Classification of
Muscle Stretch Receptor Afferents
in Humans
Akademisk avhandling
som för avläggande av doktorsgrad i medicinsk vetenskap
vid Umeå Universitet
kommer att offentligen försvaras i
Hörsal C, Universitetsbyggnad G (LU-0)
Lördagen 27 februari 1988 kl 09.30
av Benoni B. Edin
läkare
Avhandlingen baseras på nedanstående arbeten
Paper I
: Edin, B.B., Bäckström, P.A. & Bäckström, L.O. (1988). Single-unit
retrieval in microneurography: A microprocessor-based
device controlled by an operator. Journal o f Neuroscience
Methods In press.
Paper II
: Edin, B.B. & Vallbo, Å.B. (1987) Twitch contraction for iden­
tification of human muscle afferents. Acta Physiologica Scan­
dinavia 131, 129-138.
Paper III : Edin, B.B. & Vallbo, Å.B. (1988) Classification of human muscle
spindle afferents on the basis of ramp-and-hold stretches.
Journal o f Physiology Submitted.
Paper IV : Edin, B.B. & Vallbo, Å.B. (1988) Muscle afferents responses to
isometric contractions and relaxations in man Journal of
Physiology Submitted.
Paper V
: Edin, B.B. & Vallbo, Å.B. (1988) Stretch sensitization of human
muscle spindles. Journal o f Physiology In press.
Paper VI : Edin, B.B. & Vallbo, Å.B. (1988) Classification of human
muscle afferents: A Bayesian approach. Manuscript.
• ABSTRACT •
Classification of
Muscle Stretch Receptor Afferents
in Humans
by Benoni B. Edin
The Department of Physiology, University of Umeå, Sweden.
Umeå Univ Med Diss, No 209 ISSN 0346-6612
The response patterns of human stretch receptors in the finger extensor muscles of the
forearm were studied using the microneurography technique. Single-unit recordings were ob­
tained from one-hundred and twenty-four afferents. A procedure was developed to classify
the units in muscle spindle primary afferents, secondary afferents, and Golgi tendong organ af­
ferents. The procedure allows an objective and reproducible classification on the basis of the
afferents’ responses to a series of tests which individually are non-conclusive.
It was demonstrated that maximal twitch contractions can be elicited in the finger exten­
sor muscles of the forearm, without causing undue discomfort to the subjects, or hazarding
the single-unit recording. The response of the units to this test allowed, in most cases but not
always, a separation in muscle spindle and tendon organ afferents. Thus the test was not ade­
quate for an unequivocal classification.
Three discrete response parameters were extracted from ramp-and-hold stretches, viz.
the presence or absence of an initial burst and a deceleration response, and prompt silencing
at slow muscle shortening. The distributions of the parameters were significantly different
among the three unit types. These parameters which were pair-wise independent constituted a
set of considerable discriminative power. It was shown that human muscle spindles have
about the same static position sensitivity to fractional muscle stretch as previously found in
animals.
Stretch sensitization was demonstrated by rapid, repeated stretches of the muscle which
enhanced the réponse to subsequent slow stretches of muscle spindles. Sensitization was dif­
ferent with primary and secondary muscle spindle afferents whereas Golgi tendon organ af­
ferents never displayed stretch sensitization.
One-to-one driving with small-amplitude sinusoidal stretches superimposed on ramp-andhold stretches was almost exclusively seen with primary muscle spindle afferents, whereas
secondaries seldom and tendon organ afferents never displayed driving.
The afferent responses during slowly increasing isometric contractions and rapid relaxa­
tions were analysed. An increased discharge rate on relaxation was common among spindle af­
ferents whereas it was never seen in tendon organs afferents. Two separate groups of spindles
afferents were found with regard to fusimotor recruitment. The largest group was recruited at
rather low and variable contractile forces whereas the smaller group was not recruited at all.
The proportions of the three unit types, spindle primary, spindle secondary, and Golgi ten­
don organ afferents were estimated from a preliminary classification and the distribution of
the eight response features were analyzed for each class of afferents. On the basis of these es­
timates and the response pattern of the individual unit Bayes’ theorem was used to calculate
the probabilities that the unit was a spindle primary, a spindle secondary, or a tendon organ
afferent. Estimates indicate that about 19 out of 20 muscle afferents are correctly classified
when all eight features are analyzed.
Key words: Muscle spindles. Golgi tendon organs. Classification of muscle receptors.
Microneurography. Human hand. Stretch sensitization. Voluntary contraction. Static
position sensitivity. Fusimotor control.
• CONTENTS•
Classification of muscle stretch receptor afferents in humans.
Acknowledgements. (Benoni B. Edin)
Edin, B.B., Bäckström, P.A. & Bäckström, L.O. (1988). Single­
unit retrieval in microneurography: A microprocessor-based
device controlled by an operator. Journal o f Neuroscience Methods
Accepted.
