Biology subjects

Callaghan, M. F.

Publications and source records attributed to Callaghan, M. F..

At least 19 recordsLinked to original sources

bioRxiv2026

Modular Arrays for High Precision Wearable MEG

Optically pumped magnetometers (OPMs) can be used for magnetoencephalography (MEG) with equivalent or improved signal to noise ratio, relative to cryogenic MEG, when sensors are placed close to the scalp. OPM-based MEG can also be used in mobile contexts if sensors are placed in lightweight, wearable arrays. Individually tailored, rigid helmets known as scannercasts are currently the only method capable of achieving on-scalp, mobile recordings with high precision. However, these scannercasts are expensive to produce, require structural imaging in advance of the experiment, and can incur lengthy downtime while sensors are transferred between scannercasts. Here, we introduce a solution to these challenges that retains the advantages of scannercasts. We provide detailed steps for constructing a modular, cap-based design, suitable for all head sizes. Using simulations, we compare the leadfield power of this array against an idealised array and a commercially available mobile solution. We then validate our proposed solution empirically, in five participants, and provide a complete data preparation and analysis pipeline. Our design expands the accessibility of OPM-based MEG, and increases participant throughput to levels comparable to other imaging modalities. Crucially, it removes the trade-off between signal quality, mobility and practicality, promoting the unique potential of OPM-based MEG as a tool for studying naturalistic behaviour, and clinical assessment with high precision.

neuroscience↗

bioRxiv2026

Magnetoencephalography Without a Shielded Room

Magnetoencephalography (MEG) offers non-invasive neuroimaging with high temporal and spatial precision - but its adoption is hampered by the prohibitive cost and infrastructure burden of a magnetically shielded room. We have overcome that burden and present a lightweight, low-cost, multichannel magnetoencephalography system that can image brain activity without needing a magnetically shielded room. The multichannel nature of the system facilitates not just detection but also localization of brain signals that are over 300 million times smaller than environmental interference, without requiring passive shielding. Our system weighs less than 75kg, more than 100 times lighter than a typical shielded room. This is made possible through low-cost active shielding and software-based spatial filtering. We also show that the signal to noise ratio of our in-vivo recordings is comparable to what can be obtained from a conventional cryogenically-cooled MEG system sited within a shielded room. This demonstration is a crucial step towards democratizing magnetoencephalography and making it a globally accessible neuroimaging technology for healthcare and discovery research.

neuroscience↗

bioRxiv2026

Revisiting the auditory hemodynamic response function in the era of fast fMRI

Recent advances in fast fMRI now enable whole-brain imaging with a TR of [≤]1 s, which has helped to rekindle interest in characterizing the blood oxygen level dependent hemodynamic response function (BOLD HRF). Recent studies in the visual system have found intra-areal differences in temporal response characteristics, as well as HRFs that were faster and narrower than predicted by standard models. The auditory system presents a unique challenge, in that neuronal populations must operate across timescales of microseconds to minutes, and the surface of auditory cortex in particular is intricately and heavily vascularized. Here, we used fast fMRI to characterise voxelwise auditory HRFs evoked by short naturalistic sounds, assessing HRF reproducibility and variability across sessions, participants, and independent datasets. Across two studies at 3 T, participants passively listened to short environmental sounds while fMRI and quantitative MRI data were acquired with a 1s TR. Voxelwise HRFs were estimated via novel cross-session alignment routine, and exclusion of large vascular contributions. We identified a diverse set of hemodynamically plausible response shapes, which were not consistently captured by standard HRF approaches. These responses were reproducible within participants across sessions and robust across two independent acquisitions. Using data-driven gamma models, we achieved stable estimates with relatively few runs, particularly in auditory temporal regions. Within auditory cortex, we observed reproducible spatial gradients in response timing and shape, with faster and higher magnitude responses in medial regions, and slower and lower magnitude responses laterally. Together, these findings demonstrate that auditory HRFs are diverse, reliable, and regionally specific, and highlight the value of fast fMRI and data-driven modelling for advancing interpretation of fMRI data.

neuroscience↗

bioRxiv2026

Characterization and Validation of Compressed Sensing for Time-of-Flight MRI Angiography of the Human Brain at 3T and 7T

