Muscle spindles are specialized modified muscle fibres that act as sensory receptors, sending information about muscle length, speed of stretch as well as perceived effort to the central nervous system. The combined information provided by muscle spindle receptors is then used to determine the position and movement of our joints (proprioception). As muscle spindles react to changes in muscle length, they are also involved in the regulation of muscle contraction (Santuz and Akay 2023).

Of considerable interest are the older findings of Burke and colleagues, who looked into muscle spindle function. They noted that during shortening contractions the fusimotor system is activated together with the skeleto-motor system (Burke et al. 1978). However, the fusimotor drive is generally insufficient to maintain a significant spindle discharge unless movement is slow, or the muscle is shortening against an external load (isotonic contraction) (Burke et al. 1978). These authors also noted that during lengthening contractions (eccentric) the spindle responses were greater than observed during passive stretch of a similar amplitude and velocity, suggesting heightened fusimotor outflow. Indeed, they were able to measure the mean discharge from a dynamic spindle ending in the tibialis anterior muscle during voluntary movement to be in the order of 7.5 per second during stretch, but only 1.0 per second during shortening, a difference that disappeared with loading (Burke et al. 1978).

These findings raise the question as to whether the motor activity of flexion or extension results in different firing rates for the muscle spindles embedded within these muscles. One potentially important consequence of such a difference would be to have a protective effect, sending frequent signals back to the central nervous system (CNS) every time a muscle is extended whilst contracting, presenting a risk of damage, yet sending relatively few signals when a muscle is shortened under contraction, simply because the risk of injury is so much less with such motor activity.

An overview of a typical muscle spindle is given in Fig. 1.

(Source & Copyright EMB & AH)

An overview of intrafusal muscle spindles. (A) illustrates the link between extrafusal and intrafusal innervation, including ? efferent motor neurone innervation to extrafusal fibres and ? efferent innervation to the muscle spindles. Note also the Ia / II afferent innervation from the muscle spindles back to the CNS and more specifically to a region we have referred to as C (Control Centre; see (McClusky et al. 1983) where there is both a negative stimulus from the ? efferent neurone and positive stimulus from the Ia / II afferent neurone. (B) provides an overview of the types of static and dynamic muscle spindles found associated with extrafusal fibres and their efferent and afferent innervation. This figure does not illustrate the \(\:\beta\:\:\text\text\text\text\text\text\text\text\text\text\text\:\text\text\text\text\text\text\text\text\:\text\text\text\text\text\:\)innervation. This innervation comprises combined static/dynamic fibres showing both extrafusal and intrafusal fibres. γ motorneurones have the sole function of addressing fusi-motion. Spindle α motorneurones are solely extrafusal fibre related and are skeleto-motor in function. \(\:\beta\:\:\)motorneurones can be skeleto-motor and fusi-motor, but never fusi-motor alone.

The C marked on panel (A) of Fig. 1 represents a Control Centre in the region of the spinal cord (location yet to be determined by histology) that senses Ia / II afferent signals and integrates them with signals from the fusimotor system (? efferent and probably also \(\:\beta\:\) efferent), such that any signal in excess of the fusimotor signal constitutes a kinesthetic signal (McClusky et al. 1983). Various models have been proposed for the function of the region we refer to as C, such as a Signal Processing Area facilitating sensory motor performance in a task specific way and not only a measurement of posture and movement (Dimitriou and Edin 2010). Another model presents Forward Mediated Processing, created by interaction changes in length of muscle spindles and their adaptive response, used for perception of effort (Monjo and Allen 2023). Others have even suggested that there is evidence for the abundance of muscle spindles in regulating muscle contraction (Kissane et al. 2022). Kinesthetic signals are more commonly known today as proprioception, a system whereby feedback sensations relating to body position, movement and the position of body parts relative to each other are combined with muscle contractions. One could even speculate that stiffness or contracture in a muscle may to some extent be due to a mismatch between spindle signals arriving at the C-cell. Furthermore, the motor excitation signal as well as any other regulatory signal arriving at the C-cell, may override part of, or all of the spindle signal, and together these signals determine the degree of overall muscle contraction.

