Introduction: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is an investigational therapy for treatment-resistant obsessive-compulsive disorder. The ability of VC/VS DBS to evoke spontaneous mirth in patients, often accompanied by smiling and laughter, is clinically well documented. However, the neural correlates of DBS-evoked mirth remain poorly characterized.
Methods: Patients undergoing VC/VS DBS surgery underwent intraoperative evaluation in which mirth-inducing and non-mirth-inducing stimulation localizations were identified. Using dynamic causal modeling (DCM) for fMRI, the effect of mirth-inducing DBS on functional and effective connectivity among established nodes in limbic cortico-striato-thalamo-cortical (CSTC) circuitry was investigated.
Results: . Both mirth-inducing and non-mirth-inducing VC/VS DBS consistently resulted (conjunction, global null, familywise error-corrected p value < 0.05) in activation of amygdala, ventral striatum, and mediodorsal thalamus. However, only mirth-inducing DBS resulted in functional inhibition of anterior cingulate cortex. Dynamic causal modeling revealed that mirth-inducing DBS resulted in an attenuation of effective connectivity from both anterior cingulate and mediodorsal thalamus to ventral striatum relative to non-mirth-inducing stimulation.
Conclusions: These results suggest that DBS-evoked mood elevation is accompanied by distinct patterns of limbic thalamocortical connectivity. Using the novel combination of DBS-evoked mood alteration and functional MRI in human subjects, we provide new insights into the network-level mechanisms that influence affect.
Patient Care: Understanding the network-level mechanisms that mediate the effects of VC/VS DBS could potentially lead to optimization of the therapy in the future, as well as an improved understanding of the basic mechanisms that govern human mood regulation.
Learning Objectives: By the conclusion of the session, participants should be able to understand our results pertaining to the effects of mirth-inducing deep brain stimulation on functional and effective connectivity.