Co(II) Substitution Enhances the Esterase Activity of a de Novo Designed Zn(II) Carbonic Anhydrase.

Carbonic Anhydrases (CAs) have been a target for de novo protein designers due to the simplicity of the active site and rapid rate of the reaction. The first reported mimic contained a Zn(II) bound to three histidine imidazole nitrogens and an exogenous water molecule, hence closely mimicking the native enzymes' first coordination sphere. Co(II) has served as an alternative metal to interrogate CAs due to its d7 electronic configuration for more detailed solution characterization. We present here the Co(II) substituted [Co(II)(H2O/OH-)]N(TRIL2WL23H)3 n+ that behaves similarly to native Co(II) substituted human-CAs. Like the Zn(II) analogue, the cobalt-derivative at slightly basic pH is incapable of hydrolyzing p-nitrophenylacetate (pNPA); however, as the pH is increased a significant activity develops, which at pH values above 10 eventually yields a catalytic efficiency that exceeds that of the [Zn(II)(OH-)]N(TRIL2WL23H)3 + peptide complex. X-ray absorption analysis is consistent with an octahedral species at pH 7.5 that converts to a 5-coordinate species by pH 11. UV-vis spectroscopy can monitor this transition, giving a pKa for the conversion of 10.3. We assign this conversion to the formation of a 5-coordinate Co(II)(Nimid)3(OH)(H2O) species. The pH dependent kinetic analysis indicates the maximal rate (kcat), and thus the catalytic efficiency (kcat/Km), follow the same pH profile as the spectroscopic conversion to the pentacoordinate species. This correlation suggests that the chemically irreversible ester hydrolysis corresponds to the rate determining process.

Uronium peptide coupling agents: Another case of occupational airborne allergic sensitization induced by HBTU.

Uronium peptide coupling agents (HBTU, HATU, and HCTU) create a special hazard as they are immune sensitizers. Few reported cases are mentioned in the literature; despite that, it is important to raise the awareness on the subject and to highlight the risk and potential symptoms that could occur to those who directly work in contact with uronium peptide coupling agents, as well as to the safety deputies in the universities and industries. Based on a personal experience, the health impact of laboratory exposure to HBTU is described, and the insights gained from the experience are developed. A skin irritation reaction and allergy symptoms induced by HBTU exposure are shown here as well as the rate of worsening of symptoms since the first allergic reaction. Recommendations for handling coupling agents more safely in the research laboratory will also be given, and a casuistry of the matter to help other lab-users to recognize, assess, minimize, prepare for emergencies (RAMP) process.

Synthesis and Preliminary Studies for In Vitro Biological Activity of Two New Water-Soluble Bis(thio)carbohydrazones and Their Copper(II) and Zinc(II) Complexes.

Research in the field of metallodrugs is continually increasing. However, it is often limited by the poor solubility in water of the metal complexes. To try to overcome this problem, the two new ligands bis-(sodium 3-methoxy-5-sulfonate-salicylaldehyde)thiocarbohydrazone (bis-TCH, Na2H4L1) and bis-(sodium 3-methoxy-5-sulfonate-salicylaldehyde)carbohydrazone (bis-CH, Na2H4L2) were synthesized and characterized, both achieving high solubility in water. The speciation of the ligands and their coordinating behaviour towards the biologically relevant Cu(II) and Zn(II) ions were studied spectroscopically and potentiometrically, determining the pKas of the ligands and the formation constants of the complex species. The monometallic and bimetallic Cu(II) and Zn(II) complexes were isolated, and the single-crystal X-ray structure of [Cu2(NaHL1)(H2O)7].3.5H2O was discussed. Finally, preliminary studies of the in vitro cytotoxic properties of the new compounds were started on normal (Hs27) and cancer (U937) cell lines. bis-TCH was able to induce a growth inhibition effect between 40% and 45% in both cell lines; bis-CH did not produce a reduction in cell viability in Hs27 cells but revealed mild antiproliferative activity after 72 h of treatment in U937 cancer cells (GI50 = 46.5 ± 4.94 µg/mL). Coordination of the Cu(II) ions increased the toxicity of the compounds, while, in contrast, Zn(II) complexes were not cytotoxic.

Distinct neurophysiology during nonword repetition in logopenic and non-fluent variants of primary progressive aphasia.