Intrafusal muscle spindles are stretch receptors whose function is to correct for changes in muscle length when extrafusal muscle fibres are either shortened (under contraction) or lengthened (under stretch). Such muscle spindles and their reflexes operate to return extrafusal muscle to its resting length after it has been shortened or lengthened, as well as to maintain length-tension at its optimal setting (Winters et al. 2011). In terms of sensory innervation, each intrafusal muscle spindle consists of either a Ia or II afferent nerve, which innervates the central region of the nuclear bag fibres (dynamic/static: Ia) or the nuclear chain fibres (static: II) (see Fig. 1B). It is important to note that the Ia fibres are among the largest nerves in the body with some of the fastest conduction velocities (80–120 m/s), whilst II fibres have intermediate diameters and intermediate conduction velocities (33–75 m/s). Motor innervation of the intrafusal muscle spindles consists of two types of γ motor neurones (both dynamic and static), where dynamic γ motor neurones synapse on the nuclear bag fibres, and static γ motor neurones synapse on nuclear chain fibres which spread over longer distances. It is worth noting that γ motor neurones are smaller and slower than the α motor neurones that innervate the extrafusal fibres, and they serve to regulate the sensitivity of the intrafusal muscle fibres they innervate (Prochazka and Hulliger 1983).

In the feline it has been shown that \(\:\beta\:\:\)motor neurone fibre stimulation is widespread and functionally significant. Moreover, spindle morphology in man points towards great similarity between spindle function in the cat and rat (Prochazka and Hulliger 1983) suggesting that \(\:\beta\:\:\)motor neurone fibre stimulation may also be present in man, and could perhaps be a common mammalian feature?

The afferent signal from muscle spindles is generally classified as being both by a primary (Ia) and a secondary (II) motorneurone based on their differences in their dynamic sensitivities to stretch (Hagbarth 1993). At resting length discharge rates for muscle spindles are often measured to zero, and during stretch at a constant level of force the discharge rate has been shown to be typically less than 25 per second (25 Hz). Under conditions where subjects voluntarily applied the fastest stretch possible, the peak rate of discharge was less than 100 Hz and more often less than 50 Hz (Prochazka and Hulliger 1983).

Position sensitivity for muscle spindles and the afferent signal from relaxed muscles is very low (0.18–0.28 Hz) per degree of joint movement (Prochazka and Hulliger 1983). Some loss of sensitivity may occur as a result of the known decrease in the number of intrafusal fibres as well as the increase in capsular thickness, and signs of denervation in some spindles, all of which occur with increasing age (Swash and Fox 1972; Liu et al. 2002). Findings that lend support to a loss of sensitivity in muscle spindles with increasing age causing the known decrease in accurate proprioception (Lord et al. 2019).

With PD, Camptocormia, which is an axial thoracolumbar deformity, may result in a bent back angle (Schulz-Schaeffer 2016; Bloch et al. 2006). For this to happen, the sensory input from muscle spindles and joint receptors which gives a sense of joint position, of movement and the sense of muscle strength, is most likely compromised. In PD an impaired proprioception has been demonstrated and could be part of the underlying cause for occurrence of camptocormia (Bloch et al. 2006). Keeping in mind that the muscle spindle system is mature already at a young age (Österlund et al. 2011), and that PD patients typically demonstrate perfect healthy motoric skills during a substantial part of their life, this raises the question as to whether and indeed when changes in spindle activity and possibly structure take place with PD. This could, moreover, provide an early diagnosis for this disease. Accepting the hypothesis that muscle spindles participate in regulating muscle contraction, then AMG measurements of suspected CP or PD individuals where the clinical studies to date show a change in the S: T to values less than 1.0 (Celicanin et al. 2023; Pingel et al. 2019), might prove a useful technique for measuring this (see below, Table 2).

