Narcolepsy–cataplexy: deficient prepulse inhibition of blink reflex suggests pedunculopontine involvement

Abstract

Summary Hypocretin (orexin) deficiency plays a major role in the pathophysiology of narcolepsy–cataplexy. In animal models, hypocretinergic projections to the pedunculopontine nucleus are directly involved in muscle tone regulation mediating muscle atonia – a hallmark of cataplexy. We hypothesized that pedunculopontine nucleus function, tested with prepulse inhibition of the blink reflex, is altered in human narcolepsy–cataplexy. Twenty patients with narcolepsy–cataplexy and 20 healthy controls underwent a neurophysiological study of pedunculopontine nucleus function. Blink reflex, prepulse inhibition of the blink reflex and blink reflex excitability recovery were measured. Blink reflex characteristics (R1 latency and amplitude, and R2 and R2c latency and area under the curve) did not differ between patients and controls (P > 0.05). Prepulse stimulation significantly increased R2 and R2c latencies and reduced R2 and R2c areas in patients and controls. However, the R2 and R2c area suppression was significantly less in patients than in controls (to 69.8 ± 14.4 and 74.9 ± 12.6%, respectively, versus 34.5 ± 28.6 and 43.3 ± 29.5%, respectively; each P < 0.001). Blink reflex excitability recovery, as measured by paired‐pulse stimulation, which is not mediated via the pedunculopontine nucleus, did not differ between patients and controls (P > 0.05). Our data showed that prepulse inhibition is reduced in narcolepsy–cataplexy, whereas unconditioned blink reflex and its excitability recovery are normal. Because the pedunculopontine nucleus is important for prepulse inhibition, these results suggest its functional involvement in narcolepsy–cataplexy.

Prepulse inhibition of the blink reflex is abnormal in functional movement disorders

“…The R1 component of the response was used as a marker that the afferent volley generated by prepulse stimuli had effectively reached the brainstem. 29 The R3 response, 27,28 which was observed in some patients, particularly in the initial recordings, was not included in our calculations because it was not part of the planned study protocol.…”

“…The R3 response, which was observed in some patients, particularly in the initial recordings, was not included in our calculations because it was not part of the planned study protocol.…”

Threat vs control: Potentiation of the trigeminal blink reflex by threat proximity is overruled by self‐stimulation

“…On the other hand, the blink reflex was inhibited when verbal instructions and acoustic forewarning about the imminent stimulation were given (Ison et al, 1990), or by attentional shift away from the blink reflex eliciting stimulus to a simultaneous weak stimulus (Silverstein et al, 1981). In condition S 1 of experiment 1, the first shock in each block elicited a large R3 response in many participants (Figure 1), corresponding to a startle component (Frauscher et al, 2012;Kofler & Halder, 2014), which, however, habituated rapidly during subsequent trials ruling out a startling effect in condition S 1 as a mechanisms for the potentiation of TBR-R2. A faster rate of habituation of R3 as compared to that of R2 has previously been described (Rossi et al, 1995).…”

Abnormal Blink Reflex and Intermuscular Coherence in Writer's Cramp

“…In healthy people, the blink reflex is normally inhibited if conditioned by a preceding peripheral nerve stimulus, a phenomenon referred to as PPI. This is thought to be mediated via an inhibitory brainstem reticular pathway involving the pedunculo-pontine nucleus (PPN), and is typically diminished in disorders affecting the PPN or adjoining structures ( 9 , 10 ). Whilst PPI of the blink reflexes is reportedly abnormal in craniofacial dystonia ( 11 ), cervical dystonia and blepharospasm ( 12 , 13 ), in a previous study of 3 WC patients PPI was normal ( 8 ).…”