Overlapping clinical presentations in primary progressive aphasia (PPA) variants present challenges for diagnosis and understanding pathophysiology, particularly in the early stages of the disease when behavioral (speech) symptoms are not clearly evident. Divergent atrophy patterns (temporoparietal degeneration in logopenic variant lvPPA, frontal degeneration in nonfluent variant nfvPPA) can partially account for differential speech production errors in the two groups in the later stages of the disease. While the existing dogma states that neurodegeneration is the root cause of compromised behavior and cortical activity in PPA, the extent to which neurophysiological signatures of speech dysfunction manifest independent of their divergent atrophy patterns remain unknown. We test the hypothesis that nonword deficits in lvPPA and nfvPPA arise from distinct patterns of neural oscillations that are unrelated to atrophy. We use a novel structure-function imaging approach integrating magnetoencephalographic imaging of neural oscillations during a non-word repetition task with voxel-based morphometry-derived measures of gray matter volume to isolate neural oscillation abnormalities independent of atrophy. We find reduced beta band neural activity in left temporal regions associated with the late stages of auditory encoding unique to patients with lvPPA and reduced high-gamma neural activity over left frontal regions associated with the early stages of motor preparation in patients with nfvPPA. Neither of these patterns of reduced cortical oscillations was explained by cortical atrophy in our statistical model. These findings highlight the importance of structure-function imaging in revealing neurophysiological sequelae in early stages of dementia when neither structural atrophy nor behavioral deficits are clinically distinct.

Right temporal degeneration and socioemotional semantics: semantic behavioural variant frontotemporal dementia.

Focal anterior temporal lobe degeneration often preferentially affects the left or right hemisphere. While patients with left-predominant anterior temporal lobe atrophy show severe anomia and verbal semantic deficits and meet criteria for semantic variant primary progressive aphasia and semantic dementia, patients with early right anterior temporal lobe atrophy are more difficult to diagnose as their symptoms are less well understood. Focal right anterior temporal lobe atrophy is associated with prominent emotional and behavioural changes, and patients often meet, or go on to meet, criteria for behavioural variant frontotemporal dementia. Uncertainty around early symptoms and absence of an overarching clinico-anatomical framework continue to hinder proper diagnosis and care of patients with right anterior temporal lobe disease. Here, we examine a large, well-characterized, longitudinal cohort of patients with right anterior temporal lobe-predominant degeneration and propose new criteria and nosology. We identified individuals from our database with a clinical diagnosis of behavioural variant frontotemporal dementia or semantic variant primary progressive aphasia and a structural MRI (n = 478). On the basis of neuroimaging criteria, we defined three patient groups: right anterior temporal lobe-predominant atrophy with relative sparing of the frontal lobes (n = 46), frontal-predominant atrophy with relative sparing of the right anterior temporal lobe (n = 79) and left-predominant anterior temporal lobe-predominant atrophy with relative sparing of the frontal lobes (n = 75). We compared the clinical, neuropsychological, genetic and pathological profiles of these groups. In the right anterior temporal lobe-predominant group, the earliest symptoms were loss of empathy (27%), person-specific semantic impairment (23%) and complex compulsions and rigid thought process (18%). On testing, this group exhibited greater impairments in Emotional Theory of Mind, recognition of famous people (from names and faces) and facial affect naming (despite preserved face perception) than the frontal- and left-predominant anterior temporal lobe-predominant groups. The clinical symptoms in the first 3 years of the disease alone were highly sensitive (81%) and specific (84%) differentiating right anterior temporal lobe-predominant from frontal-predominant groups. Frontotemporal lobar degeneration-transactive response DNA binding protein (84%) was the most common pathology of the right anterior temporal lobe-predominant group. Right anterior temporal lobe-predominant degeneration is characterized by early loss of empathy and person-specific knowledge, deficits that are caused by progressive decline in semantic memory for concepts of socioemotional relevance. Guided by our results, we outline new diagnostic criteria and propose the name, 'semantic behavioural variant frontotemporal dementia', which highlights the underlying cognitive mechanism and the predominant symptomatology. These diagnostic criteria will facilitate early identification and care of patients with early, focal right anterior temporal lobe degeneration as well as in vivo prediction of frontotemporal lobar degeneration-transactive response DNA binding protein pathology.

