Investigation of functional near-infrared spectroscopy signal quality and development of the hemodynamic phase correlation signal

SIGNIFICANCE: There is a longstanding recommendation within the field of fNIRS to use oxygenated ( HbO 2 ) and deoxygenated (HHb) hemoglobin when analyzing and interpreting results. Despite this, many fNIRS studies do focus on HbO 2 only. Previous work has shown that HbO 2 on its own is susceptible to systemic interference and results may mostly reflect that rather than functional activation. Studies using both HbO 2 and HHb to draw their conclusions do so with varying methods and can lead to discrepancies between studies. The combination of HbO 2 and HHb has been recommended as a method to utilize both signals in analysis. AIM: We present the development of the hemodynamic phase correlation (HPC) signal to combine HbO 2 and HHb as recommended to utilize both signals in the analysis. We use synthetic and experimental data to evaluate how the HPC and current signals used for fNIRS analysis compare. APPROACH: About 18 synthetic datasets were formed using resting-state fNIRS data acquired from 16 channels over the frontal lobe. To simulate fNIRS data for a block-design task, we superimposed a synthetic task-related hemodynamic response to the resting state data. This data was used to develop an HPC-general linear model (GLM) framework. Experiments were conducted to investigate the performance of each signal at different SNR and to investigate the effect of false positives on the data. Performance was based on each signal's mean T -value across channels. Experimental data recorded from 128 participants across 134 channels during a finger-tapping task were used to investigate the performance of multiple signals [ HbO 2 , HHb, HbT, HbD, correlation-based signal improvement (CBSI), and HPC] on real data. Signal performance was evaluated on its ability to localize activation to a specific region of interest. RESULTS: Results from varying the SNR show that the HPC signal has the highest performance for high SNRs. The CBSI performed the best for medium-low SNR. The next analysis evaluated how false positives affect the signals. The analyses evaluating the effect of false positives showed that the HPC and CBSI signals reflect the effect of false positives on HbO 2 and HHb. The analysis of real experimental data revealed that the HPC and HHb signals provide localization to the primary motor cortex with the highest accuracy. CONCLUSION: We developed a new hemodynamic signal (HPC) with the potential to overcome the current limitations of using HbO 2 and HHb separately. Our results suggest that the HPC signal provides comparable accuracy to HHb to localize functional activation while at the same time being more robust against false positives

Decreased Exercise-Induced Changes in Prefrontal Cortex Hemodynamics Are Associated With Depressive Symptoms

People with a depressed mood tend to perform poorly on executive function tasks, which require much of the prefrontal cortex (PFC), an area of the brain which has also been shown to be hypo-active in this population. Recent research has suggested that these aspects of cognition might be improved through physical activity and cognitive training. However, whether the acute effects of exercise on PFC activation during executive function tasks vary with depressive symptoms remains unclear. To investigate these effects, 106 participants were given a cardiopulmonary exercise test (CPET) and were administered a set of executive function tests directly before and after the CPET assessment. The composite effects of exercise on the PFC (all experimental blocks) showed bilateral activation changes in dorsolateral (BA46/9) and ventrolateral (BA44/45) PFC, with the greatest changes occurring in rostral PFC (BA10). The effects observed in right ventrolateral PFC varied depending on level of depressive symptoms (13% variance explained); the changes in activation were less for higher levels. There was also a positive relationship between CPET scores (VO2peak) and right rostral PFC, in that greater activation changes in right BA10 were predictive of higher levels of aerobic fitness (9% variance explained). Since acute exercise ipsilaterally affected this PFC subregion and the inferior frontal gyrus during executive function tasks, this suggests physical activity might benefit the executive functions these subregions support. And because physical fitness and depressive symptoms explained some degree of cerebral upregulation to these subregions, physical activity might more specifically facilitate the engagement of executive functions that are typically associated with hypoactivation in depressed populations. Future research might investigate this possibility in clinical populations, particularly the neural effects of physical activity used in combination with mental health interventions

Immune checkpoint inhibitors for advanced non-small cell lung cancer: emerging sequencing for new treatment targets

