Hong L Elliot, Turano Kathleen A, O'Neill Hugh, Hao Lei, Wonodi Ikwunga, McMahon Robert P, Elliott Amie, Thaker Gunvant K
Maryland Psychiatric Research Center, Lions Vision Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21228, USA.
Biol Psychiatry. 2008 Mar 1;63(5):458-64. doi: 10.1016/j.biopsych.2007.06.004. Epub 2007 Jul 30.
To utilize fully a schizophrenia endophenotype in gene search and subsequent neurobiological studies, it is critical that the precise underlying physiologic deficit is identified. Abnormality in smooth pursuit eye movements is one of the endophenotypes of schizophrenia. The precise nature of the abnormality is unknown. Previous work has shown a reduced predictive pursuit response to a briefly masked (i.e., invisible) moving object in schizophrenia. However, the overt awareness of target removal can confound the measurement.
This study employed a novel method that covertly stabilized the moving target image onto the fovea. The foveal stabilization was implemented after the target on a monitor had oscillated at least for one cycle and near the change of direction when the eye velocity momentarily reached zero. Thus, the subsequent pursuit eye movements were completely predictive and internally driven. Eye velocity during this foveally stabilized smooth pursuit was compared among schizophrenia patients (n = 45), their unaffected first-degree relatives (n = 42), and healthy comparison subjects (n = 22).
Schizophrenia patients and their unaffected relatives performed similarly and both had substantially reduced predictive pursuit acceleration and velocity under the foveally stabilized condition.
These findings show that inability to maintain internal representation of the target motion or integration of such information into a predictive response may be the specific brain deficit indexed by the smooth pursuit endophenotype in schizophrenia. Similar performance between patients and unaffected relatives suggests that the refined predictive pursuit measure may index a less complex genetic origin of the eye-tracking deficits in schizophrenia families.
为了在基因搜索及后续神经生物学研究中充分利用精神分裂症的内表型,确定其精确的潜在生理缺陷至关重要。平稳跟踪眼球运动异常是精神分裂症的内表型之一。这种异常的确切性质尚不清楚。先前的研究表明,精神分裂症患者对短暂掩蔽(即不可见)的移动物体的预测性跟踪反应降低。然而,对目标移除的明显意识可能会混淆测量结果。
本研究采用了一种新方法,即将移动目标图像隐蔽地稳定在中央凹上。在显示器上的目标至少振荡一个周期后,且在眼球速度瞬间达到零时接近方向改变时,实施中央凹稳定。因此,随后的跟踪眼球运动完全是可预测的且由内部驱动。比较了精神分裂症患者(n = 45)、其未受影响的一级亲属(n = 42)和健康对照受试者(n = 22)在这种中央凹稳定的平稳跟踪过程中的眼球速度。
精神分裂症患者及其未受影响的亲属表现相似,在中央凹稳定条件下,两者的预测性跟踪加速度和速度均显著降低。
这些发现表明,无法维持目标运动的内部表征或将此类信息整合到预测反应中,可能是精神分裂症平稳跟踪内表型所指示的特定脑缺陷。患者与未受影响亲属之间的相似表现表明,精细的预测性跟踪测量可能指示了精神分裂症家族中眼球跟踪缺陷的较简单遗传起源。