Task-Free Functional Language Networks: Reproducibility and Clinical Application.

Intrinsic connectivity networks (ICNs) identified through task-free fMRI (tf-fMRI) offer the opportunity to investigate human brain circuits involved in language processes without requiring participants to perform challenging cognitive tasks. In this study, we assessed the ability of tf-fMRI to isolate reproducible networks critical for specific language functions and often damaged in primary progressive aphasia (PPA). First, we performed whole-brain seed-based correlation analyses on tf-fMRI data to identify ICNs anchored in regions known for articulatory, phonological, and semantic processes in healthy male and female controls (HCs). We then evaluated the reproducibility of these ICNs in an independent cohort of HCs, and recapitulated their functional relevance with a post hoc meta-analysis on task-based fMRI. Last, we investigated whether atrophy in these ICNs could inform the differential diagnosis of nonfluent/agrammatic, semantic, and logopenic PPA variants. The identified ICNs included a dorsal articulatory-phonological network involving inferior frontal and supramarginal regions; a ventral semantic network involving anterior middle temporal and angular gyri; a speech perception network involving superior temporal and sensorimotor regions; and a network between posterior inferior temporal and intraparietal regions likely linking visual, phonological, and attentional processes for written language. These ICNs were highly reproducible across independent groups and revealed areas consistent with those emerging from task-based meta-analysis. By comparing ICNs' spatial distribution in HCs with patients' atrophy patterns, we identified ICNs associated with each PPA variant. Our findings demonstrate the potential use of tf-fMRI to investigate the functional status of language networks in patients for whom activation studies can be methodologically challenging.SIGNIFICANCE STATEMENT We showed that a single, short, task-free fMRI acquisition is able to identify four reproducible and relatively segregated intrinsic left-dominant networks associated with articulatory, phonological, semantic, and multimodal orthography-to-phonology processes, in HCs. We also showed that these intrinsic networks relate to syndrome-specific atrophy patterns in primary progressive aphasia. Collectively, our results support the application of task-free fMRI in future research to study functionality of language circuits in patients for whom tasked-based activation studies might be methodologically challenging.

Symbolic categorization of novel multisensory stimuli in the human brain.

When primates (both human and non-human) learn to categorize simple visual or acoustic stimuli by means of non-verbal matching tasks, two types of changes occur in their brain: early sensory cortices increase the precision with which they encode sensory information, and parietal and lateral prefrontal cortices develop a categorical response to the stimuli. Contrary to non-human animals, however, our species mostly constructs categories using linguistic labels. Moreover, we naturally tend to define categories by means of multiple sensory features of the stimuli. Here we trained adult subjects to parse a novel audiovisual stimulus space into 4 orthogonal categories, by associating each category to a specific symbol. We then used multi-voxel pattern analysis (MVPA) to show that during a cross-format category repetition detection task three neural representational changes were detectable. First, visual and acoustic cortices increased both precision and selectivity to their preferred sensory feature, displaying increased sensory segregation. Second, a frontoparietal network developed a multisensory object-specific response. Third, the right hippocampus and, at least to some extent, the left angular gyrus, developed a shared representational code common to symbols and objects. In particular, the right hippocampus displayed the highest level of abstraction and generalization from a format to the other, and also predicted symbolic categorization performance outside the scanner. Taken together, these results indicate that when humans categorize multisensory objects by means of language the set of changes occurring in the brain only partially overlaps with that described by classical models of non-verbal unisensory categorization in primates.

Embracing diversity and inclusivity in an academic setting: Insights from the Organization for Human Brain Mapping.

