Toward discovery science of human brain function.

Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.

The cognitive dysfunction of claustrum on Alzheimer's disease: A mini-review.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases characterized by cognitive deficits and dementia. AD entails predominant pathological characteristics including amyloid beta (Aß) plaque formation, neurofibrillary entanglements, and brain atrophy, which gradually result in cognitive dysfunctions. Studies showed that these pathological changes are found in a myriad of brain structures, including the claustrum (CLA), a nucleus that penetrates deeply into the brain and is extensively interconnected to various brain structures. The CLA modulates many aspects of cognitive functions, with attention, executive function, visuospatial ability, language, and memory in particular. It is also implicated in multiple neuropsychiatric disorders, of which one worthy of particular attention is AD-related cognitive impairments. To inspire novel AD treatment strategies, this review has summarized the CLA functionality in discriminative cognitive dysfunctions in AD. And then propose an array of potential mechanisms that might contribute to the cognitive impairments caused by an abnormal CLA physiology. We advocate that the CLA might be a new promising therapeutic target in combination with existing anti-AD drugs and brain stimulation approaches for future AD treatment.

[Study of functional magnetic resonance imaging repeatability of linguistic-functional cortex].

OBJECTIVE: To explore the reproducibility and stability of brain functional area in the response of language tasks during Chinese word processing with functional magnetic resonance imaging (fMRI) by follow-up scanning so as to provide rationales for clinical preoperative localization and the mechanisms of recovery from aphasia. METHODS: The fMRI data were collected by scanning semantic and phonologic judgments in 15 healthy volunteers. Each subject was scanned twice by the same fMRI procedure of both language tasks with an interval of 1 month. By analyzing the effective overlapping average activation maps, the reproducibility of inter-subject imaging result for two language tasks were estimated by selecting the main language areas, such as Broca's area and Wernicke's area as the region of interest (ROI). By individually calculating the spatial distance of ROI centroid coordinates in the same activating range before and after test, the inter-subject stability in between-session was calculated quantitatively. RESULTS: Both language tasks activated more than one language-related brain areas in cerebral hemispheres. Both language tasks induced significant BOLD response in Broca's and Wernicke's areas with a tendency of left lateralization. The number of subjects in terms of the activation of both language tasks in Broca's and Wernicke's areas accounted over a half of the total subjects. As compared with the phonologic judgment task, the semantic judgment task showed better reproducibility in Broca's area. In the same spatial distance of ROI centroid coordinates, the stability of Broca's area was higher than that of Wernicke's area while the stability of semantic judgment in Broca's area higher than that of phonologic judgment. CONCLUSION: Such main language domains as Broca's and Wernicke's areas can be effectively activated by both semantic and phonologic judgments. By comparison, semantic judgment in Broca's area shows a higher level of reproducibility and stability. Thus it is applicable for clinical preoperative localization and the mechanisms of recovery from aphasia.

Prevalence of developmental dyslexia in primary school children: a protocol for systematic review and meta-analysis.

BACKGROUND: Developmental dyslexia (DD) is a specific impairment during the acquisition of reading skills and may have a lifelong negative impact on individuals. Reliable estimates of the prevalence of DD serve as the basis for evidence-based health resource allocation and policy making. However, the prevalence of DD in primary school children varies largely across studies. Moreover, it is unclear whether there are differences in prevalence in different genders and writing systems. Hence, the present study aims to conduct a systematic review and meta-analysis to assess the global prevalence of DD and to explore related factors. METHODS: We will undertake a comprehensive literature search in 14 databases, including EMBASE, PubMed, Web of Science, China National Knowledge Infrastructure and Cochrane, from their inception to June 2021. Cross-sectional and longitudinal studies that describe the prevalence of DD will be eligible. The quality of the included observational studies will be assessed using the Strengthening the Reporting of Observational Studies in Epidemiology statement. The risk of bias will be determined by sensitivity analysis to identify publication bias. RESULTS: One meta-analysis will be conducted to estimate the prevalence of DD in primary school children. Heterogeneity will be assessed in terms of the properties of subjects (e.g., gender, grade and writing system) and method of diagnosis in the included primary studies. Subgroup analyses will also be performed for population and secondary outcomes. CONCLUSION: The results will synthesize the prevalence of DD and provide information for policy-makers and public health specialists.

