Dominant hemisphere functional networks compensate for structural connectivity loss to preserve phonological retrieval with aging

Introduction Loss of hemispheric asymmetry during cognitive tasks has been previously demonstrated in the literature. In the context of language, increased right hemisphere activation is observed with aging. Whether this relates to compensation to preserve cognitive function or dedifferentiation implying loss of hemispheric specificity without functional consequence, remains unclear. Methods With a multifaceted approach, integrating structural and functional imaging data during a word retrieval task, in a group of younger and older adults with equivalent cognitive performance, we aimed to establish whether interactions between hemispheres or reorganization of dominant hemisphere networks preserve function. We examined functional and structural connectivity on data from our previously published functional activation study. Functional connectivity was measured using psychophysiological interactions analysis from the left inferior frontal gyrus (LIFG) and the left insula (LINS), based on published literature, and the right inferior frontal gyrus (RIFG) based on our previous study. Results Although RIFG showed increased activation, its connectivity decreased with age. Meanwhile, LIFG and LINS connected more bilaterally in the older adults. White matter integrity, measured by fractional anisotropy (FA) from diffusion tensor imaging, decreased significantly in the older group. Importantly, LINS functional connectivity to LIFG correlated inversely with FA. Conclusions We demonstrate that left hemispheric language areas show higher functional connectivity in older adults with intact behavioral performance, and thus, may have a role in preserving function. The inverse correlation of functional and structural connectivity with age is in keeping with emerging literature and merits further investigation with tractography studies and in other cognitive domains

A Retrospective Cohort Study to Assess Patient and Physician Reported Outcome Measures After Decompressive Hemicraniectomy for Malignant Middle Cerebral Artery Stroke.

INTRODUCTION: Decompressive hemicraniectomy for malignant middle cerebral artery (MCA) infarction is known to reduce mortality. However, there are on-going concerns in terms of the quality of life in survivors. We aimed to examine the correlation between patient and physician reported outcome measures in decompressive hemicraniectomy. PATIENTS AND METHODS: We analyzed outcomes in 21 patients who underwent decompressive hemicraniectomy for malignant MCA infarction between September 2003 and August 2013 within a regional health system. Patient and physician reported outcome measures were collected at follow-up. These were Stroke Impact Scale (SIS) Version 3, modified Rankin Scale (mRS), National Hospital Seizure Severity Scale, Headache Impact Test and Patient Health Questionnaire for depression. RESULTS: There was a good correlation between physician and patient reported outcome measures. The Spearman's rank correlation coefficient between mRS and structured SIS Version 3 was -0.887 (p < 0.001); with unstructured SIS results, the correlation coefficient was -0.663 (p = 0.001). There was no statistically significant correlation between life worth and modified Rankin Scale: r = -0.3383 (p = 0.087). DISCUSSION: Our findings of a statistically significant correlation between mRS and SIS have not previously been reported in patients with this condition. These findings provide further information to inform patient and next of kin discussions regarding outcomes from decompressive hemicraniectomy in malignant MCA infarction

PET imaging of the neurovascular interface in cerebrovascular disease

Cerebrovascular disease encompasses a range of pathologies affecting different components of the cerebral vasculature and brain parenchyma. Large artery atherosclerosis, acute cerebral ischaemia, and intracerebral small vessel disease all demonstrate metabolic processes that are key to pathogenesis. Although structural imaging has been a mainstay of stroke clinical care and research, it has limited ability to detect these pathophysiological processes in vivo. Positron emission tomography (PET) provides a means to detect and quantify metabolic processes in each facet of cerebrovascular disease non-invasively. The use of PET has helped shape the understanding of key concepts in cerebrovascular medicine, including the vulnerable atherosclerotic plaque, salvageable ischaemic penumbra, neuroinflammation and selective neuronal loss after ischaemic insult, and the relationships between chronic hypoxia, neuroinflammation, and amyloid deposition in cerebral small vessel disease. This review considers how the ability to image these processes at the neurovascular interface has contributed to our understanding of cerebrovascular disease and facilitated translational research to advance clinical care.N.R.E. is supported by a research training fellowship from The Dunhill Medical Trust (grant number RTF44/0114). J.M.T. is supported by a Wellcome Trust research training fellowship (104492/Z/14/Z). J.H.F.R. is part-supported by the Higher Education Funding Council for England (HEFCE), the British Heart Foundation, and the Wellcome Trust. H.S.M. is supported by the Medical Research Council (MRC) as a National Institute for Health Research (NIHR) Senior Investigator. E.A.W. is supported by the British Heart Foundation. H.S.M., J.H.F.R., and E.A.W. are supported by the NIHR Cambridge Biomedical Research Centre

