Developmental coupling of brain iron and intrinsic activity in infants during the first 150 days.

Brain iron is vital for core neurodevelopmental processes including myelination and neurotransmitter synthesis and, accordingly, iron accumulates in the brain with age. However, little is known about the association between brain iron and neural functioning and how they evolve with age in early infancy. This study investigated brain iron in 48 healthy infants (22 females) aged 64.00 ± 33.28 days by estimating R2 * relaxometry from multi-echo functional MRI (fMRI). Linked independent component analysis was performed to examine the association between iron deposition and spontaneous neural activity, as measured by the amplitude of low frequency fluctuations (ALFF) by interrogating shared component loadings across modalities. Further, findings were validated in an independent dataset (n = 45, 24 females, 77.93 ± 26.18 days). The analysis revealed developmental coupling between the global R2 * and ALFF within the default mode network (DMN). Furthermore, we observed that this coupling effect significantly increased with age (r = 0.78, p = 9.2e-11). Our results highlight the importance of iron-neural coupling during early development and suggest that the neural maturation of the DMN may correspond to growth in distributed brain iron.

Fetal Frontolimbic Connectivity Prospectively Associates With Aggression in Toddlers.

Background: Aggression is a major public health concern that emerges early in development and lacks optimized treatment, highlighting need for improved mechanistic understanding regarding the etiology of aggression. The present study leveraged fetal resting-state functional magnetic resonance imaging to identify candidate neurocircuitry for the onset of aggressive behaviors before symptom emergence. Methods: Pregnant mothers were recruited during the third trimester of pregnancy to complete a fetal resting-state functional magnetic resonance imaging scan. Mothers subsequently completed the Child Behavior Checklist to assess child aggression at 3 years postpartum (n = 79). Independent component analysis was used to define frontal and limbic regions of interest. Results: Child aggression was not related to within-network connectivity of subcortical limbic regions or within-medial prefrontal network connectivity in fetuses. However, weaker functional coupling between the subcortical limbic network and medial prefrontal network in fetuses was prospectively associated with greater maternal-rated child aggression at 3 years of age even after controlling for maternal emotion dysregulation and toddler language ability. We observed similar, but weaker, associations between fetal frontolimbic functional connectivity and toddler internalizing symptoms. Conclusions: Neural correlates of aggressive behavior may be detectable in utero, well before the onset of aggression symptoms. These preliminary results highlight frontolimbic connections as potential candidate neurocircuitry that should be further investigated in relation to the unfolding of child behavior and psychiatric risk.

Fetal behavior during MRI changes with age and relates to network dynamics.

Fetal motor behavior is an important clinical indicator of healthy development. However, our understanding of associations between fetal behavior and fetal brain development is limited. To fill this gap, this study introduced an approach to automatically and objectively classify long durations of fetal movement from a continuous four-dimensional functional magnetic resonance imaging (fMRI) data set, and paired behavior features with brain activity indicated by the fMRI time series. Twelve-minute fMRI scans were conducted in 120 normal fetuses. Postnatal motor function was evaluated at 7 and 36 months age. Fetal motor behavior was quantified by calculating the frame-wise displacement (FD) of fetal brains extracted by a deep-learning model along the whole time series. Analyzing only low motion data, we characterized the recurring coactivation patterns (CAPs) of the supplementary motor area (SMA). Results showed reduced motor activity with advancing gestational age (GA), likely due in part to loss of space (r = -.51, p < .001). Evaluation of individual variation in motor movement revealed a negative association between movement and the occurrence of coactivations within the left parietotemporal network, controlling for age and sex (p = .003). Further, we found that the occurrence of coactivations between the SMA to posterior brain regions, including visual cortex, was prospectively associated with postnatal motor function at 7 months (r = .43, p = .03). This is the first study to pair fetal movement and fMRI, highlighting potential for comparisons of fetal behavior and neural network development to enhance our understanding of fetal brain organization.

Empirical evaluation of human fetal fMRI preprocessing steps.

