NCMP-09. Digital Neuromodulation of the Frontoparietal Network in Cancer Survivors: A Randomized Trial of Multimodal Multistable Bias Modification (MMBM)

Abstract BACKGROUND Persistent fatigue, mood disturbance, and cognitive dysfunction are increasingly recognized as neurological complications of cancer and its treatment. These symptoms are commonly associated with frontoparietal network disruption, a mechanism implicated across multiple malignancies and therapeutic regimens. Multimodal Multistable Bias Modification (MMBM) is a smartphone-delivered digital therapeutic designed to restore frontoparietal homeostasis through audiovisual neuromodulation and implicit attentional retraining. This randomized controlled trial used breast cancer as a model system to evaluate the neurocognitive effects of MMBM. METHODS In this fully remote, single-blind, randomized controlled pilot study (NCT06136923), 81 breast cancer survivors with prior chemotherapy exposure (3 months to 5 years post-treatment) and persistent neurological symptoms were randomized to receive either 28 days of MMBM or an inert digital control (DC). MMBM consisted of daily 7-minute cognitive-perceptual tasks using multistable stimuli and embedded attentional bias modification algorithms. Key exploratory endpoints included PROMIS-29 + 2 (fatigue, cognitive function, mood, sleep), Brief Pain Inventory, and Pain Catastrophizing Scale. Post hoc analyses examined the moderating role of baseline symptom severity. Safety, usability, and adherence were also evaluated. RESULTS Seventy-eight participants completed the study (MMBM=41, DC=37). Compared to DC, MMBM produced statistically and clinically significant improvements in fatigue (−3.4, p<0.05), anxiety (−3.0, p<0.05), depression (−2.8, p<0.05), and pain outcomes. Directional improvements were also observed in sleep disturbance (−1.6 vs −0.2) and cognitive function domains. Participants with higher baseline symptom severity experienced amplified treatment effects. The intervention was well-tolerated with no serious or device-related adverse events. Mean session adherence exceeded 91%, with an average daily use of 7.3 minutes and high usability ratings. CONCLUSIONS MMBM is a safe, engaging, and mechanism-driven digital therapeutic that modulates frontoparietal function to address cancer-related neurocognitive symptoms. Though breast cancer was used as the initial model, the observed improvements across multiple neurological domains support MMBM’s broader application to malignancies. These findings position MMBM as a scalable intervention for mitigating the long-term neurological complications of cancer care.