Neural correlates of disbalanced motor control in major depression

Motor retardation is a common symptom of major depressive disorder (MDD). Despite the existence of various assessment methods, little is known on the pathobiology of motor retardation. We aimed to elucidate aspects of motor control investigating the association of objective motor activity and resting state cerebral blood flow (CBF).

Neural correlates of sleepiness induced by catecholamine depletion

Although extensive indirect evidence exists to suggest that the central dopaminergic system plays a significant role in the modulation of arousal, the functional effect of the dopaminergic influence on the regulation of the sleep-wake cycle remains unclear. Thirteen healthy volunteers and 15 unmedicated subjects with a history of major depressive disorder underwent catecholamine depletion (CD) using oral alpha-methyl-para-tyrosine in a randomized, placebo-controlled, double-blind, crossover study. The main outcome measures in both sessions were sleepiness (Stanford-Sleepiness-Scale), cerebral glucose metabolism (positron emission tomography), and serum prolactin concentration. CD consistently induced clinically relevant sleepiness in both groups. The CD-induced prolactin increase significantly correlated with CD-induced sleepiness but not with CD-induced mood and anxiety symptoms. CD-induced sleepiness correlated with CD-induced increases in metabolism in the medial and orbital frontal cortex, bilateral superior temporal cortex, left insula, cingulate motor area and in the vicinity of the periaqueductal gray. This study suggests that the association between dopamine depletion and sleepiness is independent of the brain reward system and the risk for depression. The visceromotor system, the cingulate motor area, the periaqueductal gray and the caudal hypothalamus may mediate the impact of the dopaminergic system on regulation of wakefulness and sleep.

Neural correlates of antinociception in borderline personality disorder

CONTEXT: A characteristic feature of borderline personality disorder (BPD) is self-injurious behavior in conjunction with stress-induced reduction of pain perception. Reduced pain sensitivity has been experimentally confirmed in patients with BPD, but the neural correlates of antinociceptive mechanisms in BPD are unknown. We predicted that heat stimuli in patients with BPD would activate brain areas concerned with cognitive and emotional evaluation of pain. OBJECTIVE: To assess the psychophysical properties and neural correlates of altered pain processing in patients with BPD. DESIGN: Case-control study. SETTING: A university hospital. PARTICIPANTS: Twelve women with BPD and self-injurious behavior and 12 age-matched control subjects. INTERVENTIONS: Psychophysical assessment and blood oxygen level-dependent functional magnetic resonance imaging during heat stimulation with fixed-temperature heat stimuli and individual-temperature stimuli adjusted for equal subjective pain in all the participants. MAIN OUTCOME MEASURE: Blood oxygen level-dependent functional magnetic resonance imaging signal changes during heat pain stimulation. RESULTS: Patients with BPD had higher pain thresholds and smaller overall volumes of activity than controls in response to identical heat stimuli. When the stimulus temperature was individually adjusted for equal subjective pain level, overall volumes of activity were similar, although regional patterns differed significantly. Patient response was greater in the dorsolateral prefrontal cortex and smaller in the posterior parietal cortex. Pain also produced neural deactivation in the perigenual anterior cingulate gyrus and the amygdala in patients with BPD. CONCLUSION: The interaction between increased pain-induced response in the dorsolateral prefrontal cortex and deactivation in the anterior cingulate and the amygdala is associated with an antinociceptive mechanism in patients with BPD.

Neural correlates of free T3 alteration after catecholamine depletion in subjects with remitted major depressive disorder and in controls.

RATIONALE: Thyroid hormones and their interactions with catecholamines play a potentially important role in alterations of mood and cognition. OBJECTIVES: This study aimed to examine the neurobiological effects of catecholamine depletion on thyroid hormones by measuring endocrine and cerebral metabolic function in unmedicated subjects with remitted major depressive disorder (RMDD) and in healthy controls. METHODS: This was a randomized, placebo-controlled, and double-blind crossover trial that included 15 unmedicated RMDD subjects and 13 healthy control subjects. The participants underwent two 3-day-long sessions at 1-week intervals; each participant was randomly administered oral α-methyl-para-tyrosine in one session (catecholamine depletion) and an identical capsule containing hydrous lactose (sham depletion) in the other session prior to a [(18)F]-fluorodeoxyglucose positron emission tomography scan. RESULTS: Serum concentrations of free T3 (FT3), free T4 (FT4), and TSH were obtained and assessed with respect to their relationship to regional cerebral glucose metabolism. Both serum FT3 (P = 0.002) and FT4 (P = 0.0009) levels were less suppressed after catecholamine depletion compared with placebo treatment in the entire study sample. There was a positive association between both FT3 (P = 0.0005) and FT4 (P = 0.002) and depressive symptoms measured using the Montgomery-Åsberg Depression Rating Scale. The relative elevation in FT3 level was correlated with a decrease in regional glucose metabolism in the right dorsolateral prefrontal cortex (rDLPFC; P < 0.05, corrected). CONCLUSIONS: This study provided evidence of an association between a thyroid-catecholamine interaction and mood regulation in the rDLPFC.

