The Readiness Potential (RP) is a slow negative EEG potential found in the seconds preceding voluntary actions. Here, we explore whether the RP is found only at this time, or if it also occurs when ...no action is produced. Recent theories suggest the RP reflects the average of accumulated stochastic fluctuations in neural activity, rather than a specific signal related to self-initiated action: RP-like events should then be widely present, even in the absence of actions. We investigated this hypothesis by searching for RP-like events in background EEG of an appropriate dataset for which the action-locked EEG had previously been analysed to test other hypotheses Khalighinejad, N., Brann, E., Dorgham, A., Haggard, P. Dissociating cognitive and motoric precursors of human self-initiated action. Journal of Cognitive Neuroscience. 2019, 1-14. We used the actual mean RP as a template, and searched the entire epoch for similar neural signals, using similarity metrics that capture the temporal or spatial properties of the RP. Most EEG epochs contained a number of events that were similar to the true RP, but did not lead directly to any voluntary action. However, these RP-like events were equally common in epochs that eventually terminated in voluntary actions as in those where voluntary actions were not permitted. Events matching the temporal profile of the RP were also a poor match for the spatial profile, and vice versa. We conclude that these events are false positives, and do not reflect the same mechanism as the RP itself. Finally, applying the same template-search algorithm to simulated EEG data synthesized from different noise distributions showed that RP-like events will occur in any dataset containing the 1⁄f noise ubiquitous in EEG recordings. To summarise, we found no evidence of genuinely RP-like events at any time other than immediately prior to self-initiated actions. Our findings do not support a purely stochastic model of RP generation, and suggest that the RP may be a specific precursor of self-initiated voluntary actions.
•Readiness Potential-like events occur in background EEG long before voluntary actions.•However, these events occur to the same degree in control data.•They also occur to the same degree in simulated spectrally-matched noise.•EEG more than 2 s before where voluntary actions does not differ from control data.
The decision that it is worth doing something rather than nothing is a core yet understudied feature of voluntary behaviour. Here we study "willingness to act", the probability of making a response ...given the context. Human volunteers encountered opportunities to make effortful actions in order to receive rewards, while watching a movie inside a 7 T MRI scanner. Reward and other context features determined willingness-to-act. Activity in the habenula tracked trial-by-trial variation in participants' willingness-to-act. The anterior insula encoded individual environment features that determined this willingness. We identify a multi-layered network in which contextual information is encoded in the anterior insula, converges on the habenula, and is then transmitted to the supplementary motor area, where the decision is made to either act or refrain from acting via the nigrostriatal pathway.
“Sense of agency” refers to the experience that links one’s voluntary actions to their external outcomes. It remains unclear whether this ubiquitous experience is hardwired, arising from specific ...signals within the brain’s motor systems, or rather depends on associative learning, through repeated cooccurrence of voluntary movements and their outcomes. To distinguish these two models, we asked participants to trigger a tone by a voluntary keypress action. The voluntary action was always associated with an involuntary movement of the other hand. We then tested whether the combination of the involuntary movement and tone alone might now suffice to produce a sense of agency, even when the voluntary action was omitted. Sense of agency was measured using an implicit marker based on time perception, namely a shift in the perceived time of the outcome toward the action that caused it. Across two experiments, repeatedly pairing an involuntary movement with a voluntary action induced key temporal features of agency, with the outcome now perceived as shifted toward the involuntary movement. This shift required involuntary movements to have been previously associated with voluntary actions. We show that some key aspects of agency may be transferred from voluntary actions to involuntary movements. An internal volitional signal is required for the primary acquisition of agency but, with repeated association, the involuntary movement in itself comes to produce some key temporal features of agency over the subsequent outcome. This finding may explain how humans can develop an enduring sense of agency in nonnatural cases, like brain–machine interfaces.
The orbitofrontal cortex (OFC) is a key brain region involved in complex cognitive functions such as reward processing and decision making. Neuroimaging studies have reported unilateral OFC response ...to reward-related variables; however, those studies rarely discussed this observation. Nevertheless, some lesion studies suggest that the left and right OFC contribute differently to cognitive processes. We hypothesized that the OFC asymmetrical response to reward could reflect underlying hemispherical difference in OFC functional connectivity. Using resting-state and reward-related functional MRI data from humans and from rhesus macaques, we first identified an asymmetrical response of the lateral OFC to reward in both species. Crucially, the subregion showing the highest reward-related asymmetry (RRA) overlapped with the region showing the highest functional connectivity asymmetry (FCA). Furthermore, the two types of asymmetries were found to be significantly correlated across individuals. In both species, the right lateral OFC was more connected to the default mode network compared to the left lateral OFC. Altogether, our results suggest a functional specialization of the left and right lateral OFC in primates.
Staying engaged is necessary to maintain goal-directed behaviors. Despite this, engagement exhibits continuous, intrinsic fluctuations. Even in experimental settings, animals, unlike most humans, ...repeatedly and spontaneously move between periods of complete task engagement and disengagement. We, therefore, looked at behavior in male macaques (macaca mulatta) in four tasks while recording fMRI signals. We identified consistent autocorrelation in task disengagement. This made it possible to build models capturing task-independent engagement. We identified task general patterns of neural activity linked to impending sudden task disengagement in mid-cingulate gyrus. By contrast, activity centered in perigenual anterior cingulate cortex (pgACC) was associated with maintenance of performance across tasks. Importantly, we carefully controlled for task-specific factors such as the reward history and other motivational effects, such as response vigor, in our analyses. Moreover, we showed pgACC activity had a causal link to task engagement: transcranial ultrasound stimulation of pgACC changed task engagement patterns.Intrinsic motivational fluctuation can lead to complete disengagement in the real world. Here, the authors built a model predicting such behaviors and examined neural activity as macaques spontaneously disengage, identifying a network of frontal regions regulating engagement and motivation.
