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Humans are equipped with an extraordinary ability to understand and imitate actions by mapping the observed movement onto their own cortical motor system. Long-established lines of research have identified two correlates of this motor resonance following action observation: the mu rhythm event-related desynchronization (mu-ERD) recorded through electroencephalography (EEG) and the facilitation of motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) of the primary motor cortex (M1). Yet, whether mu-ERD and MEP facilitation reflect unique or distinct mechanisms is not conclusive, as prior work did not combine simultaneous TMS-EEG recording with a trial-by-trial analysis of the two markers. To address this issue, here, we used TMS-EEG co-registration while participants observed and executed finger movements. EEG was continuously recorded while single-pulse TMS was administered over the left M1 and MEPs were recorded from the right hand. We found stronger motor cortex recruitment during action execution and observation as shown by mu-ERD. MEPs instead were larger overall during action execution and showed a facilitation specific to the muscles involved in the observed movements. Interestingly, when analyzing these two parameters using a trial-by-trial statistical approach, we did not find any relationship between mu-ERD and MEPs within the action observation condition. Our findings support the notion that EEG and TMS indices of motor resonance reflect distinct neural mechanisms.

Nucleic acids are a powerful engineering material that can be used to implement a broad range of computational circuits at the nanoscale, with potential applications in high-precision biosensing, diagnostics, and therapeutics. However, nucleic acid circuits are prone to leaks, which result from unintended displacement interactions between nucleic acid strands. Such leaks can grow combinatorially with circuit size, are challenging to mitigate, and can significantly compromise circuit behavior. While several techniques have been proposed to partially mitigate leaks, computational methods for designing new leak mitigation strategies and comparing their effectiveness on circuit behavior are limited. Here we present a general method for the automated leak analysis of nucleic acid circuits, referred to as DSD Leaks. Our method extends the logic programming functionality of the Visual DSD language, developed for the design and analysis of nucleic acid circuits, with predicates for leak generation, a leak reaction enumeration algorithm, and predicates to exclude low probability leak reactions. We use our method to identify the critical leak reactions affecting the performance of control circuits, and to analyze leak mitigation strategies by automatically generating leak reactions. Finally, we design new control circuits with substantially reduced leakage including a sophisticated proportional-integral controller circuit, which can in turn serve as building blocks for future circuits. By integrating our method within an open-source nucleic acid circuit design tool, we enable the leak analysis of a broad range of circuits, as an important step toward facilitating robust and scalable nucleic acid circuit design.

The space around our body, the so-called peripersonal space, is where interactions with nearby objects may occur. “Defensive space” and “Reaching space”, respectively, refer to two opposite poles of interaction between our body and the external environment: protecting the body and performing a goal-directed action. Here, we hypothesized that mechanisms underlying these two action spaces are differentially modulated by the valence of visual stimuli, as stimuli with negative valence are more likely to activate protective actions whereas stimuli with positive valence may activate approaching actions. To test whether such distinction in cognitive/evaluative processing exists between Reaching and Defensive spaces, we measured behavioral responses as well as neural activations over sensorimotor cortex using EEG while participants performed several tasks designed to tap into mechanisms underlying either Defensive (e.g., respond to touch) or Reaching space (e.g., estimate whether object is within reaching distance). During each task, pictures of objects with either positive or negative valence were presented at different distances from the participants' body. We found that Defensive space was smaller for positively compared with negatively valenced visual stimuli. Furthermore, sensorimotor cortex activation (reflected in modulation of beta power) during tactile processing was enhanced when coupled with negatively rather than positively valenced visual stimuli regarding Defensive space. On the contrary, both the EEG and behavioral measures capturing the mechanisms underlying Reaching space did not reveal any modulation by valence. Thus, although valence encoding had differential effects on Reaching and Defensive spaces, the distance of the visual stimulus modulated behavioral measures as well as activity over sensorimotor cortex (reflected in modulations of mu power) in a similar way for both types of spaces. Our results are compatible with the idea that Reaching and Defensive spaces involve the same distance-dependent neural representations of sensory input, whereas task goals and stimulus valence (i.e., contextual information) are implemented at a later processing stage and exert an influence on motor output rather than sensory/space encoding.

