Simone Kühn

Common biology of craving across legal and illegal drugs – a quantitative meta-analysis of cue-reactivity brain response

The present quantitative meta‐analysis set out to test whether cue‐reactivity responses in humans differ across drugs of abuse and whether these responses constitute the biological basis of drug craving as a core psychopathology of addiction. By means of activation likelihood estimation, we investigated the concurrence of brain regions activated by cue‐induced craving paradigms across studies on nicotine, alcohol and cocaine addicts. Furthermore, we analysed the concurrence of brain regions positively correlated with self‐reported craving in nicotine and alcohol studies. We found direct overlap between nicotine, alcohol and cocaine cue reactivity in the ventral striatum. In addition, regions of close proximity were observed in the anterior cingulate cortex (ACC; nicotine and cocaine) and amygdala (alcohol, nicotine and cocaine). Brain regions of concurrence in drug cue‐reactivity paradigms that overlapped with brain regions of concurrence in self‐reported craving correlations were found in the ACC, ventral striatum and right pallidum (for alcohol). This first quantitative meta‐analysis on drug cue reactivity identifies brain regions underlying nicotine, alcohol and cocaine dependency, i.e. the ventral striatum. The ACC, right pallidum and ventral striatum were related to drug cue reactivity as well as self‐reported craving, suggesting that this set of brain regions constitutes the core circuit of drug craving in nicotine and alcohol addiction.

Playing Super Mario induces structural brain plasticity: Gray matter changes resulting from training with a commercial video game

Video gaming is a highly pervasive activity, providing a multitude of complex cognitive and motor demands. Gaming can be seen as an intense training of several skills. Associated cerebral structural plasticity induced has not been investigated so far. Comparing a control with a video gaming training group that was trained for 2 months for at least 30 min per day with a platformer game, we found significant gray matter (GM) increase in right hippocampal formation (HC), right dorsolateral prefrontal cortex (DLPFC) and bilateral cerebellum in the training group. The HC increase correlated with changes from egocentric to allocentric navigation strategy. GM increases in HC and DLPFC correlated with participants’ desire for video gaming, evidence suggesting a predictive role of desire in volume change. Video game training augments GM in brain areas crucial for spatial navigation, strategic planning, working memory and motor performance going along with evidence for behavioral changes of navigation strategy. The presented video game training could therefore be used to counteract known risk factors for mental disease such as smaller hippocampus and prefrontal cortex volume in, for example, post-traumatic stress disorder, schizophrenia and neurodegenerative disease.

Experience-dependent plasticity of white-matter microstructure extends into old age

Experience-dependent alterations in the human brains white-matter microstructure occur in early adulthood, but it is unknown whether such plasticity extends throughout life. We used cognitive training, diffusion-tensor imaging (DTI), and structural MRI to investigate plasticity of the white-matter tracts that connect the left and right hemisphere of the frontal lobes. Over a period of about 180 days, 20 younger adults and 12 older adults trained for a total of one hundred and one 1-h sessions on a set of three working memory, three episodic memory, and six perceptual speed tasks. Control groups were assessed at pre- and post-test. Training affected several DTI metrics and increased the area of the anterior part of the corpus callosum. These alterations were of similar magnitude in younger and older adults. The findings indicate that experience-dependent plasticity of white-matter microstructure extends into old age and that disruptions of structural interhemispheric connectivity in old age, which are pronounced in aging, are modifiable by experience and amenable to treatment.

Resting-State Brain Activity in Schizophrenia and Major Depression: A Quantitative Meta-Analysis

Intrinsic activity of the brain during resting-state is not random and is currently discussed as a neural reflection of self-referential processing. Self-reference is typically reduced in schizophrenia as a disorder of the self while extensive self-attribution of, eg, negative thoughts is characteristic for major depression. However, a quantitative meta-analysis targeting the resting-state brain activity in both disorders is lacking. Here, we predict primarily abnormal resting-state activity in brain regions related to self-referential processing. By means of activation likelihood estimation (ALE) on functional magnetic resonance imaging and positron emission tomography studies, we investigated concurrence of hyperactivation and hypoactivation in resting-state measurements of schizophrenic and depressed patients compared with healthy controls. We found hypoactivation in ventromedial prefrontal cortex (vmPFC), left hippocampus, posterior cingulate cortex, lower precueus and the precuneus, and hyperactivation in bilateral lingual gyrus of schizophrenic patients. In major depression, we found hyperactivation in vmPFC, left ventral striatum, and left thalamus and hypoactivation in left postcentral gyrus, left fusiform gyrus, and left insula. An overall ALE analysis confirmed the proximity of hypoactivation in schizophrenia and hyperactivation in major depression in the vmPFC.The opposing resting-state activity in vmPFC for the 2 disorders is in line with the different expression of dysfunctional self-reference as core characteristics of schizophrenia and major depression. The vmPFC has previously been identified as a crucial area for self-referential processing and may represent a target to increase the diagnostic validity of resting-state activity for disorders with dysfunctions of the self.

