Mechanical analysis of infant carrying in hominoids

In all higher nonhuman primates, species survival depends upon safe carrying of infants clinging to body hair of adults. In this work, measurements of mechanical properties of ape hair (gibbon, orangutan, and gorilla) are presented, focusing on constraints for safe infant carrying. Results of hair tensile properties are shown to be species-dependent. Analysis of the mechanics of the mounting position, typical of heavier infant carrying among African apes, shows that both clinging and friction are necessary to carry heavy infants. As a consequence, a required relationship between infant weight, hair–hair friction coefficient, and body angle exists. The hair–hair friction coefficient is measured using natural ape skin samples, and dependence on load and humidity is analyzed. Numerical evaluation of the equilibrium constraint is in agreement with the knuckle-walking quadruped position of African apes. Bipedality is clearly incompatible with the usual clinging and mounting pattern of infant carrying, requiring a revision of models of hominization in relation to the divergence between apes and hominins. These results suggest that safe carrying of heavy infants justify the emergence of biped form of locomotion. Ways to test this possibility are foreseen here.
Introduction
All higher primates (except humans) carry their young clinging to their fur from birth (Jolly 1972). The correlation between infant carrying and the form of locomotion of adult primates is clear, but no detailed study has focused on the mechanics of the problem. Among nonhuman primates, there is a change in the carrying pattern of infants by adults (mostly by the mother) as the infant grows (Jolly 1972; de Vore 1965; Goodall 1967; MacKinnon 1974; Fossey 1979, 1983; Tuttle and Watts 1985). Newborns are carried clinging in close ventro-ventral contact, often with additional support from the mother (Hoff et al. 1983). Change to infant support over the adult body (dorsal or lumbar clinging) occurs some months later for all nonhuman higher primates and extends for years in apes. It seems clear that safety in infant carrying imposes limits on the weight of infants.
This work deals with the problem of infant carrying in Hominoids, characterized by increasing body size. Accepted hominoid phylogeny places the branch to the lesser ape gibbon as the oldest. It is followed by the great apes, with the older branch to the arboreal orangutan and the branch originating terrestrial gorilla and chimpanzee coming later, followed by biped hominids (Yunis and Prakash 1982; Ruvolo et al. 1994; Lockwood et al. 2004). Mechanical analyses of constraints for safe infant carrying in the usual primate pattern are reported. Measurements of tensile and friction properties of hominoid hairs are presented and conditions for mechanical equilibrium determined. The usual pattern of primate carrying of heavy infants is shown to be incompatible with bipedalism. This brings a new perspective to the hominization process and to the basic changes at the divergence between apes and hominins.
Materials and methods
Samples
For the experimental study of the mechanical properties of ape hairs, three pieces of skin with hairs were obtained from frozen limbs of dead animals at the Laboratoire d’Anatomie Comparée, Muséum National d’Histoire Naturelle, Paris, France (one gibbon, one orangutan, and one gorilla—chimpanzee was not available). Due to difficulty in obtaining animal skins, the samples came from three individual animals, one piece of about 200 cm2 from each. The three pieces of skin were transported at room temperature immersed in formaldehyde and were treated afterwards by a taxidermist. After the skin was fixed, it became leather, and chemicals were washed out from the hairs, which looked natural. The effect of formaldehyde on hair has been tested in human head hair; results are presented in the Appendix, and evidence is that no significant change occurs in the relevant tensile parameters.
The skin and hair from the different animals studied here are easily recognized by appearance and texture and are species-characteristic. Gibbon hairs are smooth and silky, while orangutan hairs are harsh, hard and very long; gorilla hair has an intermediate appearance. Estimated values of skin thickness and hair length are given in Table 1, with other parameters obtained.
Table 1Parameter values for apes GorillaGibbonOrangutanSkin thickness (mm)~1.5~0.6~2.3Hair Length (cm)~6~4~10∅ (μm)66 ± 2 (21%)52 ± 2 (19%)120 ± 4 (24%)α (N)17 ± 2 (25%)6.0 ± 0.6 (33%)32 ± 1 (13%)FE (N)0.38 ± 0.03 (30%)0.18 ± 0.02 (36%)0.49 ± 0.02 (12%)Fr (N)0.67 ± 0.09 (39%)0.29 ± 0.04 (47%)0.79 ± 0.04 (17%)Sr0.26 ± 0.05 (56%)0.28 ± 0.05 (52%)0.07 ± 0.01 (51%)E (GPa)5.0 ± 0.6 (42%)2.8 ± 0.3 (43%)2.8 ± 0.2 (36%)Skin thickness and hair length (estimated), hair diameter ∅, and results obtained from the n = 10 tensile curves for each ape hair. The regression coefficient α and the elastic limit FE are measured in the initial linear Hookean part of the curve, while the force Fr and strain Sr at rupture are measured at the end of the curve. Mean values are given with their standard errors. The Young modulus E is given by α divided by the hair cross-sectional area (with error propagation). The variation coefficient (CV = 100 × standard deviation/average value) is given in parenthesis.
The three skins provided several samples of different areas with the skin side fixed on pieces of wood, leaving the hairs exposed. The use of taxidermized specimens is the only possibility for simulating the natural situation for friction coefficient measurements. The basic data by Schultz (1931) on hair density of primates were also obtained from embalmed animals.
Methods
Several sectioned ape hair cross-sections were examined under a compound microscope (magnification up to 360), and external appearance as well as hair diameters were measured with a Zeiss Axiovert 200 microscope (several positions along the hair length). Ten single hairs of each of the three animals were cut and analyzed on an automated Instron Tensile Tester, at the standard 65 ± 2% relative humidity of the air (RH), 20 ± 2°C and speed 2.6 mm/min. The hair was fixed on one end to a fixed grip and on the other extremity to a movable grip, connected to a pulling force. The defined distance between grips (Lo) is between 20 and 50 mm. Curves of force (given in Newton, MKS unit) versus longitudinal elongation L (mm) were obtained; the strain, or relative elongation, is given by (L − Lo)/Lo. Single human head hair (with and without immersion in formaldehyde) was also analyzed as a standard, as a comparison was possible with previous data for human hairs (Robbins 1994; Nikiforidis et al. 1993; Franbourg et al. 2003). Twenty single hairs from each of the three animals, still on the skins, were also analyzed and pulled until detachment from the skin occurred.
For friction measurements, the wooden pieces with the larger areas from each animal were fixed to a movable inclined plane. The other pieces (with areas in the interval 16–76 cm2) were used in measurements of the static friction coefficient μ (hairs against hairs) using variable weights attached to the wood face. The angle of the inclined plane was carefully changed until slipping started at its critical value, and the process was repeated several times to check reproducibility. The RH and the room temperature (20–26°C) were measured and controlled with a dehumidifier and an air-conditioning system.
Results
Tensile measurements
Mechanical studies of animal fibers have been extensively performed over the last decades because of interest in textile production (mainly wool, see Feughelman 1997) as well as cosmetics (human head hair, see Robbins 1994). Animal hair is composed of three parts: an external thin cuticle (protective covering with a scale structure from root to tip), a thicker cortex with fibrous proteins, and a central porous medulla, which may be absent in finer hair. Ape hair viewed under an optical microscope are similar in structure to wool and human head hair, as in Fig. 1, where the external appearance with the cuticle scale structure is shown in Fig. 1a and the cross-section inner structure in Fig. 1b.
Fig. 1Micrographs showing orangutan hair, whose light color allows better visualization; a external appearance with typical cuticle scale structure, b transversal cross section with external cuticle, thicker cortex, and inner medulla
Mechanical properties of natural fibers are defined by the cortex of the fiber and are due to the molecular structure of keratin, which constitutes the cortex, as determined many years ago (Astbury and Street 1931; Astbury and Woods 1933). Extensive work during decades evidenced the dependence of mechanical properties essentially on the cross-sectional area of the fiber, thus enabling basic research to be conducted on relatively few single fibers, eliminating the need for statistical methods on a large number of samples (Feughelman 1997).
