Brain activation patterns during memory processes measured with functional magnetic resonance imaging are associated with human serotonin-1A receptor in vivo

The serotonergic system was previously shown to affect learning and memory processes in humans[1]. Establishing a relation between serotonin-1A receptor (5-HT1AR) distribution with memory processing would allow us to further investigate its potential as a therapeutic target. Here, we aim to investigate the effect of 5-HT1AR spatial distribution on the different memory domains. Positron emission tomography data were collected from 20 healthy volunteers using the radioligand [carbonyl-11C]WAY-100635 [2,3]. Data were quantified using multilinear reference tissue model 2 to obtain non-displaceable binding potential representing 5-HT1AR spatial distribution. Four functional magnetic resonance imaging datasets representing memory processing (Semantic/Episodic/Working memory) and retrieval brain activations were downloaded from the Neurosynth database (https://neurosynth.org/). A comparison was done using Spearman's rank correlation in cortical and subcortical regions defined in the Brainnetome atlas[4]. Positive associations between 5-HT1AR distribution and brain activation during memory processing were unveiled for semantic memory (rs=0.435) in the cortical regions and episodic memory (rs=0.438) and memory retrieval (rs=0.430) in the subcortex. A negative relation was shown for working memory (rs=−0.641) in subcortical regions (Figure1). The hippocampus was identified as a region with the clearest overlap between 5-HT1AR distribution and memory-induced brain activations. Overall, our study confirms the already-known influence of 5-HT1AR on memory processing and formation. Moreover, it allows for the further investigation of the involvement of the serotonergic system and its potential as a treatment target in memory impairment.[1]Ogren 2008 Behavioural Brain research 195(1):54-77;[2]Baldinger 2014 Int J Neuropsychopharmacol 18(4):1–9;[3]Lanzenberger 2007 Biol Psychiatry 61(9):1081-1089;[4]Fan 2016 Cereb Cortex 26(8):3508-3526