Effects of Obesity and Weight Loss Following Bariatric Surgery on Brain Function, Structural Integrity and Metabolism

Obesity is one of the key challenges to health care system worldwide and its prevalence is estimated to rise to pandemic proportions. Numerous adverse health effects follow with increasing body weight, including increased risk of hypertension, diabetes, hypercholesterolemia, musculoskeletal pain and cancer. Current evidence suggests that obesity is associated with altered cerebral reward circuit functioning and decreased inhibitory control over appetitive food cues. Furthermore, obesity causes adverse shifts in metabolism and loss of structural integrity within the brain. Prior cross-sectional studies do not allow delineating which of these cerebral changes are recoverable after weight loss. We compared morbidly obese subjects with healthy controls to unravel brain changes associated with obesity. Bariatric surgery was used as an intervention to study which cerebral changes are recoverable after weight loss. In Study I we employed functional magnetic resonance imaging (fMRI) to detect the brain basis of volitional appetite control and its alterations in obesity. In Studies II-III we used diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) to quantify the effects of obesity and the effects of weight loss on structural integrity of the brain. In study IV we used positron emission tomography (PET) with [18F]-FDG in fasting state and during euglycemic hyperinsulinemia to quantify effects of obesity and weight loss on brain glucose uptake. The fMRI experiment revealed that a fronto-parietal network is involved in volitional appetite control. Obese subjects had lower medial frontal and dorsal striatal brain activity during cognitive appetite control and increased functional connectivity within the appetite control circuit. Obese subjects had initially lower grey matter and white matter densities than healthy controls in VBM analysis and loss of integrity in white matter tracts as measured by DTI. They also had initially elevated glucose metabolism under insulin stimulation but not in fasting state. After the weight loss following bariatric surgery, obese individuals’ brain volumes recovered and the insulin-induced increase in glucose metabolism was attenuated. In conclusion, obesity is associated with altered brain function, coupled with loss of structural integrity and elevated glucose metabolism, which are likely signs of adverse health effects to the brain. These changes are reversed by weight loss after bariatric surgery, implicating that weight loss has a causal role on these adverse cerebral changes. Altogether these findings suggest that weight loss also promotes brain health.Key words: brain, obesity, bariatric surgery, appetite control, structural magnetic resonanceLihavuus yleistyy nopeasti koko maailmassa ja se on yksi suurimmista terveydenhuollon tulevaisuuden haasteista. Lihavuus lisää riskiä sairastua useisiin sairauksiin mm. verenpainetautiin, diabetekseen, tuki- ja liikuntaelinten sairauksiin ja useisiin syöpiin. Lihavilla on havaittu aivojen palkkiojärjestelmän reagoivan yliaktiivisesti ruokaan liittyviin ärsykkeisiin ja toisaalta ruokahalua hillitsevien alueiden toiminnan on havaittu olevan heikompaa kuin normaalipainoisilla. Lihavuus aiheuttaa myös haitallisia muutoksia aivosolujen rakenteessa ja aineenvaihdunnassa. Näiden muutosten palautumispotentiaalia ei voida arvioida poikkileikkaustutkimuksissa. Tässä työssä tutkimme sairaalloisen lihavia lihavuusleikkaukseen valittuja potilaita, joiden aivokuvantamistuloksia verrattiin normaalipainoisten vastaaviin kuvauksiin. Potilaat tutkittiin myös kuusi kuukautta lihavuusleikkauksen jälkeen painonlaskun aiheuttamien aivomuutosten tutkimiseksi. Ensimmäisessä tutkimuksessa ruokahalun säätelyjärjestelmän toiminnan ja lihavuuden aiheuttamien muutosten selvittämiseksi käytettiin toiminnallista magneettikuvantamista (fMRI). Rakenteellisia muutoksia arvioitiin II ja III osatyössä diffuusiotensorikuvantamisella (DTI) sekä vokseliperustaisen morfometrian avulla (VBM). Neljännessä osatyössä aivojen sokeriaineenvaihduntaa tutkittiin positroniemissiotomografian (PET) avulla käyttämällä [18F]-FDG-merkkiainetta paastotilassa ja insuliini-stimulaation aikana. VBM -ja PET-menetelmiä käytettiin myös lihavuusl eikkauksen vaikutusten arviointiin. fMRI-kokeessa havaittiin, että ruokahalun säätelyyn osallistuu laaja hermoverkko jonka keskeiset osat sijoittuvat otsa- ja päälaenlohkoihin. Lihavilla tutkittavilla havaittiin alentuneet vasteet häntätumakkeessa ja etupihtipoimun alueella. Lisäksi heillä havaittiin voimakkaammat toiminnalliset yhteydet ruokahalun säätelyverkostossa. Lihavuus aiheuttaa aivoissa laajaa aivokudoksen harventumaa ja hermoratojen eheyden alentumaa. PET-tutkimuksessa havaittiin lihavuuden lisäävän aivojen insuliiniherkkyyttä. Puoli vuotta lihavuusleikkauksen jälkeen rakenteelliset ja aineenvaihdunnan muutokset palautuivat osittain.Siirretty Doriast