Tensile measurements give curves of force against strain (relative elongation) for a single hair fiber. Force has an important meaning for this study; stress is obtained dividing the force by the cross-sectional area of the fiber. A typical result with standard human head hair is shown in Fig. 2a and is similar to earlier data on human hair (Robbins 1994; Nikiforidis et al. 1993; Franbourg et al. 2003). The curve displays an initial elastic (Hookean) linear region, followed by a plastic yield region and a postyield region before breakage. Transition from the elastic to the plastic region corresponds to a first-order transition of the alpha-keratin molecule from the coiled helices to the stretched beta-keratin form (Bendit 1957), and the plastic region is strongly influenced by the water content (Feughelman 1997).
Fig. 2Measured force × strain (relative elongation) curves for hominoid a human, b gorilla, c gibbon, and d orangutan hairs. In a are stressed the initial Hookean linear elastic region (E), the plastic plateau (P), the post-yield region (PY), and the breaking threshold (B). The different curves in b, c, and d correspond to ten hairs of each individual ape. The inset in a is a magnification of the elastic linear region, showing the slope α and the force at the elastic limit FE
The linear region extends up to 1% strain, a result well established for helical alpha-keratins of all animal hairs: the cortex composite has mechanical properties of a single material (Feughelman 1997). The value of the force at the Hookean elastic limit (called FE in this paper) corresponds to the limiting force for full recovery of the fiber after being relaxed. The regression coefficient of the linear region (called α in this paper) of the force versus strain curve divided by the cross-sectional area of the fiber gives the Young modulus of elasticity (E) of the fiber (dimension of pressure unit, GPa = 109 N/m2). The values α and FE are determined expanding the initial elastic part of the curve (which does not, in general, start precisely at zero), as seen in the insert in Fig. 2a. Further analysis of human head hair is given in the Appendix.
Apparently, no tensile studies on ape hair have been reported. Curves obtained with n = 10 ape hairs of each of the three apes (one gorilla, one gibbon, and one orangutan) are shown in Fig. 2b–d. The curves display all the classical regions of animal hair. Human hair has a larger postyield region and a larger strain at breakage, related to the usual human hair treatment (frequent washing and combing). Maximum stretching is very different in the wet (50% strain) and dry (10% strain) states and may be influenced also by hair conditioners (Robbins 1994; Colombera and Joekes 2004).
The initial linear region is well defined in all hair curves, and its variability among different hairs of the same ape is due to differences in hair cross-sectional area. The physical parameters α and FE of each of the ape curves were obtained with the procedure shown in the insert of Fig. 2a. Values of force (Fr) and strain (Sr) at rupture were measured directly at the end of the curves.
Table 1 gives statistical averages of parameters obtained from tensile curves (α, FE, Fr, Sr) and measured hair diameter ∅ for each species, together with calculated Young modulus of elasticity E, with respective errors. The average values for FE are 60% (±2%) of Fr for the hairs of the three ape species. Hair diameters ∅ in Table 1 are averages over several positions measured along ten single hairs of each ape (∼50 measurements for each ape). One-way analysis of variance (ANOVA) test for these ∅ measurements evidenced significant difference between apes (F2,155 = 177; p < 0.0001).
All tensile parameter values for gorilla hairs, with the only exception being the Young modulus E, are intermediate between gibbon and orangutan hairs. Table 2 gives statistical tests for these four parameters: significant differences result from two-population t tests and one-way ANOVA test.
Table 2Statistics for tensile parameters of ape hairs FEαFrSrGibbon × Orangutant1011188.44.4p<0.0001<0.0001<0.00010.0003Gorilla × Gibbont105.36.24.10.32p<0.0001<0.00010.00080.75Gorilla × Orangutant103.17.61.34.0p0.007<0.00010.20.0009ANOVAF2,2744119209.3p<0.0001<0.0001<0.00010.0009Results from statistical tests for the n = 10 measured values of the four parameters obtained from the force × strain curves of hairs of the three apes. Two-population t-test (t10 values and corresponding probability p) are given for each parameter and each compared population in the upper lines. ANOVA test of the four parameters in the three ape populations and corresponding probability p in the lower line
Hominoid species differ significantly regarding hair strength, which increases from gibbon to gorilla and to orangutan. However, the Young modulus has a different behavior: E values for gibbon and orangutan are equal (2.8 Gpa), but gorilla has a higher value (5.0 Gpa). The value for human head hair from literature (Robbins 1994; Nikiforidis et al. 1993) is 3.8 Gpa, intermediate between gorilla and orangutan hair. Human head hairs measured in this paper are within reported values, as detailed in the Appendix.
Results obtained indicate that the force strength and average thickness of hominoid hairs are species-dependent and may be evolutionary meaningful. Data for human hair in the Appendix give further indication of species dependence. Such direction of research, together with definition of the Young modulus in terms of the inner hair structure, have clear interest but outside the scope of this work.
For infant carrying, the really decisive parameter is FE, representative of the upper limit of the force that a single hair can safely withstand, because it is the limit for recovery after relaxing.
It is convenient to express FE in kilogram-force (and gram-force), corresponding to the force weight of a given mass at the earth surface. This unit is often still used for load (instead of N = 0.10198 kgf) because it makes the mass value of the weight clear. The important values FE are then 18 ± 2 gf for gibbon, 39 ± 3 gf for gorilla, and 50 ± 2 gf for orangutan. The value for human head hair is 29 ± 2 gf (see Appendix).
The force to pull hairs from the skin samples of the three ape species has also been measured and may be considered as an upper limit, in view of changes in skin due to taxidermy. They are typically near the elastic limit and lower than rupture value, as occurs with human head hair in the scalp (Robbins 1994), giving a further reason to focus on the FE values as upper limits for safe load carrying.
A robust conclusion can be thus extracted. It is clear that to withstand the clinging infant weight, a large number of hairs held together is required. Results obtained evidence that bunches of about 100 hairs are necessary to carry infants weighing a few kilogram-force. Infant hands (and feet) can possibly grasp a bunch of hairs available in some square centimeters of skin so that safety in the usual pattern of nonhuman primate infant carrying critically depends on the density of hairs.
Infant carrying
Values of hair density for nonhuman primates have been obtained in the extensive work of Schultz (1931, 1968); values are not gender-dependent but vary with body region: density is highest in the vertex and smaller on the ventral than on the dorsal side of the trunk. Densities are generally compatible with the carrying requirement defined above, but the great apes have the lowest hair density among primates. Hair density values on the back of primates vary, from over 1,000 hairs/cm2 for smaller species (monkeys and gibbons), down to about 100 hairs/cm2 for great apes. The problem of safely carrying heavy infants requires thus particular consideration among the great apes.
Analysis of hair density data (Schultz 1931) in many anthropoid primate taxa yield (Schwartz and Rosenblum 1981) a negative allometry of relative hair density (rhd = hair density/total surface area). This decrease in rhd with increase in primate body mass has been correlated to thermal constraints imposed by the decreasing ratios of surface area to body volume. However, chimpanzees apparently have a lower rhd than would be expected for their body volume (see Fig. 1 of Schwartz and Rosenblum 1981), with rhd similar to that of larger gorillas.
The bunch of hairs available for clinging depends also on hair length and infant hand size. Accepting that about 3 cm are necessary to roll hairs on the infant fingers, the excess in length defines the area available for clinging. Clinging area per limb may be thus estimated to be 3, 10, and 50 cm2 for, respectively, gibbon, gorilla, and orangutan. In a dynamic situation, the load should be supported instantaneously by a single limb.
The infant-carrying method of the arboreal Asian apes (gibbon and orangutan) is different from that of the terrestrial African apes (gorilla and chimpanzee). The arboreal apes carry their young over one side of the mothers’ pelvis, not on the back (de Vore 1965). In accordance with the small size (7 kgf when adults), the lesser ape gibbon has a high hair density, over 1,000 hairs/cm2, more than ten times the density of great apes (Schultz 1931, 1968). This ensures safety for carrying their light young in their acrobatic arboreal life. The arboreal but heavier orangutans (adult females weigh around 50 kgf and males 90 kgf) compensate the lower hair density by longer, thicker, and stronger hairs and thicker skin. Orangutan infants live with their mothers for about 7 years.
