Functional neuroimaging of emotional learning and autonomic reactions

This article provides a selective overview of the functional neuroimaging literature with an emphasis on emotional activation processes. Emotions are fast and flexible response systems that provide basic tendencies for adaptive action. From the range of involved component functions, we first discuss selected automatic mechanisms that control basic adaptational changes. Second, we illustrate how neuroimaging work has contributed to the mapping of the network components associated with basic emotion families (fear, anger, disgust, happiness), and secondary dimensional concepts that organise the meaning space for subjective experience and verbal labels (emotional valence, activity/intensity, approach/withdrawal, etc.). Third, results and methodological difficulties are discussed in view of own neuroimaging experiments that investigated the component functions involved in emotional learning. The amygdala, prefrontal cortex, and striatum form a network of reciprocal connections that show topographically distinct patterns of activity as a correlate of up and down regulation processes during an emotional episode. Emotional modulations of other brain systems have attracted recent research interests. Emotional neuroimaging calls for more representative designs that highlight the modulatory influences of regulation strategies and socio-cultural factors responsible for inhibitory control and extinction. We conclude by emphasising the relevance of the temporal process dynamics of emotional activations that may provide improved prediction of individual differences in emotionality.     

Reading a Suspenseful Literary Text Activates Brain Areas Related to Social Cognition and Predictive Inference

Stories can elicit powerful emotions. A key emotional response to narrative plots (e.g., novels, movies, etc.) is suspense. Suspense appears to build on basic aspects of human cognition such as processes of expectation, anticipation, and prediction. However, the neural processes underlying emotional experiences of suspense have not been previously investigated. We acquired functional magnetic resonance imaging (fMRI) data while participants read a suspenseful literary text (E.T.A. Hoffmann''s “The Sandman”) subdivided into short text passages. Individual ratings of experienced suspense obtained after each text passage were found to be related to activation in the medial frontal cortex, bilateral frontal regions (along the inferior frontal sulcus), lateral premotor cortex, as well as posterior temporal and temporo-parietal areas. The results indicate that the emotional experience of suspense depends on brain areas associated with social cognition and predictive inference.     

Rôle des androgènes dans la motivation sexuelle masculine: approche par la neuroanatomie cérébrale fonctionnelle

The central nervous system plays a crucial role in all of the successive stages of sexual behaviour, particularly for the processing of external stimuli. One important step consists of the evaluation of these stimuli and the assessment of their potential reward value, which will determine the development of the sexual response. These different stages involve complex cognitive processes interacting with emotional and physiological components. Androgens, and particularly testosterone, are closely related to the regulation of sexual behaviour. Many of the various effects of testosterone on sexual behaviour have been thought to result from its effects on the central nervous system. Several studies have demonstrated that a minimum concentration of plasma testosterone is necessary to maintain a normal level of sexual desire in human males. Consequently, in normal men, acute and profound androgen deficiency induced by an experimental pharmacological treatment results in decreased sexual desire and fantasies. This reduced sexual desire is also one of the major symptoms observed in male hypogonadism. Conversely, in hypogonadal men, androgen substitution therapy results in increased sexual interest and activity. Over recent years, the development of brain functional imaging techniques (Positron Emission Tomography, functional Magnetic Resonance Imaging) has demonstrated the brain regions participating in a neural network that controls and regulates sexual arousal. We have proposed a four component neurobehavioural model, comprising cognitive (e.g. orbitofrontal cortex), motivational (e.g. anterior cingulate gyrus), emotional (e.g. somatosensory cortex, insula) and physiological (e.g. hypothalamus) processes, to describe this cerebral control of sexual motivation in human males. This network comprises activating and inhibiting structures that interact with each other. As testosterone can modulate sexual desire via its action on cerebral function, we decided to perform a brain imaging study in hypogonadal patients (both when they were untreated and when they received hormone replacement therapy), to obtain e better understanding of the specificity of these brain regions in sexual arousal processes. This study could also help describe the brain regions via which testosterone acts to modulate sexual behaviour.     