BackgroundCerebral vasculature is a key biomarker of brain health, and time-of-flight (TOF) magnetic resonance angiography (MRA) provides noninvasive assessment of vascular anatomy. However, conventional TOF-MRA requires long scan times, increasing patient burden and susceptibility to motion artifacts. Compressed sensing (CS) offers a feasible acceleration strategy. PurposeTo quantitatively evaluate CS acceleration in TOF-MRA at 3T and 7T using automated whole-FOV vascular segmentation and semi-automatic segmentation of representative vessels. Study typeProspective Population23 healthy human participants (3T) and 8 healthy human participants (7T). Field Strength/SequenceCS TOF-MRA (CS factors 4 and 8 at 3T; 8 at 7T) was compared against non-accelerated (CS0) TOF-MRA. AssessmentVisual comparison and vascular segmentation were performed using automated whole-FOV methods and semi-automatic segmentation of the posterior cerebral artery and anterior choroidal artery. Statistical TestsContrast-to-noise ratio (CNR), voxel count, and vessel diameter were assessed using two-tailed paired t-tests. ResultsWhole-FOV CNR differed significantly across CS factors at 3T (CS0 > CS4: p < 0.001, d = 0.77; CS0 < CS8: p = 0.008, d = 0.36; CS4 < CS8: p < 0.001, d = 1.11) and 7T (CS0 < CS8: p = 0.002, d = 0.54), with semi-automatic segmentation yielding consistent findings (p < 0.01 for all comparisons). The diameter measurements for segmented vessels are also higher with high CS-factors (PCA 7T: left: p = 0.006, d = 0.93, right: p = 0.045, d = 0.43; AChA 7T: left: p < 0.001, d = 0.66, right: p = 0.009, d = 1.06; PCA 3T: p < 0.001 for all comparison dLeft = 0.52 (CS0 vs. CS4), 0.56 (CS4 vs. CS8), 1.11 (CS0 vs. CS8) and dRight = 0.78 (CS0 vs. CS4), 0.57 (CS4 vs. CS8), 1.17 (CS0 vs. CS8)). Data ConclusionCS shows promise for enhancing clinical applicability of TOF-MRA, with advantages most pronounced at 7T.

bioengineering↗

bioRxiv2025

Differences in LC integrity and fMRI activations in healthy aging and MCI associated with successful memory encoding

INTRODUCTIONWe examined whether the decline of delayed episodic memory in old age and MCI is related to structural integrity of the locus coeruleus (LC). We also tested whether LC integrity was associated with encoding-related brain activity, controlling for emotional salience. METHODSParticipants (28 young adults, 28 older adults, 25 MCI) memorized emotional and neutral images during fMRI. Delayed memory was tested four hours later and compared to immediate memory. LC integrity was measured with a neuromelanin-sensitive sequence. RESULTSMCI showed overall memory decline, independent of delay or emotional valence, and reduced LC integrity compared to older adults. Across participants, LC integrity correlated with delayed memory, but did not explain performance within OA or MCI. LC integrity was associated with lower activity related to encoding success and emotional salience. Groups remembered emotional better than neutral images, though memory was greatly impaired in MCI, matching with their reduce LC integrity. DISCUSSIONLC integrity was associated with lower brain activity during encoding and emotional salience processing, no clear relationship with delayed memory performance was observed in MCI.

neuroscience↗

bioRxiv2025

Pupil dilation as a marker of attention/effort in aging and mild cognitive impairment

Pupil dilation (PD) can be easily measured and reflects responses to subjectively salient or cognitively demanding events. It therefore holds promise as a cognitive marker especially for individuals with mild cognitive impairment (MCI) or other neurodegenerative conditions with restricted abilities to respond in cognitive assessments. We assessed PD during two tasks, an oddball task for investigating attentional allocation and a Simon task which additionally allows for investigating cognitive effort in younger adults (YAs), older adults (OAs), and patients with MCI. PD is a useful marker for investigating attention and cognitive effort in MCI, as suggested by elevated PD to salient stimuli in particular of individuals with better attentional control in MCI patients, as well as YAs and OAs. Measurement of PD may serve as an easy-to-administer measure to assess changes in cognitive function in healthy aging and MCI.