II
Edin, B.B. & Vallbo, Å.B. (1987) Twitch contraction for
identification of human muscle afferents. Acta Physiologica
Scandinavica 131,129-138.
III
Edin, B.B. & Vallbo, Å.B. (1988) Classification of human muscle
spindle afferents on the basis of ramp-and-hold stretches.
Submitted to Journal o f Physiology,
IV
Edin, B.B. & Vallbo, Å.B. (1988) Muscle afferents responses to
isometric contractions and relaxations in man. Submitted to
Journal o f Physiology.
V
Edin, B.B. & Vallbo, Å.B. (1988) Stretch sensitization of human
muscle spindles. Journal o f Physiology Accepted.
VI
Edin, B.B. & Vallbo, Å.B. (1988) Classification of human muscle
afferents: A Bayesian approach. Manuscript.
Classification of
Muscle Stretch Receptor Afferents
in Humans
Benoni B. Edin
The Department o f Physiology, University o f Umeå, Sweden
ORIGINAL PAPERS
The thesis is based on six original papers, which will be referred to by the Roman
numerals indicated below.
Paper I : Edin, B.B., Bäckström, P.A. & Bäckström, L.O. (1988). Single-unit
retrieval in microneurography: A microprocessor-based device con­
trolled by an operator. Journal of Neuroscience Methods In press.
Paper II : Edin, B.B. & Vallbo, Å.B. (1987) Twitch contraction for identification of
human muscle afferents. Acta Physiologica Scandinavica 131, 129-138.
Paper III : Edin, B.B. & Vallbo, Å.B. (1988) Classification of human muscle spindle
afferents on the basis of ramp-and-hold stretches. Journal o f Physiol­
ogy Submitted.
Paper IV : Edin, B.B. & Vallbo, Å.B. (1988) Muscle afferents responses to
isometric contractions and relaxations in man Journal o f Physiology
Submitted.
Paper V : Edin, B.B. & Vallbo, Å.B. (1988) Stretch sensitization of human muscle
spindles. Journal o f Physiology In press.
Paper VI : Edin, B.B. & Vallbo, Å.B. (1988) Classification of human muscle af­
ferents: A Bayesian approach. Manuscript.
INTRODUCTION
The neurophysiology of human muscle afferents has been studied since the
microneurography method was developed in the late 1960’s by Vallbo & Hagbarth
(Vallbo & Hagbarth, 1968; Vallbo, 1972). The method has been successfully used to
assess the basic properties of muscle spindle and Golgi tendon organ response during
voluntary movements. On the basis of these findings, important aspect of the function­
al role of muscle receptors in motor control have been clarified.
The microneurographic method has unique advantages in that proprioceptive
responses can be recorded from attending human subjects under natural conditions
with the possibility to analyse muscle afferent response during self-generated com­
plex motor activity. However, in studies of motor problems the microneurographic
method has also some limitations, the most important ones are related to sensitivty of
the recording situation to movements and to electrical disturbances from neighbour­
ing muscle activity.
These limitations are particularly relevant for single-unit recordings whereas multi­
unit recordings (Hagbarth, Wallin, Burke & Löfstedt, 1975; Burke, Hagbarth &
Skuse, 1978; Young & Hagbarth, 1980) are less sensitive in this respect. However,
multi-unit recordings are difficult to interpret particularly when recordings during ac-
s-
1
Edin
tive contractions are considered because they are almost certainly a mixture of ac­
tivity from muscle spindles, Golgi tendon organs, and efferent skeletomotor fibers.
It seems therefore essential to focus on single-unit recordings although these ex­
periments are considerably more demanding.
The sensitivity to movements put some limitations on the tests procedures that can
be applied with reasonable success. For instance it is not feasible routinely to stretch
the muscle to its maximal length and then perform the classical twitch test for unit
identification — as usually is done in animal experiments.
One area where the consequences of these limitations have been discussed to a
considerable extent is the classification of afferents. In microneurography studies the
methods of identification of units are not identical with those used in animal experi­
ments. It has even been discussed to what extent some of the differences between
data from man and animals are due to units being differently classified. The present
study is an experimental and theoretical analysis of the problem of classifying human
stretch afferents from muscles. (Paper II-Vl)
The fact that the electrical signals recorded from nerve fibres with the
microneurographic method are very small make the recording very sensitive to electri­
cal disturbances. When the subject makes contractions of muscles in the neighbour­
hood of the microneurographic recording site, the EMG activity seen by intraneural
electrode may be several times larger than the nerve impulses. In order to improve
the possibilties to study proprioceptive activity during active contractions a single-unit
retrieval device was developed based on fast shape recognition by a microprocessor
unit (Paper I).
