Brain activity and connectivity changes in response to glucose ingestion.

Objectives: The regulatory role of the brain in directing eating behavior becomes increasingly recognized. Although many areas in the brain have been found to respond to food cues, very little data is available after actual caloric intake. The aim of this study was to determine normal whole brain functional responses to ingestion of glucose after an overnight fast.Methods: Twenty-five normal weight, adult males underwent functional MRI on two separate visits. In a single-blind randomized study setup, participants received either glucose solution (50 g/300 ml of water) or plain water. We studied changes in Blood Oxygen Level Dependent (BOLD) signal, voxel-based connectivity by Eigenvector Centrality Mapping, and functional network connectivity.Results: Ingestion of glucose led to increased centrality in the thalamus and to decreases in BOLD signal in various brain areas. Decreases in connectivity in the sensory-motor and dorsal visual stream networks were found. Ingestion of water resulted in increased centrality across the brain, and increases in connectivity in the medial and lateral visual cortex network. Increased BOLD intensity was found in the intracalcarine and cingulate cortex.Discussion: Our data show that ingestion of glucose leads to decreased activity and connectivity in brain areas and networks linked to energy seeking and satiation. In contrast, drinking plain water leads to increased connectivity probably associated with continued food seeking and unfulfilled reward.Trail registration: This study combines data of two studies registered at clinicaltrails.gov under numbers NCT03202342 and NCT03247114.

Altered cortical-amygdala coupling in social anxiety disorder during the anticipation of giving a public speech.

BACKGROUND: Severe stress in social situations is a core symptom of social anxiety disorder (SAD). Connectivity between the amygdala and cortical regions is thought to be important for emotion regulation, a function that is compromised in SAD. However, it has never been tested if and how this connectivity pattern changes under conditions of stress-inducing social evaluative threat. Here we investigate changes in cortical-amygdala coupling in SAD during the anticipation of giving a public speech. METHOD: Twenty individuals with SAD and age-, gender- and education-matched controls (n = 20) participated in this study. During the functional magnetic resonance imaging (fMRI) session, participants underwent three 'resting-state' fMRI scans: one before, one during, and one after the anticipation of giving a public speech. Functional connectivity between cortical emotion regulation regions and the amygdala was investigated. RESULTS: Compared to controls, SAD participants showed reduced functional integration between cortical emotion regulation regions and the amygdala during the public speech anticipation. Moreover, in SAD participants cortical-amygdala connectivity changes correlated with social anxiety symptom severity. CONCLUSIONS: The distinctive pattern of cortical-amygdala connectivity suggests less effective cortical-subcortical communication during social stress-provoking situations in SAD.

Amygdala and anterior cingulate resting-state functional connectivity in borderline personality disorder patients with a history of interpersonal trauma.

BACKGROUND: Studies in borderline personality disorder (BPD) have consistently revealed abnormalities in fronto-limbic brain regions during emotional, somatosensory and cognitive challenges. Here we investigated changes in resting-state functional connectivity (RSFC) of three fronto-limbic core regions of specific importance to BPD. METHOD: Functional magnetic resonance imaging data were acquired in 20 unmedicated female BPD patients and 17 healthy controls (HC, matched for age, sex and education) during rest. The amygdala, and the dorsal and ventral anterior cingulate cortex (ACC) were defined as seeds to investigate RSFC patterns of a medial temporal lobe network, the salience network and default mode network. The Dissociation Experience Scale (DES), a measure of trait dissociation, was additionally used as a predictor of RSFC with these seed regions. RESULTS: Compared with HC, BPD patients showed a trend towards increased RSFC between the amygdala and the insula, orbitofrontal cortex and putamen. Compared with controls, patients furthermore exhibited diminished negative RSFC between the dorsal ACC and posterior cingulate cortex, a core region of the default mode network, and regions of the dorsomedial prefrontal cortex. Last, increased negative RSFC between the ventral ACC and medial occipital regions was observed in BPD patients. DES scores were correlated with amygdala connectivity with the dorsolateral prefrontal cortex and fusiform gyrus. CONCLUSIONS: Our findings suggest alterations in resting-state networks associated with processing of negative emotions, encoding of salient events, and self-referential processing in individuals with BPD compared with HC. These results shed more light on the role of abnormal brain connectivity in BPD.

