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Background Obesity is associated with brain intrinsic functional reorganization. However, little is known about the BMI-related interhemispheric functional connectivity (IHFC) alterations, and their link with executive function in young healthy adults. Methods We examined voxel-mirrored homotopic connectivity (VMHC) patterns in 417 young adults from the Human Connectome Project. Brain regions with significant association between BMI and VMHC were identified using multiple linear regression. Results from these analyses were then used to determine regions for seed-voxel FC analysis, and multiple linear regression was used to explore the brain regions showing significant association between BMI and FC. The correlations between BMI-related executive function measurements and VMHC, as well as seed-voxel FC, were further examined. Results BMI was negatively associated with scores of Dimensional Change Card Sort Test (DCST) assessing cognitive flexibility (r = -0.14, p = 0.006) and with VMHC of bilateral inferior parietal lobule, insula and dorsal caudate. The dorsal caudate emerged as a nexus for BMI-related findings: greater BMI was associated with greater FC between caudate and hippocampus and lower FC between caudate and several prefrontal nodes (right inferior frontal gyrus, anterior cingulate cortex, and middle frontal gyrus). The FC between right caudate and left hippocampus was negatively associated with scores of DCST (r = -0.15, p = 0.0018). Conclusions Higher BMI is associated with poorer cognitive flexibility performance and IHFC in an extensive set of brain regions implicated in cognitive control. Larger BMI was associated with higher caudate-medial temporal lobe FC and lower caudate-dorsolateral prefrontal cortex FC. These findings may have relevance for executive function associated with weight gain among otherwise healthy young adults.

The “hunger” hormone ghrelin regulates food-intake and preference for high-calorie (HC) food through modulation of the mesocortico-limbic dopaminergic pathway. Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric surgery to treat morbid obesity. We tested the hypothesis that LSG-induced reductions in appetite and total ghrelin levels in blood are associated with reduced prefrontal brain reactivity to food cues. A functional magnetic resonance imaging (fMRI) cue-reactivity task with HC and low-calorie (LC) food pictures was used to investigate brain reactivity in 22 obese participants tested before and one month after bariatric surgery (BS). Nineteen obese controls (Ctr) without surgery were also tested at baseline and one-month later. LSG significantly decreased (1) fasting plasma concentrations of total ghrelin, leptin and insulin, (2) craving for HC food, and (3) brain activation in the right dorsolateral prefrontal cortex (DLPFC) in response to HC vs. LC food cues (P(FWE) < 0.05). LSG-induced reduction in DLPFC activation to food cues were positively correlated with reduction in ghrelin levels and reduction in craving ratings for food. Psychophysiological interaction (PPI) connectivity analyses showed that the right DLPFC had stronger connectivity with the ventral anterior cingulate cortex (vACC) after LSG; and changes in BMI were negatively correlated with changes in connectivity between the right DLPFC and vACC in the LSG group only. These findings suggest that LSG-induced weight-loss may be related to reductions in ghrelin, possibly leading to decreased food craving and hypothetically reducing DLPFC response to the HC food cues.

Visual presentation of appetitive and negative cues triggers fast responses in the human brain. Here we assessed functional MRI (fMRI) responses to food, cocaine, and neutral cues presented at a subliminal ("unconscious", 33 ms) and supraliminal ("conscious", 750 and 3000 ms) level in healthy, cocaine naïve volunteers. Because there is evidence of circadian variability in reward sensitivity, our second aim was to assess diurnal variability in the brain's reactivity to cues. Sixteen participants completed two randomly ordered fMRI sessions (once 9-11 AM and another 5-7 PM). in which food, cocaine, and neutral cues were presented for 33, 750 and 3000 ms. Participants rated food cues as positive and "wanted" (more so in evenings than mornings), and cocaine cues as negative (no diurnal differences). fMRI showed occipital cortex activation for foodneutral, cocaineneutral and cocainefood; dorsolateral prefrontal cortex for cocaineneutral and cocainefood, and midbrain for cocainefood (all p

Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric surgery to treat obesity, and involves removal of the gastric fundus where ghrelin is mainly produced. Ghrelin stimulates appetite and regulates food intake through its effect on the hypothalamus and hippocampus (HIPP). While ghrelin’s role on the hypothalamus has been explored, little is known about its role on HIPP. We tested the hypothesis that LSG-induced reductions in ghrelin levels would be associated with changes in HIPP activity. Brain activity was measured with amplitude of low-frequency fluctuations (ALFF) captured with resting-state functional magnetic resonance imaging (fMRI) in 30 obese participants, both before and after 1-month of LSG, and in 26 obese controls without surgery that were studied at baseline and 1-month later. A two-way analysis of variance (ANOVA) was performed to model the group and time effects on ALFF and resting-state functional connectivity. One-month post-LSG there were significant decreases in appetite, body mass index (BMI), fasting plasma ghrelin and leptin levels, anxiety, and ALFF in HIPP and ALFF increases in posterior cingulate cortex (PCC, PFWE

Functional constipation (FC) is a common functional gastrointestinal disorder (FGID) with a higher prevalence in clinical practice. The primary brain regions involved in emotional arousal regulation, somatic, sensory and motor control processing have been identified with neuroimaging in FGID. It remains unclear how these factors interact to influence the baseline brain activity of patients with FC. In the current study, we combined resting-state fMRI (RS-fMRI) with Granger causality analysis (GCA) to investigate the causal interactions of the brain areas in 14 patients with FC and in 26 healthy controls (HC). Our data showed significant differences in baseline brain activities in a number of major brain regions implicated in emotional process modulation (i.e. dorsal anterior cingulate cortex-dACC, anterior insula-aINS, orbitofrontal cortex-OFC, hippocampus-HIPP), somatic and sensory processing, and motor control (i.e., supplementary motor area-SMA, precentral gyrus-PreCen) (P

Obesity-related brain gray (GM) and white matter (WM) abnormalities have been reported in regions associated with food-intake control and cognitive-emotional regulation. Bariatric surgery (BS) is the most effective way to treat obesity and induce structural recovery of GM/WM density and WM integrity. It is unknown whether the surgery can promote structural changes in cortical morphometry along with weight-loss. Structural Magnetic Resonance Imaging and surface-based morphometry analysis were used to investigate BS-induced alterations of cortical morphometry in 22 obese participants who were tested before and one month post-BS, and in 21 obese controls (Ctr) without surgery who were tested twice (Baseline and One-month). Results showed that fasting plasma ghrelin, insulin, and leptin levels were significantly reduced post-BS (P

Obese individuals exhibit brain alterations of resting‐state functional connectivity (RSFC) integrity of resting‐state networks (RSNs) related to food intake. Bariatric surgery is currently the most effective treatment for combating morbid obesity. How bariatric surgery influences neurocircuitry is mostly unknown. Functional connectivity density (FCD) mapping was employed to calculate local (lFCD)/global (gFCD) voxelwise connectivity metrics in 22 obese participants who underwent functional magnetic resonance imaging before and 1 month after sleeve gastrectomy (SG), and in 19 obese controls (Ctr) without surgery but tested twice (baseline and 1‐month later). Two factor (group, time) repeated measures ANOVA was used to assess main and interaction effects in lFCD/gFCD; regions of interest were identified for subsequent seed to voxel connectivity analyses to assess resting‐state functional connectivity and to examine association with weight loss. Bariatric surgery significantly decreased lFCD in VMPFC, posterior cingulate cortex (PCC)/precuneus, and dorsal anterior cingulate cortex (dACC)/dorsomedial prefrontal cortex (DMPFC) and decreased gFCD in VMPFC, right dorsolateral prefrontal cortex (DLPFC) and right insula (p (FWE)

