Anatomy and Neuroscience - Research Publications
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ItemIndividual differences in haemoglobin concentration influence bold fMRI functional connectivity and its correlation with cognition(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2020-11-01)Resting-state connectivity measures the temporal coherence of the spontaneous neural activity of spatially distinct regions, and is commonly measured using BOLD-fMRI. The BOLD response follows neuronal activity, when changes in the relative concentration of oxygenated and deoxygenated haemoglobin cause fluctuations in the MRI T2* signal. Since the BOLD signal detects changes in relative concentrations of oxy/deoxy-haemoglobin, individual differences in haemoglobin levels may influence the BOLD signal-to-noise ratio in a manner independent of the degree of neural activity. In this study, we examined whether group differences in haemoglobin may confound measures of functional connectivity. We investigated whether relationships between measures of functional connectivity and cognitive performance could be influenced by individual variability in haemoglobin. Finally, we mapped the neuroanatomical distribution of the influence of haemoglobin on functional connectivity to determine where group differences in functional connectivity are manifest. In a cohort of 518 healthy elderly subjects (259 men), each sex group was median-split into two groups with high and low haemoglobin concentration. Significant differences were obtained in functional connectivity between the high and low haemoglobin groups for both men and women (Cohen's d 0.17 and 0.03 for men and women respectively). The haemoglobin connectome in males showed a widespread systematic increase in functional connectivity correlation values, whilst the female connectome showed predominantly parietal and subcortical increases and temporo-parietal decreases. Despite the haemoglobin groups having no differences in cognitive measures, significant differences in the linear relationships between cognitive performance and functional connectivity were obtained for all 5 cognitive tests in males, and 4 out of 5 tests in females. Our findings confirm that individual variability in haemoglobin levels that give rise to group differences are an important confounding variable in BOLD-fMRI-based studies of functional connectivity. Controlling for haemoglobin variability as a potentially confounding variable is crucial to ensure the reproducibility of human brain connectome studies, especially in studies that compare groups of individuals, compare sexes, or examine connectivity-cognition relationships.
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ItemEvidence for multiple bulbar and higher brain circuits processing sensory inputs from the respiratory system in humans(WILEY, 2020-12)KEY POINTS: Unpleasant respiratory sensations contribute to morbidity in pulmonary disease. In rodents, these sensations are processed by nodose and jugular vagal sensory neurons, two distinct cell populations that differentially project to the airways and brainstem. Whether similar differences exist in bronchopulmonary sensory pathways in humans is unknown. We use functional magnetic resonance imaging during inhalation of capsaicin and ATP, showing that airway nodose pathways project centrally to the nucleus of the solitary tract, whereas jugular pathways input into the trigeminal brainstem nuclei. We also show differences between the efficacy of nodose and jugular stimuli to evoke cough and activity in motor control regions of the brain. Our data suggest that humans have two distinct vagal sensory neural systems governing airway sensations and this may have implications for the development of new antitussive therapies. ABSTRACT: In rodents, nodose vagal sensory neurons preferentially innervate the distal airways and terminate centrally in the nucleus of the solitary tract. By contrast, jugular vagal sensory neurons preferentially innervate the proximal airways and terminate in the paratrigeminal nucleus in the dorsolateral medulla. This differential organization suggests distinct roles for nodose and jugular pathways in respiratory sensory processing. However, it is unknown whether bronchopulmonary afferent pathways are similarly arranged in humans. We set out to investigate this using high resolution brainstem and whole brain functional magnetic resonance imaging in healthy human participants when they were inhaling stimuli known to differentially activate nodose and jugular pathways. Inhalation of capsaicin or ATP evoked respiratory sensations described as an urge-to-cough, although ATP was significantly less effective compared to capsaicin at evoking the motor act of coughing. The nodose and jugular neuron stimulant capsaicin increased blood oxygen level-dependent (BOLD) signals extending across the dorsomedial and dorsolateral medulla, encompassing regions containing both the nucleus of the solitary tract and the paratrigeminal nucleus. By contrast, at perceptually comparable stimulus intensities, the nodose-selective stimulant ATP resulted in BOLD signal intensity changes that were confined to the area of the nucleus of the solitary tract. During whole brain imaging, capsaicin demonstrated a wider distributed network of activity compared to ATP, with significantly increased activity in regions involved with motor control functions. These data suggest that functional and neuroanatomical differences in bronchopulmonary nodose and jugular sensory pathway organization are conserved in humans and also that this has implications for understanding the neurobiological mechanisms underpinning cough.
