Shared Characteristics of Intrinsic Connectivity Networks Underlying Interoceptive Awareness and Empathy.

Awareness of internal bodily sensations (interoceptive awareness; IA) and its connection to complex socioemotional abilities like empathy has been postulated, yet the functional neural circuitry they share remains poorly understood. The present fMRI study employs independent component analysis (ICA) to investigate which empathy facet (Cognitive or Affective) shares resting-state functional connectivity (rsFC) and/or BOLD variability (rsBOLD) with IA. Healthy participants viewed an abstract nonsocial movie demonstrated to evoke strong rsFC in brain networks resembling rest (InScapes), and resultant rsFC and rsBOLD data were correlated with self-reported empathy and IA questionnaires. We demonstrate a bidirectional behavioral and neurobiological relationship between empathy and IA, depending on the type of empathy interrogated: Affective empathy and IA share both rsFC and rsBOLD, while Cognitive empathy and IA only share rsBOLD. Specifically, increased rsFC in the right inferior frontal operculum (rIFO) of a larger attention network was associated with increased vicarious experience but decreased awareness of inner body sensations. Furthermore, increased rsBOLD between brain regions of an interoceptive network was related to increased sensitivity to internal sensations along with decreased Affective empathy. Finally, increased rsBOLD between brain regions subserving a mentalizing network related to not only an improved ability to take someone's perspective, but also a better sense of mind-body interconnectedness. Overall, these findings suggest that the awareness of one's own internal body changes (IA) is related to the socioemotional ability of feeling and understanding another's emotional state (empathy) and critically, that this relationship is reflected in the brain's resting state neuroarchitecture. Methodologically, this work highlights the importance of utilizing rsBOLD as a complementary window alongside rsFC to better understand neurological phenomena. Our results may be beneficial in aiding diagnosis in clinical populations such as autism spectrum disorder (ASD), where participants may be unable to complete tasks or questionnaires due to the severity of their symptoms.

Cortical morphometry and structural connectivity relate to executive function and estradiol level in healthy adolescents.

INTRODUCTION: Emotional and behavioral control is necessary self-regulatory processes to maintain stable goal-driven behavior. Studies indicate that variance in these executive function (EF) processes is related to morphological features of the brain and white matter (WM) differences. Furthermore, sex hormone level may modulate circuits in the brain important for cognitive function. METHODS: We aimed to investigate the structural neural correlates of EF behavior in gray matter (GM) and WM while taking into account estradiol level, in an adolescent population. The present study obtained neuroimaging behavioral and physiological data from the National Institute of Health's Pediatric Database (NIHPD). We analyzed the relationship between cortical morphometry and structural connectivity (N = 55), using a parent-administered behavioral monitoring instrument (Behavior Rating Inventory of Executive Function-BRIEF), estradiol level, as well as their interaction. RESULTS: Executive function behavior and estradiol level related to bidirectional associations with cortical morphometry in the right posterior dorsolateral prefrontal cortex (pDLPFC) and primary motor cortex (PMC), as well as fractional anisotropy (FA) in the forceps major and minor. Lastly, the interaction of EF behavior and estradiol level related to decreased volume in the right PMC and was linked to altered FA in the right inferior fronto-occipital fasciculus (iFOF). CONCLUSIONS: The study provides evidence that the relationship between EF behavior and estradiol level related to bidirectional GM and WM differences, implying estradiol level has an influence on the putative structural regions underlying EF behavior. The findings represent a crucial link between EF behavior and hormonal influence on brain structure in adolescence.

Convergent Neural Correlates of Empathy and Anxiety During Socioemotional Processing.

Empathy is characterized by the ability to understand and share an emotional experience with another person and is closely tied to compassion and concern for others. Consequently, this increased emotional awareness and sensitivity may also be related to increased anxiety. Taken from another perspective, higher general anxiety may translate into increased concern for others, or concern for how one's actions might affect others, and therefore may be linked to increased empathy. Furthermore, self-reflection is positively related to perspective-taking and empathic concern, while rumination is closely tied to anxiety, thus providing an additional connecting point between empathy and anxiety through enhanced internally generated thought. While previous literature suggests a relationship between empathy and anxiety, this has yet to be empirically studied using neuroimaging tools aimed at investigating the underlying neural correlates that may support these convergent responses. We therefore conducted an functional magnetic resonance imaging (fMRI) study (N = 49) in which participants viewed fearful and neutral human faces and rated how the faces made them feel, to promote introspection. Participants also completed questionnaires assessing empathy Toronto Empathy Questionnaire (TEQ), trait anxiety State Trait Anxiety Inventory (STAI), worry Penn State Worry Questionnaire (PSWQ) and rumination Ruminative Responses Scale (RRS). Behaviorally, empathy positively correlated with worry, worry and rumination positively correlated with anxiety, and significant indirect relationships were found between empathy and anxiety through worry and rumination. Using the neuroimaging face processing task as a backdrop on which the neurobiological mechanisms of empathy and anxiety may interact, regressions of questionnaires with brain activations revealed that empathy related to activation in the temporoparietal junction (TPJ), anxiety related to bilateral insula activation, and worry related to medial prefrontal cortex (mPFC) activation, while rumination showed increased engagement of all three aforementioned regions. Functional connectivity (FC) analyses showed increased communication between the left amygdala and insula related to higher empathy, worry and rumination. Finally, whole-brain analysis using median split groups from questionnaires revealed that the lower halves of anxiety, worry and rumination exhibited increased activation in top-down attentional networks. In sum, empathy, worry and rumination related to enhanced bottom-up processing, while worry, rumination and anxiety exhibited decreased top-down attentional control, suggesting an indirect relationship between empathy and anxiety through the ruminative tendencies of worry.