Highlights • Frontal contribution to sense of agency was measured with ‘intentional binding’. • Anodal stimulation of left DLPFC increased binding of actions to outcomes. • This effect was confined ...to tasks involving endogenous action selection. • Meta-analyses revealed a key prospective role for DLPFC in sense of agency.
Introduction Use of functional MRI in awake non-human primate (NHPs) has recently increased. Scanning animals while awake makes data collection possible in the absence of anesthetic modulation and ...with an extended range of possible experimental designs. Robust awake NHP imaging however is challenging due to the strong artifacts caused by time-varying off-resonance changes introduced by the animal's body motion. In this study, we sought to thoroughly investigate the effect of a newly proposed dynamic off-resonance correction method on brain activation estimates using extended awake NHP data. Methods We correct for dynamic B0 changes in reconstruction of highly accelerated simultaneous multi-slice EPI acquisitions by estimating and correcting for dynamic field perturbations. Functional MRI data were collected in four male rhesus monkeys performing a decision-making task in the scanner, and analyses of improvements in sensitivity and reliability were performed compared to conventional image reconstruction. Results Applying the correction resulted in reduced bias and improved temporal stability in the reconstructed time-series data. We found increased sensitivity to functional activation at the individual and group levels, as well as improved reliability of statistical parameter estimates. Conclusions Our results show significant improvements in image fidelity using our proposed correction strategy, as well as greatly enhanced and more reliable activation estimates in GLM analyses.
The sense of controlling one's own actions is fundamental to normal human mental function, and also underlies concepts of social responsibility for action. However, it remains unclear how the wider ...social context of human action influences sense of agency. Using a simple experimental design, we investigated, for the first time, how observing the action of another person or a robot could potentially influence one's own sense of agency. We assessed how observing another's action might change the perceived temporal relationship between one's own voluntary actions and their outcomes, which has been proposed as an implicit measure of sense of agency. Working in pairs, participants chose between two action alternatives, one rewarded more frequently than the other, while watching a rotating clock hand. They judged, in separate blocks, either the time of their own action, or the time of a tone that followed the action. These were compared to baseline judgements of actions alone, or tones alone, to calculate the perceptual shift of action toward outcome and vice versa. Our design focused on how these two dependent variables, which jointly provide an implicit measure of sense of agency, might be influenced by observing another's action. In the observational group, each participant could see the other's actions. Multivariate analysis showed that the perceived time of action and tone shifted progressively toward the actual time of outcome with repeated experience of this social situation. No such progressive change occurred in other groups for whom a barrier hid participants' actions from each other. However, a similar effect was observed in the group that viewed movements of a human-like robotic hand, rather than actions of another person. This finding suggests that observing the actions of others increases the salience of the external outcomes of action and this effect is not unique to observing human agents. Social contexts in which we see others controlling external events may play an important role in mentally representing the impact of our own actions on the external world.
Human voluntary actions are accompanied by a distinctive subjective experience termed “sense of agency”. We performed three experiments using transcranial direct current stimulation (tDCS) to ...modulate brain circuits involved in control of action, while measuring stimulation-induced changes in one implicit measure of sense of agency, namely the perceived temporal relationship between a voluntary action and tone triggered by the action. Participants perceived such tones as shifted towards the action that caused them, relative to baseline conditions with tones but no actions. Actions that caused tones were perceived as shifted towards the tone, relative to baseline actions without tones. This ‘intentional binding’ was diminished by anodal stimulation of the left parietal cortex targeting the angular gyrus (AG), and, to a lesser extent, by stimulation targeting the left dorsolateral prefrontal cortex (DLPFC), (Experiment 1). Cathodal AG stimulation had no effect (Experiment 2). Experiment 3 replicated the effect of left anodal AG stimulation for actions made with either the left or the right hand, and showed no effect of right anodal AG stimulation. The angular gyrus has been identified as a key area for explicit agency judgements in previous neuroimaging and lesion studies. Our study provides new causal evidence that the left angular gyrus plays a key role in the perceptual experience of agency.
Gastric cancer is one of the most common malignancies worldwide. With current therapeutic approaches the prognosis of gastric cancer is very poor, as gastric cancer accounts for the second most ...common cause of death in cancer related deaths. Gastric cancer like almost all other cancers has a molecular genetic basis which relies on disruption in normal cellular regulatory mechanisms regarding cell growth, apoptosis and cell division. Thus novel therapeutic approaches such as gene therapy promise to become the alternative choice of treatment in gastric cancer. In gene therapy, suicide genes, tumor suppressor genes and anti-angiogenesis genes among many others are introduced to cancer cells via vectors. Some of the vectors widely used in gene therapy are Adenoviral vectors. This review provides an update of the new developments in adenoviral cancer gene therapy including strategies for inducing apoptosis, inhibiting metastasis and targeting the cancer cells.
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