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Formica, S.

Publications and source records attributed to Formica, S..

8 recordsLinked to original sources

EEG frequency tagging reveals the integration of dissimilar observed actions

Extensive research has demonstrated that visual and motor cortices can simultaneously represent multiple observed actions. This ability undoubtedly constitutes a crucial ingredient for the understanding of complex visual scenes involving different agents. However, it is still unclear how these distinct representations are integrated into coherent and meaningful percepts. In line with studies of perceptual binding, we hypothesized that similar movements would be more easily integrated. To test this hypothesis, we developed an EEG frequency tagging experiment in which two hand movements were displayed simultaneously at two different presentation rates. Crucially, the degree of similarity between the two movements varied along two dimensions, namely action identity (i.e., same or different performed movement), and agent identity (i.e., one agent performing a bimanual movement, or two agents moving each one hand). Contrary to our predictions, we found a larger intermodulation oscillatory component, indexing the integrated processing of the two individual movements, when they were less similar. We propose that integration-by-dissimilarity might serve as a top-down process to solve conflict caused by incongruent movements in a complex social scene.

neuroscience↗

Coordinated social interactions are supported by integrated neural representations

Joint actions are defined as coordinated interactions of two or more agents towards a shared goal, often requiring different and complementary individual contributions. However, how humans can successfully act together without the interfering effects of observing incongruent movements is still largely unknown. It has been proposed that interpersonal predictive processes are at play to allow the formation of a Dyadic Motor Plan, encompassing both agents shares. Yet, direct empirical support for such an integrated motor plan is still limited. In this study, we aimed at testing the properties of these anticipated representations. We collected EEG data while human participants (N = 36; 27 females) drew shapes simultaneously to a virtual partner, in two social contexts: either they had to synchronize and act jointly, or they performed the movements alongside, but independently. We adopted a multivariate approach to show that the social context influenced how the upcoming action of the partner is anticipated during the interval preceding the movement. We found evidence that acting jointly induces an encoding of the partners action that is strongly intertwined with the participants action, supporting the hypothesis of an integrative motor plan in joint but not in parallel actions.

neuroscience↗

Theta-phase connectivity between medial prefrontal and posterior areas underlies novel instructions implementation

Implementing novel instructions is a complex and uniquely human cognitive ability, that requires the rapid and flexible conversion of symbolic content into a format that enables the execution of the instructed behavior. Preparing to implement novel instructions, as opposed to their mere maintenance, involves the activation of the instructed motor plans, and the binding of the action information to the specific context in which this should be executed. Recent evidence and prominent computational models suggest that this efficient configuration of the system might involve a central role of frontal theta oscillations in establishing top-down long-range synchronization between distant and task-relevant brain areas. In the present EEG study (human subjects, 30 females, 4 males), we demonstrate that proactively preparing for the implementation of novels instructions, as opposed to their maintenance, involves a strengthened degree of connectivity in the theta frequency range between medial prefrontal and motor/visual areas. Moreover, we replicated previous results showing oscillatory features associated specifically with implementation demands, and extended on them demonstrating the role of theta oscillations in mediating the effect of task demands on behavioral performance. Taken together, these findings support our hypothesis that the modulation of connectivity patterns between frontal and task-relevant posterior brain areas is a core factor in the emergence of a behavior-guiding format from novel instructions. Significance statementEveryday life requires the use and manipulation of currently available information to guide behavior and reach specific goals. In the present study we investigate how the same instructed content elicits different neural activity depending on the task being performed. We show that medial prefrontal theta oscillations are larger when novel instructions have to be implemented, rather than simply maintained. Crucially, connectivity between medial prefrontal cortex and posterior areas is strengthened during instructions implementation, suggesting that theta oscillations play a role in setting up a dynamic and flexible network of task-relevant regions optimized for the execution of the instructed behavior.

neuroscience↗

Adaptive coding of stimulus information in human fronto-parietal cortex during visual classification

The neural mechanisms of how frontal and parietal brain regions support flexible adaptation of behavior remain poorly understood. Here, we used functional magnetic resonance imaging (fMRI) and model-based representational similarity analysis (RSA) to investigate frontoparietal representations of stimulus information during visual classification under varying task demands. Based on prior research, we predicted that increasing perceptual task difficulty should lead to more categorical coding of stimulus information, and that exemplar-level stimulus coding would be restricted to posterior, sensory brain regions. Counter to our expectations, however, we found frontoparietal regions encoded exemplar-level stimulus information. Interestingly, the anterior intraparietal sulcus (aIPS) encoded stimuli equally well regardless of perceptual difficulty, and these representations were directly related to choice behavior (proportion of guessing). Overall, these findings reveal unexpected exemplar-level stimulus coding in frontoparietal cortex, and highlight the role of aIPS in supporting adaptive behavior.

neuroscience↗

Photoimmunotherapy retains its anti-tumor efficacy with increasing stromal content in heterotypic pancreatic cancer spheroids

