Biology subjects

Critchley, H.

Publications and source records attributed to Critchley, H..

6 recordsLinked to original sources

bioRxiv2026

A Double Challenge: Cerebral Blood Flow During Concurrent Breath-Hold and Motor Task

Background/Hypothesis: Challenging the brain with simultaneous global and local demands may reveal functional constraints not apparent with either challenge alone. Here, we combine breath-holding with a motor task to investigate how a global vascular challenge modifies the local neurovascular response. Methods: Fourteen healthy adults underwent arterial spin labelling magnetic resonance imaging during three conditions: finger tapping with normal breathing, 25-second inspiratory breath-holding, and finger tapping during breath-holding. Cerebral blood flow responses were assessed using whole brain voxelwise analyses and motor regions of interest. Results: In the primary motor cortex, the increase in cerebral blood flow relative to baseline was approximately halved during the combined breath-holding and motor task challenge compared with motor task alone (26.5% vs 51.3%; p<0.001). Supplementary motor area responses were also smaller (23.2% vs 41.2%), but the difference was not statistically significant (p=0.092). Regional perfusion reductions were less extensive during the combined challenge than during breath-holding alone. These regional effects occurred without significant global grey- or white-matter perfusion changes from baseline. Conclusion/Interpretation: Combining global and local challenges revealed constraints on task-evoked perfusion increases not apparent during motor activation alone. This approach could help assess whether impaired cerebrovascular reserve compromises the brains capacity to meet local functional demands.

physiology↗

bioRxiv2021

Relationship between systolic blood pressure and decision-making during emotional processing

ObjectiveEmotional states are expressed in body and mind through subjective experience of physiological changes. In previous work, subliminal priming of anger prior to lexical decisions increased systolic blood pressure (SBP). This increase predicted the slowing of response times (RT), suggesting that baroreflex-related autonomic changes and their interoceptive (feedback) representations, influence cognition. Alexithymia is a subclinical affective dysfunction characterized by difficulty in identifying emotions. Atypical autonomic and interoceptive profiles are observed in alexithymia. Therefore, we sought to identify mechanisms through which SBP fluctuations during emotional processing might influence decision-making, including whether alexithymia contributes to this relationship. MethodsThirty-two male participants performed an affect priming paradigm and completed the Toronto Alexithymia Scale. Emotional faces were briefly presented (20ms) prior a short-term memory task. RT, accuracy and SBP were recorded on a trial-by-trial basis. Generalized mixed-effects linear models were used to evaluate the impact of emotion, physiological changes, alexithymia score, and their interactions, on performances. ResultsA main effect of emotion was observed on accuracy. Participants were more accurate on trials with anger primes, compared to neutral priming. Greater accuracy was related to increased SBP. An interaction between SBP and emotion was observed on RT: Increased SBP was associated with RT prolongation in the anger priming condition, yet this relationship was absent under the sadness priming. Alexithymia did not significantly moderate the above relationships. ConclusionsOur data suggest that peripheral autonomic responses during affective challenges guide cognitive processes. We discuss our findings in the theoretical framework proposed by Lacey and Lacey (1970).

neuroscience↗

bioRxiv2021

Oxytocin reduces interoceptive influences on empathy-for-pain in the anterior insula

Empathy-for-pain states are underpinned by interoception, i.e the central representation of internal states. Cardiac signals occur in a phasic manner; baroreceptor discharges at systole communicate the heartbeats strength. These signals modulate pain and emotion processing. We tested whether these phasic interoceptive signals modulate empathy-for-pain. As oxytocin (OT) enhances empathy and modulates interoceptive signals precision, we also tested if OT administration impacts empathy-for-pain via interoceptive mechanisms. Male subjects (N=32) attended three sessions to perform psychometric tests and an fMRI empathy-for-pain task, after intranasal administration of OT or placebo (40IU). Pictures of hands in painful or non-painful context were presented at systole or diastole. Effects of drug, emotion and cardiac timing on behaviour and brain activity was tested using general and mixed-effects linear models. Across conditions, activation was observed within regions implicated in pain and empathy-for-pain, with insula activation greater in the right than left hemisphere. OT administration, compared to placebo, attenuated the reactivity of some regions, including anterior cingulate cortex, but presentation of stimuli at systole blocked the OT attenuating effect. Our data suggest that OT alters the processing of motivationally-salient social cues, interacting with interoceptive signals. Our findings may inform targeted use of OT in psychiatric conditions linked to aberrant interoceptive processing.

neuroscience↗

bioRxiv2020

Serotonergic Effects on Interoception

Interoception is the signalling, perception, and interpretation of internal physiological states. Much of the psychopharmacology of interoception is still undiscovered. However, psychiatric disorders associated with changes of interoception, including depressive, anxiety, and eating disorders are often treated with selective serotonin reuptake inhibitors (SSRIs). The causal effect of acute changes of serotonin transmission on interoceptive cognition was tested by a within-participant, crossover, placebo-controlled study. Forty-seven healthy human volunteers (31 female, 16 male) were tested both on and off a 20mg oral dose of the commonly prescribed SSRI citalopram. For each randomly ordered session, participants made judgments on the synchrony of their heartbeat to auditory tones and expressed confidence in each of these judgments. Citalopram enhanced insight into the likelihood that ones interoceptive judgment had been correct, driven primarily by enhanced confidence for correct responses. This effect was independent of measured cardiac and subjective effects of the drug. This novel result is evidence that acute serotonin changes can alter metacognitive insight into the reliability of inferences based on interoceptive information, which is a foundation for considering effects of serotonin on cognition and emotion in terms of effective top-down regulation of interoceptive influence on mental states.

