Therapeutic DBS for OCD Suppresses Default Mode Network and Associated Subcortical Circuits
Poster No:
26
Submission Type:
Abstract Submission
Authors:
Natalya Slepneva1, Genevieve Basich-Pease1, Adam Frank2, Tenzin Norbu1, Leo Sugrue3,1, Paul Larson4, Philip Starr5,6, Melanie Morrison3, A Moses Lee1,6
Institutions:
1Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA, 2Keck School of Medicine of USC, Los Angeles, CA, 3Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, 4Department of Neurological Surgery, University of Arizona, Tuscon, AZ, 5Neurological Surgery, University of California San Francisco, San Francisco, CA, 6Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA
First Author:
Natalya Slepneva
Department of Psychiatry and Behavioral Sciences, University of California San Francisco
San Francisco, CA
Department of Psychiatry and Behavioral Sciences, University of California San Francisco
San Francisco, CA
Co-Author(s):
Genevieve Basich-Pease
Department of Psychiatry and Behavioral Sciences, University of California San Francisco
San Francisco, CA
Department of Psychiatry and Behavioral Sciences, University of California San Francisco
San Francisco, CA
Tenzin Norbu
Department of Psychiatry and Behavioral Sciences, University of California San Francisco
San Francisco, CA
Department of Psychiatry and Behavioral Sciences, University of California San Francisco
San Francisco, CA
Leo Sugrue
Department of Radiology and Biomedical Imaging, University of California San Francisco|Department of Psychiatry and Behavioral Sciences, University of California San Francisco
San Francisco, CA|San Francisco, CA
Department of Radiology and Biomedical Imaging, University of California San Francisco|Department of Psychiatry and Behavioral Sciences, University of California San Francisco
San Francisco, CA|San Francisco, CA
Philip Starr
Neurological Surgery, University of California San Francisco|Weill Institute for Neurosciences, University of California San Francisco
San Francisco, CA|San Francisco, CA
Neurological Surgery, University of California San Francisco|Weill Institute for Neurosciences, University of California San Francisco
San Francisco, CA|San Francisco, CA
Melanie Morrison
Department of Radiology and Biomedical Imaging, University of California San Francisco
San Francisco, CA
Department of Radiology and Biomedical Imaging, University of California San Francisco
San Francisco, CA
A Moses Lee
Department of Psychiatry and Behavioral Sciences, University of California San Francisco|Weill Institute for Neurosciences, University of California San Francisco
San Francisco, CA|San Francisco, CA
Department of Psychiatry and Behavioral Sciences, University of California San Francisco|Weill Institute for Neurosciences, University of California San Francisco
San Francisco, CA|San Francisco, CA
Introduction:
Deep brain stimulation (DBS) is a treatment for severe, refractory obsessive-compulsive disorder (OCD) that applies direct electrical stimulation to the anterior limb of the internal capsule (ALIC). To examine the difference between therapeutic and nontherapeutic DBS, we compared BOLD response when DBS was cycled ON and off in different DBS electrode contact configurations.
Methods:
Subjects: 5 subjects with severe, refractory OCD were implanted with an MR-compatible Medtronic Percept DBS stimulator as part of clinical care. Quadripolar leads were implanted bilaterally within the ALIC region. Three subjects were classified as treatment responders based on clinical response to DBS. Among responders, contact configurations were classified as therapeutic and nontherapeutic based on long-term clinical response.
MRI: MR scans were acquired on a GE Discovery MR750 3T scanner. We collected T1-weighted structural scans and DWI pre- and post-implantation (55 direction HARDI, b=2000). Gradient-echo fMRI was acquired in low-SAR mode with a 32-channel head coil. For each 6-minute fMRI scan, we selected one of 12 bipolar contact configurations to deliver stimulation that was cycled ON/OFF for 1-minute blocks.
fMRI Processing: T1 and fMRI were preprocessed with fMRIprep, a standardized pipeline that combines tools from AFNI, ANTs, FreeSurfer, FSL, and Nipype. BOLD runs were corrected for slice-timing and head motion, and resampled to an MNI space template. ICA-AROMA was performed after removal of non-steady state volumes and spatial smoothing with an isotropric, Gaussian kernel of 6mm FWHM. Components were manually reviewed by two expert raters, and those classified as noise by both raters were removed. Using AFNI, motion outliers (FD>0.2) and additional polynomial drift terms were removed and ON-off contrasts and group comparisons were generated.
