Search bioRxiv⌕ Search

Biology subjects

McCall, C.

Publications and source records attributed to McCall, C..

5 recordsLinked to original sources

Tired and wired: sleep deprivation prevents emotional adaptation to prolonged and ambiguous threat

Sleep problems are strongly linked to anxiety, but the psychological mechanisms underpinning this relationship are poorly understood. In this pre-registered study, we combined virtual reality, psychophysiology and multidimensional experience sampling to test the hypothesis that sleep deprivation disrupts emotional adaptation to sustained or resolving threat, giving rise to a heightened state of anxiety. Following a night of restful sleep or total sleep deprivation, healthy young adults navigated an immersive virtual world that alternated between ambiguously threatening and non-threatening contexts. Despite initial increases in emotional arousal, sleep-rested individuals quickly downregulated affective responses to ambiguous threat, reflecting efficient adaptation to the aversive virtual environment. Sleep-deprived individuals, by contrast, were unable to overturn elevated arousal responses, and exhibited a breakdown of goal-orientated, emotional control. Interestingly, resting heart rate variability, an index of affective regulatory capacity, mitigated arousal responses to ambiguous threat after sleep deprivation. These findings suggest that impaired adaptation to prolonged threat may represent a key mechanistic pathway linking insufficient sleep to anxiety.

neuroscience↗

The Proximity Prediction Hypothesis: How predictive coding of CT-touch explains Autonomous Sensory Meridian Response and its therapeutic applications.

Autonomous Sensory Meridian Response (ASMR) is a pleasant tingling sensation felt across the scalp and neck, widely reported to reduce anxiety and improve sleep. The Proximity Prediction Hypothesis (PPH) is the first comprehensive predictive coding model explaining ASMRs underlying neural mechanism. PPH posits that near-field acoustic cues from common ASMR triggers (e.g., brushing sounds, whispered speech) engage the audio-tactile Peripersonal Space Network, generating a top-down prediction of gentle C-tactile (CT) touch on CT fibre-rich skin of the scalp and neck. This prediction suppresses locus coeruleus (LC) arousal and increases vagal output, offering a mechanistic explanation for the phenomenons therapeutic benefits. In a subjective-experience survey (N = 64), ASMR-labelled trials were rated significantly more pleasant but only slightly more arousing than controls. Pleasantness predicted both the presence and intensity of tingles, supporting PPHs core claim that hedonic value, rather than sympathetic activation, drives the graded somatosensory response. PPH situates ASMR within the Neurovisceral Integration framework, predicting measurable Central Nervous System-Autonomic Nervous System (CNS-ANS) markers (beta-band desynchronisation in the posterior insula and proportional increases in high-frequency heart rate variability with tingle intensity). It further predicts reduced LC activity during ASMR, stronger effects in individuals with high interoceptive prediction error (e.g., anxiety, autism), and attenuation of tingles when spatial proximity cues are removed. By integrating auditory proximity, CT-touch anticipation, and autonomic regulation into a single predictive-coding account, PPH provides a unified, testable framework for explaining ASMR, offering a blueprint for translating this sensory phenomenon into targeted, evidence-based interventions for anxiety and sleep disorders.

neuroscience↗

Hematopoietic-SLC37A2 deficiency impairs M2 macrophage polarization and accelerates atherosclerosis in LDL receptor-deficient mice

Macrophages play a central role in the pathogenesis of atherosclerosis. Our previous study demonstrated that solute carrier family 37 member 2 (SLC37A2), an endoplasmic reticulum-anchored phosphate-linked glucose-6-phosphate transporter, negatively regulates macrophage Toll-like receptor activation by fine-tuning glycolytic reprogramming in vitro. Whether macrophage SLC37A2 impacts in vivo macrophage inflammation and atherosclerosis under hyperlipidemic conditions is unknown. We generated hematopoietic cell-specific SLC37A2 knockout and control mice in C57Bl/6 Ldlr-/- mice by bone marrow transplantation. Hematopoietic-specific SLC37A2 deletion in Ldlr-/- mice increased plasma lipid concentrations 12-16 wks of Western diet induction, attenuated macrophage anti-inflammatory responses, and resulted in more atherosclerosis compared to Ldlr-/- mice transplanted with wild type bone marrow. Aortic root intimal area was inversely correlated with plasma IL-10 levels, but not total cholesterol concentrations, suggesting inflammation but not plasma cholesterol was responsible for increased atherosclerosis in bone marrow SLC37A2-deficient mice. Our in vitro study demonstrated that SLC37A2 deficiency impaired IL-4-induced macrophage activation, independently of glycolysis or mitochondrial respiration. Importantly, SLC37A2 deficiency impaired apoptotic cell-induced glycolysis, subsequently attenuating IL-10 production. Our study suggests that SLC37A2 expression is required to support alternative macrophage activation in vitro and in vivo. In vivo disruption of hematopoietic SLC37A2 accelerates atherosclerosis under hyperlipidemic pro-atherogenic conditions.

immunology↗

Dichloroacetate improves systemic energy balance and feeding behavior during sepsis

Sepsis is a life-threatening organ dysfunction by dysregulated host response to an infection. The metabolic aberrations associated with sepsis underly an acute and organism wide hyper-inflammatory response and multiple organ dysfunction; however, crosstalk between systemic metabolomic alterations and metabolic reprograming at organ levels remains unknown. We analyzed substrate utilization by the respiratory exchange ratio, energy expenditure, metabolomic screening and transcriptional profiling in a cecal ligation and puncture (CLP) model, to show that sepsis increases circulating free fatty acids and acylcarnitines but decreases levels of amino acids and carbohydrates leading to a drastic shift in systemic fuel preference. Comparative analysis of previously published metabolomics from septic liver indicates a positive correlation with hepatic and plasma metabolites during sepsis. In particular, glycine deficiency was a common abnormality of both plasma and the liver during sepsis. Interrogation of the hepatic transcriptome in septic mice suggests that the septic liver may contribute to systemic glycine deficiency by downregulating genes involved in glycine synthesis. Interestingly, intraperitoneal injection of the pyruvate dehydrogenase kinase (PDK) inhibitor dichloroacetate (DCA) reverses sepsis-induced anorexia, energy imbalance, dyslipidemia, hypoglycemia, and glycine deficiency. Collectively, our data indicate that PDK inhibition rescues systemic energy imbalance and metabolic dysfunction in sepsis partly through restoration of hepatic fuel metabolism.

immunology↗

Exploring patterns of ongoing thought under naturalistic and task-based conditions

Previous research suggests that patterns of ongoing thought are heterogeneous, varying across situations and individuals. The current study investigated the influence of a wide range of tasks and individual affective style on ongoing patterns of thought. In total, we used 9 different tasks and measured ongoing thought using multidimensional experience sampling. A Principle Component Analysis of the experience sampling data revealed four patterns of ongoing thought. Linear Mixed Modelling was used to examine the contextual distribution of the thought patterns. Different thought patterns were found to relate to different types of conditions. Intrusive and negative thought pattern expression was found to be influenced by individual affective style (depression level). Overall, these data show that patterns of thought are subject to both contextual and intrinsic variation, suggesting that understanding these important features of experience across a broad range of situations will be useful in understanding their role in human experience. HighlightsO_LIPatterns of thought vary across different task contexts C_LIO_LIThought pattern expression is influenced by individual affective style C_LIO_LIThere is a need to broaden the tasks used to study ongoing thought C_LI

neuroscience↗