Increased study and methodological innovation have led to growth in the field of fetal brain fMRI. An important gap yet to be addressed is optimization of fetal fMRI preprocessing. Rapid developmental changes, imaged within the maternal compartment using an abdominal coil, introduce novel constraints that challenge established methods used in adult fMRI. This study evaluates the impact of (1) normalization to a group mean-age template versus normalization to an age-matched template; (2) independent components analysis (ICA) denoising at two criterion thresholds; and (3) smoothing using three kernel sizes. Data were collected from 121 fetuses (25-39 weeks, 43.8% female). Results indicate that the mean age template is superior in older fetuses, but less optimal in younger fetuses. ICA denoising at a more stringent threshold is superior to less stringent denoising. A larger smoothing kernel can enhance cross-hemisphere functional connectivity. Overall, this study provides improved understanding of the impact of specific steps on fetal image quality. Findings can be used to inform a common set of best practices for fetal fMRI preprocessing.

Effects of Levodopa Therapy on Cerebral Arteries and Perfusion in Parkinson's Disease Patients.

BACKGROUND: Levodopa is the most-commonly used therapy for Parkinson's Disease (PD). Imaging findings show increased cerebral blood flow (CBF) response to levodopa, but the artery morphological change is less studied. PURPOSE: To investigate the effect of levodopa on cerebral arteries and CBF. STUDY TYPE: Prospective. POPULATION: 57 PD patients (56 ± 10 years, 26 males) and 17 age-matched healthy controls (AMC, 57 ± 9 years, 9 males) were scanned at baseline (OFF). Patients were rescanned 50 minutes after taking levodopa (ON). FIELD STRENGTH AND SEQUENCE: 3 T; Simultaneous noncontrast angiography intraplaque imaging (SNAP) based on turbo field echo; Pseudo-continuous arterial spin labeling (PCASL) based on echo-planner imaging. ASSESSMENT: The Unified Parkinson's Disease Rating Scale (UPDRS-III) was used to assess the disease severity. Length and radius of arteries were measured from SNAP images. CBF was calculated from PCASL images globally and regionally. STATISTICAL TESTS: Mann Whitney U tests were conducted in comparing PD vs. AMC. Wilcoxon matched-pairs signed rank tests were used in comparing OFF vs. ON, and the more-affected vs. the less-affected hemisphere in PD. Linear regressions were performed to test the correlations of neuroimaging findings with behavioral changes. Significance threshold was P < 0.05 with Bonferroni correction. RESULTS: PD patients were identified with significantly lower CBF (PD OFF Mean = 40.15 ± 5.99, AMC Mean = 43.48 ± 6.21 mL/100 g/min) and shortened total artery length (PD OFF Mean = 5851.07 ± 1393.45, AMC Mean = 7479.16 ± 1335.93 mm). Levodopa elevated CBF of PD brains (PD ON Mean = 41.48 ± 6.32 mL/100 g/min) and expanded radius of proximal arteries. Artery radius change significantly correlated with CBF change in corresponding territories (r = 0.559 for Internal Carotid Arteries, r = 0.448 for Basilar Artery, and r = 0.464 for Middle Cerebral Artery M1). Global CBF significantly related to UPDRS-III (r = -0.391) post-levodopa. DATA CONCLUSION: Levodopa can increase CBF by dilating proximal arteries. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 4.

Central functional reorganization and recovery following facial-hypoglossal neurorrhaphy for facial paralysis.

OBJECTIVE: Functional deficits induced by nerve injuries can be restored by achieving effective reinnervation of the denervated targets and functional reorganization of the central nervous system after nerve reconstruction. In this study, we investigated the effect and extent of cortical functional reorganization related to the ability of transferred hypoglossal neurons to restore facial function in facial paralysis patients after a surgical bridge of neurorrhaphy ectopically between the ipsilateral hypoglossal nerve and injured facial nerve. METHODS: We treated 23 patients (35.4 ± 10.3 years, 10 males) and followed them up for 2.9 ± 0.61 years. We used motor-task-related functional magnetic resonance imaging to map activation change at multiple time points before and after neurorrhaphy; 20 normal subjects were included as control. RESULTS: All patients regained facial function to some extent after neurorrhaphy. Enhanced activation in motor-related cortices gradually returned to normal levels and was positively correlated with regained facial function. The related cortical functional areas included the left middle temporal gyrus, left inferior frontal gyrus, insula, bilateral motor cortex and the supplementary motor area extending to the paracingulate involved in intensive eye closing, as well as the left superior temporal gyrus, right putamen and the bilateral motor cortex involved in lip pursing. Intriguingly, significant correlations were found between the pre-surgery activation while intensive eye closing in bilateral motor cortex and recovery of facial nerve function induced by the neurorrhaphy treatment. CONCLUSION: This is the first study mapping activation change in motor cortices at multiple time points before and after repair of the facial nerve. The cortex functional reorganization found may suggest potential treatment targets in the central nervous system for adjuvant therapies such as repetitive transcranial magnetic stimulation to further improve functional recovery.

