Early-stage use of hearing aids preserves auditory cortical structure in children with sensorineural hearing loss.

Hearing is critical to spoken language, cognitive, and social development. Little is known about how early auditory experiences impact the brain structure of children with bilateral sensorineural hearing loss. This study examined the influence of hearing aid use and residual hearing on the auditory cortex of children with severe to profound congenital sensorineural hearing loss. We evaluated cortical preservation in 103 young pediatric cochlear implant candidates (55 females and 48 males) by comparing their multivoxel pattern similarity of auditory cortical structure with that of 78 age-matched children with typical hearing. The results demonstrated that early-stage hearing aid use preserved the auditory cortex of children with bilateral congenital sensorineural hearing loss. Children with less residual hearing experienced a more pronounced advantage from hearing aid use. However, this beneficial effect gradually diminished after 17 months of hearing aid use. These findings support timely fitting of hearing aids in conjunction with early implantation to take advantage of neural preservation to maximize auditory and spoken language development.

Brain templates for Chinese babies from newborn to three months of age.

The infant brain develops rapidly and this area of research has great clinical implications. Neurodevelopmental disorders such as autism and developmental delay have their origins, potentially, in abnormal early brain maturation. Searching for potential early neural markers requires a priori knowledge about infant brain development and anatomy. One of the most common methods of characterizing brain features requires normalization of individual images into a standard stereotactic space and conduct of group-based analyses in this space. A population representative brain template is critical for these population-based studies. Little research is available on constructing brain templates for typical developing Chinese infants. In the present work, a total of 120 babies from 5 to 89 days of age were included with high resolution structural magnetic resonance imaging scans. T1-weighted and T2-weighted templates were constructed using an unbiased registration approach for babies from newborn to 3 months of age. Age-specific templates were also estimated for babies aged at 0, 1, 2 and 3 months old. Then we conducted a series of evaluations and statistical analyses over whole tissue segmentations and brain parcellations. Compared to the use of population mismatched templates, using our established templates resulted in lower deformation energy to transform individual images into the template space and produced a smaller registration error, i.e., smaller standard deviation of the registered images. Significant volumetric growth was observed across total brain tissues and most of the brain regions within the first three months of age. The total brain tissues exhibited larger volumes in baby boys compared to baby girls. To the best of our knowledge, this is the first study focusing on the construction of Chinese infant brain templates. These templates can be used for investigating birth related conditions such as preterm birth, detecting neural biomarkers for neurological and neurodevelopmental disorders in Chinese populations, and exploring genetic and cultural effects on the brain.

Conceptualizing psychological resilience through resting-state functional MRI in a mentally healthy population: a systematic review.

Conceptualizations and operational definitions of psychological resilience vary across resilience neuroimaging studies. Data on the neural features of resilience among healthy individuals has been scarce. Furthermore, findings from resting-state functional magnetic resonance imaging (fMRI) studies were inconsistent across studies. This systematic review summarized resting-state fMRI findings in different modalities from various operationally defined resilience in a mentally healthy population. The PubMed and MEDLINE databases were searched. Articles that focused on resting-state fMRI in relation to resilience, and published before 2022, were targeted. Orbitofrontal cortex, anterior cingulate cortex, insula and amygdala, were reported the most from the 19 included studies. Regions in emotional network was reported the most from the included studies. The involvement of regions like amygdala and orbitofrontal cortex indicated the relationships between emotional processing and resilience. No common brain regions or neural pathways were identified across studies. The emotional network appears to be studied the most in association with resilience. Matching fMRI modalities and operational definitions of resilience across studies are essential for meta-analysis.

Effects of dorsolateral prefrontal cortex stimulation on network topological attributes in young individuals with high-level perceived stress: A randomized controlled trial.

