Biology subjects

Jenkinson, N.

Publications and source records attributed to Jenkinson, N..

12 recordsLinked to original sources

bioRxiv2025

Time-Dependent Facilitation of Homologous Actions

Unimanual actions can interfere with or facilitate similar actions performed with the opposite hand, especially when in close temporal proximity. Across three sequential button-press experiments, we tested how effector homology - anatomical similarity between fingers - and temporal delays between actions shape these effects. Specifically, we examined whether a priming action altered the reaction time (RT) of a subsequent action. Compared with unimanual RTs, we indexed slowing of the second actions RT as interference, and quickening as facilitation. Priming with homologous actions (e.g., index finger-index finger) produced interference at short intervals ([≤]200ms) but transitioned to facilitation at longer intervals ([≥]400ms). Priming with non-homologous actions (e.g., little finger-index finger) also produced interference at short intervals, but never resulted in facilitation. Critically, these patterns emerged whether the priming actions were performed with the opposite or the same hand, indicating that interference and facilitation do not depend on interhemispheric dynamics. Our results reveal a previously undocumented time-dependent shift from interference to facilitation that is specific to homologous actions, challenging models that explain the interference between parallel actions solely by competitive interhemispheric dynamics or central bottleneck processes. We propose that facilitation and interference flexibly coexist, and are shaped by effector homology and timing. These findings extend current models of bimanual coordination and highlight new opportunities for enhancing motor performance and neurorehabilitation. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=86 SRC="FIGDIR/small/682693v1_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@20dc18org.highwire.dtl.DTLVardef@151ea4corg.highwire.dtl.DTLVardef@ed2547org.highwire.dtl.DTLVardef@12a9550_HPS_FORMAT_FIGEXP M_FIG A left-hand index finger press primed a subsequent right-hand index (homologous) or right-hand little finger (non-homologous) response at variable delays. For homologous actions (index-index), reaction times (RTs) quickened relative to unimanual single-press baseline for delays [≥]400ms, whereas for non-homologous actions (index-little), RTs slowed and gradually returned to baseline by ~600ms. This dissociation indicates that effector homology and timing dictate whether a preceding action facilitates or interferes with the execution of a subsequent one. C_FIG

neuroscience↗

bioRxiv2023

Bilateral Intracortical Inhibition during Unilateral Motor Preparation and Sequence Learning

Motor sequence learning gradually quickens reaction time, suggesting that sequence learning alters motor preparation processes. Interestingly, evidence has shown that preparing sequence movements decreases short intracortical inhibition (SICI) in the contralateral motor cortex (M1), but also that sequence learning alters motor preparation processes in both the contralateral and ipsilateral M1s. Therefore, one possibility is that sequence learning alters the SICI decreases occurring during motor preparation in bilateral M1s. To examine this, two novel hypotheses were tested: unilateral sequence preparation would decrease SICI in bilateral M1s, and sequence learning would alter such bilateral SICI responses. Paired-pulse transcranial magnetic stimulation was delivered over the contralateral and ipsilateral M1s to assess SICI in an index finger muscle during the preparation of sequences initiated by either the right index or little finger. In the absence of sequence learning, SICI decreased in both the contralateral and ipsilateral M1s during the preparation of sequences initiated by the right index finger, suggesting that SICI decreases in bilateral M1s during unilateral motor preparation. As sequence learning progressed, SICI decreased in the contralateral M1 whilst it increased in the ipsilateral M1. Moreover, these bilateral SICI responses were observed at the onset of motor preparation, suggesting that sequence learning altered baseline SICI levels rather than the SICI decreases occurring during motor preparation per se. Altogether, these results suggest that SICI responses in bilateral M1s reflect two motor processes: an acute decrease of inhibition during motor preparation, and a cooperative but bidirectional shift of baseline inhibition levels as sequence learning progresses.

neuroscience↗

bioRxiv2023

Sub-Concussive Head Impacts From Heading Footballs Do Not Acutely Alter Brain Excitability As Compared to a Control Group

BackgroundRepeated sub-concussive head impacts are a growing brain health concern, but the possible mechanisms of trauma and plausible biomarkers remain elusive. One impediment is the lack of an experimental model to study the effects of sub-concussive head impacts on the brain. ObjectivesThis works objective was to provide an experimental model to study the acute effects of sub-concussive head impacts on the brain. To do so, this study aimed to replicate previous work from Di Virgilio et al. (2016) showing that head impacts from heading footballs acutely alter brain excitability by increasing corticomotor inhibition. MethodsScores from the Rivermead Post-Concussion Questionnaire and measurements of cortical silent period (CSP) duration - obtained using transcranial magnetic stimulation to assess corticomotor inhibition in the central nervous system - were taken before and after participants performed 20 football headings (Headings; n = 30) or control (Control; n = 30). ResultsThe results revealed increased headaches and dizziness symptoms in the Headings as compared to the Control group, revealing the qualitative experience of head impacts. The results then revealed that CSP duration similarly lengthened in both the Headings and Control groups, suggesting that head impacts did not cause the increased corticomotor inhibition. ConclusionsThe results show that head impacts from football headings did not acutely alter corticomotor inhibition as compared to a control group that did not experience head impacts, suggesting that excitability changes do not reflect acute sub-concussive brain injuries. Nonetheless, this work suggests that football headings can be used as an experimental model to study the effects of sub-concussive head impacts on brain health. Future work could use the present procedures to investigate additional biomarkers of brain injury.

