title: The Impact of Mirth-Inducing Ventral Striatal Deep Brain Stimulation on Functional and Effective Connectivity.
abstract: 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. 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. Both mirth-inducing and non-mirth-inducing VC/VS DBS consistently resulted (conjunction, global null, family-wise error-corrected P < 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 enhanced effective connectivity from anterior cingulate to ventral striatum, while attenuating connectivity from thalamus to ventral striatum relative to non-mirth-inducing stimulation. 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.
authors.affiliation: Department of Neurologic Surgery.
authors.forename: William S
authors.initials: WS
authors.lastname: Gibson
authors.affiliation: Department of Neurologic Surgery.
authors.forename: Shinho
authors.initials: S
authors.lastname: Cho
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN 55906, USA.|National Institute on Drug Abuse, Baltimore, MD 21224, USA.
authors.forename: Osama A
authors.initials: OA
authors.lastname: Abulseoud
authors.affiliation: Department of Radiology.
authors.forename: Krzysztof R
authors.initials: KR
authors.lastname: Gorny
authors.affiliation: Department of Radiology.
authors.forename: Joel P
authors.initials: JP
authors.lastname: Felmlee
authors.affiliation: Department of Radiology.
authors.forename: Kirk M
authors.initials: KM
authors.lastname: Welker
authors.affiliation: Department of Neurology and.
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Klassen
authors.affiliation: Department of Neurologic Surgery.|Department of Radiology.|Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Hoon-Ki
authors.initials: HK
authors.lastname: Min
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, US.|Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Kendall H
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000339:Affect; D001499:Bayes Theorem; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000601:surgery; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000502:physiology; D046690:Deep Brain Stimulation; D004644:Emotions; D005260:Female; D006801:Humans; D007432:Intraoperative Period; D007845:Laughter / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery; D019635:Neurosurgical Procedures; D010100:Oxygen / Q000097:blood; D012904:Smiling / Q000502:physiology; D014925:Wit and Humor as Topic; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: DBS; fMRI; mood; nucleus accumbens; obsessive compulsive disorder