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ItemThe effects of a single-session cathodal transcranial pulsed current stimulation on corticospinal excitability: A randomized sham-controlled double-blinded study(WILEY, 2020-12)Transcranial pulsed current stimulation (tPCS) of the human motor cortex has received much attention in recent years. Although the effect of anodal tPCS with different frequencies has been investigated, the effect of cathodal tPCS (c-tPCS) has not been explored yet. Therefore, the aim of the present study was to investigate the effect of c-tPCS at 4 and 75 Hz frequencies on corticospinal excitability (CSE) and motor performance. In a randomized sham-controlled crossover design, fifteen healthy participants attended three experimental sessions and received either c-tPCS at 75 Hz, 4 Hz or sham with 1.5 mA for 15 min. Transcranial magnetic stimulation and grooved pegboard test were performed before, immediately after and 30 min after the completion of stimulation at rest. The findings indicate that c-tPCS at both 4 and 75 Hz significantly increased CSE compared to sham. Both c-tPCS at 75 and 4 Hz showed a significant increase in intracortical facilitation compared to sham, whereas the effect on short-interval intracortical inhibition was not significant. The c-tPCS at 4 Hz but not 75 Hz induced modulation of intracortical facilitation correlated with the CSE. Motor performance did not show any significant changes. These results suggest that, compared with sham stimulation, c-tPCS at both 4 and 75 Hz induces an increase in CSE.
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ItemApplication of compressed sensing using chirp encoded 3D GRE and MPRAGE sequences(WILEY, 2020-09)Abstract An implementation of Non‐Fourier chirp‐encoding in 3D Gradient Recalled Echo (GRE), susceptibility‐weighted imaging (SWI) and Magnetization Prepared Rapid Gradient Echo (MPRAGE) sequences is presented with compressive sensing reconstruction. 3D GRE and MPRAGE sequences were designed, in which the phase encoding (PE) direction was encoded with spatially selective chirp encoding Radio Frequency (RF) pulses, while the slice and the readout directions were Fourier encoded using gradients. During each excitation along the PE direction, a different spatially‐selective RF excitation pulse was used to encode the PE direction with a complete set of unitary chirp encoding basis. Multichannel compressive sensing reconstruction on the undersampled in vivo data demonstrated that images reconstructed from chirp encoded data were able to preserve the spatial resolution better than the Fourier encoding. The mean Structural Similarity (SSIM) across five subjects at the acceleration factor of 6, for chirp encoded MPRAGE was 0.934 compared to 0.912 for Fourier encoded MPRAGE. The implementation of prospective undersampling demonstrated the feasibility of using chirp encoding in clinical practice for accelerated imaging. The minimum intensity projection of the compressive sensing (CS) reconstructed susceptibility weighted images revealed that chirp encoding is able to delineate small vessels better than the Fourier encoding with the SSIM of 0.960 for chirp encoding compared to the SSIM of 0.949 for the Fourier encoding. Improved performance of chirp encoding for CS reconstruction and SWI, along with the feasibility of implementation makes them a practical candidate for clinical MRI scans.
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ItemNo Preview AvailableInternational Brain Initiative: An Innovative Framework for Coordinated Global Brain Research Efforts.(Elsevier BV, 2020-03-04)
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ItemUniCAR T cell immunotherapy enables efficient elimination of radioresistant cancer cells(TAYLOR & FRANCIS INC, 2020)Induction or selection of radioresistant cancer (stem) cells following standard radiotherapy is presumably one of the major causes for recurrence of metastatic disease. One possibility to prevent tumor relapse is the application of targeted immunotherapies including, e.g., chimeric antigen receptor (CAR) T cells. In light of long-term remissions, it is highly relevant to clarify whether radioresistant cancer cells are susceptible to CAR T cell-mediated killing. To answer this question, we evaluated the anti-tumor activity of the switchable universal chimeric antigen receptor (UniCAR) system against highly radioresistant head and neck squamous cell carcinoma cells both in vitro and in vivo. Following specific UniCAR T cell engagement via EGFR or CD98 target modules, T cell effector mechanisms were induced including secretion of pro-inflammatory cytokines, up-regulation of granzyme B and perforin, as well as T cell proliferation. CD98- or EGFR-redirected UniCAR T cells further possess the capability to efficiently lyse radioresistant tumor cells. Observed anti-tumor effects were comparable to those against the radiosensitive parental cell lines. Finally, redirected UniCAR T cells significantly inhibited the growth of radioresistant cancer cells in immunodeficient mice. Taken together, our obtained data underline that the UniCAR system is able to overcome radioresistance. Thus, it represents an attractive technology for the development of combined radioimmunotherapeutic approaches that might improve the outcome of patients with metastatic radioresistant tumor diseases.
