Jennifer N. Felder

fMRI of alterations in reward selection, anticipation, and feedback in major depressive disorder

The purpose of the present investigation was to evaluate reward processing in unipolar major depressive disorder (MDD). Specifically, we investigated whether adults with MDD demonstrated hyporesponsivity in striatal brain regions and/or hyperresponsivity in cortical brain regions involved in conflict monitoring using a Wheel of Fortune task designed to probe responses during reward selection, reward anticipation, and reward feedback. Functional magnetic resonance imaging (fMRI) data indicated that the MDD group was characterized by reduced activation of striatal reward regions during reward selection, reward anticipation, and reward feedback, supporting previous data indicating hyporesponsivity of reward systems in MDD. Support was not found for hyperresponsivity of cognitive control regions during reward selection or reward anticipation. Instead, MDD participants showed hyperresponsivity in orbitofrontal cortex, a region associated with assessment of risk and reward, during reward selection, as well as decreased activation of the middle frontal gyrus and the rostral cingulate gyrus during reward selection and anticipation. Finally, depression severity was predicted by activation in bilateral midfrontal gyrus during reward selection. Results indicate that MDD is characterized by striatal hyporesponsivity, and that future studies of MDD treatments that seek to improve responses to rewarding stimuli should assess striatal functioning.

Reward circuitry function in autism spectrum disorders

Social interaction deficits and restricted repetitive behaviors and interests that characterize autism spectrum disorders (ASDs) may both reflect aberrant functioning of brain reward circuits. However, no neuroimaging study to date has investigated the integrity of reward circuits using an incentive delay paradigm in individuals with ASDs. In the present study, we used functional magnetic resonance imaging to assess blood-oxygen level-dependent activation during reward anticipation and outcomes in 15 participants with an ASD and 16 matched control participants. Brain activation was assessed during anticipation of and in response to monetary incentives and object image incentives previously shown to be visually salient for individuals with ASDs (e.g., trains, electronics). Participants with ASDs showed decreased nucleus accumbens activation during monetary anticipation and outcomes, but not during object anticipation or outcomes. Group × reward-type-interaction tests revealed robust interaction effects in bilateral nucleus accumbens during reward anticipation and in ventromedial prefrontal cortex during reward outcomes, indicating differential responses contingent on reward type in these regions. Results suggest that ASDs are characterized by reward-circuitry hypoactivation in response to monetary incentives but not in response to autism-relevant object images. The clinical implications of the double dissociation of reward type and temporal phase in reward circuitry function in ASD are discussed.

The Effects of Psychotherapy on Neural Responses to Rewards in Major Depression

BACKGROUND Unipolar major depressive disorder (MDD) is characterized by anomalous neurobiological responses to pleasant stimuli, a pattern that may be linked to symptoms of anhedonia. However, the potential for psychotherapy to normalize neurobiological responses to pleasant stimuli has not been evaluated. METHODS Twelve adults with and 15 adults without MDD participated in two identical functional magnetic resonance imaging scans that used a Wheel of Fortune task. Between scans, MDD outpatients received Behavioral Activation Therapy for Depression, a psychotherapy modality designed to increase engagement with rewarding stimuli and reduce avoidance behaviors. RESULTS Seventy-five percent of adults with MDD were treatment responders, achieving post-treatment Hamilton Rating Scale for Depression score of six or below. Relative to changes in brain function in the matched nondepressed group, psychotherapy resulted in functional changes in structures that mediate responses to rewards, including the paracingulate gyrus during reward selection, the right caudate nucleus (i.e., the dorsal striatum), during reward anticipation, and the paracingulate and orbital frontal gyri during reward feedback. There was no effect of diagnostic status or psychotherapy on in-scanner task-related behavioral responses. CONCLUSIONS Behavioral Activation Therapy for Depression, a psychotherapy modality designed to increase engagement with rewarding stimuli and reduce avoidance behaviors, results in improved functioning of unique reward structures during different temporal phases of responses to pleasurable stimuli, including the dorsal striatum during reward anticipation.

