Brain Hyperconnectivity >10 Years After Cisplatin-Based Chemotherapy for Testicular Cancer

Chemotherapy for testicular cancer (TC) has been associated with neurotoxic effects shortly post-treatment. Late effects of chemotherapy on brain function in this patient group are still unknown. In this study, we investigated differences between patients with and without chemotherapy in functional brain networks at rest and during an affective processing functional magnetic resonance imaging (fMRI) task on average >14 years post-treatment. In addition, we report on changes in cognitive functioning during survivorship by comparing present and previous performance on a neuropsychological test battery on average 11 years earlier (3 years post-treatment). Twenty-eight chemotherapy (43.1 ± 7.5 years) and 23 surgery-only (48.2 ± 9.5 years) TC survivors were examined using neurocognitive tests and 3T-fMRI >10 years after treatment end. Brain functional networks were identified using dual regression independent component analysis. Task fMRI was analyzed using a block design. Standardized domain change scores were calculated for each individual to assess cognitive change. TC patients in the chemotherapy group showed functional hyperconnectivity at rest in the precuneus network, sensory and motor function network, executive control network, and the ventral stream network when compared with surgery-only patients. Furthermore, hypoactivation was found when performing the affective processing task. Cognitive data revealed that both groups showed comparable patterns of change from 3 to 14 years after initial treatment. This study provides novel insights on the possible underlying neurobiological mechanisms of late neurotoxic effects of cisplatin-based chemotherapy. Present findings reveal that functional hyperconnectivity is widespread, possibly to compensate for the pathophysiological disturbances. This concurs with our previous findings of structural hyperconnectivity in white matter. Longitudinal multimodal imaging studies are warranted to further investigate the association between long-term structural and functional network connectivity data, as well as its relationship with cognitive changes.