Arnts Hisse, Tewarie Prejaas, van Erp Willemijn, Schuurman Rick, Boon Lennard I, Pennartz Cyriel M A, Stam Cornelis J, Hillebrand Arjan, van den Munckhof Pepijn
Department of Neurosurgery, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Department of Neurosurgery, Radboud University Medical Center, Nijmegen, The Netherlands.
Sci Rep. 2024 Feb 5;14(1):2950. doi: 10.1038/s41598-024-52267-1.
After severe brain injury, zolpidem is known to cause spectacular, often short-lived, restorations of brain functions in a small subgroup of patients. Previously, we showed that these zolpidem-induced neurological recoveries can be paralleled by significant changes in functional connectivity throughout the brain. Deep brain stimulation (DBS) is a neurosurgical intervention known to modulate functional connectivity in a wide variety of neurological disorders. In this study, we used DBS to restore arousal and motivation in a zolpidem-responsive patient with severe brain injury and a concomitant disorder of diminished motivation, more than 10 years after surviving hypoxic ischemia. We found that DBS of the central thalamus, targeted at the centromedian-parafascicular complex, immediately restored arousal and was able to transition the patient from a state of deep sleep to full wakefulness. Moreover, DBS was associated with temporary restoration of communication and ability to walk and eat in an otherwise wheelchair-bound and mute patient. With the use of magnetoencephalography (MEG), we revealed that DBS was generally associated with a marked decrease in aberrantly high levels of functional connectivity throughout the brain, mimicking the effects of zolpidem. These results imply that 'pathological hyperconnectivity' after severe brain injury can be associated with reduced arousal and behavioral performance and that DBS is able to modulate connectivity towards a 'healthier baseline' with lower synchronization, and, can restore functional brain networks long after severe brain injury. The presence of hyperconnectivity after brain injury may be a possible future marker for a patient's responsiveness for restorative interventions, such as DBS, and suggests that lower degrees of overall brain synchronization may be conducive to cognition and behavioral responsiveness.
重度脑损伤后，已知唑吡坦可使一小部分患者的脑功能出现显著的、通常短暂的恢复。此前，我们发现这些由唑吡坦诱导的神经功能恢复可伴随着全脑功能连接的显著变化。深部脑刺激（DBS）是一种神经外科干预手段，已知其可调节多种神经系统疾病中的功能连接。在本研究中，我们对一名重度脑损伤且伴有动机减退障碍的唑吡坦反应性患者使用DBS来恢复觉醒和动机，该患者在经历缺氧缺血后已存活超过10年。我们发现，针对中央中核 - 束旁复合体的中央丘脑进行DBS可立即恢复觉醒，并能使患者从深度睡眠状态转变为完全清醒。此外，DBS使一名原本只能坐在轮椅上且无法言语的患者暂时恢复了交流能力以及行走和进食能力。通过使用脑磁图（MEG），我们发现DBS通常与全脑异常高水平的功能连接显著降低有关，这与唑吡坦的作用相似。这些结果表明，重度脑损伤后的“病理性高连接性”可能与觉醒和行为表现降低有关，并且DBS能够将连接性调节至同步性更低的“更健康基线”，并在重度脑损伤后很长时间恢复功能性脑网络。脑损伤后高连接性的存在可能是患者对诸如DBS等恢复性干预反应性的一个潜在未来标志物，并表明较低程度的全脑同步性可能有利于认知和行为反应性。
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