Altered white-matter architecture in treatment-naive adolescents with clinical depression.

BACKGROUND: Depressive disorders are highly prevalent in adolescence and confer a heightened risk of recurrence in adulthood. Insight into the developmental neurocircuitry of depression could advance our understanding of depression and aid the development of effective treatment strategies. Whereas white-matter (WM) abnormalities are strongly implicated in adult depression, we still lack a firm understanding of WM architecture in adolescent depression. Using diffusion tensor imaging (DTI), we set out to investigate WM microstructure in a sample of clinically depressed adolescents relative to matched controls. METHOD: We employed tract-based spatial statistics (TBSS) to examine WM microstructure in 25 treatment-naive adolescents with clinical depression relative to 21 matched controls. Using TBSS, we examined fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD). Threshold-free cluster enhancement (TFCE) with family-wise error (FWE) correction was used to control for multiple comparisons. RESULTS: Our analysis revealed abnormal WM microstructure in clinically depressed adolescents. More specifically, whole-brain analysis revealed that patients had lower FA values in the body of the corpus callosum (CC), coupled with elevated RD and MD, and preserved AD. Conversely, region-of-interest analysis revealed that patients had higher FA values in the uncinate fasciculus (UF), coupled with elevated AD, reduced RD and preserved MD. CONCLUSIONS: In line with neurocircuitry models of depression, our findings suggest that WM abnormalities within pathways facilitating cognitive and emotional functioning are involved in the pathophysiology of depression. Importantly, our findings show that these WM abnormalities are already present early in the course of the disorder.

Resting-state functional connectivity in adults with childhood emotional maltreatment.

BACKGROUND: Childhood emotional maltreatment (CEM) has been associated with disturbances in emotional and behavioral functioning, and with changes in regional brain morphology. However, whether CEM has any effect on the intrinsic organization of the brain is not known. In this study, we investigated the effects of CEM on resting-state functional connectivity (RSFC) using seeds in the limbic network, the default-mode network (DMN) and the salience network, and the left dorsomedial prefrontal cortex (dmPFC). Method Using 3-T magnetic resonance imaging (MRI), resting-state functional MRI (RS-fMRI) scans were obtained. We defined seeds in the bilateral amygdala, the dorsal anterior cingulate cortex (dACC), the posterior cingulate cortex (PCC) and the left dmPFC, and used these to examine whether individuals reporting CEM (n=44) differed from individuals reporting no CEM (n=44) in RSFC with other brain regions. The two groups were matched for age, gender, handedness and the presence of psychopathology. RESULTS: CEM was associated with decreased RSFC between the right amygdala and the bilateral precuneus and a cluster extending from the left insula to the hippocampus and putamen. In addition, CEM was associated with decreased RSFC between the dACC and the precuneus and also frontal regions of the brain. CONCLUSIONS: We found that CEM has a profound effect on RSFC in the limbic network and the salience network. Regions that show aberrant connectivity are related to episodic memory encoding, retrieval and self-processing operations.

Reduced resting-state brain activity in the "default network" in normal aging.

Normal aging is associated with cognitive decline. Functions such as attention, information processing, and working memory are compromised. It has been hypothesized that not only regional changes, but also alterations in the integration of regional brain activity (functional brain connectivity) underlie the observed age-related deficits. Here, we examined the functional properties of brain networks based on spontaneous fluctuations within brain systems using functional magnetic resonance imaging. We hypothesized that functional connectivity of intrinsic brain activity in the "default-mode" network (DMN) is affected by normal aging and that this relates to cognitive function. Ten younger and 22 older subjects were scanned at "rest," that is, lying awake with eyes closed. Our results show decreased activity in older versus younger subjects in 2 resting-state networks (RSNs) resembling the previously described DMN, containing the superior and middle frontal gyrus, posterior cingulate, middle temporal gyrus, and the superior parietal region. These results remain significant after correction for RSN-specific gray matter volume. The relevance of these findings is illustrated by the correlation between reduced activity of one of these RSNs and less effective executive functioning/processing speed in the older group.

