Biology subjects

Gazzola, V.

Publications and source records attributed to Gazzola, V..

31 records · Page 2Linked to original sources

bioRxiv2020

Significance tests for Leave-One-Out Inter-Subject Correlations in fMRI

The inter-subject correlation (ISC) of fMRI data of different subjects performing the same task is a powerful way to localize and differentiate neural processes caused by a stimulus from those that spontaneously or idiosyncratically take place in each subject. The wider adoption of this method has however been impeded by the lack of widely available tools to assess the significance of the observed correlations. Several non-parametric approaches have been proposed, but these approaches are computationally intensive, challenging to implement, and sensitive methods to correct for multiple comparison across voxels are not yet well established. More widely available, and computationally simple, parametric methods have been criticized theoretically on the basis that dependencies in the data could inflate false positives. Here, we therefore endeavored to assess the actual performance of parametric tests on leave-one-out ISC values in two ways. First, we assess whether parametric tests protect against Type I error by assessing how often they find significant clusters of synchronized activity in publicly available datasets, in which such synchronization should not occur. This includes three resting state datasets, and one dataset in which participants did view movies, but where we randomly select segments that were not taken at the same time in the same movie. Contrary to what has been suspected, we find that parametric tests with corrections for multiple comparisons do protect appropriately against Type I error in that data. This was true for FDR correction at the voxel level at q < 0.05, with a minimum cluster-size of k = 20 voxels, FWE correction at the voxel level at < 0.05, with a minimum cluster-size of k = 5, and for correction at the cluster-level with punc < 0.001 with k = max(20, FWEc). Second, we assessed how these parametric tests compare with non-parametric methods when it comes to detecting ISC when participants actually did watch the same movies. We used a dataset including 150 participants viewing two movies, and used a bootstrapping thresholding of the ISC in the entire dataset to outline our best guess of the network of brain regions that truly synchronize while viewing the movies. We then drew subsamples of between 10 and 50 participants from the entire dataset, calculated the ISC, and thresholded it using our candidate methods. We find that FDR thresholding with k = 20 in particular, was substantially more sensitive than bootstrapping methods in detecting this network even in smallish samples of N = 20 participants typical of cognitive neuroscience studies, while at the same time retaining appropriate specificity. Because the parametric tests we show to perform well are more readily available to the neuroscience community than the non-parametric tests previously championed, we trust that this finding paves the way to a wider adoption of ISC, and empowers a wider range of neuroimagers to use ISC to tackle the challenges of naturalistic neuroscience. In particular in the context of often limited sample sizes and modest effect sizes in cognitive neuroscience, we trust that using FDR correction in particular will help neuroimagers identify the contribution of higher brain regions that process stimuli in more loosely timed fashions, more effectively than non-parametric alternatives.

neuroscience↗

bioRxiv2020

Obeying orders reduces vicarious brain activation towards victim's pain

Past historical events and experimental research have shown complying with the orders from an authority has a strong impact on peoples behaviour. However, the mechanisms underlying how obeying orders influences moral behaviours remain largely unknown. Here, we test the hypothesis that when male and female humans inflict a painful stimulation to another individual, their empathic response is reduced when this action complied with the order of an experimenter (coerced condition) in comparison with being free to decide to inflict that pain (free condition). We observed that even if participants knew that the shock intensity delivered to the victim was exactly the same during coerced and free conditions, they rated the shocks as less painful in the coerced condition. MRI results further indicated that obeying orders reduced activity associated with witnessing the shocks to the victim in the ACC, insula/IFG, TPJ, the MTG and dorsal striatum (including the caudate and the putamen) as well as neural signatures of vicarious pain in comparison with being free to decide. We also observed that participants felt less responsible and showed reduced activity in a multivariate neural guilt signature in the coerced than in the free condition, suggesting that this reduction of neural response associated with empathy could be linked to a reduction of felt responsibility and guilt. These results highlight that obeying orders has a measurable influence on how people perceive and process others pain. This may help explain how peoples willingness to perform moral transgressions is altered in coerced situations.