neuroscience↗

bioRxiv2020

Feeling the beat: Temporal and spatial perception of heartbeat sensations

The majority of interoceptive tasks (i.e. measuring the sensitivity to bodily signals) are based upon the heartbeat sensations perception. However, temporal perception of heartbeats varies among individuals and confidence and spatial perception of heartbeats in relation to temporal judgements have not yet been systematically investigated. This study examined the perception of heartbeat sensations in both time and spatial domains, using a multi-interval heartbeat discrimination task. The relationship between these domains was investigated, as well as the contribution of mental health conditions and cardiovascular parameters. Heartbeat sensations occurred on average ~250ms after the ECG R-wave and were more frequently sampled from the left part of the chest. Participants confidence in their experience of heartbeat sensations was maximal for the 0 ms interval. Interestingly, higher confidence was related to reduced dispersion of sampling locations but we found evidence toward the absence of relationship between temporal and spatial heartbeat sensations perception, using Bayesian statistics. Finally, we found evidence toward a relationship between spatial precision of heartbeat sensations and state anxiety score, which seems independent from the cardiovascular parameters. This systematic investigation of heartbeat sensations perception provides important fresh insights, informing the mechanistic understanding of the interoceptive signaling contribution to emotion, cognition and behaviour.

neuroscience↗

bioRxiv2019

Profiling the expression and function of ER46 in human endometrial tissues and uterine NK cells

Study questionDoes the oestrogen receptor isoform, ER46, contribute to regulation of endometrial function?\n\nSummary answerER46 is expressed in endometrial tissues during the proliferative and secretory phases and is the predominant ER isoform in first trimester decidua. ER46 is abundantly expressed in uterine NK (uNK) cells and localised to the cell membrane. Activation of ER46 regulates the function of human uNK cells by increasing cell motility.\n\nWhat is known alreadyOestrogens acting via their cognate receptors are essential regulators of endometrial function and play key roles in establishment of pregnancy. ER46 is a 46kDa truncated isoform of full length ER (ER66, encoded by ESR1) that contains both ligand and DNA binding domains. Expression of ER46 in human endometrium has not been investigated previously. ER46 is located at the cell membrane of peripheral blood leukocytes and mediates rapid responses to oestrogens. UNK cells are a phenotypically distinct (CD56brightCD16-) population of tissue-resident immune cells that regulate vascular remodelling within the endometrium and decidua. We have shown that oestrogens stimulate rapid increases in uNK cell motility. Previous characterisation of uNK cells suggests they are ER66-negative but expression of ER46 has not been characterised. We hypothesise that uNK cells express ER46 and that rapid responses to oestrogens are mediated via this receptor.\n\nStudy design, size, durationThis laboratory-based study used primary human endometrial (n=24) and decidual tissue biopsies (n=30) as well as uNK cells which were freshly isolated from first trimester human decidua (n=18).\n\nParticipants/materials, setting, methodsPrimary human endometrial and first trimester decidual tissue biopsies were collected using methods approved by the local institutional ethics committee (LREC/05/51104/12 and LREC/10/51402/59). The expression of oestrogen receptors (ER66, ER46 and ER{beta}) was assessed by qPCR, western blot and immunohistochemistry. Uterine Natural Killer (uNK) cells were isolated from first trimester human decidua by magnetic bead sorting. Cell motility of uNK cells was measured by live cell imaging: cells were treated with oestradiol (E2)-BSA (10nM equivalent), the ER{beta}-selective agonist 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN; 10nM) or vehicle control (DMSO).\n\nMain results and the role of chanceER46 was detected in proliferative and secretory phase tissues and was the predominant ER isoform in first trimester decidua samples. Immunohistochemistry revealed ER46 was co-localised with ER66 in cell nuclei during the proliferative phase but detected in both the cytoplasm and cell membrane of stromal cells in the secretory phase and in decidua. Triple immunofluorescence staining of decidua tissues identified expression of ER46 in the cell membrane of CD56-positive uNK cells which were otherwise ER66-negative. Profiling of isolated uNK cells confirmed expression ER46 and localised ER46 protein to the cell membrane. Functional analysis of isolated uNK cells using live cell imaging demonstrated that activation of ER46 with E2-BSA significantly increased uNK cell motility.\n\nLimitations, reasons for cautionExpression patterns in endometrial tissue was only determined using samples from proliferative and secretory phases. Assessment of first trimester decidua samples was from a range of gestational ages which may have precluded insights into gestation specific changes in these tissues. Our results are based on in vitro responses of primary human cells and we cannot be certain that similar mechanisms occur in situ.\n\nWider implications of the findingsE2 is an essential regulator of reproductive competence. This study provides the first evidence for expression of ER46 in human endometrium and decidua of early pregnancy. We describe a mechanism for regulating the function of human uNK cells via expression of ER46 and demonstrate that selective targeting with E2-BSA regulates uNK cell motility. These novel findings identify a role for ER46 in human endometrium and provide unique insight into the importance of membrane-initiated signalling in modulating the impact of E2 on uNK cell function in women.\n\nStudy funding/competing interest(s)These studies were supported by MRC Programme Grants G1100356/1 and MR/N024524/1 to PTKS. HODC was supported by MRC grant G1002033.

physiology↗