Mechanisms of Forgetting: A Systematic Review of Neurocognitive and Clinical Determinants

Background and Objectives: Forgetting has been a passive process of memory failure; an active and controlled neurocognitive process is critical for cognitive efficiency, goal-directed behaviors, and emotional coping. This systematic review aims to provide a human-based summary of the scientific understanding of forgetting from neurobiological and psychological perspectives. Materials and Methods: A literature review from 2000 - 2025 was performed using PubMed/MEDLINE, PsycINFO, and Scopus. Original peer-reviewed human-based studies that used behavioral tasks, neuroimaging methods, electroencephalography, and physiological stress inductions were considered. Results: Active control processes have been identified in the forgetting paradigm, and intentional forgetting involved prefrontal-hippocampal downregulation, whereas unintentional forgetting occurred due to limited resources, interference, and competition at the stage of information retrieval. Stress-induced disruption of the ability to recall memories operated specifically via executive and inhibitory functions. Pathological forgetting in mild cognitive impairment was explained by encoding impairments and poor consolidation, but not by accelerated long-term decay. Post-Traumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD) featured pathological forgetting associated with decreased specificity, negative bias, and poor prefrontal-medial temporal lobe inhibition, resulting in asymmetrical memory retention. Forgetting has been recognized as a dynamic and multidetermined process, which involves executive control, hippocampal-cortical interactions, and emotional modulation. Different pathologies of forgetting occur depending on the disrupted domain, indicating that differential forgetting patterns specific to particular domains, such as encoding failures in Mild Cognitive Impairment (MCI) and inhibitory deficits in PTSD, may have implications for differential diagnoses and interventions. Conclusions: Executive and emotion-regulatory dysfunction leads to maladaptive forgetting and is characterized by less specificity, more interference, and weaker inhibition. Disrupted hippocampal amygdalar prefrontal networks, in disorders like PTSD and MDD, disrupt memory suppression, resulting in intrusive emotional memories with loss of context.