Kristine Rømer Thomsen

Dopaminergic stimulation enhances confidence and accuracy in seeing rapidly presented words

Liberal acceptance, overconfidence, and increased activity of the neurotransmitter dopamine have been proposed to account for abnormal sensory experiences, for instance, hallucinations in schizophrenia. In normal subjects, increased sensory experience in Yoga Nidra meditation is linked to striatal dopamine release. We therefore hypothesize that the neurotransmitter dopamine may function as a regulator of subjective confidence of visual perception in the normal brain. Although much is known about the effect of stimulation by neurotransmitters on cognitive functions, their effect on subjective confidence of perception has never been recorded experimentally before. In a controlled study of 24 normal, healthy female university students with the dopamine agonist pergolide given orally, we show that dopaminergic activation increases confidence in seeing rapidly presented words. It also improves performance in a forced-choice word recognition task. These results demonstrate neurotransmitter regulation of subjective conscious experience of perception and provide evidence for a crucial role of dopamine.

Minor structural abnormalities in the infant face disrupt neural processing: a unique window into early caregiving responses.

Infant faces elicit early, specific activity in the orbitofrontal cortex (OFC), a key cortical region for reward and affective processing. A test of the causal relationship between infant facial configuration and OFC activity is provided by naturally occurring disruptions to the face structure. One such disruption is cleft lip, a small change to one facial feature, shown to disrupt parenting. Using magnetoencephalography, we investigated neural responses to infant faces with cleft lip compared with typical infant and adult faces. We found activity in the right OFC at 140 ms in response to typical infant faces but diminished activity to infant faces with cleft lip or adult faces. Activity in the right fusiform face area was of similar magnitude for typical adult and infant faces but was significantly lower for infant faces with cleft lip. This is the first evidence that a minor change to the infant face can disrupt neural activity potentially implicated in caregiving.

Altered paralimbic interaction in behavioral addiction

The introduction of magnetoencephalography has made it possible to study electromagnetic signaling in deeper, paralimbic cortical structures such as the medial prefrontal/anterior cingulate (ACC) and medial parietal/posterior cingulate (PCC) cortices. Self-awareness and self-control have been attributed to these regions. To test the hypothesis that they are dysfunctional in pathological gambling with poor self-control, we studied gamblers with and without previous stimulant abuse and age- and sex-matched controls. We found that pathological gamblers were more impulsive than controls in a stop-signal task and attributed this to changes in the activity of the paralimbic network: Pathological gamblers had reduced synchronization at rest in the high gamma range (55–100 Hz) compared with controls and failed to show an increase in gamma synchronization during rest compared with the task, as observed in controls. Subgroup analysis revealed that pathological gamblers without a history of stimulant abuse had lower PCC power during the stop-signal task compared with controls and gamblers with previous stimulant abuse. Furthermore, gamblers with a history of stimulant abuse had up to four times higher power at the ACC site during rest and the task compared with controls. In conclusion, pathological gamblers had higher impulsivity and functional paralimbic abnormalities, which could not be explained by a history of stimulant abuse. In addition, previous stimulant abuse had a marked effect on the amplitude of oscillatory brain activity in the ACC and PCC, suggesting long-term deleterious effects of repeated dopaminergic drug exposure. These consequences should be investigated in more detail in longitudinal studies.

Measuring anhedonia: impaired ability to pursue, experience, and learn about reward

Ribot’s (1896) long standing definition of anhedonia as “the inability to experience pleasure” has been challenged recently following progress in affective neuroscience. In particular, accumulating evidence suggests that reward consists of multiple subcomponents of wanting, liking and learning, as initially outlined by Berridge and Robinson (2003), and these processes have been proposed to relate to appetitive, consummatory and satiety phases of a pleasure cycle. Building on this work, we recently proposed to reconceptualize anhedonia as “impairments in the ability to pursue, experience, and/or learn about pleasure, which is often, but not always accessible to conscious awareness.” (Rømer Thomsen et al., 2015). This framework is in line with Treadway and Zald’s (2011) proposal to differentiate between motivational and consummatory types of anhedonia, and stresses the need to combine traditional self-report measures with behavioral measures or procedures. In time, this approach may lead to improved clinical assessment and treatment. In line with our reconceptualization, increasing evidence suggests that reward processing deficits are not restricted to impaired hedonic impact in major psychiatric disorders. Successful translations of animal models have led to strong evidence of impairments in the ability to pursue and learn about reward in psychiatric disorders such as major depressive disorder, schizophrenia, and addiction. It is of high importance that we continue to systematically target impairments in all phases of reward processing across disorders using behavioral testing in combination with neuroimaging techniques. This in turn has implications for diagnosis and treatment, and is essential for the purposes of identifying the underlying neurobiological mechanisms. Here I review recent progress in the development and application of behavioral procedures that measure subcomponents of anhedonia across relevant patient groups, and discuss methodological caveats as well as implications for assessment and treatment.

Applying incentive sensitization models to behavioral addiction.

The incentive sensitization theory is a promising model for understanding the mechanisms underlying drug addiction, and has received support in animal and human studies. So far the theory has not been applied to the case of behavioral addictions like Gambling Disorder, despite sharing clinical symptoms and underlying neurobiology. We examine the relevance of this theory for Gambling Disorder and point to predictions for future studies. The theory promises a significant contribution to the understanding of behavioral addiction and opens new avenues for treatment.

