Imaginal Retraining Reduces Cigarette Smoking: A Randomized Controlled Study.

OBJECTIVES: Smoking is a highly prevalent addictive behavior with severe and life-shortening health consequences. This is the first study to evaluate the efficacy of a newly developed imaginal variant of approach bias modification (ABM) (i.e., imaginal retraining) for the reduction of craving for tobacco and actual smoking behavior. METHODS: We randomized 345 smokers to imaginal retraining (self-help manual) or a control group (either active control or wait-list control). Assessments were carried out online. The treatment interval was 6 weeks. Craving for tobacco represented the primary outcome. The study was registered as DRKS00016860. RESULTS: Retention was 79.7% with no difference between groups. The intention-to-treat (ITT) analyses were significant for the primary outcome (Visual Analogue Scale on craving for tobacco) as well as subjective reduction of smoking (45.5 vs. 26.4%) in favor of imaginal retraining. In the treatment group, 47.6% performed the exercises at least once. This subgroup (per-protocol [PP] sample) showed a significant reduction in tobacco dependency as measured with the Cigarette Dependence Scale (short and long forms) and the Fagerström Test for Nicotine Dependence relative to controls. Number of daily cigarettes declined to a greater extent in imaginal retraining in the PP but not ITT analysis. A small dose-effect relationship emerged between craving and frequency of performance of the technique. CONCLUSION: When used regularly, imaginal retraining may reduce craving for tobacco and actual smoking behavior in a subgroup of smokers. In view of the large subgroup that did not read the manual or did not perform the exercises, alternative ways of conveying the imaginal retraining technique should be sought (e.g., demonstration via video clips). To conclude, imaginal retraining may represent a simple low-threshold technique to reduce smoking and assist current evidence-based treatment programs targeted at abstinence. It needs to be tested whether its mechanism of action deviates from standard ABM.

Trauma, treatment and Tetris: video gaming increases hippocampal volume in male patients with combat-related posttraumatic stress disorder.

Background: Tetris has been proposed as a preventative intervention to reduce intrusive memories of a traumatic event. However, no neuroimaging study has assessed Tetris in patients with existing posttraumatic stress disorder (PTSD) or explored how playing Tetris may affect brain structure. Methods: We recruited patients with combat-related PTSD before psychotherapy and randomly assigned them to an experimental Tetris and therapy group (n = 20) or to a therapy-only control group (n = 20). In the control group, participants completed therapy as usual: eye movement desensitization and reprocessing (EMDR) psychotherapy. In the Tetris group, in addition to EMDR, participants also played 60 minutes of Tetris every day from onset to completion of therapy, approximately 6 weeks later. Participants completed structural MRI and psychological questionnaires before and after therapy, and we collected psychological questionnaire data at follow-up, approximately 6 months later. We hypothesized that the Tetris group would show increases in hippocampal volume and reductions in symptoms, both directly after completion of therapy and at follow-up. Results: Following therapy, hippocampal volume increased in the Tetris group, but not the control group. As well, hippocampal increases were correlated with reductions in symptoms of PTSD, depression and anxiety between completion of therapy and follow-up in the Tetris group, but not the control group. Limitations: Playing Tetris may act as a cognitive interference task and as a brain-training intervention, but it was not possible to distinguish between these 2 potential mechanisms. Conclusion: Tetris may be useful as an adjunct therapeutic intervention for PTSD. Tetris-related increases in hippocampal volume may ensure that therapeutic gains are maintained after completion of therapy.

Imaginal retraining decreases craving for high-calorie food in overweight and obese women: A randomized controlled trial.

