A feasibility study of combined intermittent theta burst stimulation and modified constraint-induced aphasia therapy in chronic post-stroke aphasia

Article type: Research Article

Authors: Szaflarski, Jerzy P.^{a; b; *} | Griffis, Joseph^{a; d; 1} | Vannest, Jennifer^g | Allendorfer, Jane B.^a | Nenert, Rodolphe^a | Amara, Amy W.^{a; f} | Sung, Victor^a | Walker, Harrison C.^{a; e} | Martin, Amber N.^a | Mark, Victor W.^{a; c; d} | Zhou, Xiaohua^c

Affiliations: [a] Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA | [b] Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA | [c] Department of Physical Medicine and Rehabilitation, University of Alabama at Birmingham, Birmingham, AL, USA | [d] Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA | [e] Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA | [f] UAB Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, AL, USA | [g] Cincinnati Children’s Hospital Medical Center, Division of Neurology and Pediatric Neuroimaging Research Consortium, Cincinnati, OH, USA | [1] Currently at Washington University in St. Louis, St. Louis, MO, USA

Correspondence: [*] Corresponding author: Jerzy P. Szaflarski, MD, PhD, Department of Neurology, University of Alabama at Birmingham, 312 Civitan International Research Center, 1719 6th Avenue South, Birmingham, AL, USA. Tel.: +1 205 934 3866; Fax: +1 2015 975 6255; E-mail: jszaflarski@uabmc.edu.

Abstract: Purpose:The purpose of this feasibility study was to assess whether combined intermittent theta burst suppression (iTBS) applied to the ipsilesional hemisphere and modified constraint-induced aphasia therapy (mCIAT) are safe and logistically feasible within the time interval associated with iTBS induced long-term potentiation in patients with post-stroke aphasia. We also wanted to determine whether combining priming with iTBS and CIAT improves language functions after treatment. Methods:Twelve participants received fMRI (semantic decision/tone decision task) and neuropsychological testing of language skills at three time points – before starting the iTBS/mCIAT intervention (T1), immediately after completing 2-week long course of intervention (T2), and at 3-months follow-up (T3). ITBS was applied to the individually determined fMRI language “hot spot” located in the left fronto-temporal regions. Results:There were no serious adverse events, and all mCIAT group therapy sessions (3–4 subjects each) were initiated within 30 minutes of the first group subject receiving iTBS. Neuropsychological assessments of language showed a significant effect of session on Western Aphasia Battery aphasia quotient (WAB-AQ; p = 0.04) and spontaneously correct responses on Boston Naming Test (BNT; p = 0.002), with improvement noted at T2 (p = 0.002) and T3 (p = 0.05) versus T1. FMRI showed significant changes between all timepoints. Post-hoc correlations showed associations between improvements in WAB-AQ from T2 to T3 and decreased BOLD signal in left inferior parietal lobe, and improvements in BNT from T1 to T3 with decreased signal in right inferior frontal gyrus. Conclusion:This study shows feasibility and safety for combining behavioral and neurostimulation interventions for chronic post-stroke aphasia. Observed changes in linguistic measures were relatively small. However, they were statistically significant and associated with parallel changes observed in the neuroimaging. Our findings support further development and testing of the combined mCIAT and iTBS protocol and comparisons to either CIAT/mCIAT or iTBS applied alone for the treatment of post-stroke aphasia.

Keywords: Aphasia, fMRI, iTBS, rTMS, rehabilitation, CIAT, WAB-AQ

DOI: 10.3233/RNN-180812

Journal: Restorative Neurology and Neuroscience, vol. 36, no. 4, pp. 503-518, 2018