Gray matter correlates of posttraumatic stress disorder: a quantitative meta-analysis

BACKGROUND Since the inception of the diagnosis posttraumatic stress disorder (PTSD), attempts have been undertaken to understand why only a subpopulation of individuals exposed to trauma develops PTSD. Cerebral gray matter reductions have been suggested to be a crucial pathobiological marker of PTSD. However, a quantitative meta-analysis of whole-brain voxel-based morphometry studies is lacking. METHODS Here, we investigated concurrence across voxel-based morphometry studies in PTSD compared with trauma-exposed individuals without PTSD (all together nine studies with 319 subjects) by means of activation likelihood estimation. RESULTS We identified brain regions of consistent gray matter reduction in anterior cingulate cortex, ventromedial prefrontal cortex, left temporal pole/middle temporal gyrus, and left hippocampus in PTSD patients compared with individuals exposed to trauma without PTSD. CONCLUSIONS This is the first quantitative whole-brain meta-analysis showing brain structure deficits in traumatized subjects with PTSD compared with trauma-exposed healthy control subjects. The gray matter deficit profile overlaps with brain networks of emotion processing, fear extinction, and emotion regulation known to be affected in PTSD. Although the data cannot clarify if this is a predisposition or a consequence of the disease, the results may facilitate the need to control for structural characteristics in future functional brain studies.

The neural basis of video gaming

Video game playing is a frequent recreational activity. Previous studies have reported an involvement of dopamine-related ventral striatum. However, structural brain correlates of video game playing have not been investigated. On magnetic resonance imaging scans of 154 14-year-olds, we computed voxel-based morphometry to explore differences between frequent and infrequent video game players. Moreover, we assessed the Monetary Incentive Delay (MID) task during functional magnetic resonance imaging and the Cambridge Gambling Task (CGT). We found higher left striatal grey matter volume when comparing frequent against infrequent video game players that was negatively correlated with deliberation time in CGT. Within the same region, we found an activity difference in MID task: frequent compared with infrequent video game players showed enhanced activity during feedback of loss compared with no loss. This activity was likewise negatively correlated with deliberation time. The association of video game playing with higher left ventral striatum volume could reflect altered reward processing and represent adaptive neural plasticity.

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.

Reduced Thickness of Medial Orbitofrontal Cortex in Smokers

BACKGROUND Structural deficiencies within the prefrontal cortex might be related to drug-taking behavior that prevails in smokers. Cortical thickness has been found to be a structural modulator of cerebral function and cognition and a subtle correlate of mental disorders. However, to date an analysis of cortical thickness in smokers compared with never-smokers has not been undertaken. METHODS We acquired high-resolution magnetic resonance imaging scans from 22 smokers and 21 never-smokers and used FreeSurfer to model the gray-white and pial surfaces for each individual cortex to compute the distance between these surfaces to obtain a measure of cortical thickness. The main cortical folds were aligned across individuals with FreeSurfers surface-based averaging technique to compare whole brain differences in cortical thickness between smokers and never-smokers. RESULTS Relative to never-smokers, smokers showed greater cortical thinning in the left medial orbitofrontal cortex (mOFC). Cortical thickness measures extracted from mOFC correlated negatively with the amount of cigarettes consumed/day and the magnitude of lifetime exposure to tobacco smoke. CONCLUSIONS The brains of smokers are structurally different from those of never-smokers in a dose-dependent manner. The cortical thinning in mOFC in smokers relative to never-smokers might imply dysfunctions of the brains reward, impulse control, and decision-making circuits. Related behavioral correlates are suggested to be relevant for smoking initiation and maintenance.

Outcome Expectancy and Not Accuracy Determines Posterror Slowing: ERP Support

A considerable number of studies have recently used event-related potentials (ERPs) to investigate the mechanisms underlying error processing. Nevertheless, how these mechanisms are associated with behavioral adjustments following errors remains unclear. In the present study, we investigated how posterror slowing is linked to outcome expectations and error feedback. We used an adaptive four-choice reaction time task to manipulate outcome expectancy. Behaviorally, the results show posterror slowing when errors are unexpected and postcorrect slowing when correct responses are unexpected, indicating that outcome expectancy is crucial for posterror slowing. ERP analyses revealed that the error-related negativity and the feedback-related negativity were not correlated with the behavioral reaction time pattern, whereas the P3 was. The results support the hypothesis that posterror slowing is caused by attentional orienting to unexpected events.

Intentional Inhibition: How the Veto-Area Exerts Control

One important aspect of self‐control is refraining voluntarily from already planned behavior, by a final intervention before commitment to action. Despite its crucial role in human existence, and clear social implications, this aspect of self‐control has proved hard to study experimentally. One recent study used a perceptual timing paradigm to identify specific activations in the dorsal fronto‐median cortex (dFMC) associated with voluntary inhibition of action (Brass and Haggard 2007 : J Neurosci 27:9141–9145). Here, we extend this work in two important new directions. First, we developed a more naturalistic task that gives participants a strong reason to inhibit or to execute actions, and therefore involves self‐control in the sense of voluntary inhibition of prepotent impulsive responses. Second, we investigated the relation between dFMC and other cognitive‐motor areas using effective connectivity analysis. We show that dFMC is activated when inhibiting prepared responses to external events. Moreover, its effective connectivity suggests that it allows intentional inhibition of action through top‐down inhibition of premotor areas. This view of dFMC is consistent with a new view of self‐control as a key stage in a cognitive‐motor interface. Hum Brain Mapp, 2009.