A Functional Magnetic Resonance Imaging (fMRI) Study of Cue-Induced Smoking Craving in Virtual Environments

Smokers who are exposed to smoking-related cues show cardiovascular reactivity and smoking craving compared with their responses to neutral cues, and increased cue reactivity predicts decreased likelihood of successful cessation. Several brain imaging studies suggested four candidate brain regions that might differ in gray matter volumes and densities between smokers and nonsmokers. However, in these studies, smokers were only exposed to smoking-related objects. In our pilot study utilizing a virtual reality (VR) technique, virtual environments (VEs) were more immersive and evoked smoking craving more effectively than traditionally used methods. In this study, we sought to test whether smokers could experience cue-induced smoking craving inside the MRI scanner by using the VR system. The smoking cue reactivity scenario was based in part on our preliminary task and consisted of 2D and 3D (or VE) conditions. The group mean of participants had increased activity in the prefrontal cortex (PFC), left anterior cingulate gyrus (ACC), left supplementary motor area, left uncus, right inferior temporal gyrus, right lingual gyrus, and right precuneus in the 2D condition. Areas of differential activation in the 3D condition were as follows: left superior temporal gyrus, right superior frontal gyrus, and left inferior occipital gyrus in the 3D condition. This finding is consistent with those of previous studies of nicotine craving showing PFC and ACC activation. However, in the 3D condition, the PFC including the superior frontal gyrus as well as the superior temporal gyrus, inferior occipital gyrus, and cerebellum were activated. Therefore, in the 3D condition, participants seemed to have more attention, visual balance, and coordinating movement than in the 2D condition.     

A general method for evaluating incubation of sucrose craving in rats

For someone on a food-restricted diet, food craving in response to food-paired cues may serve as a key behavioral transition point between abstinence and relapse to food taking. Food craving conceptualized in this way is akin to drug craving in response to drug-paired cues. A rich literature has been developed around understanding the behavioral and neurobiological determinants of drug craving; we and others have been focusing recently on translating techniques from basic addiction research to better understand addiction-like behaviors related to food. As done in previous studies of drug craving, we examine sucrose craving behavior by utilizing a rat model of relapse. In this model, rats self-administer either drug or food in sessions over several days. In a session, lever responding delivers the reward along with a tone+light stimulus. Craving behavior is then operationally defined as responding in a subsequent session where the reward is not available. Rats will reliably respond for the tone+light stimulus, likely due to its acquired conditioned reinforcing properties. This behavior is sometimes referred to as sucrose seeking or cue reactivity. In the present discussion we will use the term "sucrose craving" to subsume both of these constructs. In the past decade, we have focused on how the length of time following reward self-administration influences reward craving. Interestingly, rats increase responding for the reward-paired cue over the course of several weeks of a period of forced-abstinence. This "incubation of craving" is observed in rats that have self-administered either food or drugs of abuse. This time-dependent increase in craving we have identified in the animal model may have great potential relevance to human drug and food addiction behaviors. Here we present a protocol for assessing incubation of sucrose craving in rats. Variants of the procedure will be indicated where craving is assessed as responding for a discrete sucrose-paired cue following extinction of lever pressing within the sucrose self-administration context (Extinction without cues) or as responding for sucrose-paired cues in a general extinction context (Extinction with cues).     

Reliability-Based Weighting of Visual and Vestibular Cues in Displacement Estimation

When navigating through the environment, our brain needs to infer how far we move and in which direction we are heading. In this estimation process, the brain may rely on multiple sensory modalities, including the visual and vestibular systems. Previous research has mainly focused on heading estimation, showing that sensory cues are combined by weighting them in proportion to their reliability, consistent with statistically optimal integration. But while heading estimation could improve with the ongoing motion, due to the constant flow of information, the estimate of how far we move requires the integration of sensory information across the whole displacement. In this study, we investigate whether the brain optimally combines visual and vestibular information during a displacement estimation task, even if their reliability varies from trial to trial. Participants were seated on a linear sled, immersed in a stereoscopic virtual reality environment. They were subjected to a passive linear motion involving visual and vestibular cues with different levels of visual coherence to change relative cue reliability and with cue discrepancies to test relative cue weighting. Participants performed a two-interval two-alternative forced-choice task, indicating which of two sequentially perceived displacements was larger. Our results show that humans adapt their weighting of visual and vestibular information from trial to trial in proportion to their reliability. These results provide evidence that humans optimally integrate visual and vestibular information in order to estimate their body displacement.     