Overweight and obesity are epidemic conditions. Obesity is associated with somatic and psychological sequelae, including serious life-shortening disorders (e.g., diabetes). This study aimed to evaluate the efficacy of a newly developed imaginal variant of approach bias modification (i.e., imaginal retraining) for the reduction of craving for high-calorie food. In a randomized controlled trial, 384 women with a body mass index above 25 were allocated to a wait-list control group or to two variants of imaginal retraining (ratio: 1; 0.5; 0.5). The two intervention groups were sent a manual on imaginal retraining. One group was explicitly encouraged and instructed to use electronic reminders (RER); the standard retraining group (RS) was not encouraged to use electronic reminders. Assessments were 6 weeks apart and were carried out online. Craving for high-calorie food represented the primary outcome (based on the Visual Analog Scale, VAS). Secondary outcomes included the Food Cravings Questionnaire (FCQ-T-R). The study was registered as DRKS00017220. Women in the RER group utilized the retraining technique more often than those in the RS condition, and utilization frequency in turn was associated with improvement on craving and eating behavior scales. Both intention-to-treat and per-protocol analyses showed a favorable effect of the RER group, which achieved significance on the primary outcome, as well as on several other outcomes relative to controls at a small to medium effect size. For those participants who measured their weight before and after the assessment using a scale, weight loss in the RER group was significantly greater compared to the control group. Both retraining groups (RER: 39.4%; RS: 31.1%) reduced their subjective amount of eating relative to controls (24.2%). Approximately two-thirds of the sample (68.3%) performed the exercises at least once during the study period. The present results show that, when used regularly, imaginal retraining may reduce craving for high-calorie food in overweight and obese women. Of note, there was also evidence suggestive of weight reduction, although no diet or lifestyle change was recommended in the manual. Because a large subgroup neither read the manual nor performed the exercises, we recommend that future imaginal retraining be conveyed via short video clips.

Imaginal retraining reduces alcohol craving in problem drinkers: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: Retraining, a psychological intervention derived from the approach-avoidance paradigm, has yielded mixed results for the treatment of alcohol use disorder as well as other forms of addiction. The present study investigated the efficacy of an imaginal variant of retraining that allowed greater personalization of the content. METHODS: Within the framework of a randomized controlled trial (RCT), 84 individuals with self-reported alcohol-related problems were recruited over the Internet and allocated to either imaginal retraining (treatment manual dispatched as a pdf-file via email) or a wait-list control group (with care-as-usual). The intervention period was four weeks. Alcohol craving, as measured with a visual analogue scale (VAS), served as the primary outcome. Other emotional (e.g. self-esteem) and drinking-related variables served as secondary outcomes. RESULTS: Both per-protocol (PP) and intention-to-treat (ITT) analyses showed that imaginal retraining led to a significant reduction in alcohol craving compared to the control group at a large effect size. Self-esteem improved in the retraining condition relative to controls in the PP and one of the ITT analyses; 75% of the individuals in the treatment group reported less alcohol consumption in the treatment period, whereas drinking behavior remained essentially unchanged in the control group (p < .001) (the trial was registered at the German Clinical Trials Register, DRKS00015319). LIMITATIONS: Whether the effects of imaginal retraining are sustained over time needs to be established. Attrition was significantly higher in the retraining group (40.5%) than in the control group (16.7%). Designs with an active control condition are needed as well as dismantling studies to explore which of the treatment's multiple components best predicts improvement. Future studies should verify participants' alcohol consumption levels using objective measures. CONCLUSION: Imaginal retraining led to significant effects on the reduction of alcohol craving.

Influence of nutritional tyrosine on cognition and functional connectivity in healthy old humans.

Tyrosine is precursor for monoamine neurotransmitters such as dopamine (DA), which is one of the key neurotransmitters in the frontostriatal network and of crucial relevance for mental disorders. Recent research reported that high dose tyrosine application resulted in increased brain DA synthesis, which is consistent with the observation of positive associations between daily tyrosine intake and cognitive test performance. In the present study, we investigated the associations between working memory (WM) dependent tasks and self-reported nutritional tyrosine intake within a large group of healthy elderly humans (286 subjects) by additionally including brain functional data. We observed a negative correlation between tyrosine intake and resting-state functional connectivity (rsFC) between the striatum (putamen) and the prefrontal cortex. That is to say, we found higher rsFC in individuals consuming less tyrosine per day. At the same time, this increasedrsFC or hyperconnectivity was associated with lower WM performance. These findings suggest that lower or insufficient supply of tyrosine might result in dysfunctional connectivity between striatal and frontal regions leading to lower WM capacity in healthy elderly humans.

