Common intentional binding effects across diverse sensory modalities in touch-free voluntary actions.

The intentional binding effect refers to the phenomenon where the perceived temporal interval between a voluntary action and its sensory consequence is subjectively compressed. Prior research revealed the importance of tactile feedback from the keyboard on this effect. Here we examined the necessity of such tactile feedback by utilizing a touch-free key-press device without haptic feedback, and explored how initial/outcome sensory modalities (visual/auditory/tactile) and their consistency influence the intentional binding effect. Participants estimated three delay lengths (250, 550, or 850 ms) between the initial and outcome stimuli. Results showed that regardless of the combinations of sensory modalities between the initial and the outcome stimuli (i.e., modal consistency), the intentional binding effect was only observed in the 250 ms delay condition. This findings indicate a stable intentional binding effect both within and across sensory modalities, supporting the existence of a shared mechanism underlying the binding effect in touch-free voluntary actions.

Disappearing and appearing: Temporal binding effects are consistent across situations.

Sense of agency refers to the feeling of control over actions and action outcomes. Previous studies were mostly confined to the situation of performing actions to make objects appear, while it remains unexplored whether we experience sense of agency when making objects disappear. Here, we examined the temporal binding effect, an implicit index of sense of agency, in performing actions to make objects disappear and compared the magnitude of this effect in the appearing and disappearing situations. Results showed that the temporal binding effect emerged when object's disappearances served as action outcomes. Moreover, the temporal binding effects in the appearing and disappearing situations did not differ significantly. Our findings extend the temporal binding effect to the situation of voluntarily making objects disappear, suggesting a comparable level of implicit sense of agency when voluntarily making objects disappear and appear.

The neural network of sensory attenuation: A neuroimaging meta-analysis.

Sensory attenuation refers to the reduction in sensory intensity resulting from self-initiated actions compared to stimuli initiated externally. A classic example is scratching oneself without feeling itchy. This phenomenon extends across various sensory modalities, including visual, auditory, somatosensory, and nociceptive stimuli. The internal forward model proposes that during voluntary actions, an efferent copy of the action command is sent out to predict sensory feedback. This predicted sensory feedback is then compared with the actual sensory feedback, leading to the suppression or reduction of sensory stimuli originating from self-initiated actions. To further elucidate the neural mechanisms underlying sensory attenuation effect, we conducted an extensive meta-analysis of functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) studies. Utilizing activation likelihood estimation (ALE) analysis, our results revealed significant activations in a prominent cluster encompassing the right superior temporal gyrus (rSTG), right middle temporal gyrus (rMTG), and right insula when comparing external-generated with self-generated conditions. Additionally, significant activation was observed in the right anterior cerebellum when comparing self-generated to external-generated conditions. Further analysis using meta-analytic connectivity modeling (MACM) unveiled distinct brain networks co-activated with the rMTG and right cerebellum, respectively. Based on these findings, we propose that sensory attenuation arises from the suppression of reflexive inputs elicited by self-initiated actions through the internal forward modeling of a cerebellum-centered action prediction network, enabling the "sensory conflict detection" regions to effectively discriminate between inputs resulting from self-induced actions and those originating externally.

Confusion Effects of Facial Expression Recognition in Patients With Major Depressive Disorder and Healthy Controls.

Facial expression recognition plays a crucial role in understanding the emotion of people, as well as in social interaction. Patients with major depressive disorder (MDD) have been repeatedly reported to be impaired in recognizing facial expressions. This study aimed to investigate the confusion effects between two facial expressions that presented different emotions and to compare the difference of confusion effect for each emotion pair between patients with MDD and healthy controls. Participants were asked to judge the emotion category of each facial expression in a two-alternative forced choice paradigm. Six basic emotions (i.e., happiness, fear, sadness, anger, surprise, and disgust) were examined in pairs, resulting in 15 emotion combinations. Results showed that patients with MDD were impaired in the recognition of all basic facial expressions except for the happy expression. Moreover, patients with MDD were more inclined to confuse a negative emotion (i.e., anger and disgust) with another emotion as compared to healthy controls. These findings highlight the importance that patients with MDD show a deficit of sensitivity in distinguishing specific two facial expressions.

