Search results
Found 22706 matches for
Scene-selectivity in CA1/subicular complex: Multivoxel pattern analysis at 7T.
Prior univariate functional magnetic resonance imaging (fMRI) studies in humans suggest that the anteromedial subicular complex of the hippocampus is a hub for scene-based cognition. However, it is possible that univariate approaches were not sufficiently sensitive to detect scene-related activity in other subfields that have been implicated in spatial processing (e.g., CA1). Further, as connectivity-based functional gradients in the hippocampus do not respect classical subfield boundary definitions, category selectivity may be distributed across anatomical subfields. Region-of-interest approaches, therefore, may limit our ability to observe category selectivity across discrete subfield boundaries. To address these issues, we applied searchlight multivariate pattern analysis to 7T fMRI data of healthy adults who undertook a simultaneous visual odd-one-out discrimination task for scene and non-scene (including face) visual stimuli, hypothesising that scene classification would be possible in multiple hippocampal regions within, but not constrained to, anteromedial subicular complex and CA1. Indeed, we found that the scene-selective searchlight map overlapped not only with anteromedial subicular complex (distal subiculum, pre/para subiculum), but also inferior CA1, alongside posteromedial (including retrosplenial) and parahippocampal cortices. Probabilistic overlap maps revealed gradients of scene category selectivity, with the strongest overlap located in the medial hippocampus, converging with searchlight findings. This was contrasted with gradients of face category selectivity, which had stronger overlap in more lateral hippocampus, supporting ideas of parallel processing streams for these two categories. Our work helps to map the scene, in contrast to, face processing networks within, and connected to, the human hippocampus.
Structural Snapshots on Stepwise Anionic Oxoborane Formation: Access to an Acyclic BO Ketone Analogue and Its Metathesis Chemistry with CO2 and CS2
In this work, we disclose the synthesis and characterization of non-acid/base-stabilized anionic oxoboranes [MesTer2BO][K(L)] (MesTer = -C6H3-2,6-(2,4,6-Me3-C6H2)2, L = [2.2.2]-cryptand or 18-crown-6), which are isoelectronic and isostructural with aryl-substituted ketones. The stepwise synthetic formation of these ion-separated oxoboranes is demonstrated on the one hand by the treatment of the parent borinic acid MesTer2BOH with N-heterocyclic carbenes (NHCs) to give [MesTer2BO][HNHC] derivatives, and on the other hand by a deprotonation-sequestration sequence. Bearing polarized boron-oxygen moieties, their inherent reactivity toward both carbon disulfide and carbon dioxide reveals a unique π-bond metathesis reactivity to yield [(MesTer)2B-μ-E2C=E][K(L)] (E = O, S) derivatives.
Behavioural changes in frontotemporal dementia and their cognitive and neuroanatomical correlates.
Behavioural changes are a central feature of frontotemporal dementia (FTD); they occur in both behavioural-variant (bvFTD) and semantic dementia (SD)/semantic-variant primary progressive aphasia subtypes. In this study, we addressed two current clinical knowledge gaps; (i) are there qualitative or clear distinctions between behavioural profiles in bvFTD and SD, and (ii) what are the precise roles of the prefrontal cortex and anterior temporal lobes in supporting social behaviour? Resolving these conundrums is crucial for improving diagnostic accuracy and for the development of targeted interventions to treat challenging behaviours in FTD. Informant questionnaires to assess behavioural changes included the Cambridge Behavioural Inventory-Revised and two targeted measures of apathy and impulsivity. Participants completed a detailed neuropsychological battery to permit investigation of the relationship between cognitive status (including social-semantic knowledge, general semantic knowledge and executive function) with behaviour change in FTD. To explore changes in regional grey matter volume, a subset of patients had structural MRI. Diagnosis-based group comparisons were supplemented by a transdiagnostic approach which encompassed the spectrum of bvFTD, SD and "mixed" or intermediate cases. Such an approach is sensitive to the systematic graded variation in FTD and allows the neurobiological underpinnings of behaviour change to be explored across an FTD spectrum. We found a wide range of behavioural changes across FTD. Although quantitatively more severe on average in bvFTD, as expected, the item-level analyses found no evidence for qualitative differences in behavioural profiles or "behavioural double dissociations" between bvFTD and SD. Comparisons of self and informant ratings revealed strong discrepancies in the perspective of the caregiver versus patient. Logistic regression revealed that neuropsychological measures had better discriminative accuracy for bvFTD versus SD than caregiver-reported behavioural measures. A principal component analysis of all informant questionnaire domains extracted three components, interpreted as reflecting: (1) apathy, (2) challenging behaviours and (3) activities of daily living. More severe apathy in both FTD subtypes was associated with (a) increased levels of impaired executive function and (b) anterior cingulate cortex atrophy. Questionnaire ratings of impaired behaviour did not correlate with either anterior temporal lobe atrophy or degraded social-semantic knowledge. Together, these findings highlight the presence of a wide range of behavioural changes in both bvFTD and SD, which vary by degree rather than quality. We recommend a transdiagnostic approach for future studies of the neuropsychological and neuroanatomical underpinnings of behavioural deficits in FTD.