neuroscience↗

bioRxiv2025

Evidence for divergent cortical organisation in Parkinsons disease and Lewy Body Dementia

Dementia is a defining feature of Lewy body disease: its timing and onset distinguish different clinical diagnoses, and its effect on quality of life is profound. However, it remains unclear whether processes leading to cognitive and motor symptoms in Lewy body disease differ. To clarify this, we used in-vivo neuroimaging to assess spatial gradients of inter-regional differences in structural and functional connectivity in 108 people across the Lewy body disease spectrum (46 Parkinsons with normal cognition (PD-NC), 62 Lewy body dementia (LBD)) and 23 controls. We found divergent structural gradient differences with cognitive impairment: PD-NC showed increased inter-regional differentiation, whilst LBD showed overall gradient distribution similar to controls despite widespread organisational differences at the regional level. We then assessed cellular and molecular underpinnings of these organisational changes. We reveal similarities and also important differences in the drivers of cortical organisation between LBD and PD-NC, particularly in layer 4 excitatory neurons.

neuroscience↗

bioRxiv2025

Multi-center benchmarking of cervical spinal cord RF coils for 7 T MRI: A traveling spines study

PurposeThe depth within the body, small diameter, long length, and varying tissue surrounding the spinal cord impose specific considerations when designing radiofrequency coils. The optimal coil configuration for 7 T cervical spinal cord MRI is unknown and, currently, there are very few coil options. The purpose of this work was (1) to establish a quality control protocol for evaluating 7 T cervical spinal cord coils and (2) to use that protocol to evaluate the performance of 4 different coil designs. MethodsThree healthy volunteers and a custom anthropomorphic phantom (the traveling spines cohort) were scanned at seven 7 T imaging centers using a common protocol and each centers specific cervical spinal cord coil. Four different coil designs were tested (two in-house, one Rapid Biomedical, and one MRI.TOOLS design). ResultsThe Rapid Biomedical coil was found to have the highest B1+ efficiency, whereas one of the in-house designs (NeuroPoly Lab) had the highest SNR and the largest spinal cord coverage. The MRI.TOOLS coil had the most uniform B1+ profile along the cervical spinal cord; however, it was limited in its ability to provide the requested flip angles (especially for larger individuals). The latter was also the case for the second in-house coil (MSSM). ConclusionThe results of this study serve as a guide for the spinal cord MRI community in selecting the most suitable coil based on specific requirements and offer a standardized protocol for assessing future coils.

bioengineering↗

bioRxiv2024

Communication of perceptual predictions from the hippocampus to the deep layers of the parahippocampal cortex

Current evidence points to the hippocampus as an essential region coordinating learning and exploiting predictive relationships in the service of perception. However, it remains unclear whether the hippocampus drives the communication of predictions to the sensory cortex or acts as a recipient of predictions from else-where. Here, we collected sub-millimetre 7T fMRI data to investigate neural signals in the medial temporal lobe (MTL). We used layer-specific fMRI to infer the direction of communication between the hippocam-pus and cortex. Specifically, superficial layers of the MTL cortex project to the hippocampus, while deep MTL layers receive feedback projections. Participants performed a task in which auditory cues predicted abstract shapes. Crucially, we omitted the expected shape on 25% of trials, thus isolating the prediction signal from bottom-up input and allowing us to ask: In which direction are predictions communicated between the hippocampus and neocortex? Neural patterns in CA23, pre/parasubiculum and the parahippocampal cortex (PHC) reflected shape-specific predictions. Layer-specific informational connectivity analyses revealed that communication between CA23 and PHC was specific to the deep layers of PHC. These findings are in line with the hippocampus generating predictions through pattern completion in CA23 and feeding these pre-dictions back to the neocortex.