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ItemSimultaneous BOLD-fMRI and constant infusion FDG-PET data of the resting human brain(NATURE PORTFOLIO, 2020-10-21)Simultaneous [18 F]-fluorodeoxyglucose positron emission tomography and functional magnetic resonance imaging (FDG-PET/fMRI) provides the capability to image two sources of energetic dynamics in the brain - cerebral glucose uptake and the cerebrovascular haemodynamic response. Resting-state fMRI connectivity has been enormously useful for characterising interactions between distributed brain regions in humans. Metabolic connectivity has recently emerged as a complementary measure to investigate brain network dynamics. Functional PET (fPET) is a new approach for measuring FDG uptake with high temporal resolution and has recently shown promise for assessing the dynamics of neural metabolism. Simultaneous fMRI/fPET is a relatively new hybrid imaging modality, with only a few biomedical imaging research facilities able to acquire FDG PET and BOLD fMRI data simultaneously. We present data for n = 27 healthy young adults (18-20 yrs) who underwent a 95-min simultaneous fMRI/fPET scan while resting with their eyes open. This dataset provides significant re-use value to understand the neural dynamics of glucose metabolism and the haemodynamic response, the synchrony, and interaction between these measures, and the development of new single- and multi-modality image preparation and analysis procedures.
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ItemEditorial: Integrative Brain Function Down Under(FRONTIERS MEDIA SA, 2020-08-14)
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ItemMultiple mechanisms underpin cerebral and cerebellar white matter deficits in Friedreich ataxia: The IMAGE-FRDA study(WILEY, 2020-05)Friedreich ataxia is a progressive neurodegenerative disorder with reported abnormalities in cerebellar, brainstem, and cerebral white matter. White matter structure can be measured using in vivo neuroimaging indices sensitive to different white matter features. For the first time, we examined the relative sensitivity and relationship between multiple white matter indices in Friedreich ataxia to more richly characterize disease expression and infer possible mechanisms underlying the observed white matter abnormalities. Diffusion-tensor, magnetization transfer, and T1-weighted structural images were acquired from 31 individuals with Friedreich ataxia and 36 controls. Six white matter indices were extracted: fractional anisotropy, diffusivity (mean, axial, radial), magnetization transfer ratio (microstructure), and volume (macrostructure). For each index, whole-brain voxel-wise between-group comparisons and correlations with disease severity, onset age, and gene triplet-repeat length were undertaken. Correlations between pairs of indices were assessed in the Friedreich ataxia cohort. Spatial similarities in the voxel-level pattern of between-group differences across the indices were also assessed. Microstructural abnormalities were maximal in cerebellar and brainstem regions, but evident throughout the brain, while macroscopic abnormalities were restricted to the brainstem. Poorer microstructure and reduced macrostructural volume correlated with greater disease severity and earlier onset, particularly in peri-dentate nuclei and brainstem regions. Microstructural and macrostructural abnormalities were largely independent. Reduced fractional anisotropy was most strongly associated with axial diffusivity in cerebral tracts, and magnetization transfer in cerebellar tracts. Multiple mechanisms likely underpin white matter abnormalities in Friedreich ataxia, with differential impacts in cerebellar and cerebral pathways.
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ItemRelationship between parenthood and cortical thickness in late adulthood(PUBLIC LIBRARY SCIENCE, 2020-07-28)Pregnancy and the early postpartum period alter the structure of the brain; particularly in regions related to parental care. However, the enduring effects of this period on human brain structure and cognition in late life is unknown. Here we use magnetic resonance imaging to examine differences in cortical thickness related to parenthood in late life, for both sexes. In 235 healthy older women, we find a positive relationship between parity (number of children parented) and memory performance in mothers. Parity was also associated with differences in cortical thickness in women in the parahippocampus, precuneus, cuneus and pericalcarine sulcus. We also compared non-parents to parents of one child, in a sub-sample of older women (N = 45) and men (N = 35). For females, six regions differed in cortical thickness between parents and non-parents; these regions were consistent with those seen earlier in life in previous studies. For males, five regions differed in cortical thickness between parents and non-parents. We are first to reveal parenthood-related brain differences in late-life; our results are consistent with previously identified areas that are altered during pregnancy and the postpartum period. This study provides preliminary evidence to suggest that neural changes associated with early stages of parenthood persist into older age, and for women, may be related to marginally better cognitive outcomes.