Lung cancer is the leading cause of cancer-related deaths in the world. Immune checkpoint inhibitors (ICI) stimulate cytotoxic lymphocyte activity against tumour cells. These agents are available for the treatment of nonsmall cell lung cancer (NSCLC) after failure of platinumbased therapy. One recent study has demonstrated that ICI monotherapy was superior to platinum-based chemotherapy for first-line treatment. Nevertheless, this benefit was only for a minority of the population (30%) whose tumour programmed death receptor ligand-1 (PD-L1) expression was above 50%. Therefore, several strategies are under investigation. One option for patients with PD-L1 expression lower than 50% may be the combination of ICI with platinum-based chemotherapy or with ICIs against different targets. However, all of these combinations are at an early stage of investigation and may be very expensive or toxic, producing several harmful adverse events.info:eu-repo/semantics/publishedVersio

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of non-small cell lung cancer (NSCLC)

Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for over 85% of all cases. Until recently, chemotherapy – characterized by some benefit but only rare durable responses – was the only treatment option for patients with NSCLC whose tumors lacked targetable mutations. By contrast, immune checkpoint inhibitors have demonstrated distinctly durable responses and represent the advent of a new treatment approach for patients with NSCLC. Three immune checkpoint inhibitors, pembrolizumab, nivolumab and atezolizumab, are now approved for use in first- and/or second-line settings for selected patients with advanced NSCLC, with promising benefit also seen in patients with stage III NSCLC. Additionally, durvalumab following chemoradiation has been approved for use in patients with locally advanced disease. Due to the distinct features of cancer immunotherapy, and rapid progress in the field, clinical guidance is needed on the use of these agents, including appropriate patient selection, sequencing of therapies, response monitoring, adverse event management, and biomarker testing. The Society for Immunotherapy of Cancer (SITC) convened an expert Task Force charged with developing consensus recommendations on these key issues. Following a systematic process as outlined by the National Academy of Medicine, a literature search and panel voting were used to rate the strength of evidence for each recommendation. This consensus statement provides evidence-based recommendations to help clinicians integrate immune checkpoint inhibitors into the treatment plan for patients with NSCLC. This guidance will be updated following relevant advances in the field

Intratumoral heterogeneity of programmed cell death ligand-1 expression is common in lung cancer

Programmed cell death ligand-1 (PD-L1) expression may predict the response to both programmed cell death-1 and PD-L1 inhibitors in lung cancer. However, the extent of intratumoral heterogeneity of PD-L1 expression, which may cause false negative results, is largely unexplored. We aimed to assess the intratumoral heterogeneity of PD-L1 expression in surgically resected lung cancer specimens by applying a novel method of tissue microarray, namely Spiral Arrays, which enables us to observe the heterogeneity in spiral-shaped tissue cores. Adenocarcinoma and squamous cell carcinoma specimens were obtained from consecutive patients with lung cancer who had undergone surgical resection at Nagasaki University Hospital (Nagasaki, Japan) since 2009. Small cell lung cancer and large cell carcinoma specimens were selected from patients in the same archive who had undergone resection since 1998. Spiral Arrays were constructed of spiral-shaped cores, prepared from representative blocks of each case, which were subjected to immunohistochemistry using an anti-PD-L1 antibody. Each core was divided into 8 segments and each segment was classified as either PD-L1-positive or PD-L1-negative using thresholds of 1.0%, 5.0%, 10.0%, and 50.0%, respectively. In total, 138 specimens were selected, including 60 adenocarcinomas, 59 squamous cell carcinomas, 12 small cell lung cancers, and 7 large cell carcinomas. The majority of specimens with PD-L1-positive segments exhibited heterogeneous expression (i.e., had a mixture of PD-L1-positive and PD-L1-negative segments within a core) irrespective of the threshold (1.0%, 66.7%; 5.0%, 74.4%; 10.0%, 75.8%; and 50.0%, 85.7%]. Large variations in the ratios of PD-L1-positive segments were observed. At least 50.0% of the segments within a core were negative in no fewer than 50.0% (range, 50.0?76.0%) of cases with heterogeneous PD-L1 expression. In conclusion, intratumoral heterogeneity of PD-L1 expression was frequently observed in cases of lung cancer. Thus, multiple tumor biopsy specimens may be needed to accurately determine the PD-L1 expression status