Causal Neural Circuits in Emotion Regulation
Recent Projects
The left dorsolateral prefrontal cortex causally regulates amygdala
Emotion regulation (ER) is a core affective ability that influences the quality of social interaction and is implicated in a variety of affective disorders. Evidence has shown that the left dorsolateral prefrontal cortex (dlPFC) is a key region involved in ER and an effective target for repetitive transcranial magnetic stimulation (rTMS) treatment in depression. Yet, our understanding of the causal regulatory role of the dlPFC and how rTMS to this region exerts its antidepressant effect is minimal. We performed a series of multimodal experiments in depression. Using concurrent TMS/fMRI, we observed an inhibitory effect of the dlPFC on the amygdala in healthy controls, but this effect was perturbed in depressed patients, indicating an altered dlPFC-amygdala circuit in depression. Our second experiment demonstrated this hypothesis by showing treatment with active but not sham rTMS to the dlPFC drove the dlPFC-amygdala connectivity pattern in patients towards to that seen in healthy controls. The findings together suggest that the rTMS may have improved the regulation of the dlPFC on the amygdala in depression, providing important clinical implications for treatment optimization.
- Jiang J. #, Eshel N. #, Keller C. #, Wu W. #, …, Etkin A. (2020). Global Connectivity and Local Excitability Changes Underlie Antidepressant Effects of Repetitive Transcranial Magnetic Stimulation. Neuropsychopharmacology, 45 (6): 1018-1025 (#: co-1st author). [Link]
|
|
Emotion regulation maps to a network centered on the left ventrolateral prefrontal cortex
Lesions in multiple different brain locations have been associated with changes in emotion regulation (ER). However, it is unknown whether lesions causing ER impairment map to a connected brain network. We found that damage to these networks was associated with emotion regulation impairment in patients following focal brain injury (n = 167). Next, we used this lesion dataset to derive a de novo brain network for emotion regulation, which was defined by functional connectivity to the left ventrolateral prefrontal cortex (vlPFC). Finally, we used an independent lesion database (n = 629) to test whether damage to this lesion-derived network would increase the risk of neuropsychiatric conditions associated with emotion regulation impairment. We found that lesions causing mania, criminality, and depression intersected this network more than lesions causing other disorders. We conclude that emotion regulation maps to a connected brain network centered on the left vlPFC. Damage to this network impairs emotion regulation and may increase the risk of specific neuropsychiatric disorders.
- Jiang J., Cohen A., Ferguson M., Grafman J., Fox M.: A lesion-derived brain network for emotion regulation. [Preprint].
|
|
Ongoing Projects
Invasive and Noninvasive Causal Evidence of Amygdala Engagement by DLPFC Stimulation
Invasive modulation of amygdala activity has shown promise in treating certain refractory psychiatric cases, but its widespread use among millions of treatment-resistant patients is impractical and entails inherent neurosurgery-related risks. Recent studies indicate that transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) provides a potential noninvasive alternative. However, given the amygdala's deep location in the medial temporal lobe, there is a critical need for definitive causal evidence to determine whether and how DLPFC stimulation engages the amygdala. This study aims to obtain converging causal evidence of amygdala engagement to DLPFC stimulation using multimodal invasive and noninvasive imaging methods. This comprehensive approach seeks to elucidate the causal relationship between DLPFC stimulation and amygdala engagement, potentially informing noninvasive neuromodulatory therapies for psychiatric disorders.