Neural correlates of 'pessimistic' attitude in depression

BACKGROUND Preparing for potentially threatening events in the future is essential for survival. Anticipating the future to be unpleasant is also a cognitive key feature of depression. We hypothesized that 'pessimism'-related emotion processing would characterize brain activity in major depression.MethodDuring functional magnetic resonance imaging, depressed patients and a healthy control group were cued to expect and then perceive pictures of known emotional valences--pleasant, unpleasant and neutral--and stimuli of unknown valence that could have been either pleasant or unpleasant. Brain activation associated with the 'unknown' expectation was compared with the 'known' expectation conditions. RESULTS While anticipating pictures of unknown valence, activation patterns in depressed patients within the medial and dorsolateral prefrontal areas, inferior frontal gyrus, insula and medial thalamus were similar to activations associated with expecting unpleasant pictures, but not with expecting positive pictures. The activity within a majority of these areas correlated with the depression scores. Differences between healthy and depressed persons were found particularly for medial and dorsolateral prefrontal and insular activations. CONCLUSIONS Brain activation in depression during expecting events of unknown emotional valence was comparable with activation while expecting certainly negative, but not positive events. This neurobiological finding is consistent with cognitive models supposing that depressed patients develop a 'pessimistic' attitude towards events with an unknown emotional meaning. Thereby, particularly the role of brain areas associated with the processing of cognitive and executive control and of the internal state is emphasized in contributing to major depression.

Neural correlates of a 'pessimistic' attitude when anticipating events of unknown emotional valence

Since we do not know what future holds for us, we prepare for expected emotional events in order to deal with a pleasant or threatening environment. From an evolutionary perspective, it makes sense to be particularly prepared for the worst-case scenario. We were interested to evaluate whether this assumption is reflected in the central nervous information processing associated with expecting visual stimuli of unknown emotional valence. While being scanned with functional magnetic resonance imaging, healthy subjects were cued to expect and then perceive visual stimuli with a known emotional valence as pleasant, unpleasant, and neutral, as well as stimuli of unknown valence that could have been either pleasant or unpleasant. While anticipating pictures of unknown valence, the activity of emotion processing brain areas was similar to activity associated with expecting unpleasant pictures, but there were no areas in which the activity was similar to the activity when expecting pleasant pictures. The activity of the revealed regions, including bilateral insula, right inferior frontal gyrus, medial thalamus, and red nucleus, further correlated with the individual ratings of mood: the worse the mood, the higher the activity. These areas are supposedly involved in a network for internal adaptation and preparation processes in order to act according to potential or certain unpleasant events. Their activity appears to reflect a 'pessimistic' bias by anticipating the events of unknown valence to be unpleasant.

Neural correlates of evaluating hazards of high risk.

In personal and in society related context, people often evaluate the risk of environmental and technological hazards. Previous research addressing neuroscience of risk evaluation assessed particularly the direct personal risk of presented stimuli, which may have comprised for instance aspects of fear. Further, risk evaluation primarily was compared to tasks of other cognitive domains serving as control conditions, thus revealing general risk related brain activity, but not such specifically associated with estimating a higher level of risk. We here investigated the neural basis on which lay-persons individually evaluated the risk of different potential hazards for the society. Twenty healthy subjects underwent functional magnetic resonance imaging while evaluating the risk of fifty more or less risky conditions presented as written terms. Brain activations during the individual estimations of 'high' against 'low' risk, and of negative versus neutral and positive emotional valences were analyzed. Estimating hazards to be of high risk was associated with activation in medial thalamus, anterior insula, caudate nucleus, cingulate cortex and further prefrontal and temporo-occipital areas. These areas were not involved according to an analysis of the emotion ratings. In conclusion, we emphasize a contribution of the mentioned brain areas involved to signal high risk, here not primarily associated with the emotional valence of the risk items. These areas have earlier been reported to be associated with, beside emotional, viscerosensitive and implicit processing. This leads to assumptions of an intuitive contribution, or a "gut-feeling", not necessarily dependent of the subjective emotional valence, when estimating a high risk of environmental hazards.

Neural correlates of anticipation risk reflect risk preferences

Individual risk preferences have a large influence on decisions, such as financial investments, career and health choices, or gambling. Decision making under risk has been studied both behaviorally and on a neural level. It remains unclear, however, how risk attitudes are encoded and integrated with choice. Here, we investigate how risk preferences are reflected in neural regions known to process risk. We collected functional magnetic resonance images of 56 human subjects during a gambling task (Preuschoff et al., 2006). Subjects were grouped into risk averters and risk seekers according to the risk preferences they revealed in a separate lottery task. We found that during the anticipation of high-risk gambles, risk averters show stronger responses in ventral striatum and anterior insula compared to risk seekers. In addition, risk prediction error signals in anterior insula, inferior frontal gyrus, and anterior cingulate indicate that risk averters do not dissociate properly between gambles that are more or less risky than expected. We suggest this may result in a general overestimation of prospective risk and lead to risk avoidance behavior. This is the first study to show that behavioral risk preferences are reflected in the passive evaluation of risky situations. The results have implications on public policies in the financial and health domain.

