Biology subjects

Pattinson, K. T. S.

Publications and source records attributed to Pattinson, K. T. S..

9 recordsLinked to original sources

bioRxiv2026

Breathlessness catastrophising after COVID-19 involves both interoceptive and visceromotor connectivity

Persistent breathlessness is common after COVID-19, yet its severity typically correlates weakly with objective clinical measures. This discordance is often attributed to perceptual inference amplified by anxiety. Because breathing involves a closed perception-action loop, breathlessness may also reflect alterations in interoceptive and visceromotor pathways. We acquired 7-tesla resting-state functional MRI in 53 post-COVID patients with varying breathlessness and estimated functional connectivity across 18 pre-defined interoceptive and visceromotor regions. Linear regression identified two connections associated with breathlessness catastrophising: reduced dorsal periaqueductal grey-posterior insula (dPAG-PoI1) and increased basolateral amygdala-dorsal anterior cingulate (BLA-dACC) connectivity. The dPAG-PoI1 association was stronger in patients who had required mechanical ventilation, whereas the BLA-dACC association was attenuated at higher generalised anxiety. These findings are consistent with two potentially separable contributions to symptom burden: weakened interoceptive signalling between brainstem and sensory cortex, and heightened visceromotor influence of threat processing on autonomic control, rather than anxiety-driven misperception alone.

neuroscience↗

bioRxiv2025

Cortical motor activity modulates respiration and reduces apnoea in neonates

Respiration is governed by a widespread network of cortical and subcortical structures. This complex communication between the brain and lungs is altered in pathological conditions. Apnoea - the cessation of respiration - is a common condition in infants, particularly those born prematurely. Apnoea in infants is believed to relate to immaturity of brainstem respiratory centres; involvement of the cortex in respiration in infants has yet to be explored. We investigated if there was any evidence for cortical coupling with respiration in newborn humans and whether it relates to apnoea. Using simultaneous electroencephalography (EEG) and impedance pneumography we investigated interactions between cortical and respiratory activity (known as cortico-respiratory coupling) using phase-amplitude coupling. We show that cortico-respiratory coupling is present in premature and term newborns (104 recordings from 68 infants; 34.5 {+/-} 2.6 weeks post-menstrual age), identifying an interplay between breathing phase and EEG amplitude. We further shed light on the biological meaning by revealing that the strongest coupling occurs during inspiration and that cortical activity precedes respiration, with coupling strongest over frontocentral regions. Whilst our study was limited in spatial resolution, and determining causality is challenging, we believe these findings support the notion that the cortico-respiratory coupling observed here constitutes communication between cortical motor areas and lung effectors. Moreover, we show that cortico-respiratory coupling is negatively correlated with the rate of apnoea, revealing novel insight into this common and potentially life-threatening neonatal pathology.

neuroscience↗

bioRxiv2024

Towards the implementation and interpretation of masked ICA for identifying signatures of autonomic activation in the brainstem with resting-state BOLD fMRI

The brainstem is the site of key exchanges between the autonomic and central nervous systems but has historically presented a challenging target for study with BOLD fMRI. A potentially powerful although under-characterized approach to identifying nucleic activation within the brainstem is masked independent component analysis (mICA), which restricts signal decomposition to the brainstem itself, thus aiming to reduce the strong effect of physiological noise in nearby regions such as ventricles and large arteries. In this study, we systematically investigate the use of mICA to uncover signatures of autonomic activation in the brainstem at rest. We apply mICA on 40 subjects in a high-resolution resting state 7T dataset following different strategies for dimensionality selection, denoising, and component classification. We show that among the noise mitigation techniques investigated, cerebrospinal fluid denoising makes the largest impact in terms of mICA outcomes. We further demonstrate that across preprocessing pipelines and previously reported results the majority of components are spatially reproducible, but temporal outcomes differ widely depending on denoising strategy. Evaluating both hand-labelling and whole-brain specificity criteria, we develop an intuitive framework for mICA classifications. Finally, we make a comparison between mICA and atlas-based segmentations of brainstem nuclei, finding little consistency between these two approaches. Based on our evaluation of the effects of methodology on mICA and its relationship to other signals of interest in the brainstem, we provide recommendations for future uses of mICA to identify autonomically-relevant BOLD fluctuations in subcortical structures.