The microneurographic method
In the present studies, the orginal method as described by Vallbo & Hagbarth has
been used with small modifications. A thin (200 ixm) uninsulated tungsten electrode
was first transcutaneously introduced toward the radial nerve 5-10 cm above the
elbow. The exact location of the nerve was determined by low-intensity electrical
stimulations which elicited cutaneous sensations or contractions of extensor muscles
when the electrode came in the vicinity of the nerve.
When the location of the nerve was known, another electrode isolated but for the
tip was introduced and moved in minute steps until single-unit activity could be
recorded, i.e. a single nerve spike having an amplitude of 25-40
stood out from
the background noise (ca. 1 2 jxV). Before such single-unit activity were encountered
activity was often recorded from a large number of axons in the neighbourhood of
the electrode tip, so-called multi-unit activity.
The needle was left in place without other support than offered by the surrounding
soft tissues. To minimize movements of the recording needle, the subject’s lower arm
was stabilized by partially enclosing it in a vacuum cast which allowed palpation of
the extensor muscles of the forearm. Furthermore, the wrist joint was restrained in an
adjustable clamp. No improvement in stability was gained if the upper arm was also
put in a cast. On the other hand, it was found to be disadvantageous to externally
fixate the recording needle since it then could not yield to small limb movements or
in response to muscle contractions in the upper arm.
Only slowly adapting muscle receptor located in one of the finger extensor muscles
were investigated further, i.e. receptors located in the extensor digitorum communis,
extensor indicis or digiti minimi muscles.
The axons from which the neural activity is picked up have diameters even less
than that of the microelectrode tip, i.e. 5-20 yjn, and slight movements in the upper
arm or even rotation of the head may dislodge the needle. Furthermore, natural
S - 2
Classification of human muscle stretch receptor afférents
movements of the fingers are accompanied by considerable co-activity in muscles not
directly engaged in the motor act. These muscles do not only include direct synergists
and antagonists but also more distant muscles engaged in stabilizing the elbow and
the shoulder. Thus, records obtained during natural motor activity are prone to con­
tamination with EMG signals from the muscles close to the recording needle.
Moreover, EMG inteferences appear not only while active finger movements are per­
formed, but may also appear when the subjects simply feel uncomfortable.
SINGLE-UNIT RETRIEVAL
EMG interferences have traditionally been handled with combinations of level-discrimination techniques (Bak & Schmidt, 1977) and visual inspection of filmed
records. Due to the tedious work involved only limited amount of data contaminated
with EMG signals can be analyzed this way.
Paper I presents a microprocessor-based device for single-unit retrieval. The
device effectively copes with EMG interferences and thereby extends the experimen­
tal paradigms to include even forceful contractions of the forearm muscles. Single­
unit activity has been analyzed with near maximal contractions in finger extensor
muscles using this device. The device offers a powerful selection mechanism and al­
lows extensive records to be checked quickly.
CLASSIFICATION OF MUSCLE STRETCH RECEPTOR AFFERENTS
Before a presentation is given of the classification procedures developed in the
present studies, the different types of mammalian proprioceptors are surveyed as well
as some differences between the experimental conditions in animals and in man.
TYPES OF MUSCLE STRETCH RECEPTORS
Golgi tendon organs
Golgi tendon organs are elongated bodies found near the musculotendinous junc­
tion and connected in series with 5-15 motor units (Houk & Henneman, 1967; Mat­
thews, 1972), i.e. groups of skeletal muscle fibers controlled by a single efferent nerve
axon.
Tendon organ afferents respond with an increased discharge to stretch and are par­
ticularly sensitive to contractions of the ’in-series’ skeletal muscle fibers (Jansen &
Rudjord, 1964; Houk & Henneman, 1967), whereas their firing rate decrease when
exclusively ’in-parallel’ muscle fibers are made to contract by artificial stimulation
(Houk & Henneman, 1967).
Muscle spindles
The structure and efferent control of muscle spindles are well-known (Matthews,
1972; Prochazka & Hulliger, 1983; Hulliger, 1984). They are fusiform sensory organs
found in almost all skeletal muscles (Voss, 1959), and are connected in parallel with
all skeletal muscle fibers, although there are indications that spindles may occasional­
ly be coupled in series with motor units (Binder & Stuart, 1980). The spindles consist
of 4-12 thin intrafusal muscle fibers enclosed in a capsule of connective tissue and
they are supplied with a number of afferent and efferent nerve fibers (Ruffini, 1898).
Primary and secondary afferents originate from primary and secondary endings
(Ruffini, 1898), respectively, located at specialized sensory regions on the intrafusal
fibers. The two groups of muscle spindle afferents show considerable differences in
response properties.
s - 3
Edin
The efferent fibers, or fusimotor fibers, can be subdivided into two major groups, 7
and ß. 7 fusimotor fibers supply exclusively intrafusal muscle fibers, whereas ß fibers,
also called skeletofusimotor fibers, supply intrafusal as well as extrafusai fibers.