FDG uptake and walking ability

Includes bibliographical references.Motor impairments of the upper and lower extremities are common symptoms of multiple sclerosis (MS). While some peripheral effects like muscle weakness and loss of balance have been shown to influence these symptoms, central nervous system activity has not been fully elucidated. The purpose of this study was to determine if alterations in glucose uptake were associated with motor impairments in patients with multiple sclerosis. Eight patients with multiple sclerosis (4 men) and 8 sex matched healthy controls performed 15 minutes of treadmill walking at a self-selected pace, during which ≈ 322 MBq of the positron emission tomography glucose analogue [18F]-Fluorodeoxyglucose was injected. Immediately after the cessation of walking, participants underwent positron emission tomography imaging. Patients with MS had lower FDG uptake in ≈ 40% of the brain compared to the healthy controls (pFWE-corr > 0.001, qFDR-corr -0.75, P < 0.032). Within patients with MS only 3 of the 15 regions showed significant correlations: insula (r = -0.74, P = 0.036), hippocampus (r = -0.72, P = 0.045), and calcarine sulcus (r = -0.77, P = 0.026). This data suggests that walking impairments in patients with MS may be due to network wide alterations in glucose metabolism. Understanding how brain activity and metabolism are altered in patients with MS may allow for better measures of disability and disease status within this clinical population.Published with support from the Colorado State University Libraries Open Access Research and Scholarship Fund

Auditory Mismatch Responses to Emotional Stimuli in 3-Year-Olds in Relation to Prenatal Maternal Depression Symptoms

Maternal depression symptoms are common in pregnant women and can have negative effects on offspring's emotional development. This study investigated the association between prenatal maternal depression symptoms (assessed with the Edinburgh Postnatal Depression Scale at 24 weeks of gestation) and auditory perception of emotional stimuli in 3-year-olds (n = 58) from the FinnBrain Birth Cohort Study. Using electroencephalography (EEG), we examined mismatch responses for happy, sad, and angry sounds presented among neutral stimuli. A positive association between maternal depression symptoms and the emotional mismatch responses in an early time window (80-120 ms) was found, indicating that brain responses of children of mothers with depressive symptoms were weaker to happy sounds, though the results did not survive Bonferroni correction. There were no clear associations in the sad and angry emotional categories. Our results tentatively support that the 3-year-old children of mothers with depression symptoms may be less sensitive to automatically detect happy sounds compared to children whose mothers do not display symptoms of depression.Peer reviewe

Imaging affective and non-affective touch processing in two-year-old children

Touch is an important component of early parent-child interaction and plays a critical role in the socio-emotional development of children. However, there are limited studies on touch processing amongst children in the age range from one to three years. The present study used frequency-domain diffuse optical tomography (DOT) to investigate the processing of affective and non-affective touch over left frontotemporal brain areas contralateral to the stimulated forearm in two-year-old children. Affective touch was administered by a single stroke with a soft brush over the child's right dorsal forearm at 3 cm/s, while non-affective touch was provided by multiple brush strokes at 30 cm/s. We found that in the insula, the total haemoglobin (HbT) response to slow brushing was significantly greater than the response to fast brushing (slow > fast). Additionally, a region in the postcentral gyrus, Rolandic operculum and superior temporal gyrus exhibited greater response to fast brushing than slow brushing (fast > slow). These findings confirm that an adult-like pattern of haemodynamic responses to affective and non-affective touch can be recorded in two-year-old subjects using DOT. To improve the accuracy of modelling light transport in the two-year-old subjects, we used a published age-appropriate atlas and deformed it to match the exterior shape of each subject's head. We estimated the combined scalp and skull, and grey matter (GM) optical properties by fitting simulated data to calibrated and coupling error corrected phase and amplitude measurements. By utilizing a two-compartment cerebrospinal fluid (CSF) model, the accuracy of estimation of GM optical properties and the localization of activation in the insula was improved. The techniques presented in this paper can be used to study neural development of children at different ages and illustrate that the technology is well-tolerated by most two-year-old children and not excessively sensitive to subject movement. The study points the way towards exciting possibilities in functional imaging of deeper functional areas near sulci in small children.Peer reviewe