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bioRxiv2021

Baseline psychological traits contribute to Lake Louise Acute Mountain Sickness score at high altitude

BackgroundInteroception refers to an individuals ability to sense their internal bodily sensations. Acute mountain sickness (AMS) is a common feature of ascent to high altitude that is only partially explained by measures of peripheral physiology. We hypothesised that interoceptive ability may explain the disconnect between measures of physiology and symptom experience in AMS. Methods and MaterialTwo groups of 18 participants were recruited to complete a respiratory interoceptive task three times at two-week intervals. The control group remained in Birmingham (140m altitude) for all three tests. The altitude group completed test 1 in Birmingham, test 2 the day after arrival at 2624m, and test 3 at 2728m after an 11-day trek at high altitude (up to 4800m). ResultsBy measuring changes to metacognitive performance, we showed that acute ascent to altitude neither presented an interoceptive challenge, nor acted as interoceptive training. However, AMS symptom burden throughout the trek was found to relate to sea-level measures of anxiety, agoraphobia, and neuroticism. ConclusionsThis suggests that the Lake Louise AMS score is not solely a reflection of physiological changes on ascent to high altitude, despite often being used as such by researchers and commercial trekking companies alike.

neuroscience↗

bioRxiv2020

Dissociating breathlessness symptoms from mood in asthma

Asthma is one of many chronic diseases in which discordance between objectively measured pathophysiology and symptom burden is well recognised. Understanding the influences on symptom burden beyond pathophysiology could improve our ability to treat symptoms. While co-morbidities such as anxiety and depression may play a role, the impact of this relationship with symptoms on our ability to perceive bodily sensations (termed interoception), or even our general and symptom-specific attention is not yet understood. Here we studied 63 individuals with asthma and 30 healthy controls. Alongside physiological tests including spirometry, bronchodilator responsiveness, expired nitric oxide and blood eosinophils, we collected self-reported questionnaires covering affective factors such as anxiety and depression, as well as asthma symptoms and asthma-related quality of life (individuals with asthma only). Participants additionally completed a breathing-related interoception task and two attention tasks designed to measure responsiveness to general temporal/spatial cues and specific asthma-related threatening words. We conducted an exploratory factor analysis across the questionnaires which gave rise to key components of Mood and Symptoms, and compared these to physiological, interoceptive and attention measures. While no relationships were found between symptoms and physiological measures in asthma alone, negative mood was related to both decreased interoceptive metacognitive sensitivity ( insight into interoceptive performance) and metacognitive bias (confidence in interoceptive decisions), as well as increased effects of spatial orienting cues in both asthma and controls. Furthermore, the relationship between the extent of symptoms and negative mood revealed potential sub-groups within asthma, with those who displayed the most severe symptoms without concurrent negative mood also demonstrating altered physiological, interoceptive and attention measures. Our findings are a step towards understanding how both symptoms and mood are related to our ability to interpret bodily symptoms, and to explore how the balance between mood and symptoms may help us understand the heterogeneity in conditions such as asthma.

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bioRxiv2020

Pain and breathlessness: Salient, somatosensory and similar, but not the same

Quantifying pain currently relies upon subjective self-report. Alongside the inherent variability embedded within these metrics, added complications include the influence of ambiguous or prolonged noxious inputs, or in situations when communication may be compromised. As such, there is continued interest in the development of brain biomarkers of pain, such as in the form of neural signatures of brain activity. However, issues pertaining to pain-related specificity remain, and by understanding the current limits of these signatures we can both progress their development and investigate the potentially generalizable properties of pain to other salient and/or somatomotor tasks. Here, we utilized two independent datasets to test one of the established Neural Pain Signatures (the NPS (Wager et al. 2013)). In Study 1, brain activity was measured using functional magnetic resonance imaging (fMRI) in 40 healthy subjects during experimentally induced breathlessness, conditioned anticipation of breathlessness and a simple finger opposition task. In Study 2, brain activity was again measured during anticipation and breathlessness in 19 healthy subjects, as well as a modulation with the opioid remifentanil. We were able to identify significant NPS-related brain activity during anticipation and perception of breathlessness, as well as during finger opposition using the global NPS. Furthermore, localised NPS responses were found in early somatomotor regions, bilateral insula and dorsal anterior cingulate for breathlessness and finger opposition. In contrast, no conditions were able to activate the local signature in the dorsal posterior insula - thought to be critical for pain perception. These results provide properties of the present boundaries of the NPS, and offer insight into the overlap between breathlessness and somatomotor conditions with pain.

