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1.
J Neurol ; 2020 Mar 13.
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.

2.
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.

3.
Obesity (Silver Spring) ; 28(3): 601-608, 2020 Mar.
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.

4.
Surg Obes Relat Dis ; 16(1): 1-9, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31679986

RESUMO

BACKGROUND: Obesity is associated with decreased brain gray- (GM) and white-matter (WM) volumes in regions. Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric surgery associated with neuroplastic changes in patients with obesity at 1 month postLSG. OBJECTIVE: To investigate whether LSG can induce sustained neuroplastic recovery of brain structural abnormalities, and whether structural changes are accompanied by functional alterations. SETTING: University hospital, longitudinal study. METHODS: Structural magnetic resonance imaging and voxel-based morphometry analysis were employed to assess GM/WM volumes in 30 obese participants at preLSG and 1 and 3 months postLSG. One-way analysis of variance modeled time effects on GM/WM volumes, and then alterations in resting-state functional connectivity (RSFC) were assessed. RESULTS: Significant time effects on GM volumes were in caudate (F = 11.20), insula (INS; F = 10.11), posterior cingulate cortex (PCC; F = 13.32), and inferior frontal gyrus (F = 12.18), and on WM volumes in anterior cingulate cortex (F = 15.70), PCC (F = 15.56), and parahippocampus (F = 17.96, PFDR < .05). Post hoc tests showed significantly increased GM volumes in caudate (mean change ± SEM .018 ± .005 and P = .001, .031 ± .007 and P < .001), INS (.027 ± .008 and P = .003, .043 ± .009 and P < .001), and PCC (.008 ± .004 and P = .042, .026 ± .006 and P < .001), and increased WM volumes in anterior cingulate cortex (.029 ± .006 and P < .001, .041 ± .008 and P < .001), PCC (.017 ± .004 and P < .001, .032 ± .006 and P < .001), and parahippocampus (.031 ± .008 and P =.001, .075 ± .013 and P < .001) at 1 and 3 months postLSG compared with preLSG. Significant increases in GM volumes were in caudate (.013 ± .006 and P = .036), PCC (.019 ± .006 and P = .006), and inferior frontal gyrus (.019 ± .005 and P = .001), and in WM volumes in anterior cingulate cortex (.012 ± .005 and P = .028), PCC (.014 ± .006 and P = .017), and parahippocampus (.044 ± .014 and P = .003) at 3 relative to 1 month postLSG. GM volumes in INS and PCC showed a positive correlation at 1 (r = .57, P = .001) and 3 months postLSG (r = .55, P = .001). GM volume in INS and PCC were positively correlated with RSFC of INS-PCC (r = .40 and P = .03, r = .55 and P = .001) and PCC-INS (r = .37 and P = .046, r = .57 and P < .001) at 1 month postLSG. GM volume in INS was also positively correlated with RSFC of INS-PCC (r = .44, P = .014) and PCC-INS (r = .38, P = .037) at 3 months postLSG. CONCLUSION: LSG induces sustained structural brain changes, which might mediate long-term benefits of bariatric surgery in weight reduction. Associations between regional GM volume and RSFC suggest that LSG-induced structural changes contribute to RSFC changes.

5.
Int J Obes (Lond) ; 44(3): 590-600, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31740725

RESUMO

OBJECTIVE: Obesity is associated with impaired inhibitory control over food intake. We hypothesized that the neural circuitry underlying inhibition of food craving would be impaired in obesity. Here we assessed whether obese men show altered brain responses during attempted cognitive inhibition of craving when exposed to food cues. METHODS: Sixteen obese men (32 ± 8.7 years old, BMI = 38.6 ± 7.2) were compared with 11 age-matched non-obese men (BMI 24.2 ± 2.5) using PET and FDG. Brain glucose metabolism was evaluated in a food deprived state: no food stimulation, food stimulation with no inhibition (NI), and food stimulation with attempted inhibition (AI), each on a separate day. Individualized favorite food items were presented prior to and after FDG injection for 40 min. For AI, participants were asked to attempt to inhibit their desire for the food presented. Self-reports for hunger and food desire were recorded. RESULTS: Food stimulation compared with no stimulation increased glucose metabolism in inferior and superior frontal gyrus, default mode network and cerebellum, in both groups. For both groups, AI compared with NI-suppressed metabolism in right subgenual anterior cingulate, orbitofrontal areas, bilateral insula, and temporal gyri. There was a stimulation-by-group interaction effect in obese (but not in non-obese) men showing increased metabolism in pregenual anterior cingulate cortex (pgACC) and caudate during AI relative to NI. Changes in the food desire from NI to AI correlated negatively with changes in metabolism in pgACC/caudate in obese but not in non-obese men. CONCLUSIONS: Obese men showed higher activation in pgACC/caudate, which are regions involved with self-regulation and emotion/reward during AI. Behavioral associations suggest that successful AI is an active process requiring more energy in obese but not in non-obese men. The additional required effort to increase cognitive control in response to food stimulation in obese compared with non-obese men may contribute to their uncontrolled eating behavior.

