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Sex differences in effects of tDCS and language treatments on brain functional connectivity in primary progressive aphasia.

ABSTRACT: Primary Progressive Aphasia (PPA) is a neurodegenerative disorder primarily affecting language functions. Neuromodulatory techniques (e.g., transcranial direct current stimulation, active-tDCS) and behavioral (speech-language) therapy have shown promising results in treating speech and language deficits in PPA patients. One mechanism of active-tDCS efficacy is through modulation of network functional connectivity (FC). It remains unknown how biological sex influences FC and active-tDCS or language treatment(s). In the current study, we compared sex differences, induced by active-tDCS and language therapy alone, in the default mode and language networks, acquired during resting-state fMRI in 36 PPA patients. Using a novel statistical method, the covariate-assisted-principal-regression (CAPs) technique, we found sex and age differences in FC changes following active-tDCS. In the default mode network (DMN): (1) men (in both conditions) showed greater FC in DMN than women. (2) men who received active-tDCS showed greater FC in the DMN than men who received language-treatment only. In the language network: (1) women who received active-tDCS showed significantly greater FC across the language network than women who received sham-tDCS. As age increases, regardless of sex and treatment condition, FC in language regions decreases. The current findings suggest active-tDCS treatment in PPA alters network-specific FC in a sex-dependent manner.

SUBMITTER: Licata AE

PROVIDER: S-EPMC9883295 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Sex differences in effects of tDCS and language treatments on brain functional connectivity in primary progressive aphasia.

Licata Abigail E AE Zhao Yi Y Herrmann Olivia O Hillis Argye E AE Desmond John J Onyike Chiadi C Tsapkini Kyrana K

NeuroImage. Clinical 20230120

Primary Progressive Aphasia (PPA) is a neurodegenerative disorder primarily affecting language functions. Neuromodulatory techniques (e.g., transcranial direct current stimulation, active-tDCS) and behavioral (speech-language) therapy have shown promising results in treating speech and language deficits in PPA patients. One mechanism of active-tDCS efficacy is through modulation of network functional connectivity (FC). It remains unknown how biological sex influences FC and active-tDCS or langua ...[more]

PMID: 36701874

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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: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:Understanding the relationships between brain structure and language behaviour in primary progressive aphasia provides crucial information about these diseases' pathomechanisms. However, previous investigations have been limited from providing a statistically reliable view of broad language abilities by sample size, variant focus and task focus. In this study, the authors aimed to determine the relationship between brain structure and language behaviour in primary progressive aphasia, to determine the degree to which task-associated regions were atrophied across disease variants and to determine the degree to which task-related atrophy overlaps across disease variants. Participants were 118 primary progressive aphasia patients and 61 healthy, age-matched controls tested from 2011 to 2018 in the German Consortium for Frontotemporal Lobar Degeneration cohort. Diagnosis of primary progressive aphasia required progressive deterioration of mainly speech and language for ≥ 2 years, and variant was diagnosed by the criteria of Gorno-Tempini et al. (Classification of primary progressive aphasia and its variants. Neurology. 2011;76(11):1006-1014). Twenty-one participants not fulfilling a specific subtype were classified as mixed-variant and excluded. Language tasks of interest included the Boston naming test, a German adaptation of the Repeat and Point task, phonemic and category fluency tasks and the reading/writing subtest of the Aachen Aphasia Test. Brain structure was measured by cortical thickness. We observed networks of language task-associated temporal, frontal and parietal cortex. Overlapping task-associated atrophy was observed in the left lateral, ventral and medial temporal lobes, middle and superior frontal gyri, supramarginal gyrus and insula. Some regions, primarily in the perisylvian region, were associated with language behaviour despite showing no significant atrophy. The results crucially extend less powerful studies associating brain and language measures in primary progressive aphasia. Cross-variant atrophy in task-associated regions suggests partially shared underlying deficits, whereas unique atrophy reinforces variant-specific deficits. Language task-related regions that are not obviously atrophied suggest regions of future network disruption and encourage understanding of task deficits beyond clearly atrophied cortex. These results may pave the way for new treatment approaches.

Dataset Information

Sex differences in effects of tDCS and language treatments on brain functional connectivity in primary progressive aphasia.

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Sex differences in effects of tDCS and language treatments on brain functional connectivity in primary progressive aphasia.

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