Cognitive Changes and Brain Structural Plasticity under Long-Term Negative Emotions: Research Progress and Causal Controversies

Depression, fear, and anxiety are typical negative emotions. If these emotions persist for a long time, they can lead to cognitive biases and physical discomfort. Two common clinical subtypes are generalized anxiety disorder (GAD) and major depressive disorder (MDD). Whether these emotions causally affect structural plasticity and neural circuit function—and if so, how—remains an open question. Prior work has combined brain imaging, non-invasive brain stimulation (including Repetitive Transcranial Magnetic Stimulation), and drug intervention data to map the structural and circuit changes linked to different negative emotions. The prefrontal-amygdala circuit appears central to negative emotion processing, yet the brain changes linked to depression, anxiety, and fear differ. Because cross-sectional studies capture only one time point, they cannot resolve causality—brain abnormalities may be pre-existing traits, or they may emerge secondarily from persistent emotions. Non-invasive brain stimulation and pharmacological interventions can modulate neural circuits, which supports their potential as interventions. A single scan gives only a snapshot. It cannot show whether negative emotions reshape the brain over time, or whether pre-existing brain features shape those emotions. Longitudinal tracking of the same individuals across multiple time points, with control groups for comparison, would help clarify it.