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Aim: Acute sleep deprivation has revealed altered executive cognitive functioning, including attention, working memory, and interference resolution. In the present study, we investigated brain hemodynamics and cognitive function measures using functional near-infrared spectroscopy (fNIRS). Methods: fNIRS was used to record cortical brain activity in a resting state scan, flanker task, and n-Back tasks under well-rested (WR, >6.5 h sleep for ≥3 days) and sleep-deprived conditions (SD, 28 h awake) in a repeated-measures study in 20 participants (7 female, mean age 20.1 ± 0.413). Results: Our results indicate decreased accuracy rates in the flanker task in the SD condition, suggesting reduced response inhibition capacity. In the flanker task, a significant increase of beta estimates was observed in the SD condition in the right dl-PFC, suggesting potential compensation (BH-FDR corrected p = 0.0418, t(19) = 3.51). There were no significant differences between WR and SD in n-back task accuracy rates or reaction times or in Flanker task reaction times. Otherwise, functional connectivity strengths were not significantly different between the WR and SD sessions on a group-level analysis for the resting state and all tasks (BH-FDR correction, p > 0.05). Conclusion: Our results provide insight into how insufficient sleep patterns affect interference resolution, and that fNIRS can reveal functional connectivity differences inter- and intra-individually in SD conditions.

Abstract Background Pain is a highly prevalent symptom experienced by patients across numerous rare musculoskeletal conditions. Much remains unknown regarding the central, neurobiological processes associated with clinical pain in musculoskeletal disease states. Fibrodysplasia ossificans progressiva (FOP) is an inherited condition characterized by substantial physical disability and pain. FOP arises from mutations of the bone morphogenetic protein (BMP) receptor Activin A receptor type 1 (ACVR1) causing patients to undergo painful flare-ups as well as heterotopic ossification (HO) of skeletal muscles, tendons, ligaments, and fascia. To date, the neurobiological processes that underlie pain in FOP have rarely been investigated. We examined pain and central pain mechanism in FOP as a model primary musculoskeletal condition. Central nervous system (CNS) functional properties were investigated in FOP patients (N = 17) stratified into low (0–3; 0–10 Scale) and high (≥ 4) pain cohorts using functional near-infrared spectroscopy (fNIRS). Associations among clinical pain, mental health, and physical health were also quantified using responses derived from a battery of clinical questionnaires. Results Resting-state fNIRS revealed suppressed power of hemodynamic activity within the slow-5 frequency sub-band (0.01–0.027 Hz) in the prefrontal cortex in high pain FOP patients, where reduced power of slow-5, prefrontal cortex oscillations exhibited robust negative correlations with pain levels. Higher clinical pain intensities were also associated with higher magnitudes of depressive symptoms. Conclusions Our findings not only demonstrate a robust coupling among prefrontal cortex functionality and clinical pain in FOP but lays the groundwork for utilizing fNIRS to objectively monitor and central pain mechanisms in FOP and other musculoskeletal disorders.