The impact of sex on brain responses to smoking cues: a perfusion fMRI study

Background

Anecdotal and clinical theories purport that females are more responsive to smoking cues, yet few objective, neurophysiological examinations of these theories have been conducted. The current study examines the impact of sex on brain responses to smoking cues.

Methods

Fifty-one (31 males) cigarette-dependent sated smokers underwent pseudo- continuous arterial spin-labeled perfusion functional magnetic resonance imaging during exposure to visual smoking cues and non-smoking cues. Brain responses to smoking cues relative to non-smoking cues were examined within males and females separately and then compared between males and females. Cigarettes smoked per day was included in analyses as a covariate.

Results

Both males and females showed increased responses to smoking cues compared to non-smoking cues with males exhibiting increased medial orbitofrontal cortex and ventral striatum/ventral pallidum responses, and females showing increased medial orbitofrontal cortex responses. Direct comparisons between male and female brain responses revealed that males showed greater bilateral hippocampal/amygdala activation to smoking cues relative to non-smoking cues.

Conclusions

Males and females exhibit similar responses to smoking cues relative to non-smoking cues in a priori reward-related regions; however, direct comparisons between sexes indicate that smoking cues evoke greater bilateral hippocampal/amygdalar activation among males. Given the current literature on sex differences in smoking cue neural activity is sparse and incomplete, these results contribute to our knowledge of the neurobiological underpinnings of drug cue reactivity.

     

Development of a Data Management Tool for Investigating Multivariate Space and Free Will Experiences in Virtual Reality

Virtual reality (VR) has become mature enough to be successfully used in clinical applications such as exposure therapy, pain distraction, and neuropsychological assessment. However, we now need to go beyond the outcome data from this research and conduct the detailed scientific investigations required to better understand what factors influence why VR works (or doesn’t) in these types of clinical applications. This knowledge is required to guide the development of VR applications in the key areas of education, training, and rehabilitation and to further evolve existing VR approaches. One of the primary assets obtained with the use of VR is the ability to simulate the complexity of real world environments, within which human performance can be tested and trained. But this asset comes with a price in terms of the capture, quantification and analysis of large, multivariate and concurrent data sources that reflect the naturalistic behavioral interaction that is afforded in a virtual world. As well, while achieving realism has been a main goal in making convincing VR environments, just what constitutes realism and how much is needed is still an open question situated firmly in the research domain. Just as in real “reality,” such factors in virtual reality are complex and multivariate, and the understanding of this complexity presents exceptional challenges to the VR researcher. For certain research questions, good behavioral science often requires consistent delivery of stimuli within tightly controlled lab-based experimental conditions. However, for other important research questions we do not want to constrain naturalistic behavior and limit VR’s ability to replicate real world conditions, simply because it is easier to study human performance with traditional lab-based methodologies. By doing so we may compromise the very qualities that comprise VR’s unique capacity to mimic the experiences and challenges that exist in everyday life. What is really needed to address scientific questions that require natural exploration of a simulated environment are more usable and robust tools to instrument, organize, and visualize the complex data generated by measurements of participant behaviors within a virtual world. This paper briefly describes the rationale and methodology of an initial study in an ongoing research program that aims to investigate human performance within a virtual environment where unconstrained “free will” exploratory behavior is essential to research questions that involve the relationships between physiology, emotion, and memory. After a discussion of the research protocol and the types of data that were collected, we describe a novel tool that was borne from our need to more efficiently capture, manage, and explore the complex data that was generated in this research. An example of a research participant’s annotated display from this data management and visualization tool is then presented. It is our view that this tool provides the capacity to better visualize and understand the complex data relationships that may arise in VR research that investigates naturalistic free will behavior and its impact on other human performance variables.     

Intense passionate love attenuates cigarette cue-reactivity in nicotine-deprived smokers: an FMRI study

Self-expanding experiences like falling in love or engaging in novel, exciting and interesting activities activate the same brain reward mechanism (mesolimbic dopamine pathway) that reinforces drug use and abuse, including tobacco smoking. This suggests the possibility that reward from smoking is substitutable by self-expansion (through competition with the same neural system), potentially aiding cessation efforts. Using a model of self-expansion in the context of romantic love, the present fMRI experiment examined whether, among nicotine-deprived smokers, relationship self-expansion is associated with deactivation of cigarette cue-reactivity regions. Results indicated that among participants who were experiencing moderate levels of craving, cigarette cue-reactivity regions (e.g., cuneus and posterior cingulate cortex) showed significantly less activation during self-expansion conditions compared with control conditions. These results provide evidence that rewards from one domain (self-expansion) can act as a substitute for reward from another domain (nicotine) to attenuate cigarette cue reactivity.     

