TMS, fMRI and EEG Correlates of Recovery in Motor and Cognitive Function: A Case Study in Stroke

Poster No:

1195 

Submission Type:

Abstract Submission 

Authors:

Nicodemus Oey1, Effie Chew1, Thomas Yeo2, Shuailei Zhang3, Cuntai Guan3, Fang Ji4, Siwei Liu4, Juan Helen Zhou4

Institutions:

1National University Health System, Singapore, 2Centre for Sleep and Cognition, National University of Singapore, Singapore, 3Nanyang Technological University, Singapore, 4National University of Singapore, Singapore, Singapore

First Author:

Nicodemus Oey, MD., PhD.  
National University Health System
Singapore

Co-Author(s):

Effie Chew, MBBS, MRCP, FAMS  
National University Health System
Singapore
Thomas Yeo  
Centre for Sleep and Cognition, National University of Singapore
Singapore
Shuailei Zhang, PhD.  
Nanyang Technological University
Singapore
Cuntai Guan, PhD  
Nanyang Technological University
Singapore
Fang Ji  
National University of Singapore
Singapore, Singapore
Siwei Liu, PhD.  
National University of Singapore
Singapore, Singapore
Juan Helen Zhou, Ph.D.  
National University of Singapore
Singapore, Singapore

Introduction:

Stroke is the leading cause of dementia and a major cause of disability globally. Patients who survive acute stroke often contend with both motor and cognitive deficits, which last for years after the initial injury. Changes in neural network reorganization correlate with recovery, but the clinical use of neuroimaging and neurophysiological tools to guide stroke rehabilitation is still elusive. In this case study, a multimodal approach employing individualized functional and structural connectivity obtained through resting state and diffusion MRI, whole-brain connectivity derived from EEG, and Transcranial Magnetic Stimulation (TMS) was conducted to prognosticate the motor and cognitive recovery of a patient with a subcortical left hemispheric infarct longitudinally through the course of 2 years.
TMS revealed that recovery of upper limb function correlated with an increase in corticomotor excitability of the affected Motor Cortex, which was inversely correlated with ipsilateral Silent Period, a measure of Interhemispheric Inhibition.
EEG revealed a transient increase in frontotemporal connectivity at 6 months which was corroborated by resting state Functional Connectivity. Mean Fractional Anisotropy of the Right Ventral Cingulum Bundle increased at the 1 year timepoint, which correlated with a clinically meaningful increase in Verbal Memory as measured by the Rey's Auditory Verbal Learning Test, without any significant change in global cognition.
The use of a multimodal approach may have merits at the individual level to prognosticate functional improvements in recovery from stroke.

Methods:

Clinical and Neurophysiological Data Collection
A 53-year old man with left hemispheric subcortical stroke leading to right hemiplegic was longitudinally examined for upper limb motor performance at the 1-, 3-, 6-, 12-, and 24-month intervals post-stroke. Neurophysiological data was obtained by TMS using the Deymed DuoMag-XT system.

Resting state, task-based, and diffusion-weighted MRI
MRI scans were conducted using a 3T Siemens Magnetom Trim Trio scanner with a 32-channel head array coil. DWI processing pipeline was implemented using the MRTrix3 (Tournier et al., 2019) software package. Probabilistic tractography analysis was performed using TRActs Constrained by UnderLying Anatomy (TRACULA).

Electroencephalography
EEG data from 64 channels were collected using the ActiChamp EEG amplifier with unipolar Ag/AgCl electrodes digitally sampled at 250Hz and bandpass filtered from .05 to 40Hz. FC matrices are calculated in MATLAB using the FieldTrip Toolbox.

Results:

Upper limb motor functional recovery longitudinally correlated with TMS, fMRI, and EEG
Corticomotor excitability obtained by TMS stimulation of the lesioned motor cortex followed a u-shape pattern of recovery, which was mirrored by task-based fMRI showing a marked reduction in BOLD signal of the left hemisphere at 1-month, which increased at 3-months but reduced again at 6 months resulting in an "inverted u-shape pattern". This pattern was corroborated by functional connectivity data derived from both EEG and resting state fMRI.

Cognitive function as measured by verbal memory correlated with specific FA increase in the Cingulum but not the Arcuate Fasciculus or the Corticospinal Tract
The patient's verbal memory performance also showed an inverted u-shape pattern of recovery going from 13 --> 27 --> 21 --> 35 at 1-, 3-, 6-, and 12-months post-stroke respectively which seems to concur with motor findings. However, when we analyzed the white matter tracts, only the Ventral Cingulum Bundle showed an increase in FA at 12-months, which corresponded specifically with the increase in RAVLT total scores.
Supporting Image: Figure1-HBM2025.jpg
   ·Figure 1. Multimodal characterization of a patient’s recovery from stroke using A) diffusion-weighted MRI, B) rs-fMRI, C) Tractography, D) EEG, and E) Task-based fMRI
 

Conclusions:

The use of a multimodal approach combining neuroimaging and neurophysiological metrics may aid in increasing our understanding of how motor and cognitive performance recovers in patients with post-stroke disability.

Brain Stimulation:

Non-invasive Magnetic/TMS

Learning and Memory:

Learning and Memory Other

Modeling and Analysis Methods:

Connectivity (eg. functional, effective, structural) 1
EEG/MEG Modeling and Analysis

Novel Imaging Acquisition Methods:

Multi-Modal Imaging 2

Keywords:

Electroencephaolography (EEG)
FUNCTIONAL MRI
Memory
Neurological
Tractography
Transcranial Magnetic Stimulation (TMS)
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
Other - STROKE

1|2Indicates the priority used for review

Abstract Information

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Please indicate below if your study was a "resting state" or "task-activation” study.

Resting state
Task-activation

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Patients

Was this research conducted in the United States?

No

Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

Yes

Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

Not applicable

Please indicate which methods were used in your research:

Functional MRI
EEG/ERP
Neurophysiology
Structural MRI
Diffusion MRI
TMS
Behavior
Neuropsychological testing

For human MRI, what field strength scanner do you use?

3.0T

Which processing packages did you use for your study?

AFNI
SPM
FSL
Free Surfer

Provide references using APA citation style.

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Alexander Schaefer, Ru Kong, Evan M Gordon, Timothy O Laumann, Xi-Nian Zuo, Avram J Holmes, Simon B Eickhoff, B T Thomas Yeo, Local-Global Parcellation of the Human Cerebral Cortex from Intrinsic Functional Connectivity MRI, Cerebral Cortex, Volume 28, Issue 9, September 2018, Pages 3095–3114, https://doi.org/10.1093/cercor/bhx179

Maffei C, Lee C, Planich M, Ramprasad M, Ravi N, Trainor D, Urban Z, Kim M, Jones RJ, Henin A, Hofmann SG, Pizzagalli DA, Auerbach RP, Gabrieli JDE, Whitfield-Gabrieli S, Greve DN, Haber SN, Yendiki A. Using diffusion MRI data acquired with ultra-high gradient strength to improve tractography in routine-quality data. Neuroimage. 2021 Dec 15;245:118706. doi: 10.1016/j.neuroimage.2021.118706. Epub 2021 Nov 12. PMID: 34780916; PMCID: PMC8835483.

Liu, S., Luo, X., Chong, J. S. X., Jiaerken, Y., Youn, S. H., Zhang, M., Zhou, J. H., & Alzheimer's Disease Neuroimaging Initiative (2024). Brain structure, amyloid, and behavioral features for predicting clinical progression in subjective cognitive decline. Human Brain Mapping, 45(10), e26765. https://doi-org.libproxy1.nus.edu.sg/10.1002/hbm.26765

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