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1.
Brain Commun ; 6(1): fcad252, 2024.
Article En | MEDLINE | ID: mdl-38162898

Stroke alters blood flow to the brain resulting in damaged tissue and cell death. Moreover, the disruption of cerebral blood flow (perfusion) can be observed in areas surrounding and distal to the lesion. These structurally preserved but suboptimally perfused regions may also affect recovery. Thus, to better understand aphasia recovery, the relationship between cerebral perfusion and language needs to be systematically examined. In the current study, we aimed to evaluate (i) how stroke affects perfusion outside of lesioned areas in chronic aphasia and (ii) how perfusion in specific cortical areas and perilesional tissue relates to language outcomes in aphasia. We analysed perfusion data from a large sample of participants with chronic aphasia due to left hemisphere stroke (n = 43) and age-matched healthy controls (n = 25). We used anatomically defined regions of interest that covered the frontal, parietal, and temporal areas of the perisylvian cortex in both hemispheres, areas typically known to support language, along with several control regions not implicated in language processing. For the aphasia group, we also looked at three regions of interest in the perilesional tissue. We compared perfusion levels between the two groups and investigated the relationship between perfusion levels and language subtest scores while controlling for demographic and lesion variables. First, we observed that perfusion levels outside the lesioned areas were significantly reduced in frontal and parietal regions in the left hemisphere in people with aphasia compared to the control group, while no differences were observed for the right hemisphere regions. Second, we found that perfusion in the left temporal lobe (and most strongly in the posterior part of both superior and middle temporal gyri) and inferior parietal areas (supramarginal gyrus) was significantly related to residual expressive and receptive language abilities. In contrast, perfusion in the frontal regions did not show such a relationship; no relationship with language was also observed for perfusion levels in control areas and all right hemisphere regions. Third, perilesional perfusion was only marginally related to language production abilities. Cumulatively, the current findings demonstrate that blood flow is reduced beyond the lesion site in chronic aphasia and that hypoperfused neural tissue in critical temporoparietal language areas has a negative impact on behavioural outcomes. These results, using perfusion imaging, underscore the critical and general role that left hemisphere posterior temporal regions play in various expressive and receptive language abilities. Overall, the study highlights the importance of exploring perfusion measures in stroke.

2.
medRxiv ; 2024 Jan 11.
Article En | MEDLINE | ID: mdl-38260605

Exercise can boost physical and cognitive health in older adults. However, there are a lack of accessible exercise programs that foster adherence among older adults. In this study, we aimed to establish the safety and feasibility of APEX, a new exercise program designed to optimize fitness and cognitive gains for older adults, in addition to evaluating its acute physiological effects, and assessing its possible effects on functional fitness and cognition among healthy older adults. APEX utilizes a multimodal progressive high-intensity interval training (HIIT) design, with high-intensity intervals focused on enhancing cardiovascular fitness and muscle strength, and recovery intervals that incorporate balance and mobility exercises. The APEX training was tested in healthy older adults (n=4) over the course of four weeks. Ultimately, APEX was found to be safe and feasible, with no adverse events and high adherence. Participants met heart rate targets for all of the high-intensity exercises, and all intervals had a significant difference in heart rates between high-intensity and recovery periods in linear effects models (p<0.001). Improvements in functional fitness were observed in aerobic endurance, lower body strength, and balance. The intervention was also associated with positive trends in the cognitive domains of information processing, working memory, executive control, and attention. APEX offers a promising alternative to traditional cardiovascular exercise modalities for older adults with additional benefits for functional fitness and cognition. These results encourage further testing of the APEX program in older adults and different clinical populations.