Effects of physical exercise on the aging brain across imaging modalities: A meta-analysis of neuroimaging studies in randomized controlled trials.

BACKGROUND: Physical exercise is effective in protecting against age-related neurodegeneration and cognitive decline. Although there are many neuroimaging studies to evaluate the effect of physical exercise on aging brains, consistent conclusions are limited due to the wide variety of measuring techniques and small sample sizes. OBJECTIVE: Identify brain regions that show exercise-induced neuroplasticity consistently across various imaging modalities and correlate regional neuroplasticity with cognitive changes in older adults. METHODS: An electronic literature search for randomized controlled trials with magnetic resonance imaging measures was performed. We conducted a series of quantitative meta-analyses using activation likelihood estimation on included studies with voxel-based neuroimaging findings. Nonvoxelbased findings were summarized as a descriptive review. RESULTS: Out of 839 publications identified from the literature search, 30 experiments including 2670 participants from 22 papers met the criteria of meta-analyses. Overall, physical exercise consistently results in structural and functional changes in the hippocampus/parahippocampusl area and a cluster within the cerebellum. Although changes of medial/superior prefrontal cortex did not pass the stringent threshold, they were associated with cognitive changes. CONCLUSIONS: This study highlights the effectiveness of physical exercise in inducing hippocampus plasticity, which may be crucially relevant for maintaining memory function in older adults.

Characterizing functional regional homogeneity (ReHo) as a B-SNIP psychosis biomarker using traditional and machine learning approaches.

BACKGROUND: Recently, a biologically-driven psychosis classification (B-SNIP Biotypes) was derived using brain-based cognitive and electrophysiological markers. Here, we characterized a local functional-connectivity measure, regional homogeneity (ReHo), as a biomarker across Biotypes and conventional DSM diagnoses. METHODS: Whole-brain ReHo measures of resting-state functional MRI were examined in psychosis patients and healthy controls organized by Biotype and by DSM-IV-TR diagnosis (n = 737). Group-level ANOVA and individual-level prediction models using support vector machines (SVM) were employed to evaluate the discriminative characteristics in comparisons of 1) DSM diagnostic groups, 2) Biotypes, to controls, and 3) within-proband subgroups with each other. RESULTS: Probands grouped by Biotype versus controls showed a unique abnormality pattern: Biotype-1 displayed bidirectional ReHo differences in more widespread areas, with higher ReHo in para-hippocampus, fusiform, inferior temporal, cerebellum, thalamus and caudate, plus lower ReHo in the postcentral gyrus, middle temporal, cuneus, and middle occipital cortex; Biotype-2 and Biotype-3 showed lesser and unidirectional ReHo changes. Among diagnostic groups, only schizophrenia showed higher ReHo versus control values in the inferior/middle temporal area and fusiform gyrus. For within-patient comparisons, Biotype-1 showed characteristic ReHo when compared to Biotype-2 and Biotype-3. SVM results more accurately identified Biotypes than DSM diagnoses. CONCLUSION: We characterized patterns of ReHo abnormalities across both Biotypes and DSM sub-groups. Both group-level statistical and machine-learning methods were more sensitive in capturing ReHo deficits in Biotypes than DSM. Overall ReHo is a robust psychosis biomarker.

Suicidal ideation and attempted suicide amongst Chinese transgender persons: National population study.

