Neural substrates of L2-L1 transfer effects on phonological awareness in young Chinese-English bilingual children.

The growing trend of bilingual education between Chinese and English has contributed to a rise in the number of early bilingual children, who were exposed to L2 prior to formal language instruction of L1. The L2-L1 transfer effect in an L1-dominant environment has been well established. However, the threshold of L2 proficiency at which such transfer manifests remains unclear. This study investigated the behavioral and neural processes involved when manipulating phonemes in an auditory phonological task to uncover the transfer effect in young bilingual children. Sixty-two first graders from elementary schools in Taiwan were recruited in this study (29 Chinese monolinguals, 33 Chinese-English bilinguals). The brain activity was measured using fNIRS (functional near-infrared spectroscopy). Bilingual children showed right lateralization to process Chinese and left lateralization to process English, which supports more on the accommodation effect within the framework of the assimilation-accommodation hypothesis. Also, compared to monolinguals, bilingual children showed more bilateral frontal activation in Chinese, potentially reflecting a mixed influence from L2-L1 transfer effects and increased cognitive load of bilingual exposure. These results elucidate the developmental adjustments in the neural substrates associated with early bilingual exposure in phonological processing, offering valuable insights into the bilingual learning process.

Phonological and morphological literacy skills in English and Chinese: A cross-linguistic neuroimaging comparison of Chinese-English bilingual and monolingual English children.

Over the course of literacy development, children learn to recognize word sounds and meanings in print. Yet, they do so differently across alphabetic and character-based orthographies such as English and Chinese. To uncover cross-linguistic influences on children's literacy, we asked young Chinese-English simultaneous bilinguals and English monolinguals (N = 119, ages 5-10) to complete phonological and morphological awareness (MA) literacy tasks. Children completed the tasks in the auditory modality in each of their languages during functional near-infrared spectroscopy neuroimaging. Cross-linguistically, comparisons between bilinguals' two languages revealed that the task that was more central to reading in a given orthography, such as phonological awareness (PA) in English and MA in Chinese, elicited less activation in the left inferior frontal and parietal regions. Group comparisons between bilinguals and monolinguals in English, their shared language of academic instruction, revealed that the left inferior frontal was less active during phonology but more active during morphology in bilinguals relative to monolinguals. MA skills are generally considered to have greater language specificity than PA skills. Bilingual literacy training in a skill that is maximally similar across languages, such as PA, may therefore yield greater automaticity for this skill, as reflected in the lower activation in bilinguals relative to monolinguals. This interpretation is supported by negative correlations between proficiency and brain activation. Together, these findings suggest that both the structural characteristics and literacy experiences with a given language can exert specific influences on bilingual and monolingual children's emerging brain networks for learning to read.

Brain bases of English morphological processing: A comparison between Chinese-English, Spanish-English bilingual, and English monolingual children.

How do early bilingual experiences influence children's neural architecture for word processing? Dual language acquisition can yield common influences that may be shared across different bilingual groups, as well as language-specific influences stemming from a given language pairing. To investigate these effects, we examined bilingual English speakers of Chinese or Spanish, and English monolinguals, all raised in the US (N = 152, ages 5-10). Children completed an English morphological word processing task during fNIRS neuroimaging. The findings revealed both language-specific and shared bilingual effects. The language-specific effects were that Chinese and Spanish bilinguals showed principled differences in their neural organization for English lexical morphology. The common bilingual effects shared by the two groups were that in both bilingual groups, increased home language proficiency was associated with stronger left superior temporal gyrus (STG) activation when processing the English word structures that are most dissimilar from the home language. The findings inform theories of language and brain development during the key periods of neural reorganization for learning to read by illuminating experience-based plasticity in linguistically diverse learners.

Neural substrates of theory of mind in adults with autism spectrum disorder: An fMRI study of the social animation task.