Physiological responses to retinopathy of prematurity screening: indirect ophthalmoscopy versus ultra-widefield retinal imaging.
BACKGROUND/AIMS: Retinopathy of prematurity (ROP) screening is vital for early disease detection in very premature infants but can cause physiological instability. This study compares the physiological response to binocular indirect ophthalmoscopy (BIO) with indentation and non-contact ultra-widefield (UWF) retinal imaging in non-ventilated neonates. The impact of the Dandle WRAP, a specialised swaddling aid, on UWF imaging was also assessed. METHODS: This retrospective study included 86 ROP screening events in 66 non-ventilated infants aged 35.3 weeks (range 30.6-44.6). Vital signs were continuously recorded, evaluating immediate (within 15 min) and longer-term (within 12 h) physiological responses. RESULTS: ROP screening significantly increased heart and respiratory rates and decreased oxygen saturation within 15 min of screening. No significant differences in physiological responses were found between BIO and UWF imaging, although there was a trend towards lower maximum heart rate with UWF imaging. The Dandle WRAP did not significantly alter physiological responses but improved the ease and speed of UWF imaging. CONCLUSION: UWF imaging does not increase physiological instability compared to BIO in non-ventilated infants. Specialised swaddling aids may facilitate the imaging procedure. IMPACT: ROP screening can be distressing for premature infants and induce physiological instability during and after the examination. We deployed non-contact ultra-widefield retinal imaging as the default method of ROP screening and show that it induces comparable physiological responses as traditional indirect ophthalmoscopy in non-ventilated babies. Dandle WRAP swaddling facilitated handling and speed of retinal imaging. The study demonstrates that imaging-based ROP screening is safe and efficacious in non-ventilated neonates, and continuous multimodal physiological recordings can provide detailed assessment of the effects of procedures and medications.
Going ‘meta’: a systematic review of metacognition and functional neurological disorder
In functional neurological disorder (FND), there is a fundamental disconnect between an apparently intact nervous system and the individuals’ ability to consistently perform motor actions, perceive sensory signals and/or access effective cognition. Metacognition, the capacity to self-evaluate cognitive performance, appears highly relevant to FND pathophysiology. Poor metacognition is a potential mechanism via which abnormal models of self and the state of the world could arise and persist unchecked. There is therefore a justified enthusiasm that studies of metacognition may give substance to FND’s intangible nature. However, many assume an impairment in metacognition even though experimental studies are still in their infancy. This systematic review provides an analytical checkpoint of the evidence after the first five years of experimental work. We firstly summarize current methods for testing metacognition, prerequisite knowledge that allows readers to independently evaluate the evidence. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we then screened the 21 articles on this topic and review the experimental data of the eight studies that specifically tested metacognition in subjects with FND. Questionnaire metrics used to estimate global metacognition and general confidence in FND revealed a mixed picture of low or normal confidence. Of the five studies that used performance-controlled metrics, the gold-standard to estimate local metacognition in FND, four found metacognition to be equivalent to healthy controls and one paper supported impaired metacognition. We consequently try and broaden the debate and discuss alternative headline scenarios. We review how positive studies may offer insight and debate whether null studies could represent false negatives. However, since most studies find equivalent metacognition to controls, we also discuss whether metacognition could be intact and how this could inform mechanistic models of FND and have potential clinical utility. In summary, this review highlights signal of interest within the data, exposes current limitations and flags the many open questions.