3.
Front Neurol ; 14: 1187399, 2023.
Article En | MEDLINE | ID: mdl-37576017

Introduction: Apraxia of speech (AOS) is a motor speech disorder impairing the coordination of complex articulatory movements needed to produce speech. AOS typically co-occurs with a non-fluent aphasia, or language disorder, making it challenging to determine the specific brain structures that cause AOS. Cases of pure AOS without aphasia are rare but offer the best window into the neural correlates that support articulatory planning. The goal of the current study was to explore patterns of apraxic speech errors and their underlying neural correlates in a case of pure AOS. Methods: A 67-year-old right-handed man presented with severe AOS resulting from a fronto-insular lesion caused by an ischemic stroke. The participant's speech and language were evaluated at 1-, 3- and 12-months post-onset. High resolution structural MRI, including diffusion weighted imaging, was acquired at 12 months post-onset. Results: At the first assessment, the participant made minor errors on the Comprehensive Aphasia Test, demonstrating mild deficits in writing, auditory comprehension, and repetition. By the second assessment, he no longer had aphasia. On the Motor Speech Evaluation, the severity of his AOS was initially rated as 5 (out of 7) and improved to a score of 4 by the second visit, likely due to training by his SLP at the time to slow his speech. Structural MRI data showed a fronto-insular lesion encompassing the superior precentral gyrus of the insula and portions of the inferior and middle frontal gyri and precentral gyrus. Tractography derived from diffusion MRI showed partial damage to the frontal aslant tract and arcuate fasciculus along the white matter projections to the insula. Discussion: This pure case of severe AOS without aphasia affords a unique window into the behavioral and neural mechanisms of this motor speech disorder. The current findings support previous observations that AOS and aphasia are dissociable and confirm a role for the precentral gyrus of the insula and BA44, as well as underlying white matter in supporting the coordination of complex articulatory movements. Additionally, other regions including the precentral gyrus, Broca's area, and Area 55b are discussed regarding their potential role in successful speech production.

4.
Aphasiology ; 37(2): 260-287, 2023.
Article En | MEDLINE | ID: mdl-36699113

Background: Previous studies have shown that individuals with aphasia have impairments in switching attention compared to healthy controls. However, there is insufficient information about the characteristics of switching attention within one task and whether attention deficits vary depending on aphasia type and lesion location. We aimed to address these knowledge gaps by investigating characteristics of switching attention within one type of task in participants with different types of aphasia and distinct lesion sites. Method: Forty individuals with post-stroke aphasia (20 with non-fluent aphasia and frontal lobe damage, and 20 with fluent aphasia and temporal lobe damage) and 20 neurologically healthy age-matched individuals performed an attention switching task. They listened to sequences of high-pitched and low-pitched tones that were presented to them one by one, tallied them separately, and, at the end of each sequence, had to say how many high- and low-pitched tones they had heard. Results: Participants with aphasia performed significantly worse on the task compared to healthy controls, and the performance of two aphasia groups also differed. Specifically, individuals with both aphasia types made more errors than healthy individuals, and the participants with non-fluent aphasia responded more slowly than controls, while reaction times of the participants with fluent aphasia did not differ significantly from those of controls. Also, the two groups of participants with aphasia differed significantly in accuracy, with individuals in the non-fluent group making more errors. Conclusions: The data demonstrated that people with different types of aphasia have distinct impairments in switching attention. Since cognitive deficits impact language performance, this information is important for differentially addressing their language problems and selecting more specific and optimal rehabilitation programs that target different underlying mechanisms.

5.
Article En | MEDLINE | ID: mdl-38162928

Stroke causes a disruption in blood flow to the brain that can lead to profound language impairments. Understanding the mechanisms of language recovery after stroke is crucial for the prognosis and effective rehabilitation of people with aphasia. While the role of injured brain structures and disruptions in functional connectivity have been extensively explored, the relationship between neurovascular measures and language recovery in both early and later stages has not received sufficient attention in the field. Fully functioning healthy brain tissue requires oxygen and nutrients to be delivered promptly via its blood supply. Persistent decreases in blood flow after a stroke to the remaining non-lesioned tissue have been shown to contribute to poor language recovery. The goal of the current paper is to critically examine stroke studies looking at the relationship between different neurovascular measures and language deficits and mechanisms of language recovery via changes in neurovascular metrics. Measures of perfusion or cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) provide complementary approaches to understanding neurovascular mechanisms post stroke by capturing both cerebral metabolic demands and mechanical vascular properties. While CBF measures indicate the amount of blood delivered to a certain region and serve as a proxy for metabolic demands of that area, CVR indices reflect the ability of the vasculature to recruit blood flow in response to a shortage of oxygen, such as when one is holding their breath. Increases in CBF during recovery beyond the site of the lesion have been shown to promote language gains. Similarly, CVR changes, when collateral vessels are recruited to help reorganize the flow of blood in hypoperfused regions, have been related to functional recovery post stroke. In the current review, we highlight the main findings in the literature investigating neurovascular changes in stroke recovery with a particular emphasis on how language abilities can be affected by changes in CBF and CVR. We conclude by summarizing existing methodological challenges and knowledge gaps that need to be addressed in future work in this area, outlining a promising avenue of research.

