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

Abstract

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 imaging 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 imaging findings link perturbations in this structure to schizophrenia, mood disorders, and eating disorders, although more research is needed. 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.

Subiculum–BNST structural connectivity in humans and macaques

“…Structural and functional alterations of the hippocampus and/or BNST have previously been linked to stress-related traits and disorders ( Avery et al., 2016 ; Hur et al., 2019 ). Although we could find no examples of studies investigating subiculum - BNST tract microstructure, a small number of studies have examined dMRI associations in the fornix with stress-related traits; with varying results ( Barnea-Goraly et al., 2009 ; Benear et al., 2020 ; Modi et al., 2013 ; Yu et al., 2017 ).…”

“…Although interesting, assessing streamlines in this way should generally be avoided in favour of microstructure measures, as individual differences in streamline variation are difficult to interpret ( Jones et al., 2013 ). Whilst not specific to the BNST, white matter abnormalities of the fornix in adults with heavy drinking and alcohol use disorder have been reported ( Cardenas et al., 2013 ), although the diffusion MRI literature in general with regards to correlates of substance abuse is somewhat inconsistent ( Benear et al., 2020 ). Similar to our dispositional negativity component, a reason we did not find such an association could be that our sample consisted of a screened, relatively healthy population (median drinks consumed per week being two), which likely reduced our chances of finding any association ( Berry et al., 2020 ).…”

Association Between Microstructural Asymmetry of Temporal Lobe White Matter and Memory Decline After Anterior Temporal Lobectomy

“…49 Despite the known importance of the fornix to memory and its connections to the hippocampus, we did not include it in our analysis because the fornix is challenging to reliably reconstruct due to its narrow size and high bending angle, and is subject to significant partial voluming. 50 Advanced diffusion sequences with HARDI models are better suited to reliably reconstruct the fornix and evaluate its contribution to postoperative memory decline. Although we evaluated the contribution of MTL WM to memory outcomes, these fibers may also be important predictors of decline in other cognitive domains such as executive function.…”

Differences of resting fMRI and cognitive function between drug-naïve bipolar disorder and schizophrenia

“…A longitudinal study suggested that after standardized clinical treatment, BD patients could get cognitive recovery, left slight cognitive damage, and could be repaired to a certain extent through follow-up cognitive exercise [ 35 ]. However, the cognitive impairment of SC was usually considered irreversible because it was considered to be related to nerve injury [ 36 – 39 ]. Therefore, cognitive testing is helpful to distinguish the diagnosis of these two diseases.…”