Further evidence for a non-cortical origin of mirror movements after stroke.

Ejaz et al. (2018) are to be commended for showing no evidence for a cortical origin of post-stroke mirror movements. Using functional MRI during affected-finger presses in recovering adult-onset stroke patients, they found no consistent relationship between contralesional sensorimotor cortex (cSM1) activation and quantitative indices of mirror movements; specifically, mirror movements were not linked to the presence of cSM1 overactivation, arguing against the classic ‘transcallosal’ mechanism heretofore widely believed to cause mirror movements (Di Pino et al., 2014). We wish to report findings—previously published in abstract form (Calautti, 2008)—that further support the idea that mirror movements are not cortically mediated. We also present data that confirm that mirror movements can involve the affected (i.e. paretic) hand during movement of the unaffected (i.e. non-paretic) hand, also arguing in favour of disruption of a bilaterally-organized system

Prefrontal-Premotor Pathways and Motor Output in Well-Recovered Stroke Patients

Structural brain imaging has continuously furthered our knowledge how different pathways of the human motor system contribute to residual motor output in stroke patients. Tract-related microstructure of pathways between primary and premotor areas has been found to critically influence motor output. The motor network is not restricted in connectivity to motor and premotor areas but these brain regions are densely interconnected with prefrontal regions such as the dorsolateral (DLPFC) and ventrolateral (VLPFC) prefrontal cortex. So far, the available data about the topography of such direct pathways and their microstructural properties in humans are sparse. To what extent prefrontal-premotor connections might also relate to residual motor outcome after stroke is still an open question. The present study was designed to address this issue of structural connectivity of prefrontal-premotor pathways in 26 healthy, older participants (66 ± 10 years old, 15 male) and 30 well-recovered chronic stroke patients (64 ± 10 years old, 21 males). Probabilistic tractography was used to reconstruct direct fiber tracts between DLPFC and VLPFC and three premotor areas (dorsal and ventral premotor cortex and the supplementary motor area). Direct connections between DLPFC/VLPFC and the primary motor cortex were also tested. Tract-related microstructure was estimated for each specific tract by means of fractional anisotropy and alternative diffusion metrics. These measures were compared between the groups and related to residual motor outcome in the stroke patients. Direct prefrontal-premotor trajectories were successfully traceable in both groups. Similar in gross anatomic topography, stroke patients presented only marginal microstructural alterations of these tracts, predominantly of the affected hemisphere. However, there was no clear evidence for a significant association between tract-related microstructure of prefrontal-premotor connections and residual motor functions in the present group of well-recovered stroke patients. Direct prefrontal-motor connections between DLPFC/VLPFC and the primary motor cortex could not be reconstructed in the present healthy participants and stroke patients

Prefrontal-Premotor Pathways and Motor Output in Well-Recovered Stroke Patients

Structural brain imaging has continuously furthered our knowledge how different pathways of the human motor system contribute to residual motor output in stroke patients. Tract-related microstructure of pathways between primary and premotor areas has been found to critically influence motor output. The motor network is not restricted in connectivity to motor and premotor areas but these brain regions are densely interconnected with prefrontal regions such as the dorsolateral (DLPFC) and ventrolateral (VLPFC) prefrontal cortex. So far, the available data about the topography of such direct pathways and their microstructural properties in humans are sparse. To what extent prefrontal-premotor connections might also relate to residual motor outcome after stroke is still an open question. The present study was designed to address this issue of structural connectivity of prefrontal-premotor pathways in 26 healthy, older participants (66 ± 10 years old, 15 male) and 30 well-recovered chronic stroke patients (64 ± 10 years old, 21 males). Probabilistic tractography was used to reconstruct direct fiber tracts between DLPFC and VLPFC and three premotor areas (dorsal and ventral premotor cortex and the supplementary motor area). Direct connections between DLPFC/VLPFC and the primary motor cortex were also tested. Tract-related microstructure was estimated for each specific tract by means of fractional anisotropy and alternative diffusion metrics. These measures were compared between the groups and related to residual motor outcome in the stroke patients. Direct prefrontal-premotor trajectories were successfully traceable in both groups. Similar in gross anatomic topography, stroke patients presented only marginal microstructural alterations of these tracts, predominantly of the affected hemisphere. However, there was no clear evidence for a significant association between tract-related microstructure of prefrontal-premotor connections and residual motor functions in the present group of well-recovered stroke patients. Direct prefrontal-motor connections between DLPFC/VLPFC and the primary motor cortex could not be reconstructed in the present healthy participants and stroke patients