Retinal pigment epithelium and choroid translocation in patients with age-related macular degeneration
Some patients with neovascular age-related macular degeneration (AMD) do not respond well to anti-vascular endothelial growth factor (VEGF) treatment, such as patients with fibrotic plaques, older organized subretinal hemorrhages, and retinal pigment epithelium (RPE) tears disrupting the subfoveal RPE. In such cases an autologous RPE and choroid transplant taken from the midperiphery can preserve macular function in some patients over a long period of time. Proliferative vitreoretinopathy and, rarely, fibrosis around the graft are the most severe postoperative complications. For dry AMD autologous RPE transplantation has not been proven to be of benefit. Future developments in stem cell-derived RPE may lead to better functional outcomes, but in the meantime, for patients with neovascular AMD, the postoperative challenges encountered in autologous transplant surgery remain. It is not yet clear whether the combination of RPE and choroid transplantation is mandatory for successful function, but a lack of revascularization of the latter has been shown to lead to atrophy of the overlying retina.
TDP-43 interacts with amyloid-β, inhibits fibrillization, and worsens pathology in a model of Alzheimer’s disease
AbstractTDP-43 inclusions are found in many Alzheimer’s disease (AD) patients presenting faster disease progression and greater brain atrophy. Previously, we showed full-length TDP-43 forms spherical oligomers and perturbs amyloid-β (Aβ) fibrillization. To elucidate the role of TDP-43 in AD, here, we examined the effect of TDP-43 in Aβ aggregation and the attributed toxicity in mouse models. We found TDP-43 inhibited Aβ fibrillization at initial and oligomeric stages. Aβ fibrillization was delayed specifically in the presence of N-terminal domain containing TDP-43 variants, while C-terminal TDP-43 was not essential for Aβ interaction. TDP-43 significantly enhanced Aβ’s ability to impair long-term potentiation and, upon intrahippocampal injection, caused spatial memory deficit. Following injection to AD transgenic mice, TDP-43 induced inflammation, interacted with Aβ, and exacerbated AD-like pathology. TDP-43 oligomers mostly colocalized with intracellular Aβ in the brain of AD patients. We conclude that TDP-43 inhibits Aβ fibrillization through its interaction with Aβ and exacerbates AD pathology.
Cell-based assays to detect cytokine autoantibodies in patients with myasthenia gravis
Myasthenia gravis (MG) is an autoimmune disease that presents with fatigable muscle weakness caused by the autoantibodies mostly to acetylcholine receptor (AChR). Around 10-15% of MG patients have thymoma, which contributes to the dysregulation of negative selection and permits the production of autoantibodies to soluble cytokines, e.g., type I interferons, IL-12/IL-23 etc. Those autoantibodies can neutralize their targets and disrupt their normal functions in patients. To detect them, HEK293T cells were transfected with the DNA constructs for expressing the targeted cytokines above cell membrane. This was to provide the native substrates for antibody binding and to detect cytokine autoantibodies more sensitively. Moreover, myc tag was incorporated for our benefit to quantify the surface expression of targeted cytokines. Our platform was able to prognose the presence of thymoma in a series of thymoma-related autoimmune disorders, e.g. thymoma-associated MG (TAMG), late-onset MG (LOMG), neuromyotonia (NMT) and Good’s syndrome. In general, we have established a live cell-based assay to optimize the detection of cytokine autoantibodies in the sera from patients with thymoma for gaining proof of concept and beneficial clinical interpretations. The poster was presented at International Thymic Malignancy Interest Group (ITMIG) 2019 Annual Conference.