neuroscience↗

bioRxiv2023

Statistical analyses of motion-corrupted MRI relaxometry data

Consistent noise variance across data points (i.e. homoscedasticity) is required to ensure the validity of statistical analyses of MRI data conducted using linear regression methods. However, head motion leads to degradation of image quality, introducing noise heteroscedasticity into ordinary-least square analyses. The recently introduced QUIQI method restores noise homoscedasticity by means of weighted least square analyses in which the weights, specific for each dataset of an analysis, are computed from an index of motion-induced image quality degradation. QUIQI was first demonstrated in the context of brain maps of the MRI parameter R2*, which were computed from a single set of images with variable echo time. Here, we extend this framework to quantitative maps of the MRI parameters R1, R2*, and MTsat, which are computed from multiple sets of images. QUIQI allows for optimization of the noise model by using metrics quantifying heteroscedasticity and free energy. QUIQI restores homoscedasticity more effectively than insertion of an image quality index in the analysis design and yields higher sensitivity than simply removing the datasets most corrupted by head motion from the analysis. In sum, QUIQI provides an optimal approach to group-wise analyses of a range of quantitative MRI parameter maps that is robust to inherent homoscedasticity.

neuroscience↗

bioRxiv2022

Perceptual expectations and false percepts generate stimulus-specific activity in distinct layers of the early visual cortex

Perception has been proposed to result from the integration of feedforward sensory signals with internally generated feedback signals. The latter are believed to play an important role in driving false percepts, i.e., seeing things that are not actually there. Feedforward and feedback influences on perception can be studied using layer-specific fMRI, which we used here to interrogate neural activity underlying high confidence false percepts while healthy participants (N=25) performed a perceptual orientation discrimination task. Orientation-specific BOLD activity in the deep and superficial layers of V2 reflected perceptual expectations induced by predictive auditory cues. However, these expectations did not influence participants perception. Instead, high confidence false percepts were reflected by orientation-specific activity in the middle input layers of V2, suggesting a feedforward signal contributing to false percepts. The prevalence of high confidence false percepts was related to everyday hallucination severity in a separate online sample (N=100), suggesting a possible link with abnormal perceptual experiences. These results reveal a feedforward mechanism underlying false percepts, reflected by spontaneous stimulus-like activity in the input layers of the visual cortex, independent of top-down perceptual expectations.

neuroscience↗

bioRxiv2022

Calibration allows accurate estimation of the axonal volume fraction with diffusion MRI

Biophysical models enable the non-invasive estimation of microstructural tissue features of the central nervous system such as the axonal volume fraction using diffusion weighted imaging (DWI)-data. However, these models trade accuracy with complexity and demands for time-efficient data acquisition. In this study, we hypothesise that their accuracy can be improved substantially through biophysically motivated, linear calibration. We test this hypothesis in the context of axonal volume fraction estimation in four different DWI-models of different complexity using multi-modal data including ex-vivo diffusion MRI- and electron microscopy (EM)-data in mice with broad dynamic range, whereby the latter served as gold standard. We found that two calibration parameters, an offset accounting for the fraction of unmyelinated axons in severely hypomyelinated mice and a scaling accounting for the compartment-specific relaxation, substantially improved the accuracy of axonal volume fraction. Furthermore, we theoretically predict the scaling parameter, and demonstrate that similar accuracy improvement can be achieved for a subset of DWI-models, if the scaling parameter is fixed to the predicted value instead of estimating it on basis of data. This is of practical relevance because it allows to estimate the remaining offset calibration parameter from a limited amount of multi-modal data and thus makes the proposed method usable in human brain data.

neuroscience↗

bioRxiv2022

Signalling speed along a key white matter tract influences memory recall ability in humans

Conduction velocity is the speed at which electrical signals travel along axons and is a crucial determinant of neural communication. Inferences about conduction velocity can now be made in vivo in humans using a measure called the magnetic resonance (MR) g-ratio. This is the ratio of the inner axon diameter relative to that of the axon plus the myelin sheath that encases it. Here, in the first application to cognition, we found that variations in MR g-ratio, and by inference conduction velocity, of the parahippocampal cingulum bundle were associated with autobiographical memory recall ability in 217 healthy adults. This tract connects the hippocampus with a range of other brain areas. We further observed that the association seemed to be with inner axon diameter rather than myelin content. The extent to which neurites were coherently organised within the parahippocampal cingulum bundle was also linked with autobiographical memory recall ability. Moreover, these findings were specific to autobiographical memory recall, and were not apparent for laboratory-based memory tests. Our results offer a new perspective on individual differences in autobiographical memory recall ability, highlighting the possible influence of specific features of white matter microstructure when recalling detailed memories of our real-life past experiences.