Similar brain activation patterns for writing logographic and phonetic symbols in Chinese.

This event-related functional MRI study examined the neural correlates for Chinese writing, by comparing the writing of logographic characters and that of pinyin, a phonetic notation system for Chinese characters. The temporal profile of the activations indicated that the middle frontal gyrus, superior parietal lobule, and posterior inferior temporal gyrus reflected more central processes for writing. Although pinyin writing elicited greater activity overall than character writing, the critical finding is that the two types of symbols recruited essentially the same brain regions. The results were compared with studies in Japanese showing dissociation between logographic kanji and phonetic kana writing and frequency of use was suggested to be an important factor in accounting for result differences across the two writing systems.

fMRI study of pain reaction in the brain under state of "Qigong".

In this study, 4 male Qigong masters (aged 60 +/- 12) who had Qigong practicing experience for more than 30 years were tested. By using the technique of fMRI, the change of brain function under the state of Qigong was observed through the peripheral pain stimulation generated by potassium penetrating method. The fMRI examination was running on a GE signa VH/3.0 T MRI machine and block design was used. The test was repeated several times, which was carried out before and 15 min after Qigong practicing. The heart and respiration rate of these 4 Qigong masters were monitored during the whole test. SPM2 was used for the data analysis, and the result showed that before Qigong practicing, besides SI and SII-insula regions, many other Brodmann areas, the cigulate cortex, the thalamus, and the cerebellum were all activated, while 15 min after that, the activated areas were decreased obviously, which were mainly at the SII-insula region and some other Brodmann areas. Since the SII-insula region was activated in both of these two states, further analysis of the response curve was focused on it. Its response amplitude under the state of Qigong (3.5%) was greater than that before Qigong (1.2%). Our result indicated that the main manifestation of brain functional change under Qigong was functional suppressing, but in some particular regions such as SII-insula region in our study, the response amplitude was increased. Further study of the exact physiological mechanism of Qigong is needed.

[Functional magnetic resonance imaging of whole brain related to motor preparation and execution].

OBJECTIVE: To investigate the roles the different functional activation areas in whole human brain related to movement play during motor preparation (CUE) and execution (GO). METHODS: Event-related functional MRI technique was used on 12 right-handed healthy subjects to record the brain activation in a manner of delayed sequential finger movement. Activation maps and time-signal intensity curves were generated. RESULTS: Bilateral anterior parts of supplementary motor area (Pre-SMA), bilateral posterior parietal cortex (PPC), and bilateral anterior premotor cortex (PMC) were strongly activated during the preparation period, while bilateral SMA proper, and contralateral primary motor cortex (M1) were strongly activated during the execution period, Cerebellar cortex was activated during both periods. The time-signal intensity curves based on single voxel indicated that above-mentioned brain areas were activated during both periods to different degrees; however, the characteristics of distribution in every area were different. CONCLUSION: The brain areas related to movement are activated differently during preparation period and execution period, areas close to M1 participate in the motor execution process mainly, and the areas away from M1 are concerned with motor preparation process chiefly.

[Study of paroxysmal kinesigenic dyskinesia with fMRI].

OBJECTIVE: To detect the differences in subcortical structures between patients with paroxysmal kinesigenic dyskinesia (PKD) and normal subjects during movement preparation and execution. METHODS: The PKD patients performed a movement task, in which a CUE signal (preparation) indicated the movement sequence prior to the appearance of an imperative GO signal (execution). Event-related functional magnetic resonance imaging (fMRI) and 3dDeconvolve program of AFNI were used to estimate the hemodynamic response function and to generate activation maps. RESULT: During movement preparation, the activated brain areas in PKD patients were less than those of normal subject, and there was no activation in basal ganglia in PKD patients. During execution, the activation was also less in PKD patients except in bilateral M1. CONCLUSION: During intermission, abnormalities of the brain still exist in PKD patients when during preparing or performing movement. The movement circuit in the brain displays an unusual state. The attack may be caused by reducing of inhibition in brain areas.

Neural activity associated with cognitive regulation in heroin users: A fMRI study.

