Ned Jenkinson

BackgroundPairing intermittent theta burst stimulation (iTBS) with neuromuscular electrical stimulation (NMES) can increase corticospinal excitability (CSE) of a relaxed muscle. Whether initiating stimulation with surface electromyographic activity (sEMG-triggered) during an intentional holding task enhances this effect, and whether such facilitation is preserved with ageing, remains unknown.ObjectiveTo compare the effects of different paired and unpaired stimulation protocols on CSE in young and older adults, and to examine acute effects on hand function in older adults.MethodsYoung and older adults who responded to iTBS as ‘expected’ (increased CSE after stimulation) received sEMG-triggered iTBS+NMES, and sEMG-triggered sham iTBS+NMES targeting the abductor pollicis brevis (APB) of the dominant hand on separate occasions. A subset of young adults also received non-triggered iTBS+NMES. Stimulation was delivered while participants held a small cylinder between the thumb and index finger. Motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation were recorded at baseline and up to 30 min post-stimulation. In older adults, hand function was assessed using maximum voluntary contraction (MVC), Nine Hole Peg Test (NHPT), and Box and Block Test (BBT).ResultssEMG-triggered iTBS+NMES produced greater MEP facilitation than sham iTBS+NMES in both age groups. sEMG-triggered and non-triggered iTBS+NMES produced comparable facilitation in young adults. No group-level improvements were observed in MVC, NHPT, or BBT.ConclusionssEMG-triggered iTBS+NMES in conjunction with an intentional holding task acutely enhanced CSE in young and older adults, suggesting that intentional motor involvement during stimulation, rather than brief muscle activation per se, contributes to the observed facilitation.

Residual errors in sensorimotor adaptation are commonly attributed to an equilibrium between trial-by-trial learning and forgetting. Recent research suggested that allowing sufficient time for mental rotation eliminates these errors. In a number of experimental conditions, we show that although restricted motor preparation time does limit adaptation—consistent with mental rotation—extending preparation time fails to eliminate the residual errors in motor adaptation.

Background: There is a current discord between the foundational theories underpinning motor learning and how we currently apply transcranial direct current stimulation (TDCS): the former is dependent on tight coupling of events while the latter is conducted with very low temporal resolution. Objective: Here we aimed to investigate the temporal specificity of stimulation by applying TDCS in short epochs, and coincidentally with movement, during a motor adaptation task. Methods: Participants simultaneously adapted a reaching movement to two opposing velocity-dependent force-fields (clockwise and counter-clockwise), distinguished by a contextual leftward or rightward shift in the task display and cursor location respectively. Brief bouts (< 3 second) of event-related TDCS (er-TDCS) were applied over M1 or the cerebellum during movements for only one of these learning contexts. Results: We show that when short duration stimulation is applied to the cerebellum and yoked to movement, only those reaching movements performed simultaneously with stimulation are selectively enhanced, whilst similar and interleaved movements are left unaffected. We found no evidence of improved adaptation following M1 er-TDCS, as participants displayed equivalent levels of error during both stimulated and unstimulated movements. Similarly, participants in the sham stimulation group adapted comparably during left and right-shift trials. Conclusions: It is proposed that the coupling of cerebellar stimulation and movement influences timing-dependent (i.e., Hebbian-like) mechanisms of plasticity to facilitate enhanced learning in the stimulated context.

A consistent finding in sensorimotor adaptation is a persistent undershoot of full compensation, such that performance asymptotes with residual errors greater than seen at baseline. This behaviour has been attributed to limiting factors within the implicit adaptation system, which reaches a sub-optimal equilibrium between trial-by-trial learning and forgetting. However, recent research has suggested that allowing longer motor planning periods prior to movement eliminates these residual errors. The additional planning time allows required cognitive processes to be completed before movement onset, thus increasing accuracy. Here we looked to extend these findings by investigating the relationship between increased motor preparation time and the size of imposed visuomotor rotation (30°, 45° or 60°), with regards to the final asymptotic level of adaptation. We found that restricting preparation time to 0.35 seconds impaired adaptation for moderate and larger rotations, resulting in larger residual errors compared to groups with additional preparation time. However, we found that even extended preparation time failed to eliminate persistent errors, regardless of magnitude of cursor rotation. Thus, the asymptote of adaptation was significantly less than the degree of imposed rotation, for all experimental groups. Additionally, there was a positive relationship between asymptotic error and implicit retention. These data suggest that a prolonged motor preparation period is insufficient to reliably achieve complete adaptation and therefore our results provide support for the proposal that limitations within the implicit learning system contributes to asymptotic adaptation levels. New & Noteworthy: Residual errors in sensorimotor adaptation are commonly attributed to an equilibrium between trial-by-trial learning and forgetting. Recent research suggested that allowing sufficient time for mental rotation eliminates these errors. In a number of experimental conditions, we show that while restricted motor preparation time does limit adaptation - consistent with mental rotation - extending preparation time fails to eliminate the residual errors in motor adaptation.

We provide the first evidence that interhemispheric communication plays an important role during sudden movement cancellation of two-handed responses. Simultaneously increased inhibition onto both hemispheres assists with two-handed movement cancellation. However, this network is not responsible for the widespread suppression of motor activity observed when only one of the two hands is cancelled. Instead, communication between hemispheres enables the separation of motor activity for the two hands and helps to execute the required one-handed response.

