Prefrontal cortex activation upon a demanding virtual hand-controlled task: A new frontier for neuroergonomics

open9noFunctional near-infrared spectroscopy (fNIRS) is a non-invasive vascular-based functional neuroimaging technology that can assess, simultaneously from multiple cortical areas, concentration changes in oxygenated-deoxygenated hemoglobin at the level of the cortical microcirculation blood vessels. fNIRS, with its high degree of ecological validity and its very limited requirement of physical constraints to subjects, could represent a valid tool for monitoring cortical responses in the research field of neuroergonomics. In virtual reality (VR) real situations can be replicated with greater control than those obtainable in the real world. Therefore, VR is the ideal setting where studies about neuroergonomics applications can be performed. The aim of the present study was to investigate, by a 20-channel fNIRS system, the dorsolateral/ventrolateral prefrontal cortex (DLPFC/VLPFC) in subjects while performing a demanding VR hand-controlled task (HCT). Considering the complexity of the HCT, its execution should require the attentional resources allocation and the integration of different executive functions. The HCT simulates the interaction with a real, remotely-driven, system operating in a critical environment. The hand movements were captured by a high spatial and temporal resolution 3-dimensional (3D) hand-sensing device, the LEAP motion controller, a gesture-based control interface that could be used in VR for tele-operated applications. Fifteen University students were asked to guide, with their right hand/forearm, a virtual ball (VB) over a virtual route (VROU) reproducing a 42 m narrow road including some critical points. The subjects tried to travel as long as possible without making VB fall. The distance traveled by the guided VB was 70.2 ± 37.2 m. The less skilled subjects failed several times in guiding the VB over the VROU. Nevertheless, a bilateral VLPFC activation, in response to the HCT execution, was observed in all the subjects. No correlation was found between the distance traveled by the guided VB and the corresponding cortical activation. These results confirm the suitability of fNIRS technology to objectively evaluate cortical hemodynamic changes occurring in VR environments. Future studies could give a contribution to a better understanding of the cognitive mechanisms underlying human performance either in expert or non-expert operators during the simulation of different demanding/fatiguing activities.openCarrieri, Marika; Petracca, Andrea; Lancia, Stefania; Basso Moro, Sara; Brigadoi, Sabrina; Spezialetti, Matteo; Ferrari, Marco; Placidi, Giuseppe; Quaresima, ValentinaCarrieri, Marika; Petracca, Andrea; Lancia, Stefania; BASSO MORO, Sara; Brigadoi, Sabrina; Spezialetti, Matteo; Ferrari, Marco; Placidi, Giuseppe; Quaresima, Valentin

PREFRONTAL CORTEX ACTIVATION DURING STORY ENCODING/RETRIEVAL: A MULTI-CHANNEL FUNCTIONAL NEAR-INFRARED SPECTROSCOPY STUDY

Encoding, storage and retrieval constitute three fundamental stages in information processing and memory. They allow for the creation of new memory traces, the maintenance and the consolidation of these traces over time, and the access and recover of the stored information from short or long-term memory. Functional near-infrared spectroscopy (fNIRS) is a non-invasive neuroimaging technique that measures concentration changes of oxygenated-hemoglobin (O2Hb) and deoxygenated-hemoglobin (HHb) in cortical microcirculation blood vessels by means of the characteristic absorption spectra of hemoglobin in the near-infrared range. In the present study, we monitored, using a sixteen-channel fNIRS system, the hemodynamic response during the encoding and retrieval processes (EP and RP, respectively) over the prefrontal cortex (PFC) of thirteen healthy subjects (27.2±2.6 y.) while were performing the Logical Memory Test (LMT) of the Wechsler Memory Scale. A LMT-related PFC activation was expected; specifically, it was hypothesized a neural dissociation between EP and RP. The results showed a heterogeneous O2Hb/HHb response over the mapped area during the EP and the RP, with a O2Hb progressive and prominent increment in ventrolateral PFC since the beginning of the EP. During the RP a broader activation, including the ventrolateral PFC, the dorsolateral PFC and the frontopolar cortex, was observed. This could be explained by the different contributions of the PFC regions in the EP and the RP. Considering the fNIRS applicability for the hemodynamic monitoring during the LMT performance, this study has demonstrated that fNIRS could be utilized as a valuable clinical diagnostic tool, and that it has the potential to be adopted in patients with cognitive disorders or slight working memory deficits

The role of Notch in the cardiovascular system: potential adverse effects of investigational Notch inhibitors

Targeting the Notch pathway is a new promising therapeutic approach for cancer patients. Inhibition of Notch is effective in the oncology setting because it causes a reduction of highly proliferative tumor cells and it inhibits survival of cancer stem cells which are considered responsible for tumor recurrence and metastasis. Additionally, since Delta- like ligand 4 (Dll4)- activated Notch signalling is a major modulator of angiogenesis, anti-Dll4 agents are being investigated to reduce vascularization of the tumor. Notch plays a major role in the heart during the development and, after birth, in response to cardiac damage. Therefore, agents used to inhibit Notch in the tumors (gamma secretase inhibitors and anti-Dll4 agents) could potentially affect myocardial repair. The past experience with trastuzumab and other tyrosine kinase inhibitors used for cancer therapy demonstrates that the possible cardiotoxicity of agents targeting shared pathways between cancer and heart and the vasculature should be considered. To date, Notch inhibition in cancer patients has resulted only in mild gastrointestinal toxicity. Little is known about the potential long term cardiotoxicity associated to Notch inhibition in cancer patients. In this review we will focus on mechanisms through which inhibition of Notch signalling could lead to cardiomyocytes and endothelial dysfunctions. These adverse effects could contrast with the benefits of therapeutic responses in cancer cells during times of increased cardiac stress and/or in the presence of cardiovascular risk facto