Disorders of top–down cognitive control in students with learning difficulties

The model of fixed set (for Uznadze’s paradigm) was used to estimate the functional activity of the cortico-thalamic system of selective attention and cortico-hyppocampal system of emotional and volitional activity in second-year medical students with learning difficulties (n = 20). The control group (n = 30) consisted of successfully studying students of the same year. We observed a significant reduction of induced reactions of neocortical EEG α oscillations in response to the facial stimuli or conditioning Go/NoGo signals in underperforming students. This indicates a decrease in the functional activity of the corticothalamic system of selective attention, i.e., weakening of the top–down cognitive control. This disorder is the psychophysiological basis of cognitive difficulties in the learning process. The amplitude of θ-range cortical potentials in underperforming students is significantly higher than that in the control group, i.e., the level of functional activity of the cortico-hippocampal system is higher, which indicates a higher level of stress. These findings make it possible to conclude that psychophysiological laboratory studies should be used as a supporting tool for high school teachers and psychologists during their work with students with learning difficulties.     

The Perception of Dynamic and Static Facial Expressions of Happiness and Disgust Investigated by ERPs and fMRI Constrained Source Analysis

A recent functional magnetic resonance imaging (fMRI) study by our group demonstrated that dynamic emotional faces are more accurately recognized and evoked more widespread patterns of hemodynamic brain responses than static emotional faces. Based on this experimental design, the present study aimed at investigating the spatio-temporal processing of static and dynamic emotional facial expressions in 19 healthy women by means of multi-channel electroencephalography (EEG), event-related potentials (ERP) and fMRI-constrained regional source analyses. ERP analysis showed an increased amplitude of the LPP (late posterior positivity) over centro-parietal regions for static facial expressions of disgust compared to neutral faces. In addition, the LPP was more widespread and temporally prolonged for dynamic compared to static faces of disgust and happiness. fMRI constrained source analysis on static emotional face stimuli indicated the spatio-temporal modulation of predominantly posterior regional brain activation related to the visual processing stream for both emotional valences when compared to the neutral condition in the fusiform gyrus. The spatio-temporal processing of dynamic stimuli yielded enhanced source activity for emotional compared to neutral conditions in temporal (e.g., fusiform gyrus), and frontal regions (e.g., ventromedial prefrontal cortex, medial and inferior frontal cortex) in early and again in later time windows. The present data support the view that dynamic facial displays trigger more information reflected in complex neural networks, in particular because of their changing features potentially triggering sustained activation related to a continuing evaluation of those faces. A combined fMRI and EEG approach thus provides an advanced insight to the spatio-temporal characteristics of emotional face processing, by also revealing additional neural generators, not identifiable by the only use of an fMRI approach.     

Monitoring the mind: the neurocognitive correlates of metamemory

Memory performance in everyday life is often far from perfect and therefore needs to be monitored and controlled by metamemory evaluations, such as judgments of learning (JOLs). JOLs support monitoring for goal-directed modification of learning. Behavioral studies suggested retrieval processes as providing a basis for JOLs. Previous functional imaging research on JOLs found a dissociation between processes underlying memory prediction, located in the medial prefrontal cortex (mPFC), and actual encoding success, located in the medial temporal lobe. However, JOL-specific neural correlates could not be identified unequivocally, since JOLs were given simultaneously with encoding. Here, we aimed to identify the neurocognitive basis of JOLs, i.e., the cognitive processes and neural correlates of JOL, separate from initial encoding. Using functional magnetic resonance imaging (fMRI), we implemented a face-name paired associative design. In general, we found that actual memory success was associated with increased brain activation of the hippocampi bilaterally, whereas predicted memory success was accompanied by increased activation in mPFC, orbital frontal and anterior cingulate cortices. Masking brain activation during predicted memory success with activation during retrieval success revealed BOLD increases of the mPFC. Our findings indicate that JOLs actually incorporate retrieval processes.     