BACKGROUND: Although the neural mechanisms of the theory of mind (ToM) in children with autism spectrum disorder (ASD) through fMRI using the social animation task have been investigated, little is known in adults with ASD. Therefore, the present study aimed to explore the neural substrates of ToM in adults with ASD. Moreover, we aimed to elucidate the relationship between brain activation and behavior of social interaction in adults with ASD. METHODS: Twenty-four healthy controls and 24 adults with the clinical diagnosis of ASD were recruited. Participants were asked to complete the social animation task in functional magnetic resonance imaging. The imaging analyses of within (whole brain analysis) and between (5 regions of interest) group comparisons were conducted to explore the process of ToM. The correlation analyses were further conducted to explore the relationship between neural activations associated with ToM and social interaction abilities assessed by ADI-R. RESULTS: The ASD group showed greater activation in the left precuneus and right superior temporal gyrus (STG) than the control group. For correlation analyses, greater right STG activation was positively correlated with autistic symptoms assessed by the ADI-R in the ASD group. CONCLUSION: ASD adults might spend a lot of effort on identification processing, thereby influencing social communication skills. Also, the neural deficits of ToM in ASD adults might be associated with their social interaction difficulties.

Exploring social emotion processing in autism: evaluating the reading the mind in the eyes test using network analysis.

BACKGROUND: Features of autism spectrum disorder (ASD) include difficulties in processing and interpreting socioemotional information. The "Reading the Mind in the Eyes" test (RMET) is a validated measurement for processing socioemotional ability. However, previous RMET studies did not explore patterns of incorrect answers and the emotional valence of the test items. This study used the Taiwanese version of the RMET and the network analysis methods to examine the differences in underlying mechanisms of socioemotional processes between 30 males with autism spectrum disorder (ASD) (mean age = 18 years) and 30 healthy control males (mean age = 17 years). For each test item, a picture of a person's eyes and partial face was shown with four words describing the emotional status on picture corners. Participants were instructed to choose one of the four words that best matched the person's thinking or feeling. We further classified the words into three valences of emotional categories to examine socioemotional processes. RESULTS: Our results showed that ASD males performed poorer on the RMET than the controls. ASD males had higher network density and in-degree scores, especially in negative words, than control males. CONCLUSIONS: The findings suggest that males with ASD might have deficits in mapping the best emotional concept words to the target item, especially for processing negative emotion.

What's in a word? Cross-linguistic influences on Spanish-English and Chinese-English bilingual children's word reading development.

This study investigates the cross-linguistic transfer of literacy skills in Spanish-English, Chinese-English bilingual, and English monolingual children (N = 283, 5-10 years). Research question 1 examines English literacy and asks how phonological and morpho-semantic skills contribute to word reading as a function of children's language background. Structural equation modeling revealed contrasting bilingual effects: compared to English monolinguals, Spanish-English bilinguals relied more on phonological awareness in word reading, whereas Chinese-English bilinguals relied more on lexical knowledge. Research question 2 examines relations between bilinguals' heritage language proficiency and English literacy. Results revealed direct and indirect effects of heritage language meta-linguistic skills on English word reading. The study yields implications for reading theories and instructional practices in optimizing literacy in linguistically diverse children.

Developmental differences in neural connectivity for semantic processing in youths with autism.

BACKGROUND: Youths with autism spectrum disorder (ASD) rely more on lower-level visual processing as revealed by greater occipital activation, yet less effectively engage higher-level processing of modality-independent semantic knowledge as indicated by reduced frontal activation, compared to typically developing (TD) youths. However, little is known about age-dependent differences in neural connectivity during semantic processing in youths with ASD as compared to TD youths. METHODS: Four groups were recruited: 31 ASD children (mean age = 10.5 years old), 33 TD children (mean age = 10.4), 30 ASD adolescents (mean age = 14.9), and 34 TD adolescents (mean age = 15.1). We explored their differences in neural connectivity by using functional magnetic resonance imaging (fMRI) with psychophysiological interaction (PPI) during semantic judgments. RESULTS: In comparison with TD children, children with ASD showed greater activation in the left cuneus and weaker connectivity between the left cuneus and left middle temporal gyrus (MTG). In comparison with TD adolescents, adolescents with ASD showed less activation in the left inferior frontal gyrus (IFG) and weaker functional connectivity between the left IFG and left MTG. CONCLUSIONS: Children with ASD may rely more on visual processes in the occipital cortex that are disconnected from modality-independent semantics in the temporal cortex. However, adolescents with ASD may less effectively engage frontal mechanisms involved in the top-down control of modality-independent semantic knowledge in the temporal cortex. Our findings provide evidence of developmental differences in the neural substrates of the alterations in semantic processing in youths with ASD compared to TD youths.

Social cognition in schizophrenia: A network-based approach to a Taiwanese version of the Reading the Mind in the Eyes test.