Rivalry of homeostatic and sensory-evoked emotions: dehydration attenuates olfactory disgust and its neural correlates

Neural correlates have been described for emotions evoked by states of homeostatic imbalance (e.g. thirst, hunger, and breathlessness) and for emotions induced by external sensory stimulation (such as fear and disgust). However, the neurobiological mechanisms of their interaction, when they are experienced simultaneously, are still unknown. We investigated the interaction on the neurobiological and the perceptional level using subjective ratings, serum parameters, and functional magnetic resonance imaging (fMRI) in a situation of emotional rivalry, when both a homeostatic and a sensory-evoked emotion were experienced at the same time. Twenty highly dehydrated male subjects rated a disgusting odor as significantly less repulsive when they were thirsty. On the neurobiological level, we found that this reduction in subjective disgust during thirst was accompanied by a significantly reduced neural activity in the insular cortex, a brain area known to be considerably involved in processing of disgust. Furthermore, during the experience of disgust in the satiated condition, we observed a significant functional connectivity between brain areas responding to the disgusting odor, which was absent during the stimulation in the thirsty condition. These results suggest interference of conflicting emotions: An acute homeostatic imbalance can attenuate the experience of another emotion evoked by the sensory perception of a potentially harmful external agent. This finding offers novel insights with regard to the behavioral relevance of biologically different types of emotions, indicating that some types of emotions are more imperative for behavior than others. As a general principle, this modulatory effect during the conflict of homeostatic and sensory-evoked emotions may function to safeguard survival.

Neural correlates of wishful thinking.

Wishful thinking (WT) implies the overestimation of the likelihood of desirable events. It occurs for outcomes of personal interest, but also for events of interest to others we like. We investigated whether WT is grounded on low-level selective attention or on higher level cognitive processes including differential weighting of evidence or response formation. Participants in our MRI study predicted the likelihood that their favorite or least favorite team would win a football game. Consistent with expectations, favorite team trials were characterized by higher winning odds. Our data demonstrated activity in a cluster comprising parts of the left inferior occipital and fusiform gyri to distinguish between favorite and least favorite team trials. More importantly, functional connectivities of this cluster with the human reward system were specifically involved in the type of WT investigated in our study, thus supporting the idea of an attention bias generating WT. Prefrontal cortex activity also distinguished between the two teams. However, activity in this region and its functional connectivities with the human reward system were altogether unrelated to the degree of WT reflected in the participants' behavior and may rather be related to social identification, ensuring the affective context necessary for WT to arise.

Exploring the emotional brain: Neural correlates of homeostatic and sensory-evoked emotions and their interaction in emotional rivalry

Human emotions are essential for survival. They are vital for the satisfaction of basic needs, the regulation of personal life and successful integration into social structures. Depending on which aspect of an emotion is used in its definition, many different theories offer possible answers to the questions of what emotions are and how they can be distinguished. The systematic investigation of emotions in cognitive neuroscience is relatively new, and neuroimaging studies specifically focussing on the neural correlates of different categories of emotions are still lacking. Therefore, the current thesis aimed at investigating the behavioural and neurophysiological correlates of different human emotional levels and their interaction in healthy subjects. We differentiated between emotions according to their cerebral entry site and neural processing pathways: homeostatic emotions, which are elicited by metabolic changes and processed by the interoceptive system (such as thirst, hunger, and need for air), and sensory-evoked emotions, which are evoked by external inputs via the eyes, ears or nose, or their corresponding mental representations and processed in the brain as sensory perception (e.g. fear, disgust, or pride). Using functional magnetic resonance imaging (fMRI) and behavioural parameters, we examined both the specific neural underpinnings of a homeostatic emotion (thirst) and a sensory-evoked emotion (disgust), and their interaction in a situation of emotional rivalry when both emotions were perceived simultaneously. This thesis comprises three research articles reporting the results of this research. The first paper presents disgust-related brain imaging data in a thirsty and a satiated condition. We found that disgust mainly activated the anterior insular cortex. In the thirsty condition, however, we observed an interaction effect between disgust and thirst: when thirsty, the subjects rated the disgusting stimulus as less repulsive. On the neurobiological level, this reduction of subjective disgust was accompanied by significantly reduced neural activity in the insular cortex. These results provide new neurophysiological evidence for a hierarchical organization among homeostatic and sensory-evoked emotions, revealing that in a situation of emotional conflict, homeostatic emotions are prioritized over sensory-evoked emotions. In the second paper, findings on brain perfusion over four different thirst stages are reported, with a special focus on the parametric progression of thirst. Cerebral perfusion differences over all thirst stages were found in the posterior insular cortex. Taking this result together with the findings of the first paper, the insular cortex seems to be a key player in human emotional processing, since it comprises specific representations of homeostatic and sensory-evoked emotions and also represents the site of cortical interaction between the two levels of emotions. Finally, although this thesis focussed on the homeostatic modulation of disgust, we were also interested in whether dehydration modulates taste perception. The results of this behavioural experiment are described in the third paper, where we show that dehydration alters the perception of neutral taste stimuli.