Neuroscience
-
Fibromyalgia (FM) is a syndrome characterized by chronic pain with depression as a frequent comorbidity. However, efficient management of the pain and depressive symptoms of FM is lacking. Given that endogenous oxytocin (OXT) contributes to the regulation of pain and depressive disorders, herein, we investigated the role of OXT in an experimental reserpine-induced FM model. ⋯ Treatment of these rats with clozapine-N-oxide (CNO), an hM3Dq-activating drug, significantly improved characteristic FM model-induced pathophysiological pain, but did not alter depressive-like behavior. The chemogenetically induced effects were reversed by pre-treatment with an OXT receptor antagonist, confirming the specificity of action via the OXT pathway. These results indicate that endogenous OXT may have analgesic effects in FM, and could be a potential target for effective pain management strategies for this disorder.
-
Opioid use disorder (OUD) is a major current cause of morbidity and mortality. Long-term exposure to short-acting opioids (MOP-r agonists such as heroin or fentanyl) results in complex pathophysiological changes to neuroimmune and neuroinflammatory functions, affected in part by peripheral mechanisms (e.g., cytokines in blood), and by neuroendocrine systems such as the hypothalamic-pituitary-adrenal (HPA) stress axis. There are important findings from preclinical models, but their role in the trajectory and outcomes of OUD in humans is not well understood. ⋯ The mechanistic roles of these neuroimmune and neuroinflammatory changes in the trajectory of OUD (including recovery and medication management) cannot be examined practically with postmortem data. Collection of longitudinal data in larger-scale human cohorts would allow examination of these mechanisms associated with OUD stage and progression. Given the heterogeneity in presentation of OUD, a precision medicine approach integrating multi-omic peripheral biomarkers and comprehensive phenotyping, including neuroimaging, can be beneficial in risk stratification, and individually optimized selection of interventions for individuals who will benefit, and assessments under refractory therapy.
-
Mapping variability in cortical spontaneous activity (CSA) is an essential goal of understanding various sources of dark brain energy in human neuroscience. CSA was traditionally characterized using resting-state functional MRI (rfMRI) at 1.5T or 3T magnets while recently with 7T-rfMRI. However, the utility and interpretability of 7T-rfMRI must first be established for its variability. ⋯ These effects were primarily located in the high-order associate cortex, parsing the corresponding changes in individual differences with respect to 7T-rfMRI: (1) higher connectivity variability between participants and the lower connectivity variability within individual participants, and (2) lower amplitude variability between participants and higher amplitude variability within participants. Our work, for the first time, demonstrated the variability of the human CSA across space, rfMRI settings/platforms, and individuals. We discussed the statistical implications of our findings on CSA-based experimental designs and reproducible neuroscience as well as their translational value for personalized applications.
-
Spontaneous and visual stimulation evoked firing sequences are distinct under desflurane anesthesia.
Recurring spike sequences are thought to underlie cortical computations and may be essential for information processing in the conscious state. How anesthesia at graded levels may influence spontaneous and stimulus-related spike sequences in visual cortex has not been fully elucidated. We recorded extracellular single-unit activity in the rat primary visual cortex in vivo during wakefulness and three levels of anesthesia produced by desflurane. ⋯ Flash-evoked spike sequences showed higher reliability and longer latency when stimuli were applied during DOWN states compared to UP states. At deeper levels, desflurane altered both UP state and flash-evoked spike sequences by selectively suppressing inhibitory neuron firing. The results reveal desflurane-induced complex changes in cortical firing sequences that may influence visual information processing.
-
Altered reward processing is increasingly recognised as a crucial mechanism underpinning apathy in many brain disorders. However despite its clinical relevance, little is known about the mechanisms of apathy following moderate-to-severe traumatic brain injury (TBI). In real-life situations, reward representations encompass both foreground (gains from current activity) and background (potential gains from the broader environment) elements. This latter variable provides a crucial set-point for switching behaviour in many naturalistic settings. We hypothesised apathy post-TBI would be associated with disrupted background reward sensitivity. ⋯ These results provide the first evidence directly linking disrupted background reward processing to apathy in any brain disorder. They identify a novel mechanism for apathy following moderate-to-severe TBI, and point towards novel interventions to improve this debilitating complication of head injury.