An ultra-high-performance liquid chromatography-differential ion mobility (DMS)-tandem mass spectrometry method was developed to quantify 14 bitter-tasting lipids in 17 commercial pea-protein isolates (

Lo spazio peripersonale (SPP) rappresenta una regione privilegiata di spazio immediatamente circostante il nostro corpo in cui stimoli visivi e tattili vengono integrati nelle aree cerebrali fronto-parietali (Hunley & Lourenco, 2018). L’ampiezza di SPP non è fissa ma può essere regolata da diversi fattori (Fogassi et al., 1996). Il presente lavoro di tesi si propone di indagare come l’integrazione visuo-tattile possa essere modulata dalla valenza intrinseca e acquisita degli stimoli visivi e da stati emotivi legati all’ansia. Negli Studi 1 e 3 è stato utilizzato il paradigma di interazione visuo-tattile (Canzoneri et al., 2012) in cui stimoli tattili venivano somministrati mentre stimoli visivi in avvicinamento a valenza intrinseca (Studio 1) e acquisita (Studio 3) si trovavano a specifiche distanze dal corpo dei partecipanti. I risultati dei due studi sono analoghi: a brevi distanze, tutti gli stimoli visivi comportano una facilitazione dell’elaborazione del tattile, a lunghe distanze dal corpo, invece, solo gli stimoli connotati da valenza modulano le interazioni visuo-tattili. Lo studio 2 è stato condotto per escludere che possibili effetti di aspettativa tattile potessero spiegare i risultati ottenuti nei due precedenti studi. Utilizzando lo stesso paradigma di interazione visuo-tattile, ora gli stimoli visivi si allontanano dal corpo anziché avvicinarsi ad esso. Contrariamente ai due studi summenzionati, si è qui riscontrato che la valenza degli stimoli non esercita nessun effetto sulla percezione spaziale, confermando dunque la validità degli Studi 1 e 3. Lo Studio 4 si propone di indagare le oscillazioni neurali sottostanti le interazioni visuo-tattili. Nello specifico, si vorrebbe replicare il risultato ottenuto da Wamain et al. (2016) il quale ha riportato un gradiente di attivazione della corteccia sensorimotoria dallo spazio peripersonale a quello extrapersonale, soltanto quando il compito richiedeva al soggetto una chiara intenzione motoria. Utilizzando un compito di discriminazione tattile, i partecipanti venivano invitati a rispondere ad una vibrazione consegnata sulla mano destra mentre osservavano stimoli visivi a valenza positiva e negativa, posizionati a varie distanze dal corpo. I risultati mostrano una chiara attivazione motoria quando tutti gli stimoli sono posizionati nello spazio peripersonale ma non in quello extrapersonale, portando prove a sostegno dell’esistenza di un sistema di codifica di SPP sottostante l’integrazione visuo-tattile (Maravita et al., 2003, Làdavas & Farnè, 2004). Nessun effetto legato alla valenza è stato registrato, avvalorando dunque i dati ottenuti nei precedenti esperimenti. Lo studio 5 è volto ad indagare come la congruenza tra stimoli visivi e tattili nello spazio sia modellata da stati emotivi legati ad ansia di stato e di tratto (Spielberger, 1983). Adottando una versione rivisitata del paradigma di Ordine di Giudizio Temporale (Filbrich et al., 2017), i partecipanti venivano invitati a riportare l’ordine di presentazione di stimoli visivi posizionati vicino o lontano dal proprio corpo, ignorando degli stimoli tattili consegnati 200 ms prima degli stimoli bersaglio. Tale procedura è stata somministrata prima e dopo il compito di induzione dell’ansia. Nonostante non sia stato replicato il generale effetto di facilitazione di congruenza visuo-tattile nello spazio vicino, è stato riscontrato che i soggetti con alta ansia di stato e di tratto mostrano rispettivamente un effetto inibitorio e facilitatorio dello stimolo tattile sull’elaborazione del visivo. Questo risultato è compatibile con studi già presenti in letteratura indicanti un ridotto controllo top-down per stimoli minacciosi nei soggetti ad alta ansia di stato (Bishop et al., 2004) e un compromesso controllo esecutivo nei soggetti ad alta ansia