Search bioRxiv⌕ Search

bioRxiv · 10.1101/2022.08.25.505068

Modulation of motor vigour by expectation of reward probability trial-by-trial is preserved in healthy ageing and Parkinson's disease patients

Abstract

Motor improvements, such as faster movement times or increased velocity, have been consistently associated with reward magnitude in deterministic contexts. Yet whether individual inferences on reward probability influence motor vigour dynamically remains undetermined. Here we investigated how dynamically inferring volatile action-reward contingencies modulated motor performance trial-by-trial in healthy younger (HYA, 37) and older adults (HOA, 37), and in medicated Parkinsons Disease patients (PD, 20). We conducted an online study that coupled a standard one-armed bandit decision-making paradigm with a motor sequence task and used a validated hierarchical Bayesian model to fit trial-by-trial data. Our results showed that stronger predictions about the tendency of the action-reward contingency led to faster performance tempo on a trial-by-trial basis without modulating reaction times (RT). Using Bayesian linear mixed models, we demonstrated in HYA, HOA and PD a similar sensitivity (slope) of execution tempo to inferences about the reward probabilities, despite HOA and PD being generally slower than HYA (intercept). In a second experiment in HYA (39), we additionally showed that subjective inferences about credit assignment - whether lack of reward is associated with an incorrect decision or execution error - led to a similar modulation of motor vigour by reward expectation. Our study is the first to reveal that the dynamic updating of beliefs about volatile action-reward contingencies positively biases motor performance through faster execution tempo, without affecting RT. We also provide novel evidence for a preserved sensitivity of motor vigour to inferences about the action-reward mapping in ageing and medicated PD. SIGNIFICANCE STATEMENTNavigating a world rich in uncertainty relies on updating beliefs about the probability that our actions lead to reward. Here we investigated how inferring the action-reward contingencies in a volatile environment modulated motor vigour trial-by-trial in healthy younger and older adults, and in Parkinsons Disease patients on medication. We found an association between trial- by-trial predictions about the tendency of the action-reward contingency and performance tempo, with stronger expectations speeding performance. We additionally provided evidence for a similar sensitivity of performance tempo to the strength of these predictions in all groups. Thus, dynamic beliefs about the changing relationship between actions and their outcome invigorated motor performance. This positive bias was not compromised by age or Parkinsons disease.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Tecilla, M., Grossbach, M., Gentile, G., Holland, P., Antonini, A., Ruiz, M. H.. 2022-08-26. Modulation of motor vigour by expectation of reward probability trial-by-trial is preserved in healthy ageing and Parkinson's disease patients. https://doi.org/10.1101/2022.08.25.505068

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

A systems-level model of sleep-dependent memory-consolidation failure in neurodegeneration: the spindle-slow-oscillation decoupling cascade dissociates amyloid and tau

During non-rapid-eye-movement (NREM) sleep, the temporal coupling of cortical slow oscillations (SOs), thalamic spindles, and hippocampal sharp wave ripples drives the consolidation of declarative memories. This coupling degrades in ageing and Alzheimers disease (AD), and although A{beta} and tau leave dissociable signatures in human sleep, the mechanisms by which progressive pathology dismantles the consolidation machinery are difficult to isolate experimentally, and have not to our knowledge been reproduced in a model that can be perturbed directly. We built a systems-level model in which cortical SOs and thalamic spindles are generated by reduced oscillators, hippocampal ripples replay encoded spike sequences, and the measured per-event SO-spindle timing alignment causally gates spike-timing dependent plasticity on cortical sequence synapses. A post-sleep cued-recall test reads out consolidation. Five neurodegeneration parameters (amyloid, tau, synaptic density, GABAergic inhibition, cholinergic tone) map to dis tinct mechanisms grounded in the human and animal literature. The model reproduces graded healthy consolidation and a progressive collapse in which coupling, slow-wave power, spindle power and recall fall monotonically and the overnight memory effect flips from consolidation to net forgetting, with weak memories failing first. Scrambling SO-spindle timing while holding oscillation power fixed abolishes consolidation, establishing that coupling timing, rather than oscillation power, is what the plasticity gate depends on within the model. A{beta} and tau impair memory through orthogonal signatures (A{beta} collapses slow-wave power while sparing replay order, tau the reverse) and this orthogonality holds across the entire A{beta} x tau plane and survives simultaneous {+/-}50% resampling of every mapping coefficient (40/40 samples), so it is not an artefact of a single calibration point. The model yields a falsifiable clinical prediction: closed-loop slow-oscillation enhancement rescues memory only when the deficit is amplitude/coupling-dominated, not when it is replay(tau)-dominated, despite normalising slow-wave power in both cases. Because the therapy arms dissociate coupling from memory benefit, the model also cautions against adopting SO-spindle coupling as a standalone surrogate endpoint.

neuroscience↗

Toxicity of MAPT 4R RNA Contributes to Motor Neuron Degeneration in ALS

MAPT (Tau) dysregulation is implicated in several neurodegenerative diseases, but its contribution to amyotrophic lateral sclerosis (ALS) is poorly understood. Here we show that mRNA isoforms encoding 4-repeat (4R) Tau are upregulated and cytoplasmically enriched in iPSC-derived motor neurons (MNs) from VCP-mutant and sporadic ALS, without a corresponding change in Tau protein. Using splice-switching antisense oligonucleotides and isoform-specific siRNAs, we find that enhanced 4R expression reduces MN viability, whereas its selective knockdown improves survival, with kinetics more consistent with an RNA-intrinsic effect than altered protein synthesis. Exon 10-containing MAPT RNA shows increased predicted secondary structure, self-association and altered Tau biocondensation in vitro. In post-mortem ALS cervical spinal cord, increased relative exon 10 usage is associated with a higher-risk clinical phenotype and shorter disease duration These findings identify an isoform-specific contribution of MAPT to MN vulnerability in ALS and nominate 4R MAPT RNA as a therapeutic target.

neuroscience↗

30 Hz High-Definition Transcranial Alternating Current Stimulation at the Left Frontal Cortex Reduces the Spectral Slope of the EEG in the Contralateral Hemisphere

Background: High-definition transcranial alternating current stimulation (HD-tACS) is favored by the neurostimulation community for its precision and ability to influence neuronal dynamics. Yet, the exact mechanism by which the underlying brain structures are being affected remains unclear. We believe that the investigation of the aperiodic nature of the electroencephalograph (EEG) could shed light on the modulatory effects of HD-tACS. Methods: We analyzed the EEG of 9 participants during a compensatory tracking task (CTT) in two sessions, each with different HD-tACS protocols. Every session consisted of an initial period of no stimulation, followed by 30 Hz HD-tACS in the left motor (M30) or frontal (F30) cortex. We then isolated the aperiodic component of the EEG and calculated its spectral slope {beta}. Results and Discussion: {beta} decreased during F30 mainly in the right frontal cortex, indicating a shift towards higher frequencies and an increase of the excitatory/inhibitory balance. Additionally, we found that despite the long monotonus task the accuracy of the participants did not decrease, which might be attributed to the ability of both M30 and F30 to sustain attention for prolonged time. Finally, the change of CTT accuracy during the stimulation correlated with the {beta} of specific channels before the stimulation. This indicates the potential of {beta} to be used as a screening biomarker in future studies. In conclusion, we showed the ability of HD-tACS to alter EEG aperiodic dynamics and paved the way for future exploration of such dynamics in the field.

neuroscience↗