neuroscience↗

bioRxiv2022

Deciphering the fibre-orientation independent component of R2* (R2,iso*) in the human brain with a single multi-echo gradient-recalled-echo measurement under varying microstructural conditions

The effective transverse relaxation rate (R2*) is sensitive to the microstructure of the human brain, e.g. the g-ratio characterising the relative myelination of axons. However, R2* depends on the orientation of the fibres relative to the main magnetic field degrading its reproducibility and that of any microstructural derivative measure. To decipher its orientation-independent part (R2,iso*), a second-order polynomial in time (M2) can be applied to single multi-echo gradient-recalled-echo (meGRE) measurements at arbitrary orientation. The linear-time dependent parameter, {beta}1, of M2 can be biophysically related to R2,iso* when neglecting the signal from the myelin water (MW) in the hollow cylinder fibre model (HCFM). Here, we examined the effectiveness of M2 using experimental and simulated data with variable g-ratio and fibre dispersion. We showed that the fitted {beta}1 effectively estimates R2,iso*when using meGRE with long maximum echo time (TEmax {approx} 54 ms) but its microscopic dependence on the g-ratio was not accurately captured. This error was reduced to less than 12% when accounting for the MW contribution in a newly introduced biophysical expression for {beta}1. We further used this new expression to estimate the MW fraction (0.14) and g-ratio (0.79) in a human optic chiasm. However, the proposed method failed to estimate R2,iso* for a typical in-vivo meGRE protocol (TEmax {approx} 18 ms). At this TEmax and around the magic angle, the HCFM-based simulations failed to explain the R2*-orientation-dependence. In conclusion, estimation of R2,iso* with M2 in vivo requires meGRE protocols with very long TEmax {approx} 54 ms.

neuroscience↗

bioRxiv2021

Restoring statistical validity in group analyses of motion-corrupted MRI data

Motion during the acquisition of magnetic resonance imaging (MRI) data degrades image quality, hindering our capacity to characterize disease in patient populations. Quality control procedures allow the exclusion of the most affected images from analysis. However, the criterion for exclusion is difficult to determine objectively and exclusion can lead to a suboptimal compromise between image quality and sample size. We provide an alternative, data-driven solution that assigns weights to each image, computed from an index of image quality using restricted maximum likelihood. We illustrate this method through the analysis of brain MRI data. The proposed method restores the validity of statistical tests, and performs near optimally in all brain regions, despite local effects of head motion. This method is amenable to the analysis of a broad type of MRI data and can accommodate any measure of image quality.

neuroscience↗

bioRxiv2021

Reducing susceptibility distortion related image blurring in diffusion MRI EPI data

Diffusion magnetic resonance imaging (MRI) is an increasingly popular technique in basic and clinical neuroscience. One promising application is to combine diffusion MRI with myelin maps from complementary MRI techniques such as multi-parameter mapping (MPM) to produce g-ratio maps that represent the relative myelination of axons and predict their conduction velocity. Statistical Parametric Mapping (SPM) can process both diffusion data and MPMs, making SPM the only widely accessible software that contains all the processing steps required to perform group analyses of g-ratio data in a common space. However, limitations have been identified in its method for reducing susceptibility-related distortion in diffusion data. More generally, susceptibility-related image distortion is often corrected by combining reverse phase-encoded images (blip-up and blip-down) using the arithmetic mean (AM), however, this can lead to blurred images. In this study we sought to (1) improve the susceptibility-related distortion correction for diffusion MRI data in SPM; (2) deploy an alternative approach to the AM to reduce image blurring in diffusion MRI data when combining blip-up and blip-down EPI data after susceptibility-related distortion correction; and (3) assess the benefits of these changes for g-ratio mapping. We found that the new processing pipeline, called consecutive Hyperelastic Susceptibility Artefact Correction (HySCO) improved distortion correction when compared to the standard approach in the ACID toolbox for SPM. Moreover, using a weighted average (WA) method to combine the distortion corrected data from each phase-encoding polarity achieved greater overlap of diffusion and more anatomically faithful structural white matter probability maps derived from minimally distorted multi-parameter maps as compared to the AM. Third, we showed that the consecutive HySCO WA performed better than the AM method when combined with multi-parameter maps to perform g-ratio mapping. These improvements mean that researchers can conveniently access a wide range of diffusion-related analysis methods within one framework because they are now available within the open-source ACID toolbox as part of SPM, which can be easily combined with other SPM toolboxes, such as the hMRI toolbox, to facilitate computation of myelin biomarkers that are necessary for g-ratio mapping.

