A Multiscale, Systems-Level, Neuropharmacological Model of Cortico-Basal Ganglia System for Arm Reaching Under Normal, Parkinsonian, and Levodopa Medication Conditions

In order to understand the link between substantia nigra pars compacta (SNc) cell loss and Parkinson's disease (PD) symptoms, we developed a multiscale computational model that can replicate the symptoms at the behavioural level by incorporating the key cellular and molecular mechanisms underlying PD pathology. There is a modelling tradition that links dopamine to reward and uses reinforcement learning (RL) concepts to model the basal ganglia. In our model, we replace the abstract representations of reward with the realistic variable of extracellular DA released by a network of SNc cells and incorporate it in the RL-based behavioural model, which simulates the arm reaching task. Our results successfully replicated the impact of SNc cell loss and levodopa (L-DOPA) medication on reaching performance. It also shows the side effects of medication, such as wearing off and peak dosage dyskinesias. The model demonstrates how differential dopaminergic axonal degeneration in basal ganglia results in various cardinal symptoms of PD. It was able to predict the optimum L-DOPA medication dosage for varying degrees of cell loss. The proposed model has a potential clinical application where drug dosage can be optimised as per patient characteristics.

Even well-practiced movements benefit from repetition

Professional golf players spend years practicing, but will still perform one or two practice swings without a ball before executing the actual swing. Why do they do this? In this study we tested the hypothesis that repeating a well-practiced movement leads to a reduction of movement variability. To operationalize this hypothesis, participants were tested in a center-out reaching task with four different targets, on four different days. To probe the effect of repetition they performed random sequences from one to six movements to the same target. Our findings show that, with repetition, movements are not only initiated earlier but their variability is reduced across the entire movement trajectory. Furthermore, this effect is present within and across the four sessions. Together, our results suggest that movement repetition changes the tradeoff between movement initiation and movement precision.

Home-Based Therapy After Stroke Using the Hand Spring Operated Movement Enhancer (HandSOME II)

We have developed a passive and lightweight wearable hand exoskeleton (HandSOME II) that improves range of motion and functional task practice in laboratory testing. For this longitudinal study, we recruited 15 individuals with chronic stroke and asked them to use the device at home for 1.5 h per weekday for 8 weeks. Subjects visited the clinic once per week to report progress and troubleshoot problems. Subjects were then given the HandSOME II for the next 3 months, and asked to continue to use it, but without any scheduled contact with the project team. Clinical evaluations and biomechanical testing was performed before and after the 8 week intervention and at the 3 month followup. EEG measures were taken before and after the 8 weeks of training to examine any recovery associated brain reorganization. Ten subjects completed the study. After 8 weeks of training, functional ability (Action Research Arm Test), flexor tone (Modified Ashworth Test), and real world use of the impaired limb (Motor Activity Log) improved significantly (p < 0.05). Gains in real world use were retained at the 3-month followup (p = 0.005). At both post-training and followup time points, biomechanical testing found significant gains in finger ROM and hand displacement in a reaching task (p < 0.05). Baseline functional connectivity correlated with gains in motor function, while changes in EEG functional connectivity paralleled changes in motor recovery. HandSOME II is a low-cost, home-based intervention that elicits brain plasticity and can improve functional motor outcomes in the chronic stroke population.

Effect of bilingualism on infants’ cognitive flexibility

Research suggests that bilinguals often outperform monolinguals on tasks that tap into executive functions, such as those requiring conflict resolution and cognitive flexibility. Recently, better attentional control has been detected in infants as young as 6 months, thereby providing a possible basis for a cognitive benefit before language production. The goal of the present study was to examine if cognitive flexibility is more advanced in bilingual infants. A detour reaching task assessing conflict resolution, a delayed response task assessing shifting, and a multiple location task assessing maintaining, were administered to 17-month-old infants. The main findings revealed that being bilingual did not improve performance on any of the executive function tasks. Furthermore, current exposure to a second language or language proficiency did not impact executive functioning. We conclude that a bilingual advantage in cognitive flexibility may not be present before children have enough experience in code switching.

Mirror-mediated string-pulling task in Eurasian jays (Garrulus glandarius)

Mirror tasks can be used to investigate whether animals can instrumentally use a mirror to solve problems and can understand the correspondence between reflections and the real objects they represent. Two bird species, a corvid (New Caledonian crow) and a parrot (African grey parrot), have demonstrated the ability to use mirrors instrumentally in mirror-mediated spatial locating tasks. However, they have not been challenged with a mirror-guided reaching task, which involves a more complex understanding of the mirror’s properties. In the present study, a task approximating the mirror-guided reaching task used in primate studies was adapted for, and given to, a corvid species (Eurasian jay) using a horizontal string-pulling paradigm. Four birds learned to pull the correct string to retrieve a food reward when they could see the food directly, whereas none used the reflected information to accomplish the same objective. Based on these results, it cannot be concluded whether these birds understand the correspondence between the location of the reward and its reflected information, or if the relative lack of visual-perceptual motor feedback given by the setup interfered with their performance. This novel task is posited to be conceptually more difficult compared to mirror-mediated spatial locating tasks, and should be used in avian species that have previously been successful at using the mirror instrumentally. This would establish whether these species can still succeed at it, and thus whether the task does indeed pose additional cognitive demands.