BACKGROUND: This study aims to understand suicidal ideation and suicide attempts among transgender individuals through an in-depth analysis of a nation-wide population general survey in China. METHODS: Transgender Men (TM) and Women (TW) were investigated through a cross-sectional survey. A structured questionnaire was used to investigate participants' demographic information, perceived sexuality conflicts, childhood adversity and mental health conditions. Logistic regression models were utilized to investigate risk factors associated with suicidal ideation and suicide attempts in these groups. We also conducted a quasi-meta-analysis in order to compare the prevalence of suicidal ideation and attempted suicide between general and transgender populations in China. RESULTS: A total of 1309 participants across 32 provinces and municipalities in China took part in this survey, out of 2060 valid questionnaires. In this transgender population, the lifetime prevalence of suicidal ideation and an attempt at suicide were 56.4% and 16.1%, respectively. This estimated prevalence rate is far greater than in Chinese community samples. For all transgender people, disliking birth-assigned sex, seeking sex reassignment surgery, having intense conflicts with parents, lifetime history of suffering from major depressive disorder, a recent episode of depression, self-harm, and seeking mental health services were significantly associated with increased risk of suicidal ideation. An education level of high school or equivalent, being married and/or separated/divorced, having intense conflicts with parents, or self-harm and seeking mental health services were all significantly associated with increased risk of suicide attempt. Although most risk factors for TM and TW were equivalent across groups, differences were observed in both suicidal ideation and suicide attempt models. LIMITATIONS: The cross-sectional study design and lack of follow-up data are limitations of this study. CONCLUSIONS: This is the first study to examine suicide within a Chinese transgender population. The clinical implications of these findings for Chinese mental health professionals are discussed. Also, the evidence from this study can be used to inform the practices of suicide prevention workers, and policy makers working with the transgender population.

Physical exercise increases involvement of motor networks as a compensatory mechanism during a cognitively challenging task.

OBJECTIVE: Neuroimaging studies suggest that older adults may compensate for declines in cognitive function through neural compensation and reorganization of neural resources. While neural compensation as a key component of cognitive reserve is an important factor that mediates cognitive decline, the field lacks a quantitative measure of neural compensatory ability, and little is known about factors that may modify compensation, such as physical exercise. METHODS: Twenty-five healthy older adults participated in a 6-week dance training exercise program. Gait speed, cognitive function, and functional magnetic resonance imaging during a challenging memory task were measured before and after the exercise program. In this study, we used a newly proposed data-driven independent component analysis approach to measure neural compensatory ability and tested the effect of physical exercise on neural compensation through a longitudinal study. RESULTS: After the exercise program, participants showed significantly improved memory performance in Logical Memory Test (WMS(LM)) (P < .001) and Rey Auditory Verbal Learning Test (P = .001) and increased gait speed measured by the 6-minute walking test (P = .01). Among all identified neural networks, only the motor cortices and cerebellum showed greater involvement during the memory task after exercise. Importantly, subjects who activated the motor network only after exercise (but not before exercise) showed WMS(LM) increases. CONCLUSIONS: We conclude that physical exercise improved gait speed, cognitive function, and compensatory ability through increased involvement of motor-related networks.

A New Measure for Neural Compensation Is Positively Correlated With Working Memory and Gait Speed.

Neuroimaging studies suggest that older adults may compensate for declines in brain function and cognition through reorganization of neural resources. A limitation of prior research is reliance on between-group comparisons of neural activation (e.g., younger vs. older), which cannot be used to assess compensatory ability quantitatively. It is also unclear about the relationship between compensatory ability with cognitive function or how other factors such as physical exercise modulates compensatory ability. Here, we proposed a data-driven method to semi-quantitatively measure neural compensation under a challenging cognitive task, and we then explored connections between neural compensation to cognitive engagement and cognitive reserve (CR). Functional and structural magnetic resonance imaging scans were acquired for 26 healthy older adults during a face-name memory task. Spatial independent component analysis (ICA) identified visual, attentional and left executive as core networks. Results show that the smaller the volumes of the gray matter (GM) structures within core networks, the more networks were needed to conduct the task (r = -0.408, p = 0.035). Therefore, the number of task-activated networks controlling for the GM volume within core networks was defined as a measure of neural compensatory ability. We found that compensatory ability correlated with working memory performance (r = 0.528, p = 0.035). Among subjects with good memory task performance, those with higher CR used fewer networks than subjects with lower CR. Among poor-performance subjects, those using more networks had higher CR. Our results indicated that using a high cognitive-demanding task to measure the number of activated neural networks could be a useful and sensitive measure of neural compensation in older adults.