6.
Addict Biol ; : e12838, 2019 Nov 12.
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.

7.
Front Psychiatry ; 10: 626, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31620026

RESUMO

Opioid use in the United States has steadily risen since the 1990s, along with staggering increases in addiction and overdose fatalities. With this surge in prescription and illicit opioid abuse, it is paramount to understand the genetic risk factors and neuropsychological effects of opioid use disorder (OUD). Polymorphisms disrupting the opioid and dopamine systems have been associated with increased risk for developing substance use disorders. Molecular imaging studies have revealed how these polymorphisms impact the brain and contribute to cognitive and behavioral differences across individuals. Here, we review the current molecular imaging literature to assess how genetic variations in the opioid and dopamine systems affect function in the brain's reward, cognition, and stress pathways, potentially resulting in vulnerabilities to OUD. Continued research of the functional consequences of genetic variants and corresponding alterations in neural mechanisms will inform prevention and treatment of OUD.

8.
Int J Neuropsychopharmacol ; 22(9): 548-559, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31369670

RESUMO

BACKGROUND: Excessive alcohol consumption is associated with reduced cortical thickness (CT) and lower cerebral metabolic rate of glucose (CMRGlu), but the correlation between these 2 measures has not been investigated. METHODS: We tested the association between CT and cerebral CMRGlu in 19 participants with alcohol use disorder (AUD) and 20 healthy controls. Participants underwent 2-Deoxy-2-[18F]fluoroglucose positron emission tomography to map CMRGlu and magnetic resonance imaging to assess CT. RESULTS: Although performance accuracy on a broad range of cognitive domains did not differ significantly between AUD and HC, AUD had widespread decreases in CT and CMRGlu. CMRGlu, normalized to cerebellum (rCMRGlu), showed significant correlation with CT across participants. Although there were large group differences in CMRGlu (>17%) and CT (>6%) in medial orbitofrontal and BA 47, the superior parietal cortex showed large reductions in CMRGlu (~17%) and minimal CT differences (~2.2%). Though total lifetime alcohol (TLA) was associated with CT and rCMRGlu, the causal mediation analysis revealed significant direct effects of TLA on rCMRGlu but not on CT, and there were no significant mediation effects of TLA, CT, and rCMRGlu. CONCLUSIONS: The significant correlation between decrements in CT and CMRGlu across AUD participants is suggestive of alcohol-induced neurotoxicity, whereas the findings that the most metabolically affected regions in AUD had minimal atrophy and vice versa indicates that changes in CT and CMRGlu reflect distinct responses to alcohol across brain regions.

9.
Psychopharmacology (Berl) ; 236(11): 3245-3255, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31161452

RESUMO

RATIONALE: Human telomeres consist of tandem repeats at chromosome ends which protect chromosomal DNA from degradation. Telomere shortening occurs as part of natural aging; however, life stressors, smoking, drug use, BMI, and psychiatric disorders could disrupt cell aging and affect telomere length (TL). In this context, studies have evaluated the effects of alcohol consumption on TL; however, results have been inconsistent, which may reflect diverse drinking cut-offs and categorizations. OBJECTIVES: To help clarify this, the present study addresses the association of TL with alcohol use disorder (AUD), drinking behaviors, lifetime stress, and chronological age. METHODS: TL was quantified as the telomere to albumin ratio (T/S ratio) obtained from peripheral blood DNA using the quantitative PCR assay, from 260 participants with AUD and 449 non-dependent healthy controls (HC) from an existing National Institute on Alcohol Abuse and Alcoholism (NIAAA) database. RESULTS: AUD participants showed shorter TL compared to HC with both, age, and AUD, as independent predictors as well as a significant AUD with age interaction effect on TL. TL was also associated with impulsiveness in AUD participants. We did not observe an association between TL and chronicity of alcohol use, alcohol doses ingested, or childhood trauma exposures in either AUD or HC, although very few HC reported a history of childhood trauma. CONCLUSION: Our results support previous findings of telomere shortening with chronic alcohol exposures and show both an effect of AUD on TL that is independent of age as well as a significant AUD by age interaction on TL. These findings are consistent with accelerated cellular aging in AUD.