Age and sex differences in the cortisol stress reactivity and recovery among infants exposed to prenatal psychological distress

Background Altered hypothalamic-pituitary-adrenal axis (HPA) functioning is one of the potential mechanisms bridging exposure to maternal prenatal psychological distress (PPD) and later risk for offspring psychiatric illness. Research on infant cortisol stress reactivity, on scarcely studied recovery and their associations with maternal PPD is needed to clarify these mechanisms. Knowledge on sex differences in prospective settings is largely lacking. We aimed at filling these gaps by building upon our previous report showing that exposure to maternal prenatal depressive and anxiety symptoms associates with slower cortisol recovery among 10-week-old female infants. MethodsIn all, 363, 205 and 263 infants at 10 weeks, six and 14 months of age from the FinnBrain Birth Cohort Study participated in a stress test comprising of venipuncture and nasopharynx sampling. Five saliva cortisol samples were collected during each visit to measure cortisol reactivity and recovery. PPD was assessed from maternal self-reports for depressive, anxiety and pregnancy-related anxiety symptoms at gestational weeks 14, 24 and 34. Results An 11% enhanced recovery among 14-month-old females was associated with higher depressive and anxiety symptoms (95% CI = 1-23%) and pregnancy-related anxiety symptoms (2-21%). No alterations in the female cortisol reactivity or male cortisol stress responses were observed. Conclusions The opposite directions in the associations between the PPD exposure and infant cortisol recovery among 10-week-old and 14-month-old females suggest sex- and age-dependent associations between HPA axis functioning and PPD exposure among healthy infants. Follow-up is needed to characterize the impact of this altered negative feedback mechanism on later health.</p

Associations Between Brain Gray Matter Volumes and Adipose Tissue Metabolism in Healthy Adults

Objective Gray matter (GM) volume in different brain loci has been shown to vary in obesity and diabetes, and elevated fasting plasma nonesterified fatty acid (NEFA) levels have been suggested as one potential mechanism. The hypothesis presented in this study is that brown adipose tissue (BAT) activity may correlate with GM volume in areas negatively associated with obesity and diabetes.Methods A total of 36 healthy patients (M/F: 12/24, age 39.7 +/- 9.4 years, BMI 27.5 +/- 5.6 kg/m(2)) were imaged with positron emission tomography using fatty acid analog [F-18]FTHA to measure NEFA uptake and with [O-15]H2O to measure perfusion during cold exposure, at room temperature during fasting, or during a postprandial state. A 2-hour hyperinsulinemic euglycemic clamp was performed to measure whole-body insulin sensitivity (M value, mean 7.6 +/- 3.9 mg/kg/min). T1-weighted magnetic resonance imaging at 1.5 T was performed on all patients.Results BAT NEFA uptake was associated directly with GM volume in anterior cerebellum and occipital lobe (P <= 0.04) when adjusted for age, gender, and intra-abdominal fat volume and with anterior cerebellum, limbic lobe, and temporal lobe GM volumes when adjusted for M value.Conclusions BAT NEFA metabolism may participate in protection from cognitive degeneration associated with cardiometabolic risk factors, such as central obesity and insulin resistance. Potential causal relationships between BAT activity and GM volumes remain to be examined

Opioid Release after High-Intensity Interval Training in Healthy Human Subjects

Central opioidergic mechanisms may modulate the positive effects of physical exercise such as mood elevation and stress reduction. How exercise intensity and concomitant effective changes affect central opioidergic responses is unknown. We studied the effects of acute physical exercise on the cerebral μ-opioid receptors (MOR) of 22 healthy recreationally active males using positron emission tomography (PET) and the MOR-selective radioligand [11C]carfentanil. MOR binding was measured in three conditions on separate days: after a 60-min aerobic moderate-intensity exercise session, after a high-intensity interval training (HIIT) session, and after rest. Mood was measured repeatedly throughout the experiment. HIIT significantly decreased MOR binding selectively in the frontolimbic regions involved in pain, reward, and emotional processing (thalamus, insula, orbitofrontal cortex, hippocampus, and anterior cingulate cortex). Decreased binding correlated with increased negative emotionality. Moderate-intensity exercise did not change MOR binding, although increased euphoria correlated with decreased receptor binding. These observations, consistent with endogenous opioid release, highlight the role of the μ-opioid system in mediating affective responses to high-intensity training as opposed to recreational moderate physical exercise

Relationship between maternal pregnancy-related anxiety and infant brain responses to emotional speech – a pilot study

