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1.
Sci Adv ; 7(15)2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33837086

RESUMO

Individuals with alcohol use disorder (AUD) show elevated brain metabolism of acetate at the expense of glucose. We hypothesized that a shift in energy substrates during withdrawal may contribute to withdrawal severity and neurotoxicity in AUD and that a ketogenic diet (KD) may mitigate these effects. We found that inpatients with AUD randomized to receive KD (n = 19) required fewer benzodiazepines during the first week of detoxification, in comparison to those receiving a standard American (SA) diet (n = 14). Over a 3-week treatment, KD compared to SA showed lower "wanting" and increased dorsal anterior cingulate cortex (dACC) reactivity to alcohol cues and altered dACC bioenergetics (i.e., elevated ketones and glutamate and lower neuroinflammatory markers). In a rat model of alcohol dependence, a history of KD reduced alcohol consumption. We provide clinical and preclinical evidence for beneficial effects of KD on managing alcohol withdrawal and on reducing alcohol drinking.

2.
Cereb Cortex ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33629726

RESUMO

Here we assessed changes in subcortical volumes in alcohol use disorder (AUD). A simple morphometry-based classifier (MC) was developed to identify subcortical volumes that distinguished 32 healthy controls (HCs) from 33 AUD patients, who were scanned twice, during early and later withdrawal, to assess the effect of abstinence on MC-features (Discovery cohort). We validated the novel classifier in an independent Validation cohort (19 AUD patients and 20 HCs). MC-accuracy reached 80% (Discovery) and 72% (Validation). MC features included the hippocampus, amygdala, cerebellum, putamen, corpus callosum, and brain stem, which were smaller and showed stronger age-related decreases in AUD than HCs, and the ventricles and cerebrospinal fluid, which were larger in AUD and older participants. The volume of the amygdala showed a positive association with anxiety and negative urgency in AUD. Repeated imaging during the third week of detoxification revealed slightly larger subcortical volumes in AUD patients, consistent with partial recovery during abstinence. The steeper age-associated volumetric reductions in stress- and reward-related subcortical regions in AUD are consistent with accelerated aging, whereas the amygdalar associations with negative urgency and anxiety in AUD patients support its involvement in the "dark side of addiction".

3.
Cereb Cortex ; 31(5): 2561-2573, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33350441

RESUMO

Despite bariatric surgery being the most effective treatment for obesity, a proportion of subjects have suboptimal weight loss post-surgery. Therefore, it is necessary to understand the mechanisms behind the variance in weight loss and identify specific baseline biomarkers to predict optimal weight loss. Here, we employed functional magnetic resonance imaging (fMRI) with baseline whole-brain resting-state functional connectivity (RSFC) and a multivariate prediction framework integrating feature selection, feature transformation, and classification to prospectively identify obese patients that exhibited optimal weight loss at 6 months post-surgery. Siamese network, which is a multivariate machine learning method suitable for small sample analysis, and K-nearest neighbor (KNN) were cascaded as the classifier (Siamese-KNN). In the leave-one-out cross-validation, the Siamese-KNN achieved an accuracy of 83.78%, which was substantially higher than results from traditional classifiers. RSFC patterns contributing to the prediction consisted of brain networks related to salience, reward, self-referential, and cognitive processing. Further RSFC feature analysis indicated that the connection strength between frontal and parietal cortices was stronger in the optimal versus the suboptimal weight loss group. These findings show that specific RSFC patterns could be used as neuroimaging biomarkers to predict individual weight loss post-surgery and assist in personalized diagnosis for treatment of obesity.