Effect of flavor on neuronal responses of the hypothalamus and ventral tegmental area.

Although it is well known that food intake is affected by the palatability of food, the actual effect of flavoring on regulation of energy-homeostasis and reward perception by the brain, remains unclear. We investigated the effect of ethyl-butyrate (EB), a common non-caloric food flavoring, on the blood oxygen level dependent (BOLD) response in the hypothalamus (important in regulating energy homeostasis) and ventral tegmental area (VTA; important in reward processes). The 16 study participants (18-25 years, BMI 20-23 kg/m2) drank four study stimuli on separate visits using a crossover design during an fMRI setup in a randomized order. The stimuli were; plain water, water with EB, glucose solution (50gram/300 ml) and glucose solution with EB. BOLD responses to ingestion of the stimuli were determined in the hypothalamus and VTA as a measure of changes in neuronal activity after ingestion. In the hypothalamus and VTA, glucose had a significant effect on the BOLD response but EB flavoring did not. Glucose with and without EB led to similar decrease in hypothalamic BOLD response and glucose with EB resulted in a decrease in VTA BOLD response. Our results suggest that the changes in neuronal activity in the hypothalamus are mainly driven by energy ingestion and EB does not influence the hypothalamic response. Significant changes in VTA neuronal activity are elicited by energy combined with flavor.

Dietary sugars and non-caloric sweeteners elicit different homeostatic and hedonic responses in the brain.

OBJECTIVE: The brain is essential in regulating intake of food and beverages by balancing energy homeostasis, which is regulated by the hypothalamus, with reward perception, which is regulated by the ventral tegmental area (VTA). The aim of this study was to investigate the effects of ingestion of glucose, fructose, sucrose, and sucralose (a non-caloric artificial sweetener) on the magnitude and trajectory of the hypothalamic and the VTA blood oxygen level-dependent (BOLD) responses. METHOD: In five visits, 16 healthy men between 18 to 25 y of age with a body mass index between 20 and 23 kg/m2 drank five interventions in a randomized order while a functional magnetic resonance imaging scan was taken. The interventions consisted of 50 g of glucose, fructose, or sucrose, or 0.33 g of sucralose dissolved in 300 mL tap water. The control condition consisted of 300 mL of plain tap water. BOLD signals were determined in the hypothalamus and the VTA within a manually drawn region of interest. Differences in changes in BOLD signal between stimuli were analyzed using mixed models. RESULTS: Compared with the control condition, a decrease in BOLD signal in the hypothalamus was found after ingestion of glucose (P = 0.0003), and a lesser but delayed BOLD response was found after ingestion of sucrose (P = 0.006) and fructose (P = 0.003). Sucralose led to a smaller and transient response from the hypothalamus (P = 0.026). In the VTA, sucralose led to a very similar response to the water control condition, leading to an increase in VTA BOLD activity that continued over the measured time period. The natural sugars appeared to only lead to a transient increase in VTA activity. CONCLUSIONS: Glucose induces a deactivation in the hypothalamus immediately after ingestion and continued over the next 12 min, which is correlated with satiety signaling by the brain. Fructose and sucrose are both associated with a delayed and lesser response from the hypothalamus, likely because the sugars first have to be metabolized by the body. Sucralose leads to the smallest and most transient decrease in BOLD in the hypothalamus and leads to a similar response as plain water in the VTA, which indicates that sucralose might not have a similar satiating effect on the brain as the natural sugars.

General psychopathology factor and unresolved-disorganized attachment uniquely correlated to white matter integrity using diffusion tensor imaging.