The alexithymic brain: the neural pathways linking alexithymia to physical disorders

Alexithymia is a personality trait characterized by difficulties in identifying and describing feelings and is associated with psychiatric and psychosomatic disorders. The mechanisms underlying the link between emotional dysregulation and psychosomatic disorders are unclear. Recent progress in neuroimaging has provided important information regarding emotional experience in alexithymia. We have conducted three brain imaging studies on alexithymia, which we describe herein. This article considers the role of emotion in the development of physical symptoms and discusses a possible pathway that we have identified in our neuroimaging studies linking alexithymia with psychosomatic disorders. In terms of socio-affective processing, alexithymics demonstrate lower reactivity in brain regions associated with emotion. Many studies have reported reduced activation in limbic areas (e.g., cingulate cortex, anterior insula, amygdala) and the prefrontal cortex when alexithymics attempt to feel other people’s feelings or retrieve their own emotional episodes, compared to nonalexithymics. With respect to primitive emotional reactions such as the response to pain, alexithymics show amplified activity in areas considered to be involved in physical sensation. In addition to greater hormonal arousal responses in alexithymics during visceral pain, increased activity has been reported in the insula, anterior cingulate cortex, and midbrain. Moreover, in complex social situations, alexithymics may not be able to use feelings to guide their behavior appropriately. The Iowa gambling task (IGT) was developed to assess decision-making processes based on emotion-guided evaluation. When alexithymics perform the IGT, they fail to learn an advantageous decision-making strategy and show reduced activity in the medial prefrontal cortex, a key area for successful performance of the IGT, and increased activity in the caudate, a region associated with impulsive choice. The neural machinery in alexithymia is therefore activated more on the physiologic, motor-expressive level and less in the cognitive-experiential domains of the emotional response system. Affects may play an important role in alleviating intrinsic physiologic reactions and adapting to the environment. Deficient development of emotional neural structures may lead to hypersensitivity to bodily sensations and unhealthy behaviors, a possible mechanism linking alexithymia to psychosomatic disorders.     

Neural mechanisms of transient and sustained cognitive control during task switching

A hybrid blocked and event-related functional magnetic resonance imaging (fMRI) study decomposed brain activity during task switching into sustained and transient components. Contrasting task-switching blocks against single-task blocks revealed sustained activation in right anterior prefrontal cortex (PFC). Contrasting task-switch trials against task-repeat and single-task trials revealed activation in left lateral PFC and left superior parietal cortex. In both sets of regions, activation dynamics were strongly modulated by trial-by-trial fluctuations in response speed. In addition, right anterior PFC activity selectively covaried with the magnitude of mixing cost (i.e., task-repeat versus single-task trial performance), and left superior parietal activity selectively covaried with the magnitude of the switching cost (i.e., task-switch versus task-repeat trial performance). These results indicate a functional double dissociation in brain regions supporting different components of cognitive control during task switching and suggest that both sustained and transient control processes mediate the behavioral performance costs of task switching.     

Formal learning theory dissociates brain regions with different temporal integration

Learning can be characterized as the extraction of reliable predictions about stimulus occurrences from past experience. In two experiments, we investigated the interval of temporal integration of previous learning trials in different brain regions using implicit and explicit Pavlovian fear conditioning with a dynamically changing reinforcement regime in an experimental setting. With formal learning theory (the Rescorla-Wagner model), temporal integration is characterized by the learning rate. Using fMRI and this theoretical framework, we are able to distinguish between learning-related brain regions that show long temporal integration (e.g., amygdala) and higher perceptual regions that integrate only over a short period of time (e.g., fusiform face area, parahippocampal place area). This approach allows for the investigation of learning-related changes in brain activation, as it can dissociate brain areas that differ with respect to their integration of past learning experiences by either computing long-term outcome predictions or instantaneous reinforcement expectancies.     