Previous research has found heroin addicts to be impulsive. This study employed functional magnetic resonance imaging technology to investigate the differences between heroin addicts and normal controls in neural activity associated with cognitive regulation of behavior. Twenty-one Chinese men participated in this study, 11 of whom were newly admitted heroin-addicted patients and 10 of whom were healthy volunteers. In the experimental task, the subjects were required to first identify the correct directions of arrowheads and then give the opposite answers. Behaviorally, the heroin-dependent patients took a much shorter time to complete the more demanding second part of the task but committed more errors than the normal controls. This pattern of behavior, characteristic of people who are disinhibited and who tend to be impulsive, was consistent with previous reports of impulsivity observed in people who have abused heroin. The neural activity of the patients that was associated with performing the experimental task of cognitive regulation was different to that of the normal controls in terms of the pattern of prefrontal activation, the attenuation of activity in the anterior cingulate, and the additional recruitment of the right inferior parietal region. This study is the first that seeks to understand the neural activity associated with impulsive behavior in people who abuse heroin. The pattern of imaging data obtained resembled the pattern of data observed in immature brains attempting to exercise cognitive control of behavior. Further theoretical and clinical implications of the findings are discussed.

Functional MRI in attention-deficit hyperactivity disorder: evidence for hypofrontality.

Using event-related functional magnetic resonance imaging to study the Stroop effect on both behavioral and brain activation of ADHD children off or on methylphenidate (MPH). Nine ADHD boys (aged 9.8-14.5 years) and 9 age-matched normal controls were included. A Stroop-like paradigm was used. AFNI (Analysis of Functional NeuroImaging) and its Deconvolution Analysis were used in a descriptive comparison between ADHD and control groups. (1) Both behavioral reaction time and brain activation showed Stroop effect in controls but neither was found in ADHD children off MPH. When MPH was administered, the Stroop effect tended to appear. (2) The activation volume (AV) of prefrontal cortex (PFC) in both the neutral (NC) and interference conditions (IC) in ADHD children off MPH was smaller than in controls. AV of anterior cingulate cortex in the IC in ADHD children off MPH was smaller than that in controls, but was similar in the NC to that in controls. AV of the basal ganglia, insula and cerebellum was also smaller in the IC, but was larger in the NC for ADHD children off MPH compared with controls. These findings are consistent with prior findings of hypofrontality in ADHD children and implicate a compensatory network including basal ganglia, insula and cerebellum for relative lower cognitive load tasks.

[Heterogeneity of aging brain: a preliminary comparative study of functional magnetic resonance imaging in elderly people].

OBJECTIVE: To explore the heterogeneity of aging brain. METHODS: Blood oxygenation level dependent functional magnetic resonance imaging was performed on 10 subjects meeting the standards of successful aging (SA), 9 subjects meeting the standards of usual aging (UA), and 9 subjects meeting the criteria of mild cognitive impairment (MCI), all age, and sex-matched, under stimulation of verbal fluent test (VFT). The activation level of different regions of interest (ROI), laterality index, and the activation level of occipital lobe were analyzed. RESULTS: The achievement in VFT of the SA group was greater than that of the UA group, and much greater than that of the MCI group with significant differences between any 2 groups (all P < 0.05) except in the task of "names of vegetables". The activation volume of the SA group was greater than that of the UA group, and much greater than that of the MCI group. The main activated regions of the SA and UA groups included left precuneus, anterior cingulate gyrus, middle frontal gyrus, superior frontal gyrus and inferior parietal lobule, and bilateral occipital lobes. The main activated regions of the MCI group included the bilateral prefrontal lobe. The intensity of activation was not significantly different between the SA and UA groups, however, was significantly different between the SA and MCI groups and between the UA and MCI groups. The laterality index (LI) was 0.46 in the SA group, significantly higher than those of the UA group (-0.12) and MCI group (-0.06) (both P < 0.01), however, without a significant difference between the UA group and MCI group. The activation of left prefrontal lobe in the SA group was more obvious than that in the UA group, and much more obvious than that in the MCI group with a significant difference between the UA and MCI groups as well (all P < 0.01). The activation volume of the left dorsal lateral prefrontal cortex (DLPFC) in the SA group was 787 voxels, significantly greater than that in the UA group (292 voxels) and MCI group (0 voxel) (all P < 0.01). CONCLUSION: Heterogeneity exists in the course of aging, associated with complicated brain mechanism. The activation level of DLPFC and LI may be used as sensitive indexes in evaluation of the brain function of the elderly.

