Examining the underpinnings of loudness dependence of auditory evoked potentials with positron emission tomography

Loudness dependence of auditory evoked potentials (LDAEP) has long been considered to reflect central basal serotonin transmission. However, the relationship between LDAEP and individual serotonin receptors and transporters has not been fully explored in humans and may involve other neurotransmitter systems. To examine LDAEP's relationship with the serotonin system, we performed PET using serotonin-1A (5-HT_1A) imaging via [¹¹C]CUMI-101 and serotonin transporter (5-HTT) imaging via [¹¹C]DASB on a mixed sample of healthy controls (n ​= ​4: 4 females, 0 males), patients with unipolar (MDD, n ​= ​11: 4 females, 7 males) and bipolar depression (BD, n ​= ​8: 4 females, 4 males). On these same participants, we also performed electroencephalography (EEG) within a week of PET scanning, using 1000 ​Hz tones of varying intensity to evoke LDAEP. We then evaluated the relationship between LDAEP and 5-HT_1A or 5-HTT binding in both the raphe (5-HT_1A)/midbrain (5-HTT) areas and in the temporal cortex. We found that LDAEP was significantly correlated with 5-HT_1A positively and with 5-HTT negatively in the temporal cortex (p ​< ​0.05), but not correlated with either in midbrain or raphe. In males only, exploratory analysis showed multiple regions in which LDAEP significantly correlated with 5-HT_1A throughout the brain; we did not find this with 5-HTT. This multimodal study partially validates preclinical models of a serotonergic influence on LDAEP. Replication in larger samples is necessary to further clarify our understanding of the role of serotonin in perception of auditory tones.