Section on the Neurobiology of Fear & Anxiety, National Institute of Mental Health, 15K North Drive Rm 300-F, Bethesda, MD, 20892, USA.
Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Psychopharmacology (Berl). 2020 Jun;237(6):1873-1883. doi: 10.1007/s00213-020-05505-z. Epub 2020 Apr 19.
The thalamus is a major target of dopaminergic projections and is densely connected with the prefrontal cortex. A better understanding of how dopamine changes thalamo-cortical communication may shed light on how dopamine supports cognitive function. Methylphenidate has been shown to facilitate cognitive processing and reduce connectivity between the thalamus and lateral prefrontal cortex.
The thalamus is a heterogeneous structure, and the present study sought to clarify how the intrinsic connections of thalamic sub-regions are differentially impacted by acute dopamine transporter blockade.
Sixty healthy volunteers were orally administered either 20 mg of methylphenidate (N = 29) or placebo (N = 31) in a double-blind, randomized, between-subject design. Multi-echo fMRI was used to assess intrinsic functional connectivity of sub-regions of the thalamus during a resting state scan. An N-back working-memory paradigm provided a measure of cognitive performance.
Acute methylphenidate significantly reduced connectivity of the lateral prefrontal cortex with the motor and somatosensory sub-regions of the thalamus and reduced connectivity with the parietal and visual sub-regions at a trend level. Connectivity with the premotor, prefrontal, and temporal sub-regions was not impacted. The intrinsic connectivity between the thalamus and the lateral prefrontal cortex was not associated with working-memory performance.
Methylphenidate decreases functional connections between the lateral prefrontal cortex and thalamus broadly, while sparing intrinsic connectivity with thalamic sub-regions involved with working-memory and language related processes. Collectively, our results suggest that the dopamine transporter regulates functional connections between the prefrontal cortex and non-cognitive areas of the thalamus.
丘脑是多巴胺能投射的主要靶点，与前额叶皮层紧密相连。更好地了解多巴胺如何改变丘脑-皮层通讯，可能有助于了解多巴胺如何支持认知功能。哌甲酯已被证明可以促进认知加工，并减少丘脑与外侧前额叶皮层之间的连接。
丘脑是一个异质结构，本研究旨在阐明急性多巴胺转运体阻断如何对丘脑亚区的内在连接产生不同的影响。
60 名健康志愿者以双盲、随机、组间设计的方式分别口服 20mg 哌甲酯（N=29）或安慰剂（N=31）。多回波 fMRI 用于评估静息状态扫描期间丘脑亚区的内在功能连接。N 回工作记忆范式提供了认知表现的衡量标准。
急性哌甲酯显著降低了外侧前额叶皮层与丘脑运动和躯体感觉亚区的连接，与顶叶和视觉亚区的连接呈趋势性降低。与运动前区、前额叶和颞叶亚区的连接不受影响。丘脑与外侧前额叶皮层之间的内在连接与工作记忆性能无关。
哌甲酯广泛降低了外侧前额叶皮层与丘脑之间的功能连接，而与与工作记忆和语言相关过程相关的丘脑亚区的内在连接不受影响。总的来说，我们的结果表明，多巴胺转运体调节前额叶皮层与丘脑非认知区域之间的功能连接。
