Case Series: Cemiplimab and Nivolumab Immunotherapy as Promising Treatment in Advanced or Metastatic Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer. Surgery is usually curative; however, some locally advanced or metastatic CSCC may be unresectable. Current novel therapeutic options with immune checkpoint inhibition (ICI) of programmed-death receptor 1 (PD-1) such as cemiplimab and nivolumab have demonstrated promising and sustained results with good tolerability in patients with CSCC. This study looks at 2 cases of CSCC treated with cemiplimab and nivolumab, respectively, demonstrating dramatic response within 2 cycles with significant reduction in tumour size and minimal toxicities or adverse outcomes reported. Immunotherapy has shown positive results as an effective treatment option for unresectable, recurrent, or metastatic CSCC. It is currently approved for use in the USA and Europe.

Standardised images of novel objects created with generative adversarial networks.

An enduring question in cognitive science is how perceptually novel objects are processed. Addressing this issue has been limited by the absence of a standardised set of object-like stimuli that appear realistic, but cannot possibly have been previously encountered. To this end, we created a dataset, at the core of which are images of 400 perceptually novel objects. These stimuli were created using Generative Adversarial Networks that integrated features of everyday stimuli to produce a set of synthetic objects that appear entirely plausible, yet do not in fact exist. We curated an accompanying dataset of 400 familiar stimuli, which were matched in terms of size, contrast, luminance, and colourfulness. For each object, we quantified their key visual properties (edge density, entropy, symmetry, complexity, and spectral signatures). We also confirmed that adult observers (N = 390) perceive the novel objects to be less familiar, yet similarly engaging, relative to the familiar objects. This dataset serves as an open resource to facilitate future studies on visual perception.

When knowledge hurts: humans are willing to receive pain for obtaining non-instrumental information.

Humans and other animals value information that reduces uncertainty or leads to pleasurable anticipation, even if it cannot be used to gain tangible rewards or change outcomes. In exchange, they are willing to incur significant costs, sacrifice rewards or invest effort. We investigated whether human participants were also willing to endure pain-a highly salient and aversive cost-to obtain such information. Forty participants performed a computer-based task. On each trial, they observed a coin flip, with each side associated with different monetary rewards of varying magnitude. Participants could choose to endure a painful stimulus (low, moderate or high pain) to learn the outcome of the coin flip immediately. Importantly, regardless of their choice, winnings were always earned, rendering this information non-instrumental. Results showed that agents were willing to endure pain in exchange for information, with a lower likelihood of doing so as pain levels increased. Both higher average rewards and a larger variance between the two possible rewards independently increased the willingness to accept pain. Our results show that the intrinsic value of escaping uncertainty through non-instrumental information is sufficient to offset pain experiences, suggesting a shared mechanism through which these can be directly compared.

Acute exercise as a modifier of neocortical plasticity and aperiodic activity in the visual cortex.

Long-term potentiation (LTP) is a form of neuroplasticity commonly implicated in mechanistic models of learning and memory. Acute exercise can boost LTP in the motor cortex, and is associated with a shift in excitation/inhibition (E:I) balance, but whether this extends to other regions such as the visual cortex is unknown. We investigated the effect of a preceding bout of exercise on LTP induction and the E:I balance in the visual cortex using electroencephalography (EEG). Young adults (N = 20, mean age = 24.20) engaged in 20 min of high-intensity interval training (HIIT) exercise and rest across two counterbalanced sessions. LTP was induced using a high frequency presentation of a visual stimulus; a "visual tetanus". Established EEG markers of visual LTP, the N1b and P2 component of the visual evoked potential, and an EEG-derived measure of the E:I balance, the aperiodic exponent, were measured before and after the visual tetanus. As expected, there was a potentiation of the N1b following the visual tetanus, with specificity to the tetanised stimulus, and a non-specific potentiation of the P2. These effects were not sensitive to a preceding bout of exercise. However, the E:I balance showed a late shift towards inhibition following the visual tetanus. A preceding bout of exercise resulted in specificity of this E:I balance shift to the tetanised stimulus, that was not seen following rest. This novel finding suggests a possible exercise-induced tuning of the visual cortex to stimulus details following LTP induction.

The availability of non-instrumental information increases risky decision-making.