6.
Front Young Minds ; 102022 Apr.
Article En | MEDLINE | ID: mdl-36338831

Our brains enable us to learn language. We develop it early on in life and use it effortlessly every day. It is only when the language system breaks down that we fully realize how complicated it is to speak and understand. In this article, we will explore what happens when brain damage leads to a language disorder called aphasia. About 15 million people worldwide and about 2 million in the U.S. alone are affected by aphasia. Sadly, many people still do not know what aphasia is. Here, we will explain different types of aphasia, tell you about the language difficulties people with this disorder encounter, and provide information about how language is processed in the brain.

7.
Chemistry ; 28(71): e202202286, 2022 Dec 20.
Article En | MEDLINE | ID: mdl-36200571

We describe herein the first halogen dance (HD) in continuous flow on 2-chloro-3-bromopyridine by selectively trapping a (pyridin-4-yl)lithium species that is known to undergo the halogen-dance process. In addition, this lithiated intermediate was trapped at lower temperature before the HD occurs. The HD process was extended to fluoro-iodopyridines by using various electrophiles to afford 28 examples with yields ranging from 42 to 97 % with very short residence times. Finally, scale up of the reaction was demonstrated, affording a promising space-time yield (STY) of 4.2 kg.h-1 .L-1 .


Dancing , Halogens , Lithium , Temperature
8.
Neuroimage Clin ; 34: 103020, 2022.
Article En | MEDLINE | ID: mdl-35526498

The frontal aslant tract (FAT) is a recently described intralobar tract that connects the superior and inferior frontal gyri. The FAT has been implicated in various speech and language processes and disorders, including motor speech impairments, stuttering disorders, opercular syndrome, and verbal fluency, but the specific function(s) of the FAT have yet to be elucidated. In the current study, we aimed to address this knowledge gap by investigating the underlying role that the FAT plays in motor aspects of speech and language abilities in post-stroke aphasia. Our goals were three-fold: 1) To identify which specific motor speech or language abilities are impacted by FAT damage by utilizing a powerful imaging analysis method, High Angular Resolution Diffusion Imaging (HARDI) tractography; 2) To determine whether damage to the FAT is associated with functional deficits on a range of motor speech and language tasks even when accounting for cortical damage to adjacent cortical regions; and 3) To explore whether subsections of the FAT (lateral and medial segments) play distinct roles in motor speech performance. We hypothesized that damage to the FAT would be most strongly associated with motor speech performance in comparison to language tasks. We analyzed HARDI data from thirty-three people with aphasia (PWA) with a history of chronic left hemisphere stroke. FAT metrics were related to scores on several speech and language tests: the Motor Speech Evaluation (MSE), the Western Aphasia Battery (WAB) aphasia quotient and subtests, and the Boston Naming Test (BNT). Our results indicated that the integrity of the FAT was strongly associated with the MSE as predicted, and weakly negatively associated with WAB subtest scores including Naming, Comprehension, and Repetition, likely reflecting the fact that performance on these WAB subtests is associated with damage to posterior areas of the brain that are unlikely to be damaged with a frontal lesion. We also performed hierarchical stepwise regressions to predict language function based on FAT properties and lesion load to surrounding cortical areas. After accounting for the contributions of the inferior frontal gyrus, the ventral precentral gyrus, and the superior precentral gyrus of the insula, the FAT still remained a significant predictor of MSE apraxia scores. Our results further showed that the medial and lateral subsections of the FAT did not appear to play distinct roles but rather may indicate normal anatomical variations of the FAT. Overall, current results indicate that the FAT plays a specific and unique role in motor speech. These results further our understanding of the role that white matter tracts play in speech and language.