The emotional counting Stroop: a task for assessing emotional interference during brain imaging

The emotional counting Stroop (ecStroop) is an emotional variant of the counting Stroop. Both of these tasks require a motor response instead of a spoken response for the purpose of minimizing head movement during functional MRI (fMRI). During this task, subjects report, by button press, the number of words (1-4) that appear on a screen, regardless of word meaning. Neutral word-control trials contain common words (e.g., 'cabinet' written three times), while interference trials contain emotional words (e.g., 'murder' written three times). The degree to which this task represents a true 'Stroop' interference task, in the sense that emotional words will increase motor-response times compared with neutral words, depends upon the subjects of the study and the words that are presented. Much research on the emotional Stroop task demonstrates that interference effects are observed in psychopathological groups in response to words that are specific to their disorder, and in normal subjects when the words are related to current concerns endorsed by them. The ecStroop task described here will produce reaction time-interference effects that are comparable to the traditional color-naming emotional Stroop. This protocol can be completed in approximately 20 min per subject. The protocol described here employs neutral words and emotional words that include general-negative words, as well as words specific to combat-related trauma. However, this protocol is amenable to any emotional word lists.     

A hybrid model for the neural representation of complex mental processing in the human brain

In the present conceptual review several theoretical and empirical sources of information were integrated, and a hybrid model of the neural representation of complex mental processing in the human brain was proposed. Based on empirical evidence for strategy-related and inter-individually different task-related brain activation networks, and further based on empirical evidence for a remarkable overlap of fronto-parietal activation networks across different complex mental processes, it was concluded by the author that there might be innate and modular organized neuro-developmental starting regions, for example, in intra-parietal, and both medial and middle frontal brain regions, from which the neural organization of different kinds of complex mental processes emerge differently during individually shaped learning histories. Thus, the here proposed model provides a hybrid of both massive modular and holistic concepts of idiosyncratic brain physiological elaboration of complex mental processing. It is further concluded that 3-D information, obtained by respective methodological approaches, are not appropriate to identify the non-linear spatio-temporal dynamics of complex mental process-related brain activity in a sufficient way. How different participating network parts communicate with each other seems to be an indispensable aspect, which has to be considered in particular to improve our understanding of the neural organization of complex cognition.     

Disruption of neurocognitive decision-making mechanisms in depression

To analyze the relationship of disruptions in neurocognitive decision-making mechanisms based on logic and reasoning, or in a situation of uncertainty based on emotional experience (emotional learning) with clinical indices of depression, a multidisciplinary clinical, psychological, and neurophysiological study was conducted in 28 patients suffering from depression (women aged 18–56) and 50 healthy volunteers (women aged 18–55). The intensity of depression was estimated quantitatively by the Hamilton’s Depression Rating Scale (HDRS-17) to qualitatively estimate cognitive functions, the “Ten Words” technique, the Wisconsin Card-Sorting Test (WCST), and the Iowa Gambling Task (IGT) were used; and to assess the functional brain state of all patients suffering from depression, a multichannel recording of the background electroencephalogram (EEG) was made. It was demonstrated that in depression, a neurocognitive deficiency was observed that correlates positively with the intensity of the depressive symptomatology. As well, a reduction occurs in the ability to make decisions based both on logic and reasoning (in the WCST), which is associated with EEG features of hypofrontality, and based on emotional learning (in the IGT test). Only in patients suffering from depression with a reduced ability to make rational decisions based on logic and reasoning was a “compensatory shift” observed toward decision making based on emotions, which leads to relatively higher indices of emotional learning. It is assumed that hypofrontality, which results in difficulties in making decisions requiring logical thought, leads to interruption of subcortical, including hippocampal, structures, an increase in the activation of which is related to better indices of emotional learning.     

Imaging motor imagery: methodological issues related to expertise

Mental imagery (MI) is the mental rehearsal of movements without overt execution. Brain imaging techniques have made it possible to identify the brain regions that are activated during MI and, for voluntary motor tasks involving hand and finger movements, to make direct comparison with those areas activated during actual movement. However, the fact that brain activation differs for different types of imagery (visual or kinetic) and depends on the skill level of the individual (e.g., novice or elite athlete) raises a number of important methodological issues for the design of brain imaging protocols to study MI. These include instructing the subject concerning the type of imagery to use, objective measurement of skill level, the design of motor tasks sufficiently difficult to produce a range of skill levels, the effect of different environments on skill level (including the imaging device), and so on. It is suggested that MI is more about the neurobiology of the development of motor skills that have already been learned, but not perfected, than it is about learning motor skills de novo.     

