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SCIENCE CHINA Information Sciences, Volume 63 , Issue 7 : 170104(2020) https://doi.org/10.1007/s11432-019-2817-x

Bariatric surgery induces alterations in effective connectivity between the orbitofrontal cortex and limbic regions in obese patients

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  • ReceivedDec 3, 2019
  • AcceptedMar 10, 2020
  • PublishedMay 27, 2020

Abstract

Obese subjects show enhanced brain responses in motivation and reward neurocircuitry encompassing sensory and somatic integration-interception, motivation-reward (striatal), emotion, and memory processes, which attenuate frontal region activation during food cues. Bariatric surgery (BS) is the only reliable treatment for morbid obesity. Unfortunately, it is unknown how BS affects neurocircuitry after weight loss. We aimed to examine effects of BS on the basal activity of brain areas involved in reward and motivation processing, emotion, memory, and gut-brain interaction. We combined resting-state fMRI with amplitude of low-frequency fluctuation (ALFF) and Granger causality analysis (GCA) to assess interactions between regions within the frontal-mesolimbic circuitry in 16 obese subjects (OB) and 22 normal-weight (NW) subjects. The OB group was studied at baseline and 1 month post BS. Comparisons between OB and NW, and pre- and post BS showed significant differences in ALFF in areas involved in drive (caudate, orbitofrontal cortex (OFC)), arousal (thalamus), and conditioning/memory (amygdala, hippocampus) ($P<0.05$, FDR correction). GCA revealed that in the OB group, the OFC had greater connectivity to limbic regions (amygdala, hippocampus, and medial thalamus) and the caudate. Post BS, the connectivity of the OFC to limbic regions decreased, whereas the connectivity from the amygdala and hippocampus to the caudate and thalamus was enhanced, particularly in subjects with lower body mass index (BMI). OFC activation in the OB group was associated with BMI prior to surgery, and changes in OFC post surgery were associated with alterations in BMI. Overall, the functional connectivity of the OFC was significantly decreased. As it is important for salience attribution and connected to limbic brain regions involved with emotional reactivity and conditioning after BS, its significant association with BMI changes indicates the contribution of OFC changes to the improved control of eating behavior after surgery.


Acknowledgment

This work was supported by National Natural Science Foundation of China (Grant Nos. 61431013, 81730016, 31670828), Open Funding Project of National Key Laboratory of Human Factors Engineering (Grant No. 6142222190103), Natural Science Foundation of Shaanxi Province (Grant No. 2018JM3007), National Clinical Research Center for Digestive Diseases (Grant No. 2015BAI13B07), and in part by the Intramural Research Program of the United States NIAAA(Grant No. Y1AA3009).


Supplement

Appendix A.


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  • Figure 1

    (Color online) Correlations between baseline plasma gut peptide measures and regional ALFF.

  • Figure 2

    (Color online) Functional mapping of brain areas demonstrates significant ALFF alterations between OB and NW groups and in the OB group between before and after surgery (PreBS $>$ PostBS) during the resting state ($P~<~0.05$, FDR corrected). (a) Compared to the NW group, the OB group had increased ALFF in the OFC, AMY, and HIPP, and decreased ALFF in the caudate and thalamus. (b) After surgery, the OB group had increased ALFF in the caudate and thalamus, and decreased ALFF in the OFC, AMY, and HIPP.

  • Figure 3

    (Color online) Alterations of frontal-mesolimbic interactive causal influence in obese subjects before and after BS. GCA results showed that in OB the OFC propels the limbic regions (amygdala, hippocampus, and medial thalamus); the OFC and the medial thalamus propel the caudate. After surgery, the amygdala and hippocampus propel the caudate. In addition, there was enhanced connectivity between the amygdala and medial thalamus, and connectivity between the OFC and reward/limbic region decreased.

  • Figure 4

    (Color online) Correlation analysis between baseline brain activity/interactions and BMI changes, and between changes in brain activity and changes in BMI before and after surgery. (a) In the OB group before surgery (PreBS), BMI was significantly correlated with ALFF in the OFC ($R~=~0.67$, $P~=~0.0006$). After surgery, the OB group (PostBS) showed positive correlations between BMI and ALFF in the HIPP ($R~=~0.67$, $P~=~0.001$). Changes in ALFF in the OFC (PreBS-PostBS) was positively correlated with changes in BMI ($R~=~0.73$, $P~=~0.001$). (b) In the OB group, BMI was positively correlated with the ratio of OFC to THA ($R~=~0.68$, $P~=~0.0003$), and YFAS was negatively associated with the ratio of the AMY to THA ($R~=~-0.69$, $P~=~0.0002$). In the OB group after surgery, BMI was negatively correlated with the ratio of HIPP to THA ($R~=~-0.79$, $P~=~0.0002$).

  • Table 1  

    Table 1Demographic and clinical information of obese and normal-weight subjects$^{\rm~a)}$

    OB ($N=16$) NW ($N=22$) $P$ value
    PreBS PostBS (Mean $\pm$ SE) $F$ value
    (Mean $\pm$ SE) (Mean $\pm$ SE) a b
    Age (yrs) 25.44 $\pm$ 1.82 25.44 $\pm$ 1.82 26.77 $\pm$ 1.56 0.458 0.580 1
    Gender 6M/10F 6M/10F 8M/14F 0.041 0.945 1
    Duration of obesity (yrs) 12.75 $\pm$ 2.19 12.75 $\pm$ 2.19 19.051 1
    Weight (kg) 109.45 $\pm$ 4.28 96.91 $\pm$ 4.36 59.52 $\pm$ 2.22 48.796 0.000 0.023
    BMI (kg/m$^2$) 38.17 $\pm$ 1.45 33.72 $\pm$ 1.48 21.48 $\pm$ 0.58 50.075 0.000 0.012
    WC (cm) 117.19 $\pm$ 3.72 104.91 $\pm$ 4.38 80.98 $\pm$ 2.33 25.897 0.000 0.031
    Food intake (kg/meal) 0.80 $\pm$ 0.13 0.21 $\pm$ 0.03 0.39 $\pm$ 0.03 14.825 0.000 0.019
    YFAS 4.50 $\pm$ 0.56 2.94 $\pm$ 0.49 1.68 $\pm$ 0.27 9.659 0.000 0.017
    HAMD 11.94 $\pm$ 2.89 12.31 $\pm$ 2.01 6.27 $\pm$ 0.86 6.894 0.037 0.896
    HAMA 9.94 $\pm$ 2.37 8.38 $\pm$ 1.72 4.55 $\pm$ 0.67 2.313 0.017 0.510

    a

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