There are two major groups of intrafusal muscle fibers, bag and chain fibers, which
have different morphological appearances. The bag fibers can be further subdivided
in dynamic bagi and static bag2 fibers. The bagi fibers are exclusively supplied with
dynamic fusimotor fibers, whereas the static bag 2 fibers together with chain fibers are
supplied with static fusimotor fibers.
The muscle receptors found in man seem to be very similar to those found in cat
(Cooper & Daniel, 1963; Kucera & Dorovini-Zis, 1979). However, there are some dif­
ferences, e.g. muscle spindles in man generally contain more intrafusal fibers and in
particular chain fibers than in cat. Another difference is that human primary endings
seem to be found mainly on bag fibers (Swash & Fox, 1972; Kucera, 1986), whereas
primary endings in cat are found in abundance on chain fibers as well (Barker, 1974).
For these reasons primary afferents in man may be even more powerfully influenced
by dynamic fusimotor fibres than in cat. Lastly, whereas fusimotor axons in cat always
innervates selectively either ’dynamic’ bagi fibers or ’static’ bag2 and chain fibers,
some fusimotor axons in humans as well as in monkeys coinnervate ’dynamic’ and
’static’ intrafusal muscle fibres (Kucera, 1985, 1986).
Other mechanoreceptors in or close to muscles
A small number of paciniform receptors (morphologically resembling Pacinian cor­
puscles in skin) are known to exist in or close to skeletal muscles. These receptors
are rapidly adapting and vibration-sensitive (Hunt & McIntyre, 1960). In addition,
there are receptors in the deep tissues of the cat foreleg which respond to heavy
mechanical pressure or distortion of the interosseous membrane (Hunt & McIntyre,
1960).
Small-diameter afferents are known to supply skeletal muscles but their exact
receptor origin and function remain to be disclosed. Some of them probably subserve
nociception, since they respond only to strong mechanical stimuli or hypoxia (Mense
& Stahnke, 1983).
Lastly, paciniform receptors as well as Ruffini endings have been described in
joint tissues (Matthews, 1972).
Muscle receptors encountered in the present studies
One basic assumption of the Bayesian classification procedure as elaborated in
Paper VI was that all units were drawn from a population of well-defined unit types.
In order to guarantee that only muscle spindle afferents and Golgi tendon organ af­
ferents were included in the material, units were accepted only when three crucial
criteria were fulfilled:
Firstly, they should to respond to passive flexion or active extension of at least one
of the fingers.
Secondly, they should respond to local poking of the relevant finger extensor
muscles.
Lastly, they should be slowly adapting.
Skin and joint afferents may respond to active or passive movements of the
metacarpophalangeal (MCP) joints (Hulliger, Nordh, Thelin & Vallbo, 1979), but
they are not activated by poking the bellies of the finger extensor muscles. On the
other hand, although the receptors of the deep connective tissues of limbs described
by Hunt & McIntyre (1960) may respond to local poking over the muscle bellies, they
S - 4
Classification of human muscle stretch receptor afferents
are not expected to be both slowly adapting and responding to movements or exten­
sions at the MCP joints.
Thus, it seem justified to conclude that only three types of muscle afferents were
sampled in the present studies: muscle spindle primary and secondary afferents, and
Golgi tendon organ afferents and that they all originated in one of the finger extensor
muscles of the forearm, i.e. the extensor digitorum, indicis proprius or indicis digiti
minimi muscles.
IDENTIFICATION PROCEDURES USED IN ANIMAL STUDIES
Twitch contraction
In the earliest recordings from afferents of muscle stretch receptors, two groups of
afferents could be differentiated on the basis of their responses to electrically in­
duced contractions of their parent muscles (Matthews, 1933). Spontaneously discharg­
ing afferents of the one group displayed a pause at muscular twitch contraction,
whereas the other group instead increased their discharge. The morphology of the
stretch receptors were well known at this time (Ruffini, 1898; Fulton & Pi-Suner,
1928), and it was assumed that muscle spindles, with their ’in-parallel’ connection
with muscle fibers, should be unloaded during contractions, while Golgi tendon or­
gans should be stretched.
This simple dichotomy in response patterns is, however, not necessarily as clearcut as it initially appeared. First, the elicited contraction may not include all muscle
fibers. Some Golgi tendon organs may not be affected by the contraction if their ’in­
series’ muscle units were not recruited by the stimulation; tendon organs may even
be unloaded by the contraction of ’in-parallel’ motor units (Stuart, Moscher, Gerlach
& Reinking, 1972). Second, a few muscle spindles may be arranged in series with ex­
trafusai muscle fibres and may therefore respond with an increased discharge even
during relaxation (Stuart & Binder, 1980).
