Mapping of amygdala circuits in humans

The speaker will describe recent work examining the effects of direct electrical stimulation to the human amygdala on the autonomic nervous system, emotional experience, and long-term declarative memory. In the first study, they found that amygdala stimulation in epilepsy patients undergoing monitoring of seizures via intracranial depth electrodes elicited immediate and substantial dose-dependent increases in electrodermal activity and decelerations of heart rate, most often without eliciting any subjective emotional response. In a subsequent study, they describe work showing that brief, low-amplitude, direct electrical stimulation of the human amygdala enhances long-term declarative memory without eliciting an emotional response. Taken together, these results show that emotion-related circuitry in the human brain can provoke autonomic and subjective changes in emotion and initiate endogenous memory prioritization processes in the absence of emotional input, addressing a fundamental question and opening a path to future therapies. 

This speaker will highlight findings from precision fMRI, where functional anatomy is defined within individuals, that indicate that specific amygdala regions show intrinsic functional connectivity with a distributed association network that is recruited during social cognitive (e.g., theory of mind) tasks. The amygdalocortical network serving social cognition appears to include multiple stages of the internal amygdala circuitry, including input (basolateral complex), integrative (accessory basal and basal nuclei), and output (medial nucleus) structures. Our findings provide a rare investigation of the medial nucleus in the human and support its role in social cognition. 

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. 

The primate temporal cortex has a specialized system for representing faces, as borne out by a large literature from fMRI in humans and single-unit recordings in monkeys. Sophisticated computational models explain how population-level activity in this system represents the identity and familiarity of faces. But what happens next? How does the brain represent the social and emotional attributes of faces in regions that receive their input from temporal cortex? The most prominent structure for investigation here is the amygdala, but severe signal dropout and poor resolution greatly limits our knowledge from fMRI studies. Here we present data acquired from single-neuron recordings in human epilepsy patients. These data provide the first comprehensive inventory of face responses in the human amygdala during social trait judgement. Furthermore, they advance new models that incorporate the amygdala into a broader system for social cognition from faces.