A neuroanatomical examination of embodied cognition: semantic generation to action-related stimuli

The theory of embodied cognition postulates that the brain represents semantic knowledge as a function of the interaction between the body and the environment. The goal of our research was to provide a neuroanatomical examination of embodied cognition using action-related pictures and words. We used functional magnetic resonance imaging (fMRI) to examine whether there were shared and/or unique regions of activation between an ecologically valid semantic generation task and a motor task in the parietal-frontocentral network (PFN), as a function of stimulus format (pictures versus words) for two stimulus types (hand and foot). Unlike other methods for neuroimaging analyses involving subtractive logic or conjoint analyses, this method first isolates shared and unique regions of activation within-participants before generating an averaged map. The results demonstrated shared activation between the semantic generation and motor tasks, which was organized somatotopically in the PFN, as well as unique activation for the semantic generation tasks in proximity to the hand or foot motor cortex. We also found unique and shared regions of activation in the PFN as a function of stimulus format (pictures versus words). These results further elucidate embodied cognition in that they show that brain regions activated during actual motor movements were also activated when an individual verbally generates action-related semantic information. Disembodied cognition theories and limitations are also discussed

High Force Unimanual Handgrip Contractions Increase Ipsilateral Sensorimotor Activation and Functional Connectivity

Imaging and brain stimulation studies seem to correct the classical understanding of how brain networks, rather than contralateral focal areas, control the generation of unimanual voluntary force. However, the scaling and hemispheric-specificity of network activation remain less understood. Using fMRI, we examined the effects of parametrically increasing right-handgrip force on activation and functional connectivity among the sensorimotor network bilaterally with 25%, 50%, and 75% maximal voluntary contractions (MVC). High force (75% MVC) unimanual handgrip contractions resulted in greater ipsilateral motor activation and functional connectivity with the contralateral hemisphere compared to a low force 25% MVC condition. The ipsilateral motor cortex activation and network strength correlated with relative handgrip force (% MVC). Increases in unimanual handgrip force resulted in greater ipsilateral sensorimotor activation and greater functional connectivity between hemispheres within the sensorimotor network. (C) 2020 IBRO. Published by Elsevier Ltd. All rights reserved

Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer.

Background:Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. Methods:The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Rao's quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results:A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P < .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio [HR] = 1.98, 95% confidence interval [CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI = 1.18 to 4.99). Conclusions:Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors

Cross-species comparison of aCGH data from mouse and human BRCA1- and BRCA2-mutated breast cancers

Background: Genomic gains and losses are a result of genomic instability in many types of cancers. BRCA1- and BRCA2-mutated breast cancers are associated with increased amounts of chromosomal aberrations, presumably due their functions in genome repair. Some of these genomic aberrations may harbor genes whose absence or overexpression may give rise to cellular growth advantage. So far, it has not been easy to identify the driver genes underlying gains and losses. A powerful approach to identify these driver genes could be a cross-species comparison of array comparative genomic hybridization (aCGH) data from cognate mouse and human tumors. Orthologous regions of mouse and human tumors that are commonly gained or lost might represent essential genomic regions selected for gain or loss during tumor development. Methods: To identify genomic regions that are associated with BRCA1- and BRCA2-mutated breast cancers we compared aCGH data from 130 mouse Brca1?/?;p53?/?, Brca2?/?;p53?/? and p53?/? mammary tumor groups with 103 human BRCA1-mutated, BRCA2-mutated and non-hereditary breast cancers. Results: Our genome-wide cross-species analysis yielded a complete collection of loci and genes that are commonly gained or lost in mouse and human breast cancer. Principal common CNAs were the well known MYCassociated gain and RB1/INTS6-associated loss that occurred in all mouse and human tumor groups, and the AURKA-associated gain occurred in BRCA2-related tumors from both species. However, there were also important differences between tumor profiles of both species, such as the prominent gain on chromosome 10 in mouse Brca2?/?;p53?/? tumors and the PIK3CA associated 3q gain in human BRCA1-mutated tumors, which occurred in tumors from one species but not in tumors from the other species. This disparity in recurrent aberrations in mouse and human tumors might be due to differences in tumor cell type or genomic organization between both species. Conclusions: The selection of the oncogenome during mouse and human breast tumor development is markedly different, apart from the MYC gain and RB1-associated loss. These differences should be kept in mind when using mouse models for preclinical studies.MediamaticsElectrical Engineering, Mathematics and Computer Scienc