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by increased levels of desmoplasia that contributes to reduced drug delivery and poor treatment outcomes. In PDAC, the stromal content can account for up to 90% of the total tumor volume. The complex interplay between stromal components, including pancreatic cancer associated fibroblasts (PCAFs), and PDAC cells in the tumor microenvironment (TME) have a significant impact on prognoses and thus needs to be recapitulated in vitro when evaluating various treatment strategies. This study is a systematic evaluation of photodynamic therapy (PDT) in 3D heterotypic coculture models of PDAC with varying ratios of patient derived PCAFs that simulate heterogenous PDAC tumors with increasing stromal content. The efficacy of antibody-targeted PDT (photoimmunotherapy; PIT) using cetuximab photoimmunoconjugates (PICs) of benzoporphyrin derivative (BPD) is contrasted with that of liposomal BPD (Visudyne(R)), which is currently in PDT clinical trials for PDAC. We demonstrate that both Visudyne(R)-PDT and PIT were effective in heterotypic PDAC 3D spheroids with a low stromal content. However, as the stromal content increases above 50% in the 3D spheroids, the efficacy of Visudyne(R)-PDT is reduced by up to 10-fold, while PIT retains its efficacy. PIT was found to be 10-fold, 19-fold and 14-fold more phototoxic in spheroids with 50%, 75% and 90% PCAFs, respectively, as compared to Visudyne(R)-PDT. This marked difference in efficacy is attributed to the ability of PICs to penetrate and distribute within spheroids with a higher stromal content, whereas Visudyne(R) is restricted to the spheroid periphery. This study thus demonstrates how the stromal content in PDAC spheroids directly impacts their responsiveness to PDT and proposes PIT to be a highly suited treatment option for desmoplastic tumors with particularly high degrees of stromal content.

cancer biology↗

TREM2 alters the phagocytic, apoptotic and inflammatory response to Aβ42 in HMC3 cells

Alzheimers disease (AD) is characterized by the accumulation in the brain of extracellular amyloid {beta} (A{beta}) plaques as well as intraneuronal inclusions (neurofibrillary tangles) consisting of total tau and phosphorylated tau. Also present are dystrophic neurites, loss of synapses, neuronal death, and gliosis. AD genetic studies have highlighted the importance of inflammation in this disease by identifying several risk associated immune response genes, including TREM2. TREM2 has been strongly implicated in basic microglia function including, phagocytosis, apoptosis, and the inflammatory response to A{beta} in mouse brain and primary cells. These studies show that microglia are key players in the response to A{beta} and in the accumulation of AD pathology. However, details are still missing about which apoptotic or inflammatory factors rely on TREM2 in their response to A{beta}, especially in human cell lines. Given these previous findings our hypothesis is that TREM2 influences the response to A{beta} toxicity by enhancing phagocytosis and inhibiting both the BCL-2 family of apoptotic proteins and pro-inflammatory cytokines. A{beta}42 treatment of the human microglial cell line, HMC3 cells, was performed and TREM2 was overexpressed or silenced and the phagocytosis, apoptosis and inflammatory response were evaluated. Results indicate that a robust phagocytic response to A{beta} after 24 hours requires TREM2 in HMC3 cells. Also, TREM2 inhibits A{beta} induced apoptosis by activating the Mcl-1/Bim complex. TREM2 is involved in activation of IP-10, MIP-1a, and IL-8, while it inhibits FGF-2, VEGF and GRO. Taken together, TREM2 plays a role in enhancing the microglial functional response to A{beta} toxicity in HMC3 cells. This novel information suggests that therapeutic strategies that seek to activate TREM2 may not only enhance phagocytosis, but it may also inhibit beneficial inflammatory factors, emphasizing the need to define TREM2-related inflammatory activity in not only mouse models of AD, but also in human AD.

molecular biology↗

NEURAL OSCILLATIONS DISSOCIATE BETWEEN MAINTENANCE AND PROCEDURALIZATION OF NOVEL INSTRUCTIONS

Humans are capable of flexibly converting symbolic instructions into novel behaviors. Previous evidence and theoretical models suggest that the implementation of a novel instruction requires the reformatting of its declarative content into an action-oriented code optimized for the execution of the instructed behavior. While neuroimaging research focused on identifying the brain areas involved in such a process, the temporal and electrophysiological mechanisms remain poorly understood. These mechanisms, however, can provide information about the specific cognitive processes that characterize the proceduralization of information. In the present study, we recorded EEG activity while we asked participants to either simply maintain declaratively the content of novel S-R mappings or to proactively prepare for their implementation. By means of time-frequency analyses, we isolated the oscillatory features specific to the proceduralization of instructions. Implementation of the instructed mappings elicited stronger theta activity over frontal electrodes and suppression in mu and beta activity over central electrodes. On the contrary, activity in the alpha band, which has been shown to track the attentional deployment to task-relevant items, showed no differences between tasks. Together, these results support the idea that proceduralization of information is characterized by specific component processes such as orchestrating complex task settings and configuring the motor system that are not observed when instructions are held in a declarative format. HighlightsO_LIFrontal theta power is increased during instructions implementation C_LIO_LIAttentional orienting in WM is analogous across maintenance and implementation C_LIO_LIInstructions implementation involves motor recruitment C_LI

neuroscience↗

Frontoparietal action-oriented codes support novel task set implementation

A key aspect of human cognitive flexibility concerns the ability to convert complex symbolic instructions into novel behaviors. Previous research proposes that this transformation is supported by two neurocognitive states: an initial declarative maintenance of task knowledge, and an implementation state necessary for optimal task execution. Furthermore, current models predict a crucial role of frontal and parietal brain regions in this process. However, whether declarative and procedural signals independently contribute to implementation remains unknown. We report the results of an fMRI experiment in which participants executed novel instructed stimulus-response associations. We then used a pattern-tracking procedure to quantify the contribution of format-unique signals during instruction implementation. This revealed independent procedural and declarative representations of novel S-Rs in frontoparietal areas, prior to execution. Critically, the degree of procedural activation predicted subsequent behavioral performance. Altogether, our results suggest an important contribution of frontoparietal regions to the neural architecture that regulates cognitive flexibility.

neuroscience↗