4.
Addict Biol ; 26(1): e12838, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-31713961

RESUMO

The translocator protein (TSPO) transports cholesterol into mitochondria and is involved in steroidogenesis. The TSPO polymorphism rs6971 influences binding of cholesterol and other TSPO ligands including positron-emission tomography (PET) imaging radiotracers. Although it is recognized that alcohol increases plasma high-density lipoproteins (HDLs), its effects on total cholesterol and triglycerides along with its relationship to TSPO genotype have not been assessed. Here, we evaluated whether plasma cholesterol and triglycerides are disrupted in alcohol use disorder (AUD) and their association with rs6971 in 932 AUD participants (DSM IV or 5) and 546 controls. AUD participants compared with controls had significantly higher plasma levels of total cholesterol, HDL, and triglycerides, but not of low-density lipoprotein (LDL). In the AUD group only, TSPO rs6971 had a significant effect on plasma levels of cholesterol, LDL, and triglycerides (AA (n = 62) > AG (n = 319) > GG (n = 551)), but not on HDL levels. Additionally, we showed a significant effect of TSPO rs6971 on withdrawal scores (Clinical Institute Withdrawal Assessment for Alcohol [CIWA]), with higher scores in AA (n = 50) compared with AG (n = 238) and GG (n = 428). CIWA scores in AUD participants correlated negatively with LDL and positively with HDL, but not with total cholesterol or triglycerides. These findings corroborate elevated plasma cholesterol and HDL levels in AUD and document significant increases in triglycerides. We also reveal for the first time an association in AUD participants between TSPO rs6971 genotype and plasma cholesterol, LDL, and triglyceride levels (not for HDL) and with withdrawal severity. Mediation analyses revealed that LDL (but not HDL) influenced the association between TSPO and alcohol withdrawal severity.

5.
Brain Behav ; : e01961, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33216461

RESUMO

INTRODUCTION: Repeated exposure to high doses of alcohol triggers neuroinflammatory processes that contribute to craving and mood dysfunction in alcohol use disorder (AUD). The upregulation of the translocator protein (TSPO) is considered a biomarker of neuroinflammation, and TSPO ligands have been used as neuroimaging biomarkers of neuroinflammation. Epigenetic mechanisms are also implicated in neuroinflammatory responses to alcohol, and elevated expression of HDAC2 and HDAC6 has been reported in the brain of animals exposed to chronic alcohol. METHODS: The present study examined the transcriptional regulation of TSPO, HDAC2, and HDAC6 in human postmortem brain tissue from males previously diagnosed with AUD (n = 11) compared to age-matched nondependent males (n = 13) in four brain regions relevant to AUD: prefrontal cortex (PFC), nucleus accumbens (NAc), hippocampus (HPP), and amygdala (AMY). RESULTS: Translocator protein mRNA levels in AMY and PFC and HDAC2 and HDAC6 mRNA levels in AMY were upregulated in AUD compared to controls. In AMY, TSPO mRNA levels were positively associated with HDAC2 and HDAC6 mRNA levels, suggesting a possible regulation of TSPO by HDAC2 and HDAC6 in this brain region. In contrast, there were no group differences for TSPO, HDAC2, and HDAC6 in NAc and HPP. CONCLUSION: Our study is the first to find upregulated TSPO mRNA levels in AMY and PFC in postmortem brains from AUD consistent with neuroinflammation, and in the amygdala, they implicate epigenetic regulation of TSPO by HDAC2 and HDAC6.

6.
Front Neurosci ; 14: 565668, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33192252

RESUMO

The enzyme aromatase catalyzes the final step in estrogen biosynthesis, converting testosterone to estradiol, and is expressed in the brain of all mammals. Estrogens are thought to be important for maintenance of cognitive function in women, whereas testosterone is thought to modulate cognitive abilities in men. Here, we compare differences in cognitive performance in relation to brain aromatase availability in healthy men and women. Twenty-seven healthy participants were administered tests of verbal learning and memory and perceptual/abstract reasoning. In vivo images of brain aromatase availability were acquired in this sample using positron emission tomography (PET) with the validated aromatase radiotracer [11C]vorozole. Regions of interest were placed bilaterally on the amygdala and thalamus where aromatase availability is highest in the human brain. Though cognitive performance and aromatase availability did not differ as a function of sex, higher availability of aromatase in the amygdala was associated with lower cognitive performance in men. No such relationship was found in women; and the corresponding regression slopes were significantly different between the sexes. Thalamic aromatase availability was not significantly correlated with cognitive performance in either sex. These findings suggest that the effects of brain aromatase on cognitive performance are both region- and sex-specific and may explain some of the normal variance seen in verbal and nonverbal cognitive abilities in men and women as well as sex differences in the trajectory of cognitive decline associated with Alzheimer's disease.

