Brain structure, chemistry and function investigations in aging using MRI/MRS

在与博士合作。Chia和Egan，我们完成了“RISE研究”，这是一项CB1受体激动剂和拮抗剂对外周代谢、脑功能和脑代谢控制的影响的多方面随机安慰剂对照交叉临床研究。该研究包括强大的神经成像组件，包括fMRI和mrs。我们进行了两项激活模式的fMRI研究，一项研究发现大脑与头胰岛素分泌和CB1受体的作用相关，另一项研究评估CB1受体对食物食欲的影响。第一项研究的目的是证明在食物视觉刺激下胰岛素水平的上升（头侧胰岛素反应）是由于某些大脑区域（脑岛、前扣带、下丘脑、腹侧被盖区等）的激活。此外，考虑到候选区域中存在CB1受体，我们旨在证明CB1激动剂和拮抗剂在激活水平上的差异。第二项研究的目的是证明CB1受体刺激对食物价值（食物选择）和显著性（这种选择的强度）的可解离效应。此外，我们进行了静息fMRI研究，以评估CB1对各种脑网络功能连接的调节。最后，我们通过MRS来评估CB1对脑代谢（葡萄糖、乳酸）和神经传递（谷氨酸、GABA、甘氨酸）的调节。我们目前正在分析和解释这些研究的数据。

In collaboration with Drs. Chia and Egan, we completed the "RISE study", a multi-faceted randomized placebo-controlled cross-over clinical study of the effects of a CB1 receptor agonist and antagonist on peripheral metabolism, brain function and brain metabolic control. The study included a robust neuroimaging component including fMRI and MRS. We performed two activation-paradigm fMRI studies, one to discover brain correlates of cephalic insulin secretion and the effects of CB1 receptors, the second to assess the effects of CB1 receptors on food appetitiveness. The goal of the first study was to demonstrate a rise in insulin levels in response to food visual stimuli (cephalic insulin response) as a result of activation of certain brain areas (insula, anterior cingulate, hypothalamus, ventral tegmental area, etc). Moreover, given the presence of CB1 receptors in the candidate areas, we aimed to demonstrate a difference in their level of activation with CB1 agonists and antagonists. The goal of the second study was to demonstrate dissociable effects of CB1 receptor stimulation on food value (food choices) and salience (intensity of such choices). In addition, we performed a resting fMRI study to assess CB1 modulation of functional connectivity of the various brain networks. Finally, we performed MRS to assess CB1 modulation of brain metabolism (glucose, lactate) and neurotransmission (glutamate, GABA, glycine). We are currently in the process of analyzing and interpreting the data from these studies.