Haenschel Corinna, Bittner Robert A, Waltz James, Haertling Fabian, Wibral Michael, Singer Wolf, Linden David E J, Rodriguez Eugenio
Department of Psychiatry, Johann Wolfgang Goethe University, Frankfurt, Germany.
J Neurosci. 2009 Jul 29;29(30):9481-9. doi: 10.1523/JNEUROSCI.1428-09.2009.
Impairments in working memory (WM) are a core cognitive deficit in schizophrenia. Neurophysiological models suggest that deficits during WM maintenance in schizophrenia may be explained by abnormalities in the GABAergic system, which will lead to deficits in high-frequency oscillations. However, it is not yet clear which of the three WM phases (encoding, maintenance, retrieval) are affected by dysfunctional oscillatory activity. We investigated the relationship between impairments in oscillatory activity in a broad frequency range (3-100 Hz) and WM load in the different phases of WM in 14 patients with early-onset schizophrenia and 14 matched control participants using a delayed matching to sample paradigm. During encoding, successful memorization was predicted by evoked theta, alpha, and beta oscillatory activity in controls. Patients showed severe reductions in the evoked activity in these frequency bands. During early WM maintenance, patients showed a comparable WM load-dependent increase in induced alpha and gamma activity to controls. In contrast, during the later maintenance phase, patients showed a shift in the peak of induced gamma activity to the lower WM load conditions. Finally, induced theta and gamma activity were reduced in patients during retrieval. Our findings suggest that the WM deficit in schizophrenia is associated with impaired oscillatory activity during all phases of the task and that the cortical storage system reaches its capacity limit at lower loads. Inability to maintain oscillatory activity in specific frequency bands could thus result in the information overload that may underlie both cognitive deficits and psychopathological symptoms of schizophrenia.
工作记忆（WM）损害是精神分裂症的核心认知缺陷。神经生理学模型表明，精神分裂症患者在WM维持过程中的缺陷可能由GABA能系统异常所解释，这将导致高频振荡缺陷。然而，目前尚不清楚三个WM阶段（编码、维持、检索）中的哪一个受到振荡活动功能失调的影响。我们使用延迟匹配样本范式，研究了14例早发性精神分裂症患者和14名匹配的对照参与者在广泛频率范围（3 - 100Hz）内的振荡活动损害与WM不同阶段的WM负荷之间的关系。在编码过程中，对照组中诱发的θ波、α波和β波振荡活动可预测成功记忆。患者在这些频段的诱发活动严重减少。在WM早期维持阶段，患者与对照组相比，诱导的α波和γ波活动呈现出类似的WM负荷依赖性增加。相反，在后期维持阶段，患者诱导的γ波活动峰值向较低WM负荷条件偏移。最后，患者在检索过程中诱导的θ波和γ波活动减少。我们的研究结果表明，精神分裂症患者的WM缺陷与任务所有阶段的振荡活动受损有关，并且皮质存储系统在较低负荷时达到其容量极限。因此，无法维持特定频段的振荡活动可能导致信息过载，这可能是精神分裂症认知缺陷和精神病理症状的基础。
