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Endogenous serotonin (5‐HT) release can be measured noninvasively using positron emission tomography (PET) imaging in combination with certain serotonergic radiotracers. This allows us to investigate effects of pharmacological and nonpharmacological interventions on brain 5‐HT levels in living humans. Here, we study the neural responses to a visual stimulus using simultaneous PET/MRI. In a cross‐over design, 11 healthy individuals were PET/MRI scanned with the 5‐HT1B receptor radioligand [11C]AZ10419369, which is sensitive to changes in endogenous 5‐HT. During the last part of the scan, participants either viewed autobiographical images with positive valence (n = 11) or kept their eyes closed (n = 7). The visual stimuli increased cerebral blood flow (CBF) in the occipital cortex, as measured with pseudo‐continuous arterial spin labeling. Simultaneously, we found decreased 5‐HT1B receptor binding in the occipital cortex (−3.6 ± 3.6%), indicating synaptic 5‐HT release. Using a linear regression model, we found that the change in 5‐HT1B receptor binding was significantly negatively associated with change in CBF in the occipital cortex (p = .004). For the first time, we here demonstrate how cerebral 5‐HT levels change in response to nonpharmacological stimuli in humans, as measured with PET. Our findings more directly support a link between 5‐HT signaling and visual processing and/or visual attention., Here, we study the neural responses to a visual stimulus using simultaneous positron emission tomography/magnetic resonance imaging. We find a significant association between anincrease in cerebral blood flow (CBF) in the occipital cortex along and a decrease in [11C]AZ10419369 binding, suggesting synaptic serotonin (5‐HT) release. To the best of our knowledge, this is the first time that simultaneous changes in CBF and 5‐HT levels in response to physiological stimuli have been measured.

Brain-derived neurotrophic factor (BDNF) has been implicated in multiple aspects of brain function including regulation of serotonin signaling. The BDNF val66met polymorphism (rs6265) has been linked to aspects of serotonin signaling in humans but its effects are not well understood. To address this, we evaluated whether BDNF val66met was predictive of a putative marker of brain serotonin levels, serotonin 4 receptor (5-HT4) binding assessed with [11C]SB207145 positron emission tomography, which has also been associated with the serotonin-transporter-linked polymorphic region (5-HTTLPR) polymorphism. We applied a linear latent variable model (LVM) using regional 5-HT4 binding values (neocortex, amygdala, caudate, hippocampus, and putamen) from 68 healthy humans, allowing us to explicitly model brain-wide and region-specific genotype effects on 5-HT4 binding. Our data supported an LVM wherein BDNF val66met significantly predicted a LV reflecting [11C]SB207145 binding across regions (P = 0.005). BDNF val66met met-carriers showed 2–9% higher binding relative to val/val homozygotes. In contrast, 5-HTTLPR did not predict the LV but S-carriers showed 7% lower neocortical binding relative to LL homozygotes (P = 7.3 × 10−6). We observed no evidence for genetic interaction. Our findings indicate that BDNF val66met significantly predicts a common regulator of brain [11C]SB207145 binding, which we hypothesize reflects brain serotonin levels. In contrast, our data indicate that 5-HTTLPR specifically affects 5-HT4 binding in the neocortex. These findings implicate serotonin signaling as an important molecular mediator underlying the effects of BDNF val66met and 5-HTTLPR on behavior and related risk for neuropsychiatric illness in humans. Hum Brain Mapp, 36:313–323, 2015. © 2014 Wiley Periodicals, Inc.

Neuroimaging studies of learning focus on brain areas where the activity changes as a function of time. To circumvent the difficult problem of model selection, we used a data‐driven analytic tool, cluster analysis, which extracts representative temporal and spatial patterns from the voxel‐time series. The optimal number of clusters was chosen using a cross‐validated likelihood method, which highlights the clustering pattern that generalizes best over the subjects. Data were acquired with PET at different time points during practice of a visuomotor task. The results from cluster analysis show practice‐related activity in a fronto‐parieto‐cerebellar network, in agreement with previous studies of motor learning. These voxels were separated from a group of voxels showing an unspecific time‐effect and another group of voxels, whose activation was an artifact from smoothing. Hum. Brain Mapping 15:135–145, 2002. © 2002 Wiley‐Liss, Inc.

Brain‐derived neurotrophic factor (BDNF) has been implicated in multiple aspects of brain function including regulation of serotonin signaling. The BDNF val66met polymorphism (rs6265) has been linked to aspects of serotonin signaling in humans but its effects are not well understood. To address this, we evaluated whether BDNF val66met was predictive of a putative marker of brain serotonin levels, serotonin 4 receptor (5‐HT(4)) binding assessed with [(11)C]SB207145 positron emission tomography, which has also been associated with the serotonin‐transporter‐linked polymorphic region (5‐HTTLPR) polymorphism. We applied a linear latent variable model (LVM) using regional 5‐HT(4) binding values (neocortex, amygdala, caudate, hippocampus, and putamen) from 68 healthy humans, allowing us to explicitly model brain‐wide and region‐specific genotype effects on 5‐HT(4) binding. Our data supported an LVM wherein BDNF val66met significantly predicted a LV reflecting [(11)C]SB207145 binding across regions (P = 0.005). BDNF val66met met‐carriers showed 2–9% higher binding relative to val/val homozygotes. In contrast, 5‐HTTLPR did not predict the LV but S‐carriers showed 7% lower neocortical binding relative to LL homozygotes (P = 7.3 × 10(−6)). We observed no evidence for genetic interaction. Our findings indicate that BDNF val66met significantly predicts a common regulator of brain [(11)C]SB207145 binding, which we hypothesize reflects brain serotonin levels. In contrast, our data indicate that 5‐HTTLPR specifically affects 5‐HT(4) binding in the neocortex. These findings implicate serotonin signaling as an important molecular mediator underlying the effects of BDNF val66met and 5‐HTTLPR on behavior and related risk for neuropsychiatric illness in humans. Hum Brain Mapp, 36:313–323, 2015. © 2014 Wiley Periodicals, Inc.