Paul Pauli

Model-based analysis of rapid event-related functional near-infrared spectroscopy (NIRS) data: A parametric validation study

To validate the usefulness of a model-based analysis approach according to the general linear model (GLM) for functional near-infrared spectroscopy (fNIRS) data, a rapid event-related paradigm with an unpredictable stimulus sequence was applied to 15 healthy subjects. A parametric design was chosen wherein four differently graded contrasts of a flickering checkerboard were presented, allowing directed hypotheses about the rank order of the evoked hemodynamic response amplitudes. The results indicate the validity of amplitude estimation by three main findings (a) the GLM approach for fNIRS data is capable to identify human brain activation in the visual cortex with inter-stimulus intervals of 4-9 s (6.5 s average) whereas in non-visual areas no systematic activation was detectable; (b) the different contrast level intensities lead to the hypothesized rank order of the GLM amplitude parameters: visual cortex activation evoked by highest contrast>moderate contrast>lowest contrast>no stimulation; (c) analysis of null-events (no stimulation) did not produce any significant activation in the visual cortex or in other brain areas. We conclude that a model-based GLM approach delivers valid fNIRS amplitude estimations and enables the analysis of rapid event-related fNIRS data series, which is highly relevant in particular for cognitive fNIRS studies.

Appetitive nature of drug cues confirmed with physiological measures in a model using pictures of smoking

Abstract. Rationale: In smokers, pictures of smoking that increase desire for a cigarette are described as pleasant rather than unpleasant. This suggests that these smoking cues may be appetitive and not withdrawal-like or aversive as held by traditional theories of drug cue formation. Objective: Cues for smoking were examined using physiological measures of motivational valence. Methods: Non-deprived smokers, deprived smokers and deprived smokers who expected to smoke (n=54) viewed a computer screen presenting experimental and control scenes (experiment 1). The acoustic startle reaction and activity of the corrugator and the zygomatic facial muscles were then measured after onset of smoking cues and standardized pleasant, neutral or unpleasant control scenes. Individuals who never smoked (n=18) were also used to test for cue effects on startle (experiment 2). Results: No evidence was found that smoking cues were aversive in smokers. The smoking cues affected the startle responses and corrugator activity in a way similar to that of pleasant control material but significantly different from that of unpleasant material; the cue effects on zygomatic activity was most similar to that of neutral material. The general pattern of effects was not influenced by overnight smoke deprivation, expectancy to smoke or smoke repletion, but it was different in never smokers where the smoking scenes were found to be similar to unpleasant control scenes. Conclusions: Non-subjective measures of motivational valence further suggest that drug cues are conditioned stimuli having appetitive effects. Startle response modulated by drug cues may be useful for probing motivational processes underlying dependence in the human.

Early cortical processing of natural and artificial emotional faces differs between lower and higher socially anxious persons

Emotional facial expressions provide critical information for social interactions. Above all, angry faces are assumed to reflect potential social threat. We investigated event-related potentials (ERPs) triggered by natural and artificial faces expressing fear, anger, happiness or no emotion in participants with low and high levels of social anxiety. Overall, artificial faces elicited stronger P100 and N170 responses than natural faces. Additionally, the N170 component was larger for emotional compared to neutral facial expressions. Social anxiety was associated with an enhanced emotional modulation of the early posterior negativity (EPN) in response to fearful and angry facial expressions. Additionally, while the late positive potential (LPP) was larger for emotional than for neutral faces in low socially anxious participants, LPPs of higher socially anxious participants did not differ. LPPs might therefore be enhanced in higher socially anxious participants for both emotional and neutral faces. Furthermore, the modulations of the EPN and LPP were comparable between natural and artificial faces. These results indicate that social anxiety influences early perceptual processing of faces and that artificial faces are suitable for psychophysiological emotion research.

Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis

BACKGROUND Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis. METHODS In this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0·0156. FINDINGS Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohens d=-0·15), amygdala (d=-0·19), caudate (d=-0·11), hippocampus (d=-0·11), putamen (d=-0·14), and intracranial volume (d=-0·10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0·95) and thalamus (p=0·39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (<15 years) versus adults (>21 years): in the accumbens (Cohens d=-0·19 vs -0·10), amygdala (d=-0·18 vs -0·14), caudate (d=-0·13 vs -0·07), hippocampus (d=-0·12 vs -0·06), putamen (d=-0·18 vs -0·08), and intracranial volume (d=-0·14 vs 0·01). There was no difference between children and adults for the pallidum (p=0·79) or thalamus (p=0·89). Case-control differences in adults were non-significant (all p>0·03). Psychostimulant medication use (all p>0·15) or symptom scores (all p>0·02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0·5). INTERPRETATION With the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes. FUNDING National Institutes of Health.

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.

Neuropeptide S receptor gene—converging evidence for a role in panic disorder

Animal studies have suggested neuropeptide S (NPS) and its receptor (NPSR) to be involved in the pathogenesis of anxiety-related behavior. In this study, a multilevel approach was applied to further elucidate the role of NPS in the etiology of human anxiety. The functional NPSR A/T (Asn107Ile) variant (rs324981) was investigated for association with (1) panic disorder with and without agoraphobia in two large, independent case–control studies, (2) dimensional anxiety traits, (3) autonomic arousal level during a behavioral avoidance test and (4) brain activation correlates of anxiety-related emotional processing in panic disorder. The more active NPSR rs324981 T allele was found to be associated with panic disorder in the female subgroup of patients in both samples as well as in a meta-analytic approach. The T risk allele was further related to elevated anxiety sensitivity, increased heart rate and higher symptom reports during a behavioral avoidance test as well as decreased activity in the dorsolateral prefrontal, lateral orbitofrontal and anterior cingulate cortex during processing of fearful faces in patients with panic disorder. The present results provide converging evidence for a female-dominant role of NPSR gene variation in panic disorder potentially through heightened autonomic arousal and distorted processing of anxiety-relevant emotional stimuli.