Neural Correlates of Success and Failure Signals During Neurofeedback Learning.

Feedback-driven learning, observed across phylogeny and of clear adaptive value, is frequently operationalized in simple operant conditioning paradigms, but it can be much more complex, driven by abstract representations of success and failure. This study investigates the neural processes involved in processing success and failure during feedback learning, which are not well understood. Data analyzed were acquired during a multisession neurofeedback experiment in which ten participants were presented with, and instructed to modulate, the activity of their orbitofrontal cortex with the aim of decreasing their anxiety. We assessed the regional blood-oxygenation-level-dependent response to the individualized neurofeedback signals of success and failure across twelve functional runs acquired in two different magnetic resonance sessions in each of ten individuals. Neurofeedback signals of failure correlated early during learning with deactivation in the precuneus/posterior cingulate and neurofeedback signals of success correlated later during learning with deactivation in the medial prefrontal/anterior cingulate cortex. The intensity of the latter deactivations predicted the efficacy of the neurofeedback intervention in the reduction of anxiety. These findings indicate a role for regulation of the default mode network during feedback learning, and suggest a higher sensitivity to signals of failure during the early feedback learning and to signals of success subsequently.

Lifetime PTSD and geriatric depression symptomatology relate to altered dorsomedial frontal and amygdala morphometry.

Posttraumatic stress disorder (PTSD) affects a large portion of combat deployed Veterans. Moreover, many individuals also suffer from comorbid late life depression (geriatric depression; GD). While a great deal of research has begun to characterize the morphometric features of PTSD and depression individually, few studies have investigated the interacting effect of these two disorders, specifically in a Veteran population. The current study used cortical and subcortical surface-based morphometry (SBM) in combination with psychological assessments of PTSD and GD symptom severity to examine morphometric alterations in Vietnam War Veterans. Our results indicated that increased GD severity, PTSD symptomatology, and their interaction, was related to decreased grey matter volume (GMV) in the left dorsomedial prefrontal cortex (dmPFC). Furthermore, increased symptomatology in the PTSD subscales of reexperiencing and hyperarousal were additionally found to be related to decreased GMV in this same dmPFC region. Subcortically, the interacting effect between PTSD and GD was also significantly related to regional shape variation in the left amygdala. These results suggest that morphometry of cortical (dmPFC) and non-neocortical regions (amygdala) putatively underlying emotional reactivity and the emotional components of memory is altered in PTSD and GD.

What's Important to the Patient? Informational Needs of Patients Making Decisions About Hepatitis C Treatment.

BACKGROUND AND OBJECTIVES: Multiple treatment options with direct-acting antivirals are now available for hepatitis C virus (HCV). Study aims were to understand (1) the informational topics patients want to have to make informed treatment decisions; (2) the importance patients place on each topic; and (3) the topics patients prioritize as most important. METHODS: We used a mixed-methods study of two samples recruited from an academic liver center. Participants were not currently on treatment. Sample I (n = 45) free listed all informational topics deemed important to decision making. Raw responses were coded into several broad and subcategories. Sample II (n = 38) rated the importance of the subcategories from Sample I and ranked their highest priorities on two surveys, one containing topics for which sufficient research existed to inform patients ('static'), and the other containing topics that would require additional research. RESULTS: The topics listed by Sample I fell into six broad categories with 17 total subcategories. The most oft-cited informational topics were harms of treatment (100%), treatment benefits (62%), and treatment regimen details (84%). Sample II rated 16 of 17 subcategories as "pretty important' or "extremely important". Sample II prioritized (1) viral cure, (2) long-term survival, and (3) side effects on the survey of topics requiring additional research, and (1) liver disease, (2) lifestyle changes, and (3) medication details on the second survey of the most important static topics patients needed. CONCLUSIONS: Patients weighed several informational topics to make an informed decision about HCV treatment. These findings lay the groundwork for future patient-centered outcomes research in HCV and patient-provider communication to enhance patients' informed decision making regarding direct-acting antiviral treatment options.