Electrode reconstruction and DWI processing: DWI scans were preprocessed using QSIprep and MRtrix3. MP-PCA denoising and Gibb unringing was performed, and FSL's eddy was used for head motion and Eddy current correction. The DWI images were resampled to ACPC. Using Lead-DBS, a MATLAB toolbox for DBS electrode reconstruction and simulation of DBS stimulation, CT, T1 and DWI scans were co-registered and normalized using ANTs and SPM, after which DBS electrodes were reconstructed and manually localized. White matter tracts were reconstructed from diffusion imaging data using generalized q-sampling. The volume of activated tissue (VAT) was modeled for bipolar contact pairs, and the VATs were used as seeds to generate connectivity to parcels from Schaefer cortical atlas.
MRI: MR scans were acquired on a GE Discovery MR750 3T scanner. We collected T1-weighted structural scans and DWI pre- and post-implantation (55 direction HARDI, b=2000). Gradient-echo fMRI was acquired in low-SAR mode with a 32-channel head coil. For each 6-minute fMRI scan, we selected one of 12 bipolar contact configurations to deliver stimulation that was cycled ON/OFF for 1-minute blocks.
fMRI Processing: T1 and fMRI were preprocessed with fMRIprep, a standardized pipeline that combines tools from AFNI, ANTs, FreeSurfer, FSL, and Nipype. BOLD runs were corrected for slice-timing and head motion, and resampled to an MNI space template. ICA-AROMA was performed after removal of non-steady state volumes and spatial smoothing with an isotropric, Gaussian kernel of 6mm FWHM. Components were manually reviewed by two expert raters, and those classified as noise by both raters were removed. Using AFNI, motion outliers (FD>0.2) and additional polynomial drift terms were removed and ON-off contrasts and group comparisons were generated.
Electrode reconstruction and DWI processing: DWI scans were preprocessed using QSIprep and MRtrix3. MP-PCA denoising and Gibb unringing was performed, and FSL's eddy was used for head motion and Eddy current correction. The DWI images were resampled to ACPC. Using Lead-DBS, a MATLAB toolbox for DBS electrode reconstruction and simulation of DBS stimulation, CT, T1 and DWI scans were co-registered and normalized using ANTs and SPM, after which DBS electrodes were reconstructed and manually localized. White matter tracts were reconstructed from diffusion imaging data using generalized q-sampling. The volume of activated tissue (VAT) was modeled for bipolar contact pairs, and the VATs were used as seeds to generate connectivity to parcels from Schaefer cortical atlas.
Results:
We compared stimulation ON and off across subjects for contact pairs that had therapeutic (n=6 runs, 3 subjects) vs nontherapeutic (n=11 runs, 3 subjects) stimulation. In therapeutic compared to nontherapeutic configurations, stimulation correlated with significant BOLD suppression (p<0.05) in areas related to OCD, including the right orbitofrontal cortex, bilateral dorsomedial prefrontal cortex, and right thalamus, distant from the sites of the active electrode contacts.
We also examined the relationship between DBS and canonical resting-state fMRI networks. Comparing stimulation ON vs off, we found a significant (p<0.05) difference in BOLD signal change between therapeutic and nontherapeutic contacts bilaterally in the default mode network. In the diffusion data, a significant percentage of streamlines seeded from therapeutic electrode VAT ROIs connected to areas of the default mode and limbic networks.
We also examined the relationship between DBS and canonical resting-state fMRI networks. Comparing stimulation ON vs off, we found a significant (p<0.05) difference in BOLD signal change between therapeutic and nontherapeutic contacts bilaterally in the default mode network. In the diffusion data, a significant percentage of streamlines seeded from therapeutic electrode VAT ROIs connected to areas of the default mode and limbic networks.
·Fig 1 A. Lead-DBS reconstruction of DBS leads. B. BOLD response difference between therapeutic and nontherapeutic stimulation. C. BOLD suppression of default mode network in therapeutic stimulation.
·Fig 2 A. Tracts seeded from therapeutic bipolar configuration. B. Mean streamline counts for therapeutic DBS electrodes, highest counts in yellow. C. Streamline counts to resting state network areas.
Conclusions:
Our findings suggest that relief of OCD symptoms by DBS may be mediated by suppression within the OCD network, as well as in the default mode network via structural connections to the network. This combination of stimulation-based fMRI and diffusion imaging approach to characterizing the impact of DBS on networks may provide a novel method for optimizing contact locations and parameters to treat severe OCD.
Brain Stimulation:
Deep Brain Stimulation 1
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 2
Modeling and Analysis Methods:
Activation (eg. BOLD task-fMRI)
Connectivity (eg. functional, effective, structural)
Diffusion MRI Modeling and Analysis
Keywords:
ADULTS
Cortex
FUNCTIONAL MRI
MRI
Obessive Compulsive Disorder
Psychiatric
Psychiatric Disorders
Sub-Cortical
Tractography
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
Provide references using author date format
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