Event frequency, excitement and desire to gamble, among pathological gamblers

In this study we compared gambling behaviour of 15 pathological gamblers (PG) and 15 non-problem gamblers (NPG) on two conditions of a commercially available slot machine. One condition used a commercially available two-second event frequency (games per minute), while the other condition used an experimental three-second event frequency. The payback percentage (wins relative to losses) and reward frequency (wins over number of games played) varied randomly across conditions. The results showed that PG had significantly higher measures than NPG on time spent gambling, excitement level and desire to play again in the two-second condition. In the three-second condition there were no differences in excitement level and desire to play again. The number of PG playing the maximum time (60 minutes) was reduced in the three-second version, and reward frequency contributed to reduction in time spent gambling. The results may have implications for understanding behavioural mechanisms of pathological gambling among slot machine players.

Making sense: dopamine activates conscious self-monitoring through medial prefrontal cortex

When experiences become meaningful to the self, they are linked to synchronous activity in a paralimbic network of self‐awareness and dopaminergic activity. This network includes medial prefrontal and medial parietal/posterior cingulate cortices, where transcranial magnetic stimulation may transiently impair self‐awareness. Conversely, we hypothesize that dopaminergic stimulation may improve self‐awareness and metacognition (i.e., the ability of the brain to consciously monitor its own cognitive processes). Here, we demonstrate improved noetic (conscious) metacognition by oral administration of 100 mg dopamine in minimal self‐awareness. In a separate experiment with extended self‐awareness dopamine improved the retrieval accuracy of memories of self‐judgment (autonoetic, i.e., explicitly self‐conscious) metacognition. Concomitantly, magnetoencephalography (MEG) showed increased amplitudes of oscillations (power) preferentially in the medial prefrontal cortex. Given that electromagnetic activity in this region is instrumental in self‐awareness, this explains the specific effect of dopamine on explicit self‐awareness and autonoetic metacognition. Hum Brain Mapp 36:1866–1877, 2015.

Recommendation to reconsider examining cannabis subtypes together due to opposing effects on brain, cognition and behavior

Cannabis use represents a major public health issue throughout the globe. Yet, we still lack the most fundamental knowledge on long-term effects of cannabis on neural, cognitive, and behavioral function. Part of this stems from how cannabis has been measured historically. To this end, most empirical examinations of cannabis have consolidated all types of cannabis collectively. However, this approach obscures differences in how cannabinoids operate. In this commentary, we address the contrasting properties of tetrahydrocannabinol (THC) and cannabidiol (CBD) and their opposing effects on cognitive function. In addition, we address the increase in cannabis potency throughout the past two decades and how that impacts generalizability of early data to evaluations of contemporary public health. We underscore the urgent need for future research to disaggregate examination of THC from CBD, along with the importance of measuring cannabis potency to more effectively unravel its influence on cognitive function and other health issues.

Mapping risk factors for substance use: Introducing the YouthMap12

BACKGROUND In adolescence, psychological problems and regular use of alcohol, cigarettes, cannabis and other drugs (AOD) tend to cluster together, strongly indicating that certain groups of young people are at elevated risk of developing a problematic use of AOD. OBJECTIVE The aim of the present study was to develop an easy-to-implement screening instrument to identify subgroups of young people with different psychological problems at risk of problem use of AOD. METHOD 3589 randomly selected young Danes between 15 and 25years of age, from a national survey (n=2702) and a municipality survey (n=887), answered a 12-item questionnaire (YouthMap12) with 6 items identifying externalizing problems (EP6) and 6 items identifying internalizing problems (IP6). Latent class analysis (LCA) was used to characterize groups at risk, and associations were estimated between EP6 and IP6 and regular use of AOD, and between latent class membership and regular use of AOD. RESULTS LCA identified 6 classes with varying degrees of externalizing and internalizing problems: 70% of youth were in the low problem score class, and the remaining 30% were at various levels of risk. Regular use of cigarettes, cannabis and alcohol was strongly associated with classes characterized by externalizing problems, while over-the-counter and prescription medicine was strongly associated with classes characterized by internalizing problems. CONCLUSIONS Youth at risk of problem use of AOD can be identified using a simple and easily administered instrument.

The intersection between response inhibition and substance use among adolescents

Problems related to the capacity to successfully engage response inhibition are considered a risk factor for the development of substance use disorders (SUDs), but the evidence has been predominantly cross-sectional. In this commentary, we argue that recent longitudinal studies with multi-modal measures of response inhibition can improve understanding of how response inhibition may intersect with substance use among adolescents. Most Stop-Signal studies suggest that slower response inhibition predicts substance use progressions, with one multi-site study showing greater fronto-parietal activity indicative of risk. Most Go-NoGo studies suggest that blunted activation of prefrontal cortical areas during response inhibition predicts substance use progressions, while commission errors are less effective in identifying adolescents at risk. Studies differ in subject populations, outcome measures, statistical methods, and BOLD response contrasts, which challenge the capacity to compare and generalize findings. We encourage research teams throughout the globe to undertake multi-modal, longitudinal studies to assess brain functioning with large sample sizes, and when possible, before significant substance use potentially obscures interpretation of findings. Systematic review and meta-analysis of this growing literature are also important goals for future research.