Alexandra Touroutoglou

Dissociable large-scale networks anchored in the right anterior insula subserve affective experience and attention

Meta-analytic summaries of neuroimaging studies point to at least two major functional-anatomic subdivisions within the anterior insula that contribute to the detection and processing of salient information: a dorsal region that is routinely active during attention tasks and a ventral region that is routinely active during affective experience. In two independent samples of cognitively normal human adults, we used intrinsic functional connectivity magnetic resonance imaging to demonstrate that the right dorsal and right ventral anterior insula are nodes in separable large-scale functional networks. Furthermore, stronger intrinsic connectivity within the right dorsal anterior insula network was associated with better performance on a task involving attention and processing speed whereas stronger connectivity within the right ventral anterior insula network was associated with more intense affective experience. These results support the hypothesis that the identification and manipulation of salient information is subserved by at least two brain networks anchored in the right anterior insula that exhibit distinct large-scale topography and dissociable behavioral correlates.

Assessment of Circulating MicroRNAs for the Diagnosis and Disease Activity Evaluation in Patients with Ulcerative Colitis by Using the Nanostring Technology

Background:Clinical decision and patient care management in inflammatory bowel diseases is largely based on the assessment of clinical symptoms, while the biomarkers currently in use poorly reflect the actual disease activity. Therefore, the identification of novel biomarkers will serve an unmet clinical need for IBD screening and patient management. We examined the utility of circulating microRNAs for diagnosis and disease activity monitoring in patients with ulcerative colitis (UC). Methods:Blood serum microRNAs were isolated from patients with UC with active and inactive disease and healthy donors. High-throughput microRNA profiling was performed using the Nanostring technology platform. Clinical disease activity was captured by calculating the partial Mayo score. C-reactive protein was measured in patients with UC as part of their clinical monitoring. The profiles of circulating microRNAs and C-reactive protein were correlated with clinical disease indices. Results:We have identified a signature of 12 circulating microRNAs that differentiate patients with UC from control subjects. Moreover, 6 of these microRNAs significantly correlated with UC disease activity. Importantly, a set of 4 microRNAs (hsa-miR-4454, hsa-miR-223-3p, hsa-miR-23a-3p, and hsa-miR-320e), which correlated with UC disease activity were found to have higher sensitivity and specificity values than C-reactive protein. Conclusions:Circulating microRNAs provide a novel diagnostic and prognostic marker for patients with UC. The use of an FDA-approved platform could accelerate the application of microRNA screening in a gastrointenstinal clinical setting. When used in combination with current diagnostic and disease activity assessment modalities, microRNAs could improve both IBD screening and care management.

Youthful Brains in Older Adults: Preserved Neuroanatomy in the Default Mode and Salience Networks Contributes to Youthful Memory in Superaging

Decline in cognitive skills, especially in memory, is often viewed as part of “normal” aging. Yet some individuals “age better” than others. Building on prior research showing that cortical thickness in one brain region, the anterior midcingulate cortex, is preserved in older adults with memory performance abilities equal to or better than those of people 20–30 years younger (i.e., “superagers”), we examined the structural integrity of two large-scale intrinsic brain networks in superaging: the default mode network, typically engaged during memory encoding and retrieval tasks, and the salience network, typically engaged during attention, motivation, and executive function tasks. We predicted that superagers would have preserved cortical thickness in critical nodes in these networks. We defined superagers (60–80 years old) based on their performance compared to young adults (18–32 years old) on the California Verbal Learning Test Long Delay Free Recall test. We found regions within the networks of interest where the cerebral cortex of superagers was thicker than that of typical older adults, and where superagers were anatomically indistinguishable from young adults; hippocampal volume was also preserved in superagers. Within the full group of older adults, thickness of a number of regions, including the anterior temporal cortex, rostral medial prefrontal cortex, and anterior midcingulate cortex, correlated with memory performance, as did the volume of the hippocampus. These results indicate older adults with youthful memory abilities have youthful brain regions in key paralimbic and limbic nodes of the default mode and salience networks that support attentional, executive, and mnemonic processes subserving memory function. SIGNIFICANCE STATEMENT Memory performance typically declines with age, as does cortical structural integrity, yet some older adults maintain youthful memory. We tested the hypothesis that superagers (older individuals with youthful memory performance) would exhibit preserved neuroanatomy in key brain networks subserving memory. We found that superagers not only perform similarly to young adults on memory testing, they also do not show the typical patterns of brain atrophy in certain regions. These regions are contained largely within two major intrinsic brain networks: the default mode network, implicated in memory encoding, storage, and retrieval, and the salience network, associated with attention and executive processes involved in encoding and retrieval. Preserved neuroanatomical integrity in these networks is associated with better memory performance among older adults.

