Motor control and olfaction – Inuence of pleasant and disgusting odors on the Adaptive Force

The Adaptive Force (AF) characterizes the capability of the neuromuscular system to adapt to external forces. The aim was to measure the effects of different olfactory inputs on the AF of the hip and elbow exors, respectively. The AF of 10 subjects was examined manually by experienced testers while smelling at sning sticks with neutral, pleasant or disgusting odors. The reaction force and the position of the tested limb were recorded by a handheld device. The results show, inter alia, a signicantly lower maximal isometric AF and a signicantly higher AF at the onset of oscillations with disgusting odor compared to pleasant or neutral odors (p < 0.001). The AF seems to reect the functionality of the neuromuscular control, which can be impaired by disgusting olfactory inputs. An undisturbed functioning neuromuscular system appears to be characterized by a proper length-tension control and by an earlier onset of mutual oscillations during an external force increase under isometric conditions.


Introduction
The Adaptive Force (AF) is barely considered neither in health, sports and movement sciences nor in medicine. In general, it re ects the capability to adapt adequately to external forces with the intention to maintain a given position or motion 1,2 . The currently most relevant variant and de nition for the present investigation is the execution of AF with the intention to maintain a given position in an isometric holding manner by adapting the muscular tension to comply with an increasing external force as good as possible. If the neuromuscular system is not able to match the increasing external force isometrically, the subject deviates from the quasi-static position. In case the external force exceeds the maximal isometric AF, the subject is forced to merge into eccentric muscle action, but still tries to counteract the increasing load as good as possible. Therefore, the AF as de ned here can be realized during an isometric or an eccentric muscle action. The intention is to adapt the muscular tension with the aim to prevent or to decelerate at best a muscle lengthening. Thereby, the differentiation between a holding (HIMA) and a pushing isometric muscle action (PIMA) seems to be crucial, since the intention of the subject executing the AF is to adapt initially in a holding isometric manner. Some investigations showed that during HIMA the duration to maintain a de ned force level is signi cantly briefer compared to PIMA [3][4][5][6][7][8] . It was hypothesized that HIMA is close to eccentric muscle action 7,8 . Enoka and Duchateau suggested a more complex neuronal control during eccentric muscle action compared to concentric contractions [9][10][11][12] . In case the neuromuscular system has to adapt to a varying external force in the described holding manner or during muscle lengthening, it is reasonable to assume that the requirements regarding the neuromuscular control could be even higher 13,14 . For the processing of AF, a mixed feed-forward and feedback control is assumed to be necessary. The mixed control was suggested by Caligiore et al. 15 . It is closely related to the "forward model", which "predicts the behaviour of the motor apparatus for a motor command." 15,16 . This requires an efference copy and direct somatosensory afferences 15,16 . For an optimal execution of AF, the muscle length and joint angle should stay constant for as long as possible during the external force increase. It is assumed, that the increasing external force causes an initial minimal de ection of the homeostasis of muscle length and limb position. The corresponding afferent signals, in turn, is supposed to lead to a mismatch in the responsible regulatory control loop. A compensatory increase of muscle tension would be necessary to maintain the homeostasis of length and position. However, at the moment of muscular response the external force has already increased further.
This has to be predicted by the neuromuscular system to adapt optimally. Therefore, a forward model in the sense of a mixed feed-forward and feedback control 15 seems to be necessary to maintain the isometric position. If the maximal holding isometric AF is exceeded, the muscle is forced to lengthen.
During the enforced subsequent eccentric muscle action, the motor system tries to further adapt to the external load as good as possible.
By executing the AF, the sensorimotor control is challenged in a speci c way, because the motor output must be continuously adjusted regarding the sensory input triggered by the external force application. In case of varying forces an anticipatory feedforward control seems to be necessary. Therefore, it is hypothesized that the AF re ects the functionality of the complex sensorimotor control and its detection could particularly be suitable to identify interferences in these circuitries. The in uences of nociception 17,18 or emotions 19,20 on motor control are well-known. Furthermore, the link between olfaction and the motor system was already proven 21 . However, the effect of olfaction on motor control is a rarely considered objectively in science. Primarily, odour induced changes of the cardiovascular system 22,23 , psychophysiological brain activity 24 , cognition and behaviour 25 or the in uence of odours on the quality of life 26,27 are investigated. Motoric reactions to olfaction are considered, for instance, concerning the startle re ex with respect to pleasant, unpleasant or no odour 28 . Closer to motor control was an investigation showing that lavender odour could reduce falls in elderly nursing home residents 29 .
