Exploring the Relationship between Semantics and Space

The asymmetric distribution of human spatial attention has been repeatedly documented in both patients and healthy controls. Biases in the distribution of attention and/or in the mental representation of space may also affect some aspects of language processing. We investigated whether biases in attention and/or mental representation of space affect semantic representations. In particular, we investigated whether semantic judgments could be modulated by the location in space where the semantic information was presented and the role of the left and right parietal cortices in this task. Healthy subjects were presented with three pictures arranged horizontally (one middle and two outer pictures) of items belonging to the same semantic category. Subjects were asked to indicate the spatial position in which the semantic distance between the outer and middle pictures was smaller. Subjects systematically overestimated the semantic distance of items presented in the right side of space. We explored the neural correlates underpinning this bias using rTMS over the left and right parietal cortex. rTMS of the left parietal cortex selectively reduced this rightward bias. Our findings suggest the existence of an attentional and/or mental representational bias in semantic judgments, similar to that observed for the processing of space and numbers. Spatial manipulation of semantic material results in the activation of specialised attentional resources located in the left hemisphere

Associative agreement as a predictor of naming ability in alzheimer’s disease: A case for the semantic nature of associative links

We aimed to address the long-standing issue of the nature of the relationships that link a cue word to words associated with it. In keeping with a recently proposed neuropsychological model of semantic memory (Zannino et al., 2015), we provide support for the hypothesis that associative links are semantic in nature and not lexical. In support of this hypothesis, we demonstrate a relationship in healthy subjects between the probability of producing word X in response to cue word Y in a free association task and the probability of using word X to describe the meaning of word Y. Furthermore, we provide evidence that associative measures are altered in people suffering from Alzheimer's disease (AD) and predict their level of performance in a picture-naming task. We provide a parsimonious account of the experimental data gathered form these different sources of evidence according to the hypothesis that the links between a cue word and its associates can be viewed as binding a concept (the cue) to pieces of information regarding its meaning (the associates)

Implicit Prototype Learning in Patients With Memory Deficit: Evidence From a Study With Alzheimer’s Disease Patients

Objective: In a previous study (Zannino et al., 2012), it was demonstrated that individuals with amnestic mild cognitive impairment (MCI) were unimpaired on a new prototype learning task consisting of morphed faces (face prototype learning task [FPLT]). This paradigm was devised to improve on the classical dot pattern task by ruling out any reliance on residual episodic memory or working memory resources. In the present study, we aimed to demonstrate: first, that people with even more severe episodic memory impairment than MCI are unimpaired on a fully implicit prototype learning task and second, that the dot pattern task, at variance with the FPLT, requires a no negligible contribution from the episodic memory system. Method: Twenty-four persons with Alzheimer's disease (AD) and 48 healthy controls took part in this experiment. As in the original study, in addition to the FPLT, they were also administered the classical dot pattern task and an ordinary forced-choice face recognition task. Results: AD performed like normal controls in the FPLT but scored significantly worse on the dot pattern task and the face recognition task. Interestingly, although performance on the face recognition task did not correlate with that on the FPLT, a significant correlation was observed between the face recognition and the dot pattern task. Conclusions: Results support both of our claims: first, that also severe amnesic people can learn new visual prototypes with a fully implicit paradigm and, second, that the classical dot pattern task requires some degree of episodic resources. Further research is needed to rule out the role of working memory in solving the FPLT

Visuo-verbal distinction revisited: new insights from a study on temporal lobe epilepsy patients in the debate over the lateralization of material-specific and process-specific aspects of memory

Introduction: The automatic interaction between a cue and a memory trace can give rise to the vivid recollection of a purely sensory past experience. But are humans able to reach back intentionally to purely sensory experiences in the absence of any exogenous or endogenous cue? In the present study, we propose an alternative hypothesis, claiming that the retrieval of associated semantic memories, stored in the left hemisphere and acting as endogenous cues, is a prerequisite for intentionally recollecting sensory experience stored in the right hemisphere during mental time travels (MTT).Methods: To investigate this issue, we administered an MTT task to 26 epileptic patients (16 males and 10 females) who had undergone right or left temporal lobectomy and to 28 age and education matched controls. The task was devised so as to require the recollection of purely visual memories in the absence of external cues. Participants also performed two conventional recognition tasks with visual and verbal materials. The three between-subjects memory tasks were analyzed separately with the Kruskal-Wallis test and the Wilcoxon rank-sum test in order to investigate differences across groups. According to our hypothesis, we expected side asymmetries in the patients' performance on the two recognition tasks but not the MTT task.Results: While patients showed the well-known hemispheric asymmetry for visual and verbal material in the (external-cue dependent) recognition tasks, no side asymmetries emerged in the purely visual MTT task.Conclusions: In keeping with the view that visual memories cannot be targeted directly by a strategic search process, the lack of any side asymmetry in our MTT task can be interpreted as a trade-off between left-sided strategic search for associated semantic memories and right-sided storage of visual ones

The free association task: Proposal of a clinical tool for detecting differential profiles of semantic impairment in semantic dementia and alzheimer’s disease