di tratto (Pacheco-Unguetti et al., 2010). Peripersonal Space (PPS) is a privileged region of space, immediately surrounding our body, in which visual and bodily signals are promptly integrated in fronto-parietal areas of the brain (Hunley & Lourenco, 2018). PPS amplitude is not fixed, but it can be dynamically shaped by specific experimental manipulations (Fogassi et al., 1996). In Study 1 and 3, we tried to disentangle how visuo-tactile integration in space can be shaped by intrinsic and learned valence of objects. By using a visuo-tactile interaction paradigm, participants were asked to respond to a tactile stimulus while an approaching visual one (with intrinsic and learned valence in Study 1 and 3, respectively) was located at specific distances from their body (Canzoneri et al., 2012). The results of Study 1 and 3 seem aligned to each other: positive and negative stimuli entail larger visuo-tactile interactions in space than neutral ones. Indeed, at longer distances from the body, visuo-tactile interactions are dynamically modulated by valence-connoted looming visual stimuli. At shorter distances, instead, all stimuli acquire saliency regardless of their intrinsic or acquired valence, due to their proximity to the body. Study 3 aims to exclude that the above-mentioned results might be due to tactile expectancy (Kandula et al., 2017). Indeed, the more the visual stimulus approaches the body without tactile input, the more the bodily stimulus expectancy increases (Umbach et al. 2012). By using the same visual stimuli – that now recede away from participants’ body - and spatial distances as in Study 1, it was shown that the different valence of the stimuli is not able to produce any kind of effect in space, thus stressing the validity of the findings reported in Studies 1 and 3. Study 4 investigates the neuronal oscillations related to visuo-tactile coupling in near and far space for both positive and negative visual stimuli. In particular, we would like to replicate Wamain et al. (2016) results, which state that objects in near space are coded in motor terms, but only when the goal of the perceiver is to interact with them. By using a tactile discrimination task while valence-connoted visual stimuli were presented in near or far space, we found beta power desynchronization in near space over sensorimotor cortex, thus revealing a motor activation for valence-connoted visual stimuli close to the body but not when they were located far from it. This result corroborates the presence of such a multisensory system in the human brain (Maravita et al., 2003, Làdavas & Farnè, 2004). However, no effect of valence was found in the present EEG task, thus confirming Study 1 and 3 results. Study 5 explores how state and trait anxiety (Spielberger, 1983) can alter the prioritizing effect of congruent visuo-tactile stimulation in space. By adopting a revised version of the Temporal Order Judgment task as in Filbrich et al. (2017), participants were asked to report the order of near or far visual stimulus presentation before and after doing an anxiety provoking task, trying to ignore a tactile cue. Despite we were unable to report an overall prioritizing effect of congruent visuo-tactile interaction in near space, it has been found that participants who experienced a higher temporary state of anxiety showed an inhibitory effect of the congruent tactile cue on the near visual stimulus processing. On the other side, high trait anxiety participants’ response to the congruent multisensory stimulation seems to be more facilitated in near than in far space. This finding seems to be compatible with the reduced top-down control over threat-related distractors showed by high state anxiety individuals (Bishop et al., 2004) and with a reduced executive control in trait anxious subjects (Pacheco-Unguetti et al., 2010). Taken together, these five studies stress the privileged integration of visual and tactile stimuli inside PPS and its permeability to emotional related states.

