Congruent Embodied Representations for Visually Presented Actions and Linguistic Phrases Describing Actions

SummaryThe thesis of embodied semantics holds that conceptual representations accessed during linguistic processing are, in part, equivalent to the sensory-motor representations required for the enactment of the concepts described [1–6]. Here, using fMRI, we tested the hypothesis that areas in human premotor cortex that respond both to the execution and observation of actions—mirror neuron areas [7–18]—are key neural structures in these processes. Participants observed actions and read phrases relating to foot, hand, or mouth actions. In the premotor cortex of the left hemisphere, a clear congruence was found between effector-specific activations of visually presented actions and of actions described by literal phrases. These results suggest a key role of mirror neuron areas in the re-enactment of sensory-motor representations during conceptual processing of actions invoked by linguistic stimuli

Players of Matching Pennies automatically imitate opponents’ gestures against strong incentives

There is a large body of evidence of apparently spontaneous mimicry in humans. This phenomenon has been described as "automatic imitation" and attributed to a mirror neuron system, but there is little direct evidence that it is involuntary rather than intentional. Cook et al. supplied the first such evidence in a unique strategic game design that gave all subjects a pecuniary incentive to avoid imitation [Cook R, Bird G, Lünser G, Huck S, Heyes C (2012) Proc Biol Sci 279(1729):780-786]. Subjects played Rock-Paper-Scissors repeatedly in matches between fixed pairs, sometimes with one and sometimes with both subjects blindfolded. The frequency of draws in the blind-blind condition was at chance, but in the blind-sighted condition it was significantly higher, suggesting automatic imitation had occurred. Automatic imitation would raise novel issues concerning how strategic interactions are modeled in game theory and social science; however, inferring automatic imitation requires significant incentives to avoid it, and subjects' incentives were less than 3 US cents per 60-game match. We replaced Cook et al.'s Rock-Paper-Scissors with a Matching Pennies game, which allows far stronger incentives to avoid imitation for some subjects, with equally strong incentives to imitate for others. Our results are important in providing evidence of automatic imitation against significant incentives. That some of our subjects had incentives to imitate also enables us clearly to distinguish intentional responding from automatic imitation, and we find evidence that both occur. Thus, our results strongly confirm the occurrence of automatic imitation, and illuminate the way that automatic and intentional processes interact in a strategic context

Fast Visuomotor Processing of Redundant Targets: The Role of the Right Temporo-Parietal Junction

Parallel processing of multiple sensory stimuli is critical for efficient, successful interaction with the environment. An experimental approach to studying parallel processing in sensorimotor integration is to examine reaction times to multiple copies of the same stimulus. Reaction times to bilateral copies of light flashes are faster than to single, unilateral light flashes. These faster responses may be due to ‘statistical facilitation’ between independent processing streams engaged by the two copies of the light flash. On some trials, however, reaction times are faster than predicted by statistical facilitation. This indicates that a neural ‘coactivation’ of the two processing streams must have occurred. Here we use fMRI to investigate the neural locus of this coactivation. Subjects responded manually to the detection of unilateral light flashes presented to the left or right visual hemifield, and to the detection of bilateral light flashes. We compared the bilateral trials where subjects' reaction times exceeded the limit predicted by statistical facilitation to bilateral trials that did not exceed the limit. Activity in the right temporo-parietal junction was higher in those bilateral trials that showed coactivation than in those that did not. These results suggest the neural coactivation observed in visuomotor integration occurs at a cognitive rather than sensory or motor stage of processing

Moral exemplars in theory and practice

In this article I outline an original form of ethical theory that I call exemplarist virtue theory. The theory is intended to serve the philosophical purposes of a comprehensive moral theory, but it is also intended to serve the practical purpose of moral education by structuring the theory around a motivating emotion – the emotion of admiration. In this theory, basic moral concepts are defined via direct reference to exemplars of moral goodness, picked out through reflective admiration. The theory gives narratives a critical function, and it connects empirical studies with the a priori side of ethics.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

