Multimodal Assessment of Smoking cue Reactivity During a Smoking Cue Exposure Task.

Background. Cue-reactivity as a characteristic symptom of substance use disorders (SUD) is highly context dependent. Paradigms with high context validity need to be established for the investigation of underlying neurobiological mechanisms. While craving can be assessed by self-report as one aspect of cue-reactivity (CR), the assessment of biological measures such as the autonomous response and EEG promises a holistic perspective including CR at an automatized level. In a multimodal approach, smoking cue exposure (CE) effects on heart rate variability (HRV), EEG frequency power, and craving as well as their interrelation were assessed. This pilot study focused on the validity of CR measurements in a naturalistic CE paradigm. Methods. EEG frequency power, HRV, and craving were assessed during resting state (RS) and smoking CE in smokers (n = 14) and nonsmoking controls (n = 10) to investigate the psychophysiological and subjective reactions to CE. Results. Increased beta power was found only in smokers during CE compared to the control condition. There was an inverse correlation of beta power and maximum craving. Likewise, HRV correlated negatively with maximum smoking urges in smokers immediately after the measurements, without differentiation between CE and control condition. Conclusion. The increased beta power in smokers during CE is discussed as increased inhibitory control related to reduced craving in smokers. Furthermore, increased craving during CE seems to be associated to decreased vagal activity. The multimodal measurements during the CE showed ecological validity to be fundamental for CE assessment in clinical populations to evaluate its predictive value.

BNST and amygdala activation to threat: Effects of temporal predictability and threat mode.

Recent animal and human studies highlight the uncertainty about the onset of an aversive event as a crucial factor for the involvement of the centromedial amygdala (CM) and bed nucleus of the stria terminalis (BNST) activity. However, studies investigating temporally predictable or unpredictable threat anticipation and confrontation processes are rare. Furthermore, the few existing fMRI studies analyzing temporally predictable and unpredictable threat processes used small sample sizes or limited fMRI paradigms. Therefore, we measured functional brain activity in 109 predominantly female healthy participants during a temporally predictable-unpredictable threat paradigm, which aimed to solve limited aspects of recent studies. Results showed higher BNST activity compared to the CM during the cue indicating that the upcoming confrontation is aversive relative to the cue indicating an upcoming neutral confrontation. Both the CM and BNST showed higher activity during the confrontation with unpredictable and aversive stimuli, but the reaction to aversive confrontation relative to neutral confrontation was stronger in the CM compared to the BNST. Additional modulation analyses by NPSR1 rs324981 genotype revealed higher BNST activity relative to the CM in unpredictable anticipation relative to predictable anticipation in T-carriers compared to AA carriers. Our results indicate that during the confrontation with aversive or neutral stimuli, temporal unpredictability modulates CM and BNST activity. Further, there is a differential activity concerning threat processing, as BNST is more involved when focussing on fear-related anticipation processes and CM is more involved when focussing on threat confrontation.

The Influence of Methylphenidate on Hyperactivity and Attention Deficits in Children With ADHD: A Virtual Classroom Test.

Objective: This study compares the performance in a continuous performance test within a virtual reality classroom (CPT-VRC) between medicated children with ADHD, unmedicated children with ADHD, and healthy children. Method:N = 94 children with ADHD (n = 26 of them received methylphenidate and n = 68 were unmedicated) and n = 34 healthy children performed the CPT-VRC. Omission errors, reaction time/variability, commission errors, and body movements were assessed. Furthermore, ADHD questionnaires were administered and compared with the CPT-VRC measures. Results: The unmedicated ADHD group exhibited more omission errors and showed slower reaction times than the healthy group. Reaction time variability was higher in the unmedicated ADHD group compared with both the healthy and the medicated ADHD group. Omission errors and reaction time variability were associated with inattentiveness ratings of experimenters. Head movements were correlated with hyperactivity ratings of parents and experimenters. Conclusion: Virtual reality is a promising technology to assess ADHD symptoms in an ecologically valid environment.

Was it less painful for knights? Influence of appearance on pain perception.

BACKGROUND: Pain perception is a subjective experience shaped by different factors. In this study, we investigated the influence of a visually manipulated appearance of a virtual arm on pain perception. Specifically, we investigated how pain perception and vegetative skin responses were modified by inducing a virtual protection on the right arm by a virtual armour. METHODS: Participants (n = 32) immersed in virtual reality embodied a virtual arm, which appeared in three different versions (uncovered, neutral or protected). During the virtual reality simulation, the participants received electrical stimulations of varying intensities. Skin conductance level (SCL) was analysed for the phase anticipation (from the moment the arm appeared until the electric stimulation) and perception of pain (after the electric stimulation). Pain ratings were acquired after the painful stimuli occurred. RESULTS: The sense of embodiment was positive for the unprotected and neutral condition and lower for the protected than for the neutral arm. Pain ratings were significantly decreased in the protected arm condition compared with both the unprotected arm and the neutral arm conditions. The SCL measurements showed no significant differences for the three arm types. CONCLUSIONS: According to the pain ratings, participants felt significantly less pain in the covered arm condition compared with the unprotected and the neutral arm condition. Subjective pain perception was decreased by a virtual protection of the arm in VR. The simplicity of the manipulation suggests possible practical uses in pain therapy by strengthening the patients' own capacities to influence their pain using simple cognitive manipulations via virtual reality. SIGNIFICANCE: A virtual, covered arm causes differences in reported pain ratings. Physiological measurements do not confirm the findings. Visual information about body protection can have an impact on pain perception.

GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation: a potential neurogenetic pathway to panic disorder.

The molecular genetics of panic disorder (PD) with and without agoraphobia (AG) are still largely unknown and progress is hampered by small sample sizes. We therefore performed a genome-wide association study with a dimensional, PD/AG-related anxiety phenotype based on the Agoraphobia Cognition Questionnaire (ACQ) in a sample of 1370 healthy German volunteers of the CRC TRR58 MEGA study wave 1. A genome-wide significant association was found between ACQ and single non-coding nucleotide variants of the GLRB gene (rs78726293, P=3.3 × 10-8; rs191260602, P=3.9 × 10-8). We followed up on this finding in a larger dimensional ACQ sample (N=2547) and in independent samples with a dichotomous AG phenotype based on the Symptoms Checklist (SCL-90; N=3845) and a case-control sample with the categorical phenotype PD/AG (Ncombined =1012) obtaining highly significant P-values also for GLRB single-nucleotide variants rs17035816 (P=3.8 × 10-4) and rs7688285 (P=7.6 × 10-5). GLRB gene expression was found to be modulated by rs7688285 in brain tissue, as well as cell culture. Analyses of intermediate PD/AG phenotypes demonstrated increased startle reflex and increased fear network, as well as general sensory activation by GLRB risk gene variants rs78726293, rs191260602, rs17035816 and rs7688285. Partial Glrb knockout mice demonstrated an agoraphobic phenotype. In conjunction with the clinical observation that rare coding GLRB gene mutations are associated with the neurological disorder hyperekplexia characterized by a generalized startle reaction and agoraphobic behavior, our data provide evidence that non-coding, although functional GLRB gene polymorphisms may predispose to PD by increasing startle response and agoraphobic cognitions.

The fate of the inner nose: odor imagery in patients with olfactory loss.

Cerebral activations during olfactory mental imagery are fairly well investigated in healthy participants but little attention has been given to olfactory imagery in patients with olfactory loss. To explore whether olfactory loss leads to deficits in olfactory imagery, neural responses using functional magnetic resonance imaging (fMRI) and self-report measures were investigated in 16 participants with acquired olfactory loss and 19 control participants. Participants imagined both pleasant and unpleasant odors and their visual representations. Patients reported less vivid olfactory but not visual images than controls. Results from neuroimaging revealed that activation patterns differed between patients and controls. While the control group showed stronger activation in olfactory brain regions for unpleasant compared to pleasant odors, the patient group did not. Also, activation in critical areas for olfactory imagery was correlated with the duration of olfactory dysfunction, indicating that the longer the duration of dysfunction, the more the attentional resources were employed. This indicates that participants with olfactory loss have difficulties to perform olfactory imagery in the conventional way. Regular exposure to olfactory information may be necessary to maintain an olfactory imagery capacity.

Repeated exposure of flight phobics to flights in virtual reality.

The present study examined the effects of repeated exposure of flight phobics to flights in virtual reality (VR). Flight phobics were randomly assigned either to complete one VR test flight followed by four VR exposure flights (VR group; N=15) in one lengthy session or to complete one VR test flight followed by a lengthy relaxation training session (relaxation group; N=15). All participants completed a second VR test flight at the end of the session. Fear reports and physiological fear reactions (heart rate, skin conductance level) during VR exposures were registered, and fear of flying was assessed psychometrically from 3 weeks before to 3 months after exposure. Exposure to VR flights elicited subjective and physiological fear responses in flight phobics, and these responses attenuated within and across VR flights. Fear reduction associated with repeated VR exposure was greater than fear reduction caused by relaxation training. Fear of flying improved in both treatment groups, but several outcome measures indicated greater effects in the VR treated group than in the relaxation group. These findings indicate that exposure in virtual reality may offer a new and promising approach for the treatment of fear of flying.

An unobtrusive measurement method of the horizontal gaze angle.

A horizontal gaze angle measurement device is introduced. By combining a photoelectric viewing device to measure the horizontal eye angle with a similar head angle measurement device, it is possible to measure the horizontal gaze angle without using a headrest. After discussion of circuit diagrams and measurement principles, it is shown that the measurements made with the device yield a reasonable precision. The mean absolute measurement error is below 1 degree. This inexpensive and unobtrusive device covers a visual field of about 20 degrees and can be used in parallel with many tasks. Further, data on the successful application of the device in a driving simulation setting are discussed.