Individuals with high-level perceived stress are at higher risk of developing a psychiatric disorder. While repetitive transcranial magnetic stimulation (rTMS) is effective for improving emotional symptoms, there is little evidence of its effect on perceived stress. This randomized sham-controlled trial investigated the effect of rTMS on ameliorating high-level stress and explored the associated changes in brain network activity. Fifty participants with high-level perceived stress were randomly assigned to either the active or sham rTMS group and received 12 active/sham rTMS sessions over four weeks (three per week). Perceived stress score (PSS), Chinese affective scale (CAS) normal and now statuses, and functional network topology were measured. Our results showed greater improvements in PSS and CAS_Normal scores, and reduced path length in the default mode network after active rTMS. Functional activations of the angular gyrus, posterior insula, and prefrontal cortex were also modulated in the active group. There were significant associations between posterior insula efficiency and PSS scores, and between angular efficiency and CAS_Now scores in the active group. These cumulative findings suggest rTMS as a promising intervention for recovery from high-level perceived stress.

The efficacy of repetitive transcranial magnetic stimulation (rTMS) for young individuals with high-level perceived stress: study protocol for a randomized sham-controlled trial.

BACKGROUND: High level of perceived stress may result in negative effects both psychologically and physically on individuals and may predispose onset of mental disorders such as depression, anxiety, and posttraumatic stress disorder. However, there is no suitable intervention for it. Repetitive transcranial magnetic stimulation (rTMS) studies have shown its therapeutic efficacy in treatment resistant patients with stress-related disorders. Here we describe an exploratory study protocol to investigate the effect of the intervention for the individuals with high level of stress. METHOD: This is a single blinded, randomized sham-controlled trial, targeting at young healthy adults aging from 18 to 24 years old. Forty eligible volunteers will be recruited and randomly divided into active and sham rTMS group. All subjects will take a set of neuropsychological and biological assessments and MRI scanning before and right after the intervention. During the interventional period, 12-session stimulations will be performed in 4 weeks with three sessions per week. The primary outcome will detect the difference of Chinese 14-item perceived stress scales between active and sham rTMS groups after intervention. Secondary outcomes will examine the differences of other affective measurements, level of cortisol, and MRI-derived neural functional measures between the two groups after intervention. DISCUSSION: This trial aims to examine the effect of the 12-session rTMS intervention on individuals with high level of perceived stress. Positive or negative findings from any of the outcome measures would further our understanding of the efficacy of the stimulation and its neural impact. If effective, it would provide an evidence for a new treatment for high perceived stress. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( ChiCTR1900027662 ). Registered on 23 November 2019. And all items of the WHO Trial Registry Data set can be found within the protocol.

Integrative psycho-biophysiological markers in predicting psychological resilience.

The hypothalamic-pituitary-adrenal (HPA) and parasympathetic nervous systems have been reported to play important roles in emotion regulation and stress coping. Yet, their direct relationship with psychological resilience remains unclear. These biophysiological features should be considered together with the traditional psychometric properties in studying resilience more comprehensively. The current study aimed to examine the role of these systems during a laboratory stress task and to determine the prediction power of resilience by combining psychological and biophysiological features. One hundred and seven (52 females) university students without psychiatric disorders underwent the Trier Social Stress Task (TSST). Psychometric properties of resilience were measured at rest; vagal heart rate variability (HRV), salivary cortisol, and dehydroepiandrosterone (DHEA) levels were captured at baseline, during, and after TSST. Multivariate linear regression as well as support vector regression machine-learning analyses were performed to investigate significant predictors and the prediction power of resilience. Results showed that positive and negative affects, HRV during the anticipatory phase of stress, and the ratio of cortisol/DHEA at the first recovery time point were significant predictors of resilience. The addition of biophysiological features increased the prediction power of resilience by 1.2-fold compared to psychological features alone. Results from machine learning analyses further demonstrated that the increased prediction power of resilience by adding the ratio of cortisol/DHEA was significant in "cortisol responders"; whereas a trend level was observed in "cortisol non-responders". Our findings extend the knowledge from the literature that high vagal activity during the anticipating phase of stress and the ability to restore the balance between cortisol and DHEA after a stress event could be an important feature in predicting resilience. Our findings also further support the need of combining psychological and biophysiological features in studying/predicting resilience.

A role of the lateral prefrontal cortex in the congruency sequence effect revealed by transcranial direct current stimulation.

