Heightened interactions between a key default-mode region and a key task-positive region are linked to suboptimal current performance but to enhanced future performance.

International audienceAccording to the default-mode interference hypothesis, suboptimal performance in tasks requiring selective attention occurs when off-task processing (e.g., mind wandering) supported by default-mode regions interferes with on-task processing (e.g., attention) enabled by task-positive regions. In the present functional MRI study, we therefore investigated whether suboptimal performance in a selective attention task was linked to heightened interactions between a key default-mode region (the posterior cingulate cortex; PCC) and a key task-positive region (the left dorsolateral prefrontal cortex; DLPFC). We also investigated whether heightened interactions between the PCC and the left DLPFC were linked to enhanced future performance, consistent with prior data suggesting that such interactions index adaptive changes to the cognitive system. In line with both of these predictions, increases of current-trial functional connectivity between the PCC and the left DLPFC were linked to increases of response time in the current trial (i.e., suboptimal performance), but to decreases of response time in the next trial (i.e., enhanced performance). This double dissociation provides novel support for the default-mode interference hypothesis. Moreover, it suggests the possibility that, in at least some cases, default-mode interference indexes processes that optimize future performance

A systematic review of childhood maltreatment and resting state functional connectivity

Resting-state functional connectivity (rsFC) has the potential to shed light on how childhood abuse and neglect relates to negative psychiatric outcomes. However, a comprehensive review of the impact of childhood maltreatment on the brain's resting state functional organization has not yet been undertaken. We systematically searched rsFC studies in children and youth exposed to maltreatment. Nineteen studies (total n = 3079) met our inclusion criteria. Two consistent findings were observed. Childhood maltreatment was linked to reduced connectivity between the anterior insula and dorsal anterior cingulate cortex, and with widespread heightened amygdala connectivity with key structures in the salience, default mode, and prefrontal regulatory networks. Other brain regions showing altered connectivity included the ventral anterior cingulate cortex, dorsolateral prefrontal cortex, and hippocampus. These patterns of altered functional connectivity associated with maltreatment exposure were independent of symptoms, yet comparable to those seen in individuals with overt clinical disorder. Summative findings indicate that rsFC alterations associated with maltreatment experience are related to poor cognitive and social functioning and are prognostic of future symptoms. In conclusion, maltreatment is associated with altered rsFC in emotional reactivity, regulation, learning, and salience detection brain circuits. This indicates patterns of recalibration of putative mechanisms implicated in maladaptive developmental outcomes

fMRI Response During Figural Memory Task Performance in College Drinkers [pre-print]

Rationale: 18-25-year-olds show the highest rates of alcohol use disorders (AUD) and heavy drinking, which may have critical neurocognitive implications. Regions subserving memory may be particularly susceptible to alcohol-related impairments. Objective: We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine the neural correlates of visual encoding and recognition among heavy drinking college students. We predicted that heavy drinkers would show worse memory performance and increased frontal/parietal activation and decreased hippocampal response during encoding. Methods: Participants were 23 heavy drinkers and 33 demographically matched light drinkers, ages 18-20, characterized using quantity/frequency of drinking and AUD diagnosis. Participants performed a figural encoding and recognition task during fMRI. BOLD response during encoding was modeled based on whether each stimulus was subsequently recognized or forgotten (i.e., correct vs. incorrect encoding). Results: There were no group differences in behavioral performance. Compared to light drinkers, heavy drinkers showed: 1) greater BOLD response during correct encoding in right hippocampus/medial temporal, right dorsolateral prefrontal, left inferior frontal, and bilateral posterior parietal cortices; 2) less left inferior frontal activation and greater bilateral precuneus deactivation during incorrect encoding; and 3) less bilateral insula response during correct recognition (clusters \u3e10,233ul, p Conclusions: This is the first investigation of the neural substrates of figural memory among heavy drinking older adolescents. Heavy drinkers demonstrated compensatory hyperactivation of memory-related areas during correct encoding, greater deactivation of default mode regions during incorrect encoding, and reduced recognition-related response. Results could suggest use of different encoding and recognition strategies among heavy drinkers

Fatal bilateral pneumonitis after locoregional thoracic chemoradiation in a transplanted patient under immunosuppressive therapy