Investigating neuro-immune interaction in a humanised in vitro microfluidic coculture platform
Neuropathic pain is a devastating condition affecting 9% of the population worldwide. Among the most common causes are entrapment neuropathies and focal nerve injuries. The inadequacy of treatments stems in part from a lack of understanding regarding the pathophysiology of neuropathic pain and limited translation from preclinical murine models to humans. My research combines human tissues with humanised models to decipher the underlying mechanisms of neuropathic pain for drug development. Neuroinflammation is a main driver of neuropathic pain. Through bulk RNA sequencing and histological staining of human nerve, I have identified a pain-associated glucocorticoid-induced macrophage subtype (MGC; CD163+STAB1+MARCO+), in the painful entrapment neuropathy - Morton’s neuroma. To interrogate its role in human neuropathic pain, I have established an in vitro microfluidic platform to coculture MGC-like macrophages (CD163+STAB1+MARCOdim) with human induced pluripotent stem cell-derived sensory neurons (hiPSCdSN). I use GCaMP-based live cell calcium imaging and a 'Fast Fourier Transform'-based analysis pipeline to investigate the effect of MGC-like macrophages on the spontaneous activity of injured or healthy hiPSCdSN. My first experiment identifies MGC-like macrophages enhance the level of spontaneous activity in hiPSCdSN 4 days after in vitro axonal injury at the neurite side compared to M0 macrophages. The poster was presented at 2024 IASP in Amsterdam.
Immune system: the two-edge sword in our body
An introduction of T-cell central tolerance and autoimmunity. The talk was presented at HKScholar x Oxford University Taiwanese Student Society (OUTSS) Joint Symposium.
The impact of Exenatide on motor complications in Parkinson’s disease
Parkinson’s disease (PD) is a neurodegenerative disease caused by the progressive loss of dopaminergic cells in the substantia nigra resulting in characteristic symptoms of tremor, rigidity, bradykinesia and postural instability. Dopamine replacement with preparations of Levodopa remains the gold standard of treatment; however, continued use together with disease progression can lead to the development of motor complications including the development of uncontrollable jerky movements termed Levodopa-induced dyskinesia (LID), which can be difficult to manage. Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to have neuroprotective properties in various animal toxin model of PD and conferred motor and cognitive benefits in a small open label trial of moderate severity PD patients. In view of this, a Phase II trial was conducted – the Exenatide-PD trial – a randomized double-blinded, placebo controlled, single center, 60-week trial of Exenatide once weekly for the treatment of moderate severity Parkinson’s disease in 60 patients. In addition to other clinical rating scales, all patients had dyskinesia assessments at 12-week intervals using the Unified Dyskinesia Rating Scale, the MDS-UPDRS Part 4 and the 3-day Hauser diary. Our aims are to compare the different tools used to measure dyskinesia in Parkinson’s disease, to examine whether Exenatide could impact on Levodopa-induced dyskinesia and to explore the relationship between the change in dyskinesia severity and the change in the number of dopamine transporters via DaTSCAN analysis after the 60-week Exenatide-PD trial. The poster was presented at 2017 Queen Square Symposium.
Interaction between hSERF1a/CG17931 and hTau441 in Drosophila model
Alzheimer's disease (AD) and frontotemporal dementias (FTDs) are popular in elderly people around the world, and both relate to the pathology of microtubule-associated protein Tau. When Tau protein is hyperphosphorylated, it detaches from the microtubule and forms the pathological aggregates. Scientists have identified a positive aggregation modifier, human SERF1a (hSERF1a), which will accelerate the aggregation process of amyloid proteins, such as alpha-synuclein and Huntingtin. By using in vitro Thioflavin-T assay, we observe hSERF1a is able to accelerate the in vitro aggregation of human full-length Tau protein (hTau441). To investigate hSERF1a in vivo, we use fly Tau model. Drosophila genome contains an annotated gene CG17931, which shows evident homology to hSERF1a, so we predict it may preserve a similar function. We harnessed RNAi strategy to reduce the expression level of endogenous CG17931 in hTau441-expressing fly and observed the rough eye phenotype caused by hTau441 cytotoxicity was enhanced. Although the result was against our hypothesis, previous studies have suggested Tau oligomer is more toxic than neurofibrillary tangles (NFTs) in mouse models and post-mortem patient brains, which can explain our observations. While my study is ongoing, our results demonstrate the interaction between CG17931/hSERF1a and hTau441 could stand for the hypothetic mechanism of tauopathy and its future clinical implications. The poster was presented at 2016 NTHU Life Science Symposium and awarded the first pirze.