Lüttjohann Annika, Schoffelen Jan-Mathijs, van Luijtelaar Gilles
Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Donders Centre for Cognition, Nijmegen, The Netherlands.
Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Donders Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands; Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.
Neurobiol Dis. 2014 Oct;70:127-37. doi: 10.1016/j.nbd.2014.06.007. Epub 2014 Jun 18.
While decades of research were devoted to study generation mechanisms of spontaneous spike and wave discharges (SWD), little attention has been paid to network mechanisms associated with the spontaneous termination of SWD. In the current study coupling-dynamics at the onset and termination of SWD were studied in an extended part of the cortico-thalamo-cortical system of freely moving, genetic absence epileptic WAG/Rij rats.
Local-field potential recordings of 16 male WAG/Rij rats, equipped with multiple electrodes targeting layer 4 to 6 of the somatosensory-cortex (ctx4, ctx5, ctx6), rostral and caudal reticular thalamic nucleus (rRTN & cRTN), ventral postero medial (VPM), anterior- (ATN) and posterior (Po) thalamic nucleus, were obtained. Six seconds lasting pre-SWD->SWD, SWD->post SWD and control periods were analyzed with time-frequency methods, and between-region interactions were quantified with frequency-resolved Granger Causality (GC) analysis.
Most channel pairs showed increases in GC lasting from onset to offset of the SWD. While for most thalamo-thalamic pairs a dominant coupling direction was found during the complete SWD, most cortico-thalamic pairs only showed a dominant directional drive (always from cortex to thalamus) during the first 500ms of SWD. Channel pair ctx4-rRTN showed a longer lasting dominant cortical drive, which stopped 1.5sec prior to SWD offset. This early decrease in directional coupling was followed by an increase in directional coupling from cRTN to rRTN 1sec prior to SWD offset. For channel pairs ctx5-Po and ctx6-Po the heightened cortex->thalamus coupling remained until 1.5sec following SWD offset, while the thalamus->cortex coupling for these pairs stopped at SWD offset.
The high directional coupling from somatosensory cortex to the thalamus at SWD onset is in good agreement with the idea of a cortical epileptic focus that initiates and entrains other brain structures into seizure activity. The decrease of cortex to rRTN coupling as well as the increased coupling from cRTN to rRTN preceding SWD termination demonstrates that SWD termination is a gradual process that involves both cortico-thalamic as well as intrathalamic processes. The rostral RTN seems to be an important resonator for SWD and relevant for maintenance, while the cRTN might inhibit this oscillation. The somatosensory cortex seems to attempt to reinitiate SWD following its offset via its strong coupling to the posterior thalamus.
尽管数十年来的研究致力于探讨自发性棘波和慢波放电（SWD）的产生机制，但与SWD自发终止相关的网络机制却很少受到关注。在本研究中，我们在自由活动的遗传性失神癫痫WAG/Rij大鼠的皮质-丘脑-皮质系统的扩展部分，研究了SWD起始和终止时的耦合动力学。
对16只雄性WAG/Rij大鼠进行局部场电位记录，这些大鼠配备了多个电极，分别靶向体感皮层（ctx4、ctx5、ctx6）的第4至6层、丘脑网状核的嘴侧和尾侧（rRTN和cRTN）、腹后内侧核（VPM）、丘脑前核（ATN）和丘脑后核（Po）。采用时频方法分析持续6秒的SWD前->SWD、SWD->SWD后以及对照期，并通过频率分辨格兰杰因果关系（GC）分析对区域间相互作用进行量化。
大多数通道对在SWD从起始到结束期间，GC均增加。虽然对于大多数丘脑-丘脑通道对，在整个SWD期间都发现了主导的耦合方向，但大多数皮质-丘脑通道对仅在SWD的前500毫秒显示出主导的方向性驱动（始终从皮层到丘脑）。通道对ctx4-rRTN显示出持续时间更长的主导皮质驱动，该驱动在SWD结束前1.5秒停止。这种方向性耦合的早期下降之后，在SWD结束前1秒，从cRTN到rRTN的方向性耦合增加。对于通道对ctx5-Po和ctx6-Po，增强的皮层->丘脑耦合一直持续到SWD结束后1.5秒，而这些通道对的丘脑->皮层耦合在SWD结束时停止。
SWD起始时从体感皮层到丘脑的高方向性耦合，与引发癫痫发作并使其他脑结构陷入癫痫活动的皮质癫痫病灶的观点高度一致。SWD终止前，皮层到rRTN耦合的减少以及从cRTN到rRTN耦合的增加表明，SWD终止是一个渐进过程，涉及皮质-丘脑以及丘脑内过程。嘴侧RTN似乎是SWD的重要谐振器，与SWD的维持相关，而cRTN可能抑制这种振荡。体感皮层在SWD结束后似乎试图通过与丘脑后部的强耦合重新引发SWD。