BackgroundCatheter radiofrequency (RF) ablation for cardiac arrhythmias is a painful procedure. Prior work using functional near-infrared spectroscopy (fNIRS) in patients under general anesthesia has indicated that ablation results in activity in pain-related cortical regions, presumably due to inadequate blockade of afferent nociceptors originating within the cardiac system. Having an objective brain-based measure for nociception and analgesia may in the future allow for enhanced analgesic control during surgical procedures. Hence, the primary aim of this study is to demonstrate that the administration of remifentanil, an opioid widely used during surgery, can attenuate the fNIRS cortical responses to cardiac ablation.Methods and findingsWe investigated the effects of continuous remifentanil on cortical hemodynamics during cardiac ablation under anesthesia. In a randomized, double-blinded, placebo (PL)-controlled trial, we examined 32 pediatric patients (mean age of 15.8 years,16 females) undergoing catheter ablation for cardiac arrhythmias at the Cardiology Department of Boston Children's Hospital from October 2016 to March 2020; 9 received 0.9% NaCl, 12 received low-dose (LD) remifentanil (0.25 mcg/kg/min), and 11 received high-dose (HD) remifentanil (0.5 mcg/kg/min). The hemodynamic changes of primary somatosensory and prefrontal cortices were recorded during surgery using a continuous wave fNIRS system. The primary outcome measures were the changes in oxyhemoglobin concentration (NadirHbO, i.e., lowest oxyhemoglobin concentration and PeakHbO, i.e., peak change and area under the curve) of medial frontopolar cortex (mFPC), lateral prefrontal cortex (lPFC) and primary somatosensory cortex (S1) to ablation in PL versus remifentanil groups. Secondary measures included the fNIRS response to an auditory control condition. The data analysis was performed on an intention-to-treat (ITT) basis. Remifentanil group (dosage subgroups combined) was compared with PL, and a post hoc analysis was performed to identify dose effects. There were no adverse events. The groups were comparable in age, sex, and number of ablations. Results comparing remifentanil versus PL show that PL group exhibit greater NadirHbO in inferior mFPC (mean difference (MD) = 1.229, 95% confidence interval [CI] = 0.334, 2.124, p < 0.001) and superior mFPC (MD = 1.206, 95% CI = 0.303, 2.109, p = 0.001) and greater PeakHbO in inferior mFPC (MD = -1.138, 95% CI = -2.062, -0.214, p = 0.002) and superior mFPC (MD = -0.999, 95% CI = -1.961, -0.036, p = 0.008) in response to ablation. S1 activation from ablation was greatest in PL, then LD, and HD groups, but failed to reach significance, whereas lPFC activation to ablation was similar in all groups. Ablation versus auditory stimuli resulted in higher PeakHbO in inferior mFPC (MD = 0.053, 95% CI = 0.004, 0.101, p = 0.004) and superior mFPC (MD = 0.052, 95% CI = 0.013, 0.091, p < 0.001) and higher NadirHbO in posterior superior S1 (Pos. SS1; MD = -0.342, 95% CI = -0.680, -0.004, p = 0.007) during ablation of all patients. Remifentanil group had smaller NadirHbO in inferior mFPC (MD = 0.098, 95% CI = 0.009, 0.130, p = 0.003) and superior mFPC (MD = 0.096, 95% CI = 0.008, 0.116, p = 0.003) and smaller PeakHbO in superior mFPC (MD = -0.092, 95% CI = -0.680, -0.004, p = 0.007) during both the stimuli. Study limitations were small sample size, motion from surgery, indirect measure of nociception, and shallow penetration depth of fNIRS only allowing access to superficial cortical layers.ConclusionsWe observed cortical activity related to nociception during cardiac ablation under general anesthesia with remifentanil. It highlights the potential of fNIRS to provide an objective pain measure in unconscious patients, where cortical-based measures may be more accurate than current evaluation methods. Future research may expand on this application to produce a real-time indication of pain that will aid clinicians in providing immediate and adequate pain treatment.Trial registrationClinicalTrials.gov NCT02703090.

Chronic postsurgical pain (CPSP) results from a cascade of events in the peripheral and central nervous system following surgery. Several clinical predictors, including the prior pain state, premorbid psychological state (e.g., anxiety, catastrophizing), intraoperative surgical load (establishment of peripheral and central sensitization), and acute postoperative pain management, may contribute to the patient’s risk of developing CPSP. However, research on the neurobiological and biobehavioral mechanisms contributing to pediatric CPSP and effective preemptive/treatment strategies are still lacking. Here we evaluate the peri-surgical process by identifying key problems and propose potential solutions for the pre-, intra-, and postoperative pain states to both prevent and manage the transition of acute to chronic pain. We propose an 8-step process involving preemptive and preventative analgesia, behavioral interventions, and the use of biomarkers (brain-based, inflammatory, or genetic) to facilitate timely evaluation and treatment of premorbid psychological factors, ongoing surgical pain, and postoperative pain to provide an overall improved outcome. By achieving this, we can begin to establish personalized, precision medicine for children and adolescents presenting to surgery and subsequent treatment selection.