neuroscience↗

bioRxiv2020

Neuro-computational mechanisms of action-outcome learning under moral conflict

Predicting how actions result in conflicting outcomes for self and others is essential for social functioning. We tested whether Reinforcement Learning Theory captures how participants learn to choose between symbols that define a moral conflict between financial self-gain and other-pain. We tested whether choices are better explained by model-free learning (decisions based on combined historical values of past outcomes), or model-based learning (decisions based on the current value of separately expected outcomes) by including trials in which participants know that either self-gain or other-pain will not be delivered. Some participants favored options benefiting themselves, others, preventing other-pain. When removing the favored outcome, participants instantly altered their choices, suggesting model-based learning. Computational modelling confirmed choices were best described by model-based learning in which participants track expected values of self-gain and other-pain separately, with an individual valuation parameter capturing their relative weight. This valuation parameter predicted costly helping in an independent task. The expectations of self-gain and other-pain were also biased: the favoured outcome was associated with more differentiated symbol-outcome probability reports than the less favoured outcome. FMRI helped localize this bias: signals in the pain-observation network covaried with pain prediction errors without linear dependency on individual preferences, while the ventromedial prefrontal cortex contained separable signals covarying with pain prediction errors in ways that did and did not reflected individual preferences.

neuroscience↗

bioRxiv2019

Similar levels of emotional contagion in male and female rats

Emotional contagion, the ability to feel what other individuals feel, is thought to be an important element of social life. In humans, emotional contagion has been shown to be stronger in women than men. Emotional contagion has been shown to exist also in rodents, and a growing number of studies explore the neural basis of emotional contagion in male rats and mice. These studies promise to shed light on the mechanisms that might go astray in psychiatric disorders characterized by dysfunctions of emotional contagion and empathy. Here we explore whether there are sex differences in emotional contagion in rats. We use an established paradigm in which a demonstrator rat receives footshocks while freezing is measured in both the demonstrator and an observer rat, which can hear, smell and see each other. By comparing pairs of male rats with pairs of female rats, we find (i) that female demonstrators freeze less when submitted to footshocks, but that (ii) the emotional contagion response, i.e. the degree of influence across the rats, does not depend on the sex of the rats. This was true whether emotional contagion was quantified based on the slope of a regression linking demonstrator and observer average freezing, or on Granger causality estimates of moment-to-moment freezing. The lack of sex differences in emotional contagion is compatible with an interpretation of emotional contagion as serving selfish danger detection.

animal behavior and cognition↗

bioRxiv2019

Bayesian statistics show a lack of change in excitability following bi-hemispheric HD-TDCS over the primary somatosensory cortices

BackgroundHigh Definition transcranial Direct Current Stimulation (HD-tDCS) is a method meant to explore the causal structure-function relationship of brain areas, developed to improve the spatial resolution of tDCS, but the validity of tDCS results is currently under intense debate\n\nObjectiveThe goal of this study is to validate a new HD-tDCS protocol for bilateral modulation of the Somatosensory Cortex (SI). The new montage is meant to increase the focus of the stimulation while limiting the area of the scalp covered by electrodes. We aim to characterize the effect of the stimulation in terms of directionality, consistency and reproducibility.\n\nMethodsWe aim to leverage a 1 x 1 montage to most focally stimulate the primary somatosensory cortex (SI) and measure modulation via Somatosensory Evoked Potentials (SEP) triggered by median nerve stimulation.\n\nResultsThe results of Experiment1 suggest that our montage increases the amplitude of the SEP component N30. In Experiment2, we aim to replicate our finding and to assess the duration of the modulatory effect on N30 over time. Data from Experiment2 fails to replicate N30 modulation. A sequential Bayesian analysis performed on N30 data from both experiments indicates that the effect fluctuates across participants, without a clear homogenous directionality.\n\nConclusionThis study sets boundaries on the effect size that can be expected for this montage and illustrates the need to include replication samples or larger sample sizes to avoid overestimating effect sizes. We conclude that our montage has insufficient effect size for use in moderately sample-sized experimental studies and clinical applications.

