Low glutamate diet improves working memory and contributes to altering BOLD response and functional connectivity within working memory networks in Gulf War Illness

Gulf War Illness is a chronic multi-symptom disorder with severe cognitive impairments which may be related to glutamate excitotoxicity and central nervous system dysfunction. The low glutamate diet has been proposed as a comprehensive intervention for Gulf War Illness. We examined the effects of the low glutamate diet on verbal working memory using a fMRI N-back task. Accuracy, whole-brain blood oxygen level dependency (BOLD) response, and task-based functional connectivity were assessed at baseline and after 1 month on the diet (N = 24). Multi-voxel pattern analysis identified regions of whole-brain BOLD pattern differences after the diet to be used as seeds for subsequent seed-to-voxel functional connectivity analyses. Verbal working memory accuracy improved after the diet (+ 13%; p = 0.006). Whole-brain BOLD signal changes were observed, revealing lower activation within regions of the frontoparietal network and default mode network after the low glutamate diet. Multi-voxel pattern analysis resulted in 3 clusters comprising parts of the frontoparietal network (clusters 1 and 2) and ventral attention network (cluster 3). The seed-to-voxel analyses identified significant functional connectivity changes post-diet for clusters 1 and 2 (peak p < 0.001, cluster FDR p < 0.05). Relative to baseline, clusters 1 and 2 had decreased functional connectivity with regions in the ventral attention and somatomotor networks. Cluster 2 also had increased functional connectivity with regions of the default mode and frontoparietal networks. These findings suggest that among veterans with Gulf War Illness, the low glutamate diet improves verbal working memory accuracy, alters BOLD response, and alters functional connectivity within two networks central to working memory.

Automated summary

In this study, the effects of a low glutamate diet on verbal working memory in Gulf War Illness patients were examined using fMRI N-back task. The results showed that the diet improved verbal working memory accuracy, altered brain activity patterns, and changed functional connectivity within networks important for working memory. These findings are significant for the treatment of Gulf War Illness.