Department of Psychiatry,Psychosomatic Medicine and Psychotherapy,University Hospital Frankfurt,Frankfurt am Main,Germany.
Psychol Med. 2019 Jan;49(1):75-83. doi: 10.1017/S003329171800051X. Epub 2018 Mar 9.
Working memory (WM) deficits in schizophrenia (SCZ) have been linked to impairments in the encoding phase that are associated with aberrant neuronal functioning. Similar abnormalities have been observed in unaffected first-degree relatives (REL) and are thus discussed as candidate endophenotypes. The process of WM consolidation - i.e. the formation of durable WM representations - is assumed to be impaired in SCZ, but no study has investigated WM consolidation and neuronal correlates of visual WM encoding in REL before.
We examined whole-brain activation during the encoding phase with an event-related functional magnetic resonance imaging study design in 25 SCZ subjects, 22 REL subjects, and 25 healthy controls. Subjects performed a visual masked change detection task that assessed WM performance and consolidation.
SCZ showed deficient WM performance indicating an impairment consolidation process, accompanied by broad neuronal hypoactivation, most prominently in frontal brain regions, as well as increased activity of the anterior cingulate during the encoding phase. REL showed decreased neuronal activity in the middle and medial frontal gyrus and increased activity in the precentral gyrus and insula during encoding, but no significant behavioral deficits were observed. In respect of given consolidation times, REL showed a shift from decreased frontal activity at short time intervals to increased frontal activity at longer time intervals.
Findings suggest WM consolidation may be slowed in REL so that the deployment of compensatory neuronal resources during encoding is needed to assure proper WM performance. This supports the view of WM-related neuronal dysfunctions as a potential endophenotypic marker.
精神分裂症(SCZ)患者的工作记忆(WM)缺陷与编码阶段的损伤有关,这些损伤与异常的神经元功能有关。在未受影响的一级亲属(REL)中也观察到了类似的异常,因此被认为是候选的内表型。WM 巩固的过程——即形成持久的 WM 表现——被认为在 SCZ 中受损,但没有研究在之前调查过 REL 中的 WM 巩固和视觉 WM 编码的神经元相关性。
我们使用事件相关的功能磁共振成像研究设计,在 25 名 SCZ 患者、22 名 REL 患者和 25 名健康对照者中,检查了编码阶段的全脑激活。被试者进行了一项视觉掩蔽变化检测任务,该任务评估了 WM 表现和巩固。
SCZ 表现出 WM 表现缺陷,表明巩固过程受损,伴随着广泛的神经元活动低下,最明显的是在前额叶脑区,以及在编码阶段前扣带皮层的活动增加。REL 在编码期间表现出中内侧额回的神经元活动减少和中央前回和岛叶的活动增加,但没有观察到显著的行为缺陷。在给定的巩固时间方面,REL 表现出从短时间间隔的额部活动减少到长时间间隔的额部活动增加的转变。
研究结果表明,REL 中的 WM 巩固可能会变慢,因此需要在编码期间部署补偿性的神经元资源,以确保适当的 WM 表现。这支持了 WM 相关的神经元功能障碍作为潜在的内表型标记的观点。