BACKGROUND: A dimensional approach of psychopathology focuses on features and risk factors that are shared across diagnoses. In support for this dimensional approach, studies point to a general psychopathology factor (GPF) associated with risk for multiple psychiatric disorders. It is, however, unknown how GPF relates to white matter integrity (WMI). In the current diffusion tensor imaging (DTI) study, we examined how GPF relates to abnormalities in a skeleton representation of white matter tracts, taking into account a trans-diagnostic risk factor: unresolved-disorganized attachment (Ud) resulting from loss or trauma. METHODS: Unique associations between GPF, Ud, and WMI were examined in a combined sample of adolescents (N = 63) with childhood sexual abuse-related posttraumatic stress disorder (N = 18), anxiety and depressive disorders (N = 26) and without psychiatric disorder (N = 19). WMI was measured using DTI. Ud was measured using the Adult Attachment Interview. We controlled for puberty stage, gender, age, and IQ. RESULTS: Controlling for GPF, Ud was associated with reduced fractional anisotropy (FA) in the splenium and inferior fronto-occipital fasciculus (IFOF). Controlling for Ud, GPF was associated with reduced FA in the genu and body of the corpus callosum. CONCLUSIONS: Decreasing WMI in the genu and body with increasing psychopathology across diagnoses suggests demyelinization in these areas and may underlie comorbidity and presence of symptoms that transcend psychopathological diagnoses. In contrast, trauma-related WMI reductions in the splenium and IFOF may account for heterogeneity within diagnostic categories as a function of childhood trauma. These findings support the importance of a dimensional approach in addition to traditional diagnostic classifications in clinical research and practice.

Separable neural mechanisms contribute to feedback processing in a rule-learning task.

To adjust performance appropriately to environmental demands, it is important to monitor ongoing action and process performance feedback for possible errors. In this study, we used fMRI to test whether medial prefrontal cortex (PFC)/anterior cingulate cortex (ACC) and dorsolateral (DL) PFC have different roles in feedback processing. Twenty adults completed a rule-switch task in which rules had to be inferred on the basis of positive and negative feedback and the rules could change unexpectedly. Negative feedback resulted in increased activation in medial PFC/ACC and DLPFC relative to positive feedback, but the regions were differentially active depending on the type of negative feedback. Whereas medial PFC/ACC was most active following unexpected feedback indicating that prior performance was no longer correct, DLPFC was most active following negative feedback that was informative for correct behavior on the next trial. The current findings show that inconsistent results about the role of prefrontal cortex regions in feedback processing are most likely associated with the informative value of the performance feedback. The results are consistent with the hypothesis that medial PFC/ACC is important for signaling expectation violation whereas DLPFC is important for goal-directed actions.

Long-term effects of stimulant exposure on cerebral blood flow response to methylphenidate and behavior in attention-deficit hyperactivity disorder.

Stimulant prescription rates for attention deficit hyperactivity disorder (ADHD) are increasing, even though potential long-term effects on the developing brain have not been well-studied. A previous randomized clinical trial showed short-term age-dependent effects of stimulants on the DA system. We here assessed the long-term modifying effects of age-of-first-stimulant treatment on the human brain and behavior. 81 male adult ADHD patients were stratified into three groups: 1) early stimulant treatment (EST; <16 years of age) 2) late stimulant treatment (LST: ≥23 years of age) and 3) stimulant treatment naive (STN; no history of stimulant treatment). We used pharmacological magnetic resonance imaging (phMRI) to assess the cerebral blood flow (CBF) response to an oral methylphenidate challenge (MPH, 0.5 mg/kg), as an indirect measure of dopamine function in fronto-striatal areas. In addition, mood and anxiety scores, and recreational drug use were assessed. Baseline ACC CBF was lower in the EST than the STN group (p = 0.03), although CBF response to MPH was similar between the three groups (p = 0.23). ADHD symptom severity was higher in the STN group compared to the other groups (p < 0.01). In addition, the EST group reported more depressive symptoms (p = 0.04), but not anxiety (p = 0.26), and less recreational drug use (p = 0.04). In line with extensive pre-clinical data, our data suggest that early, but not late, stimulant treatment long-lastingly affects the human brain and behavior, possibly indicating fundamental changes in the dopamine system.

Nonlinear changes in brain activity during continuous word repetition: an event-related multiparametric functional MR imaging study.