Protein synthesis-dependent long-term functional plasticity: methods and techniques

There is growing interest in late-LTP and late-LTD, that is, distinct forms of functional plasticity that require somatic functions such as protein synthesis in addition to the transient synaptic processes that are required for short lasting forms. Interestingly, to date only these forms of lasting plastic events could be detected in healthy, freely moving animals and thus, they are considered as physiological cellular models of learning and memory formation. Late-LTP and -LTD are characterized by 'synaptic tagging' or 'capture' and 'synaptic cross-tagging', but there are only a few laboratories that can currently perform experiments studying these properties. In brain slice work, there are many different approaches to investigate these processes using different methodological variations: some allow slices to rest for long periods before the experiment starts, others do not; some run their experiments at near to physiological temperatures, others at lower temperatures; some stimulate frequently, others do not.     

Limbic justice--amygdala involvement in immediate rejection in the Ultimatum Game

Imaging studies have revealed a putative neural account of emotional bias in decision making. However, it has been difficult in previous studies to identify the causal role of the different sub-regions involved in decision making. The Ultimatum Game (UG) is a game to study the punishment of norm-violating behavior. In a previous influential paper on UG it was suggested that frontal insular cortex has a pivotal role in the rejection response. This view has not been reconciled with a vast literature that attributes a crucial role in emotional decision making to a subcortical structure (i.e., amygdala). In this study we propose an anatomy-informed model that may join these views. We also present a design that detects the functional anatomical response to unfair proposals in a subcortical network that mediates rapid reactive responses. We used a functional MRI paradigm to study the early components of decision making and challenged our paradigm with the introduction of a pharmacological intervention to perturb the elicited behavioral and neural response. Benzodiazepine treatment decreased the rejection rate (from 37.6% to 19.0%) concomitantly with a diminished amygdala response to unfair proposals, and this in spite of an unchanged feeling of unfairness and unchanged insular response. In the control group, rejection was directly linked to an increase in amygdala activity. These results allow a functional anatomical detection of the early neural components of rejection associated with the initial reactive emotional response. Thus, the act of immediate rejection seems to be mediated by the limbic system and is not solely driven by cortical processes, as previously suggested. Our results also prompt an ethical discussion as we demonstrated that a commonly used drug influences core functions in the human brain that underlie individual autonomy and economic decision making.     

The Neural Correlates of Emotion Regulation by Implementation Intentions

Several studies have investigated the neural basis of effortful emotion regulation (ER) but the neural basis of automatic ER has been less comprehensively explored. The present study investigated the neural basis of automatic ER supported by ‘implementation intentions’. 40 healthy participants underwent fMRI while viewing emotion-eliciting images and used either a previously-taught effortful ER strategy, in the form of a goal intention (e.g., try to take a detached perspective), or a more automatic ER strategy, in the form of an implementation intention (e.g., “If I see something disgusting, then I will think these are just pixels on the screen!”), to regulate their emotional response. Whereas goal intention ER strategies were associated with activation of brain areas previously reported to be involved in effortful ER (including dorsolateral prefrontal cortex), ER strategies based on an implementation intention strategy were associated with activation of right inferior frontal gyrus and ventro-parietal cortex, which may reflect the attentional control processes automatically captured by the cue for action contained within the implementation intention. Goal intentions were also associated with less effective modulation of left amygdala, supporting the increased efficacy of ER under implementation intention instructions, which showed coupling of orbitofrontal cortex and amygdala. The findings support previous behavioural studies in suggesting that forming an implementation intention enables people to enact goal-directed responses with less effort and more efficiency.     

A Sensitive and Specific Neural Signature for Picture-Induced Negative Affect

Neuroimaging has identified many correlates of emotion but has not yet yielded brain representations predictive of the intensity of emotional experiences in individuals. We used machine learning to identify a sensitive and specific signature of emotional responses to aversive images. This signature predicted the intensity of negative emotion in individual participants in cross validation (n =121) and test (n = 61) samples (high–low emotion = 93.5% accuracy). It was unresponsive to physical pain (emotion–pain = 92% discriminative accuracy), demonstrating that it is not a representation of generalized arousal or salience. The signature was comprised of mesoscale patterns spanning multiple cortical and subcortical systems, with no single system necessary or sufficient for predicting experience. Furthermore, it was not reducible to activity in traditional “emotion-related” regions (e.g., amygdala, insula) or resting-state networks (e.g., “salience,” “default mode”). Overall, this work identifies differentiable neural components of negative emotion and pain, providing a basis for new, brain-based taxonomies of affective processes.     