Improving community walking after stroke; the effect of dual task treadmill training on gait, cognition and brain control mechanisms of dual task walking in chronic stroke survivors

It is well known that improving community walking ability is one of the major goals in stroke rehabilitation. Even if motor recovery of the lower limbs does occur, the ability to walk in the community is often still impaired. This thesis set out to explore dual task ability after stroke in relation to community walking and explored dual task treadmill training in stroke survivors. In addition, functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS) in stroke survivors during single and dual gait movements were performed to examine dual task effects on brain activation before and after dual task training. In a cross-sectional trial, 27 limited community walkers were compared to 23 moderate-to-full community walkers. A significant larger proportion of limited community walkers were not confident about walking in the community compared to moderate-to-full community walkers (p = 0.042). Moreover mean cognitive response during two-minute-walk with dual task was 11.17 ± 3.62 for limited walkers and 13.48 ± 2.43 for moderate-to-full community walkers (p = 0.014). In contrast, moderate-to-full community walkers displayed relative larger reductions in walking distance as a result of dual task in comparison to limited community walkers (p = 0.068). Consequently, a randomized controlled trial was performed in 50 chronic stroke survivors to explore to what extent 10 weeks of treadmill training with concurrent cognitive distraction in comparison to 10 weeks of treadmill training with no distraction would change community walking ability. Stroke survivors who received dual task treadmill training showed larger increases in two-minute-walk distance compared to the control group from baseline to follow with an effect size r of 0.24 and a Cohen’s d of 0.50. Significant group and time interactions were seen for physical activity scale assessments favouring the dual task training group (p = 0.029). In addition, on a modified version of the University of Alabama study of Aging Life Space Assessment questionnaire, stroke survivors in the dual task training group scored 54.76 ± 26.64 compared to 41.53 ± 20.88 in the control group at follow-up, (p = 0.086). Both training groups improved on walking performance and endurance during training. Feasibility of dual task training was good, with only l0% drop out for intention to treat. The final part of this thesis focussed on results from fMRI and fNIRS measures that were taken to explore brain activation patterns during single and dual task gait before and after dual task training. At baseline, decreases in brain activation were seen in prefrontal cortex areas during dual task treadmill walking compared to single task treadmill walking. Moreover, fMRI during pedal movements with a concurrent cognitive task showed decreased brain activation compared to pedal movement alone. Dual task trained stroke survivors showed a reduction in right occipital cortex activation during pedalling at follow-up compared to baseline whereas control trained stroke survivors showed increases in this area from baseline to follow-up with a significant difference of activation change between groups (p < 0.001). In addition, stroke survivors who had received dual task training showed significant reductions in brain activation during pedalling and increase in activation during dual task pedalling from baseline to follow-up. The results from the comparisons between limited community walkers and moderate-to-full community walkers suggested that different coping strategies might apply after stroke depending on gait speed, but also indicated that both type of community walkers had difficulties with dual task walking. Dual task treadmill training showed good feasibility and positive effects on walking endurance and performance as well as training without distraction. There were trends suggesting that stroke survivors who were already physically active and had recovered their walking up to a certain standard were more likely to improve their dual task walking distance after dual training. Brain imaging measures showed decreases in activation from single to dual task locomotor movements which may relate to reduced dual task ability in stroke survivors, but these changes did not correlate with changes in behavioural measures of dual task. The changes in response to training may relate to plasticity and a recovery of the automaticity of control of normal walking as a result of dual task training. This thesis has provided novel research, insights and practical implications for dual task training after stroke. More research is needed, for instance to explore the extent to which stroke survivors could benefit from dual task training in more real-life situations. The use of neuroimaging tools in stroke rehabilitation trials helps to understand how motor control mechanisms change in response to training and could add to tailor rehabilitation to the individual’s need

