Serotonin release induced by working memory: An [18F] altanserin PET study

Objectives Data on changes in neurotransmitters during working memory (WM) processing is sparse. Here we investigate WM induced changes in [¹⁸F] altanserin binding to 5HT2a receptors assumed to reflect changes in synaptic serotonin.

Methods 10 young healthy males were scanned during a visual delayed match to sample WM task and a control condition. Every trial consisted of 3 consecutively presented male portraits followed by a 9s delay and a single target portrait either framed in purple or grey. During WM the subjects had to decide if the target matched one of the 3 initial portraits. During control they had to indicate the color of target’s frame. [¹⁸F] altanserin PET data were collected over 90min. After calculating the binding potentials (BP) with Ichise’s noninvasive plot (pmod) using the cerebellum as reference a ROI based comparison focusing on regions known to be involved in WM and a whole brain analysis were performed (SPM2). Clusters >50 voxels and p<0.05 corr (ROI analysis) or p<0.001 uncorr (whole brain analysis) were reported.

Results ROI analysis revealed a 54 voxel ACC cluster with a significantly increased BP during WM. Using the reverse contrast no clusters with increased BP were seen even at low thresholds. Whole brain analysis demonstrated further increased BP clusters during WM in posterior cingulate, retrosplenial, ventral extrastriatal, superior and middle temporal and orbitofrontal cortex. Again, the reversed contrast revealed no suprathreshold clusters.

Conclusions Data reveal regions with increased [¹⁸F] altanserin binding during WM suggesting a reduction in synaptic serotonin. This WM induced modulation of serotoninergic neurotransmission is not confined to brain areas known to be involved in WM but include a wider neocortical network.