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Widmer, M.

Publications and source records attributed to Widmer, M..

4 recordsLinked to original sources

Reinforcement Learning Is Impaired in the Sub-acute Post-stroke Period

BackgroundNeurorehabilitation approaches are frequently predicated on motor learning principles. However, much is left to be understood of how different kinds of motor learning are affected by stroke causing hemiparesis. Here we asked if two kinds of motor learning often employed in rehabilitation, (1) reinforcement learning and (2) error-based adaptation, are altered at different times after stroke. MethodsIn a cross-sectional design, we compared learning in two groups of patients with stroke, matched for their baseline motor execution deficit on the paretic side. The early group was tested within 3 months following stroke (N = 35) and the late group was tested more than 6 months after stroke (N = 30). Two types of task were studied: one based on reinforcement learning and the other on error-based learning. ResultsWe found that reinforcement learning was impaired in the early but not the late group, whereas error-based learning was unaffected compared to controls. These findings could not be attributed to differences in baseline execution, cognitive impairment, gender, age, or lesion volume and location. ConclusionsThe presence of a specific impairment in reinforcement learning in the first 3 months after stroke has important implications for rehabilitation. It might be necessary to either increase the amount of reinforcement feedback given early or even delay onset of certain forms of rehabilitation training, e.g., like constraint-induced movement therapy, and instead emphasize others forms of motor learning in this early time period. A deeper understanding of stroke-related changes in motor learning capacity has the potential to facilitate the development of new, more precise treatment interventions.

neuroscience↗

TransCistor reveals the landscape of cis-regulatory long noncoding RNAs

A key attribute of some long noncoding RNAs (lncRNAs) is their ability to regulate expression of neighbouring genes in cis. However, such cis-lncRNAs are presently defined using ad hoc criteria that, we show, are prone to false-positive predictions. The resulting lack of cis-lncRNA catalogues hinders our understanding of their extent, characteristics and mechanisms. Here, we introduce TransCistor, a framework for defining and identifying cis-lncRNAs based on enrichment of targets amongst proximal genes. TransCistors simple and conservative statistical models are compatible with functionally-defined target gene maps generated by existing and future technologies. Using transcriptome-wide perturbation experiments for 268 human and 134 mouse lncRNAs, we provide the first large-scale survey of cis-lncRNAs. Known cis-lncRNAs are correctly identified, including XIST, LINC00240 and UMLILO, and predictions are consistent across analysis methods, perturbation types and independent experiments. Our results indicate that cis-activity is detected in a minority of lncRNAs, primarily involving activators over repressors. Cis-lncRNAs are detected by both RNA interference and antisense oligonucleotide perturbations. Mechanistically, cis-lncRNA transcripts are observed to physically associate with their target-genes, and are weakly enriched with enhancer-elements. In summary, TransCistor establishes a quantitative foundation for cis-lncRNAs, opening a path to elucidating their molecular mechanisms and biological significance.

genomics↗

No evidence for motor recovery-related cortical reorganization after stroke using resting-state fMRI

Cortical reorganization has been suggested as mechanism for recovery after stroke. It has been proposed that a form of cortical reorganization (changes in functional connectivity between brain areas) can be assessed with resting-state fMRI. Here we report the largest longitudinal data-set in terms of overall sessions in 19 patients with subcortical stroke and 11 controls. Patients were imaged up to 5 times over one year. We found no evidence for post-stroke cortical reorganization despite substantial behavioral recovery. These results could be construed as questioning the value of resting-state imaging. Here we argue instead that they are consistent with other emerging reasons to challenge the idea of motor recovery-related cortical reorganization post-stroke when conceived as changes in connectivity between cortical areas.

neuroscience↗

Finger recruitment patterns during mirror movements suggest two systems for hand recovery after stroke

Accumulating behavioural and neurophysiological evidence suggests that upper-limb control relies on contributions from both cortical and subcortical motor circuits, with cortical inputs providing fine-finger function and subcortical inputs providing the ability for gross movements, respectively. During recovery of function after stroke, the relative contributions from these pathways may shift. Here we propose that mirror movements that appear after stroke provide a non-invasive assay through which relative contributions from cortical and subcortical pathways towards hand recovery can be studied. We hypothesized that mirror movements, like hand function, are generated by summed contributions from cortical and subcortical pathways, and suggest that subcortical contributions should be characterized by a broad recruitment of fingers, while cortical contributions primarily recruit the homologous finger in the passive hand. In a longitudinal stroke recovery study (Xu et al., 2016), we quantified mirror movements and paretic hand function in 53 stroke patients in the year following unilateral stroke. Mirror movements in the non-paretic hand were exaggerated early after damage (week 2), with paretic finger presses broadly recruiting multiple fingers in the non-paretic hand. On average, however, mirroring in homologous fingers was 1.76 times larger than in non-homologous fingers. Over the year, mirroring in the non-paretic hand progressively normalized with a time-course that mimicked that for the fine-finger deficits in the paretic hand. In comparison, during non-paretic finger presses, the homologous component of mirroring in the paretic hand was reduced early after stroke (week 2) but progressively normalized. Altogether, we conclude that the pattern of mirror movements across homologous and non-homologous fingers reflect the summed contributions of both cortical and subcortical systems, and we discuss the implications of our results towards hand recovery after stroke.

neuroscience↗