Human single-neuron activity is modulated by intracranial theta burst stimulation of the basolateral amygdala

Direct electrical stimulation of the human brain has been used for numerous clinical and scientific applications. Previously, we demonstrated that intracranial theta burst stimulation (TBS) of the basolateral amygdala (BLA) can enhance declarative memory, likely by modulating hippocampal-dependent memory consolidation. At present, however, little is known about how intracranial stimulation affects activity at the microscale. In this study, we recorded intracranial EEG data from a cohort of patients with medically refractory epilepsy as they completed a visual recognition memory task. During the memory task, brief trains of TBS were delivered to the BLA. Using simultaneous microelectrode recordings, we isolated neurons in the hippocampus, amygdala, orbitofrontal cortex, and anterior cingulate cortex and tested whether stimulation enhanced or suppressed firing rates. Additionally, we characterized the properties of modulated neurons, patterns of firing rate coactivity, and the extent to which modulation affected memory task performance. We observed a subset of neurons (∼30%) whose firing rate was modulated by TBS, exhibiting 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, although the impact of this neuronal modulation on memory remains unclear. These findings advance our limited understanding of how focal electrical fields influence neuronal firing at the single-cell level and motivate future neuromodulatory therapies that aim to recapitulate specific patterns of activity implicated in cognition and memory.