fMRI evidence for cortical modification during language learning

This is the publisher's official version, which the author has permission to share.Functional magnetic resonance imaging was employed before and after six native English speakers completed lexical tone training as part of a program to learn Mandarin as a second language. Language-related areas including Broca’s area, Wernicke’s area, auditory cortex, and supplementary motor regions were active in all subjects before and after training and did not vary in average location. Across all subjects, improvements in performance were associated with an increase in the spatial extent of activation in left superior temporal gyrus (Brodmann’s area 22, putative Wernicke’s area), the emergence of activity in adjacent Brodmann’s area 42, and the emergence of activity in right inferior frontal gyrus (Brodmann’s area 44), a homologue of putative Broca’s area. These findings demonstrate a form of enrichment plasticity in which the early cortical effects of learning a tone-based second language involve both expansion of preexisting language-related areas and recruitment of additional cortical regions specialized for functions similar to the new language functions

fMRI evidence for cortical modification during learning of Mandarin lexical tone

Functional magnetic resonance imaging was employed before and after six native English speakers completed lexical tone training as part of a program to learn Mandarin as a second language. Language-related areas including Broca's area, Wernicke's area, auditory cortex, and supplementary motor regions were active in all subjects before and after training and did not vary in average location. Across all subjects, improvements in performance were associated with an increase in the spatial extent of activation in left superior temporal gyrus (Brodmann's area 22, putative Wernicke's area), the emergence of activity in adjacent Brodmann's area 42, and the emergence of activity in right inferior frontal gyrus (Brodmann's area 44), a homologue of putative Broca's area. These findings demonstrate a form of enrichment plasticity in which the early cortical effects of learning a tone-based second language involve both expansion of preexisting language-related areas and recruitment of additional cortical regions specialized for functions similar to the new language functions

Neural mechanisms for emotional contagion and spontaneous mimicry of live facial expressions

Viewing a live facial expression typically elicits a similar expression by the observer (facial mimicry) that is associated with a concordant emotional experience (emotional contagion). The model of embodied emotion proposes that emotional contagion and facial mimicry are functionally linked although the neural underpinnings are not known. To address this knowledge gap, we employed a live two-person paradigm (n = 20 dyads) using functional near-infrared spectroscopy during live emotive face-processing while also measuring eye-tracking, facial classifications and ratings of emotion. One dyadic partner, ‘Movie Watcher’, was instructed to emote natural facial expressions while viewing evocative short movie clips. The other dyadic partner, ‘Face Watcher’, viewed the Movie Watcher's face. Task and rest blocks were implemented by timed epochs of clear and opaque glass that separated partners. Dyadic roles were alternated during the experiment. Mean cross-partner correlations of facial expressions (r = 0.36 ± 0.11 s.e.m.) and mean cross-partner affect ratings (r = 0.67 ± 0.04) were consistent with facial mimicry and emotional contagion, respectively. Neural correlates of emotional contagion based on covariates of partner affect ratings included angular and supramarginal gyri, whereas neural correlates of the live facial action units included motor cortex and ventral face-processing areas. Findings suggest distinct neural components for facial mimicry and emotional contagion. This article is part of a discussion meeting issue ‘Face2face: advancing the science of social interaction’

Effects of Reduced Weight Maintenance and Leptin Repletion on Functional Connectivity of the Hypothalamus in Obese Humans

Treating obesity has proven to be an intractable challenge, in part, due to the difficulty of maintaining reduced weight. In our previous studies of in-patient obese subjects, we have shown that leptin repletion following a 10% or greater weight loss reduces many of the metabolic (decreased energy expenditure, sympathetic nervous system tone, and bioactive thyroid hormones) and behavioral (delayed satiation) changes that favor regain of lost weight. FMRI studies of these same subjects have shown leptin-sensitive increases in activation of the right hypothalamus and reduced activation of the cingulate, medial frontal and parahippocampal gryi, following weight loss, in response to food stimuli. In the present study, we expanded our cohort of in-patient subjects and employed psychophysiological interaction (PPI) analysis to examine changes in the functional connectivity of the right hypothalamus. During reduced-weight maintenance with placebo injections, the functional connectivity of the hypothalamus increased with visual areas and the dorsal anterior cingulate (dorsal ACC) in response to food cues, consistent with higher sensitivity to food. During reduced-weight maintenance with leptin injections, however, the functional connectivity of the right hypothalamus increased with the mid-insula and the central and parietal operculae, suggesting increased coupling with the interoceptive system, and decreased with the orbital frontal cortex, frontal pole and the dorsal ACC, suggesting a down-regulated sensitivity to food. These findings reveal neural mechanisms that may underlie observed changes in sensitivity to food cues in the obese population during reduced-weight maintenance and leptin repletion