That muscle spindles do not necessarily silence during maximal twitch contractions
was demonstrated by Green & Kellerth (1967). As many as 8/26 (31 %) of muscle
spindle afferents showed both an early burst during rising muscle tension and a late
burst during relaxation.
In conclusion, even though an increased discharge during twitch contraction
speaks in favor of Golgi tendon organ origin it does not exclude muscle spindle
origin. Furthermore, a pause in discharge does not necessarily imply muscle spindle
origin, in particular when contraction of the parent muscles may be sub-maximal.
Thus, the twitch contraction test is non-conclusive, i.e. it does not definitely separate
muscle afferents into spindle and tendon organ afferents.
Conduction velocity
When Hunt (1954) demonstrated that the conduction velocity spectrum of the
muscle spindle afferents of cat soleus muscle displayed a bimodal distribution, he con­
cluded that the two peaks in the distribution represented afferents originating from
the two histologically defined endings (Ruffini, 1898). From then on
neurophysiologists separated muscle spindle afferents into primary and secondary af­
ferents on the basis of the conduction velocity of the afferent axon.
The conduction velocities of primary and secondary afferents, however, show a
considerably overlap (Hunt, 1954). For this reason, units with ’intermediate’
velocities are often excluded, i.e. afferents conducting at velocities somewhere be­
tween the two peaks, usually around 72 m/s in cat. However, the extent of overlap has
never been quantitatively analyzed; thus, the extent to which afferents originating in
S - 5
Edin
primary endings are falsely allocated to the group of ”secondary afferents" and vice
versa is unknown regardless of ’intermediate’ units being excluded or not.
Even though the conduction velocities of the spindle afferents in the muscle nerve
to the triceps surae in cat show a bimodal distribution, this is not true for all other
muscles (Boyd & Davey, 1968; Koeze, 1968; Browne, 1975).
Thus, the conduction velocity per se does not allow an unequivocal classification of
muscle spindle afferents, and it is not known to what extent the exclusion of ’inter­
mediates’ reduces the risk of misclassification.
Response to ramp-and-hold stretches
Cooper (1961) first demonstrated the differences in sensitivity to velocity of
stretch between primary and secondary afferents classified on the basis of conduction
velocities. Her investigation was amplified and extended by Matthews et al in the
early 1960’s (Jansen & Matthews, 1962; Matthews, 1963), who studied the basic
response patterns of muscle spindles to trapezoidal stretches.
Dynamic index. There are large differences between primary and secondary af­
ferents in their response to the dynamic component of a ramp stretch, in particular,
when considered in relation to their response to the static component of stretch. The
dynamic index, i.e. the difference between the discharge rate at the end of the ramp
stretch and discharge 0.5 s after the beginning of the hold-phase, was shown to be
much higher for a group of primary than for a group of secondary afferents (Jansen
& Matthews, 1962; Matthews, 1963; Crowe & Matthews, 1964). The overlap was con­
siderable, however, and would certainly have been even larger if units with ’inter­
mediate’ conduction velocities had been included.
Initial burst. Primary muscle spindle afferents typically show a high-frequency,
short-lasting burst of discharge at the beginning of a muscle stretch (Jansen & Mat­
thews, 1962; Matthews, 1963). Similar responses have, however, been described with
secondary afferents (Schäfer & Schäfer, 1977), and may, under some conditions, ap­
pear even with Golgi tendon organ afferents (Proske & Gregory, 1977).
Deceleration response. Many primary afferents display a temporary decrease in dis­
charge at the commencement of the hold-phase. This was reported already by Jansen
& Matthews (1962) and further investigated by Cheney & Preston (1976a, b) in the
triceps surae of Rhesus monkey. Cheney & Preston made the important observation
that a deceleration response can only be demonstrated in afferents which were in­
fluenced by dynamic y stimulation and therefore are primary afferents. The decelera­
tion response may thus be a conclusive difference between primary and secondary af­
ferents which can be assessed in microneurography.
Silencing during muscle shortening. Matthews (1963) showed that the majority of
primary afferents but only a minority of secondary afferents ceased firing at slow
muscle shortening.
Response to fusimotor stimulation
Matthews demonstrated that there are two subsets of fusimotor fibers supplying
muscle spindles which may be divided into ’dynamic’ and ’static’ y fibers on the basis
of their effects on the response of muscle spindle afferents and, in particular, of
primary afferents (Matthews, 1962).
In short, static y fibers usually enhanced the static response to stretch while
decreasing the dynamic response of primary afferents, whereas dynamic y fibers, in
addition to increasing the static response, greatly increased the dynamic response to
stretch. The dynamic fibers did not increase the dynamic responsiveness of secondary
afferents. Hence, when y stimulation can be demonstrated to enhance the dynamic
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Classification of human muscle stretch receptor afferents
responsiveness of a spindle afferent, it is considered proof that the unit is a primary
afferent.