No Language-Specific Activation during Linguistic Processing of Observed Actions

It has been suggested that cortical neural systems for language evolved from motor cortical systems, in particular from those fronto-parietal systems responding also to action observation. While previous studies have shown shared cortical systems for action--or action observation--and language, they did not address the question of whether linguistic processing of visual stimuli occurs only within a subset of fronto-parietal areas responding to action observation. If this is true, the hypothesis that language evolved from fronto-parietal systems matching action execution and action observation would be strongly reinforced.We used functional magnetic resonance imaging (fMRI) while subjects watched video stimuli of hand-object-interactions and control photo stimuli of the objects and performed linguistic (conceptual and phonological), and perceptual tasks. Since stimuli were identical for linguistic and perceptual tasks, differential activations had to be related to task demands. The results revealed that the linguistic tasks activated left inferior frontal areas that were subsets of a large bilateral fronto-parietal network activated during action perception. Not a single cortical area demonstrated exclusive--or even simply higher--activation for the linguistic tasks compared to the action perception task.These results show that linguistic tasks do not only share common neural representations but essentially activate a subset of the action observation network if identical stimuli are used. Our findings strongly support the evolutionary hypothesis that fronto-parietal systems matching action execution and observation were co-opted for language, a process known as exaptation

Influence of residual perfusion within the infarct zone on the natural history of left ventricular dysfunction after acute myocardial infarction.

This study used myocardial contrast echocardiography to investigate the extent of residual perfusion within the infarct zone in a select group of patients with recently reperfused myocardial infarction and evaluated its influence on the ultimate infarct size. BACKGROUND: Limited information is available on the status of myocardial perfusion within postischemic dysfunctional segments at predischarge and on its influence on late regional and global functional recovery. METHODS: Twenty patients with acute myocardial infarction were selected for the study. Patients met the following inclusion criteria: 1) single-vessel coronary artery disease; 2) patency of infarct-related artery with persistent postischemic dysfunctional segments at predischarge; 3) stable clinical condition up to 6 months after hospital discharge. All selected patients underwent coronary angiography and myocardial contrast echocardiography before hospital discharge and repeated the echocardiographic examination 6 months later. Patients were grouped according to the pattern of contrast enhancement in predischarge dysfunctional segments. RESULTS: In nine patients (group I), the length of segments showing abnormal contraction coincided with that of the contrast defect segments. In the remaining 11 patients (group II), postischemic dysfunctional segments were partly or completely reperfused. There was no difference between the two groups in asynergic segment length at predischarge (7.3 +/- 2.5 vs. 7.2 +/- 4.3 cm, p = NS). At follow-up study, asynergic segment length was significantly reduced in group II patients, whereas no changes were observed in group I patients (from 7.2 +/- 4.3 to 4.7 +/- 3.7 cm, p < 0.005; and from 7.3 +/- 2.5 to 7.5 +/- 2.9 cm, p = NS, respectively). CONCLUSIONS: Among patients with a predischarge patent infarct-related artery, further improvement in regional and global function may be expected during follow-up when residual perfusion in the infarct zone is present

Best Treatment Option for Patients With Refractory Aggressive B-Cell Lymphoma in the CAR-T Cell Era: Real-World Evidence From GELTAMO/GETH Spanish Groups

CAR-T cell therapy; Real world evidence; B cell lymphomaTerapia con células CAR-T; Evidencia del mundo real; Linfoma de células BTeràpia amb cèl·lules CAR-T; Evidència del món real; Limfoma de cèl·lules BReal-world evidence comparing the efficacy of chimeric antigen receptor (CAR) T-cell therapy against that of the previous standard of care (SOC) for refractory large B-cell lymphoma (LBCL) is scarce. We retrospectively collected data from patients with LBCL according to SCHOLAR-1 criteria treated with commercial CAR T-cell therapy in Spain (204 patients included and 192 treated, 101 with axicabtagene ciloleucel [axi-cel], and 91 with tisagenlecleucel [tisa-cel]) and compared the results with a historical refractory population of patients (n = 81) obtained from the GELTAMO-IPI study. We observed superior efficacy for CAR-T therapy (for both axi-cel and tisa-cel) over pSOC, with longer progression-free survival (PFS) (median of 5.6 vs. 4–6 months, p ≤ 0.001) and overall survival (OS) (median of 15 vs. 8 months, p < 0.001), independently of other prognostic factors (HR: 0.59 (95% CI: 0.44–0.80); p < 0.001] for PFS, and 0.45 [(95% CI: 0.31–0.64)] for OS). Within the CAR-T cohort, axi-cel showed longer PFS (median of 7.3 versus 2.8 months, respectively, p = 0.027) and OS (58% versus 42% at 12 months, respectively, p = 0.048) than tisa-cel. These differences were maintained in the multivariable analysis. On the other hand, axi-cel was independently associated with a higher risk of severe cytokine release syndrome and neurotoxicity. Our results suggest that the efficacy of CAR-T cell therapy is superior to pSOC in the real-world setting. Furthermore, axi-cel could be superior in efficacy to tisa-cel, although more toxic, in this group of refractory patients according to SCHOLAR-1 criteria

