If you're happy and you know it: neural correlates of self-evaluated psychological health and well-being.

Psychological health and well-being have important implications for individual and societal thriving. Research underscores the subjective nature of well-being, but how do individuals intuit this subjective sense of well-being in the moment? This pre-registered study addresses this question by examining the neural correlates of self-evaluated psychological health and their dynamic relationship with trial-level evaluations. Participants (N = 105) completed a self-evaluation task and made judgments about three facets of psychological health and positive functioning-self-oriented well-being, social well-being and ill-being. Consistent with pre-registered hypotheses, self-evaluation elicited activity in the default mode network, and there was strong spatial overlap among constructs. Trial-level analyses assessed whether and how activity in a priori regions of interest-perigenual anterior cingulate cortex (pgACC), ventromedial prefrontal cortex (vmPFC) and ventral striatum-were related to subjective evaluations. These regions explained additional variance in whether participants endorsed or rejected items but were differentially related to evaluations. Stronger activity in pgACC was associated with a higher probability of endorsement across constructs, whereas stronger activity in vmPFC was associated with a higher probability of endorsing ill-being items, but a lower probability of endorsing self-oriented and social well-being items. These results add nuance to neurocognitive accounts of self-evaluation and extend our understanding of the neurobiological basis of subjective psychological health and well-being.

Predicting Antidepressant Effects of Ketamine: the Role of the Pregenual Anterior Cingulate Cortex as a Multimodal Neuroimaging Biomarker.

BACKGROUND: Growing evidence underscores the utility of ketamine as an effective and rapid-acting treatment option for major depressive disorder (MDD). However, clinical outcomes vary between patients. Predicting successful response may enable personalized treatment decisions and increase clinical efficacy. METHODS: We here explored the potential of pregenual anterior cingulate cortex (pgACC) activity to predict antidepressant effects of ketamine in relation to ketamine-induced changes in glutamatergic metabolism. Prior to a single i.v. infusion of ketamine, 24 patients with MDD underwent functional magnetic resonance imaging during an emotional picture-viewing task and magnetic resonance spectroscopy. Changes in depressive symptoms were evaluated using the Beck Depression Inventory measured 24 hours pre- and post-intervention. A subsample of 17 patients underwent a follow-up magnetic resonance spectroscopy scan. RESULTS: Antidepressant efficacy of ketamine was predicted by pgACC activity during emotional stimulation. In addition, pgACC activity was associated with glutamate increase 24 hours after the ketamine infusion, which was in turn related to better clinical outcome. CONCLUSIONS: Our results add to the growing literature implicating a key role of the pgACC in mediating antidepressant effects and highlighting its potential as a multimodal neuroimaging biomarker of early treatment response to ketamine.

Neural signatures of individual variability in context-dependent perception of ambiguous facial expression.

How do we incorporate contextual information to infer others' emotional state? Here we employed a naturalistic context-dependent facial expression estimation task where participants estimated pleasantness levels of others' ambiguous expression faces when sniffing different contextual cues (e.g., urine, fish, water, and rose). Based on their pleasantness rating data, we placed participants on a context-dependency continuum and mapped the individual variability in the context-dependency onto the neural representation using a representational similarity analysis. We found that the individual variability in the context-dependency of facial expression estimation correlated with the activity level of the pregenual anterior cingulate cortex (pgACC) and the amygdala and was also decoded by the neural representation of the ventral anterior insula (vAI). A dynamic causal modeling revealed that those with higher context-dependency exhibited a greater degree of the modulation from vAI to the pgACC. These findings provide novel insights into the neural circuitry associated with the individual variability in context-dependent facial expression estimation and the first empirical evidence for individual variability in the predictive accounts of affective states.

Alteration of grey matter volume is associated with pain and quality of life in children with sickle cell disease.