Response to sinusoidal stretches
In a series of studies Matthews et al (Matthews & Stein, 1969; Goodwin, Hulliger
& Matthews 1975; Hulliger, Matthews & Noth, 1977) investigated the response of
muscle spindle afferents to sinusoidal stretches. In short, the earlier findings of a
greater sensitivity of primary than of secondary endings to small stretches was con­
firmed (Bianconi & van der Meulen, 1963). Thus, primary endings were more easily
driven by small-amplitude sinusoidals than were secondary endings.
Golgi tendon organs show a low sensitivity to small-amplitude movements in
relaxed muscles, but may be driven one-to-one by tendon vibrations during extrafusai
contractions (Roll, Vedel & Ribot, 1986).
Suxamethonium test
The suxamethonium test to separate muscle afferents was introduced by Rack &
Westbury (1966), although the excitatory effects of this drug on muscle spindle af­
ferents was known before (Granit, Skoglund, & Thesleff, 1953). Suxamethonium (succinylcholine) causes paralysis of extrafusai muscles and intrafusal chain fibers but
elicits sustained contractions in the bag fibers. Thus the drug greatly enhances the
response of primary endings to stretch. The increase in secondary endings was con­
siderably less and the responsiveness of Golgi tendon organ afferents was not af­
fected at all. Thus, this test might separate the muscle proprioceptors into three
groups.
Unfortunately, this test is quite time-consuming and therefore rarely used in
animal studies. Furthermore, Kidd & Kucera (1969) demonstrated that nonproprioceptive afferents could be activated by suxamethonium, although at doses
higher than those required to excite muscle spindle afferents. In addition, according
to Hulliger & Prochazka (1983), some secondary afferents may show responses "dis­
turbingly similar" to the responses of tendon organ afferents (cf. Dutia & Ferrell,
1980).
Response to extrafusai contraction
That Golgi tendon organs increase their firing rate upon extrafusai muscle contrac­
tions can be deduced from their topography (Jansen & Rudjord, 1964; Houk & Henneman, 1967), as well as that they may be unloaded by ’in-parallel’ motor units
(Houk & Henneman, 1967). Moreover, during natural contractions tendon organ af­
ferents in man (Vallbo, 1974), and in cat (Loeb, 1980), may respond by step-wise in­
creases in their discharge rate on increasing extrafusai contraction, presumably
reflecting the recruitment of additional motor units. Step-wise increases in discharge
rate, as shown by tendon organ afferents, have not been reported for muscle spindle
afferents in animals upon increasing extrafusai contractions.
In contrast, muscle spindle afferents (in particular primary afferents), are expected
to increase their firing rate on rapidly decreasing extrafusai contractile force, since
from their ’in-parallel’ connections it can be deduced that such decrements should
stretch the spindles. Responses compatible with this prediction have been reported
from muscle spindle afferents of the jaw muscles of monkeys during isometric biting
(Larson, Smith & Luschei, 1981) and in freely moving cats (Prochazka, 1981).
s- 7
Edin
Sensitization of muscle spindle afferents
Muscle spindle afferents, particularly primary afferents, show an enhanced
response to stretch following short-lasting fusimotor stimulations (Brown, Goodwin
& Matthews, 1969). A similar effect is obtained by applying repetitive rapid stretches
to the parent muscles of the muscle spindles (Poppele & Quick, 1981; EmonetDénand, Hunt & Laporte, 1985). Both of these effects are assumed to depend on the
formation of stable actomyosin bridges in the bag fibers. Similar effects on Golgi ten­
don organs have not been reported after repeated rapid stretches.
Summary
From the survey given above, it follows that classification of muscle afferents in
animals is not that straightforward since most of the tests are non-conclusive.
However, in practice the classification may still be very accurate, especially when a
number of tests are applied and when ambiguous units are excluded. It should be
pointed out, however, that there is a substantial risk of mis-classifying some muscle
spindle afferents for Golgi tendon organ afferents and vica versa, if only a twitch con­
traction test is used to separate them. The risk of incorrectly allocating the muscle
spindle afferents to either primary or secondary afferents is substantial when only con­
duction velocity measurements are considered, particularly when ’intermediate’ units
are included (cf. Paper III).
PECULIARITIES IN MAN
There are a number of obvious and important differences in experimental situa­
tions and constrains between studies of muscle afferents in alert man and in anaes­
thetized or decerebrated animals. Some of them may be worth pointing out.
