Olfaction as a Marker for Dystonia: Background, Current State and Directions

Dystonia is a heterogeneous group of hyperkinetic movement disorders. The unifying descriptor of dystonia is the motor manifestation, characterized by continuous or intermittent contractions of muscles that cause abnormal movements and postures. Additionally, there are psychiatric, cognitive, and sensory alterations that are possible or putative non-motor manifestations of dystonia. The pathophysiology of dystonia is incompletely understood. A better understanding of dystonia pathophysiology is highly relevant in the amelioration of significant disability associated with motor and non-motor manifestations of dystonia. Recently, diminished olfaction was found to be a potential non-motor manifestation that may worsen the situation of subjects with dystonia. Yet, this finding may also shed light into dystonia pathophysiology and yield novel treatment options. This article aims to provide background information on dystonia and the current understanding of its pathophysiology, including the key structures involved, namely, the basal ganglia, cerebellum, and sensorimotor cortex. Additionally, involvement of these structures in the chemical senses are reviewed to provide an overview on how olfactory (and gustatory) deficits may occur in dystonia. Finally, we describe the present findings on altered chemical senses in dystonia and discuss directions of research on olfactory dysfunction as a marker in dystonia.

Context-Dependent Modulation of Corticomuscular Coherence in a Series of Motor Initiation and Maintenance of Voluntary Contractions

For our precise motor control, we should consider “motor context,” which involves the flow from feedforward to feedback control. The present study focused on corticomuscular coherence (CMC) to physiologically evaluate how the sensorimotor integration is modulated in a series of movements depending on the motor context. We evaluated CMC between electroencephalograms over the sensorimotor cortex and rectified electromyograms from the tibialis anterior muscle during intermittent contractions with 2 contraction intensities in 4 experiments. Although sustained contractions with weak-to-moderate intensities led to no difference in CMC between intensities, intermittent ballistic-and-hold contractions with 2 intensities (10% and 15% or 25% of the maximal voluntary contraction, MVC) presented in a randomized order resulted in greater magnitude of CMC for the weaker intensity. Moreover, the relative amount of initial error was larger for trials with 10% of MVC, which indicated that initial motor output was inaccurate during weaker contractions. However, this significant difference in CMC vanished in the absence of trial randomization or the application of intermittent ramp-and-hold contractions with slower torque developments. Overall, CMC appears to be modulated context-dependently and is especially enhanced when active sensorimotor integration is required in feedback control periods because of the complexity and inaccuracy of preceding motor control.

Force-velocity relationship during isometric and isotonic fatiguing contractions

Fatiguing contractions change the force-velocity relationship, but assessment of this relationship in fatigue has usually been obtained after isometric contractions. We studied fatigue caused by isometric or isotonic contractions, by assessment of the force-velocity relationship while the contractions maintaining fatigue were continued. This approach allowed determination of the force-velocity relationship during a steady condition of fatigue. We used the in situ rat medial gastrocnemius muscle, a physiologically relevant preparation. Intermittent (1/s) stimulation at 170 Hz for 100 ms resulted in decreased isometric force to ~35% of initial or decreased peak velocity of shortening in dynamic contractions to ~45% of initial. Dynamic contractions resulted in a transient initial increase in velocity, followed by a rapid decline until a reasonably steady level was maintained. Data were fit to the classic Hill equation for determination of the force-velocity relationship. Isometric and dynamic contractions resulted in similar decreases in maximal isometric force and peak power. Only Vmax was different between the types of contraction ( P < 0.005) with greater decrease in Vmax during isotonic contractions to 171.7 ± 7.3 mm/s than during isometric contractions to 208.8 mm/s. Curvature indicated by a/Po (constants from fit to Hill equation) changed from 0.45 ± 0.04 to 0.71 ± 0.11 during isometric contractions and from 0.51 ± 0.04 to 0.85 ± 0.18 during isotonic contractions. Recovery was incomplete 45 min after stopping the intermittent contractions. At this time, recovery of low-frequency isometric force was substantially less after isometric contractions, implicating force during intermittent contractions as a determining factor with this measure of fatigue. NEW & NOTEWORTHY The force-velocity relationship was captured while fatigue was maintained at a constant level during isometric and dynamic contractions. The curvature of the force-velocity relationship was less curved during fatigue than prefatigued, but within 45 min this recovered. Low-frequency fatigue persisted with greater depression of low-frequency force after isometric contractions, possibly because of higher force contractions during intermittent contractions.

Maximal intermittent contractions of the first dorsal interosseous inhibits voluntary activation of the contralateral homologous muscle

The aim of this study was to investigate how maximal intermittent contractions for a hand muscle influence cortical and reflex activity, as well as the ability to voluntarily activate the homologous muscle in the opposite limb. Twelve healthy subjects (age 24 ± 3 yr, all right-hand dominant) performed maximal contractions of the dominant limb first dorsal interosseous (FDI), and activity of the contralateral FDI was examined in a series of experiments. Index finger abduction force, FDI electromyography (EMG), motor evoked potentials, and heteronomous reflexes were obtained from the contralateral limb during brief, nonfatiguing contractions. The same measures, as well as the ability to voluntarily activate the contralateral FDI, were then assessed in an extended intermittent contraction protocol that elicited fatigue. Brief contractions under nonfatigued conditions increased index finger abduction force, FDI EMG, and motor evoked potential amplitude of the contralateral limb. However, when intermittent maximal contractions were continued until fatigue, there was an inability to produce maximal force with the contralateral limb (∼30%), which was coupled to a decrease in the level of voluntary activation (∼20%). These declines were present without changes in reflex activity and regardless of whether cortical or motor point stimulation was used to assess voluntary activation. It is concluded that performing maximal intermittent contractions with a single limb causes an inability of the central nervous system to maximally drive the homologous muscle of the contralateral limb. This is, in part, mediated by mechanisms that involve the motor cortex ipsilateral to the contracting limb.

Changes in Elbow Flexor Power with Intermittent Contractions and Various Loads

This study examined intermittent elbow flexion every 2 see. for 1 min. using various loads to study the properties of muscle power output and their relationship to peak power, defined as the maximum power output. 18 young men performed intermittent explosive elbow flexion (30 times × min.−1) using 30%, 40%, and 50% maximal voluntary contraction (MVC). The power outputs at 30% and 40% MVC slightly decreased (rate of decrease from peak power to average power output during the 26 to 30 contractions was about 5%). However, at 50% MVC, there was a marked decrease (33.6%). Power output for 8 contractions was significantly larger at 50% MVC than at 30% and 40% MVC, but after 9 contractions there was no significant difference between 40% and 50% MVC. In addition, after 27 contractions, 40% MVC was significantly larger than 30% and 50% MVC. That is, the tendency for power output to decrease differed among the various loads. The rate of decrease of power outputs showed no significant correlation with peak power for each load. Therefore, the rate of decrease or power output in intermittent contractions may help sustain the power output and cannot be evaluated as accurately as peak power.