Biology subjects

Cormie, M. A.

Publications and source records attributed to Cormie, M. A..

4 recordsLinked to original sources

bioRxiv2025

The Contribution of Circulating Endocannabinoid Tone to Individual Differences in Human Pain Sensitivity: A Quantitative Sensory Testing Study

The endocannabinoid (eCB) system--comprising cannabinoid receptors, eCBs (anandamide-- AEA, 2-arachidonoylglycerol--2-AG) and related N-acylethanolamines (NAEs; N-palmitoylethanolamide--PEA, and N-oleoylethanolamide--OEA), and metabolizing enzymes (e.g., fatty acid amide hydrolase; FAAH)--modulates nociceptive circuits in rodents. In humans, the FAAH C385A polymorphism is associated with reduced pain sensitivity, suggesting eCB tone influences individual pain differences, but this has yet to be tested. Here, we determined whether the eCB system is associated with somatosensory and pain sensitivity measured with quantitative sensory testing (QST) in 91 healthy participants (39 males, 52 females). We tested three hypotheses: (1) FAAH C385A polymorphism, cannabis use, and sex affect serum eCB/NAE concentrations; (2) FAAH C385A carriers show altered pain sensitivity versus non-carriers; and (3) baseline serum eCB/NAE concentrations are associated with QST measures. eCB/NAE concentrations were not statistically different based on sex (p > .05), based on FAAH genotype (p > .05), and based on cannabis use (p > .05). To address collinearity of AEA, OEA and PEA, we performed a principal components analysis, which identified a single component of FAAH substrates. Linear regressions found that FAAH genotype did not affect QST measures and that baseline 2-AG and FAAH substrate concentrations were not associated with QST measures, except pressure pain thresholds (PPT; p = 0.003), which were associated with AEA and OEA. Baseline eCB/NAE levels and FAAH genotype are not associated with the outcome measures of standard QST tests that rely on point estimates in healthy adult humans; nonetheless, circulating FAAH substrate levels were associated with PPT.

neuroscience↗

bioRxiv2025

The human claustrum initiates networks for externally and internally driven task demands.

Cognitive control is believed to arise from interactions among multiple brain networks depending on task demands. Although several debilitating neuropsychiatric disorders are characterized by cognitive network dysfunction, the neural circuit mechanisms supporting task-dependent network activation are largely unknown. Because the claustrum possesses widespread connections with cortex and can synchronize distant cortical regions, we tested whether the claustrum activates task-dependent network states using fMRI during working memory (n = 420) and autobiographical memory (n = 35), tasks which elicit opposing responses from key cognitive control networks. In both tasks, the claustrum exhibited increased activity and excitatory influence on task-associated cognitive control network nodes, with corroborating underlying structural connectivity. The claustrum also displayed stronger excitatory effective connectivity during task performance and greater structural connectivity with task-related network nodes than regions prominently implicated in directing network states--the anterior insula and pulvinar. These findings establish a role for the claustrum in initiating network states for cognitive control. SignificanceCognitive functioning is supported by large-scale networks across the brain. Yet, the neural circuit mechanisms supporting task-dependent network activation are largely unknown. Circuit analyses using human functional and structural neuroimaging in this study found that the claustrum, a subcortical nucleus, activates during multiple cognitive tasks eliciting a wide range of network states, possesses strong anatomical connections with cognitive control network nodes, and exerts excitatory influence on task-associated network regions. These results establish the claustrum as a network activator subserving cognitive control.

neuroscience↗

bioRxiv2025

The Thermal Grill Elicits Central Sensitization

The thermal grill, in which innocuous warm and cool stimuli are interlaced, can produce a paradoxical burning pain sensation--the thermal grill illusion (TGI). While the mechanisms underlying TGI remain unclear, prominent theories point to spinal dorsal horn integration of innocuous thermal inputs to elicit pain. It remains unknown whether the TGI activates peripheral nociceptors, or solely thermosensitive afferents integrated within the spinal cord. Different types of sensitization have established mechanisms and can inform TGI mechanisms: if the TGI elicits (1) primary hyperalgesia, peripheral nociceptors are likely be activated; (2) secondary hyperalgesia without primary hyperalgesia, spinal integration is likely required; and (3) brush allodynia, wide-dynamic range neurons could be involved in mediating the TGI. Here, we determine whether the TGI elicits primary hyperalgesia, secondary hyperalgesia or brush allodynia. Fifty-two participants underwent individually calibrated phasic thermal grill stimulation. We found that the calibrated TGI elicited primary hyperalgesia, but only in participants with component temperatures in the noxious range (<19{degrees}C and >41{degrees}C). The TGI also elicited secondary hyperalgesia, even in participants with strictly innocuous thermal inputs. No participants developed brush allodynia. We observed sex differences in primary hyperalgesia: only males exhibited thermal grill-induced primary hyperalgesia. These findings suggest that the TGI is integrated in the spinal dorsal horn, potentially mediated by heat-pinch-cold (HPC) neurons, and, to some degree, by primary nociceptive afferents in males. This study shows that the calibrated TGI may have sex-dependent mechanisms and determines that HPC cells are involved in the illusory sensation of pain from innocuous thermal inputs.

neuroscience↗

bioRxiv2023

Pathological claustrum activity drives aberrant cognitive network processing in human chronic pain

Aberrant cognitive network activity and cognitive deficits are established features of chronic pain. However, the nature of cognitive network alterations associated with chronic pain and their underlying mechanisms require elucidation. Here, we report that the claustrum, a subcortical nucleus implicated in cognitive network modulation, is activated by acute painful stimulation and pain-predictive cues in healthy participants. Moreover, we discover pathological activity of the claustrum and a lateral aspect of the right dorsolateral prefrontal cortex (latDLPFC) in migraine patients. Dynamic causal modeling suggests a directional influence of the claustrum on activity in this latDLPFC region, and diffusion weighted imaging (DWI) verifies their structural connectivity. These findings advance understanding of claustrum function during acute pain and provide evidence of a possible circuit mechanism driving cognitive impairments in chronic pain.

neuroscience↗