neuroscience↗

bioRxiv2019

Harm to others acts as a cingulate dependent negative reinforcer in rat

Empathy, the ability to share another individuals emotional state and/or experience, has been suggested to be a source of prosocial motivation by making actions that harm others aversive. The neural underpinnings and evolution of such harm aversion remain poorly understood. Here, we characterize an animal model of harm aversion in which a rat can choose between two levers providing equal amounts of food, but one additionally delivering a footshock to a neighboring rat. We find that independently of sex and familiarity, rats reduce their usage of the preferred lever when it causes harm to a conspecific, displaying an individually varying degree of harm aversion. Prior experience with pain increases this effect. In additional experiments, we show that rats reduce the usage of the harm-inducing lever when it delivers twice, but not thrice the number of pellets than the non-preferred lever, setting boundaries on the magnitude of harm aversion. Finally, we show that pharmacological deactivation of the anterior cingulate cortex, a region we have shown to be essential for emotional contagion, reduces harm aversion, while leaving behavioral flexibility unaffected. This model of harm aversion might help shed light onto the neural basis of psychiatric disorders characterized by reduced harm aversion, including psychopathy and conduct disorders with reduced empathy, and provide an assay for the development of pharmacological treatments of such disorders.

neuroscience↗

bioRxiv2019

Does higher sampling rate (Multiband + SENSE) benefit the detection of task correlated BOLD for cognitive neuroscience applications at 3T?

Multiband (MB) or Simultaneous multi-slice (SMS) acquisition schemes allow the acquisition of MRI signals from more than one spatial coordinate at a time. Commercial availability has brought this technique within the reach of many neuroscientists and psychologists. Most early evaluation of the performance of MB acquisition employed resting state fMRI or the most basic tasks. In this study, we tested whether the advantages of using MB acquisition schemes generalize to group analyses using a cognitive task more representative of typical cognitive neuroscience applications. Twenty-three subjects were scanned on a Philips 3T scanner using five sequences up to eight-fold acceleration with MB-factors 1 to 4, SENSE factors up to 2 and corresponding TRs of 2.45s down to 0.63s, while they viewed (i) movies showing complex actions with hand object interactions and (ii) control movies without hand object interaction. Using random effects group-level, voxel-wise analysis we found that all sequences were able to detect the basic action observation network known to be recruited by our task. The highest t-values were found for sequences with MB4 acceleration. For the MB1 sequence, a 50% bigger voxel volume was needed to reach comparable t-statistics. The group-level t-values for resting state networks (RSNs) were also highest for MB4 sequences. Here the MB1 sequence with larger voxel size did not perform comparable to the MB4 sequence. Altogether, we can thus recommend the use of MB4 (and SENSE 1.5 or 2) on a Philips scanner when aiming to perform group-level analyses using cognitive block design fMRI tasks and voxel sizes in the range of cortical thickness (e.g. 2.7mm isotropic). While results will not be dramatically changed by the use of multiband, our results suggest that MB will bring a moderate but significant benefit.

neuroscience↗

bioRxiv2019

Challenges in assessing voxel-wise single-subject level benefits of MB acceleration

Multiband (MB) acceleration of functional magnetic resonance imaging has become more widely available to neuroscientists. Here we compare MB factors of 1, 2 and 4 while participants view complex hand actions vs. simpler hand movements to localize the action observation network. While in a previous study, we show that MB4 shows moderate improvements in the group-level statistics, here we explore the impact it has on single subject statistics. We find that MB4 provides an increase in p values at the first level that is of medium effect size compared to MB1, providing moderate evidence across a number of voxels that MB4 indeed improves single subject statistics. This effect was localized mostly within regions that belong to the action observation network. In parallel, we find that Cohens d at the single subject level actually decreases using MB4 compared to MB1. Intriguingly, we find that subsampling MB4 sequences, by only considering every fourth acquired volume, also leads to increased Cohens d values, suggesting that the FAST algorithm we used to correct for temporal auto-correlation may over-penalize sequences with higher temporal autocorrelation, thereby underestimating the potential gains in single subject statistics offered by MB acceleration, and alternative methods should be explored. In summary, considering the moderate gains in statistical values observed both at the group level in our previous study and at the single subject level in this study, we believe that MB technology is now ripe for neuroscientists to start using MB4 acceleration for their studies, be it to accurately map activity in single subjects of interest (e.g. for presurgical planning or to explore rare patients) or for the purpose of group studies.