Congruency effect is the increase in response time when relevant and irrelevant cues indicate incongruent rather than congruent responses. The congruency effect is smaller in the trial after an incongruent trial than after a congruent trial: this difference is known as the congruency sequence effect (CSE). Psychophysical and neural studies have suggested that the lateral prefrontal cortex (LPFC) and the medial prefrontal cortex are associated with the CSE. In the present study, we applied anodal and cathodal transcranial direct current stimulation, which is thought to result in excitation and inhibition, respectively, on the LPFC, while human participants were performing a flanker task. We found that the CSE was increased under cathodal stimulation (inhibition) of the LPFC. Moreover, the LPFC stimulation modulated the congruency effect after a congruent trial. Further analyses suggested that the results cannot be explained by any of the currently prevailing hypotheses of the CSE, including the conflict monitoring hypothesis, feature integration hypothesis, and temporal learning account. Based on our findings, we propose that a new distinct mechanism might be involved in the CSE. Specifically, the LPFC might contribute to the CSE by maintaining the attention to the task-relevant information, which is an endogenous goal-oriented function and reduces the carry-over of the task-irrelevant information after a congruent trial.

Autism spectrum disorder risk prediction: A systematic review of behavioral and neural investigations.

A reliable diagnosis of autism spectrum disorder (ASD) is difficult to make until after toddlerhood. Detection in an earlier age enables early intervention, which is typically more effective. Recent studies of the development of brain and behavior in infants and toddlers have provided important insights in the diagnosis of autism. This extensive review focuses on published studies of predicting the diagnosis of autism during infancy and toddlerhood younger than 3 years using behavioral and neuroimaging approaches. After screening a total of 782 papers, 17 neuroimaging and 43 behavioral studies were reviewed. The features for prediction consist of behavioral measures using screening tools, observational and experimental methods, brain volumetric measures, and neural functional activation and connectivity patterns. The classification approaches include logistic regression, linear discriminant function, decision trees, support vector machine, and deep learning based methods. Prediction performance has large variance across different studies. For behavioral studies, the sensitivity varies from 20% to 100%, and specificity ranges from 48% to 100%. The accuracy rates range from 61% to 94% in neuroimaging studies. Possible factors contributing to this inconsistency may be partially due to the heterogeneity of ASD, different targeted populations (i.e., high-risk group for ASD and general population), age when the features were collected, and validation procedures. The translation to clinical practice requires extensive further research including external validation with large sample size and optimized feature selection. The use of multi-modal features, e.g., combination of neuroimaging and behavior, is worth further investigation to improve the prediction accuracy.

ASPM-lexical tone association in speakers of a tone language: Direct evidence for the genetic-biasing hypothesis of language evolution.

How language has evolved into more than 7000 varieties today remains a question that puzzles linguists, anthropologists, and evolutionary scientists. The genetic-biasing hypothesis of language evolution postulates that genes and language features coevolve, such that a population that is genetically predisposed to perceiving a particular linguistic feature would tend to adopt that feature in their language. Statistical studies that correlated a large number of genetic variants and linguistic features not only generated this hypothesis but also specifically pinpointed a linkage between ASPM and lexical tone. However, there is currently no direct evidence for this association and, therefore, the hypothesis. In an experimental study, we provide evidence to link ASPM with lexical tone perception in a sample of over 400 speakers of a tone language. In addition to providing the first direct evidence for the genetic-biasing hypothesis, our results have implications for further studies of linguistic anthropology and language disorders.

Gut microbiome and brain functional connectivity in infants-a preliminary study focusing on the amygdala.