Inner Speech's Relationship With Overt Speech in Poststroke Aphasia

PURPOSE: Relatively preserved inner speech alongside poor overt speech has been documented in some persons with aphasia (PWA), but the relationship of overt speech with inner speech is still largely unclear, as few studies have directly investigated these factors. The present study investigates the relationship of relatively preserved inner speech in aphasia with selected measures of language and cognition. METHODS: Thirty-eight persons with chronic aphasia (27 men, 11 women; average age 64.53 ± 13.29 years, time since stroke 8–111 months) were classified as having relatively preserved inner and overt speech (n = 21), relatively preserved inner speech with poor overt speech (n = 8), or not classified due to insufficient measurements of inner and/or overt speech (n = 9). Inner speech scores (by group) were correlated with selected measures of language and cognition from the Comprehensive Aphasia Test (Swinburn, Porter, & Al, 2004). RESULTS: The group with poor overt speech showed a significant relationship of inner speech with overt naming (r = .95, p < .01) and with mean length of utterance produced during a written picture description (r = .96, p < .01). Correlations between inner speech and language and cognition factors were not significant for the group with relatively good overt speech. CONCLUSIONS: As in previous research, we show that relatively preserved inner speech is found alongside otherwise severe production deficits in PWA. PWA with poor overt speech may rely more on preserved inner speech for overt picture naming (perhaps due to shared resources with verbal working memory) and for written picture description (perhaps due to reliance on inner speech due to perceived task difficulty). Assessments of inner speech may be useful as a standard component of aphasia screening, and therapy focused on improving and using inner speech may prove clinically worthwhile

Atrial fibrillation in embolic stroke of undetermined source: role of advanced imaging of left atrial function

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. AIMS: Atrial fibrillation (AF) is detected in over 30% of patients following an embolic stroke of undetermined source (ESUS) when monitored with an implantable loop recorder (ILR). Identifying AF in ESUS survivors has significant therapeutic implications, and AF risk is essential to guide screening with long-term monitoring. The present study aimed to establish the role of left atrial (LA) function in subsequent AF identification and develop a risk model for AF in ESUS. METHODS AND RESULTS: We conducted a single-centre retrospective case-control study including all patients with ESUS referred to our institution for ILR implantation from December 2009 to September 2019. We recorded clinical variables at baseline and analysed transthoracic echocardiograms in sinus rhythm. Univariate and multivariable analyses were performed to inform variables associated with AF. Lasso regression analysis was used to develop a risk prediction model for AF. The risk model was internally validated using bootstrapping. Three hundred and twenty-three patients with ESUS underwent ILR implantation. In the ESUS population, 293 had a stroke, whereas 30 had suffered a transient ischaemic attack as adjudicated by a senior stroke physician. Atrial fibrillation of any duration was detected in 47.1%. The mean follow-up was 710 days. Following lasso regression with backwards elimination, we combined increasing lateral PA (the time interval from the beginning of the P wave on the surface electrocardiogram to the beginning of the A\u27 wave on pulsed wave tissue Doppler of the lateral mitral annulus) [odds ratio (OR) 1.011], increasing Age (OR 1.035), higher Diastolic blood pressure (OR 1.027), and abnormal LA reservoir Strain (OR 0.973) into a new PADS score. The probability of identifying AF can be estimated using the formula. Model discrimination was good [area under the curve (AUC) 0.72]. The PADS score was internally validated using bootstrapping with 1000 samples of 150 patients showing consistent results with an AUC of 0.73. CONCLUSION: The novel PADS score can identify the risk of AF on prolonged monitoring with ILR following ESUS and should be considered a dedicated risk stratification tool for decision-making regarding the screening strategy for AF in stroke.One-third of patients with a type of stroke called embolic stroke of undetermined source (ESUS) also have a heart condition called atrial fibrillation (AF), which increases their risk of having another stroke. However, we do not know why some patients with ESUS develop AF. To figure this out, we studied 323 patients with ESUS and used a special device to monitor their heart rhythm continuously for up to 3 years, an implantable loop recorder. We also looked at their medical history, performed a heart ultrasound, and identified some factors that increase the risk of identifying AF in the future. Factors associated with future AF include older age, higher diastolic blood pressure, and problems with the co-ordination and function of the upper left chamber of the heart called the left atrium.Based on these factors, we created a new scoring system that can identify patients who are at higher risk of developing AF better than the current scoring systems, the PADS score. This can potentially help doctors provide more targeted and effective treatment to these patients, ultimately aiming to reduce their risk of having another stroke