Food for thought: association between dietary tyrosine and cognitive performance in younger and older adults.

The fact that tyrosine increases dopamine availability that, in turn, may enhance cognitive performance has led to numerous studies on healthy young participants taking tyrosine as a food supplement. As a result of this dietary intervention, participants show performance increases in working memory and executive functions. However, the potential association between habitual dietary tyrosine intake and cognitive performance has not been investigated to date. The present study aims at clarifying the association of episodic memory (EM), working memory (WM) and fluid intelligence (Gf), and tyrosine intake in younger and older adults. To this end, we acquired habitual tyrosine intake (food frequency questionnaire) from 1724 participants of the Berlin Aging Study II (1383 older adults, 341 younger adults) and modelled its relations to cognitive performance assessed in a broad battery of cognitive tasks using structural equation modeling. We observed a significant association between tyrosine intake and the latent factor capturing WM, Gf, and EM in the younger and the older sample. Due to partial strong factorial invariance between age groups for a confirmatory factor analysis on cognitive performance, we were able to compare the relationship between tyrosine and cognition between age groups and found no difference. Above and beyond previous studies on tyrosine food supplementation the present result extend this to a cross-sectional association between habitual tyrosine intake levels in daily nutrition and cognitive performance (WM, Gf, and EM). This corroborates nutritional recommendations that are thus far derived from single-dose administration studies.

Deductive development and validation of a questionnaire to assess sensitivity to very low and very high frequency sounds: SISUS-Q (Sensitivity to Infra-Sound and Ultra-Sound Questionnaire).

OBJECTIVE: Auditory research and complaints about environmental noise indicate that there exists a significant, small subgroup within the population which is sensitive towards infra- and low-frequency or ultra- and high-frequency sounds (ILF/UHF). This paper reports on the development, factorization and validation of measures of sensitivity towards frequencies outside the common hearing range. DESIGN: A multinational, cross-sectional survey study was run. Principal component analyses and exploratory factor analyses were conducted in a sample of 267 Europeans (from the UK, Slovenia, and Germany). RESULTS: The factor analyses suggested that ILF versus UHF sensitivity constitute different factors, each characterized by sensory perception, stress-responsivity, and behavioral avoidance. A third factor comprising beliefs of dangerousness of ILF and UHF emerged. The factors explained 72% of the variance. The factor-solution was replicated separately for the English (n = 98) and German (n = 169) versions of the questionnaire (Slovenians and UK residents filled out the English version). Acceptable to excellent reliability was found. ILF and UHF sensitivity were moderately related to noise sensitivity in the normal hearing range, suggesting the new measures are not redundant. Correlations with psychiatric and somatic symptoms were small to moderate. ILF sensitivity correlated with neuroticism (small effect) and daytime sleepiness (moderate effect). ILF and UHF sensitivity were related to agreeableness (small effects). Overall, the novel ILF and UHF sensitivity scales seems to provide a solid tool for conducting further research on the role of sensitivity concerning adverse effects of ILF and UHF sound (e.g. health outcomes, annoyance ratings). The questionnaire consortium recommends using the new scales in combination with established measures of normal hearing range sensitivity.

Altered cortical and subcortical connectivity due to infrasound administered near the hearing threshold - Evidence from fMRI.

