Donati Francesco L, Mayeli Ahmad, Nascimento Couto Bruno Andry, Sharma Kamakashi, Janssen Sabine, Krafty Robert J, Casali Adenauer G, Ferrarelli Fabio
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Health Science, University of Milan, Milan, Italy.
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2025 Feb;10(2):158-166. doi: 10.1016/j.bpsc.2024.07.013. Epub 2024 Jul 25.
Abnormalities in dorsolateral prefrontal cortex (DLPFC) oscillations are neurophysiological signatures of schizophrenia thought to underlie its cognitive deficits. Transcranial magnetic stimulation with electroencephalography (TMS-EEG) provides a measure of cortical oscillations unaffected by sensory relay functionality and/or patients' level of engagement, which are important confounding factors in schizophrenia. Previous TMS-EEG work showed reduced fast, gamma-range oscillations and a slowing of the main DLPFC oscillatory frequency, or natural frequency, in chronic schizophrenia. However, it is unclear whether this DLPFC natural frequency slowing is present in early-course schizophrenia (EC-SCZ) and is associated with symptom severity and cognitive dysfunction.
We applied TMS-EEG to the left DLPFC in 30 individuals with EC-SCZ and 28 healthy control participants. Goal-directed working memory performance was assessed using the AX-Continuous Performance Task. The EEG frequency with the highest cumulative power at the stimulation site, or natural frequency, was extracted. We also calculated the local relative spectral power as the average power in each frequency band divided by the broadband power.
Compared with the healthy control group, the EC-SCZ group had reduced DLPFC natural frequency (p = .0000002, Cohen's d = -2.32) and higher DLPFC beta-range relative spectral power (p = .0003, Cohen's d = 0.77). In the EC-SCZ group, the DLPFC natural frequency was inversely associated with negative symptoms. Across all participants, the beta band relative spectral power negatively correlated with AX-Continuous Performance Task performance.
DLPFC oscillatory slowing is an early pathophysiological biomarker of schizophrenia that is associated with its symptom severity and cognitive impairments. Future work should assess whether noninvasive neurostimulation, including repetitive TMS, can ameliorate prefrontal oscillatory deficits and related clinical functions in patients with EC-SCZ.
背外侧前额叶皮层（DLPFC）振荡异常是精神分裂症的神经生理学特征，被认为是其认知缺陷的基础。经颅磁刺激结合脑电图（TMS-EEG）可测量不受感觉传导功能和/或患者参与程度影响的皮层振荡，而这些因素在精神分裂症中是重要的混杂因素。先前的TMS-EEG研究表明，慢性精神分裂症患者的快速伽马频段振荡减少，DLPFC主要振荡频率或固有频率减慢。然而，目前尚不清楚这种DLPFC固有频率减慢是否存在于早期精神分裂症（EC-SCZ）中，以及是否与症状严重程度和认知功能障碍有关。
我们对30名EC-SCZ患者和28名健康对照者的左侧DLPFC进行了TMS-EEG检查。使用AX连续性能任务评估目标导向工作记忆表现。提取刺激部位累积功率最高的脑电频率，即固有频率。我们还计算了局部相对谱功率，即每个频段的平均功率除以宽带功率。
与健康对照组相比，EC-SCZ组的DLPFC固有频率降低（p = 0.0000002，Cohen's d = -2.32），DLPFCβ频段相对谱功率升高（p = 0.0003，Cohen's d = 0.77）。在EC-SCZ组中，DLPFC固有频率与阴性症状呈负相关。在所有参与者中，β频段相对谱功率与AX连续性能任务表现呈负相关。
DLPFC振荡减慢是精神分裂症的一种早期病理生理生物标志物，与症状严重程度和认知障碍有关。未来的研究应评估包括重复经颅磁刺激在内的非侵入性神经刺激是否能改善EC-SCZ患者的前额叶振荡缺陷及相关临床功能。