Acute effects of nicotine on visual search tasks in young adult smokers

Rationale Nicotine is known to improve performance on tests involving sustained attention and recent research suggests that nicotine may also improve performance on tests involving the strategic allocation of attention and working memory. Objectives We used measures of accuracy and response latency combined with eye-tracking techniques to examine the effects of nicotine on visual search tasks. Methods In experiment 1 smokers and non-smokers performed pop-out and serial search tasks. In experiment 2, we used a within-subject design and a more demanding search task for multiple targets. In both studies, 2-h abstinent smokers were asked to smoke one of their own cigarettes between baseline and tests. Results In experiment 1, pop-out search times were faster after nicotine, without a loss in accuracy. Similar effects were observed for serial searches, but these were significant only at a trend level. In experiment 2, nicotine facilitated a strategic change in eye movements resulting in a higher proportion of fixations on target letters. If the cigarette was smoked on the first trial (when the task was novel), nicotine additionally reduced the total number of fixations and refixations on all letters in the display. Conclusions Nicotine improves visual search performance by speeding up search time and enabling a better focus of attention on task relevant items. This appears to reflect more efficient inhibition of eye movements towards task irrelevant stimuli, and better active maintenance of task goals. When the task is novel, and therefore more difficult, nicotine lessens the need to refixate previously seen letters, suggesting an improvement in working memory

Platelet collagen receptor Glycoprotein VI-dimer recognizes fibrinogen and fibrin through their D-domains, contributing to platelet adhesion and activation during thrombus formation.

UNLABELLED: Essentials Glycoprotein VI (GPVI) binds collagen, starting thrombogenesis, and fibrin, stabilizing thrombi. GPVI-dimers, not monomers, recognize immobilized fibrinogen and fibrin through their D-domains. Collagen, D-fragment and D-dimer may share a common or proximate binding site(s) on GPVI-dimer. GPVI-dimer-fibrin interaction supports spreading, activation and adhesion involving αIIbβ3. SUMMARY: Background Platelet collagen receptor Glycoprotein VI (GPVI) binds collagen, initiating thrombogenesis, and stabilizes thrombi by binding fibrin. Objectives To determine if GPVI-dimer, GPVI-monomer, or both bind to fibrinogen substrates, and which region common to these substrates contains the interaction site. Methods Recombinant GPVI monomeric extracellular domain (GPVIex ) or dimeric Fc-fusion protein (GPVI-Fc2 ) binding to immobilized fibrinogen derivatives was measured by ELISA, including competition assays involving collagenous substrates and fibrinogen derivatives. Flow adhesion was performed with normal or Glanzmann thrombasthenic (GT) platelets over immobilized fibrinogen, with or without anti-GPVI-dimer or anti-αIIbβ3. Results Under static conditions, GPVIex did not bind to any fibrinogen substrate. GPVI-Fc2 exhibited specific, saturable binding to both D-fragment and D-dimer, which was inhibited by mFab-F (anti-GPVI-dimer), but showed low binding to fibrinogen and fibrin under our conditions. GPVI-Fc2 binding to D-fragment or D-dimer was abrogated by collagen type III, Horm collagen or CRP-XL (crosslinked collagen-related peptide), suggesting proximity between the D-domain and collagen binding sites on GPVI-dimer. Under low shear, adhesion of normal platelets to D-fragment, D-dimer, fibrinogen and fibrin was inhibited by mFab-F (inhibitor of GPVI-dimer) and abolished by Eptifibatide (inhibitor of αIIbβ3), suggesting that both receptors contribute to thrombus formation on these substrates, but αIIbβ3 makes a greater contribution. Notably, thrombasthenic platelets showed limited adhesion to fibrinogen substrates under flow, which was further reduced by mFab-F, supporting some independent GPVI-dimer involvement in this interaction. Conclusion Only dimeric GPVI interacts with fibrinogen D-domain, at a site proximate to its collagen binding site, to support platelet adhesion/activation/aggregate formation on immobilized fibrinogen and polymerized fibrin