7.
Cereb Cortex ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33037819

RESUMO

The biological mediators that support cognitive-control and long-term weight-loss after laparoscopic sleeve gastrectomy (LSG) remain unclear. We measured peripheral appetitive hormones and brain functional-connectivity (FC) using magnetic-resonance-imaging with food cue-reactivity task in 25 obese participants at pre, 1 month, and 6 month after LSG, and compared with 30 normal weight controls. We also used diffusion-tensor-imaging to explore whether LSG increases brain structural-connectivity (SC) of regions involved in food cue-reactivity. LSG significantly decreased BMI, craving for high-calorie food cues, ghrelin, insulin, and leptin levels, and increased self-reported cognitive-control of eating behavior. LSG increased FC between the right dorsolateral prefrontal cortex (DLPFC) and the pregenual anterior cingulate cortex (pgACC) and increased SC between DLPFC and ACC at 1 month and 6 month after LSG. Reduction in BMI correlated negatively with increased FC of right DLPFC-pgACC at 1 month and with increased SC of DLPFC-ACC at 1 month and 6 month after LSG. Reduction in craving for high-calorie food cues correlated negatively with increased FC of DLPFC-pgACC at 6 month after LSG. Additionally, SC of DLPFC-ACC mediated the relationship between lower ghrelin levels and greater cognitive control. These findings provide evidence that LSG improved functional and structural connectivity in prefrontal regions, which contribute to enhanced cognitive-control and sustained weight-loss following surgery.

8.
Addict Biol ; : e12974, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084195

RESUMO

Obese individuals exhibit brain functional abnormalities in multiple regions implicated in reward/motivation, emotion/memory, homeostatic regulation, and executive control when exposed to food cues and during rest. However, it remains unclear whether abnormal brain responses to food cues might account for or relate to their abnormal activity in resting state. This information would be useful for understanding the neural mechanisms behind hyperactive responses to food cues, a critical marker of obesity. Resting-state functional magnetic resonance imaging (RS-fMRI) and a cue-reactivity fMRI task with high- (HiCal) and low-caloric (LoCal) food cues were employed to investigate brain baseline activity and food cue-induced activation differences in 44 obese participants (OB), in 37 overweight participants (OW), and in 37 normal weight (NW) controls. One-way analyses of variance showed there was a group difference in the left hippocampus/amygdala activity during resting state and during food-cue stimulation (pFWE < 0.05); post-hoc tests showed the OB group had both greater basal activity and greater food cue-induced activation than the OW and NW groups; OW had higher activity in the hippocampus/amygdala than the NW group, which was only significant during resting state. In the OB group, resting-state activity in the left hippocampus/amygdala was positively correlated with activation induced by HiCal food cues, and both of these measures correlated with body mass index (BMI). Mediation analysis showed that the relationship between BMI and hippocampus/amygdala response to HiCal food cues was mediated by their resting-state activity. These findings suggest a close association between obesity and brain functional abnormality in the hippocampus/amygdala. They also indicate that resting-state activity in the hippocampus/amygdala may impact these regions' responses to food cues.

