Biology subjects

Dux, P. E.

Publications and source records attributed to Dux, P. E..

10 recordsLinked to original sources

bioRxiv2024

Dopamine alters motor learning performance in the presence and absence of feedback

We often choose to learn motor skills not only because of some external reward, but also because motor learning, in and of itself, is satisfying. While dopamine is thought to drive reward-based motor learning, it remains unclear whether dopamine is implicated in motor learning under conditions ostensibly driven by intrinsic rewards/motivation (i.e., in the absence of extrinsic feedback or reward). Here, by pharmacologically manipulating dopamine using the dopamine precursor Levodopa, we investigated the role of dopamine in an explicit motor learning task guided by internally determined signals of performance success, by removing intrinsic feedback about task success. Specifically, we asked participants to strategically aim away from presented targets by various instructed angles: a form of explicit motor learning that contributes to performance in the classic visuomotor rotation task. In the feedback condition, targets jumped mid-movement by the instructed angle, such that success in target hitting depended on successfully aiming away by the instructed angle. In the no-feedback condition, intrinsic feedback about task success was removed by having targets disappear mid-movement, such that participants could not know if they succeeded at hitting the targets or not. We found that dopamine altered performance, both with and without task feedback about task success. This provides direct evidence for a role of dopamine in motor learning driven by internal task goals.

neuroscience↗

bioRxiv2024

On the neural substrates of mind wandering and dynamic thought: A drug and brain stimulation study

The impact of mind wandering on our daily lives ranges from diminishing productivity, to facilitating creativity and problem solving. There is evidence that distinct internal thought types can be modulated by transcranial direct current stimulation (tDCS), although little is known about optimal stimulation parameters or the mechanisms behind such effects. In addition, recent findings suggest changes in dopamine availability may alter the effect tDCS has on neural and behavioural outcomes. Dopaminergic functioning has also been implicated in executive processes anticorrelated with mind wandering such as attention and working memory, however the neurochemical mechanisms involved in internal thoughts are largely unknown. Here, we investigated the role of dopamine, and tDCS, on internal thought processes. Specifically, using an attentional control task, we tested whether dopamine availability (levodopa or placebo) mediated the effects of online high definition tDCS (HD-tDCS; 2mA, or sham). There was no evidence for our hypothesised effect of left prefrontal cortex HD-tDCS reducing task unrelated thought, nor freely moving thought. This failure to replicate previous HD-tDCS findings emphasises the importance of employing robust methodological practices within this field to improve confidence in the findings. However, we did find that levodopa reduced freely moving thought, relative to placebo. We also found preliminary evidence that dopamine availability may moderate the relationship between stimulation and behavioural variability performance during periods of task unrelated thought. Overall, these findings suggest that stimulation does not affect dynamic internal thought, however there is initial evidence for the potential effectiveness of targeting the dopaminergic system to reduce spontaneous internal thoughts and improve behavioural performance.

neuroscience↗

bioRxiv2024

Causal evidence for increased theta and gamma phase consistency in a parieto-frontal network during the maintenance of visual attention

Endogenous visuo-spatial attention is under the control of a fronto-parietal network of brain regions. One key node in this network, the intra-parietal sulcus (IPS), plays a crucial role in maintaining endogenous attention, but little is known about its ongoing physiology and network dynamics during different attentional states. Here, we investigated the reactivity of the left IPS in response to brain stimulation under different states of selective attention. We recorded electroencephalography (EEG) in response to single pulses of transcranial magnetic stimulation (TMS) of the IPS, while participants (N=44) viewed bilateral random-dot motion displays. Individual MRI-guided TMS pulses targeted the left IPS, while the left primary somatosensory cortex (S1) served as an active control site. In separate blocks of trials, participants were cued to attend covertly to the motion display in one hemifield (left or right) and to report brief coherent motion targets. The perceptual load of the task was manipulated by varying the degree of motion coherence of the targets. Excitability, variability and information content of the neural responses to TMS were assessed by analysing TMS-evoked potential (TEP) amplitude and inter-trial phase clustering (ITPC), and by performing multivariate decoding of attentional state. Results revealed that a left posterior region displayed reduced variability in the phase of theta and gamma oscillations following TMS of the IPS, but not of S1, when attention was directed contralaterally, rather than ipsilaterally to the stimulation site. Under these same conditions, a right frontal cluster also displayed reduced theta variability and increased amplitude of TEPs after TMS of the IPS but not S1. Reliable decoding of attentional state was achieved after TMS pulses of both S1 and IPS. Taken together, our findings suggest that endogenous control of visuo-spatial attention leads to changes in the intrinsic oscillatory properties of the IPS and its associated fronto-parietal network.

neuroscience↗

bioRxiv2023

Stimulating prefrontal cortex facilitates training transfer by increasing representational overlap