Furthermore, it would be of particular value if it was possible to slow down the development of such proposed changes in the PD spindle system. In healthy subjects exposed to eccentric exercise to the point of fatigue, muscle spindles still give the correct information concerning limb position, although some dynamic position error occurs (Celicanin et al. 2023). This would mean that whilst the angle of contraction of a joint is retained, an element of inaccuracy is introduced whilst the limb is in movement.

With advanced PD the responses to mechanical vibrations of the Ia afferents become compromised, and this is not improved by medication such as L-3,4-dihydroxyphenyalanine known medically as levodopa DOPA (Valkovic et al. 2006). This change may further be linked to the growing dependency on visual inputs to carry out certain types of movement as the disease progresses (Lee 1989), and the precision with which movement and location of the limb relative to the joint are compromised. The precise signalling behind this change is still not clear, but they might be a further development of the phenomenon associated with changes in Ia signalling (dynamic: bag fibres). In support of the findings with PD patients, it has been found in the cat that DOPA administration resulted in an enhanced muscle spindle activity in the static state for both flexor and extensor muscles, yet in the dynamic state the activity of flexor muscles was depressed (Prochazka 1981; Johansson et al. 1995). Furthermore, it has been shown that autogenetic reflex effects from large muscle afferents are relatively weak in the spinal cat treated with DOPA (Prochazka 1981). This is in accordance with the difference in diameter of the afferent nerves (Ia vs. II).

Focusing on possible changes in the function of muscle spindles in PD, the AMG data from Celicanin et al. (2023) tell a story on their own. The AMG data in Table 1 are directly taken from the Celicanin et al. (2023) study. The AMG parameters are efficiency (E-score), spatial- (S-score) and or temporal-summation (T-score) given by the E-, S-, and T-scores. As an overall measure of muscle function, the combined mean EST score (Mean EST = E-score + S-score + T-score / 3) is shown. It is interesting to note that L-DOPA administration to PD subjects improves their overall muscle function (see Table 1; Mean EST). However, the PD patients do not reach the same level of mean EST as the healthy controls, whether this be for passive or active movements. Indeed, the mean EST values typically reach a level of 66–75% of the healthy controls. Clearly then the discrepancy must be with an altered efficiency, spatial- and or temporal-summation (E-, S-, T-score). For the m.Triceps, both for passive and active activity, the discrepancy is found to be a combination of all three parameters, which remain lower than comparable values for healthy matched controls.

It is also interesting to note that for m.Triceps the passive to active ratio (P: A) returns to healthy control values for the E-score, whilst the S-score ratio is higher and the T-score ratio lower than that of healthy matched controls, indicating a persistent altered function, but one that most likely does not affect muscle spindles.

Despite the fact that PD patients seem to have a normal muscle function following medication, the EST mean reveals that they are over-working their muscles compared to age-matched controls. This is the case for both the extensor and the flexor muscles. Medication clearly improves the PD condition, but the treatment does not restore muscle function to the same level as that found in HC. The E-score following medication is the same for PD as for HC, whilst the S-score is higher and the T-score lower than that of HC, indicating a persistent altered function.

For the m.Biceps and passive activity the discrepancy is likewise to be found as a combination of all three AMG parameters, which remain lower than comparable values for the HC group, yet under active movements this muscle shows a lower E- and S-score, but a higher T-score. It was noted that for m.Biceps the passive to active ratio (P: A) returns to HC values for the S-score following medication, whilst the E-score is higher and the T-score lower than that of healthy matched controls, also indicating a persistent altered function. In consideration of these findings, one could suggest that for Biceps the change in P: A for the E-score most likely indicates a spindle effect, which could represent the chain fibres working normally but the bag fibres (dynamic) being partly disrupted. Interestingly, such changes are also observed with fatigue, as mentioned earlier (Grose et al. 2022).