Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
Schizophr Bull. 2024 Jan 1;50(1):96-106. doi: 10.1093/schbul/sbad032.
The integration of information that typifies working memory (WM) operation requires a flexible, dynamic functional relationship among brain regions. In schizophrenia, though WM capacity is prominently impaired at higher loads, the mechanistic underpinnings are unclear. As a result, we lack convincing cognitive remediation of load-dependent deficits. We hypothesize that reduced WM capacity arises from a disruption in dynamic functional connectivity when patients face cognitive demands.
We calculate the dynamic voxel-wise degree centrality (dDC) across the functional connectome in 142 patients with schizophrenia and 88 healthy controls (HCs) facing different WM loads during an n-back task. We tested associations of the altered variability in dDC and clinical symptoms and identified intermediate connectivity configurations (clustered states) across time during WM operation. These analyses were repeated in another independent dataset of 169 subjects (102 with schizophrenia).
Compared with HCs, patients showed an increased dDC variability of supplementary motor area (SMA) for the "2back vs. 0back" contrast. This instability at the SMA seen in patients correlated with increased positive symptoms and followed a limited "U-shape" pattern at rest-condition and 2 loads. In the clustering analysis, patients showed reduced centrality in the SMA, superior temporal gyrus, and putamen. These results were replicated in a constrained search in the second independent dataset.
Schizophrenia is characterized by a load-dependent reduction of stable centrality in SMA; this relates to the severity of positive symptoms, especially disorganized behaviour. Restoring SMA stability in the presence of cognitive demands may have a therapeutic effect in schizophrenia.
工作记忆（WM）操作的特征是信息的整合，这需要大脑区域之间具有灵活、动态的功能关系。在精神分裂症中，尽管在较高负荷下 WM 容量明显受损，但其机制尚不清楚。因此，我们缺乏令人信服的认知矫正来弥补与负荷相关的缺陷。我们假设，当患者面临认知需求时，动态功能连接的中断导致 WM 容量减少。
我们在 142 名精神分裂症患者和 88 名健康对照者（HCs）中计算了功能连接体的动态体素中心度（dDC），他们在 n-back 任务中面临不同的 WM 负荷。我们测试了 dDC 变化与临床症状的相关性，并确定了 WM 操作过程中跨时间的中间连接模式（聚类状态）。这些分析在另一个由 169 名受试者组成的独立数据集（102 名精神分裂症患者）中重复进行。
与 HCs 相比，患者在“2 回比 0 回”对比中表现出补充运动区（SMA）的 dDC 变异性增加。患者在 SMA 中观察到的这种不稳定性与阳性症状的增加有关，并在静息状态和 2 个负荷下呈现出有限的“U 形”模式。在聚类分析中，患者在 SMA、颞上回和壳核中表现出中心性降低。这些结果在第二个独立数据集的约束搜索中得到了复制。
精神分裂症的特征是 SMA 中稳定中心性的负荷依赖性降低；这与阳性症状的严重程度有关，尤其是紊乱行为。在存在认知需求的情况下恢复 SMA 的稳定性可能对精神分裂症具有治疗作用。
