Dataset Information

White Matter Integrity Predicts Electrical Stimulation (tDCS) and Language Therapy Effects in Primary Progressive Aphasia.

ABSTRACT:

Background

Transcranial direct current stimulation (tDCS), in conjunction with language therapy, improves language therapy outcomes in primary progressive aphasia (PPA). However, no studies show whether white matter integrity predicts language therapy or tDCS effects in PPA.

Objective

We aimed to determine whether white matter integrity, measured by diffusion tensor imaging (DTI), predicts written naming/spelling language therapy effects (letter accuracy on trained and untrained words) with and without tDCS over the left inferior frontal gyrus (IFG) in PPA.

Methods

Thirty-nine participants with PPA were randomly assigned to tDCS or sham condition, coupled with language therapy for 15 daily sessions. White matter integrity was measured by mean diffusivity (MD) and fractional anisotropy (FA) in DTI scans before therapy. Written naming outcomes were evaluated before, immediately after, 2 weeks, and 2 months posttherapy. To assess tDCS treatment effect, we used a mixed-effects model with treatment evaluation and time interaction. We considered a forward model selection approach to identify brain regions/fasciculi of which white matter integrity can predict improvement in performance of word naming.

Results

Both sham and tDCS groups significantly improved in trained items immediately after and at 2 months posttherapy. Improvement in the tDCS group was greater and generalized to untrained words. White matter integrity of ventral language pathways predicted tDCS effects in trained items whereas white matter integrity of dorsal language pathways predicted tDCS effects in untrained items.

Conclusions

White matter integrity influences both language therapy and tDCS effects. Thus, it holds promise as a biomarker for deciding which patients will benefit from language therapy and tDCS.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC7748290 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

White Matter Integrity Predicts Electrical Stimulation (tDCS) and Language Therapy Effects in Primary Progressive Aphasia.

Zhao Yi Y Ficek Bronte B Webster Kimberly K Frangakis Constantine C Caffo Brian B Hillis Argye E AE Faria Andreia A Tsapkini Kyrana K

Neurorehabilitation and neural repair 20210101 1

<h4>Background</h4>Transcranial direct current stimulation (tDCS), in conjunction with language therapy, improves language therapy outcomes in primary progressive aphasia (PPA). However, no studies show whether white matter integrity predicts language therapy or tDCS effects in PPA.<h4>Objective</h4>We aimed to determine whether white matter integrity, measured by diffusion tensor imaging (DTI), predicts written naming/spelling language therapy effects (letter accuracy on trained and untrained w ...[more]

PMID: 33317422

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Project description:Predictors of treatment effects allow individual tailoring of treatment characteristics, thereby saving resources and optimizing outcomes. Electrical stimulation coupled with language intervention has shown promising results in improving language performance in individuals with Primary Progressive Aphasia (PPA). The current study aimed to identify language and cognitive variables associated with response to therapy consisting of language intervention combined with transcranial direct current stimulation (tDCS). Forty individuals with PPA received written naming/spelling intervention combined with anodal tDCS or Sham, using a between-subjects, randomized design, with intervention delivered over a period of 3 weeks. Participants were assessed using a battery of neuropsychological tests before and after each phase. We measured letter accuracy during spelling of trained and untrained words, before, immediately after, 2 weeks, and 2 months after therapy. We used step-wise regression methods to identify variables amongst the neuropsychological measures and experimental factors that were significantly associated with therapy outcomes at each time-point. For trained words, improvement was related to pre-therapy scores, in RAVLT (5 trials sum), pseudoword spelling, object naming, digit span backward, spatial span backward and years post symptom onset. Regarding generalization to untrained words, improvement in spelling was associated with pseudoword spelling, RAVLT proactive interference, RAVLT immediate recall. Generalization effects were larger under tDCS compared to Sham at the 2-month post training measurement. We conclude that, for trained words, patients who improve the most are those who retain for longer language skills such as sublexical spelling processes (phoneme-to-grapheme correspondences) and word retrieval, and other cognitive functions such as executive functions and working memory, and those who have a better learning capacity. Generalization to untrained words occurs through improvement in knowledge of phoneme-to-grapheme correspondences. Furthermore, tDCS enhances the generalizability and duration of therapy effects.