The gorilla is about 50% heavier than orangutan, but instead of even greater hair thickness and length, the solution for terrestrial apes is the mounting position for heavier infant support. Orangutan hair and skin are, in this paper, estimated to be able to withstand about seven times more weight than gorilla hair and skin. Gorillas are the heaviest primates and have very few chest hairs (Schultz 1931, 1968). Adult gorilla is much heavier than adult human, but their newborns have only half the weight of human babies. In the first 1 or 2 months, the infant gorilla is supported manually by its mother as she walks tripedally or bipedally (Jolly 1972; de Vore 1965; Tuttle and Watts 1985; Doran 1997). The same occurs for chimpanzee babies, unable to support their own weight by clinging prior to 2 months of age (Plooij 1984). Change from quadruped to triped or biped motion occurs systematically among all great apes when infant safety requires manual support (Jolly 1972; de Vore 1965; Tuttle and Watts 1985). Slow and careful locomotion of female chimpanzees while carrying young infants has been reported (Goodall 1967). Two primary causes of mortality have been found among infant chimpanzees: inadequacy of the mother–infant bond and injuries caused by falling from the mother (Goodall 1967). It is clear that infant carrying is crucial and depends on not trivial behavior among African great apes.
Weight limit for clinging in African apes
The gorilla FE value, combined with hair density and length, indicates that load up to 40 kgf could be supported by clinging. However, the weight limit for clinging depends also on several other variables. Increase in hair pull-out or break in the dynamic situation, capacity of the infant to withstand its own weight and to grasp hairs without sliding, and skin capacity to withstand the load without rupture are all variables that may decrease the infant weight limit for clinging.
A bunch of hairs on about 1 cm2 (±10%) of gorilla skin under load was observed, still on the skin, to simulate the real load effect in the actual clinging situation. Counting hairs in this bunch gave 140 hairs (±10%), in agreement with the value reported by Schultz (1968) for the back side of the trunk of gorillas (145 hairs/cm2), evidencing that there are no marked differences between the limb sample and the back-trunk hairs. This bunch of hairs supported 1 kg without problems, even with some pendulum movement. With 2 kg, several problems became evident. Besides eventual detachment of single hairs from the skin during movement, the hair bunch started to slip from the double-face adhesive tape used to attach it to the load support. It was necessary to make a new attachment system; the hair bunch was rolled several times around the weight support. Even so, loads of 2 kg and more could be observed only with the rolled hairs attached by super glue (ester cyanoacrylate) to the weight support. This indicates a possible problem also with the clinging capacity of infant fingers, and slippage may occur. Also, the skin itself began to deform and detach from the wood support, requiring a much stronger attachment of the skin to the wood base. The bunch of hairs broke at the same hair length for all under a static load of 7 kg, compatible with the values of force at rupture (Fr) obtained from the tensile measurements of single hairs (Table 1). An upper limit of 1 kgf/cm2 for clinging without problems may be deduced from this simple experiment, but the actual limit depends on the clinging capacity of infant fingers and on the mother’s skin resistance. The effective weight limit for clinging must be obtained from careful observation of live apes.
Fossey (1979) describes physical and behavioral development of gorilla infants: at 4–6 months (weight about 5 kgf), the gorilla infant travels 60% of the time in ventral position while with 6–12 months (weight about 8 kgf), it travels in the dorsal position 80% of the time. A detailed investigation of the ontogeny of locomotion in the African ape (Doran 1997) revealed that up to 5 months of age, chimpanzees are slightly more precocious than gorillas. However, at 6 months, gorilla locomotor development becomes faster than that of chimpanzees, and surprisingly, much of the interspecific variation in behavior is explained by differences in body size (Doran 1997). Afterward, when the infants are of similar weights (although of widely disparate ages) gorillas and chimpanzees perform very similar locomotion activities (Doran 1997).
It is, in this paper, suggested that the weight level of 5 kgf may be considered the limiting value for safe support over long periods by only ventral clinging, defined probably by a combination of security factors1 related to hair strength, infant clinging capacity, and skin resistance to pressure. The limiting clinging pressure on the mother’s skin for the African great apes may be thus estimated to be 0.5 kgf/cm2 (a factor of 2 in relation to the simple test made with the skin sample). The skin is also a visco-elastic medium, reflecting properties of a strain-induced aligned-collagen network that can stretch up to 100% before permanent damage (Silver 1987). The shear modulus for the human dermis ranges from 1.2 to 3.1 MPa, while for the human hypodermis, it ranges from 3.1 to 9.7 kPa (Gennisson et al. 2004). The pressure limit 0.5 kgf/cm2 (~50 kPa) could be a limit also for danger to the skin of the mother ape. It is known that one of the important differences between the skin of humans and of African apes is the higher elasticity of the human skin (Montagna 1982).
The locomotor development of the infants must therefore adapt to such an effective weight limit. This does not mean that infants over 5 kg will fall. Larger infants may travel briefly in ventral position during stressful situations (Fossey 1979) or when the chimpanzee mother swings through trees (Goodall 1967). Usual locomotion of adult African apes is terrestrial quadrupedalism (~96% of the time in gorillas and ~86% in chimpanzees, from Doran 1997), and safe infant support over longer periods clearly requires the necessity of change to a mounting position, with the infant weight supported by the adult body.
Dorsal clinging position
In order to analyze the mechanics of the carrying system in the African great apes, it is also necessary to consider, besides the tensile properties of hairs, the hair–hair friction that prevents slipping, particularly for heavier infants in dorsal position. Fig. 3 is a sketch of the mounting position in African apes, showing the angle θ of the inclined plane where the infant stands. For simplicity in the sketch, the angle θ coincides with the angle defined by the usual knuckle-walking position of African great apes, but that is not necessary. The important parameter is the inclination of the base where the infant stands clinging; its relation to the average body inclination angle does not need to be taken into account in analysis of the friction effect.
Fig. 3Sketch of ape carrying infant. For simplicity, in the sketch, the angle θ of the inclined plane where the infant stands (to which Eq. 1 refers) coincides with the angle defined by the knuckle-walking position of African great apes, which is not necessarily so, as discussed in the text
The total infant weight, in the vertical direction, has two components, one in the inclined plane, favoring slipping, and one normal to the inclined plane, responsible for the friction force opposing slipping. Calling Wt the total infant weight carried in mounting position, Wc the effective weight limit for clinging, and μ the static friction coefficient (Bowden and Tabor 1956), the equilibrium of forces on the infant requires that force components on the inclined plane direction satisfy the condition:
In the absence of clinging (Wc = 0), slipping on the body surface of contact starts for a critical value θc, given by tan θc = μ. Both friction and clinging are thus essential to hold heavy infants in the mounting position. The requirements for dynamic equilibrium may be greater, so that in fact the mounting position in dynamic movement may be unsafe even when Eq. 1 is satisfied.
It should be stressed that Eq. 1 is a necessary condition for infant survival and therefore also for species survival. It is a very robust requirement of basic mechanics for static equilibrium. The ape hair–hair friction coefficient μ must be known to analyze the actual ape situation.
Friction measurements
Apparently, no results for hair–hair friction coefficients exist in the literature; only friction between human hair and other materials are reported (Robbins 1994). The skin samples were used to measure μ as a function of the supported load W in known conditions of relative air humidity and temperature, in a situation analogous to that depicted in Fig. 3. It was verified that μ depends on the hair direction, being larger for hairs in the parallel position (as in nature, with the two animals heading in the same direction) than in the antiparallel condition. Systematic measurements have been thus made in the parallel condition.
Figure 4a shows a typical result of μ as a function of W. For hard solid surfaces, μ is constant and independent of the load W and contact area A. This is clearly not the case for hairs, especially at low loads. Long ago, it was shown that a variation of μ with W occurs for textiles and fibers (Gralen 1952; Makinson 1952), given by the empirical equation:
Fig. 4Results for friction coefficient at 80% RH. a friction coefficient μ as a function of W for a gorilla skin with smaller area (16 cm2). The line shows a fit to the data using Eq. 2. bμ × W for (circles) gorilla with larger area (76 cm2); (squares) gorilla with smaller area (16 cm2), and (triangles) gibbon with intermediate area (42 cm2). Linear fits to the data are shown in lines
The parameter a gives the friction coefficient in the limit of high loads. It has been proposed (Gralen 1952) that the parameter b is related to the pressure inside an oil lubricating film on the fiber surface. The thickness of this film decreases due to pressure, which causes changes in the friction mechanism. Hair is a natural fiber (Howell et al. 1959) and behaves in a similar way. In fact, the data could be well-fit with Eq. 2, shown as a solid line in Fig. 4a.