Uncontrolled fusimotor activity
In animals the fusimotor activity can easily be abolished by cutting or cooling the
ventral roots. This is, of course, not applicable in man. While the ß activity may be
controlled by the experimenter by means of electromyographic recordings, there is no
way to check the 7 fusimotor system. For this reason, the experimental conditions are
not necessarily constant from one minute to the next even though indirect evidence
exist that 7 fusimotor activity in man is lacking in the absence of a motor activity (Cf
Paper V)
All tests applied in animals are not applicable in man
Suxamethonium used to identify muscle spindle primary afferents elicits paralysis
in skeletal muscles and is for ethical reasons not justified in microneurography
studies in man.
Conduction velocity measurements are not useful when recording from the radial
nerve under microneurography experiments. Proximal whole nerve stimulations
would activate all the extensor muscles of the forearm and, thereby, certainly dislo­
cate the recording needle. Distal nerve stimulations, on the other hand, similar to the
transcutaneous stimulations employed during the twitch contraction test (Paper II),
would hardly give reliable data because the actual conduction length in the nerve
from the site of excitation to the recording needle cannot be reliably assessed; in addi­
tion, the amount of tapering of the axon diameters would still be unkown (cf. Adal &
Barker, 1962).
At present, there is no feasible way in man either to record from or to stimulate 7
fusimotor fibres. Therefore, the differential sensitivity of primary and secondary afS - 8
Classification of human muscle stretch receptor afférents
ferents to dynamic
sessed.
7
fusimotor stimulations, for example, can therefore not be as­
Tests applied in man but not in animals
Voluntary activation of skeletal muscles have, in some respects, predictable effects
on muscle afferents. It may, for example, be safely assumed that Golgi tendon organs
should not increase their discharge in response to rapid decrements in extrafusai con­
tractions, whereas an increased firing may be expected of muscle spindle afferents.
CLASSIFICATION OF HUMAN MUSCLE STRETCH RECEPTORS ON
THE BASIS OF MICRONEUROGRAPHY RECORDINGS
Since none of the tests available in microneurography are conclusive with regard
to the nature of single afferents, units have to be classified on the basis of a number
of non-conclusive tests. In the present studies, several tests were investigated to ob­
tain an empirical basis for classification of muscle afferent in humans, and a formal
method of classification was developed.
Paper II: Twitch contraction
This paper demonstrated that maximal twitch contractions can be elicited in the
finger extensor muscle of the forearm without causing unbearable discomfort to the
subject or jeopardizing microneurography recordings.
It was further demonstrated that the expected responses from muscle spindle and
Golgi tendon organ afferents are obtained in the majority of units. However, it was
also shown that a clear dichotomy does not exist between muscle spindle afferents
and Golgi tendon organ afferents.
Finally, it was demonstrated that tendinous connections at the dorsum of the hand
add a considerable complexity since the radial fingers are greatly influenced by the
forces produced by the more ulnar portions of the extensor digitorum muscle.
Paper III: Ramp-and-hold stretches
Three discrete response features were analyzed in a large ensemble of muscle af­
ferents: presence or absence of an initial burst and a deceleration response, and
silencing during muscle shortening. Clear differences were found between units clas­
sified as muscle spindle primary and secondary afferents, and Golgi tendon organ af­
ferents. No evidence for interdependences between the three parameters were found
in muscle spindle afferents, and it was concluded that they may individually as well as
combined, contribute to the classification of muscle afferents.
On the basis of non-rigorous assumptions, calculations using Bayes’ theorem show
that about 19 out of 20 muscle spindle afferents are classified correctly into primary
and secondary muscle spindles when the three discrete parameters can be assessed.
In this study, in contrast to what has sometimes been claimed in the literature, the
sensitivity to fractional muscle stretch of human muscle spindles was found to be of
the same magnitude as the sensitivity obtained from studies in cat and monkey.
Paper IV: Isometric contraction and relaxation
The response of muscle afferents to slowly increasing isometric contractions and
sudden relaxation was assessed in this study.
It was concluded that there are two major populations of muscle spindle afferents
with regard to their fusimotor drive. A large sub-population of spindles are driven by
fusimotor activity during isometric contractions, whereas a smaller sub-population is
not. The recruitment of the former sub-population seems to be completed at quite
Edin
low degrees of contraction, i.e. about 10 % of the maximal voluntary torque. In addi­
tion, the drive to the individual muscle spindles of this sub-population seems to
saturate at low levels. The patterns of fusimotor drive seem to differ from spindle to
spindle, and due to the demonstration of large intra-subject variations, it was con­
cluded that the variation observed is not due to inter-subject variation in fusimotor
strategies.
Golgi tendon organs showed, at least in a substantial part of the contraction, a
close relation to torque at the MCP joint. Many of them showed an initial peak when
they were recruited, and a fair proportion showed two or more such steps, probably
in response to the recruitment of one or several motor units. None of the tendon or­
gans showed the burst on relaxation so typical of muscle spindle afferents.