Assuntos
Envelhecimento/genética , Alcoolismo/genética , Senescência Celular/genética , Encurtamento do Telômero/genética , Adulto , Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Envelhecimento/patologia , Envelhecimento/psicologia , Alcoolismo/diagnóstico , Alcoolismo/psicologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Telômero/genética , Telômero/patologia
10.
Curr Nutr Rep ; 8(2): 108-119, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30945140

RESUMO

PURPOSE OF REVIEW: We summarize neuroimaging findings related to processing of taste (fat, salt, umami, bitter, and sour) in the brain and how they influence hedonic responses and eating behaviors and their role in obesity. RECENT FINDINGS: Neuroimaging studies in obese individuals have revealed alterations in reward/motivation, executive control/self-regulation, and limbic/affective circuits that are implicated in food and drug addiction. Psychophysical studies show that sensory properties of food ingredients may be associated with anthropometric and neurocognitive outcomes in obesity. However, few studies have examined the neural correlates of taste and processing of calories and nutrient content in obesity. The literature of neural correlated of bitter, sour, and salty tastes remains sparse in obesity. Most published studies have focused on sweet, followed by fat and umami taste. Studies on calorie processing and its conditioning by preceding taste sensations have started to delineate a dynamic pattern of brain activation associated with appetition. Our expanded understanding of taste processing in the brain from neuroimaging studies is poised to reveal novel prevention and treatment targets to help address overeating and obesity.

11.
Neuropsychopharmacology ; 44(7): 1338, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30858533

RESUMO

The original version of this article contained an error in the affiliation of Dahua Yu, which was incorrectly stated as affiliation 3 (Engineering Research Center of Molecular and Neuro Imaging Ministry of Education, Xi'an Shaanxi, 710071, People's Republic of China), when this author is actually linked to affiliation 4 (Inner Mongolia Key Laboratory of Pattern Recognition and Intelligent Image Processing, School of Information Engineering, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia 014010, People's Republic of China).

12.
Transl Psychiatry ; 9(1): 93, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30770780

RESUMO

The response to drugs of abuse is affected by expectation, which is modulated in part by dopamine (DA), which encodes for a reward prediction error. Here we assessed the effect of expectation on methylphenidate (MP)-induced striatal DA changes in 23 participants with an active cocaine use disorder (CUD) and 23 healthy controls (HC) using [11C]raclopride and PET both after placebo (PL) and after MP (0.5 mg/kg, i.v.). Brain dopamine D2 and D3 receptor availability (D2R: non-displaceable binding potential (BPND)) was measured under four conditions in randomized order: (1) expecting PL/receiving PL, (2) expecting PL/receiving MP, (3) expecting MP/receiving PL, and (4) expecting MP/receiving MP. Expecting MP increased pulse rate compared to expecting PL. Receiving MP decreased D2R in striatum compared to PL, indicating MP-induced striatal DA release, and this effect was significantly blunted in CUD versus HC consistent with prior findings of decreased striatal dopamine responses both in active and detoxified CUD. There was a group × challenge × expectation effect in caudate and midbrain, with expectation of MP increasing MP-induced DA release in HC but not in CUD, and expectation of PL showing a trend to increase MP-induced DA release in CUD but not in HC. These results are consistent with the role of DA in reward prediction error in the human brain: decreasing DA signaling when rewards are less than expected (blunted DA increases to MP in CUD) and increasing them when greater than expected (for PL in CUD reflecting conditioned responses to injection). Our findings also document disruption of the expectation of drug effects in dopamine signaling in participants with CUD compared to non-addicted individuals.


Assuntos
Encéfalo/metabolismo , Estimulantes do Sistema Nervoso Central/uso terapêutico , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Dopamina/metabolismo , Metilfenidato/uso terapêutico , Recompensa , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Estudos de Casos e Controles , Estimulantes do Sistema Nervoso Central/farmacocinética , Transtornos Relacionados ao Uso de Cocaína/metabolismo , Transtornos Relacionados ao Uso de Cocaína/patologia , Feminino , Humanos , Masculino , Metilfenidato/farmacocinética , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Racloprida/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/metabolismo
13.
Nat Commun ; 10(1): 690, 2019 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-30741935

RESUMO

The correspondence between cerebral glucose metabolism (indexing energy utilization) and synchronous fluctuations in blood oxygenation (indexing neuronal activity) is relevant for neuronal specialization and is affected by brain disorders. Here, we define novel measures of relative power (rPWR, extent of concurrent energy utilization and activity) and relative cost (rCST, extent that energy utilization exceeds activity), derived from FDG-PET and fMRI. We show that resting-state networks have distinct energetic signatures and that brain could be classified into major bilateral segments based on rPWR and rCST. While medial-visual and default-mode networks have the highest rPWR, frontoparietal networks have the highest rCST. rPWR and rCST estimates are generalizable to other indexes of energy supply and neuronal activity, and are sensitive to neurocognitive effects of acute and chronic alcohol exposure. rPWR and rCST are informative metrics for characterizing brain pathology and alternative energy use, and may provide new multimodal biomarkers of neuropsychiatric disorders.


