Despite the clinical significance of prepulse inhibition (PPI), the mechanisms are not well understood. Herein, we present our investigation of PPI in the R1 component of electrically induced blink reflexes. The effect of a prepulse was explored with varying prepulse test intervals (PTIs) of 20–600 ms in 4 females and 12 males. Prepulse–test combinations included the following: stimulation of the supraorbital nerve (SON)–SON [Experiment (Exp) 1], sound–sound (Exp 2), the axon of the facial nerve–SON (Exp 3), sound–SON (Exp 4), and SON–SON with a long trial–trial interval (Exp 5). Results showed that (1) leading weak SON stimulation reduced SON-induced ipsilateral R1 with a maximum effect at a PTI of 140 ms, (2) the sound–sound paradigm resulted in a U-shaped inhibition time course of the auditory startle reflex (ASR) peaking at 140 ms PTI, (3) facial nerve stimulation showed only a weak effect on R1, (4) a weak sound prepulse facilitated R1 but strongly inhibited SON-induced late blink reflexes (LateRs) with a similar U-shaped curve, and (5) LateR in Exp 5 was almost completely absent at PTIs >80 ms. These results indicate that the principal sensory nucleus is responsible for R1 PPI. Inhibition of ASR or LateR occurs at a point in the startle reflex circuit where auditory and somatosensory signals converge. Although the two inhibitions are different in location, their similar time courses suggest similar neural mechanisms. As R1 has a simple circuit and is stable, R1 PPI helps to clarify PPI mechanisms.SIGNIFICANCE STATEMENTPrepulse inhibition (PPI) is a phenomenon in which the startle response induced by a startle stimulus is suppressed by a preceding nonstartle stimulus. This study demonstrated that the R1 component of the trigeminal blink reflex shows clear PPI despite R1 generation within a circuit consisting of the trigeminal and facial nuclei, without startle reflex circuit involvement. Thus, PPI is not specific to the startle reflex. In addition, PPI of R1, the auditory startle reflex, and the trigeminal late blink reflex showed similar time courses in response to the prepulse test interval, suggesting similar mechanisms regardless of inhibition site. R1 PPI, in conjunction with other paradigms with different prepulse–test combinations, would increase understanding of the underlying mechanisms.

論文題目We could predict good responders to vagus nerve stimulation: a surrogate marker by slow cortical potential shift (脳波の緩電位変化は迷走神経刺激療法の治療効果の代替マーカーとなる) (論文内容の要旨) Objective: Vagus nerve stimulation (VNS) is a palliative treatment option for patients with intractable epilepsy who are not good candidates for surgical resection. The stimulation of the vagus nerve is intermittent, and the usual stimulation condition is set to a signal on-time (VNS ON) of 30 s followed by an off-time (VNS OFF) of 3-5 min repeatedly. It has been reported that one third of patients have a >50% reduction in seizure frequency, another one third show a 30%-50% seizure reduction, and the remaining one third show no response. On the other hand, hyperpolarization of neurons, seen on electroencephalograms (EEGs) as positive slow cortical potential (SCP) shifts, represents activation of inhibitory postsynaptic potentials and inhibition of neuronal activity. Production of scalp-recorded positive SCP by a self-regulation training has been used for suppressing seizures, and some patients have even become seizure free. Slow hyperpolarization of cortical pyramidal neurons during the stimulation period in rat models was suggested as an underlying mechanism of action of VNS in suppressing seizures. The aim of this study was to investigate whether VNS induces a positive shift of SCPs in patients with >50% seizure reduction (responders) but not in non-responders. Methods: This retrospective study was approved by the ethics committees of the Kyoto University Hospital, Kindai University Hospital and Hiroshima University Hospital (IRB#E1736, #25-036 and #Epi1158 respectively). Routine clinical EEGs from 24 patients who were undergoing seizure treatment by VNS were analyzed. The patients were divided into 2 groups by hardware time constant (TC) of EEG: the TC 10-s group (10 patients) and TC 2-s group (14 patients). The SCPs at 5 electrodes (vertex and adjacent ones) were compared between the 2 states of VNS: during stimulation and between stimulations. A positive shift of the SCP was considered to be "present" when it was observed on the 5 electrodes during the stimulation period, and the Wilcoxon test value was <0.05. Seizure reduction was independently judged. Correlation between SCP (positivity or not) and seizure reduction (>50% or not) was estimated. Results: In the TC 10-s group, the correlation between SCP and seizure reduction was significant (p < 0.05) (i.e., both good results in 4 and both negative results in 5). In TC 2-s group, the correlation between SCP and seizure reduction was not significant (p = 0.209). Conclusions:This study compared scalp-recorded SCPs during VNS stimulation period with the inter-stimulation interval respectively from 5 electrodes in patients undergoing VNS therapy. The comparison showed that utilization of EEG with a long TC (10 s) revealed positive SCP shifts during VNS in good responders. A positive shift of SCP recorded by using a TC of 10 s could be a surrogate marker for VNS response.

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