Is eye to eye contact really threatening and avoided in social anxiety? : An eye-tracking and psychophysiology study

The effects of direct and averted gaze on autonomic arousal and gaze behavior in social anxiety were investigated using a new paradigm including animated movie stimuli and eye-tracking methodology. While high, medium, and low socially anxious (HSA vs. MSA vs. LSA) women watched animated movie clips, in which faces responded to the gaze of the participants with either direct or averted gaze, their eye movements, heart rate (HR) and skin conductance responses (SCR) were continuously recorded. Groups did not differ in their gaze behavior concerning direct vs. averted gaze, but high socially anxious women tended to fixate the eye region of the presented face longer than MSA and LSA, respectively. Furthermore, they responded to direct gaze with more pronounced cardiac acceleration. This physiological finding indicates that direct gaze may be a fear-relevant feature for socially anxious individuals in social interaction. However, this seems not to result in gaze avoidance. Future studies should examine the role of gaze direction and its interaction with facial expressions in social anxiety and its consequences for avoidance behavior and fear responses. Additionally, further research is needed to clarify the role of gaze perception in social anxiety.

Anxiety in patients with an automatic implantable cardioverter defibrillator: what differentiates them from panic patients?

OBJECTIVE Anxiety seems to be a frequent problem in patients with an automatic implantable cardioverter defibrillator (AICD). Distressing experiences before or after AICD implantation such as resuscitation, or AICD shocks are suspected as causes for enhanced anxiety levels. A closer examination of the level and structure of anxiety in AICD patients and a comparison with panic patients might help to examine additionally both conditioning and cognitive models of anxiety. METHODS There were 61 AICD patients examined with a specifically designed AICD questionnaire and standardized anxiety and depression questionnaires. Subgroups of AICD patients without, with some, and with definite anxiety related to AICD shocks were compared with panic patients and healthy control subjects. RESULTS Although fear of dying was greatly reduced by AICD implantation, approximately one third of the AICD patients, especially patients with definite anxiety related to AICD shocks, were characterized both by enhanced anxiety levels and avoidance behavior. These patients were comparable with panic patients in most questionnaire scores. Anxiety levels were not associated with objective AICD shock experiences or medical variables. CONCLUSIONS Anxiety in AICD patients seems to be unrelated to traumatic experiences, a finding that casts doubt on pure conditioning models of anxiety. Presumably, a life-threatening cardiac disorder increases the likelihood for catastrophic interpretations of bodily signs, especially in anxiety prone AICD patients. In accordance with cognitive models of panic disorder, this cognitive dysfunction could lead to anxiety and depression levels comparable with those of panic patients.

Don't look at me in anger! Enhanced processing of angry faces in anticipation of public speaking

Anxiety is supposed to enhance the processing of threatening information. Here, we investigated the cortical processing of angry faces during anticipated public speaking. To elicit anxiety, a group of participants was told that they would have to perform a public speech. As a control condition, another group was told that they would have to write a short essay. During anticipation of these tasks, participants saw facial expressions (angry, happy, and neutral) while electroencephalogram was recorded. Event-related potential analysis revealed larger N170 amplitudes for angry compared to happy and neutral faces in the anxiety group. The early posterior negativity as an index of motivated attention was also enhanced for angry compared to happy and neutral faces in participants anticipating public speaking. These results indicate that fear of public speaking influences early perceptual processing of faces such that especially the processing of angry faces is facilitated.

Brain potentials during mental arithmetic: effects of extensive practice and problem difficulty

Recent behavioral investigations indicate that the processes underlying mental arithmetic change systematically with practice from deliberate, conscious calculation to automatic, direct retrieval of answers from memory [Bourne, L.E.Jr. and Rickard, T.C., Mental calculation: The development of a cognitive skill, Paper presented at the Interamerican Congress of Psychology, San Jose, Costa Rica, 1991: Psychol. Rev., 95 (1988) 492-527]. Results reviewed by Moscovitch and Winocur [In: The handbook of aging and cognition, Erlbaum, Hillsdale, NJ, 1992, pp. 315-372] suggest that consciously controlled processes are more dependent on frontal lobe function than are automatic processes. It is appropriate, therefore to determine whether transitions in the locus of primary brain activity occur with practice on mental calculation. In this experiment, we examine the relationship between characteristics of event-related brain potentials (ERPs) and mental arithmetic. Single-digit mental multiplication problems varying in difficulty (problem size) were used, and subjects were trained on these problems for four sessions. Problem-size and practice effects were reliably found in behavioral measures (RT). The ERP was characterized by a pronounced late positivity after task presentation followed by a slow wave, and a negativity during response indication. These components responded differentially to the practice and problem-size manipulations. Practice mainly affected topography of the amplitude of positivity and offset latency of slow wave, and problem-size mainly offset latency of slow wave and pre-response negativity. Fronto-central positivity diminished from session to session, and the focus of positivity centered finally at centro-parietal regions.(ABSTRACT TRUNCATED AT 250 WORDS)