Biology subjects

Jackson, J. B.

Publications and source records attributed to Jackson, J. B..

9 recordsLinked to original sources

bioRxiv2024

Comparison of MR coil options for concurrent TMS-fMRI

Concurrent transcranial magnetic stimulation (TMS) with functional magnetic resonance imaging (fMRI) is increasingly being used to study how TMS affects neural processing in local and remote connected brain regions. However, there are many technical challenges that arise when operating this unique combination of techniques. One such challenge is MR head coil compatibility and the image resolution that can be achieved. Here we compare the temporal-signal-to noise-ratio (tSNR) between 3 different MR head coils that can be used with TMS. We show that the 7-channel TMS-dedicated surface coils result in a very high tSNR directly under the TMS and the supplementary coil in comparison to the TxRx and the Magnetica. However, there is low tSNR elsewhere. This field inhomogeneity may not be suitable for all research questions, for example where the aim is to look at distributed neural responses. In these cases, an MR coil with a more homogeneous tSNR such as the Magnetica, may be more appropriate.

neuroscience↗

bioRxiv2024

Domain general frontoparietal regions show modality-dependent coding of auditory and visual rules

A defining feature of human cognition is our ability to respond flexibly to what we see and hear, changing how we respond depending on our current goals. In fact, we can rapidly associate almost any input stimulus with any arbitrary behavioural response. This remarkable ability is thought to depend on a frontoparietal "multiple demand" circuit which is engaged by many types of cognitive demand and widely referred to as domain general. However, it is not clear how responses to multiple input modalities are structured within this system. Domain generality could be achieved by holding information in an abstract form that generalises over input modality, or in a modality-tagged form, which uses similar resources but produces unique codes to represent the information in each modality. We used a stimulus-response task, with conceptually identical rules in two sensory modalities (visual and auditory), to distinguish between these possibilities. Multivariate decoding of functional magnetic resonance imaging data showed that representations of visual and auditory rules recruited overlapping neural resources but were expressed in modality-tagged non-generalisable neural codes. Our data suggest that this frontoparietal system may draw on the same or similar resources to solve multiple tasks, but does not create modality-general representations of task rules, even when those rules are conceptually identical between domains.

neuroscience↗

bioRxiv2023

The causal roles of parietal alpha oscillations and evoked potentials in coding task-relevant information during selective attention

Selective attention is a fundamental cognitive mechanism that allows people to prioritise task-relevant information while ignoring irrelevant information. Previous research has suggested key roles of parietal evoked potentials and alpha oscillatory responses in spatial attention tasks. However, the informational content of these signals is less clear, and their causal effects on the coding of multiple task elements are yet unresolved. Here, we used concurrent TMS-EEG to causally manipulate parietal alpha power and evoked potentials and investigate their roles in coding multiple task features (where to attend, what to attend to, and visual stimulus) in a selective attention task. First, using EEG-only data, we found that evoked potentials coded all three types of task-relevant information with distinct temporal dynamics, and alpha oscillations carried information regarding both where to attend and what to attend to. Then, we applied rhythmic-TMS (rTMS) at individual alpha frequency over the right intraparietal sulcus (IPS), while concurrently measuring EEG. Compared with control arrhythmic-TMS, alpha rTMS increased alpha power and inter-trial phase coherence and yielded more negative posterior-contralateral evoked potentials. Moreover, alpha rTMS causally and specifically improved multivariate decoding of the information about where to attend (but not what to attend to or feature information) during task performance, with decoding improvements predicting changes in behavioural performance. These findings illuminate the dynamics with which the complementary aspects of a selective attention task are encoded in evoked and oscillatory brain activity. Moreover, they reveal a specific and causal role of IPS-controlled evoked and oscillatory activity in carrying behaviour-driving information about where to focus attention.

neuroscience↗

bioRxiv2021

Limited variation between SARS-CoV-2-infected individuals in domain specificity and relative potency of the antibody response against the spike glycoprotein