Contemporary models of decision-making under risk focus on estimating the final value of each alternative course of action. According to such frameworks, information that has no capacity to alter a future payoff (i.e., is "non-instrumental") should have little effect on one's preference for risk. Importantly, however, recent work has shown that information, despite being non-instrumental, may nevertheless exert a striking influence on behavior. Here, we tested whether the opportunity to passively observe the sequence of events following a decision could modulate risky behavior, even if that information could not possibly influence the final result. Across three experiments, 71 individuals chose to accept or reject gambles on a five-window slot machine. If a gamble was accepted, each window was sequentially revealed prior to the outcome being declared. Critically, we informed participants about which windows would subsequently provide veridical information about the gamble outcome, should that gamble be accepted. Our analyses revealed three key findings. First, the opportunity to observe the consequences of one's choice significantly increased the likelihood of gambling, despite that information being entirely non-instrumental. Second, this effect generalized across different stakes. Finally, choices were driven predominantly by the likelihood that information could result in an earlier resolution of uncertainty. These findings demonstrate the importance of anticipatory information to decision-making under risk. More broadly, we provide strong evidence for the utility of non-instrumental information, by demonstrating its capacity to modulate primary economic decisions that should be driven by more motivationally salient variables associated with risk and reward.

Evaluating UV254 absorbance reductions in landfill leachate for municipal sewage co-treatment through timed UV/electrooxidation.

Landfill leachate contains dissolved organic matter (DOM) exhibiting high ultraviolet absorbance at 254 nm (UVA254). The UVA254 limits leachate co-treatment with municipal sewage by hindering the downstream UV disinfection efficiency at wastewater treatment plants. Here, we alleviated the UVA254 by timing the radiation in a UV/electrooxidation (UV/EO) process to accelerate reactive species formation. At 200 A·m-2, the UV radiation was delayed by 10 min to accumulate 21 mg·L-1 as Cl2, which enhanced the initial radical formation rate by 5.25 times compared with a simultaneous UV/EO. The timed operation increased the steady-state concentrations of ClO• by 700 times to 4.11 × 10-14 M and reduced the leachate UVA254 by 78.2% after 60 min. We identified that aromatic formulas with low oxygen content were susceptible to UV/EO from Fourier-transform ion cyclotron resonance mass spectrometry analysis. The toxicity of the treated leachate and generated byproducts was assessed through specific oxygen uptake rates (SOUR) and developmental assays with Platynereis dumerilii. After quenching the residual chlorine, leachate co-treatment at 3.5% v/v presented minimal toxicological risk. Our findings provide operational insights for applying UV/EO in high UVA254 matrices such as landfill leachate.

Hedonism as a motive for information search: biased information-seeking leads to biased beliefs.

Confirmation bias in information-search contributes to the formation of polarized echo-chambers of beliefs. However, the role of valence on information source selection remains poorly understood. In Experiment 1, participants won financial rewards depending on the outcomes of a set of lotteries. They were not shown these outcomes, but instead could choose to view a prediction of each lottery outcome made by one of two sources. Before choosing their favoured source, participants were first shown a series of example predictions made by each. The sources systematically varied in the accuracy and positivity (i.e., how often they predicted a win) of their predictions. Hierarchical Bayesian modeling indicated that both source accuracy and positivity impacted participants' choices. Importantly, those that viewed more positively-biased information believed that they had won more often and had higher confidence in those beliefs. In Experiment 2, we directly assessed the effect of positivity on the perceived credibility of a source. In each trial, participants watched a single source making a series of predictions of lottery outcomes and rated the strength of their beliefs in each source. Interestingly, positively-biased sources were not seen as more credible. Together, these findings suggest that positively-biased information is sought partly due to the desirable emotional state it induces rather than having enhanced perceived credibility. Information sought on this basis nevertheless produced consequential biased beliefs about the world-state, highlighting a potentially key role for hedonic preferences in information selection and subsequent belief formation.

Resonance as a Design Strategy for AI and Social Robots.

Resonance, a powerful and pervasive phenomenon, appears to play a major role in human interactions. This article investigates the relationship between the physical mechanism of resonance and the human experience of resonance, and considers possibilities for enhancing the experience of resonance within human-robot interactions. We first introduce resonance as a widespread cultural and scientific metaphor. Then, we review the nature of "sympathetic resonance" as a physical mechanism. Following this introduction, the remainder of the article is organized in two parts. In part one, we review the role of resonance (including synchronization and rhythmic entrainment) in human cognition and social interactions. Then, in part two, we review resonance-related phenomena in robotics and artificial intelligence (AI). These two reviews serve as ground for the introduction of a design strategy and combinatorial design space for shaping resonant interactions with robots and AI. We conclude by posing hypotheses and research questions for future empirical studies and discuss a range of ethical and aesthetic issues associated with resonance in human-robot interactions.