Eating behaviors are closely related to body weight, and eating traits are depicted in three dimensions: dietary restraint, disinhibition, and hunger. The current study aims to explore whether these aspects of eating behaviors are related to intrinsic brain activation, and to further investigate the relationship between the brain activation relating to these eating traits and body weight, as well as the link between function connectivity (FC) of the correlative brain regions and body weight. Our results demonstrated positive associations between dietary restraint and baseline activation of the frontal and the temporal regions (i.e., food reward encoding) and the limbic regions (i.e., homeostatic control, including the hypothalamus). Disinhibition was positively associated with the activation of the frontal motivational system (i.e., OFC) and the premotor cortex. Hunger was positively related to extensive activations in the prefrontal, temporal, and limbic, as well as in the cerebellum. Within the brain regions relating to dietary restraint, weight status was negatively correlated with FC of the left middle temporal gyrus and left inferior temporal gyrus, and was positively associated with the FC of regions in the anterior temporal gyrus and fusiform visual cortex. Weight status was positively associated with the FC within regions in the prefrontal motor cortex and the right ACC serving inhibition, and was negatively related with the FC of regions in the frontal cortical-basal ganglia-thalamic circuits responding to hunger control. Our data depicted an association between intrinsic brain activation and dietary restraint, disinhibition, and hunger, and presented the links of their activations and FCs with weight status.

Neuroimaging studies have revealed brain functional abnormalities in frontal-mesolimbic regions in obesity. However, the effects of obesity on brain network topology remains largely unknown. In the current study, we employed resting-state functional magnetic resonance imaging and graph theory methods to investigate obesity-related changes in brain network topology in 26 obese patients and 28 normal weight subjects. Results revealed that the whole-brain networks of the two groups exhibited typical features of small-world topology. Obese patients showed significantly increased shortest path length (Lp) and decreased global efficiency (Eglob). Moreover, decreased nodal-degree/efficiency was found in frontal (medial orbitofrontal cortex-mOFC, rostral anterior cingulate cortex-rACC), striatal (caudate/nucleus accumbens) and limbic regions (insula, amygdala, hippocampus/parahippocampal gyrus) and thalamus in obese patients. Network-based statistics showed that a sub-network, composed of 31 nodes and 30 edges, was significantly disrupted in obese patients; 29 out of 30 connections were associated with the right rACC. In the obese group, Lp and Eglob were negatively correlated with body mass index (BMI, P

Background The control of food intake in environments with easy access to highly rewarding foods is challenging to most modern societies. The combination of sustained release (SR) naltrexone and SR bupropion (NB32) has been used in weight-loss and obesity management. However, the effects of NB32 on the brain circuits implicated in the regulation of food intake are unknown. Here we used functional connectivity density (FCD) mapping to evaluate the effects of NB32 on resting brain FC. Methods Thirty-six healthy women underwent magnetic resonance imaging (MRI) before and after 4-week treatment with NB32 (n = 16) or with placebo (n = 20). In each imaging visit, a 5-min resting-state functional MRI scan was conducted after 15 h of fasting. The FC of brain regions showing significant group effects on FCD were subsequently assessed using seed-voxel correlation analyses. We characterized the associations between FCD measures and craving control scores in the Control of Eating Questionnaire. Results After NB32 treatment, the group showed lower local and global FCD than the placebo group in the right superior parietal cortex and lower local FCD in the left middle frontal gyrus. Seed-voxel correlation analysis for the right superior parietal cortex seed demonstrated higher positive FC with the dorsal anterior cingulate gyrus (ACC), bilateral insula, and left superior parietal gyrus and stronger negative FC with right inferior frontal gyrus and right superior parietal cortices for the NB32 than the placebo group. Further, the NB32 group showed a significant correlation between local FCD change after treatment in left middle frontal gyrus and craving control scores (r = 0.519, p = 0.039). Conclusions NB32 treatment decreased local and global FCD in superior parietal cortex and increased its connectivity with ACC (involved with saliency attribution), insula (interoception), and decreased local FCD in the medial prefrontal cortex (craving), which might underlie NB32 improved control over eating behaviors. ClinicalTrails.gov: NCT00711.