The spike protein of SARS-CoV-2 is arranged as a trimer on the virus surface, composed of three S1 and three S2 subunits. Infected and vaccinated individuals generate antibodies against spike, which can neutralize the virus. Most antibodies target the receptor-binding domain (RBD) and N-terminal domain (NTD) of S1; however, antibodies against other regions of spike have also been isolated. The variation between infected individuals in domain specificity of the antibodies and in their relative neutralization efficacy is still poorly characterized. To this end, we tested serum and plasma samples from 85 COVID-19 convalescent subjects using 7 immunoassays that employ different domains, subunits and oligomeric forms of spike to capture the antibodies. Samples were also tested for their neutralization of pseudovirus containing SARS-CoV-2 spike and of replication-competent SARS-CoV-2. We observed strong correlations between the levels of NTD- and RBD-specific antibodies, with a fixed ratio of each type to all anti-spike antibodies. The relative potency of the response (defined as the measured neutralization efficacy relative to the total level of spike-targeting antibodies) also exhibited limited variation between subjects, and was not associated with the overall amount of anti-spike antibodies produced. Accordingly, the ability of immunoassays that use RBD, NTD and different forms of S1 or S1/S2 as capture antigens to estimate the neutralizing efficacy of convalescent samples was largely similar. These studies suggest that host-to-host variation in the polyclonal response elicited against SARS-CoV-2 spike is primarily limited to the quantity of antibodies generated rather than their domain specificity or relative neutralization potency. IMPORTANCEInfection by SARS-CoV-2 elicits antibodies against various domains of the spike protein, including the RBD, NTD and S2. Different infected individuals generate vastly different amounts of anti-spike antibodies. By contrast, as we show here, there is a remarkable similarity in the properties of the antibodies produced. Different individuals generate the same proportions of antibodies against each domain of the spike protein. Furthermore, the relationship between the amount of anti-spike antibodies produced and their neutralization efficacy of SARS-CoV-2 is highly conserved. Therefore, the observed variation in the neutralizing activity of the antibody response in COVID-19 convalescent subjects is caused by differences in the amounts of antibodies rather than their recognition properties or relative antiviral activity. These findings suggest that COVID-19 vaccine strategies that focus on enhancing the overall level of the antibodies will likely elicit a more uniformly efficacious protective response.

microbiology↗

bioRxiv2021

Now you see it, now you don't: optimal parameters for interslice stimulation in concurrent TMS-fMRI

The powerful combination of transcranial magnetic stimulation (TMS) concurrent with functional magnetic resonance imaging (fMRI) provides rare insights into the causal relationships between brain activity and behaviour. Despite a recent resurgence in popularity, TMS-fMRI remains technically challenging. Here we examined the feasibility of applying TMS during short gaps between fMRI slices to avoid incurring artefacts in the fMRI data. We quantified signal dropout and changes in temporal signal-to-noise ratio (tSNR) for TMS pulses presented at timepoints from 100ms before to 100ms after slice onset. Up to 3 pulses were delivered per volume using MagVentures MR-compatible TMS coil. We used a spherical phantom, two 7-channel TMS-dedicated surface coils, and a multiband (MB) sequence (factor=2) with interslice gaps of 100ms and 40ms, on a Siemens 3T Prisma-fit scanner. For comparison we repeated a subset of parameters with a more standard single-channel TxRx (birdcage) coil, and with a human participant and surface coil set up. We found that, even at 100% stimulator output, pulses applied at least - 40ms/+50ms from the onset of slice readout avoid incurring artifacts. This was the case for all three setups. Thus, an interslice protocol can be achieved with a frequency of up to ~10 Hz, using a standard EPI sequence (slice acquisition time: 62.5ms, interslice gap: 40ms). Faster stimulation frequencies would require shorter slice acquisition times, for example using in-plane acceleration. Interslice TMS-fMRI protocols provide a promising avenue for retaining flexible timing of stimulus delivery without incurring TMS artifacts.

neuroscience↗

bioRxiv2020

The association between pain-induced autonomic reactivity and descending pain control is mediated by the periaqueductal grey

There is a strict interaction between the autonomic nervous system (ANS) and pain, which might involve descending pain modulatory mechanisms. The periaqueductal grey (PAG) is involved both in descending pain modulation and ANS, but its role in mediating this relationship has not yet been explored. Here, we sought to determine brain regions mediating ANS and descending pain control associations. 30 participants underwent Conditioned Pain Modulation (CPM) assessments, in which they rated painful pressure stimuli applied to their thumbnail, either alone or with a painful cold contralateral stimulation. Differences in pain ratings between pressure-only and pressure+cold stimuli provided a measure of descending pain control. In 18 of the 30 participants, structural scans and two functional MRI assessments, one pain-free and one during cold-pain, were acquired. Heart Rate Variability (HRV) was simultaneously recorded. Low frequency HRV (LF-HRV) and the CPM score were negatively correlated; individuals with higher LF-HRV during pain reported reductions in pain during CPM. PAG-frontal medial cortex (FMC) and PAG-rostral ventro-medial medulla (RVM) functional connectivity correlated negatively with the CPM. Importantly, PAG-FMC functional connectivity mediated the strength of HRV-CPM association. CPM response magnitude was also negatively associated with PAG and positively associated with FMC grey matter volumes. Our multi-modal approach, using behavioral, physiological and MRI measures, provides important new evidence of interactions between ANS and descending pain mechanisms. ANS dysregulation and dysfunctional descending pain modulation are characteristics of chronic pain. We suggest that further investigation of body-brain interactions in chronic pain patients may catalyse the development of new treatments.