neuroscience↗

bioRxiv2019

Measuring shared responses across subjects using intersubject correlation

Our capacity to jointly represent information about the world underpins our social experience. By leveraging one individuals brain activity to model anothers, we can measure shared information across brains--even in dynamic, naturalistic scenarios where an explicit response model may be unobtainable. Introducing experimental manipulations allows us to measure, for example, shared responses between speakers and listeners, or between perception and recall. In this tutorial, we develop the logic of intersubject correlation (ISC) analysis and discuss the family of neuroscientific questions that stem from this approach. We also extend this logic to spatially distributed response patterns and functional network estimation. We provide a thorough and accessible treatment of methodological considerations specific to ISC analysis, and outline best practices.

neuroscience↗

bioRxiv2018

Action perception recruits the cerebellum and is impaired in spinocerebellar ataxia patients

Our cerebellum has been proposed to generate prediction signals that may help us plan and execute our motor programs. However, to what extent our cerebellum is also actively involved in perceiving the action of others remains to be elucidated. Using fMRI, we show here that observing goal-directed hand actions of others bilaterally recruits cerebellar Lobules VI, VIIb and VIIIa. Moreover, whereas healthy subjects (n=31) were found to be able to discriminate subtle differences in the kinematics of observed limb movements of others, patients suffering from spinocerebellar ataxia type 6 (SCA6; n=21) were severely impaired in performing such tasks. Our data suggest that the human cerebellum is actively involved in perceiving the kinematics of the hand actions of others and that SCA6 patients deficits include a difficulty in perceiving the actions of other individuals. This finding alerts us to the fact that cerebellar disorders can alter social cognition. Given that impairments in social cognition have been reported to be one of the most debilitating consequences of neurological disorders, this finding may be relevant to improving the quality of life of patients and their families.

neuroscience↗

bioRxiv2018

Cingulate dependent social risk assessment in rats

Social transmission of distress has been conceived of as a one-way phenomenon in which an observer catches the emotions of another. Here we use a paradigm in which an observer rat witnesses another receive electro-shocks. Bayesian model comparison and Granger causality argue against this one-way vision in favor of bidirectional information transfer: how the observer reacts to the demonstrators distress influences the behavior of the demonstrator. Intriguingly, this was true to a similar extent across highly familiar and entirely unfamiliar rats. Injecting muscimol in the anterior cingulate of observers reduced freezing in the observers and in the demonstrators receiving the shocks. That rats share the distress of unfamiliar strains is at odds with evolutionary thinking that empathy should be biased towards close individuals. Using simulations, we support the complementary notion that distress transmission could be selected to more efficiently detect dangers in a group.

neuroscience↗

bioRxiv2018

Emotional Mirrors in the Rat’s Anterior Cingulate Cortex

AbstractHow do the emotions of others affect us? The human anterior cingulate cortex (ACC) responds while experiencing pain in the self and witnessing pain in others, but underlying cellular mechanisms remain poorly understood. Here we show the ACC (area 24) contains neurons responding when a rat experiences pain and while witnessing another receive footshocks. Most of these do not respond to a fear conditioned tone (CS). Deactivating this region reduces freezing while witnessing footshocks to others but not while hearing the CS. A decoder trained on spike counts while witnessing footshocks can decode the animals own pain intensity when experiencing pain. Mirror-like neurons thus exist in ACC that encode the pain of others in a code shared with pain but not fear in the self.\n\nOne Sentence SummaryACC contains neurons responding selectively when a rat witnesses anothers pain and experiences pain in the self.

neuroscience↗

bioRxiv2018

Where and how our brain represents the temporal structure of observed action

Reacting faster to the behavior of others provides evolutionary advantages. Reacting to unpredictable events takes hundreds of milliseconds. Understanding where and how the brain represents what actions are likely to follow one another is therefore important. Everyday actions are predictable sequences of acts, yet neuroscientists focus on how brains responds to unexpected, individual motor acts. Using fMRI we show the brain encodes sequence-specific information in the motor system. Using EEG, we show visual responses were faster and smaller for predictable sequences that recruit the motor system. This study shifts the study of action observation from single acts to motor sequences, informs how we adapt to the actions of others and suggests the motor system may implement perceptual predictive coding.

neuroscience↗