BACKGROUND AND PURPOSE: Changes in brain activation as a function of continuous multiparametric word recognition have not been studied before by using functional MR imaging (fMRI), to our knowledge. Our aim was to identify linear changes in brain activation and, what is more interesting, nonlinear changes in brain activation as a function of extended word repetition. MATERIALS AND METHODS: Fifteen healthy young right-handed individuals participated in this study. An event-related extended continuous word-recognition task with 30 target words was used to study the parametric effect of word recognition on brain activation. Word-recognition-related brain activation was studied as a function of 9 word repetitions. fMRI data were analyzed with a general linear model with regressors for linearly changing signal intensity and nonlinearly changing signal intensity, according to group average reaction time (RT) and individual RTs. RESULTS: A network generally associated with episodic memory recognition showed either constant or linearly decreasing brain activation as a function of word repetition. Furthermore, both anterior and posterior cingulate cortices and the left middle frontal gyrus followed the nonlinear curve of the group RT, whereas the anterior cingulate cortex was also associated with individual RT. CONCLUSION: Linear alteration in brain activation as a function of word repetition explained most changes in blood oxygen level-dependent signal intensity. Using a hierarchically orthogonalized model, we found evidence for nonlinear activation associated with both group and individual RTs.

White matter microstructure of patients with neurofibromatosis type 1 and its relation to inhibitory control.

Neurofibromatosis Type 1 (NF1) is commonly associated with deficits in executive functions such as working memory and inhibitory control. A valid biomarker to describe the pathological basis of these deficits in NF1 is not available. The aim of this study was to investigate whether any abnormalities in white matter integrity of the executive function related anterior thalamic radiation (ATR), cingulate bundle (CB), and superior longitudinal fasciculus (SLF) may be regarded as a pathological basis for inhibitory control deficits in adolescents with NF1. Sixteen NF1 patients and 32 healthy controls underwent 3 T DTI MRI scanning. Whole brain-, ATR-, CB-, and SLF-white matter integrity were studied using fractional anisotropy, mean (MD), radial, and axial (DA) diffusivity. Correlation analyses between white matter metrics and inhibitory control (as measured with a computerized task) were performed. Also, verbal and performance abilities (IQ-estimates) were assessed and correlated with white matter metrics. Patients showed significant whole brain- and local microstructural pathology when compared to healthy controls in all measures. In NF1-patients, whole-brain (MD: r = .646 and DA: r = .673) and ATR- (r-range: -.405-.771), but not the CB- (r-range: -.307-.472) and SLF- (r-range: -.187-.406) white matter integrity, were correlated with inhibitory control. Verbal and performance abilities were not associated with white matter pathology. In NF1, white matter abnormalities are observed throughout the brain, but damage to the ATR seems specifically, or at least most strongly related to inhibitory control. Future studies should examine whether reduced white matter integrity in other brain regions or tracts is (more strongly) associated with different aspects of the cognitive-behavioral phenotype associated with NF1.

Increased brain activation during motor imagery suggests central abnormality in Neonatal Brachial Plexus Palsy.

Neonatal Brachial Plexus Palsy (NBPP) may lead to permanent impairment of arm function. As NBPP occurs when central motor programs develop, these may be ill-formed. We studied elbow flexion and motor imagery with fMRI to search for abnormal motor programming. We compared the cortical activity of adults with conservatively treated NBPP to that of healthy individuals stratified for hand dominance, using fMRI BOLD tasks of elbow flexion and motor imagery of flexion. Additionally, resting-state networks and regional gray matter volume were studied. Sixteen adult NBPP patients (seven men; median age 29 years) and sixteen healthy subjects (seven men, median age 27 years) participated. Cortical activation was significantly higher in patients during flexion imagery compared to healthy individuals and it increased with lesion extent and muscle weakness. The contralateral and ipsilateral premotor cortex, and the contralateral motor cortex showed stronger activity during imagined flexion in the right-handed NBPP subjects compared to healthy individuals. Activity patterns during actual flexion did not differ between groups. No differences in resting-state network connectivity or gray matter amount were found between the groups. NBPP affected imagined but not actual elbow flexion, suggesting an impairment of motor planning which would indicate abnormal motor programming in NBPP.

Voxel-based analysis of quantitative T1 maps demonstrates that multiple sclerosis acts throughout the normal-appearing white matter.