Heightened effort discounting is a common feature of both apathy and fatigue.

Apathy and fatigue have distinct aetiologies, yet can manifest in phenotypically similar ways. In particular, each can give rise to diminished goal-directed behaviour, which is often cited as a key characteristic of both traits. An important issue therefore is whether currently available approaches are capable of distinguishing between them. Here, we examined the relationship between commonly administered inventories of apathy and fatigue, and a measure of goal-directed activity that assesses the motivation to engage in effortful behaviour. 103 healthy adults completed self-report inventories on apathy (the Dimensional Apathy Scale), and fatigue (the Multidimensional Fatigue Inventory, and/or Modified Fatigue Impact Scale). In addition, all participants performed an effort discounting task, in which they made choices about their willingness to engage in physically effortful activity. Importantly, self-report ratings of apathy and fatigue were strongly correlated, suggesting that these inventories were insensitive to the fundamental differences between the two traits. Furthermore, greater effort discounting was strongly associated with higher ratings across all inventories, suggesting that a common feature of both traits is a lower motivation to engage in effortful behaviour. These results have significant implications for the assessment of both apathy and fatigue, particularly in clinical groups in which they commonly co-exist.

Over the rainbow: Guidelines for meaningful use of colour maps in neurophysiology.

Visualization of complex data is commonplace in neurophysiology research. Here, we highlight specific perceptual issues related to the ongoing misuse of variations of the rainbow colour scheme, with a particular emphasis on time-frequency decompositions in electrophysiology as an illustrative example. We review the risks of biased interpretation of neurophysiological data in this context, and provide guidelines to improve the use of colour maps to visualise complex, multidimensional data in neurophysiology research.

Dissociable theta networks underlie the switch and mixing costs during task switching.

During task-switching paradigms, both event-related potentials and time-frequency analyses show switch and mixing effects at frontal and parietal sites. Switch and mixing effects are associated with increased power in broad frontoparietal networks, typically stronger in the theta band (~4-8 Hz). However, it is not yet known whether mixing and switch costs rely upon common or distinct networks. In this study, we examine proactive and reactive control networks linked to task switching and mixing effects, and whether strength of connectivity in these networks is associated with behavioural outcomes. Participants (n = 197) completed a cued-trials task-switching paradigm with concurrent electroencephalography, after substantial task practice to establish strong cue-stimulus-response representations. We used inter-site phase clustering, a measure of functional connectivity across electrode sites, to establish cross-site connectivity from a frontal and a parietal seed. Distinct theta networks were activated during proactive and reactive control periods. During the preparation interval, mixing effects were associated with connectivity from the frontal seed to parietal sites, and switch effects with connectivity from the parietal seed to occipital sites. Lateralised occipital connectivity was common to both switch and mixing effects. After target onset, frontal and parietal seeds showed a similar pattern of connectivity across trial types. These findings are consistent with distinct and common proactive control networks and common reactive networks in highly practised task-switching performers.

Choosing increases the value of non-instrumental information.

Curiosity pervades all aspects of human behaviour and decision-making. Recent research indicates that the value of information is determined by its propensity to reduce uncertainty, and the hedonic value of the outcomes it predicts. Previous findings also indicate a preference for options that are freely chosen, compared to equivalently valued alternatives that are externally assigned. Here, we asked whether the value of information also varies as a function of self- or externally-imposed choices. Participants rated their preference for information that followed either a self-chosen decision, or an externally imposed condition. Our results showed that choosing a lottery significantly increased the subjective value of information about the outcome. Computational modelling indicated that this change in information-seeking behaviour was not due to changes in the subjective probability of winning, but instead reflected an independent effect of choosing on the value of resolving uncertainty. These results demonstrate that agency over a prospect is an important source of information value.

Task-switching costs have distinct phase-locked and nonphase-locked EEG power effects.