BACKGROUND: This study aimed to examine social-cognitive impairments in patients with schizophrenia using the Eyes test. In contrast to previous methods using the correct answers, we developed the Taiwanese version of the Eyes test and constructed the response network to explore impairments in the emotional aspects of theory of mind in patients with schizophrenia. METHODS: Eighteen patients with schizophrenia and 18 healthy controls were recruited to examine their performance of the Eyes test. To explore the internal structures of mental states, we used network analysis to construct the networks of choice patterns (i.e. participants' answers) by using two network indicators, including density (an index of structure diversity of a network) and centrality (an index of the choice patterns within a network). Moreover, we divided all the choices into negative, positive, and neutral item groups based on emotion polarity. RESULTS: The patient group was slower and less accurate than the control group. Moreover, there was a negative correlation between accuracy and blunted affect, and there were positive correlations between reaction time and emotional withdrawal and apathetic social withdrawal. As compared to healthy controls, patients with schizophrenia showed larger density in the network structure and higher centrality than controls. Also, patients showed poorer performance on negative words than healthy controls. CONCLUSION: Our results demonstrated more diversity to recognize negative emotions from patients' choice patterns as compared to those in the control group. These findings suggest that deficits on recognizing negative emotions might be associated with the dysfunctions of mental states in schizophrenia.

Multi-time-point analysis: A time course analysis with functional near-infrared spectroscopy.

In the data analysis of functional near-infrared spectroscopy (fNIRS), linear model frameworks, in particular mass univariate analysis, are often used when researchers consider examining the difference between conditions at each sampled time point. However, some statistical issues, such as assumptions of linearity, autocorrelation and multiple comparison problems, influence statistical inferences when mass univariate analysis is used on fNIRS time course data. In order to address these issues, the present study proposes a novel perspective, multi-time-point analysis (MTPA), to discriminate signal differences between conditions by combining temporal information from multiple time points in fNIRS. In addition, MTPA adopts the random forest algorithm from the statistical learning domain, followed by a series of cross-validation procedures, providing reasonable power for detecting significant time points and ensuring generalizability. Using a real fNIRS data set, the proposed MTPA outperformed mass univariate analysis in detecting more time points, showing significant differences between experimental conditions. Finally, MTPA was also able to make comparisons between different areas, leading to a novel viewpoint of fNIRS time course analysis and providing additional theoretical implications for future fNIRS studies. The data set and all source code are available for researchers to replicate the analyses and to adapt the program for their own needs in future fNIRS studies.

Visual processing as a potential endophenotype in youths with attention-deficit/hyperactivity disorder: A sibling study design using the counting Stroop functional MRI.

Deficits in inhibitory control and visual processing are common in youths with attention-deficit/hyperactivity disorder (ADHD), but little is known about endophenotypes for unaffected siblings of youths with ADHD. This study aimed to investigate the potential endophenotypes of brain activation and performance in inhibitory control and visual processing among ADHD probands, their unaffected siblings, and neurotypical youths. We assessed 27 ADHD probands, 27 unaffected siblings, and 27 age-, gender-, and IQ-matched neurotypical youths using the counting Stroop functional magnetic resonance imaging and two tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB): rapid visual information processing (RVP) for inhibitory control and spatial span (SSP) for visual processing. ADHD probands showed greater activation than their unaffected siblings and neurotypical youths in the right inferior frontal gyrus (IFG) and anterior cingulate cortex. Increased activation in the right IFG was positively correlated with the mean latency of the RVP in ADHD probands. Moreover, ADHD probands and their unaffected siblings showed less activation in the left superior parietal lobule (SPL) than neurotypical youths. Increased activation in the left SPL was positively correlated with the spatial length of the SSP in neurotypical youths. Our findings suggest that less activation in the left SPL might be considered as a candidate imaging endophenotype for visual processing in ADHD.

Neural correlates of atomoxetine improving inhibitory control and visual processing in Drug-naïve adults with attention-deficit/hyperactivity disorder.

