Markers of Insight

Sometimes creative ideas come to mind following a step-by-step conscious reasoning, other times they rush into consciousness unexpectedly as sudden insights. Research on insight problem solving began about a century ago with a chimpanzee having an Aha! moment on how to pile up some boxes to reach a banana that was hanging from the ceiling (Köhler, 1917). Thanks to the development of neuroscientific techniques, researchers gained a better understanding of the physiology associated with insight, supplemented classic theories, and raised new questions about the cognitive processes involved in it. With the final goal of sketching a comprehensive understanding of the neurocognitive bases of insight, this chapter describes and updates the knowledge we gained about its functioning. A review of the last two decades of research on the ‘markers of insight’ revealed that: a) insights are paired with an internal attention allocation; b) the right anterior temporal lobe is a key node for insights, and if stimulated the frequency of insights increases; c) the feeling of pleasure and excitement that accompanies insights is warranted by the involvement of the reward-dopamine system; d) pupil dilation marks the switch into awareness of Aha! moments. Taken together these results indicate that insight below awareness processing might be explained by the involvement of subcortical areas responsible for learning, alertness, and emotions which are evolutionary more ancient than the cortex and it involves areas of the cortex responsible for information integration presumably together/after the switch into awareness. In conclusion, I summarize these points in terms of the defining characteristics of having an insight.

Influence of Catechol-O-Methyltransferase Gene Polymorphism on the Correlation between Alexithymia and Hypervigilance to Pain

The psychological characteristic of having difficulty expressing emotions, known as alexithymia, is associated with hypervigilance to pain and is considered one of the risk factors for chronic pain. The correlation between alexithymia and hypervigilance to pain can be observed even in healthy individuals. However, the factors influencing this correlation remain unknown. We explored the dopamine system, which is known to be involved in emotion and pain. The dopamine-degrading enzyme catechol-O-methyltransferase (COMT) has a genetic polymorphism known to influence dopamine metabolism in the prefrontal cortex. COMT polymorphism reportedly affects various aspects of pain and increases pain sensitivity in Met allele carriers. Therefore, we investigated whether the correlation between alexithymia and hypervigilance to pain is influenced by COMT polymorphism in healthy individuals. The results revealed a significant positive correlation between the “difficulty describing feelings” of the 20-item Toronto Alexithymia Scale and the “attention to changes in pain” of the pain vigilance and awareness questionnaire in COMT Met carriers but not in Val/Val individuals. This finding suggests that the correlation between alexithymia and hypervigilance to pain is influenced by COMT polymorphism.

The Dopamine System and Automatization of Movement Sequences: A Review With Relevance for Speech and Stuttering

The last decades of research have gradually elucidated the complex functions of the dopamine system in the vertebrate brain. The multiple roles of dopamine in motor function, learning, attention, motivation, and the emotions have been difficult to reconcile. A broad and detailed understanding of the physiology of cerebral dopamine is of importance in understanding a range of human disorders. One of the core functions of dopamine involves the basal ganglia and the learning and execution of automatized sequences of movements. Speech is one of the most complex and highly automatized sequential motor behaviors, though the exact roles that the basal ganglia and dopamine play in speech have been difficult to determine. Stuttering is a speech disorder that has been hypothesized to be related to the functions of the basal ganglia and dopamine. The aim of this review was to provide an overview of the current understanding of the cerebral dopamine system, in particular the mechanisms related to motor learning and the execution of movement sequences. The primary aim was not to review research on speech and stuttering, but to provide a platform of neurophysiological mechanisms, which may be utilized for further research and theoretical development on speech, speech disorders, and other behavioral disorders. Stuttering and speech are discussed here only briefly. The review indicates that a primary mechanism for the automatization of movement sequences is the merging of isolated movements into chunks that can be executed as units. In turn, chunks can be utilized hierarchically, as building blocks of longer chunks. It is likely that these mechanisms apply also to speech, so that frequent syllables and words are produced as motor chunks. It is further indicated that the main learning principle for sequence learning is reinforcement learning, with the phasic release of dopamine as the primary teaching signal indicating successful sequences. It is proposed that the dynamics of the dopamine system constitute the main neural basis underlying the situational variability of stuttering.

Dopamine, behavior, and addiction

Addictive drugs are habit-forming. Addiction is a learned behavior; repeated exposure to addictive drugs can stamp in learning. Dopamine-depleted or dopamine-deleted animals have only unlearned reflexes; they lack learned seeking and learned avoidance. Burst-firing of dopamine neurons enables learning—long-term potentiation (LTP)—of search and avoidance responses. It sets the stage for learning that occurs between glutamatergic sensory inputs and GABAergic motor-related outputs of the striatum; this learning establishes the ability to search and avoid. Independent of burst-firing, the rate of single-spiking—or “pacemaker firing”—of dopaminergic neurons mediates motivational arousal. Motivational arousal increases during need states and its level determines the responsiveness of the animal to established predictive stimuli. Addictive drugs, while usually not serving as an external stimulus, have varying abilities to activate the dopamine system; the comparative abilities of different addictive drugs to facilitate LTP is something that might be studied in the future.

Dopamine promotes aggression in mice via ventral tegmental area to lateral septum projections

Septal-hypothalamic neuronal activity centrally mediates aggressive behavior and dopamine system hyperactivity is associated with elevated aggression. However, the causal role of dopamine in aggression and its target circuit mechanisms are largely unknown. To address this knowledge gap, we studied the modulatory role of the population- and projection-specific dopamine function in a murine model of aggressive behavior. We find that terminal activity of ventral tegmental area (VTA) dopaminergic neurons selectively projecting to the lateral septum (LS) is sufficient for promoting aggression and necessary for establishing baseline aggression. Within the LS, dopamine acts on D2-receptors to inhibit GABAergic neurons, and septal D2-signaling is necessary for VTA dopaminergic activity to promote aggression. Collectively, our data reveal a powerful modulatory influence of dopaminergic synaptic input on LS function and aggression, effectively linking the clinically pertinent hyper-dopaminergic model of aggression with the classic septal-hypothalamic aggression axis.