Difficulties in multitasking may be the price humans pay for our ability to generalise learning to new tasks. Mitigating these costs through training has been associated with reduced overlap of constituent task representations within a task-related brain network. Transcranial direct current stimulation (tDCS), which can modulate neural activity, has shown promise in generalising training gains. Whether tDCS influences the changes in task-associated representations to produce such training generalisation remains unexplored. Here, we paired prefrontal cortex tDCS with multitasking training, and collected functional magnetic resonance imaging data pre- and post- training. We found that 1mA tDCS enhanced visual search performance, and using machine learning to assess the overlap of brain activity related to the training, show that these generalised gains were predicted by changes in classification accuracy for patterns of frontal, parietal, and cerebellar activity in participants who received left prefrontal cortex stimulation. Thus, prefrontal cortex tDCS interacts with training related changes in task representations, potentially driving the generalisation of learning.

neuroscience↗

bioRxiv2023

On the role of prefrontal and parietal cortices in mind wandering and dynamic thought

Mind wandering is a common phenomenon in our daily lives and can have both an adaptive and detrimental impact. Recently, a dynamic framework has been proposed to characterise the heterogeneity of internal thoughts, suggesting there are three distinct thought types which can change over time - freely moving, deliberately constrained, and automatically constrained (thoughts). There is very little evidence on how different types of dynamic thought map onto the brain. Previous research has applied non-invasive transcranial direct current stimulation (tDCS) to causally implicate the prefrontal cortex and inferior parietal lobule in general mind wandering. However, a more recently developed and nuanced technique, high-definition tDCS (HD-tDCS), delivers more focal stimulation able to target specific brain regions. Therefore, the current study investigated the effect of anodal HD-tDCS applied to the left prefrontal and right inferior parietal cortices (with the occipital cortex included as an active control) on mind wandering, and specifically, the causal neural substrates of the three internal dynamic thought types. This was a single session study using a novel task which allows investigation into how dynamic thoughts are associated with behavioural variability and the recruitment of executive control operations across the three brain regions. Anodal stimulation to the prefrontal cortex decreased freely moving thought and anodal stimulation to the parietal lobule decreased deliberately constrained thought, with preliminary evidence for an increase in freely moving thought in the occipital cortex as well. These findings support the heterogenous nature of mind wandering, revealing that different brain regions are implicated in distinct dynamic thought types.

neuroscience↗

bioRxiv2023

Dopamine alters the effect of brain stimulation on decision-making

Non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), show promise in treating cognitive and behavioural impairments in clinical conditions. However, optimisation of such clinical applications requires a better understanding of how tDCS alters cognition and behaviour. Existing evidence implicates dopamine in the way tDCS alters brain activity and plasticity, however, there is as yet no causal evidence for a role of dopamine in tDCS effects on cognition and behaviour. Here, in a preregistered, double-blinded study, we examined how pharmacologically manipulating dopamine altered the effect of tDCS on the speed-accuracy trade-off, which taps ubiquitous strategic cognitive processes. Cathodal tDCS was delivered over the left prefrontal cortex and the superior medial frontal cortex before participants completed a dot-motion task, deciding the direction of moving dots under instructions to emphasize speed, accuracy, or both. We leveraged computational modelling to uncover how our manipulations altered latent decisional processes driving the speed-accuracy tradeoff. We show that dopamine in combination with tDCS (but not tDCS alone, nor dopamine alone) not only impaired decision accuracy, but also impaired discriminability, which suggests that these manipulations altered the encoding or representation of discriminative evidence. This is, to the best of our knowledge, the first direct evidence implicating dopamine in the way tDCS affects cognition and behaviour. Significance statementTranscranial direct current stimulation (tDCS) can improve cognitive and behavioural impairments in clinical conditions, however better understanding of its mechanisms is required to optimise future clinical applications. Here, using a pharmacological approach to manipulate brain dopamine levels in healthy adults, we demonstrate a role for dopamine in the effects of tDCS in the speed-accuracy trade-off, a strategic cognitive process ubiquitous in many contexts. In doing so, we provide direct evidence implicating dopamine in the way tDCS affects cognition and behaviour.

neuroscience↗

bioRxiv2023

Dopamine increases accuracy and lengthens deliberation time in explicit motor skill learning.