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bioRxiv2017

Modeling of dynamic cerebrovascular reactivity to spontaneous and externally induced CO2 fluctuations in the brainstem respiratory control centers in the human brain using BOLD-fMRI

In this work, we investigate the regional characteristics of the dynamic interactions between arterial CO2 and BOLD (dynamic cerebrovascular reactivity - dCVR) during normal breathing and hypercapnic, externally induced step CO2 challenges. To obtain CVR curves at each voxel, we use a custom set of basis functions based on the Laguerre and gamma basis sets. This allows us to obtain robust dCVR estimates both in larger regions of interest (ROIs) as well as in individual voxels. We also implement classification schemes to identify brain regions with similar dCVR characteristics. Our results reveal considerable variability of dCVR across different brain regions, as well as during different experimental conditions (normal breathing and hypercapnia), suggesting a differential response of cerebral vasculature to spontaneous CO2 fluctuations and larger, externally induced CO2 changes. The clustering results suggest that anatomically distinct brain regions exhibit different dCVR curves that do not exhibit the standard, positive valued curves that have been previously reported using measurements of global cerebral blood flow or using larger ROIs. They also revealed a consistent set of dCVR cluster shapes for resting and forcing conditions that exhibited different distribution patterns across brain voxels.

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bioRxiv2017

Cortical processing of breathlessness in the athletic brain

Athletes regularly endure large increases in ventilation, and accompanying perceptions of breathlessness. While breathing perceptions often correlate poorly with objective measures of lung function in both health and clinical populations, we have previously demonstrated closer matching between subjective breathlessness and changes in ventilation in endurance athletes, suggesting that athletes may be more accurate during respiratory interoception. To better understand the link between exercise and breathlessness, we sought to identify the mechanisms by which the brain processing of respiratory perception might be optimised in athletes. Twenty endurance athletes and 20 sedentary controls underwent 7 Tesla functional magnetic resonance imaging. Inspiratory resistive loading induced conscious breathing perceptions (breathlessness), and a delay-conditioning paradigm was employed to evoke preceding periods of anticipation. Athletes demonstrated anticipatory brain activity that positively correlated with resulting breathing perceptions within key interoceptive areas, such as the thalamus, insula and primary sensorimotor cortices, which was negatively correlated in sedentary controls. Athletes also exhibited greater connectivity between interoceptive attention networks and primary sensorimotor cortex. These functional differences in athletic brains suggest that exercise may optimise processing of respiratory sensations. Future work may probe whether these brain mechanisms are harnessed when exercise is employed to treat breathlessness within chronic respiratory disease.

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bioRxiv2017

Treating the lungs via the brain: Mechanisms underpinning improvements in breathlessness with pulmonary rehabilitation.

BackgroundBreathlessness in chronic obstructive pulmonary disease (COPD) is often discordant with airway pathophysiology (\"over-perception\"). Pulmonary rehabilitation has profound effects upon breathlessness, without influencing lung function. Learned associations can influence brain mechanisms of sensory perception. We therefore hypothesised that improvements in breathlessness with pulmonary rehabilitation may be explained by changing neural representations of learned associations, reducing \"over-perception\".\n\nMethodsIn 31 patients with COPD, we tested how pulmonary rehabilitation altered the relationship between brain activity during learned associations with a word-cue task (using functional magnetic resonance imaging), clinical, and psychological measures of breathlessness.\n\nResultsImprovements in breathlessness and breathlessness-anxiety correlated with reductions in word-cue related activity in the insula and anterior cingulate cortex (ACC) (breathlessness), and increased activations in attention regulation and motor networks (breathlessness-anxiety). Greater baseline (pre-rehabilitation) activity in the insula, ACC and prefrontal cortex correlated with the magnitude of improvement in breathlessness and breathlessness anxiety.\n\nConclusionsPulmonary rehabilitation reduces the influence of learned associations upon neural processes that generate breathlessness. Patients with stronger word-cue related activity at baseline benefitted more from pulmonary rehabilitation. These findings highlight the importance of targeting learned associations within treatments for COPD, demonstrating how neuroimaging may contribute to patient stratification and more successful personalised therapy.

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