The Effects of Brief Behavioral Activation Therapy for Depression on Cognitive Control in Affective Contexts: an fMRI investigation

BACKGROUND Unipolar major depressive disorder (MDD) is characterized by impaired cognitive control in affective contexts, but the potential for psychotherapy to affect the neural correlates of these functions has not been evaluated. METHOD Twelve adults with and 15 adults without MDD participated in two identical functional magnetic resonance imaging (fMRI) scans that utilized a task requiring cognitive control in both sad and neutral contexts. Between scans, MDD outpatients received Behavioral Activation Therapy for Depression, a psychotherapy modality designed to increase engagement with positive stimuli and reduce avoidance behaviors. RESULTS Seventy-five percent of adults with MDD were treatment responders, achieving post-treatment Hamilton Rating Scale for Depression score of six or below. Consistent with predictions, psychotherapy resulted in decreased activation in response to cognitive control stimuli presented within a sad context in prefrontal structures, including the paracingulate gyrus, the right orbital frontal cortex, and the right frontal pole. Furthermore, the magnitude of pretreatment activation in the paracingulate gyrus cluster responsive to psychotherapy predicted the magnitude of depressive symptom change after psychotherapy. LIMITATIONS Replication with larger samples is needed, as are follow-up studies that involve placebo control groups, wait-list control groups, and alternative forms of antidepressant intervention. CONCLUSIONS Behavioral Activation Therapy for Depression improves depressive symptoms and concomitantly influences brain systems mediating cognitive control in affective contexts.

Affective context interferes with cognitive control in unipolar depression: An fMRI investigation

BACKGROUND Unipolar major depressive disorder (MDD) is characterized by aberrant amygdala responses to sad stimuli and poor cognitive control, but the interactive effects of these impairments are poorly understood. AIM To evaluate brain activation in MDD in response to cognitive control stimuli embedded within sad and neutral contexts. METHOD Fourteen adults with MDD and fifteen matched controls participated in a mixed block/event-related functional magnetic resonance imaging (fMRI) task that presented oddball target stimuli embedded within blocks of sad or neutral images. RESULTS Target events activated similar prefrontal brain regions in both groups. However, responses to target events embedded within blocks of emotional images revealed a clear group dissociation. During neutral blocks, the control group demonstrated greater activation to targets in the midfrontal gyrus and anterior cingulate relative to the MDD group, replicating previous findings of prefrontal hypo-activation in MDD samples to cognitive control stimuli. However, during sad blocks, the MDD group demonstrated greater activation in a number of prefrontal regions, including the mid-, inferior, and orbito-frontal gyri and the anterior cingulate, suggesting that relatively more prefrontal brain activation was required to disengage from the sad images to respond to the target events. LIMITATIONS A larger sample size would have provided greater statistical power, and more standardized stimuli would have increased external validity. CONCLUSIONS This double dissociation of prefrontal responses to target events embedded within neutral and sad context suggests that MDD impacts not only responses to affective events, but extends to other cognitive processes carried out in the context of affective engagement. This implies that emotional reactivity to sad events in MDD may impact functioning more broadly than previously understood.

Staying well during pregnancy and the postpartum: A pilot randomized trial of mindfulness-based cognitive therapy for the prevention of depressive relapse/recurrence

OBJECTIVE Clinical decision-making regarding the prevention of depression is complex for pregnant women with histories of depression and their health care providers. Pregnant women with histories of depression report preference for nonpharmacological care, but few evidence-based options exist. Mindfulness-based cognitive therapy has strong evidence in the prevention of depressive relapse/recurrence among general populations and indications of promise as adapted for perinatal depression (MBCT-PD). With a pilot randomized clinical trial, our aim was to evaluate treatment acceptability and efficacy of MBCT-PD relative to treatment as usual (TAU). METHOD Pregnant adult women with depression histories were recruited from obstetric clinics at 2 sites and randomized to MBCT-PD (N = 43) or TAU (N = 43). Treatment acceptability was measured by assessing completion of sessions, at-home practice, and satisfaction. Clinical outcomes were interview-based depression relapse/recurrence status and self-reported depressive symptoms through 6 months postpartum. RESULTS Consistent with predictions, MBCT-PD for at-risk pregnant women was acceptable based on rates of completion of sessions and at-home practice assignments, and satisfaction with services was significantly higher for MBCT-PD than TAU. Moreover, at-risk women randomly assigned to MBCT-PD reported significantly improved depressive outcomes compared with participants receiving TAU, including significantly lower rates of depressive relapse/recurrence and lower depressive symptom severity during the course of the study. CONCLUSIONS MBCT-PD is an acceptable and clinically beneficial program for pregnant women with histories of depression; teaching the skills and practices of mindfulness meditation and cognitive-behavioral therapy during pregnancy may help to reduce the risk of depression during an important transition in many womens lives.

