Basal forebrain moderates the magnitude of task-dependent amygdala functional connectivity.
Animal studies reveal that the amygdala promotes attention and emotional memory, in part, by driving activity in downstream target regions including the prefrontal cortex (PFC) and hippocampus. Prior work has demonstrated that the amygdala influences these regions directly through monosynaptic glutamatergic signaling, and indirectly by driving activity of the cholinergic basal forebrain and subsequent downstream acetylcholine release. Yet to date, no work has addressed the functional relevance of the cholinergic basal forebrain in facilitating signaling from the amygdala in humans. We set out to determine how blood oxygen level-dependent signal within the amygdala and cholinergic basal forebrain interact to predict neural responses within downstream targets. Here, we use functional connectivity analyses to demonstrate that the cholinergic basal forebrain moderates increased amygdala connectivity with both the PFC and the hippocampus during the processing of biologically salient stimuli in humans. We further demonstrate that functional variation within the choline transporter gene predicts the magnitude of this modulatory effect. Collectively, our results provide novel evidence for the importance of cholinergic signaling in modulating neural pathways supporting arousal, attention and memory in humans. Further, our results may shed light on prior association studies linking functional variation within the choline transporter gene and diagnoses of major depression and attention-deficit hyperactivity disorder.
Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Institute for Genome Sciences & Policy, Duke University, Durham, 27708 NC, USA axgorka@gmail.com.
Adam X
AX
Gorka
Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Institute for Genome Sciences & Policy, Duke University, Durham, 27708 NC, USA.
Annchen R
AR
Knodt
Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Institute for Genome Sciences & Policy, Duke University, Durham, 27708 NC, USA.
Ahmad R
AR
Hariri
D000293:Adolescent; D000679:Amygdala / Q000502:physiology*; D066187:Basal Forebrain / Q000502:physiology*; D001931:Brain Mapping; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D009434:Neural Pathways / Q000502:physiology*; D059906:Neuroimaging; D010100:Oxygen / Q000097:blood; D010275:Parasympathetic Nervous System / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology*; D055815:Young Adult
D026901:Membrane Transport Proteins; C065637:choline transporter; D004247:DNA; D010100:Oxygen
amygdala; basal forebrain; choline transporter; functional connectivity; imaging genetics