Endofenotipos neurocognitivos potenciales para el trastorno bipolar: velocidad motora manual, memoria visual, velocidad de procesamiento

Antecedentes: Son pocas las investigaciones que se centran en el estudio de las disfunciones neurocognitivas en pacientes con trastorno bipolar (TB) como posibles marcadores de rasgo para esta enfermedad, menos aún son las que comparan el rendimiento motor, la memoria visual o la velocidad de procesamiento de la información, en estudios transversales o longitudinales, incluyendo a la vez, controles (CS) y familiares sanos de primer grado de los pacientes (TB-F); hasta la redacción de esta tesis, aunque el número va en aumento, en la investigación psiquiátrica el trastorno bipolar sigue ocupando un lugar secundario frente a la esquizofrenia, siendo insuficientes los estudios que buscan evidencias sobre posibles endofenotipos neurocognitivos de esta enfermedad mental. El objetivo de la presente tesis, en formato de “compendio de estudios”, es contribuir a esclarecer si tres de las disfunciones neurocognitivas menos estudiadas actualmente en el trastorno bipolar: 1) Velocidad Motora Manual (VMM), 2) Memoria Visual (MV) y 3) Velocidad de Procesamiento de la Información (VPI), podrían ser incluidas dentro del perfil endofenotípico de esta enfermedad mental, siguiendo los criterios tradicionalmente utilizados para su selección. Método: Se presentan separadamente 3 estudios, en cada uno de los cuales se siguió similar metodología investigativa, pero se utilizaron pruebas neurocognitivas diferentes: 1) Finger-Tapping Test (FTT), 2) Test de Copia y de Reproducción de Memoria de Figuras Geométricas Complejas (REY) y 3) subtest “Símbolos” o “Clave de Números” del WAIS (CN). Las evaluaciones se realizaron en tres tiempos investigativos a lo largo de cinco años, con tres grupos: pacientes con trastorno bipolar, sus familiares sanos de primer grado y controles sanos no relacionados genéticamente. La influencia de la edad sobre el desempeño de los participantes, en las pruebas, fue controlada con un modelo de regresión lineal sobre las medias de los CS. Las diferencias entre los grupos se compararon con un test ANOVA. Para determinar los endofenotipos, se creó y siguió una lista de verificación o protocolo, con los criterios de selección más utilizados en este campo de investigación. Resultados: En los tres estudios se observa que los pacientes siempre presentan peores rendimientos que los controles, manteniéndose estas diferencias a lo largo de los tres tiempos de estudio, con independencia de la mayoría de las variables sociodemográficas y clínicas. Las puntuaciones medias de los familiares, a pesar de presentar un comportamiento inestable, equiparándose a las de los pacientes en algunos momentos y en otros a las de los controles, siempre conservaron el mismo perfil o patrón intermedio (TB≤TB-F≤CS). Limitaciones: En el estudio 1 sólo se incluyeron sujetos diestros. En los estudios 2 y 3 se detectó una disminución importante en el número de casos de familiares en el tiempo 3, por lo cual fuera necesario excluir del análisis los resultados de este grupo de familiares en ese momento del estudio. Conclusiones: Los pacientes con trastorno bipolar presentan déficits cognitivos en la VMM, en la MV y en la VPI, con independencia de la mayoría de los factores sociodemográficos y clínicos. Los familiares de los pacientes presentan déficits en la VMM y en la MV en T1. Además, en todos los momentos y pruebas utilizadas, los rendimientos de los familiares presentan un perfil o patrón intermedio entre los rendimientos de los otros dos grupos. Teniendo en cuenta estos elementos y el cumplimiento de algunos otros de los criterios de la lista de verificación, podemos concluir que, los déficits en la velocidad de procesamiento de la información son un endofenotipo potencial, la disfunción en la velocidad motora manual es un endofenotipo bastante probable, y la memoria visual es de los tres, el más adecuado para ser incluido dentro del perfil endofenotípico del Trastorno Bipolar. Todo esto a la espera de nuevos estudios con resultados similares que apoyen estas conclusiones