Self-Regulation of Amygdala Activation Using Real-Time fMRI Neurofeedback

Real-time functional magnetic resonance imaging (rtfMRI) with neurofeedback allows investigation of human brain neuroplastic changes that arise as subjects learn to modulate neurophysiological function using real-time feedback regarding their own hemodynamic responses to stimuli. We investigated the feasibility of training healthy humans to self-regulate the hemodynamic activity of the amygdala, which plays major roles in emotional processing. Participants in the experimental group were provided with ongoing information about the blood oxygen level dependent (BOLD) activity in the left amygdala (LA) and were instructed to raise the BOLD rtfMRI signal by contemplating positive autobiographical memories. A control group was assigned the same task but was instead provided with sham feedback from the left horizontal segment of the intraparietal sulcus (HIPS) region. In the LA, we found a significant BOLD signal increase due to rtfMRI neurofeedback training in the experimental group versus the control group. This effect persisted during the Transfer run without neurofeedback. For the individual subjects in the experimental group the training effect on the LA BOLD activity correlated inversely with scores on the Difficulty Identifying Feelings subscale of the Toronto Alexithymia Scale. The whole brain data analysis revealed significant differences for Happy Memories versus Rest condition between the experimental and control groups. Functional connectivity analysis of the amygdala network revealed significant widespread correlations in a fronto-temporo-limbic network. Additionally, we identified six regions — right medial frontal polar cortex, bilateral dorsomedial prefrontal cortex, left anterior cingulate cortex, and bilateral superior frontal gyrus — where the functional connectivity with the LA increased significantly across the rtfMRI neurofeedback runs and the Transfer run. The findings demonstrate that healthy subjects can learn to regulate their amygdala activation using rtfMRI neurofeedback, suggesting possible applications of rtfMRI neurofeedback training in the treatment of patients with neuropsychiatric disorders

SCOTROC 2B: feasibility of carboplatin followed by docetaxel or docetaxel–irinotecan as first-line therapy for ovarian cancer

The feasibility of combination irinotecan, carboplatin and docetaxel chemotherapy as first-line treatment for advanced epithelial ovarian carcinoma was assessed. One hundred patients were randomised to receive four 3-weekly cycles of carboplatin (area under the curve (AUC) 7) followed by four 3-weekly cycles of docetaxel 100 mg m−2 (arm A, n=51) or docetaxel 60 mg m−2 with irinotecan 200 mg m−2 (arm B, n=49). Neither arm met the formal feasibility criterion of an eight-cycle treatment completion rate that was statistically greater than 60% (arm A 71% (90% confidence interval (CI) 58–81%; P=0.079; arm B 67% (90% CI 55–78%; P=0.184)). Median-dose intensities were >85% of planned dose for all agents. In arms A and B, 15.6 and 12.2% of patients, respectively, withdrew owing to treatment-related toxicity. Grade 3–4 sensory neurotoxicity was more common in arm A (1.9 vs 0%) and grade 3–4 diarrhoea was more common in arm B (0.6 vs 3.5%). Of patients with radiologically evaluable disease at baseline, 50 and 48% responded to therapy in arms A and B, respectively; at median 17.1 months' follow-up, median progression-free survival was 17.1 and 15.9 months, respectively. Although both arms just failed to meet the formal statistical feasibility criteria, the observed completion rates of around 70% were reasonable. The addition of irinotecan to first-line carboplatin and docetaxel chemotherapy was generally well tolerated although associated with increased gastrointestinal toxicity. Further exploratory studies of topoisomerase-I inhibitors in this setting may be warranted

Nonsurgical Management of Cervical Cancer: Locally Advanced, Recurrent, and Metastatic Disease, Survivorship, and Beyond

Despite the declining incidence of cervical cancer as a result of the introduction of screening programs, globally it remains a leading cause of cancer-related death in women. Outcomes for patients who are diagnosed with anything but early-stage disease remain poor. Here we examine emerging strategies to improve the treatment of locally advanced disease. We discuss emerging biologic data, which are informing our investigation of new therapeutic interventions in persistent, recurrent, and metastatic cervical cancer. We recognize the importance of interventions to improve quality of life and to prevent long-term sequelae in women undergoing treatment. Finally, and perhaps most importantly, we recognize the need for global collaboration and advocacy to improve the outcome for all women at risk of and diagnosed with this disease