Assessments concerning the in uence of olfactory inputs on muscle function remain disregarded in research to our knowledge. Since the AF is considered as a special function of the sensorimotor control it seems to be conceivable that pleasant or disgusting odours might modulate that aspect of sensorimotor control. The cerebellum as well as the ventrolateral thalamus are, inter alia, involved in olfaction [30][31][32] and both structures are relevant for adaptive motor control. Additionally, olfaction and emotion are evolutionary strongly coupled [33][34][35] . And, as mentioned above, the effect of emotions on motor control are secured. Therefore, it seems reasonable to assume that the AF might be in uenced by olfaction.
The assessment of AF can be performed manually (clinical, with or without a handheld device) or using an equipment system based on pneumatics 2,36 . In each case, the subject should adapt to the external increasing force application with the intention to maintain the position by holding isometrically for as long as possible. Thereby, the force pro le differs depending on the test procedure. During the measurement with the pneumatic-based system, the participant will always be forced into eccentric muscle action after an isometric phase. Thereby, rstly it reaches its maximum isometric AF (AFiso max ), which indicates the highest force reached during isometric muscle action. If the individual AFiso max is exceeded, the muscle starts to lengthen and the subject merges into eccentric muscle action, but still should adapt to the increasing force. Thereby, the AF usually increases further on and the maximal eccentric AF (AFecc max ) is reached. During the manually assessed AF, the participant will not be forced into eccentric muscle action per se as described below. For scienti c purposes, the kinematics and dynamics during execution of AF are recorded by a handheld device during manual muscle test (MMT) in the sense of a "break test" 36,37 . Since this has the advantages of a highly exible and time saving objective assessment tool, it was used for the present investigation. The MMT in the sense of a "break test" is de ned according to Conable and Rosner 37 : "The subject is asked to resist the tester`s gradually increasing pressure. If the muscle breaks away, there is also eccentric lengthening." The manually performed break test is usually conducted in submaximal intensity areas 37 . If the adaptation during the force increase is optimal, the muscle length will therefore stay quasi-isometric during the whole test until an oscillating force equilibrium on a considerably high force level is perceived by the tester 36 . Thus, the aim is not to force the subject into muscle lengthening and to perform a test of maximum strength thereby. A muscle lengthening would always occur if the tester applies a force that would exceed the maximal voluntary isometric contraction of the subject. However, the main focus during AF assessment using the MMT is to determine, if the subject is able to hold the position isometrically during the whole submaximal force rise up to an considerably high force level 36, 37 . In case of a failing adaptation, the muscle would already start to lengthen ("breaking point") in submaximal areas clearly below the MVIClevel during force increase. Therefore, during the MMT the force maximum of the test (AFmax) can arise during isometric (AFiso max ) or during eccentric (AFecc max ) conditions. Thereby, the AFmax must not be equivalent to the MVIC of the participant but refers to the maximum force reached during the test either under isometric or eccentric behavior.
The aim of this pilot study was to investigate whether the AF in healthy participants shows different patterns in reaction to neutral, pleasant and disgusting odors. Since disgusting odours are linked to negative emotions (disgust), we assume a rather inhibiting effect on the motoric system. Because of the complex control processes during execution of AF suggested above, especially adjusting the muscular tension by maintaining constant muscle length and limb position, it is assumed that the AFiso max might be more vulnerable in reaction to probable in uencing factors such as a disgusting odor compared to the AFecc max , MVIC or the commonly assessed eccentric or concentric strength. We therefore hypothesize that disgusting odor will reduce the maximal isometric AF (AFiso max ) but will have no effect on the maximal eccentric AF (AFecc max ). Pleasant or neutral odors are assumed to have no reducing effect on the AFiso max or AFecc max .

Participants
The Adaptive Force (AF) of the hip exors or the biceps brachii muscle, respectively, of n = 10 healthy participants was recorded by a handheld device during the manual muscle test (MMT) performed by two experienced testers (tester 1: female, 34 years, 168, 55kg; 8 yrs. of MMT experience; tester 2: male, 63 years, 185 cm, 87 kg; 25 yrs. of MMT experience). The anthropometric data of the healthy participants are given in Table 1 (detailed information are given in supplementary material Table S1). Exclusion criteria were any kind of health issues and an impaired neuromuscular function of the tested muscles assessed by the MMT prior to the measurements.

Manual muscle testing
The MMT is a clinical method of testing the AF as a marker of neuromuscular functioning 37 . For the present investigation, the so-called "break test" was applied (for description see introduction) 36,37 . Thereby, the tester applies an increasing force by pushing against the subject's limb. On the tester's side the maximally producible force is limited by the prescribed positioning to execute the test. The muscular strength of the tester would easily allow to generate a higher force, but it would lead to a displacement of the tester´s stance. Of course, individual anthropometric properties are additional factors which in uence the maximum applicable force, but the testing position is the crucial limit. In preceding measurements, the two involved testers developed maximum forces around 280 N. With this amount one would normally not be able to overcome a well-functioning rectus femoris muscle or elbow exor group, respectively, of young healthy subjects. Therefore, the MMT is not designed to measure the subject´s maximum strength.