Aphasia , Speech , Aphasia/diagnostic imaging , Aphasia/etiology , Aphasia/pathology , Brain Mapping/methods , Diffusion Tensor Imaging , Frontal Lobe , Humans , Language
9.
Brain Lang ; 224: 105057, 2022 01.
Article En | MEDLINE | ID: mdl-34883333

Unlike stroke, neurosurgical removal of left-hemisphere gliomas acts upon a reorganized language network and involves brain areas rarely damaged by stroke. We addressed whether this causes the profiles of neurosurgery- and stroke-induced language impairments to be distinct. K-means clustering of language assessment data (neurosurgery cohort: N = 88, stroke cohort: N = 95) identified similar profiles in both cohorts. But critically, a cluster of individuals with specific phonological deficits was only evident in the stroke but not in the neurosurgery cohort. Thus, phonological deficits are less clearly distinguished from other language deficits after glioma surgery compared to stroke. Furthermore, the correlations between language production and comprehension scores at different linguistic levels were more extensive in the neurosurgery than in the stroke cohort. Our findings suggest that neurosurgery-induced language impairments do not correspond to those caused by stroke, but rather manifest as a 'moderate global aphasia' - a generalized decline of language processing abilities.


Aphasia , Glioma , Language Disorders , Stroke , Aphasia/etiology , Comprehension , Glioma/complications , Glioma/surgery , Humans , Language , Language Disorders/complications , Language Disorders/etiology , Magnetic Resonance Imaging , Stroke/complications
10.
PLoS One ; 16(11): e0258946, 2021.
Article En | MEDLINE | ID: mdl-34793469

The lack of standardized language assessment tools in Russian impedes clinical work, evidence-based practice, and research in Russian-speaking clinical populations. To address this gap in assessment of neurogenic language disorders, we developed and standardized a new comprehensive assessment instrument-the Russian Aphasia Test (RAT). The principal novelty of the RAT is that each subtest corresponds to a specific level of linguistic processing (phonological, lexical-semantic, syntactic, and discourse) in different domains: auditory comprehension, repetition, and oral production. In designing the test, we took into consideration various (psycho)linguistic factors known to influence language performance, as well as specific properties of Russian. The current paper describes the development of the RAT and reports its psychometric properties. A tablet-based version of the RAT was administered to 85 patients with different types and severity of aphasia and to 106 age-matched neurologically healthy controls. We established cutoff values for each subtest indicating deficit in a given task and cutoff values for aphasia based on the Receiver Operating Characteristic curve analysis of the composite score. The RAT showed very high sensitivity (> .93) and specificity (> .96), substantiating its validity for determining presence of aphasia. The test's high construct validity was evidenced by strong correlations between subtests measuring similar linguistic processes. The concurrent validity of the test was also strong as demonstrated by a high correlation with an existing aphasia battery. Overall high internal, inter-rater, and test-retest reliability were obtained. The RAT is the first comprehensive aphasia language battery in Russian with properly established psychometric properties. It is sensitive to a wide range of language deficits in aphasia and can reliably characterize individual profiles of language impairments. Notably, the RAT is the first comprehensive aphasia test in any language to be fully automatized for administration on a tablet, maximizing further standardization of presentation and scoring procedures.


Aphasia/diagnosis , Language Tests/standards , Language , Psychometrics , Adolescent , Adult , Aphasia/epidemiology , Aphasia/pathology , Aphasia/psychology , Comprehension/physiology , Computers , Female , Humans , Male , Middle Aged , Reference Standards , Russia/epidemiology , Semantics , Young Adult
11.
Front Psychol ; 12: 702038, 2021.
Article En | MEDLINE | ID: mdl-34539503

Russia has rich theoretical and behavioral research traditions in neurolinguistics and neuropsychology, but at the beginning of the twenty-first century contemporary experimental research in these disciplines remained limited, leading to proliferation of non-evidence-based approaches in education, healthcare, and public beliefs. An academic response to this was the establishment of the Center for Language and Brain at the HSE University, Moscow, which focused on experimental psycho- and neurolinguistic research and related evidence-based practices. The Center has grown from a small group of young researchers to a large interdisciplinary unit that conducts cutting-edge research utilizing multi-site settings and novel structural and functional neuroimaging methods. The overarching aim of the Center's research is to promote scientifically grounded treatment of the language-brain relationship in the educational, clinical, and industry settings. Specifically, translational research at the Center is contributing to the advancement of clinical practice in Russia: from providing the first standardized aphasia language test to implementing protocols for intraoperative language mapping in neurosurgery departments across the country. Within research projects, a new generation of scientists is successfully being fostered, while a broader student audience is reached via courses taught by staff of the Center to students of different majors. Notable examples of public outreach programs at the Center are the Annual Summer Neurolinguistics School attracting hundreds of attendees from different countries each year, and community projects focused on raising awareness about aphasia. Together, these efforts aim to increase scientific knowledge in a multi-professional audience. In this paper, we will share our joint experiences in establishing, building, and promoting a neurolinguistics research center in Russia and the impact that this work has had on the broader public. We will delineate specific milestones of this journey and focus on the main pillars that have contributed to our progress: research, clinical work, teaching, and public outreach programs. We hope that this critical appraisal of our experiences can serve simultaneously as an inspiration and a practical guide for other groups developing research, clinical, and educational programs in different neuroscientific disciplines across the globe and aiming to improve the quality of the neuroscientific information available to the public.