Event-related potentials (ERPs) and total time-frequency power analyses have shown that performance costs during task switching are related to differential preparation to switch tasks (switch cost) and repeat the same task (mixing cost) during both proactive control (cue-to-target interval; CTI) and reactive control (post-target). The time-frequency EEG signal is comprised of both phase-locked activity (associated with stimulus-specific processes) and nonphase-locked activity (represents processes thought to persist over longer timeframes and do not contribute to the average ERP). In the present study, we used a cued task-switching paradigm to examine whether phase-locked and nonphase-locked power are differentially modulated by switch and mixing effects in intervals associated with the need for proactive control (CTI) and reactive control (post-target interval). Phase-locked activity was observed in the theta and alpha bands, closely resembled that seen for total power, and was consistent with switch and mixing ERP positivities. Nonphase-locked analyses showed theta and alpha power effects for both switch and mixing effects early in the CTI and as well as more sustained alpha and beta activity around cue onset, and extending from mid-CTI into the post-target interval. Nonphase-locked activity in pretarget alpha and posttarget theta power were both correlated with response time mixing cost. These findings provide novel insight into phase-locked and nonphase-locked activity associated with switch and mixing costs that are not evident with ERP or total time-frequency analyses.

Does cognitive control ability mediate the relationship between reward-related mechanisms, impulsivity, and maladaptive outcomes in adolescence and young adulthood?

Neurobiological models explain increased risk-taking behaviours in adolescence and young adulthood as arising from staggered development of subcortical reward networks and prefrontal control networks. In this study, we examined whether individual variability in impulsivity and reward-related mechanisms is associated with higher level of engagement in risky behaviours and vulnerability to maladaptive outcomes and whether this relationship is mediated by cognitive control ability. A community sample of adolescents, young adults, and adults (age = 15-35 years) completed self-report measures and behavioural tasks of cognitive control, impulsivity, and reward-related mechanisms, and self-reported level of maladaptive outcomes. Behavioural, event-related potential (ERP), and multivariate pattern analysis (MVPA) measures of proactive control were derived from a task-switching paradigm. Adolescents, but not young adults, reported higher levels of impulsivity, reward-seeking behaviours and maladaptive outcomes than adults. They also had lower cognitive control ability, as measured by both self-report and task-based measures. Consistent with models of risk-taking behaviour, self-reported level of cognitive control mediated the relationship between self-reported levels of impulsivity and psychological distress, but the effect was not moderated by age. In contrast, there was no mediation effect of behavioural or EEG-based measures of cognitive control. These findings suggest that individual variability in cognitive control is more crucial to the relationship between risk-taking/impulsivity and outcomes than age itself. They also highlight large differences in measurement between self-report and task-based measures of cognitive control and decision-making under reward conditions, which should be considered in any studies of cognitive control.

Frontal theta predicts specific cognitive control-induced behavioural changes beyond general reaction time slowing.

Investigations into the neurophysiological underpinnings of control suggest that frontal theta activity is increased with the need for control. However, these studies typically show this link by reporting associations between increased theta and RT slowing - a process that is contemporaneous with cognitive control but does not strictly reflect the specific use of control. In this study, we assessed frontal theta responses that underpinned the switch cost in task switching - a specific index of cognitive control that does not rely exclusively on RT slowing. Here, we utilised a single-trial regression approach to assess 1) how cognitive control demands beyond simple RT slowing were linked to midfrontal theta and 2) whether midfrontal theta effects remained stable over time. In a large cohort that included a longitudinal subsample, we found that midfrontal theta was modulated by switch costs, with enhanced theta power when preparing to switch vs. repeating a task. These effects were reliable after a two-year interval (Cronbach's α.39-0.74). In contrast, we found that trial-by-trial modulations of midfrontal theta power predicted the size of the switch cost - so that switch trials with increased theta produced smaller switch costs. Interestingly, these relationships between theta and behaviour were less stable over time (Cronbach's α 0-0.61), with participants first using both delta and theta bands to influence behaviour whereas after two years only theta associations with behaviour remained. Together, these findings suggest midfrontal theta supports the need for control beyond simple RT slowing and reveal that midfrontal theta effects remain relatively stable over time.

Neurosurgery and Medical Management of Severe Head Injury.

Management of the patient with moderate to severe brain injury in any environment can be time consuming and resource intensive. In the austere or hostile environment, the challenges to deliver care to this patient population are magnified. These guidelines have been developed by acknowledging commonly recognized recommendations for neurosurgical and neuro-critical care patients and augmenting those evaluations and interventions based on the experience of neurosurgeons, trauma surgeons, and intensivists who have delivered care during recent coalition conflicts.

