Cerebral Oxygenation and Activity During Surgical Repair of Neonates With Congenital Diaphragmatic Hernia: A Center Comparison Analysis

Background and aim: Neonatal brain monitoring is increasingly used due to reports of brain injury perioperatively. Little is known about the effect of sedatives (midazolam) and anesthetics (sevoflurane) on cerebral oxygenation (rScO2) and cerebral activity. This study aims to determine these effects in the perioperative period.Methods: This is an observational, prospective study in two tertiary pediatric surgical centers. All neonates with a congenital diaphragmatic hernia received perioperative cerebral oxygenation and activity measurements. Patients were stratified based on intraoperatively administrated medication: the sevoflurane group (continuous sevoflurane, bolus fentanyl, bolus rocuronium) and the midazolam group (continuous midazolam, continuous fentanyl, and continuous vecuronium).Results: Intraoperatively, rScO2 was higher in the sevoflurane compared to the midazolam group (84%, IQR 77–95 vs. 65%, IQR 59–76, p = < 0.001), fractional tissue oxygen extraction was lower (14%, IQR 5–21 vs. 31%, IQR 29–40, p = < 0.001), the duration of hypoxia was shorter (2%, IQR 0.4–9.6 vs. 38.6%, IQR 4.9–70, p = 0.023), and cerebral activity decreased more: slow delta: 2.16 vs. 4.35 μV2 (p = 0.0049), fast delta: 0.73 vs. 1.37 μV2 (p = < 0.001). In the first 30 min of the surgical procedure, a 3-fold increase in fast delta (10.48–31.22 μV2) and a 5-fold increase in gamma (1.42–7.58 μV2) were observed in the midazolam group.Conclusion: Sevoflurane-based anesthesia resulted in increased cerebral oxygenation and decreased cerebral activity, suggesting adequate anesthesia. Midazolam-based anesthesia in neonates with a more severe CDH led to alarmingly low rScO2 values, below hypoxia threshold, and increased values of EEG power during the first 30 min of surgery. This might indicate conscious experience of pain. Integrating population-pharmacokinetic models and multimodal neuromonitoring are needed for personalized pharmacotherapy in these vulnerable patients.Trial Registration:https://www.trialregister.nl/trial/6972, identifier: NL6972.

Therapeutic Effects and Central Mechanism of Acupuncture and Moxibustion for Treating Functional Dyspepsia: Study Protocol for An fMRI-Based Randomized Controlled Trial

Background: Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders, with a high prevalence and significant influence on the quality of life (QoL). Either acupuncture or moxibustion is effective for dyspepsia, which is confirmed by both ancient documents and modern research. However, the therapeutic advantage and underlying mechanism between acupuncture and moxibustion for FD remain unclear. Methods: This randomized controlled fMRI trial aims to (i) evaluate the therapeutic advantages of acupuncture and moxibustion treatment for FD; (ii) investigate the similarities and differences in cerebral activity elicited by acupuncture and moxibustion; and (iii) analyze the possible correlations between brain responses and clinical variables thus to explore the potential central mechanism of acupuncture and moxibustion for treating FD. Ninety-two FD patients will be randomly assigned to either the acupuncture group or the moxibustion group in a 1:1 ratio. Twenty sessions of acupuncture or moxibustion treatment over 4 weeks will be performed on each patient. The short form Leeds Dyspepsia Questionnaire, the Nepean Dyspepsia Index, etc. are used to evaluate the therapeutic effects. The Heart Rate Variability will be analyzed to investigate the autonomic nerve function. Thirty-six FD patients in each group will be randomly selected for the fMRI scan to detect cerebral activity changes. Discussion: We expect the results will deepen our knowledge on the clinical value and underlying mechanism of acupuncture and moxibustion, and provide a reference for a better selection of interventions for treating FD.Trial Registration: Chinese Clinical Trial Registry (www.chictr.org.cn), ChiCTR2100049496 (registration date: 2nd August, 2021).