9.
Psychiatry Res Neuroimaging ; 305: 111185, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32957041

RESUMO

Alcohol induces neuroinflammation but its role in cognitive impairment and impulsivity in alcohol use disorder (AUD) has been poorly investigated. We used proton magnetic resonance spectroscopy to measure brain glutamate (Glu) levels and diffusion-weighted imaging to measure functional anisotropy (FA) in the thalamus and ventral anterior cingulate cortex (vACC) in 15 recently detoxified patients with AUD and 14 matched controls. Compared to controls, AUD patients showed higher Glu levels (p = 0.04) and lower FA in the thalamus (p = 0.04) but not in the vACC. In AUD, thalamic Glu levels (r = 0.62, p = 0.019) and FA (r=-0.55, p = 0.034) were associated with severity of drinking (drinks/week). Compared to controls, AUD patients showed higher scores on Conners' Adult ADHD Rating Scale for impulsivity (p = 0.03), which correlated with glutamate levels in the thalamus (r = 0.58, p = 0.03) and vACC (r = 0.55, p = 0.036). In a second cohort of AUD patients (n = 32), Glu in dorsal ACC (dACC) also correlated with Barrett Impulsiveness Scale total score (r = 0.43, p = 0.014). We interpret the elevated thalamic Glu levels and the parallel reduction in FA in AUD-which correlated with drinking severity-as possible evidence of neurotoxicity from neuroinflammation. The association of Glu with impulsivity suggests that neurotoxic effects of chronic alcohol exposure in the thalamus and dACC may contribute to impulsivity.

10.
Proc Natl Acad Sci U S A ; 117(37): 22962-22966, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32868418

RESUMO

Gonadal hormones are linked to mechanisms that govern appetitive behavior and its suppression. Estrogens are synthesized from androgens by the enzyme aromatase, highly expressed in the ovaries of reproductive-aged women and in the brains of men and women of all ages. We measured aromatase availability in the amygdala using positron emission tomography (PET) with the aromatase inhibitor [11C]vorozole in a sample of 43 adult, normal-weight, overweight, or obese men and women. A subsample of 27 also completed personality measures to examine the relationship between aromatase and personality traits related to self-regulation and inhibitory control. Results indicated that aromatase availability in the amygdala was negatively associated with body mass index (BMI) (in kilograms per square meter) and positively correlated with scores of the personality trait constraint independent of sex or age. Individual variations in the brain's capacity to synthesize estrogen may influence the risk of obesity and self-control in men and women.


Assuntos
Apetite/fisiologia , Estrogênios/metabolismo , Obesidade/metabolismo , Adulto , Idoso , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/metabolismo , Androgênios , Aromatase/análise , Inibidores da Aromatase , Índice de Massa Corporal , Encéfalo/metabolismo , Estrogênios/fisiologia , Feminino , Humanos , Lipogênese , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Autocontrole
11.
J Neurol Sci ; 418: 117099, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-32866814

RESUMO

Adolescence is a period of rapid neural and behavioral development that often precipitates substance use, substance use disorders (SUDs), and other psychopathology. While externalizing disorders have been closely linked to SUD epidemiologically, the comorbidity of internalizing disorders and SUD is less well understood. Neuroimaging studies can be used to measure structural and functional developments in the brain that mediate the relationship between psychopathology and SUD in adolescence. Externalizing disorders and SUD are both associated with structural and functional changes in the basal ganglia and prefrontal cortex in adolescence. The neural mechanisms underlying internalizing disorders and SUD are less clear, but evidence points to involvement of the amygdala and prefrontal cortex. We also highlight independent contributions of SUD, which may vary in certain ways by the substances assessed. A deeper understanding of the neural basis of the relationship between psychopathology and SUD will allow for more informed interventions in this critical developmental stage.

12.
Nutrients ; 12(7)2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32629783

RESUMO

While the global prevalence of obesity has risen among both men and women over the past 40 years, obesity has consistently been more prevalent among women relative to men. Neuroimaging studies have highlighted several potential mechanisms underlying an individual's propensity to become obese, including sex/gender differences. Obesity has been associated with structural, functional, and chemical alterations throughout the brain. Whereas changes in somatosensory regions appear to be associated with obesity in men, reward regions appear to have greater involvement in obesity among women than men. Sex/gender differences have also been observed in the neural response to taste among people with obesity. A more thorough understanding of these neural and behavioral differences will allow for more tailored interventions, including diet suggestions, for the prevention and treatment of obesity.