Resting State Electroencephalography and Sports-Related Concussion: A Systematic Review.

Sports-related concussion is associated with a range of short-term functional deficits that are commonly thought to recover within a two-week post-injury period for most, but certainly not all, persons. Resting state electroencephalography (rs-EEG) may prove to be an affordable, accessible, and sensitive method of assessing severity of brain injury and rate of recovery after a concussion. This article presents a systematic review of rs-EEG in sports-related concussion. A systematic review of articles published in the English language, up to June 2017, was retrieved via PsychINFO, Medline, Medline In Process, Embase, SportDiscus, CINAHL, and Cochrane Library, Reviews, and Trials. The following key words were used for database searches: electroencephalography, quantitative electroencephalography, qEEG, cranio-cerebral trauma, mild traumatic brain injury, mTBI, traumatic brain injury, brain concussion, concussion, brain damage, sport, athletic, and athlete. Observational, cohort, correlational, cross-sectional, and longitudinal studies were all included in the current review. Sixteen articles met inclusion criteria, which included data on 504 athletes and 367 controls. All 16 articles reported some abnormality in rs-EEG activity after a concussion; however, the cortical rhythms that were affected varied. Despite substantial methodological and analytical differences across the 16 studies, the current review suggests that rs-EEG may provide a reliable technique to identify persistent functional changes in athletes after a concussion. Because of the varied approaches, however, considerable work is needed to establish a systematic methodology to assess its efficacy as a marker of return-to-play.

Event-Related Potential Responses to Task Switching Are Sensitive to Choice of Spatial Filter.

Event-related potential (ERP) studies using the task-switching paradigm show that multiple ERP components are modulated by activation of proactive control processes involved in preparing to repeat or switch task and reactive control processes involved in implementation of the current or new task. Our understanding of the functional significance of these ERP components has been hampered by variability in their robustness, as well as their temporal and scalp distribution across studies. The aim of this study is to examine the effect of choice of reference electrode or spatial filter on the number, timing and scalp distribution of ERP elicited during task-switching. We compared four configurations, including the two most common (i.e., average mastoid reference and common average reference) and two novel ones that aim to reduce volume conduction (i.e., reference electrode standardization technique (REST) and surface Laplacian) on mixing cost and switch cost effects in cue-locked and target-locked ERP waveforms in 201 healthy participants. All four spatial filters showed the same well-characterized ERP components that are typically seen in task-switching paradigms: the cue-locked switch positivity and target-locked N2/P3 effect. However, both the number of ERP effects associated with mixing and switch cost, and their temporal and spatial resolution were greater with the surface Laplacian transformation which revealed rapid temporal adjustments that were not identifiable with other spatial filters. We conclude that the surface Laplacian transformation may be more suited to characterize EEG signatures of complex spatiotemporal networks involved in cognitive control.

An information theory account of late frontoparietal ERP positivities in cognitive control.

ERP research on task switching has revealed distinct transient and sustained positive waveforms (latency circa 300-900 ms) while shifting task rules or stimulus-response (S-R) mappings. However, it remains unclear whether such switch-related positivities show similar scalp topography and index context-updating mechanisms akin to those posed for domain-general (i.e., classic P300) positivities in many task domains. To examine this question, ERPs were recorded from 31 young adults (18-30 years) while they were intermittently cued to switch or repeat their perceptual categorization of Gabor gratings varying in color and thickness (switch task), or else they performed two visually identical control tasks (go/no-go and oddball). Our task cueing paradigm examined two temporarily distinct stages of proactive rule updating and reactive rule execution. A simple information theory model helped us gauge cognitive demands under distinct temporal and task contexts in terms of low-level S-R pathways and higher-order rule updating operations. Task demands modulated domain-general (indexed by classic oddball P3) and switch positivities-indexed by both a cue-locked late positive complex and a sustained positivity ensuing task transitions. Topographic scalp analyses confirmed subtle yet significant split-second changes in the configuration of neural sources for both domain-general P3s and switch positivities as a function of both the temporal and task context. These findings partly meet predictions from information estimates, and are compatible with a family of P3-like potentials indexing functionally distinct neural operations within a common frontoparietal "multiple demand" system during the preparation and execution of simple task rules.