Efficacy and central mechanism of acupuncture treatment in patients with neck pain: study protocol for a randomized controlled trial

Background Acupuncture is effective for reducing the symptoms of neck pain (NP). However, the underlying mechanisms are not fully elucidated. Based on evaluating the efficacy of two acupuncture prescriptions for treating NP, this study aims to investigate the potential central mechanism of acupuncture treatment for NP by functional magnetic resonance imaging (fMRI). Methods This is a randomized controlled trial; 86 patients will be randomly assigned into two acupuncture treatment groups at a ratio of 1:1. The whole study period includes 2 weeks baseline, 2 weeks treatments, and 12 weeks follow-up (4 and 12 weeks after treatment). The pain severity, the neck disability index, the cervical range of motion, and the pressure pain threshold, etc., will be used to evaluate the clinical efficacy of two acupuncture prescriptions for NP treatment. The MRI scans will be performed to detect cerebral activity changes of 20 patients in each group. The clinical data and MRI data will be analyzed, respectively. Pearson correlation coefficient will be used to evaluate the association between changes of cerebral activity features and improvement of clinical symptoms. Discussion The results will provide further evidence for the clinical application of acupuncture in the treatment of NP. Trial registration Chinese Clinical Trial Registry ChiCTR2000040930. Registered on 16 December 2020.

Feasibility and Biological Activity of a Ketogenic/Intermittent-Fasting Diet in Patients With Glioma

OBJECTIVE:To examine the feasibility, safety, systemic biological activity, and cerebral activity of a ketogenic dietary intervention in patients with glioma.METHODS:25 patients with biopsy-confirmed WHO Grade 2-4 astrocytoma with stable disease following adjuvant chemotherapy were enrolled in an 8-week GLioma Atkins-based Diet (GLAD). GLAD consisted of 2 fasting days (calories<20% calculated estimated needs) interleaved between 5 modified Atkins diet days (net carbohydrates≤20 gm/day) each week. The primary outcome was dietary adherence by food records. Markers of systemic and cerebral activity included weekly urine ketones, serum insulin, glucose, hemoglobin A1c, IGF-1, and MR spectroscopy at baseline and week 8.RESULTS:21 patients completed the study (84%). 80% of patients reached ≥40 mg/dL urine acetoacetate during the study. 48% of patients were adherent by food record. The diet was well-tolerated with two grade 3 adverse events (neutropenia, seizure). Measures of systemic activity including hemoglobin A1c, insulin, and fat body mass decreased significantly, while lean body mass increased. MR spectroscopy demonstrated increased ketone concentrations (β-hydroxybutyrate (bHB) and acetone (Ace)) in both lesional and contralateral brain, compared to baseline. Average ketonuria correlated with cerebral ketones in lesional (tumor) and contralateral brain (bHB Rs 0.52, p=0.05). Sub-group analysis of IDH-mutant glioma showed no differences in cerebral metabolites after controlling for ketonuria.CONCLUSIONS:The GLAD dietary intervention, while demanding, produced meaningful ketonuria, and significant systemic and cerebral metabolic changes in participants. Ketonuria in participants correlated with cerebral ketone concentration and appear to be a better indicator of systemic activity than patient-reported food records.

EEG Activity During Mental Influence on a Random Signal Generator

This preliminary study is based on 38 experimental sittings in which 22 participants attempted to mentally influence an electronic circuit called RSG (Random Signal Generator), while their cerebral activity was recorded by a 14-channel EEG. Subject to sampling, signal peaks with an absolute value greater than a predetermined threshold were selected from the analogical RSG output by a computer program. Whenever a signal exceeded the threshold, an audible ‘beep’ sounded and the participant was asked to mentally increase the frequency of these beeps as much as possible, because a higher beep rate meant a successful mental influence attempt on the RSG. An important objective was to verify the existence of any relationship between a successful mental influence of the RSG and cerebral activity in the participant attempting the influence. Compared to an equal number of ‘inactive’ sittings made without anyone attempting mental action, the ‘active’ sittings show a small increase in the average number of beeps/minute, but in particular a significant increase in the emitted beeps within 1.5 seconds of the previous beep (P <0.025). The experimental sittings were divided into two groups (around 50% each), of which the first had better results, and only the frontal and fronto-temporal symmetrical EEG locations (AF3, AF4, F7, F8, F3, F4, Fc5, Fc6) were examined. The better group showed a significant reduction in Brain Synchrony (P < 0.03) together with an equally significant increase in Beta and Gamma 15-42 Hz (P < 0.03) activity. These differences were interpreted as an effect of greater mental work performed by the better group during mental influence of the RSG. This is the first study to investigate the relationship between EEG activity and mind-matter (PK) interaction at a distance; indeed all studies devoted to PK have only focused attention on the object of attempted mental action, which was predominantly an RNG (Random Number Generator).