(This could be done using technical devices which could easily overwhelm the subject.) The MMT evaluates the submaximal stability of the muscle. On this account, the referred AFmax does not represent the subject´s maximum strength, but the force which is maximally applied to the subject during interaction.
The assessment of the MMT by the tester is differentiated into two conditions 36, 37 : In case the limb of the subject maintains the isometric position during the whole force increase, the MMT is assessed as "stable". In case it yields during the force rise on a submaximal force level (breaking point), the MMT is rated as "unstable". Because of this manual approach, the test and its interpretation are subjective. By using the newly developed handheld device the force pro le and the position of the tested limb can be objecti ed simultaneously during the MMT by recording the dynamics and kinematics. A recent investigation showed that experienced testers are able to reproduce the force application in a reliable way (see below), which is one prerequisite for the present investigation 36 .
Characteristic and reproducibility of force pro le The applied force pro le during the MMT was de ned to have the progression as displayed in Figure 1 36 . During phase 1, the tester and the subject get in contact on a low force level for 1-2s. This is necessary to create a starting force level, so that the subject gets the opportunity to adapt to the external force of the tester at all, initially on a consistent and low force level. In phase 2, the tester increases the force smoothly in an exponential way. At the beginning, small steps of force rise are necessary, so that the subject gets a chance to adapt to the increasing force (for neurophysiological explanation see 36 ). This second exponential phase merges into a linear force rise in phase 3. If an oscillating force equilibrium between tester and subject is reached, this should be maintained for a few seconds, whereby the maximal AF of the test is reached (phase 4) before the tester stops the interaction and the force decreases again. The duration of this whole force rise (phase 2 to 4) until the maximum reaction force should be within 4s.
Of course, this force application depends especially on the tester. A su cient reproducibility of the applied force pro les is a necessary precondition for valid data.
Prior to the study, both testers proofed their ability to test in a reproducible way by performing 10 repeated force increases against a stable resistance in the MMT setting of the hip exors. The setting was equivalent to the here performed one (see below), except for a xed leg of the participant to exclude its reaction as a second in uencing factor 36 . The force pro les of both testers are illustrated in Figure 2. The coe cient of variation of the maximum force amounted 5.6% (tester 1) and 4.6% (tester 2), respectively. Both testers showed a reliable slope from start to maximum force comparing the 10 trials with an intraclass correlation coe cient of ICC(3,1) = 0.992 (tester 1) and 0.995 (tester 2), respectively.
Furthermore, the inter-tester reproducibility of both testers is considered as high with ICC(3,1) = 0.989 and a Cronbach's alpha of 1.0. Therefore, the force pro les of the two experienced testers, which performed the MMT here, can be considered as reliable. Group comparisons between experienced, little experienced and unexperienced testers showed signi cant differences in several parameters of force pro le in a previous study 36 .

Setting and procedure
Prior to the measurements, the participant was introduced to the procedure and gave its written consent to participate. Subsequently, the rectus femoris muscle was tested in a preliminary MMT. In case of full stability, the rectus femoris muscle was chosen for the investigation. If it did not ful l this requirement, the biceps brachii muscle was used provided it was fully stable. Afterwards, the participants selected the most pleasant and most disgusting odor out of 12 standardized sni ng sticks (olfasense GmbH). Those sni ng sticks are normally used for testing the olfactory capacity in clinical circumstances for e.g., in Parkinson´s disease. After a break for neutralization of the olfactory sense, the AF of the participant was tested by the MMT performed by the same tester with the handheld device while smelling at different odors (single-blinded, randomized): 3 x neutral, 3 x pleasant, 3 x disgusting (in some subjects less than three trials per odor were performed; 1 trial had to be excluded because of technical problems; for further information see supplementary material Table S2). A double-blinded study is not possible since the participant will always smell the odor. However, the participants were instructed to not show any reaction with respect to the odors, so that the tester was not in uenced by possible hints on which odor was presented. The order of stick presentation was randomized. An assistant gave the sticks to the participant and recorded the measurements. Tester 1 tested n = 6 subjects (1 x biceps brachii, 5 x hip exors), tester 2 tested n = 4 subjects (1 x biceps brachii, 3 x hip exors) (for further information see supplementary material Table S2).
The MMT was performed in the following way: The subject lay in supine position with a hip and knee angle of 90° for testing the rectus femoris muscle ( Figure 3B). The tester had contact to the distal end of the thigh of the participant. The handheld device ( Figure 3A) was located between the tester's palm and the participant's thigh to measure the dynamics and kinematics during the MMT. For testing the biceps brachii muscle, the participant was supine and exed its elbow joint in 90° with a maximal supination ( Figure 3C). The tester had contact with the handheld device at the distal forearm of the participant. In both settings, the exact placement of the device at the respective limb was marked to reproduce the position during subsequent measurements. The force rise was applied by the tester in direction of muscle lengthening of the participant's rectus femoris muscle (hip extension) or biceps brachii muscle (elbow extension), respectively.