Assuntos
Química Encefálica/fisiologia , Mapeamento Encefálico , Encéfalo/fisiologia , Glucose/metabolismo , Adulto , Biomarcadores/metabolismo , Encéfalo/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Rede Nervosa/fisiologia , Neurônios/metabolismo , Tomografia por Emissão de Pósitrons , Adulto Jovem
14.
Eur J Neurosci ; 50(1): 1831-1842, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30803059

RESUMO

Excessive alcohol consumption is associated with neuroinflammation, which likely contributes to alcohol-related pathology. However, positron emission tomography (PET) studies using radioligands for the 18-kDa translocator protein (TSPO), which is considered a biomarker of neuroinflammation, reported decreased binding in alcohol use disorder (AUD) participants compared to controls. In contrast, autoradiographic findings in alcohol exposed rats reported increases in TSPO radioligand binding. To assess if these discrepancies reflected differences between in vitro and in vivo methodologies, we compared in vitro autoradiography (using [3 H]PBR28 and [3 H]PK11195) with in vivo PET (using [11 C]PBR28) in male, Wistar rats exposed to chronic alcohol-vapor (dependent n = 10) and in rats exposed to air-vapor (nondependent n = 10). PET scans were obtained with [11 C]PBR28, after which rats were euthanized and the brains were harvested for autoradiography with [3 H]PBR28 and [3 H]PK11195 (n = 7 dependent and n = 7 nondependent), and binding quantified in hippocampus, thalamus, and parietal cortex. Autoradiography revealed significantly higher binding in alcohol-dependent rats for both radioligands in thalamus and hippocampus (trend level for [3 H]PBR28) compared to nondependent rats, and these group differences were stronger for [3 H]PK11195 than [3 H]PBR28. In contrast, PET measures obtained in the same rats showed no group difference in [11 C]PBR28 binding. Our in vitro data are consistent with neuroinflammation associated with chronic alcohol exposure. Failure to observe similar increases in [11 C]PBR28 binding in vivo suggests the possibility that a mechanism mediated by chronic alcohol exposure interferes with [11 C]PBR28 binding to TSPO in vivo. These data question the sensitivity of PBR28 PET as a methodology to assess neuroinflammation in AUD.

15.
Brain Imaging Behav ; 13(4): 1172-1181, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30054871

RESUMO

Dopamine projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and from the substantia nigra (SN) to the dorsal striatum are involved in addiction. However, relatively little is known about the implication of these circuits in Internet gaming disorder (IGD). This study examined the alteration of resting-state functional connectivity (RSFC) and diffusion tensor imaging (DTI) -based structural connectivity of VTA/SN circuits in 61 young male participants (33 IGD and 28 healthy controls). Correlation analysis was carried out to investigate the relationship between the neuroimaging findings and the behavioral Internet Addiction Test (IAT). Both the NAc and medial orbitofrontal cortex (mOFC) showed lower RSFC with VTA in IGD subjects compared with controls. Moreover, the RSFC strength of VTA-right NAc and VTA-left mOFC correlated negatively with IAT in IGD subjects. The IGD subjects also showed lower structural connectivity in bilateral VTA-NAc tracts compared with controls, but the connectivity did not correlate with IAT in IGD. We provide evidence that functional and structural connectivity of the VTA-NAc pathway, and functional connectivity of the VTA-mOFC pathway are implicated in IGD. Since these pathways are important for dopamine reward signals and salience attribution, the findings suggest involvement of the brain DA reward system in the neurobiology of IGD. The association of functional but not structural connectivity of VTA circuits with IAT suggests that while lower structural connectivity might underlie vulnerability for IGD, lower functional connectivity may modulate severity. These results strengthen the evidence that IGD shares similar neuropathology with other addictions.


Assuntos
Comportamento Aditivo/fisiopatologia , Área Tegmentar Ventral/fisiopatologia , Jogos de Vídeo/efeitos adversos , Adolescente , Adulto , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Córtex Cerebral/fisiopatologia , Imagem de Tensor de Difusão , Substância Cinzenta , Humanos , Internet , Imagem por Ressonância Magnética , Masculino , Vias Neurais/fisiopatologia , Núcleo Accumbens/fisiopatologia , Descanso , Adulto Jovem
16.
Int J Obes (Lond) ; 43(4): 842-851, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29915363

RESUMO

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.