[Functional MRI of human brain in musicians and non-musicians].

OBJECTIVE: To explore the differences in brain activation between musicians and non-musicians by use of functional MRI. METHODS: Twelve right-handed musicians and twelve right-handed non-musicians were recruited in the study. During a listening task, they were scanned on the Sigma 1.5T scanner (GE) while they were passively listening to several segments of music of "the Butterfly Love" and the white noise with same physical energy. RESULT: Both musicians and non-musicians demonstrated bilateral transverse gyrus weak activated while listening to the white noise. But when listening to music, they showed bilateral temporal areas strongly activated including superior temporal gyrus, transverse gyrus and some middle temporal areas. Moreover, musicians showed relative left dominance (10/12), whereas non-musicians demonstrated right dominance(11/12). Furthermore,besides bilateral temporal areas, more and stronger activated areas were found in musicians such as cuneus, precuneus,medial frontal and left middle occipital gyrus. CONCLUSION: There are different neuro-patterns between musicians and non-musicians.

[Lateralized distribution of motor areas involved in voluntary movement].

OBJECTIVE: To investigate the brain functional laterality in motor areas during motor execution systematically. METHODS: Functional magnetic resonance imaging (fMRI) was employed combined with right hand sequential finger movement task to investigate brain activation pattern and laterality in 8 right-handed subjects. 3dDeconvolve program of AFNI was used to estimate the hemodynamic response function and to generate activation maps. Then the laterality index (LI) was calculated and tested statistically. RESULT: All motor areas including the areas which were previously considered to be engage in movement preparation only were activated in movement execution. In the activation map, it appeared left lateralization in cerebra and right lateralization in cerebella. After further statistical test, it was found that in primary motor area (M1), supplementary motor area (SMA) and posterior parietal cortex (PPC), there were left lateralization. While in premotor cortex (PMC), cingulate gyrus and basal ganglia (BG), the lateralization tendency was not obvious. The activation in cerebella is characterized with right lateralization. CONCLUSION: Though there are tiny differences among subjects, most of the motor areas appear lateralized activation. Past studies only observed laterality in several motor areas. It may be due to the difficulty of the task or the experimental design.

Individual Variability and Test-Retest Reliability Revealed by Ten Repeated Resting-State Brain Scans over One Month.

Individual differences in mind and behavior are believed to reflect the functional variability of the human brain. Due to the lack of a large-scale longitudinal dataset, the full landscape of variability within and between individual functional connectomes is largely unknown. We collected 300 resting-state functional magnetic resonance imaging (rfMRI) datasets from 30 healthy participants who were scanned every three days for one month. With these data, both intra- and inter-individual variability of six common rfMRI metrics, as well as their test-retest reliability, were estimated across multiple spatial scales. Global metrics were more dynamic than local regional metrics. Cognitive components involving working memory, inhibition, attention, language and related neural networks exhibited high intra-individual variability. In contrast, inter-individual variability demonstrated a more complex picture across the multiple scales of metrics. Limbic, default, frontoparietal and visual networks and their related cognitive components were more differentiable than somatomotor and attention networks across the participants. Analyzing both intra- and inter-individual variability revealed a set of high-resolution maps on test-retest reliability of the multi-scale connectomic metrics. These findings represent the first collection of individual differences in multi-scale and multi-metric characterization of the human functional connectomes in-vivo, serving as normal references for the field to guide the use of common functional metrics in rfMRI-based applications.

Continuous representation of human portraits and natural scenery in human ventral temporal cortex: evidence from functional magnetic resonance imaging.

