SUMMARY
The amygdala is a highly connected cluster of nuclei with input from multiple sensory modalities, particularly the ventral visual stream, and vast projections to distributed cortical and subcortical regions involved in autonomic regulation and cognition.1–4 Numerous studies have described the amygdala’s capacity to facilitate the encoding of long-lasting emotional memories.5–15 Recently, direct electrical stimulation of the basolateral complex of the amygdala (BLA) in humans revealed a more generalized ability to enhance declarative memory irrespective of the emotional valence16, likely by promoting synaptic plasticity-related processes underlying memory consolidation in the hippocampus and medial temporal lobe.17–20 These effects were achieved with rhythmic theta-burst stimulation (TBS), which is known to induce long-term potentiation (LTP), a key mechanism in memory formation.21 Emerging evidence suggests that intracranial TBS may also enhance memory specificity22, evoke theta-frequency oscillations23, and facilitate short-term plasticity in local field potential recordings.24,25 However, how amygdalar TBS modulates activity at the single-cell level and to what extent this modulation is associated with memory performance remain poorly understood. Here, we address this knowledge gap by conducting simultaneous microelectrode recordings from prefrontal and medial temporal structures during a memory task in which intracranial TBS was applied to the BLA. We observed a subset of neurons whose firing rate was modulated by TBS and exhibited highly heterogeneous responses with respect to onset latency, duration, and direction of effect. Notably, location and baseline activity predicted which neurons were most susceptible to modulation. These findings provide direct empirical support for stimulation-evoked modulation of single-neuron activity in humans, which has implications for the development and refinement of neuromodulatory therapies.
Highlights
– Individual neurons in the human brain were responsive to theta burst stimulation
– Basolateral amygdala stimulation preferentially modulated neurons in the hippocampus, orbitofrontal cortex, and amygdala
– Neurons modulated by stimulation tended to have greater baseline firing rates
– Duration, onset, and valence of neuronal modulation were heterogeneous
In Brief Campbell et al. identify a subset of neurons in humans whose firing rate is modulated by intracranial theta burst stimulation of the basolateral amygdala. Location and baseline activity of detected neurons were associated with responsiveness to stimulation. These results provide a link between micro- and macroscale responses evoked by stimulation.
Competing Interest Statement
The authors have declared no competing interest.