neuroscience↗

bioRxiv2023

The Neurochemical Mechanisms Underlying the Enhancing Effects of Rewards and Punishments on Motor Performance

Monetary rewards and punishments enhance motor performance and are associated with corticospinal excitability (CSE) increases within the motor cortex (M1) during movement preparation. However, such CSE changes have unclear origins; they could stem from increased glutamatergic (GLUTergic) facilitation and/or decreased type A gamma-aminobutyric acid (GABAA)-mediated inhibition within M1. To investigate this, paired-pulse transcranial magnetic stimulation was used to assess GLUTergic facilitation and GABAA inhibition within M1 whilst participants prepared to execute 4-element finger-press sequences. Behaviourally, rewards and punishments enhanced both reaction and movement times. Neurochemically, regardless of rewards or punishments, a digit-specific increase in GLUTergic facilitation and digit-unspecific decrease in GABAA inhibition occurred during preparation as movement onset approached. In parallel, both rewards and punishments non-specifically increased GLUTergic facilitation, but only rewards non-specifically decreased GABAA inhibition during preparation. This suggests that, to enhance performance, rewards both increase GLUTergic facilitation and decrease GABAA inhibition whilst punishments selectively increase GLUTergic facilitation. A control experiment revealed that such changes were not observed post-movement as participants processed reward and punishment feedback, indicating they were selective to movement preparation. Collectively, these results map the neurochemical changes in M1 by which incentives enhance motor performance.

neuroscience↗

bioRxiv2022

Exploring Stop Signal Reaction Time Over Two Sessions of the Anticipatory Response Inhibition Task

Various behavioural tasks can measure the motor component of impulse control, response inhibition. Response inhibition encompasses the ability to cancel unwanted actions and is evaluated via stop signal reaction time (SSRT). The current study explored the effect of two sessions on SSRT within the anticipatory response inhibition task (ARIT) and how this compared to the stop signal task (SST). Forty-four participants completed two sessions of the ARIT and SST, 24 hours apart. SSRT and its constituent measures (Go trial reaction time, stop signal delay) were calculated. SSRT reflecting non-selective inhibition was consistent between sessions in both tasks (both p > .293). Reaction time and stop signal delay also remained stable across sessions in the ARIT (all p > .063), whereas in the SST, both reaction time (p = .013) and stop signal delay (p = .009) increased. Across the two sessions, SSRT reflecting partial inhibition improved (p < .001), which was underpinned by changes to reaction time (p < .001) and stop signal delay (p < .001). The maximal efficiency of non-selective inhibition remained stable across two sessions in the ARIT. Results of the SST confirmed that non-selective inhibition can however be affected by more than inhibitory network integrity when Go trial reaction times are not constrained in task design. Partial response inhibition measures changed across sessions, suggesting the sequential process captured by the SSRT occurred more quickly in session two. These findings highlight the absence/extent of inherent SSRT changes possible during multiple-session study designs e.g., pre/post, or active/sham comparisons.

neuroscience↗

bioRxiv2021

Cerebellar GABA change during visuomotor adaptation relates to adaptation performance and cerebellar network connectivity: A Magnetic Resonance Spectroscopic Imaging study.