The task of the participant was to maintain (hold isometrically) the respective starting position for as long as possible while adapting to the external force rise applied by the tester. The device detected the limb´s position during the force rise. After the test, the tester gave his or her judgement regarding the subjectively felt stability during the test. In case, the position of the limb stayed stable by maintaining the same muscle length and joint angle during the whole duration of force rise the MMT was assessed as "stable". If the participant merged into eccentric muscle action in the course of force increase the MMT was rated as "unstable".

Data processing and statistical analysis
For evaluation, the force and gyrometer signals were used. The csv-les were transferred to DIAdem 2017 (National Instruments). All signals were interpolated (linear spline interpolation) to ensure equidistant time channels (1000 Hz) and ltered (Butterworth, cut-off frequency 20 Hz, lter degree 5; for slope parameter to eliminate the oscillations: cut-off frequency 3 Hz, lter degree 10). The parameters of interest are the following: The maximal Adaptive Force (AFmax) This parameter refers to the maximal reached force value during the whole trial. AFmax (N) can be reached under two different circumstances. If the muscle length stayed stable over the whole force rise, AFmax was reached under isometric conditions (AFiso max ). In case of yielding during force increase, this value was obtained during eccentric muscle action (AFecc max ). The AFmax does not re ect the maximal strength of the participant, since it depends on the amount of force applicated by the tester (see above).

The maximal isometric Adaptive Force (AFiso max )
This parameter refers to the maximal reached AF during holding isometric muscle action, thus no muscle lengthening occurred until this moment. The gyrometer signal was used to determine the breaking point indicating the starting of muscle lengthening. It oscillates around zero under isometric circumstances. In case the muscle lengthened the gyrometer signal decreased below zero. The force value at the moment of last zero crossing of the gyrometer signal was de ned as AFiso max (N) indicating a deviation of the angle over time. In case the muscle did not lengthen, objecti ed by a gyrometer signal oscillating around zero over the whole MMT, the maximum force value AFmax = AFiso max . The parameters AFiso max and the ratio of AFiso max to AFmax (%) were used for further considerations.
The Adaptive Force in the moment of onset of oscillations (AFosc) The force signal showed an onset of oscillation in the course of force rise in some trials. Therefore, the oscillations of force signal were evaluated in NI DIAdem 2017. If three consecutive maxima with a time distance of < 0.15s were identi ed, this was de ned as the onset of oscillations. The border of 0.15s was set since muscular oscillations occur in a low frequency range of 10 Hz 38-41 . The AF value at the rst of those three oscillations referred to AFosc (N). If no onset of oscillation was present, AFmax = AFosc. The parameter AFosc and the ratio of AFosc to AFmax (%) were used for further considerations.
Slope of force rise This parameter was evaluated to ensure the reproducibility of force rise comparing the trials with neutral, pleasant and disgusting odors. According to neurophysiological considerations and empirical experience, 36 the characteristic of the force rise might affect the outcome. To compare the slopes of neutral, pleasant and disgusting odor until the breaking point, the slope in phase 3 was calculated with reference to the breaking point in trials with unstable condition. For that, the arithmetic means of the AFiso max values of the trials assessed as unstable was used as reference for each participant (AFiso unst ). The slope of force curve was then calculated by the difference quotient from the time and force values at 60% of AFiso unst to 100% of AFiso unst for each trial and participant. Due to the exponential force rise, the decadic logarithm was taken from the slope values. The logarithmized slope is given by lg(N/s). In ve as stable assessed trials, the 100% of AFiso unst was reached in the transition to phase 4. To avoid a distortion of slope results those trials were excluded from the analysis of slope.
The arithmetic means (M), standard deviations (SD) and 95%-con dence intervals (CI) of all parameters were calculated per participant separately for trials with neutral, pleasant and disgusting odors. All parameters were statistically compared between the three odors using IBM SPSS Statistics 27 to identify possible differences between the odors. For that, the normal distribution was checked with the Shapiro-Wilk test. In case normal distribution was not ful lled the Friedman test was used. This was the case for both ratios (; ). All other parameters were normally distributed and the ANOVA for repeated measurements was performed (RM ANOVA

Results
Exemplary force and gyrometer signals during the MMT of the hip exors of one female participant during neutral, pleasant and disgusting odors are displayed in Figure 4. As can be seen, the force rises are nearly identical for all three trials, especially in the rst three phases (Figure 4 above). This illustrates the high reliability of the tester's force application during the MMT. Furthermore, the gyrometer signal ( Figure  4, below) of disgusting odor decreases clearly, whereas during neutral (blue) and pleasant (green) odors, the gyrometer signal stays stable, oscillating around zero (de ned as isometric behavior) until the  (Figure 4). The AFosc during neutral and pleasant odors amount to 56% and 63% of the AFosc during disgusting odor and appear at a lower force level than the AFiso max during disgusting odor.