Background: Maternal pregnancy-related anxiety (PRA) is reportedly related to neurodevelopmental outcomes of infants. However, the relationship between maternal PRA and the processing of emotions in the infant brain has not been extensively studied with neuroimaging. The objective of the present pilot study is to investigate the relationship between maternal PRA and infant hemodynamic responses to emotional speech at two months of age. Methods: The study sample included 19 mother-infant dyads from a general sample of a population of Caucasian mothers. Self-reported Pregnancy-Related Anxiety Questionnaire (PRAQ-R2) data was collected from mothers during pregnancy at gestational weeks (gwks) 24 (N = 19) and 34 (N = 18). When their infants were two months old, the infants' brains functional responses to emotional speech in the left fronto-temporoparietal cortex were recorded using diffuse optical tomography (DOT). Results: Maternal PRAQ-R2 scores at gwk 24 correlated negatively with the total hemoglobin (HbT) responses to sad speech on both sides of the temporoparietal junction (Spearman's rank correlation coefficient rho = -0.87). The correlation was significantly greater at gwk 24 than gwk 34 (rho = -0.42). Limitations: The field of view of the measurement did not include the right hemisphere or parts of the frontal cortex. The sample size is moderate and the mothers were relatively highly educated, thus there may be some differences between the study sample and the general population. Conclusions: Maternal pregnancy-related anxiety may affect child brain emotion processing development. Further research is needed to understand the functional and developmental significance of the findings.Peer reviewe

Aerobic exercise modulates anticipatory reward processing via the mu-opioid receptor system

Physical exercise modulates food reward and helps control body weight. The endogenous mu-opioid receptor (MOR) system is involved in rewarding aspects of both food and physical exercise, yet interaction between endogenous opioid release following exercise and anticipatory food reward remains unresolved. Here we tested whether exercise-induced opioid release correlates with increased anticipatory reward processing in humans. We scanned 24 healthy lean men after rest and after a 1 h session of aerobic exercise with positron emission tomography (PET) using MOR-selective radioligand [C-11]carfentanil. After both PET scans, the subjects underwent a functional magnetic resonance imaging (fMRI) experiment where they viewed pictures of palatable versus nonpalatable foods to trigger anticipatory food reward responses. Exercise-induced changes in MOR binding in key regions of reward circuit (amygdala, thalamus, ventral and dorsal striatum, and orbitofrontal and cingulate cortices) were used to predict the changes in anticipatory reward responses in fMRI. Exercise-induced changes in MOR binding correlated negatively with the exercise-induced changes in neural anticipatory food reward responses in orbitofrontal and cingulate cortices, insula, ventral striatum, amygdala, and thalamus: higher exercise-induced opioid release predicted higher brain responses to palatable versus nonpalatable foods. We conclude that MOR activation following exercise may contribute to the considerable interindividual variation in food craving and consumption after exercise, which might promote compensatory eating and compromise weight control

Imaging affective and non-affective touch processing in two-year-old children

Touch is an important component of early parent-child interaction and plays a critical role in the socio-emotional development of children. However, there are limited studies on touch processing amongst children in the age range from one to three years. The present study used frequency-domain diffuse optical tomography (DOT) to investigate the processing of affective and non-affective touch over left frontotemporal brain areas contralateral to the stimulated forearm in two-year-old children. Affective touch was administered by a single stroke with a soft brush over the child's right dorsal forearm at 3 cm/s, while non-affective touch was provided by multiple brush strokes at 30 cm/s. We found that in the insula, the total haemoglobin (HbT) response to slow brushing was significantly greater than the response to fast brushing (slow > fast). Additionally, a region in the postcentral gyrus, Rolandic operculum and superior temporal gyrus exhibited greater response to fast brushing than slow brushing (fast > slow). These findings confirm that an adult-like pattern of haemodynamic responses to affective and non-affective touch can be recorded in two-year-old subjects using DOT. To improve the accuracy of modelling light transport in the two-year-old subjects, we used a published age-appropriate atlas and deformed it to match the exterior shape of each subject's head. We estimated the combined scalp and skull, and grey matter (GM) optical properties by fitting simulated data to calibrated and coupling error corrected phase and amplitude measurements. By utilizing a two-compartment cerebrospinal fluid (CSF) model, the accuracy of estimation of GM optical properties and the localization of activation in the insula was improved. The techniques presented in this paper can be used to study neural development of children at different ages and illustrate that the technology is well-tolerated by most two-year-old children and not excessively sensitive to subject movement. The study points the way towards exciting possibilities in functional imaging of deeper functional areas near sulci in small children