neuroscience↗

bioRxiv2020

Heterogeneous relationships between white matter and behaviour

Several studies have established specific relationships between White Matter (WM) and behaviour. However, these studies have typically focussed on fractional anisotropy (FA), a neuroimaging metric that is sensitive to multiple tissue properties, making it difficult to identify what biological aspects of WM may drive such relationships. Here, we carry out a pre-registered assessment of WM-behaviour relationships in 50 healthy individuals across multiple behavioural and anatomical domains, and complementing FA with myelin-sensitive quantitative MR modalities (MT, R1, R2*). Surprisingly, we only find support for predicted relationships between FA and behaviour in one of three pre-registered tests. For one behavioural domain, where we failed to detect an FA-behaviour correlation, we instead find evidence for a correlation between behaviour and R1. This hints that multimodal approaches are able to identify a wider range of WM-behaviour relationships than focusing on FA alone. To test whether a common biological substrate such as myelin underlies WM-behaviour relationships, we then ran joint multimodal analyses, combining across all MRI parameters considered. No significant multimodal signatures were found and power analyses suggested that sample sizes of 40 to 200 may be required to detect such joint multimodal effects, depending on the task being considered. These results demonstrate that FA-behaviour relationships from the literature can be replicated, but may not be easily generalisable across domains. Instead, multimodal microstructural imaging may be best placed to detect a wider range of WM-behaviour relationships, as different MRI modalities provide distinct biological sensitivities. Our findings highlight a broad heterogeneity in WMs relationship with behaviour, suggesting that variable biological effects may be shaping their interaction. HighlightsO_LIPre-registered testing of microstructural imaging across modalities (FA, MT, R1, R2*) to test WM-behaviour relationships. C_LIO_LIPartial support for FA-behaviour relationships hypothesised based on previous literature. C_LIO_LIMultimodal approaches can help detect WM-behaviour relationships that are not detected with FA alone. C_LIO_LISample sizes of 40 to 200 may be needed to detect myelin-behaviour relationships in joint multimodal analyses. C_LIO_LIVariable biological effects may be shaping WM-behaviour relationships. C_LI

neuroscience↗

bioRxiv2020

Hippocampal grey matter tissue microstructure does not explain individual differences in hippocampal-dependent task performance

Individual differences in scene imagination, autobiographical memory recall, future thinking and spatial navigation have long been linked with hippocampal structure in healthy people, although evidence for such relationships is, in fact, mixed. Extant studies have predominantly concentrated on hippocampal volume. However, it is now possible to use quantitative neuroimaging techniques to model different properties of tissue microstructure in vivo such as myelination and iron. Previous work has linked such measures with cognitive task performance, particularly in older adults. Here we investigated whether performance on scene imagination, autobiographical memory, future thinking and spatial navigation tasks was associated with hippocampal grey matter myelination or iron content in young, healthy adult participants. MRI data were collected using a multi-parameter mapping protocol (0.8mm isotropic voxels) from a large sample of 217 people with widely-varying cognitive task scores. We found little evidence that hippocampal grey matter myelination or iron content was related to task performance. This was the case using different analysis methods (voxel-based quantification, partial correlations), when whole brain, hippocampal regions of interest, and posterior:anterior hippocampal ratios were examined, and across different participant sub-groups (divided by gender, task performance). Variations in hippocampal grey matter myelin and iron levels may not, therefore, help to explain individual differences in performance on hippocampal-dependent tasks, at least in young, healthy individuals.

neuroscience↗