12.
Front Neurol ; 12: 680248, 2021.
Article En | MEDLINE | ID: mdl-34456845

Introduction: One of the most challenging symptoms of aphasia is an impairment in auditory comprehension. The inability to understand others has a direct impact on a person's quality of life and ability to benefit from treatment. Despite its importance, limited research has examined the recovery pattern of auditory comprehension and instead has focused on aphasia recovery more generally. Thus, little is known about the time frame for auditory comprehension recovery following stroke, and whether specific neurologic and demographic variables contribute to recovery and outcome. Methods: This study included 168 left hemisphere chronic stroke patients stroke patients with auditory comprehension impairments ranging from mild to severe. Univariate and multivariate lesion-symptom mapping (LSM) was used to identify brain regions associated with auditory comprehension outcomes on three different tasks: Single-word comprehension, yes/no sentence comprehension, and comprehension of sequential commands. Demographic variables (age, gender, and education) were also examined for their role in these outcomes. In a subset of patients who completed language testing at two or more time points, we also analyzed the trajectory of recovery in auditory comprehension using survival curve-based time compression. Results: LSM analyses revealed that poor single-word auditory comprehension was associated with lesions involving the left mid- to posterior middle temporal gyrus, and portions of the angular and inferior-middle occipital gyri. Poor yes/no sentence comprehension was associated almost exclusively with the left mid-posterior middle temporal gyrus. Poor comprehension of sequential commands was associated with lesions in the left posterior middle temporal gyrus. There was a small region of convergence between the three comprehension tasks, in the very posterior portion of the left middle temporal gyrus. The recovery analysis revealed that auditory comprehension scores continued to improve beyond the first year post-stroke. Higher education was associated with better outcome on all auditory comprehension tasks. Age and gender were not associated with outcome or recovery slopes. Conclusions: The current findings suggest a critical role for the posterior left middle temporal gyrus in the recovery of auditory comprehension following stroke, and that spontaneous recovery of auditory comprehension can continue well beyond the first year post-stroke.

13.
Neuron ; 109(13): 2047-2074, 2021 07 07.
Article En | MEDLINE | ID: mdl-34237278

Despite increased awareness of the lack of gender equity in academia and a growing number of initiatives to address issues of diversity, change is slow, and inequalities remain. A major source of inequity is gender bias, which has a substantial negative impact on the careers, work-life balance, and mental health of underrepresented groups in science. Here, we argue that gender bias is not a single problem but manifests as a collection of distinct issues that impact researchers' lives. We disentangle these facets and propose concrete solutions that can be adopted by individuals, academic institutions, and society.


Gender Equity , Research Personnel , Sexism , Universities/organization & administration , Female , Humans , Male , Research/organization & administration
14.
Front Hum Neurosci ; 15: 672665, 2021.
Article En | MEDLINE | ID: mdl-34248526