The Preponderant Role of Fusiform Face Area for the Facial Expression Confusion Effect: An MEG Study.

Although the recognition of facial expressions seems automatic and effortless, discrimination of expressions can still be error prone. Common errors are often due to visual similarities between some expressions (e.g., fear and surprise). However, little is known about the neural mechanisms underlying such a confusion effect. To address this question, we recorded the magnetoencephalography (MEG) while participants judged facial expressions that were either easily confused with or easily distinguished from other expressions. The results showed that the fusiform face area (FFA), rather than the posterior superior temporal sulcus (pSTS), played a preponderant role in discriminating confusable facial expressions. No difference between high confusion and low confusion conditions was observed on the M170 component in either the FFA or the pSTS, whilst a difference between two conditions started to emerge in the late positive potential (LPP), with the low confusion condition eliciting a larger LPP amplitude in the FFA. In addition, the power of delta was stronger in the time window of LPP component. This confusion effect was reflected in the FFA, which might be associated with the perceptual-to-conceptual shift.

Determinants of sensitivity of human T-cell leukemia CCRF-CEM cells to immucillin-H.

Immucillin-H (BCX-1777, forodesine) is a transition state analogue and potent inhibitor of PNP that shows promise as a specific agent against activated human T-cells and T-cell leukemias. The immunosuppressive or antileukemic effects of Immucillin-H (ImmH) in cultured cells require co-administration with deoxyguanosine (dGuo) to attain therapeutic levels of intracellular dGTP. In this study we investigated the requirements for sensitivity and resistance to ImmH and dGuo. (3)H-ImmH transport assays demonstrated that the equilibrative nucleoside transporters (ENT1 and ENT2) facilitated the uptake of ImmH in human leukemia CCRF-CEM cells whereas (3)H-dGuo uptake was primarily dependent upon concentrative nucleoside transporters (CNTs). Analysis of lysates from ImmH-resistant CCRF-CEM-AraC-8D cells demonstrated undetectable deoxycytidine kinase (dCK) activity, suggesting that dCK and not deoxyguanosine kinase (dGK) was the rate-limiting enzyme for phosphorylation of dGuo in these cells. Examination of ImmH cytotoxicity in a hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-deficient cell line CCRF-CEM-AraC-8C, demonstrated enhanced sensitivity to low concentrations of ImmH and dGuo. RT-PCR and sequencing of HGPRT from the HGPRT-deficient CCRF-CEM-AraC-8C cells identified an Exon 8 deletion mutation in this enzyme. Thus these studies show that specific nucleoside transporters are required for ImmH cytotoxicity and predict that ImmH may be more cytotoxic to 6-thioguanine (6-TG) or 6-thiopurine-resistant leukemia cells caused by HGPRT deficiency.

Regulation of the interaction of inosine monophosphate dehydrogenase with mycophenolic Acid by GTP.

Inosine monophosphate dehydrogenase (IMPDH), a rate-limiting enzyme in the de novo synthesis of guanine nucleotides, is a major therapeutic target. A prototypic uncompetitive inhibitor of IMPDH, mycophenolic acid (MPA), is the active form of mycophenolate mofeteil (CellCept), a widely used immunosuppressive drug. We have found that MPA interacts with intracellular IMPDH in vivo to alter its mobility on SDS-polyacrylamide gels. MPA also induces a striking conformational change in IMPDH protein in intact cells, resulting in the formation of annular aggregates of protein with concomitant inhibition of IMPDH activity. These aggregates are not associated with any known intracellular organelles and are reversible by incubating cells with guanosine, which repletes intracellular GTP, or with GTPgammaS. GTP also restores IMPDH activity. Treatment of highly purified IMPDH with MPA also results in the formation of large aggregates of protein, a process that is both prevented and reversed by the addition of GTP. Finally, GTP binds to IMPDH at physiologic concentrations, induces the formation of linear arrays of tetrameric protein, and prevents the aggregation of protein induced by MPA. We conclude that intracellular GTP acts as an antagonist to MPA by directly binding to IMPDH and reversing the conformational changes in the protein.