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R1 component of the electrically induced blink reflex recorded by an accelerometer. An example of R1 elicited by electrical stimulation of the supraorbital nerve. A, Superimposed 15 waveforms elicited by the test stimulus alone, prepulse alone, and test plus prepulse with a PTI of 110 ms. Filled triangles and circles indicate the test stimulus onset and prepulse onset, respectively. B, Full rectified waveforms of the 15 sweeps (blue) and their average (black).
Source publication
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 combin...
Contexts in source publication
Context 1
... R3, the later components were evaluated using an AUC at 60-100 ms in Exp 4 and Exp 5. Although the R2 component starts at ;30 ms with a duration of ;30 ms on EMGs (Kugelberg, 1952;Aramideh and Ongerboer de Visser, 2002), we selected a 60-100 ms analysis period because eyelid movement because of the R1 component appears to continue up to ;60 ms [ Fig. 1 (see also Fig. 3)]. The R2 and R3 components were not distinguishable in the present study, and therefore, the later component analyzed at this latency was referred to as the late blink reflex ...
Context 2
... stimulation of the SON elicited a biphasic R1 response ipsilaterally with the first signal peak at 20-25 ms (Fig. 1A), which is delayed by 10-15 ms from the corresponding peak in the EMG. The time gap closely matched the 11-12 ms delay between EMG R1 and eyelid closure as reported by Evinger et al. (1991). In Exp 1, effects because of a weak prepulse (0.9 times the R1 threshold) of SON stimulation on R1 elicited by test SON stimulation (1.5 times the ...
Citations
... However, translating this to humans is challenging due to the pathway's complexity and incomplete knowledge of the mechanisms involved in PPI. Considering this, we recently developed a method using the trigeminal blink reflex R1 component to observe PPI (Inui et al., 2023). The reflex elicited by electrical stimulation of the supraorbital nerve (SON) has multiple components, including an early and ipsilateral component (R1) and a later bilateral component (R2). ...
... Another advantage to this method is that early inhibition may be explored due to the sharp and brief nature of electrical stimulation. Recently, clear PPI of the R1 component was demonstrated using the principal trigeminal nucleus as the target site of inhibition (Inui et al., 2023). ...
... The method of electrical stimulation, recording of the blink reflex, and the procedure for analysis followed a recent study (Inui et al., 2023). To elicit blink reflexes, the right SON was stimulated with a square wave pulse of 0.5 ms using two disposable Ag/AgCl gel electrodes 10 mm in diameter (Biorode SDC-H, Vyaire Medical, Tokyo), one placed near the supraorbital foramen and the other approximately 3 cm above it. ...
Prepulse inhibition (PPI) is a well-established phenomenon wherein a weak sensory stimulus attenuates the startle reflex triggered by a subsequent strong stimulus. Within the circuit, variations in target responses observed for PPI paradigms represent prepulse-induced excitability changes. However, little is known about the mechanism of PPI. Here, we focused on short-latency PPI of the trigeminal blink reflex R1 signal with an oligosynaptic reflex arc through the principal sensory trigeminal nucleus and the facial nucleus. As the facial nucleus is facilitatory to any input, R1 PPI is the phenomenon in the former nucleus. Considering that GABAergic modulation may be involved in PPI, this study investigated whether the PPI mechanism includes GABA-A equivalent inhibition, which peaks at approximately 30 ms in humans. In 12 healthy volunteers, the reflex was elicited by electrical stimulation of the supraorbital nerve, and recorded at the ipsilateral lower eyelid by accelerometer. Stimulus intensity was 1.5 times the R1 threshold for test stimulus and 0.9 times for the prepulse. The prepulse-test interval (PTI) was 5-150 ms. Results showed significant inhibition at 40-and 80-150-ms PTIs but not at 20-, 30-, 50-, 60-, and 70-ms PTIs, yielding two distinct inhibitions of different time scales. This corresponds well to the early and late components of inhibitory post synaptic potentials by GABA-A and GABA-B receptor activation. Thus, the data support the contribution of inhibitory post synaptic potentials elicited by the prepulse to the observed PPI. As inhibitory function-related diseases may impair the different inhibition components to varying degrees, methods deconvoluting each inhibitory component contribution are of clinical importance.
... In the present study, a reduction in the test response by a weak leading stimulus, irrespective of the neural circuit, is referred to as PPI. In addition to the startle reflex and cortical responses, we showed that the R1 component of the trigeminal blink reflex with an oligosynaptic pathway showed PPI over a similar time course to conventional PPI (Inui et al., 2023). In the present study, the auditory change-related response was used as the test response. ...