13.
Theranostics ; 10(16): 7369-7383, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32641997

RESUMO

Rationale: Neuroadaptations in the medial prefrontal cortex (mPFC) and Nucleus Accumbens (NAc) play a role in the disruption of control-reward circuits in opioid addiction. Small Conductance Calcium-Activated Potassium (SK) channels in the mPFC have been implicated in neuronal excitability changes during morphine withdrawal. However, the mechanism that modulates SK channels during withdrawal is still unknown. Methods: Rats were exposed for one week to daily morphine injections (10 mg·kg-1 s.c.) followed by conditional place preference (CPP) assessment. One week after withdrawal, electrophysiological, morphological and molecular biological methods were applied to investigate the effects of morphine on SK channels in mPFC, including infralimbic (IL), prelimbic (PrL) cortices and NAc (core and shell). We verified the hypothesis that Rac1, a member of Rho family of small GTPases, implicated in SK channel regulation, modulate SK channel neuroadaptations during opiate withdrawal. Results: One week after morphine withdrawal, the neuronal excitability of layer 5 pyramidal neurons in IL was decreased, but not in PrL. Whereas, the excitability was increased in NAc-shell, but not in NAc-core. In mPFC, the expression of the SK3 subunit was enhanced after one-week of withdrawal compared to controls. In the IL, Rac1 signaling was increased during withdrawal, and the Rac1 inhibitor NSC23766 disrupted SK current, which increased neuronal firing. Suppression of Rac1 inhibited morphine-induced CPP and expression of SK channels in IL. Conclusions: These findings highlight the potential value of SK channels and the upstream molecule Rac1, which may throw light on the therapeutic mechanism of neuromodulation treatment for opioid dependence.

14.
Cereb Cortex ; 30(11): 5930-5942, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32564073

RESUMO

The human brain is organized into segregated networks with strong within-network connections and relatively weaker between-network connections. This "small-world" organization may be essential for maintaining an energetically efficient system, crucial to the brain which consumes 20% of the body's energy. Brain network segregation and glucose energy utilization both change throughout the lifespan. However, it remains unclear whether these processes interact to contribute to differences in cognitive performance with age. To address this, we examined fluorodeoxyglucose-positron emission tomography and resting-state functional magnetic resonance imaging from 88 participants aged 18-73 years old. Consistent with prior work, brain network segregation showed a negative association with age across both sensorimotor and association networks. However, relative glucose metabolism demonstrated an interaction with age, showing a negative slope in association networks but a positive slope in sensorimotor networks. Overall, brain networks with lower segregation showed significantly steeper age-related differences in glucose metabolism, compared with highly segregated networks. Sensorimotor network segregation mediated the association between age and poorer spatial cognition performance, and sensorimotor network metabolism mediated the association between age and slower response time. These data provide evidence that sensorimotor segregation and glucose metabolism underlie some age-related changes in cognition. Interventions that stimulate somatosensory networks could be important for treatment of age-related cognitive decline.

15.
Addiction ; 115(11): 2130-2139, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32350970

RESUMO

BACKGROUND AND AIMS: Although personality traits are implicated in substance use disorders (SUDs) and obesity, differences and similarities between them have not been assessed. Our main aim was to compare personality traits between people with different SUDs, obese people and healthy controls. DESIGN: This was a secondary analysis of personality scores obtained from participants in neuroimaging studies from Brookhaven National Laboratory and the Laboratory of Neuroimaging, National Institutes of Health. SETTING: United States. PARTICIPANTS/CASES: Individuals with obesity (OB) n = 41, alcohol use disorder (AUD) n = 39, marijuana use disorder (MUD) n = 24, cocaine use disorder (CUD) n = 100, and healthy controls (HC) n = 117 (237 males and 84 females). MEASUREMENTS: The Multidimensional Personality Questionnaire, which characterizes positive emotionality (PEM), negative emotionality (NEM) and constraint (CON) traits. Adjusted covariates included cigarette smoking status, age, gender and body mass index (BMI). FINDINGS: Multivariate analysis of covariance showed a main group effect (i.e. OB, AUD, MUD, CUD and HC) only on NEM (P < 0.0001, η2  = 0.17) and CON (P = 0.005, η2  = 0.12). Specifically, NEM was higher in AUD (P < 0.0001, d = 10.4), CUD (P < 0.0001, d = 8.2) and MUD (P = 0.001, d = 9.2), but not in OB (P > 0.05, d = 2.8) relative to HC. CUD showed lower CON (P = 0.015, d = 5.4) and PEM (P = 0.018, d = 4.8) than HC; however, these differences were not significant in the other groups. NEM and CON were negatively correlated for groups combined (r = -0.26, P < 0.0001), and separately for OB (r = -0.49, P = 0.001) and CUD (r = -0.22, P = 0.03). Cigarette smoking status did not influence group differences in NEM, PEM or CON. CONCLUSIONS: Compared with healthy controls, people with substance use disorders appear to show higher negative emotionality, and people with cocaine use disorders appear to show lower positive emotionality and constraint traits. Similar findings were not found among people with obesity.