Kinematic Changes in the Uninjured Limb After a Traumatic Brachial Plexus Injury

Background: Traumatic brachial plexus injury (TBPI) typically causes sensory, motor and autonomic deficits of the affected upper limb. Recent studies have suggested that a unilateral TBPI can also affect the cortical representations associated to the uninjured limb.Objective: To investigate the kinematic features of the uninjured upper limb in participants with TBPI.Methods: Eleven participants with unilateral TBPI and twelve healthy controls matched in gender, age and anthropometric characteristics were recruited. Kinematic parameters collected from the index finger marker were measured while participants performed a free-endpoint whole-body reaching task and a cup-to-mouth task with the uninjured upper limb in a standing position.Results: For the whole-body reaching task, lower time to peak velocity (p = 0.01), lower peak of velocity (p = 0.003), greater movement duration (p = 0.04) and shorter trajectory length (p = 0.01) were observed in the TBPI group compared to the control group. For the cup-to-mouth task, only a lower time to peak velocity was found for the TBPI group compared to the control group (p = 0.02). Interestingly, no differences between groups were observed for the finger endpoint height parameter in either of the tasks. Taken together, these results suggest that TBPI leads to a higher cost for motor planning when it comes to movements of the uninjured limb as compared to healthy participants. This cost is even higher in a task with a greater postural balance challenge.Conclusion: This study expands the current knowledge on bilateral sensorimotor alterations after unilateral TBPI and should guide rehabilitation after a peripheral injury.

Hybrid dedicated and distributed coding in PMd/M1 provides separation and interaction of bilateral arm signals

Pronounced activity is observed in both hemispheres of the motor cortex during preparation and execution of unimanual movements. The organizational principles of bi-hemispheric signals and the functions they serve throughout motor planning remain unclear. Using an instructed-delay reaching task in monkeys, we identified two components in population responses spanning PMd and M1. A “dedicated” component, which segregated activity at the level of individual units, emerged in PMd during preparation. It was most prominent following movement when M1 became strongly engaged, and principally involved the contralateral hemisphere. In contrast to recent reports, these dedicated signals solely accounted for divergence of arm-specific neural subspaces. The other “distributed” component mixed signals for each arm within units, and the subspace containing it did not discriminate between arms at any stage. The statistics of the population response suggest two functional aspects of the cortical network: one that spans both hemispheres for supporting preparatory and ongoing processes, and another that is predominantly housed in the contralateral hemisphere and specifies unilateral output.

Portable, open-source solutions for estimating wrist position during reaching in people with stroke

Arm movement kinematics may provide a more sensitive way to assess neurorehabilitation outcomes than existing metrics. However, measuring arm kinematics in people with stroke can be challenging for traditional optical tracking systems due to non-ideal environments, expense, and difficulty performing required calibration. Here, we present two open-source methods, one using inertial measurement units (IMUs) and another using virtual reality (Vive) sensors, for accurate measurements of wrist position with respect to the shoulder during reaching movements in people with stroke. We assessed the accuracy of each method during a 3D reaching task. We also demonstrated each method’s ability to track two metrics derived from kinematics-sweep area and smoothness-in people with chronic stroke. We computed correlation coefficients between the kinematics estimated by each method when appropriate. Compared to a traditional optical tracking system, both methods accurately tracked the wrist during reaching, with mean signed errors of 0.09 ± 1.81 cm and 0.48 ± 1.58 cm for the IMUs and Vive, respectively. Furthermore, both methods’ estimated kinematics were highly correlated with each other (p < 0.01). By using relatively inexpensive wearable sensors, these methods may be useful for developing kinematic metrics to evaluate stroke rehabilitation outcomes in both laboratory and clinical environments.

Beta-band desynchronization reflects uncertainty in effector selection during motor planning

While beta-band activity during motor planning is known to be modulated by uncertainty about where to act, less is known about its modulations to uncertainty about how to act. To investigate this issue, we recorded oscillatory brain activity with EEG while human participants (n = 17) performed a hand choice reaching task. The reaching hand was either predetermined or of participants' choice, and the target was close to one of the two hands or at about equal distance from both. To measure neural activity in a motion-artifact-free time window, the location of the upcoming target was cued 1000-1500 ms before the presentation of the target, whereby the cue was valid in 50% of trials. As evidence for motor planning during the cueing phase, behavioral observations showed that the cue affected later hand choice. Furthermore, reaction times were longer in the choice than in the predetermined trials, supporting the notion of a competitive process for hand selection. Modulations of beta-band power over central cortical regions, but not alpha-band or theta-band power, were in line with these observations. During the cueing period, reaches in predetermined trials were preceded by larger decreases in beta-band power than reaches in choice trials. Cue direction did not affect reaction times or beta-band power, which may be due to the cue being invalid in 50% of trials, retaining effector uncertainty during motor planning. Our findings suggest that effector uncertainty, similar to target uncertainty, selectively modulates beta-band power during motor planning.