Poster No:
1342
Submission Type:
Abstract Submission
Authors:
Vi Nguyen1, Ashley Meyer2, Jessica Hudson3, Scott Norris3, Evan Gordon4
Institutions:
1Washington University in St Louis, St Louis, MO, 2Washington University in St. Louis, St. Louis, MO, 3Washington University in St Louis School of Medicine, St Louis, MO, 4Washington University, St. Louis, MO
First Author:
Vi Nguyen
Washington University in St Louis
St Louis, MO
Co-Author(s):
Ashley Meyer
Washington University in St. Louis
St. Louis, MO
Jessica Hudson
Washington University in St Louis School of Medicine
St Louis, MO
Introduction:
Adductor laryngeal dystonia (ADLD) is a task-specific focal dystonia that involves excessive laryngeal muscle contraction during speech. Focal dystonia like ADLD is associated with dysfunction of the basal ganglia, primary motor cortex (M1), thalamus, and cerebellum1,4,6 . ADLD-related vocal disability improves with recurring, invasive application of botox into laryngeal muscles. A deeper understanding of central neural mechanisms related to this transient therapeutic response may improve understanding of pathophysiological mechanisms and therapeutic potential (i.e. advance engagement targets for central acting neuromodulation approaches). Prior work suggested alterations in resting-state functional magnetic resonance imaging (rs-fMRI) functional connectivity (FC) in dystonia patients after successful botox therapy5. However, this work collected low amounts of per-patient data, and thus could not detect individual-specific therapeutic alterations. Here, we employed precision functional mapping (PFM), which collects large quantities of per-patient data to precisely characterize individual-specific brain networks without averaging across patients2,3. We aimed to determine the vocalization-related functional motor network in ADLD subjects and assess how this vocalization network FC was altered in each individual patient by applying therapeutic botox injections.
Methods:
We conducted a treatment response of PFM in 4 ADLD patients. In each patient, both before and after successful injections, we collected up to 5 scanning sessions totaling 125 minutes of rs-fMRI and 40 minutes of task fMRI collected while performing vocalization impairment-specific motor task.
FMRI images were corrected for motion, slice-time, distortion, and registered to an MNI template. We applied nuisance regression, band-pass filtering, and motion censoring7 to rs-MRI data. All fMRI data were sampled to the cortical surface and subcortical structures and smoothed at 4mm FWHM.
To identify individual-specific vocalization-related brain regions, we fit each patient's task fMRI data to a general linear model and entered vocalization beta weights into a one-sample t-test across sessions. To determine whether vocalization-related fMRI activity differed after injection in each patient, a paired t-test compared vocalization-related beta weights between pre and post-injection timepoints. Finally, in each subject, vocalization-related regions of interest were delineated within M1 as cortical seeds for FC. FC was calculated as correlations between the ROI signal time course and every time course in the brain. A paired t-test between the pre- and post-injection timepoints determined whether FC differed after injection in each patient.
Results:
Vocalization-related brain regions were identified in every subject and consisted of a dual representation in M1. Within each subject, vocalization-related activation within subcortical structures was reduced post- compared to pre-injection, most consistently in the posterior putamen and motor cerebellum, and less in the thalamus. Similarly, resting-state FC seeded from vocalization-related M1 regions was consistently reduced in motor cerebellum and posterior putamen and less in thalamus in post- compared to pre-injection.
Conclusions:
Application of PFM in task-specific dystonia pinpoints a more precise patient-specific cortical and subcortical mapping of the functional motor. Further, it identifies patient-specific alterations in this network's function and connectivity resulting from therapeutic botulinum toxin injection. The identified locations of these alterations suggest potential target engagement sites for future therapeutic trials. These alterations were partially consistent across subjects, but also exhibited some degree of individual specificity, highlighting the potential for patient-specific PFM when considering pathophysiological mechanisms and advancing therapeutic potential in dystonia.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s)
Modeling and Analysis Methods:
Activation (eg. BOLD task-fMRI) 1
fMRI Connectivity and Network Modeling 2
Motor Behavior:
Motor Behavior Other
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Cortical Anatomy and Brain Mapping
Keywords:
Degenerative Disease
FUNCTIONAL MRI
Other - focal dystonia; precision imaging; vocalization network, patienti-specific, functional connectivity
1|2Indicates the priority used for review
Provide references using author date format
1. Battistella, Giovanni, Pichet Termsarasab, Ritesh A. Ramdhani, Stefan Fuertinger, and Kristina Simonyan. 2017. “Isolated Focal Dystonia as a Disorder of Large-Scale Functional Networks.” Cerebral Cortex (New York, N.Y.: 1991) 27 (2): 1203–15. https://doi.org/10.1093/cercor/bhv313.
2. Gordon, Evan M., Timothy O. Laumann, Adrian W. Gilmore, Dillan J. Newbold, Deanna J. Greene, Jeffrey J. Berg, Mario Ortega, et al. 2017. “Precision Functional Mapping of Individual Human Brains.” Neuron 95 (4): 791-807.e7. https://doi.org/10.1016/j.neuron.2017.07.011.
3. Gordon, Evan M., Timothy O. Laumann, Scott Marek, Dillan J. Newbold, Jacqueline M. Hampton, Nicole A. Seider, David F. Montez, et al. 2021. “Human Fronto-Striatal Connectivity Is Organized into Discrete Functional Subnetworks.” bioRxiv. https://doi.org/10.1101/2021.04.12.439415.
4. Hanekamp, Sandra, and Kristina Simonyan. 2020. “The Large‐scale Structural Connectome of Task‐specific Focal Dystonia.” Human Brain Mapping 41 (12): 3253–65. https://doi.org/10.1002/hbm.25012.
5. Nevrlý, Martin, Petr Hluštík, Pavel Hok, Pavel Otruba, Zbyněk Tüdös, and Petr Kaňovský. n.d. “Changes in Sensorimotor Network Activation after Botulinum Toxin Type A Injections in Patients with Cervical Dystonia: A Functional MRI Study | Experimental Brain Research.” Accessed November 9, 2023. https://link.springer.com/article/10.1007/s00221-018-5322-3.
6. Norris, Scott A., Aimee E. Morris, Meghan C. Campbell, Morvarid Karimi, Babatunde Adeyemo, Randal C. Paniello, Abraham Z. Snyder, Steven E. Petersen, Jonathan W. Mink, and Joel S. Perlmutter. 2020. “Regional, Not Global, Functional Connectivity Contributes to Isolated Focal Dystonia.” Neurology 95 (16): e2246–58. https://doi.org/10.1212/WNL.0000000000010791.
7. Power, Jonathan D., Anish Mitra, Timothy O. Laumann, Abraham Z. Snyder, Bradley L. Schlaggar, and Steven E. Petersen. 2014. “Methods to Detect, Characterize, and Remove Motion Artifact in Resting State fMRI.” NeuroImage 84 (January): 320–41. https://doi.org/10.1016/j.neuroimage.2013.08.048.