors have been identified as potential predictors for rTMS response in stroke patients with motor impairment. These factors can inform the design of future clinical trials, before being considered for optimization of individual rehabilitation therapy for stroke patients. Pre-clinical models for stroke recovery, specifically developed in a clinical context, may accelerate this process.

Developmental changes within the extended face processing network: A cross-sectional functional magnetic resonance imaging study.

In the field of face processing, the so-called "core network" has been intensively researched. Its neural activity can be reliably detected in children and adults using functional magnetic resonance imaging (fMRI). However, the core network's counterpart, the so-called "extended network," has been less researched. In the present study, we compared children's and adults' brain activity in the extended system, in particular in the amygdala, the insula, and the inferior frontal gyrus (IFG). Using fMRI, we compared the brain activation pattern between children aged 7-9 years and adults during an emotional face processing task. On the one hand, children showed increased activity in the extended face processing system in relation to adults, particularly in the left amygdala, the right insula, and the left IFG. On the other hand, lateralization indices revealed a "leftward bias" in children's IFG compared to adults. These results suggest that brain activity associated with face processing is characterized by a developmental decrease in activity. They further show that the development is associated with a rightward migration of face-related IFG activation, possibly due to the competition for neural space between several developing brain functions ("developmental competition hypothesis").

Nucleus basalis of Meynert damage and cognition in patients with multiple sclerosis.

BACKGROUND: The nucleus basalis of Meynert (NBM), representing the major source of cerebral cholinergic innervations, is vulnerable to neurodegeneration in Alzheimer's and Parkinson's disease. OBJECTIVE: To determine associations between NBM properties and cognitive outcomes in patients with multiple sclerosis (PwMS). METHODS: 84 PwMS and 19 controls underwent 3T MRI, the Paced Auditory Serial Addition Test (PASAT) and subtests of the Brief International Cognitive Assessment for MS (BICAMS). NBM volume, fractional anisotropy, mean diffusivity (MD), axial diffusivity and radial diffusivity (D⊥) were calculated. Analyses assessed relationships between cognition and NBM measures. Linear regressions evaluated the prognostic value of baseline measures in predicting cognitive change over 3 years of follow-up (n = 67). RESULTS: Cognitive tests correlated with NBM diffusivity in PwMS (range r = - 0.29 to r = - 0.40, p < 0.05). After accounting for NBM volume, NBM MD and D⊥ explained additional variance (adjusted R2 range 0.08-0.20, p < 0.05). Correlations between NBM imaging metrics and cognitive tests remained significant when including imaging parameters of other cognitive key brain regions in the models. After controlling for age, education, and baseline cognitive test score, NBM measures predicted change in cognition over follow-up in 5 of 10 and 2 of 10 assessments in the relapsing-remitting sample (n = 43) (adjusted R2 range from 0.23 to 0.38, p < 0.05) and secondary progressive sample (adjusted R2 of 0.280 and 0.183), respectively. CONCLUSIONS: NBM damage is linked to cognitive impairment in PwMS.

Leptomeningeal, dura mater and meningeal vessel wall enhancements in multiple sclerosis.

BACKGROUND: Leptomeningeal contrast enhancement (LMCE) has previously shown potential to be an indirect marker for leptomeningeal inflammation in multiple sclerosis (MS). Dura mater (DME), inclusive falx cerebri (FCE) enhancement and meningeal vessel wall enhancement (VWE) represent two other meningeal enhancement patterns in MS that have not been extensively studied. OBJECTIVES: To investigate the frequency of LMCE, DME/FCE and VWE in patients with MS and their associations with demographic, clinical and MRI characteristics in a longitudinal retrospective study. METHODS: 217 MS patients (193 relapsing-remitting MS, 24 progressive MS) were assessed at baseline and over 18 months follow-up using 3T 3D FLAIR pre- and post-contrast and subtraction images. Lesion and brain volume outcomes were additionally calculated. Analyses were adjusted for age, and corrected for multiple comparisons. RESULTS: LMCE and VWE frequency was associated with higher age (p<0.02), but the presence of DME/FCE was not (p=0.402). 24% of MS patients revealed LMCE and VWE, respectively, and 47% showed DME/FCE. Presence of LMCE, VWE and DME/FCE was not significantly associated with clinical or imaging markers of disease severity. All three patterns of meningeal enhancement showed a high persistence in shape and size at follow-up. CONCLUSIONS: LMCE, DME/FCE and VWE can be identified by gadolinium-enhanced 3D FLAIR MR imaging. Meningeal enhancement is associated with higher age. DME/FCE is the most frequent meningeal enhancement pattern in MS, however further case-control studies should determine whether this represents abnormal lymphatic drainage in these patients or is an age-dependent physiologic phenomenon.

The Trajectory of Hemispheric Lateralization in the Core System of Face Processing: A Cross-Sectional Functional Magnetic Resonance Imaging Pilot Study.

Face processing is mediated by a distributed neural network commonly divided into a "core system" and an "extended system." The core system consists of several, typically right-lateralized brain regions in the occipito-temporal cortex, including the occipital face area (OFA), the fusiform face area (FFA) and the posterior superior temporal sulcus (pSTS). It was recently proposed that the face processing network is initially bilateral and becomes right-specialized in the course of the development of reading abilities due to the competition between language-related regions in the left occipito-temporal cortex (e.g., the visual word form area, VWFA) and the FFA for common neural resources. In the present pilot study, we assessed the neural face processing network in 12 children (aged 7-9 years) and 10 adults with functional magnetic resonance imaging (fMRI). The hemispheric lateralization of the core face regions was compared between both groups. The study had two goals: First, we aimed to establish an fMRI paradigm suitable for assessing activation in the core system of face processing in young children at the single subject level. Second, we planned to collect data for a power analysis to calculate the necessary group size for a large-scale cross-sectional imaging study assessing the ontogenetic development of the lateralization of the face processing network, with focus on the FFA. It was possible to detect brain activity in the core system of 75% of children at the single subject level. The average scan-to-scan motion of the included children was comparable to adults, ruling out that potential activation differences between groups are caused by unequal motion artifacts. Hemispheric lateralization of the FFA was 0.07 ± 0.48 in children (indicating bilateral activation) and -0.32 ± 0.52 in adults (indicating right-hemispheric dominance). These results thus showed, as expected, a trend for increased lateralization in adults. The estimated effect size for the FFA lateralization difference was d = 0.78 (indicating medium to large effects). An adequately powered follow-up study (sensitivity 0.8) testing developmental changes of FFA lateralization would therefore require the inclusion of 18 children and 26 adults.