Mindboggle: Automated brain labeling with multiple atlases

BACKGROUND: To make inferences about brain structures or activity across multiple individuals, one first needs to determine the structural correspondences across their image data. We have recently developed Mindboggle as a fully automated, feature-matching approach to assign anatomical labels to cortical structures and activity in human brain MRI data. Label assignment is based on structural correspondences between labeled atlases and unlabeled image data, where an atlas consists of a set of labels manually assigned to a single brain image. In the present work, we study the influence of using variable numbers of individual atlases to nonlinearly label human brain image data. METHODS: Each brain image voxel of each of 20 human subjects is assigned a label by each of the remaining 19 atlases using Mindboggle. The most common label is selected and is given a confidence rating based on the number of atlases that assigned that label. The automatically assigned labels for each subject brain are compared with the manual labels for that subject (its atlas). Unlike recent approaches that transform subject data to a labeled, probabilistic atlas space (constructed from a database of atlases), Mindboggle labels a subject by each atlas in a database independently. RESULTS: When Mindboggle labels a human subject's brain image with at least four atlases, the resulting label agreement with coregistered manual labels is significantly higher than when only a single atlas is used. Different numbers of atlases provide significantly higher label agreements for individual brain regions. CONCLUSION: Increasing the number of reference brains used to automatically label a human subject brain improves labeling accuracy with respect to manually assigned labels. Mindboggle software can provide confidence measures for labels based on probabilistic assignment of labels and could be applied to large databases of brain images

Can Depression be Diagnosed by Response to Mother's Face? A Personalized Attachment-Based Paradigm for Diagnostic fMRI

OBJECTIVE: Objective measurement of depression remains elusive. Depression has been associated with insecure attachment, and both have been associated with changes in brain reactivity in response to viewing standard emotional and neutral faces. In this study, we developed a method to calculate predicted scores for the Beck Depression Inventory II (BDI-II) using personalized stimuli: fMRI imaging of subjects viewing pictures of their own mothers. METHODS: 28 female subjects ages 18-30 (14 healthy controls and 14 unipolar depressed diagnosed by MINI psychiatric interview) were scored on the Beck Depression Inventory II (BDI-II) and the Adult Attachment Interview (AAI) coherence of mind scale of global attachment security. Subjects viewed pictures of Mother (M), Friend (F) and Stranger (S), during functional magnetic resonance imaging (fMRI). Using a principal component regression method (PCR), a predicted Beck Depression Inventory II (BDI-II) score was obtained from activity patterns in the paracingulate gyrus (Brodmann area 32) and compared to clinical diagnosis and the measured BDI-II score. The same procedure was performed for AAI coherence of mind scores. RESULTS: Activity patterns in BA-32 identified depressed subjects. The categorical agreement between the derived BDI-II score (using the standard clinical cut-score of 14 on the BDI-II) and depression diagnosis by MINI psychiatric interview was 89%, with sensitivity 85.7% and specificity 92.8%. Predicted and measured BDI-II scores had a correlation of 0.55. Prediction of attachment security was not statistically significant. CONCLUSIONS: Brain activity in response to viewing one's mother may be diagnostic of depression. Functional magnetic resonance imaging using personalized paradigms has the potential to provide objective assessments, even when behavioral measures are not informative. Further, fMRI based diagnostic algorithms may enhance our understanding of the neural mechanisms of depression by identifying distinctive neural features of the illness

Activation in Right Dorsolateral Prefrontal Cortex Underlies Stuttering Anticipation