Functional magnetic resonance imaging (fMRI) has been used to investigate sex-related differences in brain abnormalities in patients with irritable bowel syndrome (IBS). Like IBS, women with functional constipation (FC) are 2.1 times as many as men. No study has been performed yet to examine sex-related differences in brain activity and connectivity in patients with FC. Here, we employed resting-state fMRI with amplitude of low-frequency fluctuation (ALFF) to investigate brain functional differences in 51 patients with FC (34 females) and 52 healthy controls (34 females). Results showed abdominal pain and abdominal distension correlated with trait (TAI) and state (SAI) anxiety ratings in the female FC group, and abdominal distension correlated with sensation of incomplete evacuation in the male FC group. Two-way ANOVA revealed sex effects on ALFF in precentral gyrus, thalamus, insula (INS), and orbital frontal cortex (OFC, PFWE

To study top-down face processing, the present study used an experimental paradigm in which participants detected non-existent faces in pure noise images. Conventional BOLD signal analysis identified three regions involved in this illusory face detection. These regions included the left orbitofrontal cortex (OFC) in addition to the right fusiform face area (FFA) and right occipital face area (OFA), both of which were previously known to be involved in both top-down and bottom-up processing of faces. We used Dynamic Causal Modeling (DCM) and Bayesian model selection to further analyze the data, revealing both intrinsic and modulatory effective connectivities among these three cortical regions. Specifically, our results support the claim that the orbitofrontal cortex plays a crucial role in the top-down processing of faces by regulating the activities of the occipital face area, and the occipital face area in turn detects the illusory face features in the visual stimuli and then provides this information to the fusiform face area for further analysis.

Resting-state magnetic resonance imaging has uncovered abnormal functional connectivity in heroin-dependent individuals (HDIs). However, it remains unclear how brain regions implicated in addictions are related in baseline state without conditioned cues in heroin dependent individuals during opioid maintenance treatment (HDIs-OMT). Previous connectivity analysis assessed the strength of correlated activity between brain regions but lacked the ability to infer directional neural interactions. In the current study, we employed Granger causality analysis to investigate directional causal influences among the brain circuits in HDIs-OMT and non-opioid users. The results revealed a weaker effective connectivity between the caudate nucleus implicated in mediating the reward circuit and other brain regions and also a weaker connectivity between the anterior cingulate cortex and medial prefrontal cortex implicated in mediating inhibitory control. Conversely, HDIs-OMT exhibited stronger effective connectivity between the hippocampus and amygdala implicated in mediating learning-memory, and the anterior cingulate cortex involved in mediating inhibitory control while the putamen mediated learned habits, suggesting that the hippocampus and amygdala may propel the memory circuit to override the control circuit and drive the learned habit in HDIs-OMT. Alterations in learning-memory and inhibitory control may contribute jointly and form a basis for relapse risk even after a period of heroin abstinence. Sustained neural effect of opioid dependence on methadone maintenance including hyperactivation in the memory circuit and impairment in the control circuit support the role of the memory circuitry in relapse and may help redefine targets for treatment.

Perceived social support emphasizes subjective feeling of provisions offered by family, friends and significant others. In consideration of the great significance of perceived social support to health outcomes, attempt to reveal the neural substrates of perceived social support will facilitate its application in a series of mental disorders. Perceived social support potentially relies on healthy interpersonal relationships calling for cognitive processes like perspective taking, empathy and theory of mind. Interestingly, functional activations and connectivity within the default mode network (DMN) are extensively involved in these interpersonal skills. As a result, it is proposed that synchronous activities among brain regions within the DMN will correlate with self-report of perceived social support. In the present study, we tried to investigate the associations between coherence among the DMN regions and perceived social support at resting state. A total of 333 (145 men) participants were directed to fulfill the Multidimensional Scale of Perceived Social Support (MSPSS) after a 484-s functional magnetic resonance imaging (fMRI) scanning without any task. As a result, seed-based functional connectivity and power spectrum analyses revealed that heightened synchronicity among the DMN regions was associated with better performance on perceived social support. Moreover, results in the present study were independent of different methods, structural changes, and general cognitive performance.