Although animal research implicates a central role for dopamine in motor skill learning, a direct causal link has yet to be established in neurotypical humans. Here, we tested if a pharmacological manipulation of dopamine alters motor learning, using a paradigm which engaged explicit, goal-directed strategies. Participants (27 females, 11 males, aged 18-29 years) first consumed either 100mg of Levodopa (n=19), a dopamine precursor that increases dopamine availability, or placebo (n=19). Then, during training, participants learnt the explicit strategy of aiming away from presented targets by instructed angles of varying sizes. Targets shifted mid-movement by the instructed aiming angle. Task success was thus contingent upon aiming accuracy. The effect of the dopamine manipulations on skill learning was assessed during training, and at an overnight follow-up. Increasing dopamine availability improved aiming accuracy and lengthened reaction times, particularly for larger, more difficult aiming angles, both at training, and at follow-up. Results support the proposal that dopamine is important in decisions to engage instrumental motivation to optimise performance, particularly when learning to execute goal-directed strategies in motor skill learning.

neuroscience↗

bioRxiv2021

Not Quite All in Our Head: Intervention is a Better Predictor of tDCS Mind-Wandering Effects than Subjective Beliefs About Experimental Results

BackgroundEstablishing adequate blinding for non-invasive brain stimulation research is a topic of extensive debate, especially regarding the efficacy of sham control methods for transcranial direct current stimulation (tDCS) studies. Fassi and Cohen Kadosh [1] assessed the influence of subjective participant belief regarding stimulation type (active or sham) and dosage on behaviour using data from Filmer et al. [2] who applied five stimulation protocols (anodal 1.0mA, cathodal 1.0mA, cathodal 1.5mA, cathodal 2.0mA and sham) to assess the neural substrates of mind wandering. Fassi and Cohen Kadosh [1] concluded that subjective belief drove the pattern of results observed by Filmer et al. [2]. ObjectiveFassi and Cohen Kadosh [1] did not assess the key contrast between conditions in Filmer et al. (2019) - 2mA vs sham - rather they examined all stimulation conditions. Here, we consider the relationship between objective and subjective intervention in this key contrast. MethodsWe replicated the analysis and findings of both Filmer et al. [2] and Fassi and Cohen Kadosh [1] before assessing 2mA vs. sham via Bayesian ANOVA on subjective belief regarding stimulation type and dosage. ResultsOur results support objective intervention as the strongest predictor of stimulation effects on mind-wandering when 2mA vs sham was examined, over and above that of subjective intervention. ConclusionsThe conclusions made by Filmer et al. [2] are confirmed. However, it is important to control for and understand the possible effects of subjective beliefs in sham-controlled studies. Best practice to prevent these issues remains the inclusion of active control conditions.

neuroscience↗

bioRxiv2020

Age-related differences in the role of the prefrontal cortex in sensory-motor training gains: A tDCS study

The ability to process multiple sources of information concurrently is particularly impaired as individuals age and such age-related increases in multitasking costs have been linked to impairments in response selection. Previous neuroimaging studies with young adults have implicated the left hemisphere prefrontal cortex (PFC) as a key neural substrate of response selection. In addition, several transcranial direct current stimulation studies (tDCS) have provided causal evidence implicating this region in response selection and multitasking operations. For example, Filmer at al. (2013b) demonstrated that typically observed response selection learning/training gains in young adults were disrupted via offline transcranial direct current stimulation (tDCS) of left, but not right, PFC. Here, considering evidence of functional dedifferentiation in the brains of older adults, we assessed if this pattern of response selection learning disruption via tDCS to the left PFC is observed in older adults, testing if this region remains a key response selection node as individuals age. In a pre-registered study with 58 older adults, we applied anodal, cathodal, and sham stimulation to left and right PFC, and measured performance as participants trained on low- and high-response selection load tasks. Active stimulation did not disrupt training in older adults as compared to younger adults. However, there was evidence of enhanced training gains via tDCS, which scaled with response selection task difficulty. The results highlight age-related differences in the casual neural substrates that subserve response selection and learning.

neuroscience↗

bioRxiv2019

Cognitive capacity limits are remediated by practice-induced plasticity in a striatal-cortical network

Humans show striking limitations in information processing when multitasking, yet can modify these limits with practice. Such limitations have been linked to a frontal-parietal network, but recent models of decision-making implicate a striatal-cortical network. We adjudicated these accounts by investigating the circuitry underpinning multitasking in 100 individuals and the plasticity caused by practice. We observed that multitasking costs, and their practice induced remediation, are best explained by modulations in information transfer between the striatum and the cortical areas that represent stimulus-response mappings. Specifically, our results support the view that multitasking stems at least in part from taxation in information sharing between the putamen and pre-supplementary motor area (pre-SMA). Moreover, we propose that modulations to information transfer between these two regions leads to practice-induced improvements in multitasking. Significance statementHumans show striking limitations in information processing when multitasking, yet can modify these limits with practice. Such limitations have been linked to a frontal-parietal network, but recent models of decision-making implicate a striatal-cortical network. We adjudicated these accounts by investigating the circuitry underpinning multitasking in 100 individuals and the plasticity caused by practice. Our results support the view that multitasking stems at least in part from taxation in information sharing between the putamen and pre-supplementary motor area (pre-SMA). We therefore show that models of cognitive capacity limits must consider how subcortical and cortical structures interface to produce cognitive behaviours, and we propose a novel neurophysiological substrate of multitasking limitations.

neuroscience↗