16.
Sleep ; 43(10)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-32333599

RESUMO

STUDY OBJECTIVES: Sleep deprivation and circadian disruptions impair brain function and cognitive performance, but few studies have examined the effect of sleep inconsistency. Here, we investigated how inconsistent sleep duration and sleep timing between weekends (WE) and weekdays (WD) correlated with changes in behavior and brain function during task and at rest in 56 (30 female) healthy human participants. METHODS: WE-WD differences in sleep duration and sleep midpoint were calculated using 1-week actigraphy data. All participants underwent 3 Tesla blood-oxygen-level-dependent functional Magnetic Resonance Imaging (fMRI) to measure brain activity during a visual attention task (VAT) and in resting-state condition. RESULTS: We found that WE-WD inconsistency of sleep duration and sleep midpoint were uncorrelated with each other (r = .08, p = .58) and influenced behavior and brain function differently. Our healthy participants showed relatively small WE-WD differences (WE-WD: 0.59 hours). Longer WE sleep duration (relative to WD sleep duration) was associated with better attentional performance (3-ball: ß = .30, t = 2.35, p = .023; 4-ball: ß = .30, t = 2.21, p = .032) and greater deactivation of the default mode network (DMN) during VAT (p < .05, cluster-corrected) and greater resting-state functional connectivity (RSFC) between anterior DMN and occipital cortex (p < .01, cluster-corrected). In contrast, later WE sleep timing (relative to WD sleep timing) (WE-WD: 1.11 hours) was associated with worse performance (4-ball: ß = -.33, t = -2.42, p = .020) and with lower occipital activation during VAT and with lower RSFC within the DMN. CONCLUSIONS: Our results document the importance of consistent sleep timing for brain function in particular of the DMN and provide evidence of the benefits of WE catch-up sleep in healthy adults.

17.
Front Aging Neurosci ; 12: 20, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32161532

RESUMO

Age-related alterations of functional brain networks contribute to cognitive decline. Current theories indicate that age-related intrinsic brain functional reorganization may be a critical marker of cognitive aging. Yet, little is known about how intrinsic interhemispheric functional connectivity changes with age in adults, and how this relates to critical executive functions. To address this, we examined voxel-mirrored homotopic connectivity (VMHC), a metric that quantifies interhemispheric communication, in 93 healthy volunteers (age range: 19-85) with executive function assessment using the Delis-Kaplan Executive Function System (D-KEFS) scales. Resting functional MRI data were analyzed to assess VMHC, and then a multiple linear regression model was employed to evaluate the relationship between age and the whole-brain VMHC. We observed age-related reductions in VMHC of ventromedial prefrontal cortex (vmPFC) and hippocampus in the medial temporal lobe subsystem, dorsal anterior cingulate cortex and insula in salience network, and inferior parietal lobule in frontoparietal control network. Performance on the color-word inhibition task was associated with VMHC of vmPFC and insula, and VMHC of vmPFC mediated the relationship between age and CWIT inhibition reaction times. The percent ratio of correct design scores in design fluency test correlated positively with VMHC of the inferior parietal lobule. The current study suggests that brain interhemispheric functional alterations may be a promising new avenue for understanding age-related cognitive decline.