Dopamine Circuit Mechanisms of Addiction-Like Behaviors

Addiction is a complex disease that impacts millions of people around the world. Clinically, addiction is formalized as substance use disorder (SUD), with three primary symptom categories: exaggerated substance use, social or lifestyle impairment, and risky substance use. Considerable efforts have been made to model features of these criteria in non-human animal research subjects, for insight into the underlying neurobiological mechanisms. Here we review evidence from rodent models of SUD-inspired criteria, focusing on the role of the striatal dopamine system. We identify distinct mesostriatal and nigrostriatal dopamine circuit functions in behavioral outcomes that are relevant to addictions and SUDs. This work suggests that striatal dopamine is essential for not only positive symptom features of SUDs, such as elevated intake and craving, but also for impairments in decision making that underlie compulsive behavior, reduced sociality, and risk taking. Understanding the functional heterogeneity of the dopamine system and related networks can offer insight into this complex symptomatology and may lead to more targeted treatments.

Sex differences in methylphenidate-induced dopamine increases in ventral striatum

Sex differences in the prevalence of dopamine-related neuropsychiatric diseases and in the sensitivity to dopamine-boosting drugs such as stimulants is well recognized. Here we assessed whether there are sex differences in the brain dopamine system in humans that could contribute to these effects. We analyzed data from two independent [11C]raclopride PET brain imaging studies that measured methylphenidate-induced dopamine increases in the striatum using different routes of administration (Cohort A = oral 60 mg; Cohort B = intravenous 0.5 mg/kg; total n = 95; 65 male, 30 female), in blinded placebo-controlled designs. Females when compared to males reported stronger feeling of “drug effects” and showed significantly greater dopamine release in the ventral striatum (where nucleus accumbens is located) to both oral and intravenous methylphenidate. In contrast, there were no significant differences in methylphenidate-induced increases in dorsal striatum for either oral or intravenous administration nor were there differences in levels of methylphenidate in plasma. The greater dopamine increases with methylphenidate in ventral but not dorsal striatum in females compared to males suggests an enhanced sensitivity specific to the dopamine reward system that might underlie sex differences in the vulnerability to substance use disorders and to attention-deficit/hyperactivity disorder (ADHD).

Medication overuse headache associated with decreased dopamine transporter availability in the left orbitofrontal cortex: A 11CFT PET/MR study

BackgroundsThe dysfunction of dopamine in the mesocorticolimbic dopamine system in MOH is unknown. Dopamine transporter (DAT) regulates dopamine clearance and neurotransmission and is sensitive to dopamine levels. A decrease in DAT availability can reflect a decrease in dopamine. To determine DAT availability abnormalities in the mesocorticolimbic dopamine system and explore functional network changes in medication overuse headache (MOH) patients.MethodsWe examined 17 MOH patients and 16 healthy controls (HCs) using integrated positron emission tomography (PET)/magnetic resonance (MR) brain scans with 11CFT, a radioligand that binds to DAT. Standardized uptake value ratio (SUVr) images were compared voxelwise between MOH patients and HCs. Then, the significantly changed cluster (p < 0.01, GRF correction) with abnormal DAT availability was selected as a specific seed region to further evaluate altered functional connectivity (FC) in MOH. SUVr and mean FC values from significantly changed regions were extracted, and partial correlation analyses with clinical measures were conducted.ResultsMOH patients had lower SUVr levels in the left rather than right orbitofrontal cortex (OFC) than HCs. There was altered FC between the left OFC and the left superior temporal pole and bilateral calcarine gyri. SUVr levels in the left OFC and the connectivity strength linking the positive brain regions with the left OFC were not correlated with clinical measures in the MOH patients.ConclusionsMOH is characterized by decreased DAT availability in the left OFC, which might reflect compensatory downregulation due to low dopamine signalling within the mesocorticolimbic dopamine system. In addition, the OFC on both sides may have different functions in the pathogenesis of MOH. Altered intrinsic FC in the left OFC was identified in MOH patients, which may provide a new perspective to understand the pathogenesis of MOH.

Reward prediction error in the ERP following unconditioned aversive stimuli

Reinforcement learning in humans and other animals is driven by reward prediction errors: deviations between the amount of reward or punishment initially expected and that which is obtained. Temporal difference methods of reinforcement learning generate this reward prediction error at the earliest time at which a revision in reward or punishment likelihood is signalled, for example by a conditioned stimulus. Midbrain dopamine neurons, believed to compute reward prediction errors, generate this signal in response to both conditioned and unconditioned stimuli, as predicted by temporal difference learning. Electroencephalographic recordings of human participants have suggested that a component named the feedback-related negativity (FRN) is generated when this signal is carried to the cortex. If this is so, the FRN should be expected to respond equivalently to conditioned and unconditioned stimuli. However, very few studies have attempted to measure the FRN’s response to unconditioned stimuli. The present study attempted to elicit the FRN in response to a primary aversive stimulus (electric shock) using a design that varied reward prediction error while holding physical intensity constant. The FRN was strongly elicited, but earlier and more transiently than typically seen, suggesting that it may incorporate other processes than the midbrain dopamine system.