Background: After thoracic radiotherapy a pneumonitis may occur, mostly confined to the irradiated volume of the lung. In general, it resolves spontaneously without long-term effects. Case Report: A 68-year-old man was diagnosed with a stage IIIA adenocarcinoma of the lung and was treated with sequential chemoradiation. He had a heart and kidney transplant for which an immunosuppressant was taken. During the fourth week of radiotherapy, he developed a bilateral interstitial pneumonia. Despite antibiotics and steroids, the patient died twelve days after the onset of complaints due to respiratory failure. Autopsy showed in all pulmonary lobes extensive diffuse alveolar damage, probably leading to respiratory insufficiency and death. Literature and Conclusion: Bilateral pneumonitis after radiotherapy is thought to be an immunologically-mediated response, which usually resolves without long-term effects. Since in radiation pneumonitis an increase in T-cells is described, the suppression of these cells by an immunosuppressant might have exaggerated the pulmonary toxicity

Childhood Trauma And Emotion Processing Neurocircuitry

Childhood trauma is one of the strongest risk factors for a range of common and debilitating neuropsychiatric disorders, including anxiety, depression, and posttraumatic stress disorder (PTSD). These emotion-related disorders have their roots in childhood and adolescence, underscoring a critical need to understand their biological bases in early life. In this dissertation, we evaluate how childhood trauma impacts emotion processing neurocircuitry in a sample of high-risk urban youth, ages 7-15. In four inter-related studies, we test neural function and functional connectivity of core emotion processing regions, including the amygdala, insula, and pregenual/subgenual anterior cingulate cortex (pgACC/sgACC). To examine the relevance of observed neurological changes, we evaluate behavioral performance on emotion processing neuropsychological tasks, as well as specific dimensions of subjective affective experience. Results indicate that, relative to matched comparison youth, trauma-exposed youth have (1) increased neural response to salient emotional cues in amygdala and insula, (2) reduced functional connectivity between amygdala and pgACC/sgACC, a pathway critical for emotion regulation, and (3) altered within- and between-network connectivity of the salience network, involved in detecting and orienting attention to salient emotional stimuli. These neurological changes are accompanied by behavioral alterations: trauma-exposed youth have a lower ability to ignore distracting emotional information, and to automatically regulate emotion. Additionally, observed neurobehavioral changes relate to a specific dimension of affective experience – reward sensitivity (RS), rather than negative affect. Moreover, trauma-exposed youth with the greatest neurobehavioral impairment report lower RS, suggesting reduced positive environmental engagement. These results suggest that RS may be a marker of stress susceptibility, a notion supported by emerging basic and clinical research. Based on our neurobehavioral findings, we discuss potential implications for intervention, and relay an emerging framework that dissociates neurological effects of different trauma types (i.e., threat/victimization vs. deprivation/neglect). In closing, we discuss future directions, including longitudinal research and evaluating the modulation of learned fear – a neurobehavioral mechanism that depends on emotion processing neurocircuitry, but has yet to be tested in trauma-exposed youth

Sliding-window analysis tracks fluctuations in amygdala functional connectivity associated with physiological arousal and vigilance during fear conditioning

We evaluated whether sliding-window analysis can reveal functionally relevant brain network dynamics during a well-established fear conditioning paradigm. To this end, we tested if fMRI fluctuations in amygdala functional connectivity (FC) can be related to task-induced changes in physiological arousal and vigilance, as reflected in the skin conductance level (SCL). Thirty-two healthy individuals participated in the study. For the sliding-window analysis we used windows that were shifted by one volume at a time. Amygdala FC was calculated for each of these windows. Simultaneously acquired SCL time series were averaged over time frames that corresponded to the sliding-window FC analysis, which were subsequently associated with the whole-brain seed-based amygdala sliding-window FC using the GLM. Surrogate time series were generated to test whether connectivity dynamics could have occurred by chance. In addition, results were contrasted against static amygdala FC and sliding-window FC of the primary visual cortex, which was chosen as a control seed, while a physio-physiological interaction (PPI) was performed as cross-validation. During periods of increased SCL, the left amygdala became more strongly coupled with the bilateral insula and medial prefrontal cortex, core areas of the salience network. The sliding-window analysis yielded a connectivity pattern that was unlikely to have occurred by chance, was spatially distinct from static amygdala FC and from sliding-window FC of the primary visual cortex, but was highly comparable to that of the PPI analysis. We conclude that sliding-window analysis can reveal functionally relevant fluctuations in connectivity in the context of an externally cued task