BACKGROUND AND PURPOSE: Disease activity in normal-appearing white matter (NAWM) in multiple sclerosis (MS) has been demonstrated in vivo with T1 relaxation time measurements. We aimed to investigate the spatial distribution of T1 increases in MS NAWM without a priori selection of specific regions. METHODS: Whole-brain quantitative T1 maps were measured in 67 patients with one of the 3 main clinical types of MS (13 primary progressive [PP], 36 relapsing-remitting [RR], and 18 secondary progressive [SP]) and in 23 healthy control subjects. After registration to standard space and segmentation of NAWM, the maps were analyzed by using voxel-based analyses with a cluster-based corrected P threshold of .05. RESULTS: Group mean T1 relaxation times throughout NAWM increased when going from control subjects to PP to RR to SP MS. In the RR and SP MS groups, the T1 increases compared with control subjects were significant throughout the NAWM, without apparent preference for specific brain regions. In RR MS, 16% of NAWM voxels displayed a significant increase in T1 compared with control subjects, and in SP, this fraction was 49%. The comparison between RR MS and the subsequent phase SP MS revealed that, in these patients, disease progression occurs throughout the NAWM. In patients with PP MS, the spatial extent of significant T1 increases is limited. There were no correlations with clinical disability scales or brain volume in a substantial fraction of voxels. CONCLUSION: This study demonstrates that in patients with RR MS and SP MS, NAWM disease processes have no regional preferences but can occur throughout the brain.

Is the brain of complex regional pain syndrome patients truly different?

BACKGROUND: In recent years, changes in brain structure and function have been studied extensively in patients with complex regional pain syndrome (CRPS) following clinical observations of altered central processing of sensory stimuli and motor control. However, concerning MRI data, the evidence is complex to interpret due to heterogeneity in statistical methods and results. METHOD: The aim of this study was to determine if CRPS patients exhibit specific, clinically relevant changes in brain structure and function in rest. We do this by presenting MRI data on brain structure and function in 19 chronic, female CRPS patients and age- and sex-matched healthy controls (HCs). In addition, we analyse and report the data in multiple ways to make comparison with previous studies possible and to demonstrate the effect of different statistical methods, in particular, concerning the correction for multiple testing. RESULTS: Using family-wise error (FWE) correction for multiple testing, in our group of CRPS patients, we find no specific difference in brain structure or function in rest in comparison to HCs. In addition, we argue that previously found MRI results in the literature are inconsistent in terms of localization, quantity and directionality of the reported changes in brain structure and function. CONCLUSION: Previously published MRI-based evidence for altered brain structure and function in rest in CRPS patients is not consistent and our data suggests that no such phenomenon exists. WHAT DOES THIS STUDY ADD?: This article does not replicate the previous found results. The reported evidence in MRI literature of aberrant neuroplasticity in CRPS patients is inconsistent in terms of localization, quantity and directionality of changes in brain structure and function.

Reduced functional connectivity within the primary motor cortex of patients with brachial plexus injury.

This study aims at the effects of traumatic brachial plexus lesion with root avulsions (BPA) upon the organization of the primary motor cortex (M1). Nine right-handed patients with a right BPA in whom an intercostal to musculocutaneous (ICN-MC) nerve transfer was performed had post-operative resting state fMRI scanning. The analysis of empirical functional correlations between neighboring voxels revealed faster correlation decay as a function of distance in the M1 region corresponding to the arm in BPA patients as compared to the control group. No differences between the two groups were found in the face area. We also investigated whether such larger decay in patients could be attributed to a gray matter diminution in M1. Structural imaging analysis showed no difference in gray matter density between groups. Our findings suggest that the faster decay in neighboring functional correlations without significant gray matter diminution in BPA patients could be related to a reduced activity in intrinsic horizontal connections in M1 responsible for upper limb motor synergies.

Disturbed fluctuations of resting state EEG synchronization in Alzheimer's disease.