Multiple Neuroimaging Measures for Examining Exercise-induced Neuroplasticity in Older Adults: A Quasi-experimental Study.

Physical exercise can improve physical and mental health. A number of imaging studies have examined the role of neuroplasticity in improving cognition with physical exercise; however, such neuroplasticity changes are not consistent across the reports partly due to small sample sizes in some studies. We thought to explore the concept that identifying consistent findings across multi-modality imaging measures would provide relatively reliable results. We designed a 6-week quasi-experiment with Wii-fitness exercise program in 24 healthy adults older than 60, and then examined the changes on neuroimaging measures including brain volume, the amplitude of low-frequency oscillation function (ALFF), regional homogeneity (ReHo), seed-based functional connectivity (FC), and the global efficiency of nodal connectivity during resting state. We focused on whether there were common regions showing changes after exercise across these measures and which measure was closely correlated with cognitive improvement. After the six-week exercise program, participants demonstrated a significant improvement in memory and executive function on neuropsychological tests, and in memory recall on an emotional memory task. The common brain regions that showed significant changes across different measures were the right striatum and the posterior cingulate (PCC). After exercise, the PCC showed decreased ReHo and increased volume, and the striatum did not show volume loss as the control group did and increased its FC with the cingulate, temporal, parietal, and occipital regions. Moreover, the connectivity change between the striatum and the thalamus was correlated with the improvement of executive function. This result implicates the striatum and the PCC associated network in physical exercise. Our work highlights the effectiveness of multi-modality neuroimaging measures in investigating neuroplasticity.

Identification of the major constituents in Xuebijing injection by HPLC-ESI-MS.

INTRODUCTION: Xuebijing injection (XBJ) is a traditional Chinese herbal prescription widely used in the treatment of sepsis. This is the first report concerning the identification of XBJ constituents. In addition, to evaluate XBJ's quality, partial least square discrimination analysis (PLS-DA) was performed on chemical fingerprint data. OBJECTIVE: Establish an LC-MS method to identify the components in XBJ for the purpose of quality control. METHODOLOGY: Compounds were separated by HPLC using a C(18) column and gradient elution of acetonitrile-methanol (60:40, v/v) and water-acetic acid (100 : 0.5, v/v) in 80 min. HPLC equipped with diode array detector (DAD) coupled with time-of-flight (TOF) tandem mass spectrometry and HPLC electrospray ionisation (ESI) multi-stage tandem ion-trap mass spectrometry (IT-MS(n) ) method was developed to analyse XBJ's major components. Both positive and negative ionisation modes were employed. RESULTS: Twenty-one compounds including amino acids, phenolic acids, flavonoid glycoside, terpene glycoside and phthalide were identified or tentatively characterised. Their retention times, UV and MS spectra were compared with those of authentic compounds or literature data. The score plot of PLS-DA clearly revealed variations among samples produced in different commercial batches. CONCLUSIONS: The analytical method developed is highly effective for the discrimination and quality control of XBJ.

[Simultaneous HPLC determination of 11 essential compounds in Xuebijing injection].

OBJECTIVE: To establish a HPLC method for the determination of 11 essential compounds in Xuebijing injection. METHOD: Chromatogaphic analysis was performed on Aglient Zorbax SB-C18 (4.6 mm x 250 mm, 5 microm). The mobile phase 0. 5% acetic acid and methanol-acetonitrile-acetic acid (40: 60: 0.5). The flow rate was 1.0 mL x min(-1) with the detection wavelength at 280 nm; column temperature at 35 degrees C, and automatic sampling volume of 20 microL. RESULT: All the 11 essential compounds showed good linearity (r = 0.9982-0.9999)in the range of the tests concentration. The RSD of the precision, reproducibility and stability tests were less than 3%; the average recoveries of the method were in the range of 95.02%-104.94%. CONCLUSION: The method is simple, rapid and accurate, so it is proposed for the quality control of compounds of Xuebijing injection.