Many curves were analyzed for different values of the contact area A and RH. A strong dependence of μ on A was observed, probably due to shear among the several hairs in contact. The fits to the linear equation μW = aW + b are more convenient for yielding the parameters a and b, as shown in Fig. 4b. Both a and b increase with A, but a is less sensitive to A, while b is roughly proportional to A, so that the term b/W in Eq. 1 is inversely proportional to the pressure W/A exerted on the surfaces in contact.
Results indicate that the friction coefficient might be considered constant for pressures higher than 20 gf/cm2. This pressure corresponds to infant weight around 1 kgf, from the relation between body surface area and weight (Schwartz and Rosenblum 1981; Kleiber 1975) and estimating the contact area as one third of the infant surface area.
The average value is μ = 0.27 ± 0.03 for gorilla hairs and μ = 0.20 ± 0.02 for gibbon hairs at 60% RH, in agreement with the expected null or small difference on friction depending on the fiber diameter (Robbins 1994). Such values are in good agreement with known values for single fibers (Bowden and Tabor 1956; Howell et al. 1959). The orangutan skin was not as perfect and homogeneous as the gibbon and gorilla skins, showing some parts without hairs, and provided only two samples, so dependence on area could not be analyzed. However, experiments of μ as a function of load gave similar values to those for the other apes.
The hair–hair friction coefficient of apes obtained is intermediate between values for friction between human hair and hard rubber with dry (μ = 0.19) and wet (μ = 0.38) surface conditions (Robbins 1994), indicating that results obtained can be considered of general validity. Note that Robbins (1994) mentions the difficulty of testing hair–hair friction, important in hair combing, and that it should be similar to hair–rubber friction.
Equilibrium condition in African apes
It is possible now to focus the problem on our nearest relatives, the great apes gorilla and chimpanzee, applying Eq. 1 to their mounting condition, in which clinging and friction act together for safe infant carrying.
The effective weight limit for constant ventral clinging, already discussed, is estimated to be 5 kgf. As the hair density in the back is higher (30% for chimpanzees), the estimate is Wc ~ 5–7 kgf. The maximum value Wt can be estimated from the weight of infants when they are no longer carried by mothers. This occurs when gorillas are about 2.5 years old and chimpanzees 5 years old, both weighing around 20 kgf (Fossey 1979; Doran 1997).
By inserting such values in Eq. 1, and using the estimated constant friction coefficient μ, it is possible to obtain the maximum inclination of the plane supporting the infant for the safe carrying system in the African great apes. The condition θ < 29 to 34° is obtained.
This basic equilibrium constraint related to friction in the mother–infant contact is satisfied in ape knuckle-walking quadruped position2.
It should be stated that it is frequently reported that in the dorsal position, the African ape infant rides high on the mother’s neck and lies stretched and prostate (de Vore 1965; Fossey 1979). This position increases the fixed base of the load and places it in a body region with a promontory and a smaller inclination angle (θ ~ 20° as estimated2 from the same Fig. 7–20 in Schultz 1968). Older infants ride in a jockey position; they do not normally grip hairs with their feet, but press the sides of their ankles against the mother’s flank (Goodall 1967). Clearly, among terrestrial great apes, infant safety does not rely only in grasping hairs.
It may be concluded that slipping imposes clear limits on the maximum body angle attained by heavy ape species carrying infants, representing a hindrance against evolution towards bipedality. This might explain the persistence of knuckle-walking among the great African apes.
Effect of humidity on friction
The two most relevant variables to friction in hairs (Robbins 1994) are the load pressing the two surfaces together, as analyzed previously, and the relative humidity RH. Dependence of μ on RH was reported for fibers (Howell et al. 1959) and human hair (Robbins 1994), and a similar effect was verified for ape hairs.
Reduction in RH, from 80 to 38%, led to a decrease of gorilla hair μ by about 30%. The friction coefficient between human hair and hard rubber is reduced by 50% between the wet and dry states (Robbins 1994).
Friction of gorilla hairs has been also measured in wet conditions (immersion in water, followed by slight shaking of the sample). The result is μ = 0.35 ± 0.03, in good agreement with reported values for human hair and hard rubber in the wet condition. The larger μ value in wet condition is possibly due to network of hydrogen bonds connecting hairs in contact. The thin outer epicuticle membrane of hair is hydrophobic, but hydrogen bonds may occur through the thicker exocuticle and endocuticle, especially the latter, which swells much more in water (Feughelman 1997, Robbins 1994). Such structures may be accessible to external water through the ratchet scale structure of hair.
It should be concluded that reduction in humidity destroys the delicate balance between friction and clinging (Eq. 1) necessary for survival of infants of heavy ape species. Figure 5 shows the maximum carrying weight Wt obtained from Eq. 1 as a function of the inclination angle θ for μ varying from zero up to 0.40, with Wc = 5 kgf.
Fig. 5Curves of total weight Wt supported in dorsal position as function of the inclination angle θ of the infant base on the mother’s trunk, obtained from Eq. 1, for several values of the friction coefficient μ (0–0.4, as indicated on top), with Wc = 5 kgf (limit value shown with dashed line). The line with cross is for Wc = 10 kgf and μ = 0.4. Vertical position corresponds to θ = 90°
Discussion
In this section, the relevance of the above results for models of hominization is discussed. Safe infant carrying is clearly very important for species survival and has to be considered in the discussion of the transition from apes to hominins. The mechanical analysis made in this paper evidenced that habitual bipedalism, with a large θ angle, is incompatible with the usual primate type of infant carrying. Even if one considers Wc = 10 kgf and μ = 0.40, the maximum attainable angle is θ ~ 49°, as seen in Fig. 5.
It seems clear that together with bipedality probably also came the characteristic human type of infant carrying in the arms and hands of their mothers, making their locomotion and foraging particularly difficult. Females would not adopt bipedality if they could avoid it, and the species would not adopt bipedalism if females with infants would not engage in it. The transition to bipedality was not trivial.
Etkin (1954) considered the problem of the burden on females “almost continuously carrying a child,” just to conclude that the female could not be an effective hunter, turning to a theory of the monogamous family unit. It is clear now that such a scenario could be considered only for Homo at a much later period. Iwamoto (1985) recalled examples of facultative bipedalism among monkeys and speculated that the “decisive factor (for habitual bipedalism) may have been some everyday necessity to carry something in both hands”. After criticizing proposals in which the “something” is food, Iwamoto suggested that the “something” could be their helpless babies. However, this proposal has been dismissed under the hypothesis that babies became helpless only with increase of brain in Homo.
Now models for bipedalism origin based on “food acquisition and foraging strategies” are considered “likely” but are in fact based on the premises that bipedal locomotion frees the arms and hands and does not have high costs. However, such premises just forget the fundamental fact that bipedalism frees the arms and hands only of males and juveniles, but females, on the contrary, have arms and hands occupied by infant carrying, which represents a high cost for bipedalism, not considered up to now. A review of bipedalism mentions: “infants (from early hominin biped) probably clung to their mothers’ hair, as is the case for most other primates” (Richmond et al. 2001).
It seems that the not trivial mechanical constraint of safe carrying of heavy infants has never been considered before.
Current evidence suggests (Richmond et al. 2001; Kingston et al. 1994; Potts 1998) that the key adaptation to bipedalism originated in wooded environments during a drier period in East Africa. The equilibrium condition (Eq. 1) shows that reduction of friction in the dorsal clinging position would most probably lead to a decrease in infant weight and decrease in the body inclination angle θ, corresponding to the solution adopted by quadruped savanna monkeys in the arid savanna. It seems clear that habitual bipedalism would not be reached by continuous increase of the body angle. However, among hominoids, reduction of friction between infant fingers and mother hairs could reduce infant grasping capacity, increasing the period of mother’s manual support of newborns and eventually inducing habitual bipedalism.
Concluding remarks and future perspectives
An important conclusion from this work refers to interest in systematic study of tensile properties of hairs from an evolutionary point of view. The other clear conclusion is that models on locomotion and bipedalism evolution must focus on females carrying infants, who are the target of the strongest selective pressures, and this conclusion is independent of the form of locomotion of hominid ancestors (knuckle-walkers, terrestrial or arboreal quadrupeds, or full-time arboreal climbers).