Recently, there has been a surge of interest in the possibility that microbial communities inhabiting the human gut could affect cognitive development and increase risk for mental illness via the "microbiome-gut-brain axis." Infancy likely represents a critical period for the establishment of these relationships, as it is the most dynamic stage of postnatal brain development and a key period in the maturation of the microbiome. Indeed, recent reports indicate that characteristics of the infant gut microbiome are associated with both temperament and cognitive performance. The neural circuits underlying these relationships have not yet been delineated. To address this gap, resting-state fMRI scans were acquired from 39 1-year-old human infants who had provided fecal samples for identification and relative quantification of bacterial taxa. Measures of alpha diversity were generated and tested for associations with measures of functional connectivity. Primary analyses focused on the amygdala as manipulation of the gut microbiota in animal models alters the structure and neurochemistry of this brain region. Secondary analyses explored functional connectivity of nine canonical resting-state functional networks. Alpha diversity was significantly associated with functional connectivity between the amygdala and thalamus and between the anterior cingulate cortex and anterior insula. These regions play an important role in processing/responding to threat. Alpha diversity was also associated with functional connectivity between the supplementary motor area (SMA, representing the sensorimotor network) and the inferior parietal lobule (IPL). Importantly, SMA-IPL connectivity also related to cognitive outcomes at 2 years of age, suggesting a potential pathway linking gut microbiome diversity and cognitive outcomes during infancy. These results provide exciting new insights into the gut-brain axis during early human development and should stimulate further studies into whether microbiome-associated changes in brain circuitry influence later risk for psychopathology.

The Neuroanatomical Basis of Two Subcomponents of Rumination: A VBM Study.

Rumination is a trait that includes two subcomponents, namely brooding and reflective pondering, respectively construed as maladaptive and adaptive response styles to negative experiences. Existing evidence indicates that rumination in general is associated with structural and functional differences in the anterior cingulate cortex (ACC) and the dorsal lateral prefrontal cortex (DLPFC). However, conclusive evidence on the specific neural structural basis of each of the two subcomponents is lacking. In this voxel-based morphometry study, we investigated the independent and specific neural structural basis of brooding and reflective pondering in 30 healthy young adults, who belonged to high or low brooding or reflective pondering groups. Consistent with past research, modest but significant positive correlation was found between brooding and reflective pondering. When controlling for reflective pondering, high-brooding group showed increased gray matter volumes in the left DLPFC and ACC. Further analysis on extracted gray matter values showed that gray matter of the same DLPFC and ACC regions also showed significant negative effects of reflective pondering. Taken together, our findings indicate that the two subcomponents of rumination might share some common processes yet also have distinct neural basis. In view of the significant roles of the left DLPFC and ACC in attention and self-related emotional processing/regulation, our findings provide insight into how the potentially shared and distinct cognitive, affective and neural processes of brooding and reflective pondering can be extended to clinical populations to further elucidate the neurobehavioral relationships between rumination and prefrontal abnormality.

Neurodevelopmental changes in the relationship between stress perception and prefrontal-amygdala functional circuitry.

Our brain during distinct developmental phases may show differential responses to perceived psychological stress, yet existing research specifically examining neurodevelopmental changes in stress processing is scarce. To fill in this research gap, this functional magnetic resonance imaging (fMRI) study examined the relationship between perceived stress and resting-state neural connectivity patterns among 67 healthy volunteers belonging to three age groups (adolescents, young adults and adults), who were supposed to be at separate neurodevelopmental phases and exhibit different affect regulatory processes in the brain. While the groups showed no significant difference in self-reported general perceived stress levels, the functional connectivity between amygdala and ventromedial prefrontal cortex (vmPFC) was positively and negatively correlated with perceived stress in adolescents and young adults respectively, while no significant correlations were observed in adults. Furthermore, among adolescents, the causal functional interaction between amygdala and vmPFC exhibited bottom-up connectivity, and that between amygdala and subgenual anterior cingulate cortex exhibited top-down connectivity, both of which changed to bilateral directions, i.e. both bottom-up and top-down connections, in both young adults and adults, supporting the notion that the amygdala and prefrontal cortical circuitries undergo functional reorganizations during brain development. These novel findings have important clinical implications in treating stress-related affective disorders in young individuals.

Illness, at-risk and resilience neural markers of early-stage bipolar disorder.

