Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Department of Nuclear Medicine, Lille University Hospitals, Lille, France.
Mol Psychiatry. 2022 Aug;27(8):3493-3500. doi: 10.1038/s41380-022-01596-6. Epub 2022 May 11.
Prefrontal cortex has been shown to regulate striatal dopaminergic function via glutamatergic mechanisms in preclinical studies. Concurrent disruption of these systems is also often seen in neuropsychiatric disease. The simultaneous measurement of striatal dopamine signaling, cortical gray matter, and glutamate levels is therefore of major interest, but has not been previously reported. In the current study, twenty-eight healthy subjects underwent 2 simultaneous [C]-( + )-PHNO PET-MRI scans, once after placebo and once after amphetamine in a double-blind randomized cross-over design, to measure striatal dopamine release, striatal dopamine receptor (DR) availability, anterior cingulate glutamate+glutamine (Glx) levels, and cortical gray matter volumes at the same time. Voxel-based morphometry was used to investigate associations between neurochemical measures and gray matter volumes. Whole striatum DR availability was positively associated with prefrontal cortex gray matter volume (pFWE corrected = 0.048). This relationship was mainly driven by associative receptor availability (pFWE corrected = 0.023). In addition, an interaction effect was observed between sensorimotor striatum DR availability and anterior cingulate Glx, such that in individuals with greater anterior cingulate Glx concentrations, DR availability was negatively associated with right frontal cortex gray matter volumes, while a positive DR-gray matter association was observed in individuals with lower anterior cingulate Glx levels (pFWE corrected = 0.047). These results are consistent with the hypothesis that the prefrontal cortex is involved in regulation of striatal dopamine function. Furthermore, the observed associations raise the possibility that this regulation may be modulated by anterior cingulate glutamate concentrations.
前额皮质通过神经临床前研究中的谷氨酸能机制来调节纹状体多巴胺能功能。这些系统的并发破坏在神经精神疾病中也经常出现。因此，同时测量纹状体多巴胺信号、皮质灰质和谷氨酸水平非常重要，但以前尚未报道过。在当前的研究中，28 名健康受试者在双盲随机交叉设计中，同时进行了 2 次[C]-（+）-PHNO PET-MRI 扫描，一次在安慰剂后，一次在安非他命后，以同时测量纹状体多巴胺释放、纹状体多巴胺受体（DR）可用性、前扣带皮层谷氨酸+谷氨酰胺（Glx）水平和皮质灰质体积。体素形态测量法用于研究神经化学测量值与灰质体积之间的关联。整个纹状体 DR 可用性与前额皮质灰质体积呈正相关（经 pFWE 校正的 = 0.048）。这种关系主要是由关联受体可用性驱动的（经 pFWE 校正的 = 0.023）。此外，还观察到感觉运动纹状体 DR 可用性与前扣带皮层 Glx 之间存在交互作用，即在前扣带皮层 Glx 浓度较高的个体中，DR 可用性与右侧额皮质灰质体积呈负相关，而在前扣带皮层 Glx 水平较低的个体中则观察到 DR-灰质的正相关（经 pFWE 校正的 = 0.047）。这些结果与前额皮质参与调节纹状体多巴胺功能的假设一致。此外，观察到的关联提出了这样一种可能性，即这种调节可能受到前扣带皮层谷氨酸浓度的调节。