Reduced lateral prefrontal cortical volume is associated with performance on the modified Iowa Gambling Task: A surface based morphometric analysis of previously deployed veterans.

Post-traumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are two of the most common consequences of combat deployment. Estimates of comorbidity of PTSD and mTBI are as high as 42% in combat exposed Operation Enduring Freedom, Operation Iraqi Freedom and Operation New Dawn (OEF/OIF/OND) Veterans. Combat deployed Veterans with PTSD and/or mTBI exhibit deficits in classic executive function (EF) tasks. Similarly, the extant neuroimaging literature consistently indicates abnormalities of the ventromedial prefrontal cortex (vmPFC) and amygdala/hippocampal complex in these individuals. While studies examining deficits in classical EF constructs and aberrant neural circuitry have been widely replicated, it is surprising that little research examining reward processing and decision-making has been conducted in these individuals, specifically, because the vmPFC has long been implicated in underlying such processes. Therefore, the current study employed the modified Iowa Gambling Task (mIGT) and structural neuroimaging to assess whether behavioral measures related to reward processing and decision-making were compromised and related to cortical morphometric features of OEF/OIF/OND Veterans with PTSD, mTBI, or co-occurring PTSD/mTBI. Results indicated that gray matter morphometry in the lateral prefrontal cortex (lPFC) predicted performance on the mIGT among all three groups and was significantly reduced, as compared to the control group.

Resting state functional connectivity predicts neurofeedback response.

Tailoring treatments to the specific needs and biology of individual patients-personalized medicine-requires delineation of reliable predictors of response. Unfortunately, these have been slow to emerge, especially in neuropsychiatric disorders. We have recently described a real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback protocol that can reduce contamination-related anxiety, a prominent symptom of many cases of obsessive-compulsive disorder (OCD). Individual response to this intervention is variable. Here we used patterns of brain functional connectivity, as measured by baseline resting-state fMRI (rs-fMRI), to predict improvements in contamination anxiety after neurofeedback training. Activity of a region of the orbitofrontal cortex (OFC) and anterior prefrontal cortex, Brodmann area (BA) 10, associated with contamination anxiety in each subject was measured in real time and presented as a neurofeedback signal, permitting subjects to learn to modulate this target brain region. We have previously reported both enhanced OFC/BA 10 control and improved anxiety in a group of subclinically anxious subjects after neurofeedback. Five individuals with contamination-related OCD who underwent the same protocol also showed improved clinical symptomatology. In both groups, these behavioral improvements were strongly correlated with baseline whole-brain connectivity in the OFC/BA 10, computed from rs-fMRI collected several days prior to neurofeedback training. These pilot data suggest that rs-fMRI can be used to identify individuals likely to benefit from rt-fMRI neurofeedback training to control contamination anxiety.

Real-time fMRI biofeedback targeting the orbitofrontal cortex for contamination anxiety.

We present a method for training subjects to control activity in a region of their orbitofrontal cortex associated with contamination anxiety using biofeedback of real-time functional magnetic resonance imaging (rt-fMRI) data. Increased activity of this region is seen in relationship with contamination anxiety both in control subjects and in individuals with obsessive-compulsive disorder (OCD), a relatively common and often debilitating psychiatric disorder involving contamination anxiety. Although many brain regions have been implicated in OCD, abnormality in the orbitofrontal cortex (OFC) is one of the most consistent findings. Furthermore, hyperactivity in the OFC has been found to correlate with OCD symptom severity and decreases in hyperactivity in this region have been reported to correlate with decreased symptom severity. Therefore, the ability to control this brain area may translate into clinical improvements in obsessive-compulsive symptoms including contamination anxiety. Biofeedback of rt-fMRI data is a new technique in which the temporal pattern of activity in a specific region (or associated with a specific distributed pattern of brain activity) in a subject's brain is provided as a feedback signal to the subject. Recent reports indicate that people are able to develop control over the activity of specific brain areas when provided with rt-fMRI biofeedback. In particular, several studies using this technique to target brain areas involved in emotion processing have reported success in training subjects to control these regions. In several cases, rt-fMRI biofeedback training has been reported to induce cognitive, emotional, or clinical changes in subjects. Here we illustrate this technique as applied to the treatment of contamination anxiety in healthy subjects. This biofeedback intervention will be a valuable basic research tool: it allows researchers to perturb brain function, measure the resulting changes in brain dynamics and relate those to changes in contamination anxiety or other behavioral measures. In addition, the establishment of this method serves as a first step towards the investigation of fMRI-based biofeedback as a therapeutic intervention for OCD. Given that approximately a quarter of patients with OCD receive little benefit from the currently available forms of treatment, and that those who do benefit rarely recover completely, new approaches for treating this population are urgently needed.