BACKGROUND: Current knowledge on objective and specific neural markers for bipolar risk and resilience-related processes is lacking, partly due to not subdividing high-risk individuals manifesting different levels of subclinical symptoms who possibly possess different levels of resilience. METHODS: We delineated grey matter markers for bipolar illness, genetic high risk (endophenotype) and resilience, through comparing across 42 young non-comorbid bipolar patients, 42 healthy controls, and 72 diagnosis-free, medication-naive high-genetic-risk individuals subdivided into a combined-high-risk group who additionally manifested bipolar risk-relevant subsyndromes (N = 38), and an asymptomatic high-risk group (N = 34). Complementary analyses assessed the additional predictive and classification values of grey matter markers beyond those of clinical scores, through using logistic regression and support vector machine analyses. RESULTS: Illness-related effects manifested as reduced grey matter volumes of bilateral temporal limbic-striatal and cerebellar regions, which significantly differentiated bipolar patients from healthy controls and improved clinical classification specificity by 20%. Reduced bilateral cerebellar grey matter volume emerged as a potential endophenotype and (along with parieto-occipital grey matter changes) separated combined-high-risk individuals from healthy and high-risk individuals, and increased clinical classification specificity by approximately 10% and 27%, respectively, while the relatively normalized cerebellar grey matter volumes in the high-risk sample may confer resilience. LIMITATIONS: The cross-validation procedure was not performed on an independent sample using independently-derived features. The BD group had different age and sex distributions than some other groups which may not be fully addressable statistically. CONCLUSIONS: Our framework can be applied in other measurement domains to derive complete profiles for bipolar patients and at-risk individuals, towards forming strategies for promoting resilience and preclinical intervention.

Infant Gut Microbiome Associated With Cognitive Development.

BACKGROUND: Studies in rodents provide compelling evidence that microorganisms inhabiting the gut influence neurodevelopment. In particular, experimental manipulations that alter intestinal microbiota impact exploratory and communicative behaviors and cognitive performance. In humans, the first years of life are a dynamic time in gut colonization and brain development, but little is known about the relationship between these two processes. METHODS: We tested whether microbial composition at 1 year of age is associated with cognitive outcomes using the Mullen Scales of Early Learning and with global and regional brain volumes using structural magnetic resonance imaging at 1 and 2 years of age. Fecal samples were collected from 89 typically developing 1-year-olds. 16S ribosomal RNA amplicon sequencing was used for identification and relative quantification of bacterial taxa. RESULTS: Cluster analysis identified 3 groups of infants defined by their bacterial composition. Mullen scores at 2 years of age differed significantly between clusters. In addition, higher alpha diversity was associated with lower scores on the overall composite score, visual reception scale, and expressive language scale at 2 years of age. Exploratory analyses of neuroimaging data suggest the gut microbiome has minimal effects on regional brain volumes at 1 and 2 years of age. CONCLUSIONS: This is the first study to demonstrate associations between the gut microbiota and cognition in human infants. As such, it represents an essential first step in translating animal data into the clinic.

Large-scale functional neural network correlates of response inhibition: an fMRI meta-analysis.

An influential hypothesis from the last decade proposed that regions within the right inferior frontal cortex of the human brain were dedicated to supporting response inhibition. There is growing evidence, however, to support an alternative model, which proposes that neural areas associated with specific inhibitory control tasks co-exist as common network mechanisms, supporting diverse cognitive processes. This meta-analysis of 225 studies comprising 323 experiments examined the common and distinct neural correlates of cognitive processes for response inhibition, namely interference resolution, action withholding, and action cancellation. Activation coordinates for each subcategory were extracted using multilevel kernel density analysis (MKDA). The extracted activity patterns were then mapped onto the brain functional network atlas to derive the common (i.e., process-general) and distinct (i.e., domain-oriented) neural network correlates of these processes. Independent of the task types, activation of the right hemispheric regions (inferior frontal gyrus, insula, median cingulate, and paracingulate gyri) and superior parietal gyrus was common across the cognitive processes studied. Mapping the activation patterns to a brain functional network atlas revealed that the fronto-parietal and ventral attention networks were the core neural systems that were commonly engaged in different processes of response inhibition. Subtraction analyses elucidated the distinct neural substrates of interference resolution, action withholding, and action cancellation, revealing stronger activation in the ventral attention network for interference resolution than action inhibition. On the other hand, action withholding/cancellation primarily engaged the fronto-striatal circuit. Overall, our results suggest that response inhibition is a multidimensional cognitive process involving multiple neural regions and networks for coordinating optimal performance. This finding has significant implications for the understanding and assessment of response inhibition.

Salience and default mode network dysregulation in chronic cocaine users predict treatment outcome.