Paper V: Stretch sensitization
Stretch sensitization, i.e. an enhanced response to slow stretch following repeated
rapid stretches of muscle, was demonstrated in a majority of muscle spindle afferents.
Furthermore, the pattern exhibited by primary afferents was found to be different
from that of secondary afferents in accordance with earlier studies on cat.
No Golgi tendon organs displayed stretch sensitization.
Paper VI: Sinusoidal stretches
Small-amplitude sinusoidal stretches was superimposed on ramp-and-hold
stretches and the occurence of driving was assessed for all units. As expected from
studies in cat, primary afferents were much more prone than secondary afferents to
become driven by the sinusoidal stretches. Furthermore, none of the Golgi tendon
organ afferents showed one-to-one driving except during (unintentional) concommitant extrafusai contraction.
CLASSIFICATION ON NON-CONCLUSIVE EVIDENCE: THE
BAYESIAN APPROACH
Papers II-VI described a set of tests which can be performed in succession in
about 4 minutes with the appropriate equipment. The three classes of muscle af­
ferents investigated show significant differences in response to these tests.
Several of the eight differentiating features had a high discriminative power, and
seemed almost conclusive: e.g. a deceleration response was seen only in primary af­
ferents; an early burst on isometric relaxation was seen only with muscle spindle af­
ferents; Golgi tendon organs never displayed stretch sensitization whereas those
primary and secondary afferents which showed such sensitization exhibited different
response patterns; Golgi tendon organ never exhibited one-to-one driving to smallamplitude sinsuoidals superimposed on ramp-and-hold stretches, whereas this was
common with primary and uncommon with secondary afferents.
The claim that specific tests are conclusive is, however, not easily justified mainly
because we have no ’ultimate’ way of classifying the afferents. Therefore, we consider
them all as ’non-conclusive’ and let the classification depend on the balance of
evidence when all tests have been considered.
The Bayesian method of classification as introduced in Paper III and expanded in
more detail in Paper VI, offers a way by which the classification on non-conclusive
grounds becomes objective, reproducible, and possible to communicate.
In short, the method requires some knowledge about the distribution of responses
to individual tests among the afferents considered. Such knowledge may be only
qualitative but also, as in the present studies, based on empirical data. By taking into
account the proportion of the different unit types in the population from which they
S - 10
Classification of human muscle stretch receptor afferents
are drawn, the probability that an individual unit is of a certain type can easily be cal­
culated when the outcomes of individual tests are known.
Paper VI demonstrated that a conservative estimate of the distribution of the
responses to a set of tests will yield a correct classification in a high proportion of af­
férents.
ACKNOWLEDGEMENTS
These studies were carried out in one of the most creative environments I can im­
agine, the Department of Physiology, University of Umeå. Many people have con­
tributed, directly or indirectly to the work, but, in particular, I wish to express my sin­
cere gratitude and appreciation to:
Professor Åke Vallbo, my supervisor and head of the department. Without his sup­
port, wisdom, patience, ability to listen and remember (and not the least, ability to
forget) combined with his marvellous capacity in organizing practical details, this
work would never have been completed.
Lars Bäckström, who is a remarkably skillful engineer and for whom nothing
seems impossible. He has been responsible for the development of the hardware and
software employed in the neurophysiological experiments.
Anders Bäckström, who, like his brother Lars, is a gifted engineer with remark­
able patience when presented with seemingly impossible tasks.
Docent Roland Johansson, M.D., Ph.D., for his willingness to share ideas not only
in neurophysiology but also on any esoteric subject.
Göran Westling, M.D., Ph.D. for his enthusiasm and daily encouragement as well
as his willingness to share his profound knowledge in engineering and electronics.
Sven-Olof Johansson, who skillfully assisted me throughout most of the
neurophysiolocial experiments and Jonas Ringqvist for keeping the main computer
in shape.
Professor Sven Landgren, for inviting me to many interesting, fruitful and some­
times revellingly upsetting discussions.
Stephen Grill, Ph.D., Chicago, for participating in a number of experiments, and
making me enjoy what I was doing.
Masanori Nagaoka and Nadjem Al-Falahe who participated in a number of the
neurophysiological experiments.
Helena Öhlund and Marieluise Svensson for excellent photographic work, and
Lennart Sjögren and his collègues for professional typographical work.
All those who were subjects in the neurophysiological experiments.
Finally and most important, my beloved wife Kerstin for her support and outmost
patience throughout these years.
This work was supported by the Swedich Research Council (Grant 14X-3548),
Forskningsrådsnämnden, Gunvor and Josef Anérs Stiftelse, Torsten och Ragnar Söderbergs Stiftelse
and the Medical Faculty, University of Umeå (Anslag för ograduerade forskare).
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