Motor adaptation is crucial for performing accurate movements in a changing environment and relies on the cerebellum. Although cerebellar involvement has been well characterized, the neurochemical changes in the cerebellum underpinning human motor adaptation remain unknown. We used a novel Magnetic Resonance Spectroscopic Imaging (MRSI) technique to measure changes in the inhibitory neurotransmitter {gamma}-aminobutyric acid (GABA) in the human cerebellum during visuomotor adaptation. Participants used their right hand to adapt to a rotated cursor in the scanner, compared with a control task requiring no adaptation. We spatially resolved adaptation-driven GABA changes at the cerebellar nuclei and cerebellar cortex in the left and the right cerebellar hemisphere independently and found that simple right-hand movements increase GABA in the right cerebellar nuclei and decreases GABA in the left. When isolating adaptation-driven GABA changes, we found an increase in GABA in the left cerebellar nuclei and decrease in GABA in the right cerebellar nuclei. Early adaptation-driven GABA change in the right cerebellar nuclei correlated with adaptation performance: Participants showing greater GABA decrease adapted better, suggesting early GABA change is behaviourally relevant. Early GABA change also correlated with functional connectivity change in a cerebellar network: Participants showing greater decreases in GABA showed greater strength increases in cerebellar network connectivity. Results were specific to GABA, to adaptation and to the cerebellar network. This study provides first evidence for plastic changes in cerebellar neurochemistry during motor adaptation. Characterising these naturally occurring neurochemical changes may provide a basis for developing therapeutic interventions to facilitate human motor adaptation. Significance StatementDespite motor adaptation being fundamental to maintaining accurate movements, its neurochemical basis remains poorly understood, perhaps because measuring neurochemicals in the human cerebellum is technically challenging. Using a novel magnetic resonance spectroscopic imaging method, this study provides evidence for GABA changes in the left and right cerebellar nuclei driven by both simple movement and motor adaptation. The adaptation-driven GABA change in the right cerebellar nuclei correlated with adaptation performance, and with functional connectivity change in a cerebellar network. These results show the first evidence for plastic changes in cerebellar neurochemistry during a cerebellar learning task. This provides the basis for developing therapeutic interventions that facilitate these naturally occurring changes to amplify cerebellar-dependent learning.

neuroscience↗

bioRxiv2021

Timing is everything: event-related transcranial direct current stimulation improves motor adaptation

BackgroundThere 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. ObjectiveHere we aimed to investigate the temporal specificity of stimulation by applying TDCS in short epochs, and coincidentally with movement, during a motor adaptation task. MethodsParticipants 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. ResultsWe 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. ConclusionsIt 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.

neuroscience↗

bioRxiv2021

Residual errors in visuomotor adaptation persist despite extended motor preparation periods

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{degrees}, 45{degrees} or 60{degrees}), 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 & NoteworthyResidual 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.

neuroscience↗

bioRxiv2020

GABA relates to functional connectivity changes and retention in visuomotor adaptation

Motor adaptation is fundamental to maintaining accurate movements under changing conditions, but the neurochemical basis of human motor adaptation is not well understood. Here, we used an ultra-high-field MR multimodal acquisition to address the hypothesis that M1 GABA and M1-Cerebellar functional connectivity would relate to retention of adaptation, but not acquisition of adaptation. As such, we demonstrate higher baseline M1 [GABA] relates to greater retention but does not relate to adaptation-acquisition. This relationship is mediated by change in M1-Cerebellar functional connectivity: higher M1 [GABA] relates to a decreased M1-Cerebellar connectivity, resulting in greater retention. These findings showed anatomical, neurochemical and behavioural specificity: As expected, no relationship was found between retention and a control metabolite, retention and connectivity change between control regions and between M1 [GABA] and behaviour in a control condition. The implication of a mechanistic link from neurochemistry to retention advances our understanding of population variability in retention and provides a step towards therapeutic interventions to restore motor abilities.

neuroscience↗

bioRxiv2019

Dopamine-dependent loss aversion during 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 Parkinsons 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.\n\nSignificance StatementLoss 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 Parkinsons 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.

animal behavior and cognition↗

bioRxiv2019

Nicotinamide riboside augments the human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures in aged subjects: a placebo-controlled, randomized trial

NAD+ is modulated by conditions of metabolic stress and has been reported to decline with aging, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD+ metabolome, and questioned if tissue NAD+ levels are depressed with aging. We supplemented 12 aged men with NR 1g per day for 21-days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways. NR also depressed levels of circulating inflammatory cytokines. In an additional study, 31P magnetic resonance spectroscopy-based NAD+ measurement in muscle and brain showed no difference between young and aged individuals. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR, while suggesting that NAD+ decline is not associated with chronological aging per se in human muscle or brain.

clinical trials↗

bioRxiv2019

Impaired Desynchronization of Beta Activity Underlies Memory Deficits in People with Parkinson’s Disease

There is a pressing need to better understand the mechanisms underpinning the increasingly recognised non-motor deficits in Parkinsons disease. Brain activity during Parkinsons disease is excessively synchronized within the beta range (12-30Hz). However, relatively little is known about how the abnormal beta rhythms impact on non-motor symptoms. In healthy adults, beta desynchronization is necessary for successful episodic memory formation. We investigated whether there was a direct relationship between decreased beta modulation and memory formation in Parkinsons disease. Electroencephalography recordings were made during an established memory-encoding paradigm. Parkinsons participants showed impaired memory strength (P = 0.023) and reduced beta desynchronization (P = 0.014) relative to controls. Longer disease duration was correlated with a larger reduction in beta desynchronization, and a concomitant reduction in memory performance. These novel results extend the notion that pathological beta activity is causally implicated in the motor and (lesser appreciated) non-motor deficits inherent to Parkinsons disease.

neuroscience↗