Treatment of depression with deep brain stimulation works by altering in specific ways the conscious perception of the core symptoms of sadness or anhedonia, not by modulating network circuitry

Abstract

An important advance in the management of treatment-resistant depression has recently been reported: deep brain stimulation (DBS) of the subgenual cingulate (Brodmann area 25 or Cg 25) or the nucleus accumbens (NAcc). These treatments produce a response rate, meaning significant clinical improvement, of about 50%, but only a few patients are returned completely to normal. The authors of these papers generally attribute the therapeutic response to restoration of an altered or perturbed neural network. In contrast, the idea advanced here is that DBS works by altering conscious perception of the core symptoms of sadness and anhedonia, not by modulating network circuitry. In the case of Cg25, the crucial thing about this site is that it is where conscious perception of sadness localizes. However, the stimulus frequency of DBS (130Hz) was too fast to support consciousness, which is associated with gamma frequencies (35–85Hz). Therefore, the imposed rapid frequency instantaneously blocked the subjective experience of sadness. In the case of the NAcc, the treatment worked by stimulating hot zones in the NAcc, which, in animal models, are known to intensify the perception of pleasure. This magnifier effect on the perception of pleasure was able to alleviate anhedonia. The response was not instantaneous but could begin within hours. In both cases, patients’ realization that a core symptom had been relieved led to a moderate overall improvement in other symptoms.