Jizheng Zhao

Intrinsic brain subsystem associated with dietary restraint, disinhibition and hunger: an fMRI study.

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.

Distinct resting-state brain activity in patients with functional constipation.

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<0.05, FDR correction). The GCA results revealed stronger effective connectivity from the OFC and dACC, which are regions involved with emotional regulation, propel limbic regions at the aINS and HIPP to induce abnormal emotional processing regulating visceral responses; and weaker effective connectivity from the SMA and PreCen, which are regions involved with somatic, sensory and motor control, propel the aINS and HIPP, suggesting abnormalities of sensory and behavioral responses. Such information of basal level functional abnormalities expands our current understanding of neural mechanisms underlying functional constipation.

Granger causality reveals a dominant role of memory circuit in chronic opioid dependence

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.

Effect of combined naltrexone and bupropion therapy on the brain’s functional connectivity

BackgroundThe 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.MethodsThirty-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.ResultsAfter 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).ConclusionsNB32 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.

Ghrelin reductions following bariatric surgery were associated with decreased resting state activity in the hippocampus

Background/objective: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.Subjects/methods: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.Results: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 < 0.05). Decreases in HIPP ALFF correlated positively with decreases in fasting ghrelin and anxiety, and increases in PCC ALFF correlated positively with decreases in anxiety. Seed-voxel correlation analysis showed stronger connectivity between HIPP and insula, and between PCC and dorsolateral prefrontal cortex (DLPFC) post-LSG.Conclusions:These findings suggest that ghrelin effects in HIPP modulate connectivity with the insula, which processes interoception and might be relevant to LSG-induced reductions in appetite/anxiety. Role of LSG in PCC and its enhanced connectivity with DLPFC in improving self-regulation following LSG requires further investigation.

Bariatric surgery in obese patients reduced resting connectivity of brain regions involved with self-referential processing

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 (pFWE < .05). lFCD decreased in VMPFC and PCC/precuneus correlated with reduction in BMI after surgery. Seed to voxel connectivity analyses showed the VMPFC had stronger connectivity with left DLPFC and weaker connectivity with hippocampus/parahippocampus, and PCC/precuneus had stronger connectivity with right caudate and left DLPFC after surgery. Bariatric surgery significantly decreased FCD in regions involved in self‐referential processing (VMPFC, DMPFC, dACC, and precuneus), and interoception (insula), and changes in VMPFC/precuneus were associated with reduction in BMI suggesting a role in improving control of eating behaviors following surgery.

Structural changes in brain regions involved in executive-control and self-referential processing after sleeve gastrectomy in obese patients

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 < 0.001). Post-BS there were significant decreases in cortical thickness in the precuneus (PFDR < 0.05) that were associated with decreases in BMI. There were also significant increases post-BS in cortical thickness in middle (MFG) and superior (SFG) frontal gyri, superior temporal gyrus (STG), insula and ventral anterior cingulate cortex (vACC); and in cortical volume in left postcentral gyrus (PostCen) and vACC (PFDR < 0.05). Post-BS changes in SFG were associated with decreases in BMI. These findings suggest that structural changes in brain regions implicated in executive control and self-referential processing are associated with BS-induced weight-loss.

Disrupted topological organization of the frontal-mesolimbic network in obese patients

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 < 0.005), and BMI was negatively correlated with nodal-degree/efficiency of the mOFC (P < 0.001). Findings suggest disruption of the small-world organization and a global reduction of integration of functional brain networks involving the right rACC in obesity and implicating the mOFC in mediating severity.

Correlation between Traits of Emotion-Based Impulsivity and Intrinsic Default-Mode Network Activity

Negative urgency (NU) and positive urgency (PU) are implicated in several high-risk behaviors, such as eating disorders, substance use disorders, and nonsuicidal self-injury behavior. The current study aimed to explore the possible link between trait of urgency and brain activity at rest. We assessed the amplitude of low-frequency fluctuations (ALFF) of the resting-state functional magnetic resonance imaging (fMRI) signal in 85 healthy volunteers. Trait urgency measures were related to ALFF in the lateral orbitofrontal cortex, dorsolateral prefrontal cortex, ventral and dorsal medial frontal cortex, anterior cingulate, and posterior cingulate cortex/precuneus. In addition, trait urgency measures showed significant correlations with the functional connectivity of the posterior cingulate cortex/precuneus seed with the thalamus and midbrain region. These findings suggest an association between intrinsic brain activity and impulsive behaviors in healthy humans.