Atomoxetine improves inhibitory control and visual processing in healthy volunteers and adults with attention-deficit/hyperactivity disorder (ADHD). However, little is known about the neural correlates of these two functions after chronic treatment with atomoxetine. This study aimed to use the counting Stroop task with functional magnetic resonance imaging (fMRI) and the Cambridge Neuropsychological Test Automated Battery (CANTAB) to investigate the changes related to inhibitory control and visual processing in adults with ADHD. This study is an 8-week, placebo-controlled, double-blind, randomized clinical trial of atomoxetine in 24 drug-naïve adults with ADHD. We investigated the changes of treatment with atomoxetine compared to placebo-treated counterparts using the counting Stroop fMRI and two CANTAB tests: rapid visual information processing (RVP) for inhibitory control and delayed matching to sample (DMS) for visual processing. Atomoxetine decreased activations in the right inferior frontal gyrus and anterior cingulate cortex, which were correlated with the improvement in inhibitory control assessed by the RVP. Also, atomoxetine increased activation in the left precuneus, which was correlated with the improvement in the mean latency of correct responses assessed by the DMS. Moreover, anterior cingulate activation in the pre-treatment was able to predict the improvements of clinical symptoms. Treatment with atomoxetine may improve inhibitory control to suppress interference and may enhance the visual processing to process numbers. In addition, the anterior cingulate cortex might play an important role as a biological marker for the treatment effectiveness of atomoxetine. Hum Brain Mapp 38:4850-4864, 2017. © 2017 Wiley Periodicals, Inc.

Neighborhood Frequency Effect in Chinese Word Recognition: Evidence from Naming and Lexical Decision.

Neighborhood frequency is a crucial variable to know the nature of word recognition. Different from alphabetic scripts, neighborhood frequency in Chinese is usually confounded by component character frequency and neighborhood size. Three experiments were designed to explore the role of the neighborhood frequency effect in Chinese and the stimuli were all two-character words. This effect was evaluated on targets with- and without-higher frequency neighbors with neighborhood size matched. Among the experiments, the patterns of the leading character frequency effect and word frequency effect in the naming and lexical decision tasks were compared. The results implied an inhibitory neighborhood frequency effect in Chinese word recognition. Accordingly, a possible cognitive mechanism of the neighborhood frequency effect was thus proposed.

Temporo-parietal connectivity uniquely predicts reading change from childhood to adolescence.

Previous research has shown that left posterior middle temporal gyrus (pMTG) is a core node in the semantic network, and cross-sectional studies have shown that activation in this region changes developmentally and is related to skill measured concurrently. However, it is not known how functional connectivity with this region changes developmentally, and whether functional connectivity is related to future gains in reading. We conducted a longitudinal functional magnetic resonance imaging (fMRI) study in 30 typically developing children (aged 8-15) to examine whether initial brain measures, including activation and connectivity, can predict future behavioral improvement in a semantic judgment task. Participants were scanned on entering the study (time 1, T1) and a follow-up period of 2years (time 2, T2). Character pairs were arranged in a continuous variable according to association strength (i.e. strong versus weak), and participants were asked to determine if these visually presented pairs were related in meaning. Our results demonstrated greater developmental changes from time 1 to time 2 for weaker association pairs in the left pMTG for the children (aged 8-11) as compared to the adolescents (aged 12-15). Moreover, the results showed greater developmental changes from time 1 to time 2 for weaker association pairs in connectivity between the pMTG and inferior parietal lobule (IPL) for the children as compared to the adolescents. Furthermore, a hierarchical stepwise regression model revealed that connectivity between the pMTG and IPL in weak association pairs was uniquely predictive of behavioral improvement from time 1 to time 2 for the children, but not the adolescents. Taken together, the activation results suggest relatively rapid development before adolescence of semantic representations in the pMTG. Moreover, the connectivity results of pMTG with IPL tentatively suggest that early development of semantic representations may be facilitated by enhanced engagement of phonological short-term memory.

The role of orthographic neighborhood size effects in Chinese word recognition.

Previous studies about the orthographic neighborhood size (NS) in Chinese have overlooked the morphological processing, and the co-variation between the character frequency and the the NS. The present study manipulated the word frequency and the NS simultaneously, with the leading character frequency controlled, to explore their influences on word lexical decision (Experiment 1) and naming (Experiment 2). The results showed a robust effect that words with a larger NS produced shorter reaction time than those with a smaller NS, irrespective of the word frequency and the tasks. This facilitative effect may occur due to a semantic network formed by neighbor words, resulting in the semantic activation to accelerate the word recognition. Moreover, the comparison of the effect sizes of word frequency between the two tasks showed that lexical decision responses demonstrated a larger word frequency effect, indicating that the sub-word processing was involved in the multi-character word recognition.