Psychophysiological mechanisms of cognition disorders and optimization of their correction: I. Psychophysiological effects of transcranial micropolarization used as a corrective therapy for different disturbances in the control of wakefulness,emotions, and cognition in schoolchildren aged 10–12 years with learning difficulties

We have summarized the results of psychophysiological studies in schoolchildren aged 10–12 years with cerebral functional disturbances of hypoxic-ischemic or traumatic origin with learning difficulties. We have differentiated three types of disintegration of ultraslow information-controlling systems that reflect specific disturbances in the interaction of cortical-brainstem, limbic-reticular, and suprasegmental mechanisms of regulation of the wakefulness level and are characterized by emotional and cognitive disturbances typical of each type of disintegration. Adolescents with moderately and strongly decreased resistance to transitory hypoxia differed in psychological and psychophysiological effects of corrective and recovery therapy, which included transcranial micropolarization (TCMP) and psychological-pedagogical sessions during and between TCMP sessions and during the intervals between repeated TCMP courses. We discuss the psychophysiological mechanisms of the corrective effect of low-intensity direct currents with parameters close to the native ultraslow processes of the brain and the body systems regulated by these parameters.     

Neuroimaging of children following prenatal drug exposure

Recent advances in MR-based brain imaging methods have provided unprecedented capabilities to visualize the brain. Application of these methods has allowed identification of brain structures and patterns of functional activation altered in offspring of mothers who used licit (e.g., alcohol and tobacco) and illicit (e.g., cocaine, methamphetamine, and marijuana) drugs during pregnancy. Here we review that literature, which though somewhat limited by the complexities of separating the specific effects of each drug from other confounding variables, points to sets of interconnected brain structures as being altered following prenatal exposure to drugs of abuse. In particular, dopamine-rich cortical (e.g., frontal cortex) and subcortical (e.g., basal ganglia) fetal brain structures show evidence of vulnerability to intrauterine drug exposure suggesting that during brain development drugs of abuse share a specific profile of developmental neurotoxicity. Such brain malformations may shed light on mechanisms underlying prenatal drug-induced brain injury, may serve as bio-markers of significant intrauterine drug exposure, and may additionally be predictors of subsequent neuro-developmental compromise. Wider clinical use of these research-based non-invasive methods will allow for improved diagnosis and allocation of therapeutic resources for affected infants, children, and young adults.     

Rapid Plasticity in the Prefrontal Cortex during Affective Associative Learning

MultiCS conditioning is an affective associative learning paradigm, in which affective categories consist of many similar and complex stimuli. Comparing visual processing before and after learning, recent MultiCS conditioning studies using time-sensitive magnetoencephalography (MEG) revealed enhanced activation of prefrontal cortex (PFC) regions towards emotionally paired versus neutral stimuli already during short-latency processing stages (i.e., 50 to 80 ms after stimulus onset). The present study aimed at showing that this rapid differential activation develops as a function of the acquisition and not the extinction of the emotional meaning associated with affectively paired stimuli. MEG data of a MultiCS conditioning study were analyzed with respect to rapid changes in PFC activation towards aversively (electric shock) paired and unpaired faces that occurred during the learning of stimulus-reinforcer contingencies. Analyses revealed an increased PFC activation towards paired stimuli during 50 to 80 ms already during the acquisition of contingencies, which emerged after a single pairing with the electric shock. Corresponding changes in stimulus valence could be observed in ratings of hedonic valence, although participants did not seem to be aware of contingencies. These results suggest rapid formation and access of emotional stimulus meaning in the PFC as well as a great capacity for adaptive and highly resolving learning in the brain under challenging circumstances.