Assessment of excitability in brainstem circuits mediating the blink reflex and the startle reaction

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Abstract

Excitability is probably the concept that fits better with the definition of the role of neurophysiology in the study of brainstem functions and circuits. Neurophysiological techniques are likely the best suited of all paraclinical tests for documenting the eventual excitability changes that may occur in certain physiological states and in many neurological disorders. The best known test of brainstem excitability is the blink reflex. While a single stimulus can already indicate the readiness of the interneuronal path and the facial motoneurons to fire, pairs of stimuli (conditioning and test) are suited to analyze the degree of excitability recovery after a single discharge. Another brainstem reflex circuit, which excitability testing can be of interest for physiological and clinical exams is the one involved in the startle reaction. The size of the responses and their habituation are the typical measures of excitability of the startle reflex circuit. Prepulse inhibition is a method to modulate both, the blink reflex and the startle reaction. It is defined as the inhibitory effect caused by a stimulus of an intensity low enough not to induce a response by itself on the response elicited by a subsequent stimulus. The circuits of the blink reflex, startle reaction and prepulse inhibition share some commonalities but they are different enough for the three techniques to provide unique, clinically relevant, information in certain conditions. The role of neurophysiology is not limited to testing those functions. It is important also for the assessment of many other circuits, such as those implicated in eye movements, vestibular reflexes, arousal, sleep, breathing, or autonomic reactions, which are not considered in this review.

Highlights

► One of the most important domains in neurophysiology studies is testing excitability of neural circuits. ► Excitability of the blink reflex and the startle reaction reflect basal ganglia modulation of brainstem interneuronal circuits. ► Prepulse inhibition is a common mechanism for control of excitability changes in the blink reflex and the startle reaction.

Introduction

Many neurophysiological techniques are useful for the study of brainstem reflexes and functions of physiological and clinical relevance. Neurophysiology is still the first choice among paraclinical tests for the documentation of some physiological aspects as well as the pathophysiological mechanisms underlying abnormal function of the cranial nerves or the brainstem (Aramideh et al., 2002a, Aramideh et al., 2002b). Some techniques are useful for the study of dysfunctions that primarily affect the brainstem nuclei and circuitry while others can document the abnormalities involving the control of brainstem reflex circuits by rostral structures, but the unifying concept among all these neurophysiological techniques is, probably, excitability. This is defined as the reactivity of neural structures to sensory inputs. The changes in excitability of brainstem neurons and circuits are the domain in which neurophysiology can contribute most to the understanding of pathophysiological mechanisms and their eventual impairment in some neurological disorders. This review is intended to cover the unique contribution of neurophysiological tests in the evaluation of excitability of two brainstem circuits: the blink reflex and the startle reaction, and a common modulatory test for both of them, prepulse inhibition. Changes in excitability of reflex circuits may be the expression of neurological dysfunctions not only in the reflex arc itself but also at distant sites if the effects of the disorder induce synaptic reorganization. The study of excitability changes may offer a cue to understand the extent of a disorder in some neurodegenerative diseases and allows the neurophysiologist to have an observation window for central nervous system functions. The study of brainstem reflexes is also an important neurophysiological asset for obtaining clinically relevant data. However, I have not dealt in here with the clinical applications of the neurophysiological study of the brainstem and cranial nerves. The interested reader can find a large number of review papers in the clinical utility of neurophysiological testing of the brainstem and cranial nerves (Hopf, 1994, Cruccu and Deuschl, 2000, Aramideh et al., 2002b, Meinck, 2006, Bakker et al., 2006, Tinazzi et al., 2009).

Section snippets

Blink reflex

Blinking is one of the most frequent motor actions that humans do in every day life. It consists of a brief eyelid closure involving activation of the orbicularis oculi, innervated by the facial nerve, and relaxation of the levator palpebrae, innervated by the IIIrd cranial nerve. Blinking serves in physiological terms to spread a layer of tears on the corneal surface but has likely other roles for cognition, communication or emotional expressions (Boelhouwer and Brunia, 1977). Although

The startle reaction

The startle reaction (SR) is the consequence of the involuntary activation of the motor tracts generated in the brainstem, mainly in the pontomedullary reticular formation (Davis et al., 1982, Wilkins et al., 1986, Brown et al., 1991). The most apparent manifestation of the SR in humans is its early component: a fast involuntary reflex contraction of face and limb muscles that follows a rostro-caudal progression and serves a protective function. However, the same stimulus may trigger a later

Prepulse inhibition

The concept of prepulse refers to any low intensity stimulus that is unable to cause a recordable response by itself but induces significant changes in the response to a subsequent suprathreshold stimulus. Mostly, the effects are inhibitory but a window of facilitation likely precedes the inhibitory effect (Valls-Solé et al., 1999b). Although prepulse inhibition is considered the best known mechanism of control over the SR (Graham 1975), the functional anatomy of the prepulse circuit is not

Conclusions

Neurophysiological techniques are essential in the study of excitability changes of braintem structures that can be related to several aspects of normal behavior as well as to abnormal function of higher order structures. Tests assessing excitability in the brainstem circuits of the blink reflex and the SR are useful in many clinical conditions. The study of prepulse inhibition is inseparable from that of the blink reflex and the SR. Abnormalities in prepulse inhibition are likely to generate

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