Radiologic evidence that hypothalamic gliosis is improved after bariatric surgery in obese women with type 2 diabetes.

BACKGROUND/OBJECTIVES: Hypothalamic neurons play a major role in the control of body mass. Obese subjects present radiologic signs of gliosis in the hypothalamus, which may reflect the damage or loss of neurons involved in whole-body energy homeostasis. It is currently unknown if hypothalamic gliosis (1) differs between obese nondiabetic (ND) and obese diabetic subjects (T2D) or (2) is modified by extensive body mass reduction via Roux-n-Y gastric bypass (RYGB). SUBJECTS/METHODS: Fifty-five subjects (all female) including lean controls (CT; n = 13), ND (n = 28), and T2D (n = 14) completed at least one study visit. Subjects underwent anthropometrics and a multi-echo MRI sequence to measure mean bilateral T2 relaxation time in the mediobasal hypothalamus (MBH) and two reference regions (amygdala and putamen). The obese groups underwent RYGB and were re-evaluated 9 months later. Analyses were by linear mixed models. RESULTS: Analyses of T2 relaxation time at baseline showed a group by region interaction only in the MBH (P < 0.0001). T2D had longer T2 relaxation times compared to either CT or ND groups. To examine the effects of RYGB on hypothalamic gliosis a three-way (group by region by time) mixed effects model adjusted for age was executed. Group by region (P < 0.0001) and region by time (P = 0.0005) interactions were significant. There was a reduction in MBH relaxation time by RYGB, and, although the T2D group still had higher T2 relaxation time overall compared to the ND group, the T2D group had significantly lower T2 relaxation time after surgery and the ND group showed a trend. The degree of reduction in MBH T2 relaxation time by RYGB was unrelated to clinical outcomes. CONCLUSION: T2 relaxation times, a marker of hypothalamic gliosis, are higher in obese women with T2D and are reduced by RYGB-induced weight loss.

Radiologic evidence that hypothalamic gliosis is associated with obesity and insulin resistance in humans.

OBJECTIVE: To use quantitative magnetic resonance imaging (MRI) to test whether mediobasal hypothalamic (MBH) gliosis is associated with obesity and insulin resistance in humans. METHODS: Sixty-seven participants underwent a fasting blood draw and MRI. Cases with radiologic evidence of MBH gliosis (N = 22) were identified as the upper tertile of left MBH T2 relaxation time and were compared to controls (N = 23) from the lowest tertile. In a separate postmortem study, brain slices (N = 10) through the MBH were imaged by MRI and stained for glial fibrillary acidic protein (GFAP). RESULTS: In all participants, longer T2 relaxation time in the left MBH was associated with higher BMI (P = 0.01). Compared with controls, cases had longer T2 relaxation times in the right MBH (P < 0.05), as well as higher BMI (P < 0.05), fasting insulin concentrations (P < 0.01), and HOMA-IR values (P < 0.01), adjusted for sex and age. Elevations in insulin and HOMA-IR were also independent of BMI. In the postmortem study, GFAP staining intensity was positively associated with MBH T2 relaxation time (P < 0.05), validating an MRI-based method for the detection of MBH gliosis in humans. CONCLUSIONS: These findings link hypothalamic gliosis to insulin resistance in humans and suggest that the link is independent of the level of adiposity.

Obesity is associated with hypothalamic injury in rodents and humans.

Rodent models of obesity induced by consuming high-fat diet (HFD) are characterized by inflammation both in peripheral tissues and in hypothalamic areas critical for energy homeostasis. Here we report that unlike inflammation in peripheral tissues, which develops as a consequence of obesity, hypothalamic inflammatory signaling was evident in both rats and mice within 1 to 3 days of HFD onset, prior to substantial weight gain. Furthermore, both reactive gliosis and markers suggestive of neuron injury were evident in the hypothalamic arcuate nucleus of rats and mice within the first week of HFD feeding. Although these responses temporarily subsided, suggesting that neuroprotective mechanisms may initially limit the damage, with continued HFD feeding, inflammation and gliosis returned permanently to the mediobasal hypothalamus. Consistent with these data in rodents, we found evidence of increased gliosis in the mediobasal hypothalamus of obese humans, as assessed by MRI. These findings collectively suggest that, in both humans and rodent models, obesity is associated with neuronal injury in a brain area crucial for body weight control.

Functional MRI activation in children with and without dyslexia during pseudoword aural repeat and visual decode: before and after treatment.

Children without dyslexia (n=10) received nonphonological treatment, and those with dyslexia received phonological (n=11) or nonphonological (n=9) treatment. Before and after treatment they performed aural repeat, visual decode, and aural match pseudoword tasks during functional MRI scanning that separated stimulus input from response production. Group map analysis indicated that children with dyslexia overactivated compared with good readers during the aural-repeat/aural-match contrast in bilateral frontal (Brodmann's area [BA] 3, 4, 5, 6, 9), left parietal (BA 2, 3), left temporal (BA 38), and right temporal (BA 20, 21, 37) regions (stimulus input) and underactivated in right frontal (BA 24, 32) and right insula (BA 48) regions (response production); they underactivated in BA 19/V5 during the visual-decode/aural-match contrast (response production). Individual brain analysis for children with dyslexia revealed that during the aural-repeat/aural-match contrast (stimulus input), phonological treatment decreased and normalized activation in left supramarginal gyrus and postcentral gyrus. Nonphonological treatment increased and normalized activation during the visual-decode/aural-match contrast (response production) in BA19/V5 and changed activation in the same direction as good readers during aural-repeat/aural-match contrast (stimulus input) in left postcentral gyrus. The significance of the findings for competing theories of dyslexia is discussed.

FMRI investigation of cross-cultural music comprehension.

The popular view of music as a "universal" language ignores the privileged position of the cultural insider in comprehending musical information unique to their own tradition. The purpose of this study was to test the hypothesis that listeners would demonstrate different neural activity in response to culturally familiar and unfamiliar music and that those differences may be affected by the extent of subjects' formal musical training. Just as familiar languages have been shown to use distinct brain processes, we hypothesized that an analogous difference might be found in music and that it may depend in part on subjects' formal musical knowledge. Using fMRI we compared the activation patterns of professional musicians and untrained controls reared in the United States as they listened to music from their culture (Western) and from an unfamiliar culture (Chinese). No overall differences in activation were observed for either subject group in response to the two musical styles, although there were differences in recall performance based on style and there were activation differences based on training. Trained listeners demonstrated additional activation in the right STG for both musics and in the right and left midfrontal regions for Western music and Chinese music, respectively. Our findings indicate that listening to culturally different musics may activate similar neural resources but with dissimilar results in recall performance.