To disentangle the divergence between apes and hominins, several directions of research become clear from this work. Studies of living apes focused on the mechanical problem of infant carrying, as well as determination of the elastic limits of the ape skin and the limits for grasping capacity of ape infants, which are all essential to identify the critical factor responsible for emergence of bipedalism.
It should be stressed that in a scenario with bipedalism emerging for safe infant carrying, the selective pressure would act particularly on females. This is not a problem, as only genes in the nonrecombinant part of the Y chromosome are not transmitted to both sexes and therefore cannot be associated with species locomotion. The process correlates with increase in the mother–infant bond, characteristic of the human lineage.
Other hypotheses for emergence of bipedality (see Richmond et al. 2001 for a review) do not, in fact, explain why other primates did not follow such line. The many scenarios invoked previously for bipedalism evolution may sound plausible, but are not necessary; neither take into account the problem of infant carrying and can be considered complementary and a consequence of the selective pressure on females carrying infants. The difficulties in locomotion and food gathering for biped females carrying infants may well be at the origin of the necessity of group cooperation, which could initially have been among females, with males in their usual role of primate group protection.
A fundamental question is the possible correlation between bipedalism and reduction of body hairs, the two basic biological modifications of hominins. It is evident that decrease in body hair as the initial modification would bring on bipedality as a necessary consequence (Amaral 1989), through the strong selective pressure of safe infant carrying, when infants could no longer cling to body hairs.
The timing of reduction of body hairs is very controversial, since Darwin’s original (1871) emphasis on the issue. Several works indicated a very early beginning of body hair reduction, still in forested environments, based on thermoregulatory requirements (Newman 1970), rhd of Australopithecines (Schwartz and Rosenblum 1981), and comparison of human and ape skin (Montagna 1982, 1985). Bipedality preadaptive to nakedness was suggested later from water-consumption requirements under reduced humidity (Wheeler 1992). However, detailed analysis of thermal loads and water consumption for quadrupeds and bipeds in the furred and naked conditions suggested again that reduction of body hair started in a forested environment becoming drier (Amaral 1996). Savanna monkeys tolerate heat even at high levels of exercise, evidencing that the biological avenue to cope with heat stress in an open environment is to keep a hair covering, increase sweating capacity, and have a variable conductance (patas monkeys, Mahoney 1980, and baboons, Rogers et al. 1992). The only situation in which nakedness is favorable concerns dissipation of heat loads that do not come from sun absorption but from activity in a more closed forest condition at temperatures below that of the body (Amaral 1996). Furthermore, regarding water requirements, advantages for nakedness exist in dry ambients with temperatures below body temperature (Amaral 1996).
Recent genetic work has focused on evolution of black skin as a result of naked unprotected skin under solar stress, estimated to have occurred at least 1.2 mya (Rogers et al. 2004), while clothing is a recent innovation of only about 70,000 years ago (Kittler et al. 2003). However, up to now, there is no date for the beginning of reduction of body hairs. Therefore, localization of the genetic changes responsible for reduction of body hairs in humans is necessary to settle the issue.
The new perspective developed in this paper evidences continuity between physical and behavioral aspects of early hominins and their ancestors. The more differentiated aspects of humans are left to the emergence of Homo, at a much later period.

infant carrying
clinging
friction
bipedalism
hair strength
reduction of body hairs


Viscosupplementation in the hip: evaluation of hyaluronic acid formulations

This study compares three different hyaluronate formulations and evaluates functionality, time of satisfactory pain relief and also the delay in performing a total hip arthroplasty. One hundred and twenty patients (126 hips) received viscosupplementation with one of the three hyaluronate formulations. All patients were candidate for surgical treatment with a total hip arthroplasty. Three different products were consecutively used: Adant®, Synocrom® or Synvisc®. Patients were assessed 6 weeks after each infiltration using Visual Analogue Scale and Harris Hip Score. The Harris Hip Score increased significantly in two of the three groups compared to baseline, but no statistical significant difference was noted between the groups. Viscosupplementation provides significant pain reduction in two of the three groups. There is no significant difference in duration of the effect of the first infiltration between the three groups. The positive effect was still ongoing at the end point of the study in 46 hips: 51% of the patients did not undergo total hip arthroplasty, 3 years after viscosupplementation.
Introduction
Severe osteoarthritis (OA) of the hip is characterized by pain and reduced mobility. It affects primarily adults aged over 50 years, but the age of onset of hip OA linked complaints seems to decrease over the last decennia [12]. First-line treatment consists of pain reduction with analgesics and non steroidal anti inflammatory drugs (NSAID). Rehabilitation treatment, education and the use of walking aids can help providing pain relief and improving mobility. When those therapeutic options fail or the analgesic treatment causes intolerable side effects, joint lavage, hip osteotomy or total hip arthroplasty (THA) can be considered. This arthroplasty technique has greatly improved and patients experience pain reduction and improvement of the quality of life. However, the intervention still requires prolonged anaesthesia, and is followed by a long-term rehabilitation program. Though complications are rare and protheses have an increasing duration of life, reinterventions are still needed [4].
Viscosupplementation (VS) is the administration of hyaluronan and/or hyaluronic acid preparations to joint synovial fluid for the treatment of OA in order to restore the biologic properties of normal hyaluronic acid (HA).
The use of VS with HA was first described to provide pain relief and to increase mobility of the knee joint. The VS is an effective treatment for OA of the knee with beneficial effects on pain, function and patient global assessment [14]. HA products have more prolonged effects than intra-articular corticosteroids [14]. Since 1984, this technique is also used for the management of OA of the hip joint [2]. In the available literature there is no consensus on the number of injections, the dosage per injection, the most appropriate formulation of HA, and the optimal method for controlling the needle positioning in the hip joint. Moreover, the patient selection criteria differ from one study to another. To our knowledge there is no documentation available on the possible time gain for patients treated with VS of the hip joint before they have to undergo THA.
The results of a trial comparing three formulations of HA were presented. All patients were candidates for THA. The time of satisfactory pain relief, improved functionality obtained with each infiltration of HA and the delay in surgery were evaluated.
Patients and methods
Patient selection
The use of VS in patients with severe OA is common practise in our hospital, thus not requiring approval of the ethical committee. Patients gave their informed consent for this prospective study. Between March 2001 and February 2005, 120 patients (126 hips), 49 males and 71 females, responding to the eligibility criteria listed below, received viscosupplementation. Three different products were consecutively used: Adant® (Tedec-Meiji Failma, Madrid, Spain) (Group 1) (Synthetic hyaluronic acid with an average molecular weight of 0.6–1.2 million Da), Synocrom® (Croma Pharma, Leobendorf, Austria) (Group 2) (Sodium hyaluronate with a average molecular weight of 1.6 million Da) or Synvisc® (Altana Pharma, Konstanz, Germany) (Group 3) (Hylan GF 20 with an average molecular weight of 6.0 million Da) (Table 1).
Table 1Characteristics of infiltrated populationPeriod of treatmentPatientsGenderAgeAdant27-11-02 till 23-02-059135 ♂ and 65 ♀61.8 ± 12.8Synocrom19-01-04 till 04-10-04207 ♂ and 13 ♀62.1 ± 14.5Synvisc15-03-01 till 24-04-03157 ♂ and 8 ♀61.9 ± 15.3
Eligibility criteria
Age between 30 and 70 years and suffering idiopathic radiologically confirmed hip OA.
Visual Analogue Scale (VAS) score for pain greater then 30 (on a 100-point scale; 0 no pain and 100 “the worst pain imaginable”)
Have persistent pain for longer than 1 month despite use of analgesics or NSAID’s.
Be candidate for surgical treatment with a THA, according to the following criteria:
continuous hip pain, also during the night, requiring daily intake of NSAID’s or pain medicationdisabled gait pattern and need of walking aid
Be able to understand the information relative to viscosupplementation and to give informed consent.