Backround and Objectives: It is widely agreed that patients suffering from Alzheimer’s disease (AD) and patients suffering from semantic dementia (SD) might fail clinically administered semantic tasks due to a different combination of underlying cognitive deficits: namely, degraded semantic representations in SD and degraded representations plus executive control deficit in AD. However, no easy administrable test or test battery for differentiating the semantic impairment profile in these populations has been devised yet. Materials and Methods: In this study, we propose a new easy administrable task based on a free association procedure (F-Assoc) to be used in conjunction with category fluency (Cat-Fl) and letter fluency (Lett-Fl) for quantifying pure representational and pure control deficits, thus teasing apart the semantic profile of SD and AD patients. Results: In a sample of 10 AD and 10 SD subjects, matched for disease severity, we show that indices of asymmetric performance contrasting F-Assoc and each of the two verbal fluency tasks yield a clearly distinguishable discrepancy pattern across SD and AD. We also provide empirical support for the validity of an asymmetry measure contrasting F-Assoc and Cat-FL as an index of control impairment. Conclusions: The present study suggests that the free association procedure provides a pure measure of degradation of semantic representations avoiding the confound of possible concomitant executive deficits

Long-term outcomes after first-onset arrhythmia in Fontan physiology

Objectives: Patients living with a Fontan circulation are prone to develop arrhythmias. However, their prognostic impact has been seldom studied. As such, we aimed to determine the incidence and predictors of arrhythmias after the Fontan procedure and the long-term outcomes after the first onset of arrhythmias

Coagulation/Complement Activation and Cerebral Hypoperfusion in Relapsing-Remitting Multiple Sclerosis

Introduction: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with an underlying immune-mediated and inflammatory pathogenesis. Innate immunity, in addition to the adaptive immune system, plays a relevant role in MS pathogenesis. It represents the immediate non-specific defense against infections through the intrinsic effector mechanism \u201cimmunothrombosis\u201d linking inflammation and coagulation. Moreover, decreased cerebral blood volume (CBV), cerebral blood flow (CBF), and prolonged mean transit time (MTT) have been widely demonstrated by MRI in MS patients. We hypothesized that coagulation/complement and platelet activation during MS relapse, likely during viral infections, could be related to CBF decrease. Our specific aims are to evaluate whether there are differences in serum/plasma levels of coagulation/complement factors between relapsing-remitting (RR) MS patients (RRMS) in relapse and those in remission and healthy controls as well as to assess whether brain hemodynamic changes detected by MRI occur in relapse compared with remission. This will allow us to correlate coagulation status with perfusion and demographic/clinical features in MS patients. Materials and Methods: This is a multi-center, prospective, controlled study. RRMS patients (1\ub0 group: 30 patients in relapse; 2\ub0 group: 30 patients in remission) and age/sex-matched controls (3\ub0 group: 30 subjects) will be enrolled in the study. Patients and controls will be tested for either coagulation/complement (C3, C4, C4a, C9, PT, aPTT, fibrinogen, factor II, VIII, and X, D-dimer, antithrombin, protein C, protein S, von-Willebrand factor), soluble markers of endothelial damage (thrombomodulin, Endothelial Protein C Receptor), antiphospholipid antibodies, lupus anticoagulant, complete blood count, viral serological assays, or microRNA microarray. Patients will undergo dynamic susceptibility contrast-enhanced MRI using a 3.0-T scanner to evaluate CBF, CBV, MTT, lesion number, and volume. Statistical Analysis: ANOVA and unpaired t-tests will be used. The level of significance was set at p 64 0.05. Discussion: Identifying a link between activation of coagulation/complement system and cerebral hypoperfusion could improve the identification of novel molecular and/or imaging biomarkers and targets, leading to the development of new effective therapeutic strategies in MS. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT04380220

Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian gastrointestinal trials group randomized phase III MAX study

Purpose: To determine whether adding bevacizumab, with or without mitomycin, to capecitabine monotherapy improves progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC) in an open-label, three-arm randomized trial. Patients and Methods: Overall, 471 patients in Australia, New Zealand, and the United Kingdom with previously untreated, unresectable mCRC were randomly assigned to the following: capecitabine; capecitabine plus bevacizumab (CB); or capecitabine, bevacizumab, and mitomycin (CBM). We compared CB with capecitabine and CBM with capecitabine for progression-free survival (PFS). Secondary end points included overall survival (OS), toxicity, response rate (RR), and quality of life (QOL). Results: Median PFS was 5.7 months for capecitabine, 8.5 months for CB, and 8.4 months for CBM (capecitabine v CB: hazard ratio [HR], 0.63; 95% CI, 0.50 to 0.79; P < .001; C v CBM: HR, 0.59; 95% CI, 0.47 to 0.75; P < .001). After a median follow-up of 31 months, median OS was 18.9 months for capecitabine and was 16.4 months for CBM; these data were not significantly different. Toxicity rates were acceptable, and all treatment regimens well tolerated. Bevacizumab toxicities were similar to those in previous studies. Measures of overall QOL were similar in all groups. Conclusion: Adding bevacizumab to capecitabine, with or without mitomycin, significantly improves PFS without major additional toxicity or impairment of QOL.Niall C. Tebbutt, Kate Wilson, Val J. Gebski, Michelle M. Cummins, Diana Zannino, Guy A. van Hazel, Bridget Robinson, Adam Broad, Vinod Ganju, Stephen P. Ackland, Garry Forgeson, David Cunningham, Mark P. Saunders, Martin R. Stockler, YuJo Chua, John R. Zalcberg, R. John Simes and Timothy J. Pric