Scientific research aims to bring forward innovative ideas and constantly challenges existing knowledge structures and stereotypes. However, women, ethnic and cultural minorities, as well as individuals with disabilities, are systematically discriminated against or even excluded from promotions, publications, and general visibility. A more diverse workforce is more productive, and thus discrimination has a negative impact on science and the wider society, as well as on the education, careers, and well-being of individuals who are discriminated against. Moreover, the lack of diversity at scientific gatherings can lead to micro-aggressions or harassment, making such meetings unpleasant, or even unsafe environments for early career and underrepresented scientists. At the Organization for Human Brain Mapping (OHBM), we recognized the need for promoting underrepresented scientists and creating diverse role models in the field of neuroimaging. To foster this, the OHBM has created a Diversity and Inclusivity Committee (DIC). In this article, we review the composition and activities of the DIC that have promoted diversity within OHBM, in order to inspire other organizations to implement similar initiatives. Activities of the committee over the past four years have included (a) creating a code of conduct, (b) providing diversity and inclusivity education for OHBM members, (c) organizing interviews and symposia on diversity issues, and (d) organizing family-friendly activities and providing childcare grants during the OHBM annual meetings. We strongly believe that these activities have brought positive change within the wider OHBM community, improving inclusivity and fostering diversity while promoting rigorous, ground-breaking science. These positive changes could not have been so rapidly implemented without the enthusiastic support from the leadership, including OHBM Council and Program Committee, and the OHBM Special Interest Groups (SIGs), namely the Open Science, Student and Postdoc, and Brain-Art SIGs. Nevertheless, there remains ample room for improvement, in all areas, and even more so in the area of targeted attempts to increase inclusivity for women, individuals with disabilities, members of the LGBTQ+ community, racial/ethnic minorities, and individuals of lower socioeconomic status or from low and middle-income countries. Here, we present an overview of the DIC's composition, its activities, future directions and challenges. Our goal is to share our experiences with a wider audience to provide information to other organizations and institutions wishing to implement similar comprehensive diversity initiatives. We propose that scientific organizations can push the boundaries of scientific progress only by moving beyond existing power structures and by integrating principles of equity and inclusivity in their core values.

The Open Brain Consent: Informing research participants and obtaining consent to share brain imaging data.

Having the means to share research data openly is essential to modern science. For human research, a key aspect in this endeavor is obtaining consent from participants, not just to take part in a study, which is a basic ethical principle, but also to share their data with the scientific community. To ensure that the participants' privacy is respected, national and/or supranational regulations and laws are in place. It is, however, not always clear to researchers what the implications of those are, nor how to comply with them. The Open Brain Consent (https://open-brain-consent.readthedocs.io) is an international initiative that aims to provide researchers in the brain imaging community with information about data sharing options and tools. We present here a short history of this project and its latest developments, and share pointers to consent forms, including a template consent form that is compliant with the EU general data protection regulation. We also share pointers to an associated data user agreement that is not only useful in the EU context, but also for any researchers dealing with personal (clinical) data elsewhere.

Impact of N-Truncated Aß Peptides on Cu- and Cu(Aß)-Generated ROS: CuI Matters!

In vitro Cu(Aß1-x )-induced ROS production has been extensively studied. Conversely, the ability of N-truncated isoforms of Aß to alter the Cu-induced ROS production has been overlooked, even though they are main constituents of amyloid plaques found in the human brain. N-Truncated peptides at the positions 4 and 11 (Aß4-x and Aß11-x ) contain an amino-terminal copper and nickel (ATCUN) binding motif (H2 N-Xxx-Zzz-His) that confer them different coordination sites and higher affinities for CuII compared to the Aß1-x peptide. It has further been proposed that the role of Aß4-x peptide is to quench CuII toxicity in the brain. However, the role of CuI coordination has not been investigated to date. In contrast to CuII , CuI coordination is expected to be the same for N-truncated and N-intact peptides. Herein, we report in-depth characterizations and ROS production studies of Cu (CuI and CuII ) complexes of the Aß4-16 and Aß11-16 N-truncated peptides. Our findings show that the N-truncated peptides do produce ROS when CuI is present in the medium, albeit to a lesser extent than the unmodified counterpart. In addition, when used as competitor ligands (i.e., in the presence of Aß1-16 ), the N-truncated peptides are not able to fully preclude Cu(Aß1-16 )-induced ROS production.

Taking the sublexical route: brain dynamics of reading in the semantic variant of primary progressive aphasia.