Lack of effects of eight-week left dorsolateral prefrontal theta burst stimulation on white matter macro/microstructure and connection in autism.

Whether brain stimulation could modulate brain structure in autism remains unknown. This study explored the impact of continuous theta burst stimulation (cTBS) over the left dorsolateral prefrontal cortex (DLPFC) on white matter macro/microstructure in intellectually able children and emerging adults with autism. Sixty autistic participants were randomized (30 active) and received active or sham cTBS for eight weeks twice per week, 16 total sessions using a double-blind (participant-, rater-, analyst-blinded) design. All participants received high-angular resolution diffusion MR imaging at baseline and week 8. Twenty-eight participants in the active group and twenty-seven in the sham group with good imaging quality entered the final analysis. With longitudinal fixel-based analysis and network-based statistics, we found no significant difference between the active and sham groups in changes of white matter macro/microstructure and connections following cTBS. In addition, we found no association between baseline white matter macro/microstructure and autistic symptom changes from baseline to week 8 in the active group. In conclusion, we did not find a significant impact of left DLPFC cTBS on white matter macro/microstructure and connections in children and emerging adults with autism. These findings need to be interpreted in the context that the current intellectually able cohort in a single university hospital site limits the generalizability. Future studies are required to investigate if higher stimulation intensities and/or doses, other personal factors, or rTMS parameters might confer significant brain structural changes visible on MRI in ASD.

Towards a neural circuit model of verbal humor processing: an fMRI study of the neural substrates of incongruity detection and resolution.

The present study builds on our previous study within the framework of Wyer and Collin's comprehension-elaboration theory of humor processing. In this study, an attempt is made to segregate the neural substrates of incongruity detection and incongruity resolution during the comprehension of verbal jokes. Although a number of fMRI studies have investigated the incongruity-resolution process, the differential neurological substrates of comprehension are still not fully understood. The present study utilized an event-related fMRI design incorporating three conditions (unfunny, nonsensical and funny) to examine distinct brain regions associated with the detection and resolution of incongruities. Stimuli in the unfunny condition contained no incongruities; stimuli in the nonsensical condition contained irresolvable incongruities; and stimuli in the funny condition contained resolvable incongruities. The results showed that the detection of incongruities was associated with greater activation in the right middle temporal gyrus and right medial frontal gyrus, and the resolution of incongruities with greater activation in the left superior frontal gyrus and left inferior parietal lobule. Further analysis based on participants' rating scores provided converging results. Our findings suggest a three-stage neural circuit model of verbal humor processing: incongruity detection and incongruity resolution during humor comprehension and inducement of the feeling of amusement during humor elaboration.

Money or funny: Effective connectivity during service recovery with a DCM-PEB approach.

While monetary compensation is considered the most effective service recovery strategy, relief theory claims that humor may also be useful in service recovery situations. This study investigated the effects of humor in service recovery using dynamic causal modeling and parametric empirical Bayes analysis to identify effective connectivity (EC) patterns in the dopaminergic reward system across four conditions representing different service recovery strategies: monetary compensation and humor (MH), monetary compensation and an apology (MA), non-monetary compensation using humor (H), and non-monetary compensation using an apology (CON, the control condition). The findings support the importance of the nucleus accumbens (NAc) in the monetary compensation (MH and MA) conditions and the amygdala in the non-monetary compensation (H and CON) conditions. Monetary compensation (MH and MA) resulted in right substantia nigra (rSN) to NAc EC, suggesting the processing of recovery satisfaction associated with perceived outcome fairness. Conversely, non-monetary compensation strategies (H and CON) resulted in left substantia nigra (lSN) to amygdala EC, suggesting the processing of satisfaction related to perceived interactional fairness. The use of humor for service recovery resulted in VTA-to-lSN-to-amygdala EC during humor appreciation, while the use of apologies (CON and MA) resulted in lSN-to-amygdala and lSN-to-VTA connectivity. Surprisingly, processing satisfaction in the MH condition did not activate the amygdala during humor appreciation. Coping humor could be norm-violating for service recovery, and its effectiveness depends on multiple factors. The results suggest that monetary compensation, humorous responses, and apologies play key roles in neurological responses to service recovery strategies.

The neurocognitive basis of Chinese idiomatic constructions and processing differences between native speakers and L2 learners of Mandarin.

