Anxiety is a core human emotion but can become pathologically dysregulated. We used functional magnetic resonance imaging (fMRI) neurofeedback (NF) to noninvasively alter patterns of brain connectivity, as measured by resting-state fMRI, and to reduce contamination anxiety. Activity of a region of the orbitofrontal cortex associated with contamination anxiety was measured in real time and provided to subjects with significant but subclinical anxiety as a NF signal, permitting them to learn to modulate the target brain region. NF altered network connectivity of brain regions involved in anxiety regulation: subjects exhibited reduced resting-state connectivity in limbic circuitry and increased connectivity in the dorsolateral prefrontal cortex. NF has been shown to alter brain connectivity in other contexts, but it has been unclear whether these changes persist; critically, we observed changes in connectivity several days after the completion of NF training, demonstrating that such training can lead to lasting modifications of brain functional architecture. Training also increased subjects' control over contamination anxiety several days after the completion of NF training. Changes in resting-state connectivity in the target orbitofrontal region correlated with these improvements in anxiety. Matched subjects undergoing a sham feedback control task showed neither a reorganization of resting-state functional connectivity nor an improvement in anxiety. These data suggest that NF can enable enhanced control over anxiety by persistently reorganizing relevant brain networks and thus support the potential of NF as a clinically useful therapy.

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.

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.

Background & Objectives Multiple treatment options with direct-acting antivirals (DAAs) 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 Mixed methods study utilizing 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 6 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 DAA treatment options.

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.