Reading aloud requires mapping an orthographic form to a phonological one. The mapping process relies on sublexical statistical regularities (e.g. 'oo' to |uː|) or on learned lexical associations between a specific visual form and a series of sounds (e.g. yacht to/jɑt/). Computational, neuroimaging, and neuropsychological evidence suggest that sublexical, phonological and lexico-semantic processes rely on partially distinct neural substrates: a dorsal (occipito-parietal) and a ventral (occipito-temporal) route, respectively. Here, we investigated the spatiotemporal features of orthography-to-phonology mapping, capitalizing on the time resolution of magnetoencephalography and the unique clinical model offered by patients with semantic variant of primary progressive aphasia (svPPA). Behaviourally, patients with svPPA manifest marked lexico-semantic impairments including difficulties in reading words with exceptional orthographic to phonological correspondence (irregular words). Moreover, they present with focal neurodegeneration in the anterior temporal lobe, affecting primarily the ventral, occipito-temporal, lexical route. Therefore, this clinical population allows for testing of specific hypotheses on the neural implementation of the dual-route model for reading, such as whether damage to one route can be compensated by over-reliance on the other. To this end, we reconstructed and analysed time-resolved whole-brain activity in 12 svPPA patients and 12 healthy age-matched control subjects while reading irregular words (e.g. yacht) and pseudowords (e.g. pook). Consistent with previous findings that the dorsal route is involved in sublexical, phonological processes, in control participants we observed enhanced neural activity over dorsal occipito-parietal cortices for pseudowords, when compared to irregular words. This activation was manifested in the beta-band (12-30 Hz), ramping up slowly over 500 ms after stimulus onset and peaking at ∼800 ms, around response selection and production. Consistent with our prediction, svPPA patients did not exhibit this temporal pattern of neural activity observed in controls this contrast. Furthermore, a direct comparison of neural activity between patients and controls revealed a dorsal spatiotemporal cluster during irregular word reading. These findings suggest that the sublexical/phonological route is involved in processing both irregular and pseudowords in svPPA. Together these results provide further evidence supporting a dual-route model for reading aloud mediated by the interplay between lexico-semantic and sublexical/phonological neurocognitive systems. When the ventral route is damaged, as in the case of neurodegeneration affecting the anterior temporal lobe, partial compensation appears to be possible by over-recruitment of the slower, serial attention-dependent, dorsal one.

State and trait characteristics of anterior insula time-varying functional connectivity.

The human anterior insula (aINS) is a topographically organized brain region, in which ventral portions contribute to socio-emotional function through limbic and autonomic connections, whereas the dorsal aINS contributes to cognitive processes through frontal and parietal connections. Open questions remain, however, regarding how aINS connectivity varies over time. We implemented a novel approach combining seed-to-whole-brain sliding-window functional connectivity MRI and k-means clustering to assess time-varying functional connectivity of aINS subregions. We studied three independent large samples of healthy participants and longitudinal datasets to assess inter- and intra-subject stability, and related aINS time-varying functional connectivity profiles to dispositional empathy. We identified four robust aINS time-varying functional connectivity modes that displayed both "state" and "trait" characteristics: while modes featuring connectivity to sensory regions were modulated by eye closure, modes featuring connectivity to higher cognitive and emotional processing regions were stable over time and related to empathy measures.

Conceptual and Perceptual Dimensions of Word Meaning Are Recovered Rapidly and in Parallel during Reading.

A single word (the noun "elephant") encapsulates a complex multidimensional meaning, including both perceptual ("big", "gray", "trumpeting") and conceptual ("mammal", "can be found in India") features. Opposing theories make different predictions as to whether different features (also conceivable as dimensions of the semantic space) are stored in similar neural regions and recovered with similar temporal dynamics during word reading. In this magnetoencephalography study, we tracked the brain activity of healthy human participants while reading single words varying orthogonally across three semantic dimensions: two perceptual ones (i.e., the average implied real-world size and the average strength of association with a prototypical sound) and a conceptual one (i.e., the semantic category). The results indicate that perceptual and conceptual representations are supported by partially segregated neural networks: Whereas visual and auditory dimensions are encoded in the phase coherence of low-frequency oscillations of occipital and superior temporal regions, respectively, semantic features are encoded in the power of low-frequency oscillations of anterior temporal and inferior parietal areas. However, despite the differences, these representations appear to emerge at the same latency: around 200 msec after stimulus onset. Taken together, these findings suggest that perceptual and conceptual dimensions of the semantic space are recovered automatically, rapidly, and in parallel during word reading.

The Neural Representations of Movement across Semantic Categories.

