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. 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 intracranial theta burst stimulation (TBS) were delivered to the basolateral amygdala (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, clustered presumed excitatory and inhibitory neurons by waveform morphology, and examined 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. HighlightsIndividual neurons in the human brain were responsive to theta burst stimulation Basolateral amygdala stimulation preferentially modulated neurons in the hippocampus, orbitofrontal cortex, and amygdala Excitatory and inhibitory neurons were modulated equally Neurons modulated by stimulation tended to have greater baseline firing rates Duration, onset, and valence of neuronal modulation were heterogeneous