While chronic cocaine use is associated with abnormalities in both brain structure and function within and interactions between regions, previous studies have been limited to interrogating structure and function independently, and the detected neural differences have not been applied to independent samples to assess the clinical relevance of results. We investigated consequences of structural differences on resting-state functional connectivity in cocaine addiction and tested whether resting-state functional connectivity of the identified circuits predict relapse in an independent cohort. Subjects included 64 non-treatment-seeking cocaine users (NTSCUs) and 67 healthy control subjects and an independent treatment-completed cohort (n = 45) of cocaine-dependent individuals scanned at the end of a 30-day residential treatment programme. Differences in cortical thickness and related resting-state functional connectivity between NTSCUs and healthy control subjects were identified. Survival analysis, applying cortical thickness of the identified regions, resting-state functional connectivity of the identified circuits and clinical characteristics to the treatment cohort, was used to predict relapse. Lower cortical thickness in bilateral insula and higher thickness in bilateral temporal pole were found in NTSCUs versus healthy control subjects. Whole brain resting-state functional connectivity analyses with these four different anatomical regions as seeds revealed eight weaker circuits including within the salience network (insula seeds) and between temporal pole and elements of the default mode network in NTSCUs. Applying these circuits and clinical characteristics to the independent cocaine-dependent treatment cohort, functional connectivity between right temporal pole and medial prefrontal cortex, combined with years of education, predicted relapse status at 150 days with 88% accuracy. Deficits in the salience network suggest an impaired ability to process physiologically salient events, while abnormalities in a temporal pole-medial prefrontal cortex circuit might speak to the social-emotional functional alterations in cocaine addiction. The involvement of the temporal pole-medial prefrontal cortex circuit in a model highly predictive of relapse highlights the importance of social-emotional functions in cocaine dependence, and provides a potential underlying neural target for therapeutic interventions, and for identifying those at high risk of relapse.

Structural and Maturational Covariance in Early Childhood Brain Development.

Brain structural covariance networks (SCNs) composed of regions with correlated variation are altered in neuropsychiatric disease and change with age. Little is known about the development of SCNs in early childhood, a period of rapid cortical growth. We investigated the development of structural and maturational covariance networks, including default, dorsal attention, primary visual and sensorimotor networks in a longitudinal population of 118 children after birth to 2 years old and compared them with intrinsic functional connectivity networks. We found that structural covariance of all networks exhibit strong correlations mostly limited to their seed regions. By Age 2, default and dorsal attention structural networks are much less distributed compared with their functional maps. The maturational covariance maps, however, revealed significant couplings in rates of change between distributed regions, which partially recapitulate their functional networks. The structural and maturational covariance of the primary visual and sensorimotor networks shows similar patterns to the corresponding functional networks. Results indicate that functional networks are in place prior to structural networks, that correlated structural patterns in adult may arise in part from coordinated cortical maturation, and that regional co-activation in functional networks may guide and refine the maturation of SCNs over childhood development.

Pons to Posterior Cingulate Functional Projections Predict Affective Processing Changes in the Elderly Following Eight Weeks of Meditation Training.

Evidence indicates meditation facilitates affective regulation and reduces negative affect. It also influences resting-state functional connectivity between affective networks and the posterior cingulate (PCC)/precuneus, regions critically implicated in self-referential processing. However, no longitudinal study employing active control group has examined the effect of meditation training on affective processing, PCC/precuneus connectivity, and their association. Here, we report that eight-week meditation, but not relaxation, training 'neutralized' affective processing of positive and negative stimuli in healthy elderly participants. Additionally, meditation versus relaxation training increased the positive connectivity between the PCC/precuneus and the pons, the direction of which was largely directed from the pons to the PCC/precuneus, as revealed by dynamic causal modeling. Further, changes in connectivity between the PCC/precuneus and pons predicted changes in affective processing after meditation training. These findings indicate meditation promotes self-referential affective regulation based on increased regulatory influence of the pons on PCC/precuneus, which new affective-processing strategy is employed across both resting state and when evaluating affective stimuli. Such insights have clinical implications on interventions on elderly individuals with affective disorders.