Sex differences in the neural correlates of affective experience

People believe that women are more emotionally intense than men, but the scientific evidence is equivocal. In this study, we tested the novel hypothesis that men and women differ in the neural correlates of affective experience, rather than in the intensity of neural activity, with women being more internally (interoceptively) focused and men being more externally (visually) focused. Adult men (n = 17) and women (n = 17) completed a functional magnetic resonance imaging study while viewing affectively potent images and rating their moment-to-moment feelings of subjective arousal. We found that men and women do not differ overall in their intensity of moment-to-moment affective experiences when viewing evocative images, but instead, as predicted, women showed a greater association between the momentary arousal ratings and neural responses in the anterior insula cortex, which represents bodily sensations, whereas men showed stronger correlations between their momentary arousal ratings and neural responses in the visual cortex. Men also showed enhanced functional connectivity between the dorsal anterior insula cortex and the dorsal anterior cingulate cortex, which constitutes the circuitry involved with regulating shifts of attention to the world. These results demonstrate that the same affective experience is realized differently in different people, such that womens feelings are relatively more self-focused, whereas mens feelings are relatively more world-focused.

Functional connectivity dynamics during film viewing reveal common networks for different emotional experiences

Recent theoretical and empirical work has highlighted the role of domain-general, large-scale brain networks in generating emotional experiences. These networks are hypothesized to process aspects of emotional experiences that are not unique to a specific emotional category (e.g., “sadness,” “happiness”), but rather that generalize across categories. In this article, we examined the dynamic interactions (i.e., changing cohesiveness) between specific domain-general networks across time while participants experienced various instances of sadness, fear, and anger. We used a novel method for probing the network connectivity dynamics between two salience networks and three amygdala-based networks. We hypothesized, and found, that the functional connectivity between these networks covaried with the intensity of different emotional experiences. Stronger connectivity between the dorsal salience network and the medial amygdala network was associated with more intense ratings of emotional experience across six different instances of the three emotion categories examined. Also, stronger connectivity between the dorsal salience network and the ventrolateral amygdala network was associated with more intense ratings of emotional experience across five out of the six different instances. Our findings demonstrate that a variety of emotional experiences are associated with dynamic interactions of domain-general neural systems.

Amygdala task-evoked activity and task-free connectivity independently contribute to feelings of arousal.

Individual differences in the intensity of feelings of arousal while viewing emotional pictures have been associated with the magnitude of task‐evoked blood‐oxygen dependent (BOLD) response in the amygdala. Recently, we reported that individual differences in feelings of arousal are associated with task‐free (resting state) connectivity within the salience network. There has not yet been an investigation of whether these two types of functional magnetic resonance imaging (MRI) measures are redundant or independent in their relationships to behavior. Here we tested the hypothesis that a combination of task‐evoked amygdala activation and task‐free amygdala connectivity within the salience network relate to individual differences in feelings of arousal while viewing of negatively potent images. In 25 young adults, results revealed that greater task‐evoked amygdala activation and stronger task‐free amygdala connectivity within the salience network each contributed independently to feelings of arousal, predicting a total of 45% of its variance. Individuals who had both increased task‐evoked amygdala activation and stronger task‐free amygdala connectivity within the salience network had the most heightened levels of arousal. Task‐evoked amygdala activation and task‐free amygdala connectivity within the salience network were not related to each other, suggesting that resting‐state and task‐evoked dynamic brain imaging measures may provide independent and complementary information about affective experience, and likely other kinds of behaviors as well. Hum Brain Mapp 35:5316–5327, 2014.