17.
Neuroimage ; 185: 263-273, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30342236

RESUMO

The role of sleep in brain physiology is poorly understood. Recently rodent studies have shown that the glymphatic system clears waste products from brain more efficiently during sleep compared to wakefulness due to the expansion of the interstitial fluid space facilitating entry of cerebrospinal fluid (CSF) into the brain. Here, we studied water diffusivity in the brain during sleep and awake conditions, hypothesizing that an increase in water diffusivity during sleep would occur concomitantly with an expansion of CSF volume - an effect that we predicted based on preclinical findings would be most prominent in cerebellum. We used MRI to measure slow and fast components of the apparent diffusion coefficient (ADC) of water in the brain in 50 healthy participants, in 30 of whom we compared awake versus sleep conditions and in 20 of whom we compared rested-wakefulness versus wakefulness following one night of sleep-deprivation. Sleep compared to wakefulness was associated with increases in slow-ADC in cerebellum and left temporal pole and with decreases in fast-ADC in thalamus, insula, parahippocampus and striatal regions, and the density of sleep arousals was inversely associated with ADC changes. The CSF volume was also increased during sleep and was associated with sleep-induced changes in ADCs in cerebellum. There were no differences in ADCs with wakefulness following sleep deprivation compared to rested-wakefulness. Although we hypothesized increases in ADC with sleep, our findings uncovered both increases in slow ADC (mostly in cerebellum) as well as decreases in fast ADC, which could reflect the distinct biological significance of fast- and slow-ADC values in relation to sleep. While preliminary, our findings suggest a more complex sleep-related glymphatic function in the human brain compared to rodents. On the other hand, our findings of sleep-induced changes in CSF volume provide preliminary evidence that is consistent with a glymphatic transport process in the human brain.


Assuntos
Encéfalo/metabolismo , Líquido Cefalorraquidiano/metabolismo , Sistema Glinfático/fisiologia , Sono/fisiologia , Adulto , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Masculino
18.
Drug Alcohol Depend ; 194: 430-437, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30502544

RESUMO

Numerous studies have documented cognitive impairments in multiple domains in patients with an alcohol use disorder (AUD), including perceptuomotor, executive, and visuospatial functions. Although the neural underpinnings of cognitive deficits in AUD have been studied extensively, the neural basis of attention deficits in AUD remains relatively unexplored. Here, we investigated neural responses to a visual attention task (VAT) in 19 recently abstinent patients with AUD and 23 healthy control participants (HC) using functional MRI (fMRI). AUD had a mean number of 62 ± 34SD drinks per week and 29 ± 13 years' history of alcohol use. Results show that there were no behavioral differences (accuracy or reaction time) between groups during the VAT. For both groups, the VAT activated brain areas associated with visual attention load (i.e., parietal and prefrontal cortices) and visual processing (i.e., occipital cortex), which is in line with previous reports on the same task in healthy volunteers. Despite similar behavioral performances, AUD participants showed decreased VAT activation in regions of the dorsal and ventral attention networks, including parietal and prefrontal cortices, and in the insula as compared to controls. These findings corroborate differences in attention networks in AUD compared to HC that might underlie attention deficits in AUD, whereas impairments in the insula could reflect a disruption of interoception processing as found in other addictions.


Assuntos
Alcoolismo/diagnóstico por imagem , Atenção/fisiologia , Encéfalo/diagnóstico por imagem , Percepção Visual/fisiologia , Adulto , Alcoolismo/fisiopatologia , Encéfalo/fisiopatologia , Mapeamento Encefálico , Cognição/fisiologia , Feminino , Neuroimagem Funcional , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tempo de Reação/fisiologia
19.
Psychoneuroendocrinology ; 100: 229-236, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30388597

RESUMO

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 (PFWE < 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.

20.
Brain Imaging Behav ; 13(3): 830-840, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29948904

RESUMO

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.


Assuntos
Encéfalo/patologia , Função Executiva/fisiologia , Gastrectomia/efeitos adversos , Adulto , Cirurgia Bariátrica/métodos , Córtex Cerebral/patologia , Emoções/fisiologia , Feminino , Gastrectomia/métodos , Gastrectomia/psicologia , Substância Cinzenta/patologia , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética/métodos , Masculino , Obesidade/psicologia , Autoavaliação , Substância Branca/patologia
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