Project description:ObjectiveTranscranial direct current stimulation (tDCS) has shown promising results when used as an adjunct to behavioral training in neurodegenerative diseases. However, the underlying neural mechanisms are not understood and neuroimaging evidence from pre/post treatment has been sparse. In this study, we examined tDCS-induced neural changes in a language intervention study for primary progressive aphasia (PPA), a neurodegenerative syndrome with language impairment as the primary clinical presentation. Anodal tDCS was applied to the left inferior frontal gyrus (LIFG). To evaluate the hypothesis that tDCS promotes system segregation, analysis focused on understanding tDCS-induced changes in the brain-wide functional network connectivity of the targeted LIFG.MethodsResting-state fMRI data were obtained from 32 participants with PPA before and after receiving a written naming therapy, accompanied either by tDCS or sham stimulation. We focused on evaluating changes in the global connectivity of the stimulated LIFG-triangularis (LIFG-tri) region given its important role in lexical processing. Global connectivity was indexed by the graph-theoretic measure participation coefficient (PC) which quantifies a region's level of system segregation. The values before and after treatment were compared for each condition (tDCS or Sham) as well as with age-matched healthy controls (n = 19).ResultsHigher global connectivity of the LIFG-tri before treatment was associated with greater dementia severity. After treatment, the tDCS group showed a significant decrease in global connectivity whereas the Sham group's did not change, suggesting specific neural effects induced by tDCS. Further examination revealed that the decrease was driven by reduced connectivity between the LIFG-tri and regions outside the perisylvian language area, consistent with the hypothesis that tDCS enhances the segregation of the language system and improves processing efficiency. Additionally, we found that these effects were specific to the LIFG-tri and not observed in other control regions.ConclusionTDCS-augmented language therapy in PPA increased the functional segregation of the language system, a normalization of the hyper-connectivity observed before treatment. These findings add to our understanding of the nature of tDCS-induced neural changes in disease treatment and have applications for validating treatment efficacy and designing future tDCS and other non-invasive brain stimulation (NIBS) treatments.

Project description:Frontoparietal white matter supports information transfer between brain areas involved in complex haptic tasks such as somatosensory discrimination. The purpose of this study was to gain an understanding of the relationship between microstructural integrity of frontoparietal network white matter and haptic performance in persons with chronic stroke and to compare frontoparietal network integrity in participants with stroke and age matched control participants. Nineteen individuals with stroke and 16 controls participated. Haptic performance was quantified using the Hand Active Sensation Test (HASTe), an 18-item match-to-sample test of weight and texture discrimination. Three tesla MRI was used to obtain diffusion-weighted and high-resolution anatomical images of the whole brain. Probabilistic tractography was used to define 10 frontoparietal tracts total; Four intrahemispheric tracts measured bilaterally 1) thalamus to primary somatosensory cortex (T-S1), 2) thalamus to primary motor cortex (T-M1), 3) primary to secondary somatosensory cortex (S1 to SII) and 4) primary somatosensory cortex to middle frontal gyrus (S1 to MFG) and, 2 interhemispheric tracts; S1-S1 and precuneus interhemispheric. A control tract outside the network, the cuneus interhemispheric tract, was also examined. The diffusion metrics fractional anisotropy (FA), mean diffusivity (MD), axial (AD) and radial diffusivity (RD) were quantified for each tract. Diminished FA and elevated MD values are associated with poorer white matter integrity in chronic stroke. Nine of 10 tracts quantified in the frontoparietal network had diminished structural integrity poststroke compared to the controls. The precuneus interhemispheric tract was not significantly different between groups. Principle component analysis across all frontoparietal white matter tract MD values indicated a single factor explained 47% and 57% of the variance in tract mean diffusivity in stroke and control groups respectively. Age strongly correlated with the shared variance across tracts in the control, but not in the poststroke participants. A moderate to good relationship was found between ipsilesional T-M1 MD and affected hand HASTe score (r = - 0.62, p = 0.006) and less affected hand HASTe score (r = - 0.53, p = 0.022). Regression analysis revealed approximately 90% of the variance in affected hand HASTe score was predicted by the white matter integrity in the frontoparietal network (as indexed by MD) in poststroke participants while 87% of the variance in HASTe score was predicted in control participants. This study demonstrates the importance of frontoparietal white matter in mediating haptic performance and specifically identifies that T-M1 and precuneus interhemispheric tracts may be appropriate targets for piloting rehabilitation interventions, such as noninvasive brain stimulation, when the goal is to improve poststroke haptic performance.

Dataset Information

White Matter Integrity Predicts Electrical Stimulation (tDCS) and Language Therapy Effects in Primary Progressive Aphasia.

Background

Objective

Methods

Results

Conclusions

Publications

White Matter Integrity Predicts Electrical Stimulation (tDCS) and Language Therapy Effects in Primary Progressive Aphasia.

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