Current evidence strongly suggests that the arcuate fasciculus (AF) is critical for language, from spontaneous speech and word retrieval to repetition and comprehension abilities. However, to further pinpoint its unique and differential role in language, its anatomy needs to be explored in greater detail and its contribution to language processing beyond that of known cortical language areas must be established. We address this in a comprehensive evaluation of the specific functional role of the AF in a well-characterized cohort of individuals with chronic aphasia (n = 33) following left hemisphere stroke. To evaluate macro- and microstructural integrity of the AF, tractography based on the constrained spherical deconvolution model was performed. The AF in the left and right hemispheres were then manually reconstructed using a modified 3-segment model (Catani et al., 2005), and a modified 2-segment model (Glasser and Rilling, 2008). The normalized volume and a measure of microstructural integrity of the long and the posterior segments of the AF were significantly correlated with language indices while controlling for gender and lesion volume. Specific contributions of AF segments to language while accounting for the role of specific cortical language areas - inferior frontal, inferior parietal, and posterior temporal - were tested using multiple regression analyses. Involvement of the following tract segments in the left hemisphere in language processing beyond the contribution of cortical areas was demonstrated: the long segment of the AF contributed to naming abilities; anterior segment - to fluency and naming; the posterior segment - to comprehension. The results highlight the important contributions of the AF fiber pathways to language impairments beyond that of known cortical language areas. At the same time, no clear role of the right hemisphere AF tracts in language processing could be ascertained. In sum, our findings lend support to the broader role of the left AF in language processing, with particular emphasis on comprehension and naming, and point to the posterior segment of this tract as being most crucial for supporting residual language abilities.

15.
Hum Brain Mapp ; 42(4): 1070-1101, 2021 03.
Article En | MEDLINE | ID: mdl-33216425

Lesion symptom mapping (LSM) tools are used on brain injury data to identify the neural structures critical for a given behavior or symptom. Univariate lesion symptom mapping (ULSM) methods provide statistical comparisons of behavioral test scores in patients with and without a lesion on a voxel by voxel basis. More recently, multivariate lesion symptom mapping (MLSM) methods have been developed that consider the effects of all lesioned voxels in one model simultaneously. In the current study, we provide a much-needed systematic comparison of several ULSM and MLSM methods, using both synthetic and real data to identify the potential strengths and weaknesses of both approaches. We tested the spatial precision of each LSM method for both single and dual (network type) anatomical target simulations across anatomical target location, sample size, noise level, and lesion smoothing. Additionally, we performed false positive simulations to identify the characteristics associated with each method's spurious findings. Simulations showed no clear superiority of either ULSM or MLSM methods overall, but rather highlighted specific advantages of different methods. No single method produced a thresholded LSM map that exclusively delineated brain regions associated with the target behavior. Thus, different LSM methods are indicated, depending on the particular study design, specific hypotheses, and sample size. Overall, we recommend the use of both ULSM and MLSM methods in tandem to enhance confidence in the results: Brain foci identified as significant across both types of methods are unlikely to be spurious and can be confidently reported as robust results.


Brain Mapping/methods , Cerebral Cortex/diagnostic imaging , Image Processing, Computer-Assisted/methods , Nerve Net/diagnostic imaging , Stroke/diagnostic imaging , Adult , Aged , Aged, 80 and over , Analysis of Variance , Brain Mapping/standards , Cerebral Cortex/pathology , Cerebral Cortex/physiopathology , Computer Simulation , Female , Humans , Image Processing, Computer-Assisted/standards , Magnetic Resonance Imaging , Male , Middle Aged , Nerve Net/pathology , Nerve Net/physiopathology , Stroke/pathology , Stroke/physiopathology
16.
Chemistry ; 25(67): 15262-15266, 2019 Dec 02.
Article En | MEDLINE | ID: mdl-31517410

The catalytic asymmetric synthesis of ß-trifluoromethylated esters or nitriles is reported. The use of an in situ formed chiral Cu-H complex allowed the enantioselective reduction of ß-trifluoromethylated acrylates or acrylonitriles. The reaction proceeds smoothly affording the corresponding enantioenriched products in good to excellent yields and outstanding enantioselectivities (up to 98 % ee). The mechanism of the reaction was studied, and a plausible reaction pathway was suggested accordingly. Finally, the versatility of the products was highlighted through functional group manipulations.

17.
Angew Chem Int Ed Engl ; 57(52): 17249-17253, 2018 Dec 21.
Article En | MEDLINE | ID: mdl-30290045

The selective chloromethylenation of functionalized esters using chloroacetic acid (CA) and LiHMDS (HMDS=hexamethyldisilazide) in a continuous-flow setup is reported. This Claisen homologation is for the first time extended to bis-chloromethylenation using dichloroacetic acid (DCA), thus giving access to under-explored α,α'-bis-chloroketones. The use of flow conditions enables efficient generation and reaction of the unstable chloroacetate dianion intermediates, leading to unprecedented mild and scalable reaction conditions at an economical reagent stoichiometry (-10 °C, <1 min, 1.0-2.4 equiv dianion). The clean reaction profiles allow subsequent use of the unpurified crude products, which is demonstrated in the synthesis of various heterocycles of broad interest. Furthermore, we report a novel, catalyst-free substitution of the obtained monochloro ketone products with (hetero)aryl zinc enolates to give valuable 1,4-diketones.