Vascular Imaging With 18^{18}F-Fluorodeoxyglucose Positron Emission Tomography Is Influenced by Hypoxia

This study was funded by a programme grant (RG/10/007/28300) from the British Heart Foundation (BHF). Dr. Joshi was supported by a BHF Clinical Research Training Fellowship (FS/12/29/29463), a British Atherosclerosis Society Binks Trust Travel Award, and a Raymond and Beverly Sackler PhD Studentship. Dr. Manavaki is funded by the NIHR Cambridge Biomedical Research Centre. Dr. Rudd is partially supported by the NIHR Cambridge Biomedical Research Centre, the BHF, The Wellcome Trust, and the EPSRC Cambridge Centre for Mathematical Imaging in Healthcare

Ultrafast optical control of entanglement between two quantum dot spins

The interaction between two quantum bits enables entanglement, the two-particle correlations that are at the heart of quantum information science. In semiconductor quantum dots much work has focused on demonstrating single spin qubit control using optical techniques. However, optical control of entanglement of two spin qubits remains a major challenge for scaling from a single qubit to a full-fledged quantum information platform. Here, we combine advances in vertically-stacked quantum dots with ultrafast laser techniques to achieve optical control of the entangled state of two electron spins. Each electron is in a separate InAs quantum dot, and the spins interact through tunneling, where the tunneling rate determines how rapidly entangling operations can be performed. The two-qubit gate speeds achieved here are over an order of magnitude faster than in other systems. These results demonstrate the viability and advantages of optically controlled quantum dot spins for multi-qubit systems.Comment: 24 pages, 5 figure

Risk factors for delay in symptomatic presentation of leukaemia, lymphoma and myeloma

Background: UK policy aims to improve cancer outcomes by promoting early diagnosis, which for many haematological malignancies is particularly challenging as the pathways leading to diagnosis can be difficult and prolonged. Methods: A survey about symptoms was sent to patients in England with acute leukaemia, chronic lymphocytic leukaemia (CLL), chronic myeloid leukaemia (CML), myeloma and non-Hodgkin lymphoma (NHL). Symptoms and barriers to first help seeking were examined for each subtype, along with the relative risk of waiting >3 months’ time from symptom onset to first presentation to a doctor, controlling for age, sex and deprivation. Results: Of the 785 respondents, 654 (83.3%) reported symptoms; most commonly for NHL (95%) and least commonly for CLL (67.9%). Some symptoms were frequent across diseases while others were more disease-specific. Overall, 16% of patients (n=114) waited >3 months before presentation; most often in CML (24%) and least in acute leukaemia (9%). Significant risk factors for >3 months to presentation were: night sweats (particularly CLL and NHL), thirst, abdominal pain/discomfort, looking pale (particularly acute leukaemias), and extreme fatigue/tiredness (particularly CML and NHL); and not realising symptom(s) were serious. Conclusions: These findings demonstrate important differences by subtype, which should be considered in strategies promoting early presentation. Not realising the seriousness of some symptoms indicates a worrying lack of public awareness