Neurobiological Impact of HIV Infection and Chronic Cannabis Use

Neuroimaging research has identified brain alterations linked with the human immunodeficiency virus (HIV) that contribute to cognitive declines characterizing the disease. Given cannabis’s (CB’s) anti-inflammatory properties, use prevalence among people living with HIV (PLWH), and impact on neurocognition, my dissertation utilizes a between-groups study design to interrogate separate and interactive effects of HIV and CB on fMRI measures of brain activity. We investigate (1) task-based brain activity at the regional-level, (2) insular resting-state functional connectivity (rsFC) at the circuit-level, and (3) large-scale brain network interactions at the systems-level. Participants (N=114) were stratified into four groups (HIV+/CB+; HIV+/CB-; HIV-/CB+; HIV-/CB-) and underwent fMRI scanning while completing an Error Awareness Task (EAT) and while at rest. Participants also completed a battery of instruments including subjective reports of cognitive failures, and objective measures of cognition and medication management abilities. Blood samples quantified disease severity (viral load) and inflammation (tumor necrosis factor alpha [TNF-α]). Regarding task-based brain activity, PLWH displayed a lack of error-related deactivation in two default mode network (DMN) regions (posterior cingulate cortex [PCC], medial prefrontal cortex [mPFC]). Across all participants, reduced error-related PCC deactivation correlated with reduced medication management abilities and mediated the effect of HIV on such abilities. Regarding insular circuitry, we observed interactive HIVxCB effects on rsFC between two anterior insula (aI) subregions and sensorimotor cortices such that, CB use normalized altered rsFC that was observed among non-using PLWH and correlated with decreased somatic complaints and increased inflammation. Finally, regarding large-scale network interactions, PLWH displayed increased salience network (SN)-DMN rsFC that was associated with diminished error-awareness. These results demonstrate that insufficient error-related DMN suppression and heightened SN-DMN rsFC are linked with HIV and have consequences for error-processing and medication management. Additionally, these outcomes suggest a potential normalizing effect of CB on altered insula-sensorimotor neurocircuitries among PLWH and begin to elucidate inflammatory mechanisms through which CB use may impact brain function in the context of HIV

Adolescent Development in Context: Social, Psychological, and Neurological Foundations

This project was funded by KU Libraries’ Parent’s Campaign with support from the David Shulenburger Office of Scholarly Communication & Copyright and the Open Educational Resources Working Group in the University of Kansas Libraries.Increasingly, there is a tendency to characterize the teenage years as a time of general moral degeneration and deviance. This is unfortunate because the teenage years represent a key developmental period of the typical human lifespan, and from an evolutionary point of view, the actual characteristics that define adolescence represent critical learning opportunities. The increased sensitivity to social influences, identity formation, and social-emotional skills are just a few of such opportunities that require appropriate environments and contexts for optimal, healthy outcomes. Research in the field of adolescent development has not been immune to the negative stereotypes surrounding adolescence, and it is common to see researchers, either implicitly or explicitly, refer to adolescence as a high-risk, anomalous developmental stage that must be controlled, managed, or simply endured until adult-level abilities emerge spontaneously as a result of having survived an intrinsically tumultuous developmental time. More enlightened views of adolescence recognize that all biological adaptations have a cause and a purpose, and that the purpose of adolescence can be discerned from understanding the complex evolutionary history of humans as a group-based, family-based, highly social, sometimes competitive, abstract-thinking species. Understanding the biological foundations of adolescence is meaningless if one does not also consider how biology and environment interact. In humans, these interactions are highly complex and involve not only immediate physical realities, but also social, cultural, and historical realities that create complex contexts and webs of interactions. Therefore, this textbook seeks to reconcile the biological and neurological foundations of human development with the psychological and sociological mechanisms that formed and continue to influence human developmental trajectories. To this end, we have divided the textbook into three main sections. The first, Foundations of Adolescent Development, introduces the historical science of studying adolescence and the biological foundations of puberty. The second section, Contexts of Adolescent Development, considers the primary contextual factors that influence developmental outcomes during adolescence. These include work and employment, peers, in-school and out-of-school contexts, leisure time, and the family. The final section, Milestones of Adolescent Development, addresses the primary psychological milestones that represent healthy adjustment to adult roles and responsibilities in society. The domains of these milestones include cognition and decision-making; identity, meaning, and purpose, moral development, and sexuality. From an educational point of view, the objective of this textbook is to provide a resource that is capable of fostering advanced conceptual change and learning in the field of adolescent development in order to go beyond stereotypical portrayals of adolescence as a pathological condition. Organized in a manner designed to scaffold increasingly complex ideas, the textbook redefines adolescence a sensitive period of development characterized by phylogenetically derived experience-expectant states and complex interactions of biological, psychological, and social factors. The textbook draws from the latest advances in neuroscience and psychology to construct a practical framework for use in a wide range of academic and professional contexts, and it presents historical as well as contemporary research to accomplish a radical redefining of an often misunderstood and maligned developmental period