This example illustrates the behavior of AF during different odors, which consistently appears in 73 of all 76 measurements (the three exceptions are described below). This is supported by the following statistical group comparisons (Table 2). In total, 24 of 25 trials with neutral odor were rated as "stable" by the testers. One trial was assessed as "unstable" by tester 1. With pleasant odor, 25 of in total 26 trials were assessed as "stable" and one as "unstable" (tester 2), whereby the patient reported "sensing" her groin (no pain, appeared in no further measurement). 24 of in total 25 trials with disgusting odor were assessed as "unstable", one trial was assessed as "stable" (tester 1). (For detailed information see supplementary material Table S2). Regardless of the testers' subjective assessments, the following evaluation is only based on the grouping related to the presented odors.

Slope of force pro les
The slope is the main parameter to investigate the reproducibility of the testers' force rises. As can be seen in Table 2, Figure 4 and 5, the slopes did not differ signi cantly between neutral, pleasant and disgusting odors (F(2,14) = 0.762, p = 0.485). Therefore, the following considerations of AF parameters are done based on the requirement of reproducible force pro les between the MMTs of the three odors.

Maximal Adaptive Force and maximal isometric Adaptive Force
The overall maximum AF (AFmax), which occurred under isometric or eccentric muscle conditions, is slightly but not signi cantly higher in measurements with disgusting odor compared to neutral (p = 0.050) or pleasant odors (p = 0.086), respectively ( Figure 6A).  Figure 6B). The AFiso max does not differ signi cantly between neutral and pleasant odors (p = 0.105, r = 0.52). In the trials with disgusting odor, the AFiso max amounts averagely 60 ± 10% of the related AFmax, whereas with neutral or pleasant odors, the ratio is signi cantly higher with around 98 ± 3% (p adj = 0.001, r = 0.52) and 98 ± 2% (p adj = 0.008, r = 0.43), respectively (Table 2, Figure 6C). Furthermore, the AFiso max during disgusting odor amounts averagely 73.23 ± 12.06% of the AFiso max with neutral and 67.62 ± 15.85% of AFiso max with pleasant odors, respectively. That indicates that during perception of a disgusting odor, the maximal isometric AF is signi cantly lower compared to neutral or pleasant odors. The participant is not able to appropriately resist the external increasing force in an isometric way under the perception of a disgusting odor; the muscle starts to lengthen at a substantially and signi cantly lower force level compared to neutral or pleasant odors, respectively, whereby the AFmax is statistical similar between all odors.
Adaptive Force at the onset of oscillations The measurements with neutral or pleasant odors are characterized by an onset of oscillations during force rise at a submaximal force level. Those oscillations do not or only slightly occur at a high force level during perception of a disgusting odor. Signi cant differences with p < 0.001 arise comparing AFosc between neutral, pleasant and disgusting odors ( Table 2). The pairwise comparisons reveal a signi cant difference between disgusting and neural odors (t(9) = -4.952, p = 0.001, r = 0.86) and between disgusting and pleasant odors (t(9) = -4.432, p = 0.002, r = 0.83) ( Figure 7A). The AFosc does not differ signi cantly between neutral and pleasant odors (t(9) = -1.579, p = 0.149, r = 0.47).
Looking at the ratio of AFosc to AFmax, the signi cant difference is con rmed by the Friedman test (χ² ( Figure 7B).

Discussion
The presented study investigated the dynamics and kinematics during the manually tested AF utilizing a handheld device in healthy participants under the in uence of neutral, pleasant or disgusting odors, respectively. The evaluation of the slope of force rises reveal a non-signi cant difference between the three odors. Accordingly, the following discussion is based on reliable force applications of the testers. The main outcomes are: The maximum AF (AFmax) does not differ signi cantly between the three odors. The main difference is that smelling neutral and pleasant odors, the AFmax was reached under isometric conditions (AFiso max ), whereas with disgusting odor, the AFmax was obtained during muscle lengthening (AFecc max ). The AFiso max was signi cantly lower by perceiving disgusting compared to pleasant and neutral odors, indicating that during disgusting odor, the participants merged into eccentric muscle action at a signi cantly lower force level (60% of AFecc max ), whereas under neutral or pleasant olfactory in uence isometric stability was maintained almost until the maximum. That con rms the hypothesis that the maximal isometric AF, but not the AFmax, decreases during perception of a disgusting odor.