The peripersonal space (PPS) is the space surrounding our body, represented in a multisensory fashion by integrating stimuli of different modalities. Recently, it has been demonstrated that PPS is emotionally connoted, being sensitive to the different affective valence of the stimuli located inside it. However, how visuo-tactile interactions can be spatially shaped by intrinsic or acquired valence of stimuli is not clear. To investigate this, we conducted three experiments in which participants performed a visuo-tactile interaction task, while the intrinsic valence (Exp. 1 and 2) or the learned valence (Exp. 3) of visual stimuli was manipulated. Participants were asked to respond as fast as possible to a tactile stimulus that was delivered while a visual stimulus was approaching (Exp.1 and 3) or receding (Exp.2) from the hand. Touch was synchronized with different distances of the visual stimulus from the hand. We found that both the expectancy of stimulus and the distance of the visual one from the hand impact RTs to tactile targets. Crucially, we found that spatial modulation was also influenced by stimulus valence, but only for the approaching and not the receding stimuli. At far distances, neutral stimuli yielded overall slower RTs than intrinsically positive or negative stimuli (Experiment 1), while no modulation was exerted by the level of conditioning (Experiment 3). At near distances, response to touches accompanied by looming neutral stimuli became as fast as that occurring with positive and negative ones. Stimulus valence did not interact with the expectancy of a tactile stimulus (Experiment 2). Overall, these findings support the vision that visuo-tactile interactions can be dynamically modulated by the valence of looming visual stimuli when these are located at longer distances from the body. When closer to it, all stimuli acquire saliency, regardless of their intrinsic or acquired valence, due to their proximity, and then relevance, to the body. Overall, a view of PPS as a gradient modulating visuo-tactile integration, also based on stimulus valence, is discussed.

Peripersonal Space (PPS) is the multisensory space immediately surrounding our body. Visual and tactile stimuli here are promptly processed, since their interaction gradually strengthens as the distance between visual stimulus and the body decreases. Recently, a modified version of the Temporal Order Judgment (TOJ) task was proposed to assess PPS based on the spatial congruence between somatosensory and visual stimuli. Here, we used this paradigm to explore how a temporary vs a permanent state of anxiety can alter PPS. Indeed, previous research showed that PPS boundaries are not fixed, but they can be enlarged by contingent factors (i.e. emotional features). Participants performed the TOJ paradigm twice, just before and after completing an anxiety-inducing task (experimental breathing condition) or a neutral one (control breathing condition), while their trait and state anxiety levels were repeatedly measured. We found that the pattern of visuo-tactile integration in PPS changes in the very opposite way following the two breathing tasks for participants with high levels of temporary anxiety, by strengthening and weakening its power after the experimental and control conditions, respectively. On the contrary, both the breathing tasks are capable of reducing the cross-modal interplay as compared to baseline for high trait-anxious participants, who show an overall stronger visuo-tactile integration inside the PPS than low trait anxious individuals. These results are discussed in the light of the double dissociation between orienting and alerting attentional network over-functioning, reported in state anxiety participants, and impoverished prefrontal attentional control shown by trait anxiety individuals.

The dynamic behavior of synthetic gene circuits plays a key role in ensuring their correct function. Although there has been substantial work on modeling dynamic behavior after circuit construction, the forward engineering of dynamic behavior remains a major challenge. Previous engineering methods have focused on quantifying average behaviors of circuits over an extended time window, however this provides a static characterization of behavior that is a poor predictor of dynamics. Here we present a method for characterizing the dynamic behavior of synthetic gene circuits, using parameter inference of dynamical system models applied to time-series measurements of cell cultures growing in microtiter plates. We demonstrate that the behaviors of simple devices can be characterized dynamically and used to predict the behaviors of more complex circuits. Specifically, we compose 23 biological parts into 9 devices and use them to design 9 synthetic gene circuits in E. coli that provide core functionality for engineering cell behavior at the population level, including relays, receivers and a degrader. We embody our method in a software package and corresponding programming language. Our method supports the notion of an inference graph for iterative inference of models as new circuits are constructed, without the need to infer all models from scratch, and lays the foundation for characterizing large libraries of synthetic gene circuits in a scalable manner.