Dissecting the Fornix in Basic Memory Processes and Neuropsychiatric Disease: A Review

The fornix is the primary axonal tract of the hippocampus, connecting it to modulatory subcortical structures. This review reveals that fornix damage causes cognitive deficits that closely mirror those resulting from hippocampal lesions. In rodents and non-human primates, this is demonstrated by deficits in conditioning, reversal learning, and navigation. In humans, this manifests as anterograde amnesia. The fornix is essential for memory formation because it serves as the conduit for theta rhythms and acetylcholine, as well as providing mnemonic representations to deep brain structures that guide motivated behavior, such as when and where to eat. Diffusion weighted imaging (DWI) research is revealing that the fornix plays a key role in mild cognitive impairment and Alzheimer's Disease, and can potentially predict conversion from the former to the latter. Emerging DWI findings link perturbations in this structure to schizophrenia, mood disorders, and eating disorders, although more research is needed. This research needs to use optimized DWI methods, which we discuss, given the difficult nature of fornix reconstruction. Cutting-edge research is currently investigating how deep brain stimulation of the fornix can potentially halt memory loss, control epileptic seizures, and even improve mood.