Deep brain stimulation (DBS) is currently an established treatment for medical refractory Parkinson’s disease, essential tremor and obsessive-compulsive disorder. More recently, DBS has been proposed as a possible treatment for neuropsychiatric disorders such as depression, addiction, and post-traumatic stress disorder (PTSD). Specifically, a clinical trial of DBS of the amygdala for combat PTSD is currently underway at the WLA VA. These subjects provide a unique opportunity to understand the role of the amygdala in human behavior. The amygdala is known for its role in emotional processing, anxiety, and reward; however, evidence supporting this relies mainly on results from animal models. The present study aims to correlate the structural connectivity of the amygdala with behavioral and physiological data obtained during awake DBS stimulation of a single subject with PTSD. The goal of this study is to understand how amygdala network connectivity mediates specific behaviors.
We performed stimulation mapping in a 40-year-old male patient with treatment refractory PTSD one month after placement of bilateral amygdala DBS electrodes (parameters: 160 Hz, 90 ms pulse width and voltage: 0V to 5V). Behavioral and physiologic data were recorded systematically at sequential contacts with increasing voltage levels. The subject’s pre-op MRI scans and post-op CT scans were co-registered and normalized to MNI space. Seed masks were created that simulate the volume of tissue activated (VTA) by each electrode at different voltages (1V to 5V) (Lead-DBS Software). We previously created population statistical maps of amygdala connectivity to several target structures using probabilistic tractography: brainstem, dorsolateral prefrontal cortex (DLPFC), hippocampus, insula, nucleus accumbens (NAc), orbitofrontal cortex (OFC), and rostral anterior cingulate cortex (rACC). VTA masks were then overlaid with the statistical maps to correlate stimulation with network connectivity. IRB approval was obtained for all aspects of the study.
Our findings showed that stimulation of the right hippocampal contact induced profound sleepiness at various voltages (2V to 4V), which was correlated with diffuse slowing on EEG. In contrast, the left hippocampal contact induced anxiety and distress and were only induced at high voltages (4V and 5V). In addition, stimulation of more dorsal basolateral amygdala, bilaterally, induced feelings of euphoria at lower voltages whereas higher voltages induced aggressive behavior. These stimulation findings correlated with structural connectivity of the amygdala with other limbic targets as defined by diffusion tensor imaging (DTI)-based probabilistic tractography.
These results illustrated that direct stimulation of the dorsal basolateral amygdala may induce feelings of euphoria and anger, which correlates to many studies that posit the amygdala’s major role in emotional processing. Although the mechanism of action of DBS isn’t fully understood, current theories suggest that electrical stimulation may inhibit activity in the target nucleus. A hyper-responsive or hyper-functioning amygdala is believed to play a role in the pathophysiology of PTSD. The lower voltage stimulation may inhibit the amygdala, which results in euphoria. The higher voltage stimulation may induce aggressive behavior as a larger volume of tissue is activated by the higher voltage. The electrical stimulation may also be inhibiting other structures adjacent to the amygdala, which may explain the contrasting behaviors induced by different stimulation intensities.