Ornithine transcarbamylase deficiency (OTCD) is the most common form of urea cycle disorder characterized by the presence of hyperammonemia (HA). In patients with OTCD, HA is known to cause impairments in domains of executive function and working memory. Monitoring OTCD progression and investigating neurocognitive biomarkers can, therefore, become critical in understanding the underlying brain function in a population with OTCD. We used functional near infrared spectroscopy (fNIRS) to examine the hemodynamics of prefrontal cortex (PFC) in a fraternal twin with and without OTCD. fNIRS is a non-invasive and wearable optical technology that can be used to assess cortical hemodynamics in a realistic clinical setting. We quantified the hemodynamic variations in total-hemoglobin as assessed by fNIRS while subjects performed the N-back working memory (WM) task. Our preliminary results showed that the sibling with OTCD had higher variation in a very low frequency band (<0.03 Hz, related to mechanism of cerebral autoregulation) compared to the control sibling. The difference between these variations was not as prominent in the higher frequency band, indicating the possible role of impaired autoregulation and cognitive function due to presence of HA. We further examined the functional connectivity in PFC, where the OTCD sibling showed lower interhemispheric functional connectivity as the task load increased. Our pilot results are the first to show the utility of fNIRS in monitoring OTCD cortical hemodynamics, indicating the possibility of inefficient neurocognitive function. This study provides a novel insight into the monitoring of OTCD focusing on the contribution of physiological process and neurocognitive function in this population.

中文翻译：

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鸟氨酸转氨甲酰酶缺乏症中前额皮质的血流动力学：双胞胎案例研究。


鸟氨酸转氨甲酰酶缺乏症 (OTCD) 是尿素循环障碍的最常见形式，其特征是存在高氨血症 (HA)。在 OTCD 患者中，已知 HA 会导致执行功能和工作记忆领域受损。因此，监测 OTCD 进展和研究神经认知生物标志物对于了解 OTCD 人群的潜在大脑功能至关重要。我们使用功能性近红外光谱 (fNIRS) 来检查有或没有 OTCD 的异卵双胞胎的前额皮质 (PFC) 的血流动力学。 fNIRS 是一种非侵入式可穿戴光学技术，可用于在现实的临床环境中评估皮质血流动力学。我们量化了受试者执行 N-back 工作记忆 (WM) 任务时通过 fNIRS 评估的总血红蛋白的血流动力学变化。我们的初步结果表明，与对照兄弟姐妹相比，患有 OTCD 的兄弟姐妹在极低频段（<0.03 Hz，与大脑自动调节机制相关）具有更高的变异。这些变化之间的差异在较高频段中并不那么显着，表明由于 HA 的存在可能导致自动调节和认知功能受损。我们进一步检查了 PFC 的功能连接，随着任务负荷的增加，OTCD 兄弟显示出较低的半球间功能连接。我们的试点结果首次展示了 fNIRS 在监测 OTCD 皮质血流动力学方面的实用性，表明神经认知功能可能存在低效。这项研究为 OTCD 的监测提供了新的见解，重点关注该人群生理过程和神经认知功能的贡献。