In the present study, the brain's response towards near- and supra-threshold infrasound (IS) stimulation (sound frequency < 20 Hz) was investigated under resting-state fMRI conditions. The study involved two consecutive sessions. In the first session, 14 healthy participants underwent a hearing threshold-as well as a categorical loudness scaling measurement in which the individual loudness perception for IS was assessed across different sound pressure levels (SPL). In the second session, these participants underwent three resting-state acquisitions, one without auditory stimulation (no-tone), one with a monaurally presented 12-Hz IS tone (near-threshold) and one with a similar tone above the individual hearing threshold corresponding to a 'medium loud' hearing sensation (supra-threshold). Data analysis mainly focused on local connectivity measures by means of regional homogeneity (ReHo), but also involved independent component analysis (ICA) to investigate inter-regional connectivity. ReHo analysis revealed significantly higher local connectivity in right superior temporal gyrus (STG) adjacent to primary auditory cortex, in anterior cingulate cortex (ACC) and, when allowing smaller cluster sizes, also in the right amygdala (rAmyg) during the near-threshold, compared to both the supra-threshold and the no-tone condition. Additional independent component analysis (ICA) revealed large-scale changes of functional connectivity, reflected in a stronger activation of the right amygdala (rAmyg) in the opposite contrast (no-tone > near-threshold) as well as the right superior frontal gyrus (rSFG) during the near-threshold condition. In summary, this study is the first to demonstrate that infrasound near the hearing threshold may induce changes of neural activity across several brain regions, some of which are known to be involved in auditory processing, while others are regarded as keyplayers in emotional and autonomic control. These findings thus allow us to speculate on how continuous exposure to (sub-)liminal IS could exert a pathogenic influence on the organism, yet further (especially longitudinal) studies are required in order to substantialize these findings.

Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands--A review.

Consuming the amino-acid tyrosine (TYR), the precursor of dopamine (DA) and norepinephrine (NE), may counteract decrements in neurotransmitter function and cognitive performance. However, reports on the effectiveness of TYR supplementation vary considerably, with some studies finding beneficial effects, whereas others do not. Here we review the available cognitive/behavioral studies on TYR, to elucidate whether and when TYR supplementation can be beneficial for performance. The potential of using TYR supplementation to treat clinical disorders seems limited and its benefits are likely determined by the presence and extent of impaired neurotransmitter function and synthesis. Likewise, the potential of TYR supplementation for enhancing physical exercise seems minimal as well, perhaps because the link between physical exercise and catecholamine function is mediated by many other factors. In contrast, TYR does seem to effectively enhance cognitive performance, particularly in short-term stressful and/or cognitively demanding situations. We conclude that TYR is an effective enhancer of cognition, but only when neurotransmitter function is intact and DA and/or NE is temporarily depleted.

Prefrontal and Striatal Glutamate Differently Relate to Striatal Dopamine: Potential Regulatory Mechanisms of Striatal Presynaptic Dopamine Function?

Theoretical and animal work has proposed that prefrontal cortex (PFC) glutamate inhibits dopaminergic inputs to the ventral striatum (VS) indirectly, whereas direct VS glutamatergic afferents have been suggested to enhance dopaminergic inputs to the VS. In the present study, we aimed to investigate relationships of glutamate and dopamine measures in prefrontostriatal circuitries of healthy humans. We hypothesized that PFC and VS glutamate, as well as their balance, are differently associated with VS dopamine. Glutamate concentrations in the left lateral PFC and left striatum were assessed using 3-Tesla proton magnetic resonance spectroscopy. Striatal presynaptic dopamine synthesis capacity was measured by fluorine-18-l-dihydroxyphenylalanine (F-18-FDOPA) positron emission tomography. First, a negative relationship was observed between glutamate concentrations in lateral PFC and VS dopamine synthesis capacity (n = 28). Second, a positive relationship was revealed between striatal glutamate and VS dopamine synthesis capacity (n = 26). Additionally, the intraindividual difference between PFC and striatal glutamate concentrations correlated negatively with VS dopamine synthesis capacity (n = 24). The present results indicate an involvement of a balance in PFC and striatal glutamate in the regulation of VS dopamine synthesis capacity. This notion points toward a potential mechanism how VS presynaptic dopamine levels are kept in a fine-tuned range. A disruption of this mechanism may account for alterations in striatal dopamine turnover as observed in mental diseases (e.g., in schizophrenia). SIGNIFICANCE STATEMENT: The present work demonstrates complementary relationships between prefrontal and striatal glutamate and ventral striatal presynaptic dopamine using human imaging measures: a negative correlation between prefrontal glutamate and presynaptic dopamine and a positive relationship between striatal glutamate and presynaptic dopamine are revealed. The results may reflect a regulatory role of prefrontal and striatal glutamate for ventral striatal presynaptic dopamine levels. Such glutamate-dopamine relationships improve our understanding of neurochemical interactions in prefrontostriatal circuits and have implications for the neurobiology of mental disease.