The AF at the oscillation onset is signi cantly lower for neutral and pleasant compared to disgusting odor, in which no or only poor oscillations occurred at a high force level. This indicates that the AF in healthy persons perceiving neutral or pleasant odors is characterized by oscillations, which emerge during force rise at 75% of the maximum.

Limitations
The testers' force pro le application might be the main limitation in this investigation. As mentioned above, the force application must be reproducible and appropriate as suggested in 36 . A smooth start followed by a faster linear force increase might be suitable to test the adaptive capability of the neuromuscular system 36 . The testers proofed their ability to test reproducibly prior to the investigation and the slope was used as parameter to control the force increase. The slopes did not differ signi cantly in the present measurements between the MMTs with different odors. The slope prior to the breaking point is even slightly lower in measurement with disgusting compared to pleasant odor (-3%). This speaks against the frequently appearing criticism that an unstable MMT is due to a steeper force rise. Nevertheless, the slope might be one crucial parameter when applying the force rise and must be controlled. An assessment of the force application by recording the dynamics and kinematics during MMT should take place to verify reliable and valid results.
Furthermore, the reached maximum force of a stable muscle depends not only on the participant, but also on the tester. The force pro le is a result of their interaction. Because the participant is only reacting in a holding way, the tester determines the course of force including its maximum when a stable muscle is tested. That is why it depends on the tester to what extend the participant´s holding capability is challenged under stable conditions. Due to biomechanical aspects, it is mostly not possible to overcome the here tested rectus femoris and biceps brachii muscles. However, if the tester applies a lower maximum force, the participant's response will naturally be lower, too. Therefore, the AFmax does not re ect the real maximum strength of the participant, since it depends on the amount of force applicated by the tester. As mentioned above, the "break test" is characterized by a force application in submaximal areas. However, the AFiso max under unstable conditions will refer to the maximal holding AF under the obviously impairing in uence of a disgusting odor. The AFecc max monitors the maximal eccentric force of the participants under the given circumstances. Since the AFiso max under stable conditions and the AFecc max under unstable conditions are not differing signi cantly in the present study, it is assumable the applied force of the tester is close to the maximal force capacity of the participants; with the assumption that the AFecc max is not changed by the in uence of disgusting olfaction. Since the MMT was performed in submaximal areas, no statement can be made concerning the behavior of AFecc max under the effect of neutral or pleasant odors. This investigation remains.
A tendency of a lower AFmax is visible for the tests under stable (neutral/pleasant) compared to unstable conditions (disgusting) ( Figure 6A). This could be comprehended as a possible reason for the different muscle states. However, the decisive difference is that the breaking point (AFiso max ) in unstable conditions (disgusting) appeared at a substantially and signi cantly lower level compared to the maximum force the muscle reached under stable conditions (neutral/pleasant) without muscle lengthening.
Another limitation is the small sample size (n = 10). However, the signi cances and effect sizes are considerably high. That is why we regard these preliminary results as a valuable rst consideration re ecting the neuromuscular control of healthy subjects. The sample size must, of course, be increased to verify the found results.
Eventually, there could be a concern regarding a possible confounding factor. Although the subjects were instructed to show no verbal or nonverbal reaction to the exposed odors and the tester avoided to get into visual contact with the subject prior to and during the test an unconscious in uence cannot ruled out completely. In this case the tester involuntary could have changed his or her pro le of force application and therefore in uenced the outcome. An unaware sudden start and steeper course of force rise would have favored an unstable behavior of the tested muscle. This is one reason why the slope before the breaking point was considered. The results invalidate the concern about unconscious manipulations by the tester because there is no relevant difference between the odors.
Characterization of "stable" and "unstable" adaptation Taken the above-mentioned results together, it is suggested to de ne a "stable" and an "unstable" adaptation to an increasing external force as follows. A stable adaptation can be characterized by two conditions: (1) the AFiso max ≈ AFmax (≥ 98% of AFmax), thus, the muscle length stays quasi-isometric during the whole force rise (slight muscle suspensions are acceptable); (2) Oscillations of force with about 10 Hz arise during force increase, thus, AFosc is signi cantly lower than AFmax. Based on the data a percentage of averagely 76 ± 9% of AFosc to AFmax can be expected. An unstable adaptation is characterized by the following two conditions: (1) AFiso max is considerably lower than AFmax. Thus, the muscle lengthens during the force rise in submaximal areas and the maximum is reached under eccentric conditions (AFecc max ). Based on the data a percentage of 60 ± 10% of AFiso max to AFecc max can be expected. (2) No or only poor oscillations on a high force level occur during the force rise, thus, AFosc is close to AFecc max with a ratio of 94 ± 7%.
