Fornix as an imaging marker for episodic memory deficits in healthy aging and in various neurological disorders

The fornix is a part of the limbic system and constitutes the major efferent and afferent white matter tracts from the hippocampi. The underdevelopment of or injuries to the fornix are strongly associated with memory deficits. Its role in memory impairments was suggested long ago with cases of surgical forniceal transections. However, recent advances in brain imaging techniques, such as diffusion tensor imaging, have revealed that macrostructural and microstructural abnormalities of the fornix correlated highly with declarative and episodic memory performance. This structure appears to provide a robust and early imaging predictor for memory deficits not only in neurodegenerative and neuroinflammatory diseases, such as Alzheimer's disease and multiple sclerosis, but also in schizophrenia and psychiatric disorders, and during neurodevelopment and “typical” aging. The objective of the manuscript is to present a systematic review regarding published brain imaging research on the fornix, including the development of its tracts, its role in various neurological diseases, and its relationship to neurocognitive performance in human studies.