Changes in neural resting state activity in primary and higher-order motor areas induced by a short sensorimotor intervention based on the Feldenkrais method.

We use functional magnetic resonance imaging to investigate short-term neural effects of a brief sensorimotor intervention adapted from the Feldenkrais method, a movement-based learning method. Twenty-one participants (10 men, 19-30 years) took part in the study. Participants were in a supine position in the scanner with extended legs while an experienced Feldenkrais practitioner used a planar board to touch and apply minimal force to different parts of the sole and toes of their left foot under two experimental conditions. In the local condition, the practitioner explored movement within foot and ankle. In the global condition, the practitioner focused on the connection and support from the foot to the rest of the body. Before (baseline) and after each intervention (post-local, post-global), we measured brain activity during intermittent pushing/releasing with the left leg and during resting state. Independent localizer tasks were used to identify regions of interest (ROI). Brain activity during left-foot pushing did not significantly differ between conditions in sensorimotor areas. Resting state activity (regional homogeneity, ReHo) increased from baseline to post-local in medial right motor cortex, and from baseline to post-global in the left supplementary/cingulate motor area. Contrasting post-global to post-local showed higher ReHo in right lateral motor cortex. ROI analyses showed significant increases in ReHo in pushing-related areas from baseline to both post-local and post-global, and this increase tended to be more pronounced post-local. The results of this exploratory study show that a short, non-intrusive sensorimotor intervention can have short-term effects on spontaneous cortical activity in functionally related brain regions. Increased resting state activity in higher-order motor areas supports the hypothesis that the global intervention engages action-related neural processes.

Frontal glutamate and reward processing in adolescence and adulthood.

The fronto-limbic network interaction, driven by glutamatergic and dopaminergic neurotransmission, represents a core mechanism of motivated behavior and personality traits. Reward seeking behavior undergoes tremendous changes in adolescence paralleled by neurobiological changes of this network including the prefrontal cortex, striatum and amygdala. Since fronto-limbic dysfunctions also underlie major psychiatric diseases beginning in adolescence, this investigation focuses on network characteristics separating adolescents from adults. To investigate differences in network interactions, the brain reward system activity (slot machine task) together with frontal glutamate concentration (anterior cingulate cortex, ACC) was measured in 28 adolescents and 26 adults employing functional magnetic resonance imaging and magnetic resonance spectroscopy, respectively. An inverse coupling of glutamate concentrations in the ACC and activation of the ventral striatum was observed in adolescents. Further, amygdala response in adolescents was negatively correlated with the personality trait impulsivity. For adults, no significant associations of network components or correlations with impulsivity were found. The inverse association between frontal glutamate concentration and striatal activation in adolescents is in line with the triadic model of motivated behavior stressing the important role of frontal top-down inhibition on limbic structures. Our data identified glutamate as the mediating neurotransmitter of this inhibitory process and demonstrates the relevance of glutamate on the reward system and related behavioral traits like impulsivity. This fronto-limbic coupling may represent a vulnerability factor for psychiatric disorders starting in adolescence but not in adulthood.

The neural correlates of subjective pleasantness.

Processing of subjective pleasantness is essential in daily life decision making, particularly in the context of cognitive and environmental factors. Pleasure is mediated by a neural network and this network has been suggested to be the biological basis of pleasure including a whole range of different modalities and domains of pleasantness. This quantitative meta-analysis of brain imaging data focuses on studies 1) based on correlations between self-reported judgements of pleasantness and brain regions and investigates whether 2) immediate (during scanning) versus subsequent judgements (after scanning) differ in brain activity. We investigated concurrence across 40 studies reporting brain regions correlated with self-reported judgements of subjective pleasantness (attractiveness, liking or beauty) by means of activation likelihood estimation (ALE). Positive correlates of subjective pleasantness were found in mOFC, ventromedial prefrontal cortex, left ventral striatum, pregenual cortex, right cerebellum, left thalamus and the mid cingulate cortex. Negative correlates were found in left precentral gyrus, right cerebellum and right inferior frontal gyrus. A comparison of studies with subjective pleasantness judgement during or after scanning revealed no significant differences in brain activation. We conclude that subjective pleasantness judgements are directly related to brain regions that have been described as part of the reward circuitry (mOFC, ventral striatum). The results suggest that the evaluation of likability or pleasure is an automatic process and that it is neither elicited nor enhanced by instructions to report the outcome of these judgements.