OBJECTIVE: We examined the hypothesis that cognitive dysfunction in Alzheimer's disease is associated with abnormal spontaneous fluctuations of EEG synchronization levels during an eyes-closed resting state. METHODS: EEGs were recorded during an eyes-closed resting state in Alzheimer patients (N=24; 9 males; mean age 76.3 years; SD 7.8; range 59-86) and non-demented subjects with subjective memory complaints (N=19; 9 males; mean age 76.1 years; SD 6.7; range: 67-89). The mean level of synchronization was determined in different frequency bands with the synchronization likelihood and fluctuations of the synchronization level were analysed with detrended fluctuation analysis (DFA). RESULTS: The mean level of EEG synchronization was lower in Alzheimer patients in the upper alpha (10-13Hz) and beta (13-30Hz) band. Spontaneous fluctuations of synchronization were diminished in Alzheimer patients in the lower alpha (8-10Hz) and beta bands. In patients as well as controls the synchronization fluctuations showed a scale-free pattern. CONCLUSIONS: Alzheimer's disease is characterized both by a lower mean level of functional connectivity as well as by diminished fluctuations in the level of synchronization. The dynamics of these fluctuations in patients and controls was scale-free which might point to self-organized criticality of neural networks in the brain. SIGNIFICANCE: Impaired functional connectivity can manifest itself not only in decreased levels of synchronization but also in disturbed fluctuations of synchronization levels.

Obesity is marked by distinct functional connectivity in brain networks involved in food reward and salience.

We hypothesized that brain circuits involved in reward and salience respond differently to fasting in obese versus lean individuals. We compared functional connectivity networks related to food reward and saliency after an overnight fast (baseline) and after a prolonged fast of 48 h in lean versus obese subjects. We included 13 obese (2 males, 11 females, BMI 35.4 ± 1.2 kg/m(2), age 31 ± 3 years) and 11 lean subjects (2 males, 9 females, BMI 23.2 ± 0.5 kg/m(2), age 28 ± 3 years). Resting-state functional magnetic resonance imaging scans were made after an overnight fast (baseline) and after a prolonged 48 h fast. Functional connectivity of the amygdala, hypothalamus and posterior cingulate cortex (default-mode) networks was assessed using seed-based correlations. At baseline, we found a stronger connectivity between hypothalamus and left insula in the obese subjects. This effect diminished upon the prolonged fast. After prolonged fasting, connectivity of the hypothalamus with the dorsal anterior cingulate cortex (dACC) increased in lean subjects and decreased in obese subjects. Amygdala connectivity with the ventromedial prefrontal cortex was stronger in lean subjects at baseline, which did not change upon the prolonged fast. No differences in posterior cingulate cortex connectivity were observed. In conclusion, obesity is marked by alterations in functional connectivity networks involved in food reward and salience. Prolonged fasting differentially affected hypothalamic connections with the dACC and the insula between obese and lean subjects. Our data support the idea that food reward and nutrient deprivation are differently perceived and/or processed in obesity.

Investigating distinct and common abnormalities of resting-state functional connectivity in depression, anxiety, and their comorbid states.

Depression and anxiety disorders are highly comorbid and share neurobiological characteristics. However, this is usually not explicitly addressed in studies on intrinsic brain functioning in these disorders. Contrary to previous resting-state reports on small, monodiagnostic subsets of the current sample, we investigated resting-state functional connectivity (RSFC) in medication-free patients with depression, anxiety, comorbid depression and anxiety, and a healthy control group. RSFC was investigated in 140 medication-free subjects: 37 major depressive disorder patients (MDD), 30 patients with one or more anxiety disorders (ANX), 25 patients with MDD and one or more anxiety disorders (COM), and 48 healthy controls (HC). RSFC networks were calculated using a probabilistic independent component analysis. Using a dual regression approach, individuals׳ timecourses were extracted and regressed to obtain subjects-specific spatial maps, which were used for group comparisons in four networks of interest (limbic, default mode, salience and sensory-motor networks). When compared to HC, the COM group showed increased RSFC of the limbic network with a cluster containing the bilateral precuneus, intracalcarine cortex, lingual gyrus, and posterior cingulate, and with a cluster including the right precentral gyrus, inferior frontal gyrus, and middle frontal gyrus. This effect was specific for comorbid depression and anxiety. No abnormal RSFC of other networks or in the MDD and ANX groups was observed. No association was found between strength of RSFC and symptom severity. These results indicate that altered RSFC of cortical regions with a limbic network could be specific for comorbid depression and anxiety.