The primate amygdala is a complex consisting of over a dozen nuclei, each with distinct connectivity patterns that have been implicated in a host of cognitive functions, individual differences, and psychiatric illnesses. The most robust functional distinction in humans is between medial and lateral nuclei, but connectivity profiles of these subdivisions are based primarily on correlations observed in blood oxygenation-level dependent functional MRI (BOLD-fMRI), limiting spatiotemporal resolution and causal conclusions. Here we conducted concurrent focal bipolar electrical stimulation through depth electrodes with intracranial electroencephalography (electrical stimulation tract-tracing; es-TT), and with fMRI (electrical stimulation fMRI; es-fMRI) in 25 neurosurgical patients (13 es-TT, 16 es-fMRI).
es-TT (51 sessions recorded over 3000 intracranial electrodes) produced profiles of effective connectivity with characteristic latencies of 15 ms (N/P15) and 150 ms (P150) that distinguished medial from lateral amygdala. Whereas lateral stimulation induced greater N/P15 potentials in anterior cingulate, sensorimotor cortex, superior temporal sulcus (STS) and superior parietal lobe (SPL), medial amygdala stimulation produced greater N150 responses in orbitofrontal cortex (OFC), superior temporal gyrus (STG), middle temporal gyrus (MTG) and prefrontal cortex (PFC). es-fMRI confirmed a similar spatial segregation of responses. Orbitofrontal cortex and anterior cingulate cortex were the key components of an amygdala network and received rapid signal propagation from the amygdala, which then continued to PFC and lateral temporal lobe, before reaching to sensorimotor and parietal cortices. Second-order effects of stimulation engaged network over broad areas of cortex, further distinguishing the site of amygdala stimulation. The findings provide a uniquely detailed characterization of human amygdala functional connectivity that will inform functional neuroimaging studies in healthy and clinical populations.