Riedinger Joséphine, Hutt Axel
MLMS, MIMESIS, Université de Strasbourg, CNRS, lnria, ICube, 67000 Strasbourg, France.
INSERM, U1114, Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie, 67085 Strasbourg, France.
J Clin Med. 2022 Mar 26;11(7):1845. doi: 10.3390/jcm11071845.
Schizophrenia is a psychotic disease that develops progressively over years with a transition from prodromal to psychotic state associated with a disruption in brain activity. Transcranial Direct Current Stimulation (tDCS), known to alleviate pharmaco-resistant symptoms in patients suffering from schizophrenia, promises to prevent such a psychotic transition. To understand better how tDCS affects brain activity, we propose a neural cortico-thalamo-cortical (CTC) circuit model involving the Ascending Reticular Arousal System (ARAS) that permits to describe major impact features of tDCS, such as excitability for short-duration stimulation and electroencephalography (EEG) power modulation for long-duration stimulation. To this end, the mathematical model relates stimulus duration and Long-Term Plasticity (LTP) effect, in addition to describing the temporal LTP decay after stimulus offset. This new relation promises to optimize future stimulation protocols. Moreover, we reproduce successfully EEG-power modulation under tDCS in a ketamine-induced psychosis model and confirm the N-methyl-d-aspartate (NMDA) receptor hypofunction hypothesis in the etiopathophysiology of schizophrenia. The model description points to an important role of the ARAS and the δ-rhythm synchronicity in CTC circuit in early-stage psychosis.
精神分裂症是一种精神病性疾病，多年来逐渐发展，从前驱期过渡到精神病状态，伴有大脑活动紊乱。经颅直流电刺激（tDCS）已知可缓解精神分裂症患者的药物抵抗症状，有望预防这种精神病性转变。为了更好地理解tDCS如何影响大脑活动，我们提出了一种涉及上行网状激活系统（ARAS）的神经皮质-丘脑-皮质（CTC）电路模型，该模型能够描述tDCS的主要影响特征，如短时间刺激的兴奋性和长时间刺激的脑电图（EEG）功率调制。为此，该数学模型除了描述刺激停止后的时间性长时程增强（LTP）衰减外，还将刺激持续时间与LTP效应联系起来。这种新关系有望优化未来的刺激方案。此外，我们在氯胺酮诱导的精神病模型中成功再现了tDCS下的EEG功率调制，并证实了精神分裂症病因病理生理学中的N-甲基-D-天冬氨酸（NMDA）受体功能低下假说。模型描述指出了ARAS和早期精神病中CTC电路中δ节律同步性的重要作用。