BACKGROUND: Functional magnetic resonance imaging (fMRI) has become a powerful tool for tracking human brain activity in vivo. This technique is mainly based on blood oxygenation level dependence (BOLD) contrast. In the present study, we employed this newly developed technique to characterize the neural representations of human portraits and natural sceneries in the human brain. METHODS: Nine subjects were scanned with a 1.5 T magnetic resonance imaging (MRI) scanner using gradient-recalled echo and echo-planar imaging (GRE-EPI) pulse sequence while they were visually presented with 3 types of white-black photographs: natural scenery, human portraits, and scrambled nonsense pictures. Multiple linear regression was used to identify brain regions responding preferentially to each type of stimulus and common regions for both human portraits and natural scenery. The relative contributions of each type of stimulus to activation in these regions were examined using linear combinations of a general linear test. RESULTS: Multiple linear regression analysis revealed two distinct but adjacent regions in both sides of the ventral temporal cortex. The medial region preferentially responded to natural scenery, whereas the lateral one preferentially responded to the human portraits. The general linear test further revealed a distribution gradient such that a change from portraits to scenes shifted areas of activation from lateral to medial. CONCLUSIONS: The boundary between portrait-associated and scenery-associated areas is not as clear as previously demonstrated. The representations of portraits and scenes in ventral temporal cortex appear to be continuous and overlap.

Cortical language activation in aphasia: a functional MRI study.

BACKGROUND: Functional neuroimaging has been used in neurolinguistic research on normal subjects and on patients with brain damage. This study was designed to investigate the differences of the neural basis underlying language processing between normal subjects and aphasics. METHODS: Functional magnetic resonance imaging (fMRI) was used to map the language network in 6 normal subjects and 3 patients with aphasia who were in the stage of recovery from acute stroke. The participants performed a word generation task during multi-slice functional scanning for the measurement of signal change associated with regional neural activity induced by the task. RESULTS: In normal subjects, a distributed language network was activated. Activations were present in the frontal, temporal, parietal and occipital regions. In the patient group, however, no activation was detected in the left inferior frontal gyrus whether the patient had a lesion in the left frontal lobe or not. Two patients showed activations in some right hemisphere regions where no activation appeared in normal subjects. CONCLUSIONS: fMRI with word generation task is feasible for evaluating language function in aphasic patients. Remote effect of focal lesion and functional redistribution or reorganisation can be found in aphasic patients.

Different neural manifestations of two slow frequency bands in resting functional magnetic resonance imaging: a systemic survey at regional, interregional, and network levels.

Temporal and spectral perspectives are two fundamental facets in deciphering fluctuating signals. In resting state, the dynamics of blood oxygen level-dependent (BOLD) signals recorded by functional magnetic resonance imaging (fMRI) have been proven to be strikingly informative (0.01-0.1 Hz). The distinction between slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz) has been described, but the pertinent data have never been systematically investigated. This study used fMRI to measure spontaneous brain activity and to explore the different spectral characteristics of slow-4 and slow-5 at regional, interregional, and network levels, respectively assessed by regional homogeneity (ReHo) and mean amplitude of low-frequency fluctuation (mALFF), functional connectivity (FC) patterns, and graph theory. Results of paired t-tests supported/replicated recent research dividing low-frequency BOLD fluctuation into slow-4 and slow-5 for ReHo and mALFF. Interregional analyses showed that for brain regions reaching statistical significance, FC strengths at slow-4 were always weaker than those at slow-5. Community detection algorithm was applied to FC data and unveiled two modules sensitive to frequency effects: one comprised sensorimotor structure, and the other encompassed limbic/paralimbic system. Graph theoretical analysis verified that slow-4 and slow-5 differed in local segregation measures. Although the manifestation of frequency differences seemed complicated, the associated brain regions can be grossly categorized into limbic/paralimbic, midline, and sensorimotor systems. Our results suggest that future resting fMRI research addressing the three above systems either from neuropsychiatric or psychological perspectives may consider using spectrum-specific analytical strategies.

Developmental changes in the role of different metalinguistic awareness skills in Chinese reading acquisition from preschool to third grade.

The present study investigated the relationship between Chinese reading skills and metalinguistic awareness skills such as phonological, morphological, and orthographic awareness for 101 Preschool, 94 Grade-1, 98 Grade-2, and 98 Grade-3 children from two primary schools in Mainland China. The aim of the study was to examine how each of these metalinguistic awareness skills would exert their influence on the success of reading in Chinese with age. The results showed that all three metalinguistic awareness skills significantly predicted reading success. It further revealed that orthographic awareness played a dominant role in the early stages of reading acquisition, and its influence decreased with age, while the opposite was true for the contribution of morphological awareness. The results were in stark contrast with studies in English, where phonological awareness is typically shown as the single most potent metalinguistic awareness factor in literacy acquisition. In order to account for the current data, a three-stage model of reading acquisition in Chinese is discussed.