Classic linguistic analyses assume that syntax is the center of linguistic system. Under this assumption, a finite set of rules can produce an infinite number of sentences. By contrast, construction grammar posits that grammar emerges from language use. Chinese quadrisyllabic idiomatic expressions (QIEs) offer a testing ground for this theoretical construct owing to their high productivity. To understand the cognitive processing of structure and meaning during reading comprehension, we used a semantic judgment task to measure behavioral performance and brain activation (functional MRI). Participants were 19 Mandarin native speakers and 19 L2 learners of intermediate and advanced levels of Mandarin. In the task, participants were instructed to indicate whether the interpretation of a QIE was correct. Our behavioral results showed that L2 learners processed high frequency QIEs faster than low frequency ones. By contrast, low frequency QIEs were processed faster than high frequency ones by native speakers. This phenomenon may be attributed to semantic satiation which impedes the interpretation of high frequency QIEs. To unravel the puzzle, a further functional MRI experiment on native speakers was conducted. The results revealed that the comparison of high-frequency and low-frequency QIEs promoted significant anterior cingulate activation. Also, the comparison of idiomatic and pseudo-idiomatic constructions exhibited significant activation in the bilateral temporal poles, a region that computes semantics rather than syntactic structure. This result indicated that, for native speakers, processing Chinese idiomatic constructions is a conceptually driven process.

Sex differences in medication-naïve adults with attention-deficit/hyperactivity disorder: A counting Stroop functional MRI study.

Emerging evidence supports deficits in executive functions in the fronto-striato-parietal network in individuals with attention-deficit/hyperactivity disorder (ADHD). However, most functional studies recruited men with ADHD only, leaving it unclear whether executive deficits are also demonstrated in women with ADHD. Thus, we used functional magnetic resonance imaging to examine the sex differences in a counting Stroop task that explored interference control. The sample consisted of 55 medication-naïve adults with ADHD (28 men, 27 women) and 52 healthy controls (HC, 26 men, 26 women). The Conners' Continuous Performance Test further evaluated the performance of focused attention (standard deviation of the reaction time, RTSD) and vigilance (the reaction time change across different inter-stimulus intervals, RTISI). First, for the main effect of diagnosis, compared to the HC group, the ADHD group showed less activation in the caudate nucleus and inferior frontal gyrus (IFG). Second, for the main effect of sex, no significant effects were found. Third, a diagnosis-by-sex interaction indicated that the magnitude of ADHD-HC difference was greater for women than men in the right IFG and precuneus, reflecting greater difficulties for ADHD women to resolve interference. Conversely, no significant brain activation showed greater ADHD-HC difference in men than women. Also, reduced right IFG and precuneus activation was negatively associated with the scores assessing focused attention and vigilance in ADHD women, indicating that the attentional abilities are disrupted in ADHD women. Abnormalities in the frontoparietal areas may represent the main difference between ADHD women and ADHD men.

Lack of effects of four-week theta burst stimulation on white matter macro/microstructure in children and adolescents with autism.

Following the published behavioral and cognitive results of this single-blind parallel sham-controlled randomized clinical trial, the current study aimed to explore the impact of intermittent theta burst stimulation (iTBS), a variant of excitatory transcranial magnetic stimulation, over the bilateral posterior superior temporal sulci (pSTS) on white matter macro/microstructure in intellectually able children and adolescents with autism. Participants were randomized and blindly received active or sham iTBS for 4 weeks (the single-blind sham-controlled phase). Then, all participants continued to receive active iTBS for another 4 weeks (the open-label phase). The clinical results were published elsewhere. Here, we present diffusion magnetic resonance imaging data on potential changes in white matter measures after iTBS. Twenty-two participants in Active-Active group and 27 participants in Sham-Active group underwent multi-shell high angular resolution diffusion imaging (64-direction for b = 2000 & 1000 s/mm2, respectively) at baseline, week 4, and week 8. With longitudinal fixel-based analysis, we found no white matter changes following iTBS from baseline to week 4 (a null treatment by time interaction and a null within-group paired comparison in the Active-Active group), nor from baseline to week 8 (null within-group paired comparisons in both Active-Active and Sham-Active groups). As for the brain-symptoms relationship, we did not find baseline white matter metrics associated with symptom changes at week 4 in either group. Our results raise the question of what the minimal cumulative stimulation dose required to induce the white matter plasticity is.