Pain is the most common symptom experienced by patients with sickle cell disease (SCD) and is associated with poor quality of life. We investigated the association between grey matter volume (GMV) and the frequency of pain crises in the preceding 12 months and SCD-specific quality of life (QOL) assessed by the PedsQLTM SCD module in 38 pediatric patients with SCD. Using voxel-based morphometry methodology, high-resolution T1 structural scans were preprocessed using SPM and further analyzed in SPSS. The whole brain multiple regression analysis identified that perigenual anterior cingulate cortex (ACC) GMV was negatively associated with the frequency of pain crises (r = -0.656, P = 0.003). A two-group t-test analysis showed that the subgroup having pain crisis/crises in the past year also showed significantly lower GMV at left supratemporal gyrus than the group without any pain crisis (p=0.024). The further 21 pain-related regions of interest (ROI) analyses identified a negative correlation between pregenual ACC (r = -0.551, P = 0.001), subgenual ACC (r = -0.540, P = 0.001) and the frequency of pain crises. Additionally, the subgroup with poorer QOL displayed significantly reduced GMV in the parahippocampus (left: P = 0.047; right: P = 0.024). The correlations between the cerebral structural alterations and the accentuated pain experience and QOL suggests a possible role of central mechanisms in SCD pain.

Pain Control by Co-adaptive Learning in a Brain-Machine Interface.

Innovation in the field of brain-machine interfacing offers a new approach to managing human pain. In principle, it should be possible to use brain activity to directly control a therapeutic intervention in an interactive, closed-loop manner. But this raises the question as to whether the brain activity changes as a function of this interaction. Here, we used real-time decoded functional MRI responses from the insula cortex as input into a closed-loop control system aimed at reducing pain and looked for co-adaptive neural and behavioral changes. As subjects engaged in active cognitive strategies orientated toward the control system, such as trying to enhance their brain activity, pain encoding in the insula was paradoxically degraded. From a mechanistic perspective, we found that cognitive engagement was accompanied by activation of the endogenous pain modulation system, manifested by the attentional modulation of pain ratings and enhanced pain responses in pregenual anterior cingulate cortex and periaqueductal gray. Further behavioral evidence of endogenous modulation was confirmed in a second experiment using an EEG-based closed-loop system. Overall, the results show that implementing brain-machine control systems for pain induces a parallel set of co-adaptive changes in the brain, and this can interfere with the brain signals and behavior under control. More generally, this illustrates a fundamental challenge of brain decoding applications-that the brain inherently adapts to being decoded, especially as a result of cognitive processes related to learning and cooperation. Understanding the nature of these co-adaptive processes informs strategies to mitigate or exploit them.

The effects of age on cerebral responses to self-initiated actions during social interactions: An exploratory study.

Self-initiated action is critical to social interaction and individuals with social anxiety find it particularly difficult to initiate social interactions. We showed earlier that social exclusion encumbered self-initiated actions in the Cyberball task in young adults. Here, we examined whether the behavioral performance and regional responses during self-initiated actions vary with age in 53 participants (21-74 years; 27 men). Behaviorally, participants were slower in tossing the ball during exclusion (EX) than during fair game (FG) sessions in both men and women. In women but not in men the reaction time (RT) burden (RT_EX - RT_FG; RT prolonged during social exclusion) of ball toss was positively correlated with age despite no observed sex difference in Social Interaction Anxiety Scale scores. The pregenual anterior cingulate cortex, thalamus, left occipital cortex (OC) and left insula/orbitofrontal cortex responded to ball toss in EX vs. FG in negative correlation with age in women but not in men. Further, the activation of left OC fully mediated the relationship between age and RT burden in women. Thus, older women are more encumbered in self-initiated action during social exclusion, although this behavioral burden is not reflected in subjective reports of social anxiety. Age-related diminution in OC activities may reflect the neural processes underlying the difficulty in initiating social interactions in women. Together, the findings identified age-sensitive behavioral and neural processes of self-initiated action in the Cyberball task and suggest the importance of considering age and sex differences in studies of social interaction.

Rostral Anterior Cingulate Glutamine/Glutamate Disbalance in Major Depressive Disorder Depends on Symptom Severity.