Exclusion criteria
Pregnancy
Contraindications to intra-articular hyaluronic-acid preparations
Major hip dysplasia or congenital abnormality of the hip
Patients with systemic corticosteroids or intra-articular corticosteroid injections in the last 6 months
Contra-lateral THA or hip arthroscopy in the last 6 months
Oral or parenteral anticoagulant therapy
Previous hyaluronic acid hip infiltrations
Skin diseases or infections
Signs of haemarthrosis
History of allergy or hypersensitivity to iodated contrast
Treatment
Patients received an intra articular infiltration with one of the three products. The manufacturer’s treatment recommendations were followed. Patients having initially experienced a satisfactory pain relief are offered a second and third infiltration or THA when the condition deteriorates. Injection of the viscosupplementation was performed under sterile conditions by the same experienced orthopaedic surgeon (MM) in all patients. After skin cleaning a lumbar puncture needle was inserted in a lateral approach. Layer by layer local anaesthesia was performed using lidocaine 1%. Iodinated contrast agent Ultravist® (Schering, Berlin, Germany) was injected. The needle positioning into the joint cavity was fluoroscopically controlled (Fig. 1). Arthrocentesis was carefully performed prior to each injection to remove any effusion.
Fig. 1a Needle placement for injection of the viscosupplementation. b Fluoroscopic image of the needle insertion in the hip joint space
After resting for 2 h, the patient was allowed to walk and to return home. The patient was advised to rest at home until the next morning.
Oral symptomatic slow acting drugs for osteoarthritis were authorized if they were taken at a stable dose for more than 3 months prior to inclusion in the study. These analgesics were continued at a stable dose during the VS treatment.
Evaluation
All patients were assessed at baseline and 6 weeks after each infiltration. During this consultation in the outpatient clinic, the pain and functionality were evaluated using the VAS pain during walking score (100-point scale) and the Harris Hip Score (HHS). The latter is a clinical scoring system on a total of 100 points whereby the following subscales are rated: function (47 points), pain (44 points), range of motion of the hip (5 points) and absence of muscle contractures and length discrepancy (4 points). All side effects and complications of viscosupplementation were noted. In April 2005, all patients were contacted for follow-up assessment over the phone VAS and HHS.
Statistical analysis
Software (MS Excel)® was used to collect the data. Statistical analyses were of two kinds, first the differences in HHS and VAS pre-infiltration and post-infiltration (in the three groups) were compared using the paired t test and with the Wilcoxon paired test in the Synvisc group because this group is too small to analyse with the paired t test.
The second comparison was made between the three groups (Synvisc, Synocrom and Adant). The differences in HHS and VAS evolution between the three groups were checked by the analysis of variance statistics with Tukey extension, which also was used for controlling if the groups were initially homogeneous.
The duration of the viscosupplementation effect of the first infiltration was analysed using the Kaplan-Meier survival curves. The delay for the need of hip surgery was also analysed using a Kaplan-Meier survival curve. The statistical significance was set on P ≤ 0.05.
Results
The mean pre-infiltration HHS was comparable for the three groups and varied from 64.8 points in the Adant group to 66.8 points in the Synocrom-group. The post-infiltration HHS increased with 6.3 points in the Adant group (P < 0.001), with 10.6 points in the Synocrom group (P < 0.05) and with 6.1 points in the Synvisc-group (P > 0.05; Table 2). There was no statistical significant difference in the evolution of the HHS between the three groups (Table 2).
Table 2Evolution in average HHS scoreHHS preHHS postDifferencePAdant64.8 ± 13.871.1 ± 15.7+ 6.3< 0.001Synocrom66.8 ± 13.877.4 ± 14.7+ 10.6< 0.05Synvisc66.3 ± 13.572.4 ± 14.5+ 6.1> 0.05
Viscosupplementation provided a highly significant pain reduction in the Adant-group (P < 0.0001), a significant pain reduction in the Synocrom-group (P < 0.05) and a pain reduction that did not reach significance in the Synvisc-group (P > 0.05). There was no significant difference in pain relief between the three treatment products (Fig. 2, Table 3).
Fig. 2Pain relief in the three treatment groups a Adant, b Synocrom and c Synvisc
The duration of the effect of the first infiltration in the three groups is shown in a Kaplan-Meier curve (Fig. 3). The first infiltration was the starting point. Endpoints were the second infiltration or operation of the afflicted hip, or when these were not applicable the latest patient contact, which can be considered as ongoing effect.
Fig. 3Kaplan-Meier survival curve of the duration of effect of the first infiltration in days for the three different treatment groups
There is no significant difference between the three groups (χ2 = 0.988 and P = 0.61). Figure 4 illustrates the duration of effect of the three groups globally.
Fig. 4Kaplan-Meier survival curve of the duration of effect of the first infiltration in days (three treatment groups together)
The positive effect was still ongoing in 46 hips, while in 80 hips patients had either received a second infiltration or THA at, the end of the study (Table 4).
Table 3Evolution in average VAS pain during walking scoreVAS preVAS postDifference PAdant51 ± 2339 ± 27− 12< 0.0001Synocrom43 ± 2229 ± 23− 14< 0.02Synvisc47 ± 2630 ± 29− 17> 0.05Pre: at first infiltrationPost: at follow-up
The delay in performing a hip operation is analysed using a Kaplan-Meier survival curve (Fig. 4). After 3 years, 51% of the patients have not undergone surgery. Because of the comparable outcome achieved with the three HA formulations, we did not differentiate between the three products in this survival analysis (Fig. 5).
Fig. 5Kaplan-Meier survival curve for the delay to surgery in days for the three groups confounded
Discussion
The patients attending our outpatient clinic, who were judged eligible for THA, were offered the possibility of a VS therapy. Hundred twenty patients choose this treatment option and 126 hips were treated with Adant, Synocrom or Synvisc. All studies, published up till now, studying the effect of VS in the treatment of hip OA were performed in small patient groups (12–57 patients) [6, 9].
Table 4Duration of treatment effect after first infiltrationPatientsAverage duration (days)Effect of 1st infiltration still going on46 352 ± 258 (range 6–886)Effect of 1st infiltration terminated80174 ± 163 (range 13–724)
The three preparations provided a significant pain relief and improvement of the HHS. The isolated Synvisc group never reached statistical significance in HHS score evolution and VAS during walk test after VS treatment; possibly due to the small number of patients (N = 15) in this group. As in the study of Tikiz [13], we found no significant difference between lower and higher molecular weight hyaluronic acids.
We could identify two groups of responders, the ongoing responders who last on average for 352 days after the first infiltration. The second group, where patients either received a second infiltration or THA had an average duration of effect of 174 days.
The VS method is widely used for OA of the knee joint, but there are only a few studies about its use in OA of the hip. Most authors agree that there should be a role for viscosupplementation in the treatment of hip OA. [1–3, 6, 7, 9–11] Our findings confirm the effect of VS in patients suffering OA of the hip. To our knowledge, this is the largest series of patients with hip osteoarthritis treated with viscosupplementation. There are no guidelines regarding the optimal number of injections needed to obtain optimal clinical response, which seems to be different [1, 2, 8, 10, 11] between products and dependent on the molecular weight (MW) [7]. We evaluated the time to relapse of one infiltration.
Other authors advocated the use of ultrasound for controlling the needle position in the hip joint. [9, 3] In our series, we performed the infiltrations under fluoroscopy, in experienced hands this approach has proven to be accurate and safe. We use a very low amount of contrast liquid to avoid dilution of the product.
Of all the reports published, we have the longest follow-up, up to approximately 3 years. The analysis by means of the Kaplan-Meier survival curve learns that there is a 50% probability of long-term effect (more than 2 years).
We saw no infectious adverse events and no serious systemic reactions, but all the interventions are performed in the operating theatre under strict aseptic conditions. The adverse events rates ranged from 10 to 30% which is slightly higher than the rates reported in VS treatment of knee OA [7]. Repeated injections did not increase the risk of adverse events [7]. Some patients experienced transient hip pain after the infiltration but made a full recovery in the next days. In the study of Conrozier [6], transient hip pain was reported after 10.1% of the injections. The products used in this study were all well tolerated. Complications are rare but a single case of septic arthritis was reported after multiple injections of hyaluronate and glucocorticoid [5]. Gout, pseudogout and chondrocalcinosis have not been reported after hip infiltrations.