Objective fidelity evaluation in multisensory virtual environments: auditory cue fidelity in flight simulation

We argue that objective fidelity evaluation of virtual environments, such as flight simulation, should be human-performance-centred and task-specific rather than measure the match between simulation and physical reality. We show how principled experimental paradigms and behavioural models to quantify human performance in simulated environments that have emerged from research in multisensory perception provide a framework for the objective evaluation of the contribution of individual cues to human performance measures of fidelity. We present three examples in a flight simulation environment as a case study: Experiment 1: Detection and categorisation of auditory and kinematic motion cues; Experiment 2: Performance evaluation in a target-tracking task; Experiment 3: Transferrable learning of auditory motion cues. We show how the contribution of individual cues to human performance can be robustly evaluated for each task and that the contribution is highly task dependent. The same auditory cues that can be discriminated and are optimally integrated in experiment 1, do not contribute to target-tracking performance in an in-flight refuelling simulation without training, experiment 2. In experiment 3, however, we demonstrate that the auditory cue leads to significant, transferrable, performance improvements with training. We conclude that objective fidelity evaluation requires a task-specific analysis of the contribution of individual cues.     

KinImmerse: Macromolecular VR for NMR ensembles

Background  

In molecular applications, virtual reality (VR) and immersive virtual environments have generally been used and valued for the visual and interactive experience – to enhance intuition and communicate excitement – rather than as part of the actual research process. In contrast, this work develops a software infrastructure for research use and illustrates such use on a specific case.     

Cue-reactors: individual differences in cue-induced craving after food or smoking abstinence

Background

Pavlovian conditioning plays a critical role in both drug addiction and binge eating. Recent animal research suggests that certain individuals are highly sensitive to conditioned cues, whether they signal food or drugs. Are certain humans also more reactive to both food and drug cues?

Methods

We examined cue-induced craving for both cigarettes and food, in the same individuals (n = 15 adult smokers). Subjects viewed smoking-related or food-related images after abstaining from either smoking or eating.

Results

Certain individuals reported strong cue-induced craving after both smoking and food cues. That is, subjects who reported strong cue-induced craving for cigarettes also rated stronger cue-induced food craving.

Conclusions

In humans, like in nonhumans, there may be a “cue-reactive” phenotype, consisting of individuals who are highly sensitive to conditioned stimuli. This finding extends recent reports from nonhuman studies. Further understanding this subgroup of smokers may allow clinicians to individually tailor therapies for smoking cessation.     

Developing a Novel Measure of Body Satisfaction Using Virtual Reality

Body image disturbance (BID), considered a key feature in eating disorders, is a pervasive issue among young women. Accurate assessment of BID is critical, but the field is currently limited to self-report assessment methods. In the present study, we build upon existing research, and explore the utility of virtual reality (VR) to elicit and detect changes in BID across various immersive virtual environments. College-aged women with elevated weight and shape concerns (n = 38) and a non-weight and shape concerned control group (n = 40) were randomly exposed to four distinct virtual environments with high or low levels of body salience and social presence (i.e., presence of virtual others). Participants interacted with avatars of thin, normal weight, and overweight body size (BMI of approximately 18, 22, and 27 respectively) in virtual social settings (i.e., beach, party). We measured state-level body satisfaction (state BD) immediately after exposure to each environment. In addition, we measured participants’ minimum interpersonal distance, visual attention, and approach preference toward avatars of each size. Women with higher baseline BID reported significantly higher state BD in all settings compared to controls. Both groups reported significantly higher state BD in a beach with avatars as compared to other environments. In addition, women with elevated BID approached closer to normal weight avatars and looked longer at thin avatars compared to women in the control group. Our findings indicate that VR may serve as a novel tool for measuring state-level BID, with applications for measuring treatment outcomes. Implications for future research and clinical interventions are discussed.     