BACKGROUND: Patients with major depressive disorder (MDD) show glutamatergic deficits in the ventral anterior cingulate cortex. The glutamine/glutamate (Gln/Glu) ratio was proposed to be connected to glutamatergic cycling, which is hypothesized to be dysregulated in MDD. As an indicator of regional metabolite status, this ratio might be a robust state marker sensitive to clinical heterogeneity. METHODS: Thirty-two MDD patients (mean age 40.88 ± 13.66 years, 19 women) and control subjects (mean age 33.09 ± 8.24 years, 19 women) were compared for pregenual anterior cingulate cortex levels of Gln/Glu, Gln/total creatine (tCr), Glu/tCr, and gamma-aminobutyric acid/tCr as determined by high-field magnetic resonance spectroscopy. We tested if symptom severity (Hamilton Depression Rating Scale) and anhedonia (Snaith-Hamilton Pleasure Scale) influence the relation of metabolites to clinical symptoms. RESULTS: MDD patients showed higher Gln/Glu. This was driven by marginally higher Gln/tCr and nonsignificantly lower Glu/tCr. Groups defined by severity moderated relationship between Gln/Glu and the Hamilton Depression Rating Scale. Moreover, severe cases differed from both control subjects and moderate cases. Groups defined by the Snaith-Hamilton Pleasure Scale also displayed differential relationship between Gln/Glu and levels of anhedonia, predominantly driven by Gln/tCr. CONCLUSIONS: We elaborate previous accounts of metabolite deficits in the anterior cingulate cortex toward increased Gln/Glu. There is a moderated relationship between severity and the ratio, which suggests consideration of different mechanisms or disease state for the respective subgroups in future studies.

Imaging stress: an overview of stress induction methods in the MR scanner.

Processing of acute stress has potential implications for mental and physical health. At the same time, individuals differ largely in how strongly they react to stress. Neuroimaging paradigms have been developed to characterize the neural underpinnings of the stress response in general and to understand the mechanisms that differentiate high and low susceptible individuals. The goal of the present review was to summarize the current literature on psychosocial stress in the brain imaging environment. That is, we focused on the most common neuroimaging paradigms that have been used to induce acute stress and map out the questions that have been addressed with respect to the determinants, the consequences, and the processing of stress. We identified four major paradigms that have been used with different scientific aims. The Montreal Imaging Stress Test and the ScanSTRESS involve cognitive challenge and social-evaluative threat and yielded a stress-related network including most significantly the perigenual ACC, the hippocampus, and the amygdala. The social-evaluative threat paradigm was used to predict the autonomic stress response on the basis of multivariate pattern analysis. The aversive video paradigm, on the other hand, was mainly used to investigate the consequences of stress on emotional and cognitive processes and their neural correlates. We conclude our review with a critical evaluation of methodological and conceptual issues in the study of the neural correlates of acute stress.

Fear avoidance beliefs in back pain-free subjects are reflected by amygdala-cingulate responses.

In most individuals suffering from chronic low back pain, psychosocial factors, specifically fear avoidance beliefs (FABs), play central roles in the absence of identifiable organic pathology. On a neurobiological level, encouraging research has shown brain system correlates of somatic and psychological factors during the transition from (sub) acute to chronic low back pain. The characterization of brain imaging signatures in pain-free individuals before any injury will be of high importance regarding the identification of relevant networks for low back pain (LBP) vulnerability. Fear-avoidance beliefs serve as strong predictors of disability and chronification in LBP and current research indicates that back pain related FABs already exist in the general and pain-free population. Therefore, we aimed at investigating possible differential neural functioning between high- and low fear-avoidant individuals in the general population using functional magnetic resonance imaging. Results revealed that pain-free individuals without a history of chronic pain episodes could be differentiated in amygdala activity and connectivity to the pregenual anterior cingulate cortex by their level of back pain related FABs. These results shed new light on brain networks underlying psychological factors that may become relevant for enhanced disability in a future LBP episode.