neuroscience↗

bioRxiv2020

Concurrent neuroimaging and neurostimulation reveals a causal role for dlPFC in coding of task-relevant information

The way in which the brain prioritises processing of information relevant for our current goals is widely contested. Many studies implicate the dorsolateral prefrontal cortex (dlPFC), and propose that it drives brain-wide focus by biasing processing in favour of relevant information. An alternative, however, is that dlPFC is involved in the inhibition of irrelevant information. Here, we address this longstanding debate using the inferentially powerful approach of applying transcranial magnetic stimulation during functional magnetic resonance imaging (concurrent TMS-fMRI) and testing for changes in information coding using multivariate pattern analysis (MVPA). We ask whether dlPFC plays a causal role in prioritising information processing, and whether this is through selection of relevant information or inhibition of irrelevant information. Participants attended to one object feature whilst ignoring another feature of the same object. We reasoned that, if dlPFC is necessary for selection, active (disruptive) TMS should decrease coding of attended information compared to the low intensity (control) condition. Conversely, if right dlPFC is crucial for inhibition, active TMS should increase coding of irrelevant information relative to the control condition. The results showed that active TMS decreased coding of relevant information throughout the frontoparietal multiple demand regions, and that this impact was significantly stronger than the effect of TMS on irrelevant information coding, which was not statistically detectable. These data provide causal evidence for a specific role of dlPFC in supporting the representation of task-relevant information and demonstrate the crucial insights into high level cognitive-neural mechanisms possible with the combination of TMS-fMRI and MVPA.

neuroscience↗

bioRxiv2019

Sustained perturbation in functional connectivity induced by cold pain

Functional connectivity (FC) perturbations have been reported in multiple chronic pain phenotypes, but the nature of reported changes is varied and inconsistent between cohorts. Increases and decreases in connectivity strength in task negative and positive networks, for example, the default mode and salience networks (DMN/SN), respectively, have been described, but how other networks are effected, for example, descending pain control networks, remains unknown. Whether connectivity changes relate to peripherally-mediated nociceptive afferent input, represent coping strategies or are sequelae of chronic pain, e.g. anxiety/depression, is also unknown. Here, we examined FC changes in response to experimentally-administered tonic cold pain in healthy volunteers as a means of disambiguating the nature of connectivity changes. We assessed FC prior to, during, and following tonic cold painful stimulation in four seed regions: ventromedial prefrontal cortex (vmPFC), rostral anterior insula (rAI), subgenual anterior cingulate cortex (ACC) and periaqueductal grey (PAG) and recorded subjectively reported pain using a computerised visual analogue scale. We saw DMN FC changes during painful stimulation and that inter-network communication between the rAI and sgACC seeds with the vmPFC became less anti-correlated during pain, whereas PAG-precuneus FC decreased. Pain-induced FC alterations largely persisted during a 6-minute recovery period following cessation of the painful stimulus. Observed FC changes related to the magnitude of individuals subjectively reported pain. We provide new insights into FC changes during and following tonic cold-pain and suggest that some FC changes observed in chronic pain patients may relate to the presence of an ongoing afferent peripheral drive.

neuroscience↗

bioRxiv2017

Diagnostic utility of telomere length measurement in a hospital setting

Very short telomere length (TL) provokes cellular senescence in vitro, but the clinical utility of TL measurement in a hospital-based setting has not been determined. We tested the diagnostic and prognostic value of TL measurement by flow cytometry and fluorescence in situ hybridization (flowFISH) in individuals with mutations in telomerase and telomere maintenance genes, and examined prospectively whether TL altered treatment decisions for patients with bone marrow failure. TL had a definable normal range across populations with discrete lower and upper boundaries. TL above the 50th age-adjusted percentile had a 100% negative predictive value for clinically relevant mutations in telomere maintenance genes, but the lower threshold for diagnosis was age-dependent. The extent of deviation from the age-adjusted median correlated with the age at diagnosis of a telomere syndrome as well as the predominant complication. Mild short telomere defects manifested in adults as pulmonary fibrosis-emphysema, while severely short TL manifested in children as bone marrow failure and immunodeficiency. Among 38 newly diagnosed patients with bone marrow failure, TL shorter than the 1st age-adjusted percentile enriched for patients with germline mutations in inherited bone marrow failure genes, such as RUNX1, in addition to telomere maintenance genes. The TL result modified the hematopoietic stem cell donor choice and/or treatment regimen in one-fourth of the cases (9 of 38,24%). TL testing by flowFISH has diagnostic and predictive value in definable clinical settings. In patients with bone marrow failure, it altered treatment decisions for a significant subset.

genetics↗