Neural mechanisms underlying word processing have been extensively studied. It has been revealed that when individuals are engaged in active word processing, a complex network of cortical regions is activated. However, it is entirely unknown whether the word-processing regions are intrinsically organized without any explicit processing tasks during the resting state. The present study investigated the intrinsic functional connectivity between word-processing regions during the resting state with the use of fMRI methodology. The low-frequency fluctuations were observed between the left middle fusiform gyrus and a number of cortical regions. They included the left angular gyrus, left supramarginal gyrus, bilateral pars opercularis, and left pars triangularis of the inferior frontal gyrus, which have been implicated in phonological and semantic processing. Additionally, the activations were also observed in the bilateral superior parietal lobule and dorsal lateral prefrontal cortex, which have been suggested to provide top-down monitoring on the visual–spatial processing of words. The findings of our study indicate an intrinsically organized network during the resting state that likely prepares the visual system to anticipate the highly probable word input for ready and effective processing.

Although top-down perceptual process plays an important role in face processing, its neural substrate is still puzzling because the top-down stream is extracted difficultly from the activation pattern associated with contamination caused by bottom-up face perception input. In the present study, a novel paradigm of instructing participants to detect faces from pure noise images is employed, which could efficiently eliminate the interference of bottom-up face perception in topdown face processing. Analyzing the map of functional connectivity with right FFA analyzed by conventional Pearson's correlation, a possible face processing pattern induced by top-down perception can be obtained. Apart from the brain areas of bilateral fusiform gyrus (FG), left inferior occipital gyrus (IOG) and left superior temporal sulcus (STS), which are consistent with a core system in the distributed cortical network for face perception, activation induced by top-down face processing is also found in these regions that include the anterior cingulate gyrus (ACC), right oribitofrontal cortex (OFC), left precuneus, right parahippocampal cortex, left dorsolateral prefrontal cortex (DLPFC), right frontal pole, bilateral premotor cortex, left inferior parietal cortex and bilateral thalamus. The results indicate that making-decision, attention, episodic memory retrieving and contextual associative processing network cooperate with general face processing regions to process face information under top-down perception.

The statistic of RV-coefficient is a good substitute for the Pearson correlation coefficient to measure the temporal similarity of two local brain regions. However, the hypothesis test of RV-coefficient is a hard problem which limits its application. This paper discussed the problem in details. Since the distribution of RV-coefficient is unknown, we do not know a critical p-value to statistically test its significance. We proposed a new strategy to test the significance of RV calculated from fMRI. In order to approximate the p-value, we elicited the first two moments of the population permutation distribution of RV; we then derived a formula to more closely approximate the normal distribution with these transformed statistics. These transformations of statistics are suggested for a precise approximation to the permutational p-value even under large number of observations. This strategy of test can greatly reduce the computational complexity and avoid "calculation catastrophe", we then use the statistic of RV to extract the map of functional connectivity from fMRI and test its significance with the strategy proposed here.

Evidence suggests that the neural system associated with face processing is a distributed cortical network containing both bottom-up and top-down mechanisms. While bottom-up face processing has been the focus of many studies, the neural areas involved in the top-down face processing have not been extensively investigated due to difficulty in isolating top-down influences from the bottom-up response engendered by presentation of a face. In the present study, we used a novel experimental method to induce illusory face-detection. This method allowed for directly examining the neural systems involved in top-down face processing while minimizing the influence of bottom-up perceptual input. A distributed cortical network of top-down face processing was identified by analyzing the functional connectivity patterns of the right fusiform face area (FFA). This distributed cortical network model for face processing includes both "core" and "extended" face processing areas. It also includes left anterior cingulate cortex (ACC), bilateral orbitofrontal cortex (OFC), left dorsolateral prefrontal cortex (DLPFC), left premotor cortex, and left inferior parietal cortex. These findings suggest that top-down face processing contains not only regions for analyzing the visual appearance of faces, but also those involved in processing low spatial frequency (LSF) information, decision-making, and working memory.