It is suggested that the unstable behavior re ects an inadequate adaptation of muscle length and tension to external increasing force applications. In the present study, this emerged by presenting a disgusting odor. This obviously is impairing the muscle function in the sense of AF in the here investigated small sample size of 10 healthy participants. For a rst cautious summary thereof, a well-functioning undisturbed neuromuscular adaptation to an external force increase seems to be characterized by a su ciently adapted muscle tension maintaining muscle length and limb position as well as by the occurrence of mechanical oscillations.
Neurophysiological explanation of muscular adaptations with regard to perception of olfactory inputs Based on the own research, there are no comparable investigations concerning the behavior of AF -or other motor functions -as reaction to different odors. Trying to understand the underlying mechanisms, the suggestion of neuromuscular AF processing should be regarded more detailed. During the manual assessment of AF, the tested participant receives sensory inputs due to the tester's contact and force application. Hereby, skin and joint receptors, muscle spindle cells and Golgi tendon organs are perceiving mechanical inputs. The sensory signals are forwarded through the posterior horn to other spinal and supraspinal structures [42][43][44] and provide the current muscle length, tension and joint status. Sighting the literature, one can assume that at least the thalamus, cerebellum, inferior olivary nucleus (ION), red nucleus, basal ganglia, cingulate cortex and the sensorimotor cortex are involved in the complex processing of adaptive motor control and are interconnected directly or indirectly [13][14][15]20, . The cerebellum is considered as one of the most relevant sensorimotor structures concerning the temporalspatial processing 47,54 . Its anterior part seems to be especially relevant for sensorimotor functions and the posterior part for cognition and emotions 60 . However, the posterior cerebellum also seems to be involved in the "prediction of sensory events", especially for "timing perception and adjustment" 54 .
Therefore, the cerebellum is relevant regarding the motoric adaptation 15,61 , whereby it seems to be of particular importance in the beginning of an adaptation 61 . As mentioned in the introduction, a mixed mechanism of feedback and feedforward control is assumed to be involved in the adaptive process 15 .
The cerebellum seems to work as the forward controller in cooperation with the ION, which provides the motoric time signal [45][46][47][48] . Thereby, the cerebellum can learn to predict the accurate timing of connected events and, thereby, intervenes in motor control 45,46,72 . This ows into the error processing of motor control and provides the rhythmic neuronal signal to enable temporal coordinated movements [45][46][47] . The cerebellum receives information of the muscle spindle, Golgi tendon organs and skin receptors 42 . Therefore, it might be essential for the target-actual comparison of muscle length and tension.
Reafferences are compared with a copy of the initial motoric command 13 . Mismatches are then corrected by adjustments of the motor output. It was suggested that the cerebellum is a kind of "error-correcting machine", which compares the "expected and actual outcome of a sensory prediction or motor command" 51 . Also, other central structures seem to be relevant thereby. The parietal cortex was suggested as a central interface between sensory and motor processes concerning temporal processing 71 . Additionally, the thalamus is a central switching point for sensory and motor processes 64 , with its main task of modulating and regulating the ow of information to the cortex 65 . Meanwhile, the involvement of the cingulate cortex in emotions, pain processing as well as in spatial and motor control is secured 14,20,57,68 . This area reacts to different sensory inputs, e.g. exteroception, proprioception and nociception, and has a wide interconnection to other central structures 20,57 . Additionally, the basal ganglia work as a kind of ltration station for the muscle tone, including temporal processing, by facilitating desirable and inhibiting undesired motoric programs 14,52,80 . Last but not least the motor cortex receives information of the thalamus, the cerebellum, the basal ganglia, the red nucleus and of the limbic system 54,58 . The premotor cortex as well as the supplementary motor area of the cerebral cortex are involved in the temporal processing of motor activity 71,73,81 . Therefore, all those networked structures seem to be relevant in controlling the muscle length and tension during adaptation to external forces.
Jörntell suggests, that "the nal motor command, i.e. the nal spatiotemporal structure of the activation of the α-motoneurons and thereby the muscles, is a sum or a product of all the motor command signals issued and the pattern of sensory feedback" 53  If the regulative circuitries are working properly, the adaptation in the sense of AF ought to be performed adequately ("stable"). The neuromuscular system should be able to adapt appropriately to the external force increase in time and space if the force increases not too abrupt or intense. However, the present study showed that this neuromuscular adaptation might be impaired by perceiving disgusting odor.
Olfactory inputs are not transferred to the thalamus 14 . Initially, the cingulate cortex was reported to be associated with olfaction 57 . Olfactory afferences, with latencies of around 300ms 90 , are rstly transmitted to the olfactory bulb 91 and then are projected directly to the piriform cortex and the limbic system (amygdala, hippocampus) 91,92 , which displays the close connection of olfaction and emotion [33][34][35]93,94 . Especially with perception of pleasant or disgusting odors, we assume the occurrence of positive or negative emotions, respectively. Therefore, it is likely that the here found reduced AFiso max and later occurred AFosc at a higher force level during perception of a disgusting odor might be related to a negative emotional component. A pilot-study investigating the AF under the in uence of different emotions was performed and the results will be presented soon.