Web-Based Intervention in Mindfulness Meditation for Reducing Residual Depressive Symptoms and Relapse Prophylaxis: A Qualitative Study

Background Mindful Mood Balance (MMB) is a Web-based intervention designed to treat residual depressive symptoms and prevent relapse. MMB was designed to deliver the core concepts of mindfulness-based cognitive therapy (MBCT), a group treatment, which, despite its strong evidence base, faces a number of dissemination challenges. Objective The present study is a qualitative investigation of participants’ experiences with MMB. Methods Qualitative content analysis was conducted via 38 exit interviews with MMB participants. Study inclusion required a current PHQ-9 (Patient Health Questionnaire) score ≤12 and lifetime history ≥1 major depressive episode. Feedback was obtained on specific website components, program content, and administration as well as skills learned. Results Codes were assigned to interview responses and organized into four main themes: MBCT Web content, MBCT Web-based group process, home practice, and evidence of concept comprehension. Within these four areas, participants highlighted the advantages and obstacles of translating and delivering MBCT in a Web-based format. Adding increased support was suggested for troubleshooting session content as well as managing time challenges for completing home mindfulness practice. Participants endorsed developing affect regulation skills and identified several advantages to Web-based delivery including flexibility, reduced cost, and time commitment. Conclusions These findings support the viability of providing MBCT online and are consistent with prior qualitative accounts derived from in-person MBCT groups. While there is certainly room for innovation in the domains of program support and engagement, the high levels of participant satisfaction indicated that MMB can significantly increase access to evidence-based psychological treatments for sub-threshold symptoms of unipolar affective disorder.

Collaboration in mindfulness-based cognitive therapy.

In this article, we describe the nature of therapeutic collaboration between psychotherapist and group participants in mindfulness-based cognitive therapy (MBCT), which occurs in a group format and incorporates cognitive therapy and mindfulness practices with the aim of preventing depression relapse. Collaboration is a central part of two components of MBCT: inquiry and leading mindfulness practices. During the process of inquiry, the therapist-initiated questions about the participants moment-to-moment experience of the practice occurs in a context of curious, open, and warm attitudes. In addition, collaboration is maintained through co-participation in mindfulness practices. We provide a case illustration of collaboration in these contexts and conclude with recommendations for clinical practice.

The Effects of Repeated Opioid Administration on Locomotor Activity: I. Opposing Actions of μ and κ Receptors

Repeated administration of many addictive drugs leads to a progressive increase in their locomotor effects. This increase in locomotor activity often develops concomitantly with increases in their positive-reinforcing effects, which are believed to contribute to the etiology of substance use disorders. The purpose of this study was to examine changes in sensitivity to the locomotor effects of opioids after their repeated administration and to determine the role of μ and κ receptors in mediating these effects. Separate groups of rats were treated with opioid receptor agonists and antagonists every other day for 10 days, and changes in locomotor activity were measured. Repeated administration of the μ agonists, morphine and buprenorphine, produced a progressive increase in locomotor activity during the treatment period, and this effect was blocked by coadministration of the opioid antagonist naltrexone. The κ agonist spiradoline decreased locomotor activity when administered alone and blocked the progressive increase in locomotor activity produced by morphine. The ability of spiradoline to block morphine-induced increases in locomotor activity was itself blocked by pretreatment with the κ antagonist nor-binaltorphimine. Repeated administration of high doses, but not low or moderate doses, of the mixed μ/κ agonists butorphanol, nalbuphine, and nalorphine produced a progressive increase in locomotor activity during the treatment period. Doses of butorphanol, nalbuphine, and nalorphine that failed to produce a progressive increase in locomotor activity when administered alone did so when subjects were pretreated with nor-binaltorphimine. These findings suggest that μ and κ receptors have functionally opposing effects on opioid-mediated locomotor activity and sensitization-related processes.

Mapping social target detection with functional magnetic resonance imaging

The neural correlates of cognitive control and social processing functions, as well as the characteristic patterns of anomalous brain activation patterns in psychiatric conditions associated with impairment in these functions, have been well characterized. However, these domains have primarily been examined in isolation. The present study used event-related functional magnetic resonance imaging to map brain areas recruited during a target-detection task designed to evaluate responses to both non-social (i.e. shape) and social (i.e. face) target stimuli. Both shape and face targets activated a similar brain network, including the postcentral gyrus, the anterior and posterior cingulate gyri and the right midfrontal gyrus, whereas face targets additionally activated the thalamus, fusiform and temporooccipital cortex, lingual gyrus and paracingulate gyrus. Comparison of activations to social and non-social target events revealed that a small portion of the dorsal anterior cingulate gyrus (Brodmanns area 32) and the supracalcarine cortex were preferentially activated to face targets. These findings indicate that non-social and social stimuli embedded within a cognitive control task activate overlapping and distinct brain regions. Clinical cognitive neuroscience research of disorders characterized by cognitive dysfunction and impaired social processing would benefit from the use of tasks that evaluate the combined effects of deficits in these two domains.