18.
Brain Imaging Behav ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125616

RESUMO

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 food>neutral, cocaine>neutral and cocaine>food; dorsolateral prefrontal cortex for cocaine>neutral and cocaine>food, and midbrain for cocaine>food (all pFWE < 0.05). When comparing unconscious (33 ms) > conscious (750 and 3000 ms) presentations, we observed significant differences for cocaine>neutral and cocaine>food in occipital cortex, for cocaine>neutral in the insula/temporal lobe, and for food>neutral in the middle temporal gyrus (pFWE < 0.05). No diurnal differences for brain activations were observed. We interpret these findings to suggest that negative items (e.g., cocaine) might be perceived at a faster speed than positive ones (e.g., food), although we cannot rule out that the higher saliency of cocaine cues, which would be novel to non-drug using individuals, contributed to the faster speed of detection.

19.
J Neurol ; 267(7): 1931-1940, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32170447

RESUMO

OBJECTIVE: Obese individuals have shown functional abnormalities in frontal-limbic regions, and bariatric surgery is an effective treatment for morbid obesity. The aim of the study was to investigate how bariatric surgery modulates brain regional activation and functional connectivity (FC) to food cues, and whether the underlying structural connectivity (SC) alterations contribute to these functional changes as well as behavioral changes. METHODS: A functional magnetic resonance imaging cue-reactivity task with high- (HiCal) and low-calorie (LoCal) food pictures and diffusion tensor imaging (DTI) with deterministic tractography were used to investigate brain reactivity, FC and SC in 28 obese participants tested before and 1 month after laparoscopic sleeve gastrectomy (LSG). Twenty-two obese controls (Ctr) without surgery were also tested at baseline and 1 month later. RESULTS: LSG significantly decreased right dorsolateral prefrontal cortex (DLPFC) activation to HiCal versus LoCal cues and increased FC between DLPFC and ventral anterior cingulate cortex (vACC), which are regions involved in self-regulation of feeding behaviors. LSG also increased SC between DLPFC and ACC as quantified by fractional anisotropy. Increases in SC and FC between DLPFC and ACC were associated with greater reductions in BMI, and SC changes were positively correlated with FC changes. Increased SC between right DLPFC and ACC mediated the relationship between reduced BMI and increased right DLPFC-vACC FC; likewise, increases in right DLPFC-vACC FC mediated the relationship between increased right DLPFC-ACC SC and reduced BMI. CONCLUSION: LSG might induce weight loss in part by increasing SC and FC between DLPFC and ACC, and thus strengthening top-down control over food intake.

20.
Obesity (Silver Spring) ; 28(3): 601-608, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32090510

RESUMO

OBJECTIVE: The aim of this study was to investigate alterations in functional connectivity (FC) within and interactions between resting-state networks involved in salience, executive control, and interoception in participants with obesity (OB). METHODS: Using resting-state functional magnetic resonance imaging with independent component analysis and FC, alterations within and interactions between resting-state networks in 35 OB and 35 normal-weight controls (NW) were investigated. RESULTS: Compared with NW, OB showed reduced FC strength in the ventromedial prefrontal cortex and posterior cingulate cortex/precuneus within the default-mode network, dorsal anterior cingulate cortex within the salience network (SN), bilateral dorsolateral prefrontal cortex-angular gyrus within the frontoparietal network (FPN), and increased FC strength in the insula (INS) (Pfamilywise error < 0.0125). The dorsal anterior cingulate cortex FC strength was negatively correlated with craving for food cues, left dorsolateral prefrontal cortex FC strength was negatively correlated with Yale Food Addiction Scale scores, and right INS FC strength was positively correlated with craving for high-calorie food cues. Compared with NW, OB also showed increased FC between the SN and FPN driven by altered FC of bilateral INS and anterior cingulate cortex-angular gyrus. CONCLUSIONS: Alterations in FC within and interactions between the SN, default-mode network, and FPN might contribute to the high incentive value of food (craving), lack of control of overeating (compulsive overeating), and increased awareness of hunger (impaired interoception) in OB.


Assuntos
Mapeamento Encefálico/métodos , Imagem por Ressonância Magnética/métodos , Vias Neurais/fisiopatologia , Obesidade/fisiopatologia , Adulto , Função Executiva , Feminino , Humanos , Masculino , Voluntários
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