Intra articular injection of hyaluronic acid can provide long-term pain relief and improvement of joint function even in patients eligible for THA. Despite the use of fluoroscopy, this technique can be performed in an outpatient clinic, allowing patients to return home on the day of the intervention. At present, viscosupplementation therapy for OA of the hip is only palliative. It can be an alternative for young THA candidates, patients with surgical contra-indications and patients in whom NSAID use is not appropriate. There is only 1 randomised, double blind, placebo controlled trial of patients with hip OA [15]. The study was designed with a three-armed parallel-group (Hyalgan vs. methylprednisolone vs. lidocaine). One hundred and one were treated. There was no statistically significant difference between the three products on any outcome measure including the primary outcome measure, i.e., ‘Pain on walking’, at three 3 months of follow-up.
The results of our study should be considered in the light of the limitations of the design of this study. It is a non placebo controlled non randomised prospective study. It is known from experience with knee OA that the placebo effect of VS tends to be substantial [8]. The dimension of the groups treated with the three different products differs from 15 to 91 patients.
Viscosupplementation with hyaluronic acid seems to be a valuable technique for the management of painful OA of the hip that may delay the need for surgical intervention. Further prospective randomised placebo controlled studies are necessary to draw definite conclusions.

viscosupplementation
hyaluronic acid
hyaluronan
intra-articular
injections
hip osteoarthritis
non-operative treatment


The effect of age on task-related modulation of interhemispheric balance

Normal aging is associated with less lateralised task-related activation of the primary motor cortices. It has been hypothesized, but not tested, that this phenomenon is mediated transcallosaly. We have used Transcranial Magnetic Stimulation to look for age-related changes in interhemispheric inhibition (IHI). Thirty healthy individuals (aged 19–78 years) were studied using a paired-pulse protocol at rest and during a low-strength isometric contraction with the right hand. The IHI targeting the right motor cortex was assessed at two intervals, 10 ms (IHI10) and 40 ms (IHI40). The corticospinal excitability of the left hemisphere was assessed by means of input–output curves constructed during voluntary construction. Age was not correlated with IHI10 or IHI40 at rest. During muscle contraction IHI tended to increase at both intervals. However, this increase in IHI during the active condition (changeIHI) was less evident with advancing age for the 40 ms interval (r = 0.444, P = 0.02); in fact a degree of disinhibition was often present. There was no correlation between age and changeIHI10. Age was negatively correlated with the area under the recruitment curve (r = −0.585, P = 0.001) and the size of the maximum MEP collected (r = −0.485, P = 0.007). ChangeIHI and measures of corticospinal excitability were not intercorrelated. In conclusion, task-related increases in interhemispheric inhibition seem to diminish with advancing age. This phenomenon is specific for long-latency IHI and may underlie the age-related bihemispheric activation seen in functional imaging studies. The mechanism underlying changes in IHI with advancing age and the association with changes in corticospinal excitability need further investigation.
Introduction
Physical performance declines with increasing age (Hackel et al. 1992; Smith et al. 1999). Although age-related changes in muscular (Vandervoort 2002) and neural architecture (Dorfman and Bosley 1979; Haug and Eggers 1991; Madden et al. 2004) are an important cause of this decline, there is increasing interest in the role of functional alterations occurring throughout the motor system. Excitation–contraction uncoupling (Delbono et al. 1995), motor unit remodelling (Wang et al. 1999), changes in the agonist–antagonist activation pattern (Hortobagyi and Devita 2006) and reorganization of the central motor pathways (Kido et al. 2004; Ward and Frackowiak 2003; Minati et al. 2007) are all areas currently under study. Understanding the mechanisms underlying these phenomena will aid differentiation between inevitable functional failure and potential compensatory strategies which in turn may allow the development strategies to combat this age-related decline (Delbono 2003).
Functional imaging has been used to assess age-dependent changes in the cerebral motor system in humans (for review see Ward 2006). In general, motor task-related brain activation is seen in a wider network with advancing age. The exact pattern of age-related change depends on the task being performed. However, it has been repeatedly shown that in older individuals there is increased bihemispheric activation during the execution of motor tasks that in younger individuals involve mainly lateralized processing. In particular, with advancing age there is less de-activation of the primary motor cortex (M1) ipsilateral to the moving hand (Ward and Frackowiak 2003; Naccarato et al. 2006; Ward et al. 2007). It has been suggested, but not tested, that the underlying mechanism for this phenomenon involves changes in interhemispheric connections between the motor cortices.
Transcranial magnetic stimulation (TMS) can be used to study interhemispheric connectivity between the motor cortices. At rest, this connectivity consists primarily of an inhibitory effect (interhemispheric inhibition, IHI) with a latency of 6–50 ms (Ferbert et al. 1992; Di Lazzaro et al. 1999; Daskalakis et al. 2002; Chen 2004). This tonic IHI is modulated and follows a specific time course during preparation and execution of voluntary movement (Murase et al. 2004; Duque et al. 2005, 2007). During the execution of an isometric muscle contraction, the IHI (at 10 ms latency) targeting the M1 ipsilateral to the moving hand has been shown to increase (Ferbert et al. 1992). This “extra” inhibition is in keeping with the primarily unilateral activation pattern seen in imaging studies of movement and has been interpreted as a means of minimizing mirror activity (Leocani et al. 2000; Duque et al. 2005). Task-related changes in longer latency IHI, i.e. 40 ms, have not been studied in detail but there is some evidence that they may be distinct to the ones seen in short latency IHI (Chen et al. 2003).
Previous TMS studies have shown that there is reduction of activity in the intracortical inhibitory circuits in the elderly (Peinemann et al. 2001; Hortobagyi et al. 2006). It has been suggested that reduced inhibition represents a mechanism to compensate for the deleterious effects of aging on several levels of the motor system including the primary motor cortex (Pitcher et al. 2003; Oliviero et al. 2006) but these notions remain mainly hypothetical (Wassermann 2002).
The main purpose of this study was to investigate whether normal aging has an effect on the task-related modulation of IHI measured at two different latencies, 10 and 40 ms. We hypothesized that with increasing age there would be less extra activation in the inhibitory circuits targeting the M1 ipsilateral to the moving hand. In order to gain some insight of the mechanisms and the physiological meaning of these changes we also performed measures of corticospinal excitability on the side contralateral to the moving hand and looked for correlations with age and IHI measures.
Methods
Subjects
Thirty healthy right-handed volunteers (mean age 42.9 years, range 19–78; 30% female) participated in the study after giving informed consent. They reported no history of neurological illness, psychiatric history, vascular disease or hypertension and they were not taking regular medication. The study was approved by local Ethics Committee.
Transcranial magnetic stimulation
Subjects were seated in an armchair with their eyes open. EMGs were recorded via Ag/AgCl electrodes placed over the First Dorsal Intersosseus (FDI) bilaterally, using a belly-tendon montage. Signals were filtered (30 Hz to 10 kHz), amplified using a Digitimer 360 (Digitimer Ltd, Welwyn Garden City, Herts., UK) and stored on computer via a Power 1401 data acquisition interface (Cambridge Electronic Design Ltd, Cambridge, UK). Analysis of data was carried out using Signal Software (Cambridge Electronic Design).
Two figure-of-eight coils connected to two monophasic Magstim 200 stimulators were used for the experiments (all Magstim Co., UK). A 70-mm coil was used for motor hot spot identification and threshold measurements on both sides of the brain. The motor hotspot was defined as the scalp location where TMS consistently resulted in the largest MEP. The resting motor threshold (RMT) was defined as the lowest intensity needed to evoke an EMG response of 50 μV in 50% of the trials with the FDI relaxed; the active motor threshold (AMT) was defined as the intensity which evoked a 200 μV EMG response in 50% of the trials with a background FDI contraction of 10–15% of the maximum voluntary contraction (MVC). For all studies requiring activation of the FDI, visual feedback was provided using an oscilloscope.
A recruitment curve (RC) for the active MEP amplitude elicited in the left FDI was obtained using the 70 mm coil while the subjects maintained a background FDI contraction of 15–20% MVC. Ten MEPs were collected and averaged at the following stimulus intensities: 90, 100, 110, 120, 140, 150, 160 and 170% AMT. The contraction level was tested by measuring the mean value of the rectified EMG in the 80 ms preceding the TMS pulse. The averaged peak-to-peak amplitude of the unrectified MEPs was then expressed as a ratio of the maximum peak-to-peak amplitude of the unrectified compound action potential (CMAP) evoked by supramaximal electrical stimulation of the ulnar nerve at the wrist using a Digitimer pulse stimulator (model DS7).