Molecular Visualization on the Holodeck

Can virtual reality be useful for visualizing and analyzing molecular structures and three-dimensional (3D) microscopy? Uses we are exploring include studies of drug binding to proteins and the effects of mutations, building accurate atomic models in electron microscopy and x-ray density maps, understanding how immune system cells move using 3D light microscopy, and teaching schoolchildren about biomolecules that are the machinery of life. Virtual reality (VR) offers immersive display with a wide field of view and head tracking for better perception of molecular architectures and uses 6-degree-of-freedom hand controllers for simple manipulation of 3D data. Conventional computer displays with trackpad, mouse and keyboard excel at two-dimensional tasks such as writing and studying research literature, uses for which VR technology is at present far inferior. Adding VR to the conventional computing environment could improve 3D capabilities if new user-interface problems can be solved. We have developed three VR applications: ChimeraX for analyzing molecular structures and electron and light microscopy data, AltPDB for collaborative discussions around atomic models, and Molecular Zoo for teaching young students characteristics of biomolecules. Investigations over three decades have produced an extensive literature evaluating the potential of VR in research and education. Consumer VR headsets are now affordable to researchers and educators, allowing direct tests of whether the technology is valuable in these areas. We survey here advantages and disadvantages of VR for molecular biology in the context of affordable and dramatically more powerful VR and graphics hardware than has been available in the past.     

Exploring virtual environments with an EEG-based BCI through motor imagery.

In this paper, we describe the possibility of navigating in a virtual environment using the output signal of an EEG-based Brain-Computer Interface (BCI). The graphical capabilities of virtual reality (VR) should help to create new BCI-paradigms and improve feedback presentation. The objective of this combination is to enhance the subject's learning process of gaining control of the BCI. In this study, the participant had to imagine left or right hand movements while exploring a virtual conference room. By imaging a left hand movement the subject turned virtually to the left inside the room and with right hand imagery to the right. In fact, three trained subjects reached 80% to 100% BCI classification accuracy in the course of the experimental sessions. All subjects were able to achieve a rotation in the VR to the left or right by approximately 45 degrees during one trial.     

Novel Simulation Tools for Materials Engineering Education

Abstract

A novel simulation interface is being developed as an educational tool to help students better understand fundamentals of materials science. This interface makes use of virtual reality (VR) technology consisting of PC-based graphics and a force-feedback haptic device. Visualization of atomistic processes with simultaneous tactile sensation via the haptic provides a powerful method for understanding complex phenomena that are otherwise difficult to comprehend. Modules are described that allow students to interactively explore interatomic bonding and single-atom diffusion through materials.     

Kinase interest you in treating incubated cocaine‐craving? A hypothetical model for treatment intervention during protracted withdrawal from cocaine

A diagnostic criterion for drug addiction, persistent drug‐craving continues to be the most treatment‐resistant aspect of addiction that maintains the chronic, relapsing, nature of this disease. Despite the high prevalence of psychomotor stimulant addiction, there currently exists no FDA‐approved medication for craving reduction. In good part, this reflects our lack of understanding of the neurobiological underpinnings of drug‐craving. In humans, cue‐elicited drug‐craving is associated with the hyperexcitability of prefrontal cortical regions. Rodent models of cocaine addiction indicate that a history of excessive cocaine‐taking impacts excitatory glutamate signaling within the prefrontal cortex to drive drug‐seeking behavior during protracted withdrawal. This review summarizes evidence that the capacity of cocaine‐associated cues to augment craving in highly drug‐experienced rats relates to a withdrawal‐dependent incubation of glutamate release within prelimbic cortex. We discuss how stimulation of mGlu1/5 receptors increases the activational state of both canonical and noncanonical intracellular signaling pathways and present a theoretical molecular model in which the activation of several kinase effectors, including protein kinase C, extracellular signal‐regulated kinase and phosphoinositide 3‐kinase (PI3K) might lead to receptor desensitization to account for persistent cocaine‐craving during protracted withdrawal. Finally, this review discusses the potential for existing, FDA‐approved, pharmacotherapeutic agents that target kinase function as a novel approach to craving intervention in cocaine addiction.     

Predator recognition learning in rainbow darters Etheostoma caeruleum: specific learning and neophobia

This study investigated whether rainbow darters Etheostoma caeruleum can learn to recognize unfamiliar predators through the process of classical conditioning. Etheostoma caeruleum were conditioned by exposing them simultaneously to their chemical alarm cues (a known fright stimulus) and either chemical cues from larval ringed salamanders Ambystoma annulatum (unfamiliar predator) or to a blank water cue (control). Conditioning could result in either specific learning of the A. annulatum cue or increased wariness in response to any novel cue (neophobia). To distinguish between these possibilities, E. caeruleum in both groups were exposed to either A. annulatum cues alone or to chemical cues from western rat snakes Pantherophis obsoletus (novel cue) 2 days after conditioning. Treatment (A. annulatum‐conditioned) E. caeruleum, but not control E. caeruleum, showed a fright response when they were exposed to both the conditioned (A. annulatum) and novel (P. obsoletus) cues, indicating increased sensitivity to new stimuli. When E. caeruleum were retested after an additional 32 days, however, the fright response occurred only following exposure to the conditioned (A. annulatum) stimulus, indicating that specific learning of the A. annulatum cue had been retained whereas the neophobia to novel stimuli was temporary.     