The functional and neural mechanism of action preparation: roles of EBA and FFA in voluntary action control.

Ideomotor theory claims that actions are cognitively represented and accessed via representations of the sensory effects they evoke. Previous studies provide support for this claim by showing that the presentation of action effects primes activation in corresponding motor structures. However, whether people actually use action-effect representations to control their motor behavior is not yet clear. In our fMRI study, we had participants prepare for manual or facial actions on a trial-by-trial basis, and hypothesized that preparation would be mediated by the cortical areas that code for the perceptual effects of these actions. Preparing for manual action induced higher activation of hand-related areas of motor cortex (demonstrating actual preparation) and of the extrastriate body area, which is known to mediate the perception of body parts. In contrast, preparing for facial action induced higher activation of face-related motor areas and of the fusiform face area, known to mediate face perception. These observations provide further support for the ideomotor theory and suggest that visual imagery might play a role in voluntary action control.

Planning not to do something: Does intending not to do something activate associated sensory consequences?

The present fMRI study investigated the central assumptions of ideomotor theory that actions become associated with their sensory consequences. Furthermore, we tested whether sensory effects can also become associated with the voluntary omission of an action. In a training phase, participants had to decide between executing an action and not executing it. Both decisions were followed by a specific effect tone. In the test phase, the participants had to carry out actions without hearing the effect tone. They either had to decide whether to execute an action or not or were instructed to execute an action or not. Our results reveal an increased activity in the auditory cortex elicited by responses that formerly elicited a tone-namely, self-chosen actions and self-chosen nonactions. Moreover, we found binding effects for stimulus-cued actions, but not for stimulus-cued nonactions. These findings support ideomotor theory by showing that a link exists between actions and their effects. Furthermore, our data demonstrate on a neural level that effect tones can become associated with intentionally not acting, therewith supporting the idea of a binding between the voluntary omission of an action and its effects in the environment.

Dissociating mental states related to doing nothing by means of fMRI pattern classification.

Most juridical systems recognize intentional non-actions - the failure to render assistance - as intentional acts by regarding them as in principle culpable. This raises the fundamental question whether intentional non-actions can be distinguished from simply not doing anything. Classical GLM analysis on functional magnetic resonance imaging (fMRI) data reveals that not doing anything is associated with resting state brain areas whereas intentionally non-acting is associated with brain activity in left inferior parietal lobe and left dorsal premotor cortex. By means of pattern classification we quantify the accuracy with which we can distinguish these two mental states on the basis of brain activity. In order to identify brain regions that harbour a distributed, overlapping representation of voluntary non-actions and the decision not to act we performed pattern classification on brain areas that did not appear in the GLM contrasts. The prediction rate is not reduced and we show that the prediction relies mostly on brain areas that have been associated with action production and motor imagery as supplementary motor area, right inferior frontal gyrus and right middle temporal area (V5/MT). Hence our data support the implicit assumption of legal practice that voluntary non-action shares important features with overt voluntary action.

The neural correlates of intending not to do something.

There has been plenty of research concerning the representation of voluntary action in the human brain. However, the question of how we represent the voluntary omission of an action has been largely neglected. Therefore this study aimed at investigating the representation of intentionally not doing something by means of event-related potentials (ERPs). Free-choice nonactions elicit similar evoked potentials as free-choice actions and instructed actions (augmented P2 and attenuated N2), which leads us to assume that the voluntary intention, not the overt nonaction, is the characteristic feature of free-choice nonaction. Beyond that we reveal differences between free-choice nonactions and instructed nonactions that resemble the typical N2 and P3 augmentation usually seen for NoGo trials in Go/NoGo paradigms, with the difference that the free-choice nonaction ERP takes the place of the typical Go ERP.