Enhanced activation of the left inferior frontal gyrus in deaf and dyslexic adults during rhyming

Hearing developmental dyslexics and profoundly deaf individuals both have difficulties processing the internal structure of words (phonological processing) and learning to read. In hearing non-impaired readers, the development of phonological representations depends on audition. In hearing dyslexics, many argue, auditory processes may be impaired. In congenitally profoundly deaf individuals, auditory speech processing is essentially absent. Two separate literatures have previously reported enhanced activation in the left inferior frontal gyrus in both deaf and dyslexic adults when contrasted with hearing non-dyslexics during reading or phonological tasks. Here, we used a rhyme judgement task to compare adults from these two special populations to a hearing non-dyslexic control group. All groups were matched on non-verbal intelligence quotient, reading age and rhyme performance. Picture stimuli were used since this requires participants to generate their own phonological representations, rather than have them partially provided via text. By testing well-matched groups of participants on the same task, we aimed to establish whether previous literatures reporting differences between individuals with and without phonological processing difficulties have identified the same regions of differential activation in these two distinct populations. The data indicate greater activation in the deaf and dyslexic groups than in the hearing non-dyslexic group across a large portion of the left inferior frontal gyrus. This includes the pars triangularis, extending superiorly into the middle frontal gyrus and posteriorly to include the pars opercularis, and the junction with the ventral precentral gyrus. Within the left inferior frontal gyrus, there was variability between the two groups with phonological processing difficulties. The superior posterior tip of the left pars opercularis, extending into the precentral gyrus, was activated to a greater extent by deaf than dyslexic participants, whereas the superior posterior portion of the pars triangularis extending into the ventral pars opercularis, was activated to a greater extent by dyslexic than deaf participants. Whether these regions play differing roles in compensating for poor phonological processing is not clear. However, we argue that our main finding of greater inferior frontal gyrus activation in both groups with phonological processing difficulties in contrast to controls suggests greater reliance on the articulatory component of speech during phonological processing when auditory processes are absent (deaf group) or impaired (dyslexic group). Thus, the brain appears to develop a similar solution to a processing problem that has different antecedents in these two populations

Real-world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B-cell lymphoma

Recerca clínica del càncer; Càncer hematològic; Limfoma no HodgkinInvestigación clínica del cáncer; Cáncer hematológico; Linfoma no HodgkinClinical cancer research; Hematological cancer; Non-Hodgkin's lymphomaTisagenlecleucel (tisa-cel) is a second-generation autologous CD19-targeted chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). The approval was based on the results of phase II JULIET trial, with a best overall response rate (ORR) and complete response (CR) rate in infused patients of 52% and 40%, respectively. We report outcomes with tisa-cel in the standard-of-care (SOC) setting for R/R LBCL. Data from all patients with R/R LBCL who underwent leukapheresis from December 2018 until June 2020 with the intent to receive SOC tisa-cel were retrospectively collected at 10 Spanish institutions. Toxicities were graded according to ASTCT criteria and responses were assessed as per Lugano 2014 classification. Of 91 patients who underwent leukapheresis, 75 (82%) received tisa-cel therapy. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 5% and 1%, respectively; non-relapse mortality was 4%. Among the infused patients, best ORR and CR were 60% and 32%, respectively, with a median duration of response of 8.9 months. With a median follow-up of 14.1 months from CAR T-cell infusion, median progression-free survival and overall survival were 3 months and 10.7 months, respectively. At 12 months, patients in CR at first disease evaluation had a PFS of 87% and OS of 93%. Patients with an elevated lactate dehydrogenase showed a shorter PFS and OS on multivariate analysis. Treatment with tisa-cel for patients with relapsed/refractory LBCL in a European SOC setting showed a manageable safety profile and durable complete responses