... Although there are some paradigms for observing PPI, each PPI appears to reflect a similar automatic process (Ellwanger et al., 2003). A recent study using the trigeminal blink reflex showed that PPI of the early component of the blink reflex occurred in the first stage of brain processing in the principal nucleus of the trigeminal nerve and did not involve higher complex processes (Inui et al., 2023). In studies with PPI of the acoustic startle reflex, one reported decreased inhibition in older subjects (de Oliveira et al., 2023), while others reported no effect of age (Filion and Poje, 2003;Scholes and Martin-Iverson, 2009) or an inverted U-shaped relationship between age and PPI, with the strongest inhibition in middle age (Ellwanger et al., 2003). ...
Responses to a sensory stimulus are inhibited by a preceding stimulus; if the two stimuli are identical, paired-pulse suppression (PPS) occurs; if the preceding stimulus is too weak to reliably elicit the target response, prepulse inhibition (PPI) occurs. PPS and PPI represent excitability changes in neural circuits induced by the first stimulus, but involve different mechanisms and are impaired in different diseases, e.g., impaired PPS in schizophrenia and Alzheimer’s disease and impaired PPI in schizophrenia and movement disorders. Therefore, these measures provide information on several inhibitory mechanisms that may have roles in clinical conditions. In the present study, PPS and PPI of the auditory change-related cortical response were examined to establish normative data on healthy subjects (35 females and 32 males, aged 19–70 years). We also investigated the effects of age and sex on PPS and PPI to clarify whether these variables need to be considered as biases. The test response was elicited by an abrupt increase in sound pressure in a continuous sound and was recorded by electroencephalography. In the PPS experiment, the two change stimuli to elicit the cortical response were a 15-dB increase from the background of 65 dB separated by 600 ms. In the PPI experiment, the prepulse and test stimuli were 2- and 10-dB increases, respectively, with an interval of 50 ms. The results obtained showed that sex exerted similar effects on the two measures, with females having stronger test responses and weaker inhibition. On the other hand, age exerted different effects: aging correlated with stronger test responses and weaker inhibition in the PPS experiment, but had no effects in the PPI experiment. The present results suggest age and sex biases in addition to normative data on PPS and PPI of auditory change-related potentials. PPS and PPI, as well as other similar paradigms, such as P50 gating, may have different and common mechanisms. Collectively, they may provide insights into the pathophysiologies of diseases with impaired inhibitory function.
... Furthermore, the re ex suppression mechanism is almost entirely unknown. Considering this, we recently developed a method using the trigeminal blink re ex R1 component to observe PPI [9]. The re ex elicited by electrical stimulation of the supraorbital nerve (SON) has multiple components, but we focus on the early component (R1), a sharp component occurring during the rst 10 to 20 ms of the blink re ex and is formed by a two-synapse re ex circuit via the trigeminal principal sensory nucleus and facial nerve nucleus [10]. ...
... In humans, the late GABA-B mediated IPSP reportedly peaks at 135 ms [14]. These values are consistent with the present, longer than 80 ms, PTI inhibition times as well as our previous study showing peak R1 inhibition at 140 ms [9]. Therefore, the biphasic inhibition time course in the present study matches well with the early and late IPSPs common across mammals [13] and brain areas [19]. ...
... It is possible that clinical conditions may be due to abnormalities in speci c interneurons or receptors, thereby showing PPI changes at speci c PTIs. The R1 circuit is simple with the trigeminal principal nucleus and facial nucleus, with the former previously demonstrated as the R1 PPI target site [9]. However, this does not mean that the inhibitory control is simple. ...
Prepulse inhibition (PPI) refers to the phenomenon in which a weak sensory input, that by itself does not reliably induce a startle reflex, suppresses the startle reflex induced by a subsequent strong sensory stimulus. A major challenge in studying PPI is the incomplete understanding of the startle reflex pathway as well as inhibition mechanisms. Here we focused on short-latency PPI of the trigeminal blink reflex R1 signal with an oligosynaptic reflex arc to clarify whether the PPI mechanism involves GABA-A equivalent inhibition. The reflex was elicited by electrical stimulation of the supraorbital nerve, and was recorded from the ipsilateral lower eyelid using an accelerometer. The stimulus intensity was 1.5 times the R1 threshold for the test stimulus and 0.9 times for the prepulse. The prepulse–test interval (PTI) was 5–150 ms. Results yielded two distinct inhibitions with different time scales; early inhibition peaking at 40-ms PTI or earlier, and a later one after 80-ms PTIs, which corresponds well to the common early and late components of inhibitory post synaptic potentials. There is clinical benefit to understanding the relative behavior of these two components in inhibitory function related diseases.