Previous evidence from neuropsychological and neuroimaging studies suggests functional specialization for tools and related semantic knowledge in a left frontoparietal network. It is still debated whether these areas are involved in the representation of rudimentary movement-relevant knowledge regardless of semantic domains (animate vs. inanimate) or categories (tools vs. nontool objects). Here, we used fMRI to record brain activity while 13 volunteers performed two semantic judgment tasks on visually presented items from three different categories: animals, tools, and nontool objects. Participants had to judge two distinct semantic features: whether two items typically move in a similar way (e.g., a fan and a windmill move in circular motion) or whether they are usually found in the same environment (e.g., a seesaw and a swing are found in a playground). We investigated differences in overall activation (which areas are involved) as well as representational content (which information is encoded) across semantic features and categories. Results of voxel-wise mass univariate analysis showed that, regardless of semantic category, a dissociation emerges between processing information on prototypical location (involving the anterior temporal cortex and the angular gyrus) and movement (linked to left inferior parietal and frontal activation). Multivoxel pattern correlation analyses confirmed the representational segregation of networks encoding task- and category-related aspects of semantic processing. Taken together, these findings suggest that the left frontoparietal network is recruited to process movement properties of items (including both biological and nonbiological motion) regardless of their semantic category.

Mutations of Histidine†13 to Arginine and Arginine 5 to Glycine Are Responsible for Different Coordination Sites of Zinc(II) to Human and Murine Peptides.

Because mice and rats do not naturally develop Alzheimer's disease, genetically modified animals are required to study this pathology. This striking difference in terms of disease onset could be due to three alterations in the murine sequence (R5G, Y10F and H13R) of the amyloid-ß peptide with respect to the human counterpart. Whether the metal-ion binding properties of the murine peptide are at the origin of such different amyloidogenicity of the two peptides is still an open question. Herein, the main zinc binding site to the murine amyloid-ß at physiological pH has been determined through the combination of several spectroscopic and analytical methods applied to a series of six peptides with one or two of the key mutations. These results have been compared with the zinc binding site encountered in the human peptide. A coordination mechanism that demonstrates the importance of the H13R and R5G mutations in the different zinc environments present in the murine and human peptides is proposed. The nature of the minor zinc species present at physiological pH is also suggested for both peptides. Finally, the biological relevance and fallouts of the differences determined in zinc binding to human versus murine amyloid-ß are also discussed.

Cu(II) binding to various forms of amyloid-ß peptides. Are they friends or foes?

In the present micro-review, we describe the Cu(II) binding to several forms of amyloid-ß peptides, the peptides involved in Alzheimer's disease. It has indeed been shown that in addition to the "full-length" peptide originating from the precursor protein after cleavage at position 1, several other shorter peptides do exist in large proportion and may be involved in the disease as well. Cu(II) binding to amyloid-ß peptides is one of the key interactions that impact both the aggregating properties of the amyloid peptides and the Reactive Oxygen Species (ROS) production, two events linked to the etiology of the disease. Binding sites and affinity are described in correlation with Cu(II) induced ROS formation and Cu(II) altered aggregation, for amyloid peptides starting at position 1, 3, 4, 11 and for the corresponding pyroglutamate forms when they could be obtained (i.e. for peptides cleaved at positions 3 and 11). It appears that the current paradigm which points out a toxic role of the Cu(II) - amyloid-ß interaction might well be shifted towards a possible protective role when the peptides considered are the N-terminally truncated ones.

Link between Affinity and Cu(II) Binding Sites to Amyloid-ß Peptides Evaluated by a New Water-Soluble UV-Visible Ratiometric Dye with a Moderate Cu(II) Affinity.

Being able to easily determine the Cu(II) affinity for biomolecules of moderate affinity is important. Such biomolecules include amyloidogenic peptides, such as the well-known amyloid-ß peptide involved in Alzheimer's disease. Here, we report the synthesis of a new water-soluble ratiometric Cu(II) dye with a moderate affinity (109 M-1 at pH 7.1) and the characterizations of the Cu(II) corresponding complex by X-ray crystallography, EPR, and XAS spectroscopic methods. UV-vis competition was performed on the Aß peptide as well as on a wide series of modified peptides, leading to an affinity value of 1.6 × 109 M-1 at pH 7.1 for the Aß peptide and to a coordination model for the Cu(II) site within the Aß peptide that agrees with the one mostly accepted currently.

Word meaning in the ventral visual path: a perceptual to conceptual gradient of semantic coding.

