Introduction upon the cortex [24,32,34]. However, comparing with its

Brain Research 882 2000 103–111 www.elsevier.com locate bres Research report Dual control of the brainstem on the spindle oscillation in humans a , a b c Shinobu Kohsaka , Taeko Sakai , Masako Kohsaka , Noriko Fukuda , a Kunihiko Kobayashi a Department of Pediatrics , Hokkaido University School of Medicine, N-15 W-7, Kita-ku, Sapporo 060, Japan b Sapporo Hanazono Hospital , Sapporo 064, Japan c Department of Laboratory Technology , College of Medical Technology, Hokkaido University, Sapporo 060, Japan Accepted 8 August 2000 Abstract In human subjects, the excitability change of the brainstem was investigated over the course of the spindle oscillation. The investigation was carried out by a sequential analysis of brainstem auditory evoked potentials BAEPs with reference to one sequence of spindle oscillation. The method was based on the characteristics of BAEPs, i.e. far-field evoked potential. The brainstem revealed two types of excitability change: one in the lower ventral brainstem wave-III components, and the other in the upper dorsal brainstem wave-V components. The excitability in the dorsal brainstem showed an oscillation with one cycle period of about 1.5 s, whereas in the ventral brainstem, the excitability showed a long-range biphasic decaying–growing fluctuation. Both excitability changes in the brainstem preceded the spindle oscillation, and the phase was reversed during the emerging period of spindle oscillation. The results suggest a primary triggering mechanism of the brainstem for the spindle oscillation, which is independent of preceding cortical drives K-complexes upon the thalamus. The difference of the excitability change between the spindle oscillation and the paroxysmal discharge spike-and-wave complex was also discussed.  2000 Elsevier Science B.V. All rights reserved. Theme : Neural basis of behaviour Topic : Biological rhythms and sleep Keywords : Sleep spindle; Brainstem; Brainstem auditory evoked potential; Excitability change 1. Introduction upon the cortex [24,32,34]. However, comparing with its established mechanism for the rhythm generation, the Spindle oscillations are the most salient synchronized triggering mechanism for the spindle seems less clear neuronal activities in the cortex during sleep. These except for the hypothesis that widespread hyperpolariza- oscillations are the hallmark of a transitional state from tions in both the cortex and the thalamus might trigger the moderate to deep sleep slow-wave sleep on electroence- spindle [8,9]. phalographs EEGs [29]. Spindle oscillations appear with Spindle oscillations are also important for the underlying a crescendo–decrescendo shape waxing–waning with a mechanism of generalized epileptic seizures with spike- duration of about 0.5–1.0 s, with a repetition rate of 5–6 and-wave complex SWC. Gloor et al. disclosed a gradual times min in humans [12,14]. The mechanism for the shift from spindle oscillations to SWC in cats with rhythm generation 12–14 Hz in humans has been investi- systemic application of penicillin feline generalized gated in experimental animal models. The results from penicillin epilepsy, FGPE [13]. Although recent experi- animal models disclosed that the reciprocally connected ments reevaluated the results from FGPE model [35,36], two groups of neurons in the thalamus reticular thalamic, the question — why patients with absence epilepsy RE; thalamocortical, TC generate the rhythm by recip- experience their seizures 3-Hz SWC, prototype of SWC rocal reverberation, and TC neurons project the rhythm even in a preceding vigilant state — has been left unanswered. To solve the problem, we have recently disclosed a functional change in the brainstem, a long- Corresponding author. Fax: 181-11-706-7898. E-mail address : shinobu-masakomm.neweb.ne.jp S. Kohsaka. range fluctuation superimposed with rhythmic oscillations, 0006-8993 00 – see front matter  2000 Elsevier Science B.V. All rights reserved. P I I : S 0 0 0 6 - 8 9 9 3 0 0 0 2 8 3 9 - 0 104 S that precedes 3-Hz SWC in patients with absence epilepsy sampled EEG data; two sequences of spindle appear in Fig. [22]. The investigation was carried out by a simultaneous 1A. We excluded the spindle oscillation with a preceding analysis of far-field evoked potentials brainstem auditory large negative EEG transient K-complex or vertex sharp evoked potentials, BAEPs with reference to the paroxys- transient from the analysis. An example of the spindle mal discharges SWC. oscillation with K-complex is also shown in Fig. 1A Here, we investigated the brainstem function over the marked with ‘1’. K-complexes can be detected easily, course of a spindle oscillation before and during with a because they show regular phase reversals between C3–Cz similar analytic method in humans. Probably, spindle and Cz–C4 according to the distribution pattern in the oscillations are more suitable candidates for the analysis EEG field [6]. because of their periodic characteristics rather than in- The method for obtaining sequential BAEPs over one frequent EEG events such as epileptic discharges. spindle oscillation was as follows. i The EEG data just before one spindle oscillation were selected with a series of 16 segments in a manner that

2. Materials and methods the last segment in the series positioned the first spindle

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