Virtual Reality Based Support System for Layout Planning and Programming of an Industrial Robotic Work Cell

Traditional robotic work cell design and programming are considered inefficient and outdated in current industrial and market demands. In this research, virtual reality (VR) technology is used to improve human-robot interface, whereby complicated commands or programming knowledge is not required. The proposed solution, known as VR-based Programming of a Robotic Work Cell (VR-Rocell), consists of two sub-programmes, which are VR-Robotic Work Cell Layout (VR-RoWL) and VR-based Robot Teaching System (VR-RoT). VR-RoWL is developed to assign the layout design for an industrial robotic work cell, whereby VR-RoT is developed to overcome safety issues and lack of trained personnel in robot programming. Simple and user-friendly interfaces are designed for inexperienced users to generate robot commands without damaging the robot or interrupting the production line. The user is able to attempt numerous times to attain an optimum solution. A case study is conducted in the Robotics Laboratory to assemble an electronics casing and it is found that the output models are compatible with commercial software without loss of information. Furthermore, the generated KUKA commands are workable when loaded into a commercial simulator. The operation of the actual robotic work cell shows that the errors may be due to the dynamics of the KUKA robot rather than the accuracy of the generated programme. Therefore, it is concluded that the virtual reality based solution approach can be implemented in an industrial robotic work cell.     

Intentional modulation of the late positive potential in response to smoking cues by cognitive strategies in smokers

Attentional bias is considered an important concept in addiction since it has been found to correlate with subjective craving and is strongly associated with relapse after periods of abstinence. Hence, investigating in ways to regulate attention for drug cues would be of major clinical relevance. The present study examined deliberate, cognitive modulation of motivated attention for smoking cues in smokers. The effects of three different reappraisal strategies on an electrophysiological measure of attentive processing were investigated. Early and late LPP components in response to passively viewed neutral and smoking pictures were compared with LPPs in response to smoking pictures that were reappraised with three different reappraisal strategies. Results show that when smokers actively imagine how pleasant it would be to smoke (pleasant condition), their early LPP in response to smoking cues increases, but when smokers actively focus on an alternative stimulus (distraction condition) or think of a rational, uninvolved interpretation of the situation (rational condition), smoking-related late LPP amplitude decreases to the processing level of neutral stimuli. Present results are the first to indicate that smoking cue-elicited LPP amplitudes can be modulated by cognitive strategies, suggesting that attentive processing of smoking cues can be intentionally regulated by smokers with various levels of dependence. Although cognitive strategies can lead to enhanced processing of smoking cues, it is not completely clear whether cognitive strategies are also successful in reducing smoking-related motivated attention. Although findings do point in this direction, present study is best considered preliminary and a starting point for other research on this topic. A focus on the distraction strategy is proposed, as there are indications that this strategy is more successful than the rational strategy in decreasing LPP amplitude.     

When to approach novel prey cues? Social learning strategies in frog-eating bats

Animals can use different sources of information when making decisions. Foraging animals often have access to both self-acquired and socially acquired information about prey. The fringe-lipped bat, Trachops cirrhosus, hunts frogs by approaching the calls that frogs produce to attract mates. We examined how the reliability of self-acquired prey cues affects social learning of novel prey cues. We trained bats to associate an artificial acoustic cue (mobile phone ringtone) with food rewards. Bats were assigned to treatments in which the trained cue was either an unreliable indicator of reward (rewarded 50% of the presentations) or a reliable indicator (rewarded 100% of the presentations), and they were exposed to a conspecific tutor foraging on a reliable (rewarded 100%) novel cue or to the novel cue with no tutor. Bats whose trained cue was unreliable and who had a tutor were significantly more likely to preferentially approach the novel cue when compared with bats whose trained cue was reliable, and to bats that had no tutor. Reliability of self-acquired prey cues therefore affects social learning of novel prey cues by frog-eating bats. Examining when animals use social information to learn about novel prey is key to understanding the social transmission of foraging innovations.