Fera F, Passamonti L, Cerasa A, Gioia MC, Liguori M, Manna I, Valentino P, Quattrone A. The BDNF Val<sup>66</sup>Met Polymorphism Has Opposite Effects on Memory Circuits of Multiple Sclerosis Patients and Controls. PLoS One. 2013 Apr 11;8(4):e61063. Print 2013.
Episodic memory deficits are frequent symptoms in Multiple Sclerosis and have been associated with dysfunctions of the hippocampus, a key region for learning. However, it is unclear whether genetic factors that influence neural plasticity modulate episodic memory in MS. We thus studied how the Brain Derived Neurotrophic Factor Val66Met genotype, a common polymorphism influencing the hippocampal function in healthy controls, impacted on brain networks underlying episodic memory in patients with Multiple Sclerosis. Functional magnetic resonance imaging was used to assess how the Brain Derived Neurotrophic Factor Val66Met polymorphism modulated brain regional activity and functional connectivity in 26 cognitively unimpaired Multiple Sclerosis patients and 25 age- and education-matched healthy controls while performing an episodic memory task that included encoding and retrieving visual scenes.
We found a highly significant group by genotype interaction in the left posterior hippocampus, bilateral parahippocampus, and left posterior cingulate cortex. In particular, Multiple Sclerosis patients homozygous for the Val66 allele (Valine at position 66), relative to Met66 (Methionine at postion 66) carriers, showed greater brain responses during both encoding and retrieval while the opposite was true for healthy controls. Furthermore, a robust group by genotype by task interaction was detected for the functional connectivity between the left posterior hippocampus and the ipsilateral posterior cingulate cortex. Here, greater hippocampus-posterior cingulate cortex connectivity was observed in Multiple Sclerosis Met66 carriers relative to Val66homozygous during retrieval (but not encoding) while, again, the reverse was true for healthy controls. The Val66Met polymorphism has opposite effects on hippocampal circuitry underlying episodic memory in Multiple Sclerosis patients and healthy controls. Enhancing the knowledge of how genetic factors influence cognitive functions may improve the clinical management of memory deficits in patients with Multiple Sclerosis.
In this study they looked at the effects of memory tasks and did imaging and can see changes in the brains during these task and the regions that are activated differ between individuals that have one form of brain derived neurotrophic factor verses another genetic variant of this nerve growth factor. However these effects differed in MSers verses health controls. I am not sure of the significance of this but does show that MSers have adaptive changes in their brains as neural circuitry is affected.