194 Postscript: Plaut and Booth’s (2006) New Simulations— What Have We Learned?

Plaut and Booth’s (2006) first simulation shows that there is essentially perfect discrimination between word and nonwords sharing the same orthographic structure when the simulation is carried out in the way we suggested. We are therefore satisfied that their model can (now) be characterized as a parallel distributed processing (PDP) model of lexical processing (with the caveat that although it is beyond the scope of the present work, it is important to show at some point that the model “scales up ” when it has a more realistically sized vocabulary of 40,000 words or so). We voiced concern that their model makes lexical decisions at the semantic level but there are patients with severe damage to semantics who are nonetheless as accurate at lexical decision as control patients without such damage (Coltheart, 2004). Can a model that makes lexical decisions at the semantic level simulate these data? In reply, Plaut and Booth (2006) reported new simulation

Semantic ambiguity effects in word identification

The influence of semantic ambiguity on word identification processes was explored in a series of word naming and lexical-decision experiments. There was no reliable ambiguity effect in 2 naming experiments, although an ambiguity advantage in lexical decision was obtained when orthographi-cally legal nonwords were used. No ambiguity effect was found in iexical decision when orthographically illegal nonwords were used, implying a semantic locus for the ambiguity advantage. These results were simulated by using a distributed memory model that also produces the ambiguity disadvantage in gaze duration that has been obtained with a reading comprehension task. Ambiguity effects in the model arise from the model's attempt to activate multiple meanings of an ambiguous word in response to presentation of that word's orthographic pattern. Reasons for discrepancies in empirical results and implications for distributed memory models are considered. Any comprehensive theory of mental representation and process must accommodate the complex means by which concepts are communicated through language. Through the course of history, humans have developed tools of communica-tion that facilitate the relaying of ideas and concepts, such as a writing system or orthography. This mapping of concepts to orthography is not entirely one to one, however, resulting in some words that correspond to multiple concepts, which are known as semantically ambiguous words. When reading text, the context provided by preceding words and sentences pro-vides a means of disambiguating such words. As a result, we may not even notice the ambiguity in words that we are reading in context. If, on the other hand, semantically ambiguous words are presented in isolation, their alternative meanings are readily accessible, and thus their ambiguous nature is noticed. In the research reported in this article, we compare performance on semantically ambiguous words with that of semantically unambiguous words in isolated word identifica-tion tasks and describe simulations of the empirical effects within the framework of a distributed memory architectur

More than meets the eye: Context effects in word identification

The influence of semantic context on word identification was examined using masked target displays. Related prime words enhanced a signal detection measure of sensitivity in making lexical decisions and in determining whether a probe word matched the target word. When line drawings were used as primes, a similar benefit was obtained with the probe task. Although these results suggest that contextual information affects perceptual encoding, this conclusion is questioned on the grounds that sensitivity in these tasks may be determined by independent contributions of perceptual and contextual information. The plausibility of this view is supported by a simulation of the experiments using a connectionist model in which perceptual and semantic information make independent contributions to word identification. The model also predicts results with two other analytic methods that have been used to argue for priming effects on perceptual encoding. The identification of objects or events in the environment, including written and spoken language, benefits from the availability of conceptually relevant information provided by the context in which an object or event occurs. For example, the identification of visually presented individual letters is enhanced when they are placed in the context of a familiar word (see, e.g., McClelland & Rumelhart