Intracranial measures of amygdala connectivity in humans

The amygdala has extensive connections with the anterior cingulate (ACC), medial and orbital frontal cortices, the insula, and visual cortex; areas routinely implicated in associative learning, encoding positive and negative valence, arousal, attention, and hedonic value. We have developed intracranial stimulation protocols and single-unit isolation methods in human neurosurgical participants to complement other types of connectivity measures in humans (e.g. functional or resting state connectivity). To characterize temporal dynamics of spiking following intracranial stimulation of the amygdala, and compare with sites of intracranial cortical stimulation, we have analyzed recordings from over 1000 Behnke-Fried (BF) microwires implanted across the above-mentioned areas in 14 patients, while delivering single-pulse bi-phasic stimulation across adjacent BF macro-contacts during rest. Three patterns of single-unit spiking were identified in the cortex, hippocampus, and amygdala following intracranial stimulation: 1) increased spiking followed by suppression; 2) increased spiking without suppression; and 3) suppression followed by increased spiking. Increased spiking with late onset latencies (>100 ms) was apparent in some cases, suggesting some spikes were triggered by indirect/multi-synaptic connections, perhaps involving thalamocortical circuits. The reliable identification of spikes elicited by intracranial stimulation is necessary to determine how experimentally activated (“stimulated”) neurons might influence ongoing behaviors during task performance. By surveying areas activated, we can also identify areas that are not affected by stimulation and therefore unlikely to influence behavior. By probing activity elicited in the human brain by direct intracranial stimulation, we can broaden our understanding of functional circuits in humans involving the amygdala.