Biology subjects

Luft, A. R.

Publications and source records attributed to Luft, A. R..

4 recordsLinked to original sources

bioRxiv2025

Impaired Peri-infarct Long-Term Potentiation Suggests Alternative Mechanisms of Post-stroke Recovery in Rats

BackgroundEarly after stroke, a period of heightened plasticity in the peri-infarct cortex is thought to provide the physiological substrate for functional motor recovery through increased expression of long-term potentiation (LTP). Prior slice electrophysiology studies on the capacity for LTP after stroke reported conflicting results. Slice preparation could have influenced the results by disrupting neuromodulatory processes altered after stroke. Therefore, whether LTP can be induced in the peri-infarct cortex remains to be elucidated. We investigated LTP in the peri-infarct cortex of anesthetized rats using a novel in vivo method that preserves local and long-range circuit dynamics. MethodsLTP, synaptic transmission and short-term plasticity were assessed under urethane anaesthesia in 15 rats (11 with focal stroke to the primary motor cortex, and 4 sham operated controls). Rats were tested one or two weeks after stroke using a minimally perturbed in vivo LTP induction protocol validated in naive rats. Motor function was evaluated using the cylinder test at baseline and at one or two-weeks post stroke. ResultsLTP in the peri-infarct cortex was supressed in the stroke group compared to sham controls. In addition, synaptic transmission was reduced for higher stimulation intensities, and short-term plasticity shifted from facilitation to depression, indicating impaired synaptic function at one- and two-weeks post-stroke. Behaviorally, the lesioned rats exhibited motor deficits at one week but showed full recovery by two weeks post-stroke. ConclusionIn recovering animals, both LTP and synaptic transmission are profoundly impaired in the peri-infarct cortex. These findings suggest that mechanisms other than LTP-based plasticity underlie motor recovery during this stage.

neuroscience↗

bioRxiv2023

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↗

bioRxiv2020

Technology-aided assessment of functionally relevant sensorimotor impairments in arm and hand of post-stroke individuals

BackgroundAssessing arm and hand sensorimotor impairments that are functionally relevant is essential to optimize the impact of neurorehabilitation interventions. Technology-aided assessments should provide a sensitive and objective characterization of upper limb impairments, but often provide arm weight support and neglect the importance of the hand, thereby questioning their functional relevance. The Virtual Peg Insertion Test (VPIT) addresses these limitations by quantifying arm movements and grip forces during a goal-directed manipulation task without arm weight support. The aim of this work was to evaluate the potential and robustness of the VPIT metrics to inform on sensorimotor impairments in arm and hand, and especially identify the functional relevance of the detected impairments. MethodsArm and hand sensorimotor impairments were systematically characterized in 30 chronic stroke patients using conventional clinical scales and the VPIT. For the latter, ten previously established kinematic and kinetic core metrics were extracted and compared to conventional clinical scales of impairment and activity limitations. Additionally, the robustness of the VPIT metrics was investigated by analyzing their clinimetric properties (test-retest reliability, measurement error, and learning effects). ResultsTwenty-three of the participants, the ones with mild to moderate sensorimotor impairments and without strong cognitive deficits, were able to successfully complete the VPIT protocol (duration 16.6 min). The VPIT metrics detected impairments in arm and hand in 90.0% of the participants, and were sensitive to increased muscle tone and pathological joint coupling. Most importantly, moderate to high significant correlations between conventional scales of activity limitations and the VPIT metrics were found, thereby indicating their functional relevance when grasping and transporting lightweight objects as well as dexterous finger manipulations. Lastly, the robustness of three out of the ten VPIT core metrics in post-stroke individuals was confirmed. ConclusionsThis work provides evidence that technology-aided assessments requiring goal-directed manipulations without arm weight support can provide an objective, robust, and clinically feasible way to assess functionally relevant sensorimotor impairments in arm and hand in chronic post-stroke individuals with mild to moderate deficits. This allows better identifying impairments with high functional relevance and can contribute to optimizing the functional benefits of neurorehabilitation interventions. Retrospectively registered: clinicaltrials.gov/ct2/show/NCT03135093

neuroscience↗

bioRxiv2019

An Objective Technology-based Assessment of Arm and Hand Sensorimotor Disability in Neurological Disorders

BackgroundDetailed assessments of upper limb disability are essential to understand and monitor sensorimotor recovery. Usually, multiple timeconsuming assessments are required to define a holistic sensorimotor profile of proximal (shoulder-elbow) and distal (wrist-hand) impairments and their impact on the capacity to perform activities. We propose and evaluate a novel physiologically-motivated computational framework for objectively assessing sensorimotor profiles in neurological patients using a single, rapid technology-based assessment involving goal-directed arm and hand movements. MethodsThe Virtual Peg Insertion Test (VPIT) was administered to 121 healthy and 80 neurological subjects. The framework provides 25 kinematic and kinetic metrics expected to describe 12 sensorimotor components representative of ataxia and paresis and their influence on task performance, as well as one overall disability measure. The feasibility (protocol duration), structural validity (factor analysis and correlations{rho} between sensorimotor components), concurrent validity (correlation with Action Research Arm Test; ARAT), and discriminant validity (comparing healthy controls and patients, and patients with different disability levels) were evaluated. ResultsThe median VPIT protocol duration was 16.5min in neurological patients. The sensor-based metrics could unambiguously be grouped into 12 mostly independent (median |{rho}|=0.14) components. Ten components showed significant differences between healthy and impaired subjects and nine components indicated clear trends across disability levels, without any ceiling effects. The VPIT overall disability measure and ARAT were moderately correlated ({rho}=-0.53, p<0.001). ConclusionsThis work demonstrates the possibility to rapidly, holistically, and objectively assess proximal and distal sensorimotor impairments and their influence on the capacity to perform activities with a single assessment.

neuroscience↗