Nestor Liam J, Luijten Maartje, Ziauddeen Hisham, Regenthal Ralf, Sahakian Barbara J, Robbins Trevor W, Ersche Karen D
Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
Behavioural Science Institute, Radboud University, Nijmegen, the Netherlands.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 Mar;9(3):314-325. doi: 10.1016/j.bpsc.2023.08.003. Epub 2023 Aug 22.
Cocaine use disorder is associated with cognitive deficits that reflect dysfunctional processing across neural systems. Because there are currently no approved medications, treatment centers provide behavioral interventions that have only short-term efficacy. This suggests that behavioral interventions are not sufficient by themselves to lead to the maintenance of abstinence in patients with cocaine use disorder. Self-control, which includes the regulation of attention, is critical for dealing with many daily challenges that would benefit from medication interventions that can ameliorate cognitive neural disturbances.
To address this important clinical gap, we conducted a randomized, double-blind, placebo-controlled, crossover design study in patients with cocaine use disorder (n = 23) and healthy control participants (n = 28). We assessed the modulatory effects of acute atomoxetine (40 mg) on attention and conflict monitoring and their associated neural activation and connectivity correlates during performance on the Eriksen flanker task. The Eriksen flanker task examines basic attentional processing using congruent stimuli and the effects of conflict monitoring and response inhibition using incongruent stimuli, the latter of which necessitates the executive control of attention.
We found that atomoxetine improved task accuracy only in the cocaine group but modulated connectivity within distinct brain networks in both groups during congruent trials. During incongruent trials, the cocaine group showed increased task-related activation in the right inferior frontal and anterior cingulate gyri, as well as greater network connectivity than the control group across treatments.
The findings of the current study support a modulatory effect of acute atomoxetine on attention and associated connectivity in cocaine use disorder.
可卡因使用障碍与认知缺陷相关,这些缺陷反映了跨神经系统的功能失调处理。由于目前尚无获批的药物,治疗中心提供的行为干预仅具有短期疗效。这表明行为干预本身不足以使可卡因使用障碍患者维持戒断状态。自我控制,包括注意力调节,对于应对许多日常挑战至关重要,而这些挑战可能受益于能够改善认知神经紊乱的药物干预。
为填补这一重要的临床空白,我们对可卡因使用障碍患者(n = 23)和健康对照参与者(n = 28)进行了一项随机、双盲、安慰剂对照的交叉设计研究。我们评估了急性阿托西汀(40毫克)对注意力和冲突监测的调节作用,以及在埃里克森侧翼任务执行过程中它们与相关神经激活和连接的相关性。埃里克森侧翼任务使用一致刺激来检验基本的注意力处理,并使用不一致刺激来检验冲突监测和反应抑制的效果,后者需要对注意力进行执行控制。
我们发现,阿托西汀仅在可卡因组中提高了任务准确性,但在一致试验期间调节了两组不同脑网络内的连接性。在不一致试验期间,可卡因组在右侧额下回和前扣带回中显示出与任务相关的激活增加,并且在所有治疗中其网络连接性均高于对照组。
本研究结果支持急性阿托西汀对可卡因使用障碍患者的注意力及相关连接性具有调节作用。