Auditory discrimination and frequency modulation learning in schizophrenia patients: amphetamine within-subject dose response and time course.
Auditory discrimination and frequency modulation learning in schizophrenia patients: amphetamine within-subject dose response and time course.
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DOI：
10.1017/s0033291721001239
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发表时间：
2023-01
影响因子：
6.9
通讯作者：
Light GA
中科院分区：
文献类型：
--
作者：
Swerdlow NR;Bhakta SG;Talledo J;Benster L;Kotz J;Vinogradov S;Molina JL;Light GA
听觉频率调制学习（“听觉学习”）是精神分裂症目标认知训练（TCT）的关键组成部分。TCT可以有效地增强精神分裂症患者的神经认知和功能，但这样的收获需要大量的时间和精力，并且许多患者都无法获得。作为增加和/或加速TCT诱导的临床获益的策略，我们测试了促注意药物安非他明（AMPH;安慰剂，2.5，5或10 mg po;受试者内双盲，顺序平衡）对精神分裂症患者听觉学习的剂量和时间过程效应[n = 32; M：F = 19：13;年龄42.0岁（24-55）]。为了了解AMPH增强TCT的预测因子和/或机制，我们还测量了听觉保真度（噪声中的单词（WIN），噪声中的快速语音（QuickSIN））和神经认知（MATRICS综合认知电池（MCCB））。还从年龄匹配的健康受试者（无药物; n = 10; M：F = 5：5）中获得一些测量值。患者表现出预期的神经认知缺陷。在MCCB注意力/警觉（A/V）评分低与高的患者中，低信号强度下的WIN和QuickSIN性能受损;这些缺陷可通过AMPH纠正，最大剂量为2.5-5 mg（d = 0.79-1.29）。AMPH还增强了听觉学习，在5 mg时效果最大（d = 0.93），在服药后60和210 min时效果相当。AMPH和AMPH诱导的听觉保真度增益的“前学习”效应在MCCB A/V评分低的患者中最为明显。这些研究结果推进了我们对促注意干预对听觉信息处理的影响的理解，并为评估AMPH增强TCT在精神分裂症患者中临床获益的能力的研究提供了剂量和时间过程参数。
Auditory frequency modulation learning (‘auditory learning’) is a key component of targeted cognitive training (TCT) for schizophrenia. TCT can be effective in enhancing neurocognition and function in schizophrenia, but such gains require significant time and effort and elude many patients. As a strategy to increase and/or accelerate TCT-induced clinical gains, we tested the dose- and time-course effects of the pro-attentional drug, amphetamine (AMPH; placebo, 2.5, 5 or 10 mg po; within-subject double-blind, order balanced) on auditory learning in schizophrenia patients [n = 32; M:F = 19:13; age 42.0 years (24–55)]. To understand predictors and/or mechanisms of AMPH-enhanced TCT, we also measured auditory fidelity (words-in-noise (WIN), quick speech-in-noise (QuickSIN)) and neurocognition (MATRICS comprehensive cognitive battery (MCCB)). Some measures were also acquired from age-matched healthy subjects (drug free; n = 10; M:F = 5:5). Patients exhibited expected deficits in neurocognition. WIN and QuickSIN performance at low signal intensities was impaired in patients with low v. high MCCB attention/vigilance (A/V) scores; these deficits were corrected by AMPH, maximally at 2.5–5 mg (d's = 0.79–1.29). AMPH also enhanced auditory learning, with maximal effects at 5 mg (d = 0.93), and comparable effects 60 and 210 min post pill. ‘Pro-learning’ effects of AMPH and AMPH-induced gains in auditory fidelity were most evident in patients with low MCCB A/V scores. These findings advance our understanding of the impact of pro-attentional interventions on auditory information processing and suggest dose- and time-course parameters for studies that assess the ability of AMPH to enhance the clinical benefits of TCT in schizophrenia patients.