People who stutter learn to anticipate many of their overt stuttering events. Despite the critical role of anticipation, particularly how responses to anticipation shape stuttering behaviors, the neural bases associated with anticipation are unknown. We used a novel approach to identify anticipated and unanticipated words in 22 adult stutterers, which were produced in a delayed-response task while hemodynamic activity was measured using functional near infrared spectroscopy (fNIRS). Twenty-two control participants were included such that each individualized set of anticipated/unanticipated words was produced by one stutterer and one control. We conducted an analysis on the right dorsolateral prefrontal cortex (R-DLPFC) based on converging lines of evidence from the stuttering and cognitive control literatures. We also assessed connectivity between the R-DLPFC and right supramarginal gyrus (R-SMG), two key nodes of the frontoparietal network (FPN), to assess the role of cognitive control, particularly error-likelihood monitoring, in stuttering anticipation. All analyses focused on the five-second anticipation phase preceding the go signal to produce speech. Results indicate that anticipated words are associated with elevated activation in the R-DLPFC, and that compared to non-stutterers, stutterers exhibit greater activity in the R-DLPFC, irrespective of anticipation. Further, anticipated words are associated with reduced connectivity between the R-DLPFC and R-SMG. These findings highlight the potential roles of the R-DLPFC and the greater FPN as a neural substrate of stuttering anticipation. The results also support previous accounts of error-likelihood monitoring and action-stopping in stuttering anticipation. Overall, this work offers numerous directions for future research with clinical implications for targeted neuromodulation

Investigation of functional near-infrared spectroscopy signal quality and development of the hemodynamic phase correlation signal

SIGNIFICANCE: There is a longstanding recommendation within the field of fNIRS to use oxygenated ( HbO 2 ) and deoxygenated (HHb) hemoglobin when analyzing and interpreting results. Despite this, many fNIRS studies do focus on HbO 2 only. Previous work has shown that HbO 2 on its own is susceptible to systemic interference and results may mostly reflect that rather than functional activation. Studies using both HbO 2 and HHb to draw their conclusions do so with varying methods and can lead to discrepancies between studies. The combination of HbO 2 and HHb has been recommended as a method to utilize both signals in analysis. AIM: We present the development of the hemodynamic phase correlation (HPC) signal to combine HbO 2 and HHb as recommended to utilize both signals in the analysis. We use synthetic and experimental data to evaluate how the HPC and current signals used for fNIRS analysis compare. APPROACH: About 18 synthetic datasets were formed using resting-state fNIRS data acquired from 16 channels over the frontal lobe. To simulate fNIRS data for a block-design task, we superimposed a synthetic task-related hemodynamic response to the resting state data. This data was used to develop an HPC-general linear model (GLM) framework. Experiments were conducted to investigate the performance of each signal at different SNR and to investigate the effect of false positives on the data. Performance was based on each signal's mean T -value across channels. Experimental data recorded from 128 participants across 134 channels during a finger-tapping task were used to investigate the performance of multiple signals [ HbO 2 , HHb, HbT, HbD, correlation-based signal improvement (CBSI), and HPC] on real data. Signal performance was evaluated on its ability to localize activation to a specific region of interest. RESULTS: Results from varying the SNR show that the HPC signal has the highest performance for high SNRs. The CBSI performed the best for medium-low SNR. The next analysis evaluated how false positives affect the signals. The analyses evaluating the effect of false positives showed that the HPC and CBSI signals reflect the effect of false positives on HbO 2 and HHb. The analysis of real experimental data revealed that the HPC and HHb signals provide localization to the primary motor cortex with the highest accuracy. CONCLUSION: We developed a new hemodynamic signal (HPC) with the potential to overcome the current limitations of using HbO 2 and HHb separately. Our results suggest that the HPC signal provides comparable accuracy to HHb to localize functional activation while at the same time being more robust against false positives

Neural correlates of eye contact and social function in autism spectrum disorder

Reluctance to make eye contact during natural interactions is a central diagnostic criterion for autism spectrum disorder (ASD). However, the underlying neural correlates for eye contacts in ASD are unknown, and diagnostic biomarkers are active areas of investigation. Here, neuroimaging, eye-tracking, and pupillometry data were acquired simultaneously using two-person functional near-infrared spectroscopy (fNIRS) during live "in-person" eye-to-eye contact and eye-gaze at a video face for typically-developed (TD) and participants with ASD to identify the neural correlates of live eye-to-eye contact in both groups. Comparisons between ASD and TD showed decreased right dorsal-parietal activity and increased right ventral temporal-parietal activity for ASD during live eye-to-eye contact (p≤0.05, FDR-corrected) and reduced cross-brain coherence consistent with atypical neural systems for live eye contact. Hypoactivity of right dorsal-parietal regions during eye contact in ASD was further associated with gold standard measures of social performance by the correlation of neural responses and individual measures of: ADOS-2, Autism Diagnostic Observation Schedule, 2nd Edition (r = -0.76, -0.92 and -0.77); and SRS-2, Social Responsiveness Scale, Second Edition (r = -0.58). The findings indicate that as categorized social ability decreases, neural responses to real eye-contact in the right dorsal parietal region also decrease consistent with a neural correlate for social characteristics in ASD