From psychology to economics, there has been substantial interest in how costs (e.g., delay, risk) are represented asymmetrically during decision-making when attempting to gain reward or avoid punishment. For example, in decision-making under risk, individuals show a tendency to prefer to avoid punishment rather than to acquire the equivalent reward (loss aversion). Although the cost of physical effort has recently received significant attention, it remains unclear whether loss aversion exists during effort-based decision-making. On the one hand, loss aversion may be hardwired due to asymmetric evolutionary pressure on losses and gains and therefore exists across decision-making contexts. On the other hand, distinct brain regions are involved with different decision costs, making it questionable whether similar asymmetries exist. Here, we demonstrate that young healthy human participants (females, 16; males, 6) exhibit loss aversion during effort-based decision-making by exerting more physical effort to avoid punishment than to gain a same-size reward. Next, we show that medicated Parkinson's disease (PD) patients (females, 9; males, 9) show a reduction in loss aversion compared with age-matched control subjects (females, 11; males, 9). Behavioral and computational analysis revealed that people with PD exerted similar physical effort in return for a reward but were less willing to produce effort to avoid punishment. Therefore, loss aversion is present during effort-based decision-making and can be modulated by altered dopaminergic state. This finding could have important implications for our understanding of clinical disorders that show a reduced willingness to exert effort in the pursuit of reward.SIGNIFICANCE STATEMENTLoss aversion—preferring to avoid punishment rather than to acquire equivalent reward—is an important concept in decision-making under risk. However, little is known about whether loss aversion also exists during decisions where the cost is physical effort. This is surprising given that motor cost shapes human behavior, and a reduced willingness to exert effort is a characteristic of many clinical disorders. Here, we show that healthy human individuals exert more effort to minimize punishment than to maximize reward (loss aversion). We also demonstrate that medicated Parkinson's disease patients exert similar effort to gain reward but less effort to avoid punishment when compared with healthy age-matched control subjects. This indicates that dopamine-dependent loss aversion is crucial for explaining effort-based decision-making.

From psychology to economics there has been substantial interest in how costs (e.g., delay, risk) are represented asymmetrically during decision-making when attempting to gain reward or to avoid punishment. For example, in decision-making under risk, individuals show a tendency to prefer to avoid punishment than to acquire the equivalent reward (loss aversion). Although the cost of physical effort has received significant recent attention due to the evaluation of motor costs being crucial in our daily decisions, it remains unclear whether loss aversion exists during effort-based decision-making. On the one hand, loss aversion may be hardwired due to asymmetric evolutionary pressure on losses and gains and therefore exists across decision-making contexts. On the other hand, distinct brain regions are involved with different decision costs, making it questionable whether similar asymmetries exist. Here, we demonstrate that young healthy participants exhibit loss aversion during effort-based decision-making by exerting more physical effort in order to avoid punishment than to gain a same-size reward. Next, we show that medicated Parkinson’s disease (PD) patients show a reduction in loss aversion compared to age-matched controls. Behavioural and computational analysis revealed that people with PD exerted similar physical effort in return for a reward, but were less willing to produce effort in order to avoid punishment. Therefore, loss aversion is present during effort-based decision-making and can be modulated by altered dopaminergic state. This finding could have important implications for our understanding of clinical disorders that show a reduced willingness to exert effort in the pursuit of reward. Significance Statement: Loss aversion – preferring to avoid punishment than to acquire equivalent reward – is an important concept in decision-making under risk. However, little is known about whether loss aversion also exists during decisions where the cost is physical effort. This is surprising given that motor cost shapes human behaviour, and a reduced willingness to exert effort is a characteristic of many clinical disorders. Here, we show that healthy individuals exert more effort to minimise punishment than to maximise reward (loss aversion). We also demonstrate that loss aversion is modulated by altered dopaminergic state by showing that medicated Parkinson’s disease patients exert similar effort to gain reward but less effort to avoid punishment. Therefore, dopamine-dependent loss aversion is crucial for explaining effort-based decision-making.

Early detection of the behavioural deficits of neurodegenerative diseases may help to describe the pathogenesis of such diseases and establish important biomarkers of disease progression. The aim of this study was to identify how sensorimotor adaptation of the upper limb, a cerebellar-dependent process restoring movement accuracy after introduction of a perturbation, is affected at the pre-clinical and clinical stages of spinocerebellar ataxia type 6 (SCA6), an inherited neurodegenerative disease. We demonstrate that initial adaptation to the perturbation was significantly impaired in the eighteen individuals with clinical motor symptoms but mostly preserved in the five pre-clinical individuals. Moreover, the amount of error reduction correlated with the clinical symptoms, with the most symptomatic patients adapting the least. Finally both pre-clinical and clinical individuals showed significantly reduced de-adaptation performance after the perturbation was removed in comparison to the control participants. Thus, in this large study of motor features in SCA6, we provide novel evidence for the existence of subclinical motor dysfunction at a pre-clinical stage of SCA6. Our findings show that testing sensorimotor de-adaptation could provide a potential predictor of future motor deficits in SCA6.