The meaning of words referring to concrete items is thought of as a multidimensional representation that includes both perceptual (e.g., average size, prototypical color) and conceptual (e.g., taxonomic class) dimensions. Are these different dimensions coded in different brain regions? In healthy human subjects, we tested the presence of a mapping between the implied real object size (a perceptual dimension) and the taxonomic categories at different levels of specificity (conceptual dimensions) of a series of words, and the patterns of brain activity recorded with functional magnetic resonance imaging in six areas along the ventral occipito-temporal cortical path. Combining multivariate pattern classification and representational similarity analysis, we found that the real object size implied by a word appears to be primarily encoded in early visual regions, while the taxonomic category and sub-categorical cluster in more anterior temporal regions. This anteroposterior gradient of information content indicates that different areas along the ventral stream encode complementary dimensions of the semantic space.

What we mean when we say semantic: Toward a multidisciplinary semantic glossary.

Tulving characterized semantic memory as a vast repository of meaning that underlies language and many other cognitive processes. This perspective on lexical and conceptual knowledge galvanized a new era of research undertaken by numerous fields, each with their own idiosyncratic methods and terminology. For example, "concept" has different meanings in philosophy, linguistics, and psychology. As such, many fundamental constructs used to delineate semantic theories remain underspecified and/or opaque. Weak construct specificity is among the leading causes of the replication crisis now facing psychology and related fields. Term ambiguity hinders cross-disciplinary communication, falsifiability, and incremental theory-building. Numerous cognitive subdisciplines (e.g., vision, affective neuroscience) have recently addressed these limitations via the development of consensus-based guidelines and definitions. The project to follow represents our effort to produce a multidisciplinary semantic glossary consisting of succinct definitions, background, principled dissenting views, ratings of agreement, and subjective confidence for 17 target constructs (e.g., abstractness, abstraction, concreteness, concept, embodied cognition, event semantics, lexical-semantic, modality, representation, semantic control, semantic feature, simulation, semantic distance, semantic dimension). We discuss potential benefits and pitfalls (e.g., implicit bias, prescriptiveness) of these efforts to specify a common nomenclature that other researchers might index in specifying their own theoretical perspectives (e.g., They said X, but I mean Y).

Diminished baseline autonomic outflow in semantic dementia relates to left-lateralized insula atrophy.

In semantic dementia (SD), asymmetric degeneration of the anterior temporal lobes is associated with loss of semantic knowledge and alterations in socioemotional behavior. There are two clinical variants of SD: semantic variant primary progressive aphasia (svPPA), which is characterized by predominant atrophy in the anterior temporal lobe and insula in the left hemisphere, and semantic behavioral variant frontotemporal dementia (sbvFTD), which is characterized by predominant atrophy in those structures in the right hemisphere. Previous studies of behavioral variant frontotemporal dementia, an associated clinical syndrome that targets the frontal lobes and anterior insula, have found impairments in baseline autonomic nervous system activity that correlate with left-lateralized frontotemporal atrophy patterns and disruptions in socioemotional functioning. Here, we evaluated whether there are similar impairments in resting autonomic nervous system activity in SD that also reflect left-lateralized atrophy and relate to diminished affiliative behavior. A total of 82 participants including 33 people with SD (20 svPPA and 13 sbvFTD) and 49 healthy older controls completed a laboratory-based assessment of respiratory sinus arrhythmia (RSA; a parasympathetic measure) and skin conductance level (SCL; a sympathetic measure) during a two-minute resting baseline period. Participants also underwent structural magnetic resonance imaging, and informants rated their current affiliative behavior on the Interpersonal Adjective Scale. Results indicated that baseline RSA and SCL were lower in SD than in healthy controls, with significant impairments present in both svPPA and sbvFTD. Voxel-based morphometry analyses revealed left-greater-than-right atrophy related to diminished parasympathetic and sympathetic outflow in SD. While left-lateralized atrophy in the mid-to-posterior insula correlated with lower RSA, left-lateralized atrophy in the ventral anterior insula correlated with lower SCL. In SD, lower baseline RSA, but not lower SCL, was associated with lower gregariousness/extraversion. Neither autonomic measure related to warmth/agreeableness, however. Through the assessment of baseline autonomic nervous system physiology, the present study contributes to expanding conceptualizations of the biological basis of socioemotional alterations in svPPA and sbvFTD.