Coffman Brian A, Haas Gretchen, Olson Carl, Cho Raymond, Ghuman Avniel Singh, Salisbury Dean F
Clinical Neurophysiology Research Laboratory, Western Psychiatric Hospital of UPMC, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
Western Psychiatric Hospital of UPMC, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
Front Psychiatry. 2020 Aug 4;11:743. doi: 10.3389/fpsyt.2020.00743. eCollection 2020.
Cognitive deficits in people with schizophrenia are among the hardest to treat and strongly predict functional outcome. The ability to maintain sensory precepts in memory over a short delay is impacted early in the progression of schizophrenia and has been linked to reliable neurophysiological markers. Yet, little is known about the mechanisms of these deficits. Here, we investigated possible neurophysiological mechanisms of impaired visual short-term memory (vSTM, aka working memory maintenance) in the first-episode schizophrenia spectrum (FESz) using magnetoencephalography (MEG). Twenty-eight FESz and 25 matched controls performed a lateralized change detection task where they were cued to selectively attend and remember colors of circles presented in either the left or right peripheral visual field over a 1 s delay. Contralateral alpha suppression (CAS) during the delay period was used to assess selective attention to cued visual hemifields held in vSTM. Delay-period CAS was compared between FESz and controls and between trials presenting one vs three items per visual hemifield. CAS in dorsal visual cortex was reduced in FESz compared to controls in high-load trials, but not low-load trials. Group differences in CAS were found beginning 100 ms after the disappearance of the memory set, suggesting deficits were not due to the initial deployment of attention to the cued visual hemifield prior to stimulus presentation. CAS was not greater for high-load vs low-load trials in FESz subjects, although this effect was prominent in controls. Further, lateralized gamma (34-40 Hz) power emerged in dorsal visual cortex prior to the onset of CAS in controls but not FESz. Gamma power in this cluster differed between groups at both high and low load. CAS deficits observed in FESz were correlated with change detection accuracy, working memory function, estimated IQ, and negative symptoms. Our results implicate deficits in CAS in trials requiring broad, but not narrow, focus of attention to spatially distributed objects maintained in vSTM in FESz, possibly due to reduced ability to broadly distribute visuospatial attention (alpha) or disruption of object-location binding (gamma) during encoding/consolidation. This early pathophysiology may shed light upon mechanisms of emerging working memory deficits that are intrinsic to schizophrenia.
精神分裂症患者的认知缺陷是最难治疗的，并且对功能预后有很强的预测作用。在精神分裂症进展早期，在短时间延迟内将感觉知觉维持在记忆中的能力就受到影响，并且与可靠的神经生理学标志物有关。然而，对于这些缺陷的机制知之甚少。在这里，我们使用脑磁图（MEG）研究了首发精神分裂症谱系（FESz）中视觉短期记忆（vSTM，即工作记忆维持）受损的可能神经生理机制。28名FESz患者和25名匹配的对照组进行了一项侧化变化检测任务，在该任务中，他们被提示选择性地关注并记住在1秒延迟期间出现在左或右外周视野中的圆圈颜色。延迟期的对侧α抑制（CAS）用于评估对vSTM中提示的视觉半视野的选择性注意。比较了FESz患者和对照组之间以及每个视觉半视野呈现一个与三个项目的试验之间的延迟期CAS。在高负荷试验中，与对照组相比，FESz患者背侧视觉皮层的CAS降低，但在低负荷试验中没有。在记忆组消失后100毫秒开始发现CAS的组间差异，这表明缺陷不是由于在刺激呈现之前对提示的视觉半视野进行初始注意力分配所致。在FESz受试者中，高负荷试验与低负荷试验的CAS没有更大差异，尽管这种效应在对照组中很明显。此外，在对照组中，背侧视觉皮层在CAS开始之前出现了侧化伽马（34 - 40 Hz）功率，而在FESz患者中则没有。该簇中的伽马功率在高负荷和低负荷时两组之间均有差异。在FESz患者中观察到的CAS缺陷与变化检测准确性、工作记忆功能、估计智商和阴性症状相关。我们的结果表明，在FESz患者中，在需要对vSTM中维持的空间分布对象进行广泛而非狭窄的注意力集中的试验中，CAS存在缺陷，这可能是由于在编码/巩固过程中广泛分布视觉空间注意力（α）的能力降低或对象位置绑定（γ）受到破坏。这种早期病理生理学可能有助于揭示精神分裂症内在的新兴工作记忆缺陷的机制。