Dopamine in the medial amygdala network mediates human bonding

Significance Early life bonding in humans has critical long-term implications for health, productivity, and well-being in society. Nonetheless, neural mechanisms of bonding are typically studied in rodents, and no studies to date had examined the neurochemistry of human social affiliation. This study utilizes a state-of-the-art technology to demonstrate that human maternal bonding is associated with striatal dopamine function and the recruitment of a cortico–striatal–amygdala brain network that supports affiliation. The simultaneous probing of neurochemical responses and whole-brain network function in mothers watching their infants provides a unique observation into an “affiliating brain.” These results advance the mechanistic understanding of human social bonding and promote basic and clinical research in social neuroscience, development, and psychopathology. Research in humans and nonhuman animals indicates that social affiliation, and particularly maternal bonding, depends on reward circuitry. Although numerous mechanistic studies in rodents demonstrated that maternal bonding depends on striatal dopamine transmission, the neurochemistry supporting maternal behavior in humans has not been described so far. In this study, we tested the role of central dopamine in human bonding. We applied a combined functional MRI-PET scanner to simultaneously probe mothers’ dopamine responses to their infants and the connectivity between the nucleus accumbens (NAcc), the amygdala, and the medial prefrontal cortex (mPFC), which form an intrinsic network (referred to as the “medial amygdala network”) that supports social functioning. We also measured the mothers’ behavioral synchrony with their infants and plasma oxytocin. The results of this study suggest that synchronous maternal behavior is associated with increased dopamine responses to the mother’s infant and stronger intrinsic connectivity within the medial amygdala network. Moreover, stronger network connectivity is associated with increased dopamine responses within the network and decreased plasma oxytocin. Together, these data indicate that dopamine is involved in human bonding. Compared with other mammals, humans have an unusually complex social life. The complexity of human bonding cannot be fully captured in nonhuman animal models, particularly in pathological bonding, such as that in autistic spectrum disorder or postpartum depression. Thus, investigations of the neurochemistry of social bonding in humans, for which this study provides initial evidence, are warranted.

Oral contraceptive pill use is associated with localized decreases in cortical thickness

Oral contraceptive pills (OCs), which are used to prevent pregnancy by the majority of women in the United States, contain steroid hormones that may affect the brains structure and function. In this investigation, we tested the hypothesis that OC use is associated with differences in brain structure using a hypothesis‐driven, surface‐based approach. In 90 women, (44 OC users, 46 naturally‐cycling women), we compared the cortical thickness of brain regions that participate in the salience network and the default mode network, as well as the volume of subcortical regions in these networks. We found that OC use was associated with significantly lower cortical thickness measurements in the lateral orbitofrontal cortex and the posterior cingulate cortex. These regions are believed to be important for responding to rewards and evaluating internal states/incoming stimuli, respectively. Further investigations are needed to determine if cortical thinning in these regions are associated with behavioral changes, and also to identify whether OC use is causally or only indirectly related to these changes in brain morphology. Hum Brain Mapp 36:2644–2654, 2015.

Cognitive Interruption as an Object of Metacognitive Monitoring: Feeling of Difficulty and Surprise

An important question regarding metacognition in problem solving is what triggers the metacognitive experience of feeling of difficulty? In this chapter, we present three experiments suggesting that feeling of difficulty arises from lack of fluency in processing due to either working memory load or cognitive interruption. Experiments 1 and 2 showed that working memory load reduces performance (as measured by accuracy of response and reaction times) and increases feeling of difficulty. Experiment 3 further demonstrated that reaction times and feeling of difficulty ratings increase with cognitive interruption caused by discrepancies in processing. Interestingly, in Experiment 3, feeling of difficulty correlated highly and positively with surprise, which is another response to discrepant events. The implications of these findings are discussed as are suggestions for future research.

Brain network connectivity–behavioral relationships exhibit trait-like properties: Evidence from hippocampal connectivity and memory

Despite a growing number of studies showing relationships between behavior and resting‐state functional MRI measures of large‐scale brain network connectivity, no study to our knowledge has sought to investigate whether intrinsic connectivity–behavioral relationships are stable over time. In this study, we investigated the stability of such brain–behavior relationships at two timepoints, approximately 1 week apart. We focused on the relationship between the strength of hippocampal connectivity to posterior cingulate cortex and episodic memory performance. Our results showed that this relationship is stable across samples of a different age and reliable over two points in time. These findings provide the first evidence that the relationship between large‐scale intrinsic network connectivity and episodic memory performance is a stable characteristic that varies between individuals.