Grief and bereavement: A pre-registered systematic review of neuroimaging studies

Grief is a universally experienced response to the loss of a significant person, representing a profoundly stressful life event that can have lasting impacts on mental and physical health. Despite its inevitability, the neural mechanisms underlying grief remain poorly understood, hindering the development of effective interventions to improve outcomes for individuals coping with loss. To address this gap, we systematically reviewed functional and structural magnetic resonance imaging (MRI) studies related to brain connectivity, structural changes, peripheral physiology, and neuroendocrine, immune, and psychological correlates of grief. Functional MRI (fMRI) studies report associations between grief and neural activity, connectivity, and structure in networks related to emotion regulation, reward processing, and cognitive control, with some studies noting heightened reactivity in regions such as the posterior and subgenual anterior cingulate cortex, medial/superior frontal gyrus, cerebellum, and amygdala. Structural MRI studies report reductions or differences in hippocampal, amygdala and supramarginal gyrus volumes, white matter abnormalities, and potential cognitive decline in those with prolonged grief. These neurobiological measures have been associated with clinical outcomes, including prolonged grief disorder, posttraumatic stress disorder, depressive disorders, and increased risk of cardiovascular disease. Studies focusing on individuals with PTSD or prolonged grief, especially following the loss of a child or spouse, reveal hippocampal atrophy and an increased risk for brain pathologies, including neurodegenerative diseases. Future research should employ longitudinal, multi-modal, and prospective study designs to identify neurobiological markers of prolonged grief. Integrating these findings with interventional research may inform individualized strategies to promote neuroimmune resilience and improve grief management. • Grief is a universally experienced response to the loss of a significant person, however, the neural mechanisms underlying grief remain poorly understood, hindering the development of effective interventions to improve outcomes for individuals coping with loss. • Our findings reveal potentially lasting disruptions in networks related to emotion regulation, reward processing, and cognitive control in grieving individuals, with heightened neural reactivity in regions like the posterior and subgenual anterior cingulate cortex, medial/superior frontal gyrus, cerebellum, and amygdala. • We propose that these alterations may lead to dysregulation of both the neuroendocrine and immune systems, contributing to disruption in emotional, cognitive, and behavioral functioning. • Future research within this field should endeavor to include more longitudinal studies to better understand the neural, endocrine, and immune trajectories of grief, prolonged grief, and grief coupled with PTSD.