Functional adaptive changes within the hippocampal memory system of patients with multiple sclerosis.

Memory deficits are highly prevalent in multiple sclerosis (MS). As the hippocampus is crucial to memory processing, a functional magnetic resonance imaging (fMRI) task was used to investigate changes in hippocampal function in MS patients with and without cognitive decline. Fifty patients with MS, (34 cognitively preserved (CP) and 16 cognitively impaired (CI)) and 30 healthy controls completed an episodic memory fMRI task (encoding and retrieval) that was used to specifically activate the hippocampus. During encoding of correctly remembered items, increased brain activation was seen in the parahippocampal areas bilaterally and in the left anterior cingulate gyrus in the CP patients compared to the controls (unclustered, Z ≥ 3.1, P ≤ 0.001). No brain areas showed less activation. In CI patients the right (para)hippocampal areas and the prefrontal cortex showed less brain activation compared to controls (cluster-corrected, P < 0.05). The posterior cingulate gyrus and the left precuneus showed increased activation in CI patients when compared to controls (unclustered Z ≥ 3.1, P ≤ 0.001). No significant differences were found on structural MRI measures between the CP and CI patients. These results suggest the presence of functional adaptation in the memory network before cognitive decline becomes evident in MS, as displayed by the increased brain activation in the hippocampal-cingulate memory system in CP patients. Interestingly, CI patients showed less activation in the hippocampal network during correct encoding. These findings are important for future cognitive therapeutic studies, since cognitive intervention might be most effective before cognitive impairment is present and when adaptive changes of the brain are most prominent.