Efficacy And Central Mechanism of Acupuncture Treatment In Patients With Neck Pain: Study Protocol For A Randomized Controlled Trial

Background: Acupuncture is effective for reducing the symptoms of neck pain (NP). However, the underlying mechanisms are not fully elucidated. Based on evaluating the efficacy of two acupuncture prescriptions for treating NP. This study aims to investigate the potential central mechanism of acupuncture treatment for NP by functional magnetic resonance imaging (fMRI). Methods: This is a randomized controlled trial, 86 patients will be randomly assigned into two acupuncture treatment groups at a ratio of 1:1. The whole study period includes 2 weeks baseline, 2 weeks treatments and 12 weeks follow-up (4 and 12 weeks after treatment). The pain severity, the neck disability index, the cervical range of motion, the pressure pain threshold, etc. will be used to evaluate clinical efficacy of two acupuncture prescriptions for NP treatment. The MRI scans will be performed to detect cerebral activity changes of 20 patients in each group. The clinical data and MRI data will be analysed, respectively. Pearson correlation coefficient will be used to evaluate the association between changes of cerebral activity features and improvement of clinical symptoms.Discussion: The results might provide further evidence for the clinical application of acupuncture in the treatment of NP.Trial registration: Chinese Clinical Trial Registry, ChiCTR2000040930. Registered on December 16, 2020.

DDRE-31. FEASIBILITY AND BIOLOGIC ACTIVITY OF A KETOGENIC / INTERMITTENT FASTING DIET IN GLIOMA PATIENTS

BACKGROUND There has been increasing interest in exploring ketogenic diet therapies (KDT) in patients with glioma given the poor prognosis. The purpose of this single-arm, open label phase 2 study was to rigorously examine the feasibility, safety, systemic biological activity, and cerebral activity of a KDT in patients with glioma. METHODS 25 patients with biopsy-confirmed WHO Grade 2–4 astrocytoma with stable disease following adjuvant chemotherapy were enrolled in an 8-week GLioma Atkins-based Diet (GLAD). GLAD consisted of 2 fasting days (calories&lt;20% calculated estimated needs) interleaved between 5 modified Atkins diet days (net carbohydrates≤20 gm/day) each week. The primary outcome was dietary adherence by food records. Markers of systemic and cerebral activity included weekly urine ketones, serum insulin, glucose, hemoglobin A1c, IGF-1, and MR spectroscopy at baseline and week 8. RESULTS 21 patients completed the study. 80% of patients reached ≥40 mg/dL urine acetoacetate during the study. 48% of patients were adherent by food record. The diet was well-tolerated with two grade 3 adverse events (neutropenia, seizure). Measures of systemic activity including hemoglobin A1c, insulin, and fat body mass decreased significantly, while lean body mass increased. MR spectroscopy demonstrated increased ketone concentrations (β-hydroxybutyrate (bHB) and acetone (Ace)) in both lesional and contralateral brain, compared to baseline. Higher total choline (tCho) and glutamine (Gln) levels were observed in lesional as compared to contralateral brain at baseline, and both decreased following intervention. Average ketonuria correlated with cerebral ketones in lesional (tumor) and contralateral brain (bHB Rs0.52, p=0.05). There were no differences in cerebral metabolites in IDH-mutant glioma after controlling for ketonuria. CONCLUSIONS The GLAD dietary intervention, while demanding, produced meaningful ketonuria, and significant systemic and cerebral metabolic changes in participants. Participant ketonuria correlated with cerebral ketone concentration and appears to be a better indicator of systemic activity than patient-reported food records.

Dynamic Changes of Amplitude of Low-Frequency Fluctuations in Patients With Diabetic Retinopathy

Background: Growing evidence demonstrate that diabetic retinopathy (DR) patients have a high risk of cognitive decline and exhibit abnormal brain activity. However, neuroimaging studies thus far have focused on static cerebral activity changes in DR patients. The characteristics of dynamic cerebral activity in patients with DR are poorly understood.Purpose: The purpose of the study was to investigate the dynamic cerebral activity changes in patients with DR using the dynamic amplitude of low-frequency fluctuation (dALFF) method.Materials and methods: Thirty-four DR patients (18 men and 16 women) and 38 healthy controls (HCs) (18 males and 20 females) closely matched in age, sex, and education were enrolled in this study. The dALFF method was used to investigate dynamic intrinsic brain activity differences between the DR and HC groups.Results: Compared with HCs, DR patients exhibited increased dALFF variability in the right brainstem, left cerebellum_8, left cerebellum_9, and left parahippocampal gyrus. In contrast, DR patients exhibited decreased dALFF variability in the left middle occipital gyrus and right middle occipital gyrus.Conclusion: Our study highlighted that DR patients showed abnormal variability of dALFF in the visual cortices, cerebellum, and parahippocampal gyrus. These findings suggest impaired visual and motor and memory function in DR individuals. Thus, abnormal dynamic spontaneous brain activity might be involved in the pathophysiology of DR.