Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA.
McLean Hospital, Belmont, MA 02478, USA.
Int J Neuropsychopharmacol. 2024 Nov 1;27(11). doi: 10.1093/ijnp/pyae050.
Deficits in cognitive control are implicated in numerous neuropsychiatric disorders. However, relevant pharmacological treatments are limited, likely due to weak translational validity of applicable preclinical models used. Neural indices derived from electroencephalography may prove useful in comparing and translating the effects of cognition-enhancing drugs between species. In the current study, we aimed to extend our previous cross-species results by examining if methylphenidate (MPH) modulates behavioral and neural indices of cognitive control in independent cohorts of humans and rats.
We measured continuous electroencephalography data from healthy adults (n = 25; 14 female) and Long Evans rats (n = 22; 8 female) and compared both stimulus- and response-locked event-related potentials and spectral power measures across species, and their MPH-related moderation following treatment with vehicle (placebo) or 1 of 2 doses of MPH.
Across both species, linear mixed effects modeling confirmed the expected Flanker interference effect on behavior (eg, accuracy) and response-related event-related potentials. Unexpectedly, in contrast to past work, we did not observe any task-related effects on the spectral power of rodents. Moreover, MPH generally did not modulate cognitive control of either species, although some species-specific patterns offer insight for future research.
Collectively, these findings in independent human and rodent subjects replicate some of our previously reported behavioral and neurophysiological patterns partly consistent with the notion that similar neural mechanisms may regulate cognitive control in both species. Nonetheless, these results showcase an approach to accelerate translation using a coordinated between-species platform to evaluate pro-cognitive treatments.
认知控制缺陷与许多神经精神疾病有关。然而，相关的药物治疗方法有限，这可能是由于应用于临床前模型的转化效度较弱。从脑电图中得出的神经指标可能有助于比较和翻译不同物种中认知增强药物的效果。在目前的研究中，我们旨在通过检查哌醋甲酯（MPH）是否能调节独立的人类和大鼠队列的认知控制的行为和神经指标，来扩展我们以前的跨物种研究结果。
我们从健康成年人（n=25；14 名女性）和长耳大仓鼠（n=22；8 名女性）中测量了连续的脑电图数据，并比较了物种之间的刺激和反应锁相关事件相关电位和光谱功率测量值，以及它们在接受载体（安慰剂）或 1 种或 2 种 MPH 剂量治疗后的 MPH 相关调节。
在两个物种中，线性混合效应模型都证实了预期的 Flanker 干扰效应对行为（例如准确性）和反应相关事件相关电位的影响。出乎意料的是，与过去的工作相反，我们没有观察到啮齿动物的光谱功率与任务有关的任何影响。此外，MPH 通常没有调节两种物种的认知控制，尽管有些种间特定的模式为未来的研究提供了一些见解。
总的来说，这些在独立的人类和啮齿动物受试者中的发现复制了我们以前报告的一些行为和神经生理模式，部分与以下观点一致，即类似的神经机制可能调节两种物种的认知控制。尽管如此，这些结果展示了一种使用协调的种间平台来评估认知增强治疗方法的加速转化的方法。
