title: Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor.
abstract: Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson's disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal modelling revealed a correlation between therapeutic effectiveness and attenuated within-region inhibitory connectivity in cerebellum. Finally, specific subregions of sensorimotor cortex were identified in which deep brain stimulation-evoked activation correlated with the presence of unwanted paraesthesias. These results suggest that thalamic deep brain stimulation in tremor likely exerts its effects through modulation of both olivocerebellar and thalamocortical circuits. In addition, our findings indicate that deep brain stimulation-evoked functional activation maps obtained intraoperatively may contain predictive information pertaining to the therapeutic and adverse effects induced by deep brain stimulation.media-1vid110.1093/brain/aww145_video_abstractaww145_video_abstract.
authors.affiliation: 1 Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA 55905, USA.
authors.forename: William S
authors.initials: WS
authors.lastname: Gibson
authors.affiliation: 1 Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA 55905, USA.
authors.forename: Hang Joon
authors.initials: HJ
authors.lastname: Jo
authors.affiliation: 1 Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA 55905, USA.
authors.forename: Paola
authors.initials: P
authors.lastname: Testini
authors.affiliation: 1 Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA 55905, USA.
authors.forename: Shinho
authors.initials: S
authors.lastname: Cho
authors.affiliation: 2 Department of Radiology, Mayo Clinic, Rochester, MN, USA 55905, USA.
authors.forename: Joel P
authors.initials: JP
authors.lastname: Felmlee
authors.affiliation: 2 Department of Radiology, Mayo Clinic, Rochester, MN, USA 55905, USA.
authors.forename: Kirk M
authors.initials: KM
authors.lastname: Welker
authors.affiliation: 3 Department of Neurology, Mayo Clinic, Rochester, MN, USA 55905, USA.
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Klassen
authors.affiliation: 1 Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA 55905, USA 2 Department of Radiology, Mayo Clinic, Rochester, MN, USA 55905, USA 4 Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, 55905, USA.
authors.forename: Hoon-Ki
authors.initials: HK
authors.lastname: Min
authors.affiliation: 1 Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA 55905, USA 4 Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, 55905, USA lee.kendall@mayo.edu.
authors.forename: Kendall H
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000368:Aged; D001921:Brain / Q000503:physiopathology*; D046690:Deep Brain Stimulation / Q000009:adverse effects / Q000379:methods*; D020329:Essential Tremor / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D059907:Functional Neuroimaging / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016343:Monitoring, Intraoperative; D017063:Outcome Assessment, Health Care; D010292:Paresthesia / Q000209:etiology*; D020651:Ventral Thalamic Nuclei
keywords: deep brain stimulation; essential tremor; functional MRI; thalamus; ventralis intermedius nucleus