18.
J Int Neuropsychol Soc ; 23(9-10): 741-754, 2017 10.
Article En | MEDLINE | ID: mdl-29198286

Studies of language disorders have shaped our understanding of brain-language relationships over the last two centuries. This article provides a review of this research and how our thinking has changed over the years regarding how the brain processes language. In the 19th century, a series of famous case studies linked distinct speech and language functions to specific portions of the left hemisphere of the brain, regions that later came to be known as Broca's and Wernicke's areas. One hundred years later, the emergence of new brain imaging tools allowed for the visualization of brain injuries in vivo that ushered in a new era of brain-behavior research and greatly expanded our understanding of the neural processes of language. Toward the end of the 20th century, sophisticated neuroimaging approaches allowed for the visualization of both structural and functional brain activity associated with language processing in both healthy individuals and in those with language disturbance. More recently, language is thought to be mediated by a much broader expanse of neural networks that covers a large number of cortical and subcortical regions and their interconnecting fiber pathways. Injury to both grey and white matter has been seen to affect the complexities of language in unique ways that have altered how we think about brain-language relationships. The findings that support this paradigm shift are described here along with the methodologies that helped to discover them, with some final thoughts on future directions, techniques, and treatment interventions for those with communication impairments. (JINS, 2017, 23, 741-754).


Brain Mapping , Brain/physiopathology , Language Disorders/pathology , Brain/diagnostic imaging , Brain/pathology , Brain Mapping/history , Brain Mapping/methods , History, 19th Century , History, 20th Century , History, Ancient , Humans , Language Disorders/diagnostic imaging , Language Disorders/history , Models, Neurological , Neuroimaging
19.
Chemistry ; 23(68): 17318-17338, 2017 Dec 06.
Article En | MEDLINE | ID: mdl-28945297

Herein, a general procedure to access CF2 PO(OEt)2 -containing molecules is reported. The reagent CuCF2 PO(OEt)2 is accessible by a simple protocol and a broad range of substrates can be functionalised. The procedure allows the conversion of aryl diazonium salts, as well as aryl, heteroaryl, vinyl and alkynyl iodonium salts, into the corresponding fluorinated molecules at room temperature. Mechanistic studies were performed to gain a better understanding of the reaction pathway. Under similar conditions, vinyl and aryl iodides, allyl halides, and benzyl bromides were also functionalised, and the scope and limitations of the reaction were studied. Finally, the procedure was extended to disulfides to offer new access to SCF2 PO(OEt)2 -containing molecules.

20.
J Speech Lang Hear Res ; 60(5): 1348-1361, 2017 05 24.
Article En | MEDLINE | ID: mdl-28520866

Purpose: Language comprehension in people with aphasia (PWA) is frequently evaluated using multiple-choice displays: PWA are asked to choose the image that best corresponds to the verbal stimulus in a display. When a nontarget image is selected, comprehension failure is assumed. However, stimulus-driven factors unrelated to linguistic comprehension may influence performance. In this study we explore the influence of physical image characteristics of multiple-choice image displays on visual attention allocation by PWA. Method: Eye fixations of 41 PWA were recorded while they viewed 40 multiple-choice image sets presented with and without verbal stimuli. Within each display, 3 images (majority images) were the same and 1 (singleton image) differed in terms of 1 image characteristic. The mean proportion of fixation duration (PFD) allocated across majority images was compared against the PFD allocated to singleton images. Results: PWA allocated significantly greater PFD to the singleton than to the majority images in both nonverbal and verbal conditions. Those with greater severity of comprehension deficits allocated greater PFD to nontarget singleton images in the verbal condition. Conclusion: When using tasks that rely on multiple-choice displays and verbal stimuli, one cannot assume that verbal stimuli will override the effect of visual-stimulus characteristics.


Aphasia/diagnosis , Aphasia/psychology , Attention , Comprehension , Speech Perception , Visual Perception , Adolescent , Adult , Aged , Female , Humans , Language Tests , Male , Middle Aged , Photic Stimulation , Young Adult
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