Characterization and specialty of the isometric Adaptive Force
The results strongly indicate that under particular circumstances a muscle can yield in length at a substantial submaximal force level. In this case the muscle loses its stability (ability to hold) despite of its further increase of tension. The maximum holding capacity (AFiso max ) changes within a few seconds depending on the in uence of odor. Therefore, in contrast to AFecc max , AFiso max it seems to be sensitive regarding a disgusting olfactory in uence, which is interpreted as a possible disturbing factor. The arising oscillations 10 Hz under stable conditions suggest this could not only be a characteristic for maintaining muscular stability but perhaps a prerequisite. A loss of this function could be a sign of a disturbed sensorimotor processing characterized by a muscle lengthening at a considerably low AF. It is suggested that the AFiso max , presumably depending on the onset of oscillations, seems to be the most vulnerable and, therefore, the possibly most relevant parameter in adapting to external forces. The immediate responses of AFiso max to the here investigated olfactory input strongly indicate to be based on regulatory mechanisms. Because of the close linkage of olfactory and emotional processing, the observed effect could possibly run via the in uence of the limbic system on motor control 95,96 . However, the integration of the different central structures during adaptive motor processes leads to the conceivable and even likely assumption that also other internal and external inputs which enter the control circuitries might in uence the adaptive motor control processes. The in uence of health complaints on muscle function is reported for several indications, e.g. for infections as COVID-19 97 , post-infectious diseases 98 , CFS/ME 99,100 , cancer 101 , sarcopenia 102,103 , hormonal dysfunctions 104,105 or bromyalgia 106 . Thereby, possible nociception or other disturbing inputs might function as interferences in the complex motor control processes. We assume an impairment of the AFiso max thereby.
When a muscle gets unstable under certain circumstances this could lead to a destabilization of joints especially when they are under strain. A higher vulnerability regarding joint complaints or even injuries might arise in the process. In contrast to measure maximal forces as usual, the assessment of the special parameter AFiso max could provide a novel approach to understand injuries or orthopedic pathomechanisms.
Summarizing, the results highlight not only the suggested possibility of measuring a special adaptive neuromuscular control by the AF but might also deliver an approach for investigating the neuromuscular system regarding disturbances in the control circuits. The literature speaks for a complex control cascade as well as parallel working processes between the central areas characterized by oscillations which are involved in the control of the spatio-temporal structure of motor output. In an undisturbed, healthy neuromuscular system those complex control processes should enable the participant to adapt adequately to the external force stimuli.
In conclusion, the present study showed different adaptive motor outputs as a reaction to neutral, pleasant and disgusting odors in healthy persons. Assuming that the AF in reaction to neutral and pleasant odors re ect "normal" muscle function, the AF patterns during disgusting odor are interpreted as a disturbance of the neuromuscular control due to the unpleasant olfactory input. Based on the presented preliminary results, it is suggested that the length-tension control of muscles is affected thereby.
Therefore, the isometric holding function including the peripheral mechanical muscle oscillations might be one or even the decisive parameter characterizing a well-functioning neuromuscular control of AFaction. It is hypothesized that measuring the AF, in particular the parameters AFiso max and AFosc, might be a suitable diagnostic tool to assess the functionality of neuromuscular control.
Based on the complex neuronal control, which is assumed to underlie the processing of AF, it is presumed that also other inputs as mental stress (negative emotions), nociception of joints or tissues or others might in uence the AF as shown here for disgusting odors. If this hypothesis could be veri ed by further investigations, this might offer the possibility to use the measurement of AF as an individual diagnostic tool. The MMT is already used since decades 36,37 . However, due to the reasonable criticism of subjectivity, some skepticism concerning the AF tested by the MMT remains in different elds for which it might have potential. The acceptance could be improved by objecti cation using appropriate devices. The assessment and recording of the manually tested AF are necessary to secure a reliable and valid force pro le of the tester. Because of the preliminary character of the present study further measurements with an enlarged data base are needed. In a next step, the AF in reaction to emotions and nociception should verify further evidence of the possible responses of the neuromuscular control to different inputs. Figure 1 Schematic force pro le. The force increase applied externally by the tester during the MMT consists of the four illustrated phases. (according to Bittmann et al. 36).

Figure 2
Repeated force pro les against stable resistance. Ten repeated force pro les of tester 1 (female, red) and tester 2 (male, blue) against a stable resistance in the MMT setting of the hip exors ( ltered with Butterworth, cut-off frequency 20 Hz, lter degree 5).