Interhemispheric inhibition (IHI) was measured using a standardised paired-pulse paradigm (Ferbert et al. 1992). IHI is expressed as the reduction in the response to a suprathreshold TMS pulse (test) delivered to the M1 when another suprathreshold pulse is delivered to the contralateral M1 6–50 ms earlier (conditioning). Here, we concentrated on the IHI targeting the right M1. Hence the conditioning pulse was given over the left M1 using the same 70-mm coil. For the test pulse a smaller 50 mm figure-of-eight coil was held over the right M1; this allowed us to accommodate two coils on the head of all the subjects without compromising the exact positioning of the coils over the motor hot-spot (Ferbert 1992). MEPs were measured from the left FDI. Ten single (test) and ten paired-pulse (conditioning + test) trials were randomly intermingled and averaged. IHI was defined as the conditioned/test MEP amplitude ratio, smaller values reflecting stronger IHI. Interstimulus intervals (ISIs) of 10 and 40 ms were studied in different blocks. IHI was initially measured at rest (restIHI10 and restIHI40). The stimulation intensity for both the conditioning and the test stimuli was adjusted to evoke an MEP of 1–1.5 mV in the contralateral FDI muscle. For the active condition (activeIHI10 and activeIHI40) the subjects were instructed to contract the right FDI to 15–20% of their MVC in response to an auditory cue preceding the conditioning stimulus by 600 ms. In this way, we made sure that the subject had reached the target level of background contraction for at least 200 ms before the conditioning pulse. This was to avoid measuring changes in IHI that are associated with the preparation of the movement rather than a steady isometric contraction (Duque et al. 2005, 2007). EMG activity in the left FDI was also recorded and contaminated trials were rejected to avoid the confounding effect of mirror activity. The stimulation intensity both for the conditioning and test stimulus was the same as in the resting state, as in previous studies (Ferbert et al. 1992). The absolute values of activeIHI were then expressed as a ratio to the values at rest for the respective ISI (changeIHI10 and changeIHI40). ChangeIHI therefore reflects the change seen in the IHI targeting the right motor cortex when the right hand is active. Values <1 reflect stronger inhibition, while values >1 reflect less inhibition.
Statistical analysis
Analysis was performed using SPSS v.14 (SPSS Inc., USA). Exploratory plotting and statistical tests (Shapiro-Wilk) confirmed normal distribution for most variables. Some of the variables were skewed by a single outlier and this could not be corrected by logarithmic transformations; the outlier was therefore discarded from the dataset to allow use of parametric tests.
Data obtained during the RC paradigm were plotted against the stimulation intensity. In most subjects the resulting curves were sigmoidal in shape. Two representative examples, one from a young and one from an old subject, are shown in Fig. 1. The area under the RC (AUC) was calculated using the method of trapezoid integration to provide a summary measure of the corticospinal output across all stimulation intensities. Data points were then fitted in the Boltzmann sigmoidal model based on the modified Levenberg–Marquardt nonlinear least-mean-squares algorithm (Press et al. 1986). This function is often used to provide parameter estimates for RCs (Capaday et al. 1999; Devanne et al. 1997). The data were best fitted by a 4-parameter equation in which the amplitude of the MEP at a given stimulation intensity (I) is estimated as:  MEPmax and MEPmin represent the maximum and minimum MEP amplitude, respectively; I50 represents the stimulation intensity required to get a response 50% of the maximum. The inverse of the slope parameter (1/slope) is directly proportional to the maximal steepness of the curve, which occurs at I50 (Devanne et al. 1997). The R2 co-efficient of determination was greater than 0.89 in all subjects.
Fig. 1Representative examples of the recruitment curves plotting the amplitude of the active MEPs against the stimulation intensity. The circles represent the collected data. The line represents the relation predicted by the Boltzmann model. The area under the curve (grey area) was calculated with the method of trapezoid integration using the actual data collected during the construction of the curves. CMAP, compound motor action potential, AMT, active motor threshold
Pair-wise comparisons between different TMS measures were performed using paired t tests. Correlations with age and between TMS measures were assessed by computing Pearson’s product-moment correlation coefficient. We have also looked for correlations between these parameters and gender. Partial and part correlations were employed as appropriate. Significance level was set at P < 0.05.
Results
The mean and range of the values for all TMS measures are summarized in the Table 1.
Table 1TMS measures of corticospinal excitability and interhemispheric inhibitionCorticospinal excitabilityLeft hemisphere Right hemisphereMotor thresholds (% stimulator’s intensity)Resting (RMT)37.6 (28–65)36.4 (29–50)Active (AMT)28.4 (19–45)28 (22–39)RC of active MEP amplitude(CMAP corrected)Mean MEP amplitude recorded 90% AMT0.02 (0.01–0.06)– 100% AMT0.03 (0.01–0.07)*– 110% AMT0.06 (0.02–0.18)*– 120% AMT0.09 (0.03–0.35)*– 140% AMT0.25 (0.06–0.51)*– 150% AMT0.30 (0.10–0.57)*– 160% AMT0.34 (0.13–0.56)*– 170% AMT0.22 (0.39–0.62)–Maximum MEP amplitude recorded0.38 (0.13–0.62)*–AUC12.8 (1.8–23.4)*–Parameter estimates (Boltzman model) MEPmax/CMAP0.4 (0.13–0.72)*– I50 (%AMT)137 (115–168)– 1/slope0.14 (0.05–0.37)–IHI (targeting the right M1)10 ms40 msrest IHI0.61 (0.32–0.9)0.6 (0.28–1.1)activeIHI0.54 (0.1–0.89)0.57 (0.2–1)changeIHI (activeIHI/restIHI)0.96 (0.42–2.47)0.97 (0.5–1.49)*CMAP, compound motor action potential; AUC, area under the curve; MEPmax, maximum MEP amplitude estimated; I50, stimulation intensity needed to get a response of 50% of the maximal MEP; IHI, interhemispheric inhibition; restIHI, IHI measured with both hands relaxed; activeIHI, IHI measured during a tonic contraction of the dominant hand at 15–20% MVC; changeIHI, values <1 indicate stronger IHI at the active condition* Significant correlation with advancing age (P < 0.05)
Corticospinal excitability
Threshold values were not different between the left and right M1. Age was not correlated with RMT or AMT on either side or the amplitude of the CMAP. The mean amplitude (CMAP corrected) of the active MEPs recorded during the construction of the recruitment curves was negatively correlated with age at all stimulation intensities between 100–160%AMT (100%AMT: r = −0.431, P = 0.02; 110%AMT: r = −0.397, P = 0.03; 120%AMT: r = −0.481, P = 0.007; 140%AMT: r = −0.556, P = 0.001; 150%AMT: r = −0.457, P = 0.11; 160%AMT: r = −0.463, P = 0.01). The same was true for the amplitude of the maximum MEP recorded (Pearson’s r = −0.485, P = 0.007) (Fig. 2a). Age was negatively correlated with the total area under the RC (Pearson’s r = −0.585, P = 0.001) (Fig. 2b). From the parameters estimated using the Boltzmann model, MEPmax showed a weak correlation with age (r = −0.397, P = 0.04); age was not correlated with the maximum slope or I50.
Fig. 2Correlations between age and TMS parameters. There was a significant negative correlation between the amplitude of the maximum MEP recorded during the construction of the RC (a) and the total area under the RC (b). Age was negatively correlated with changeIHI at 40 ms (d) but not at 10 ms (c). CMAP, compound motor action potential, RC, recruitment curve constructed during tonic contraction of the target muscle, IHI, interhemispheric inhibition, restIHI, IHI measured with both hands relaxed, activeIHI, IHI measured during a tonic contraction of the dominant hand at 15–20% MVC, changeIHI, values <1 indicate stronger IHI at the active condition
Gender was not correlated with any of the TMS measures of corticospinal excitability.
Interhemispheric inhibition
Most subjects showed some amount of IHI at rest; only in one subject could restIHI40 not be elicited. Paired-samples t test did not show any difference between restIHI10 and restIHI40 (P = 0.44). Because the amount of IHI depends on the intensity used for both the conditioning and the test stimulus (Ferbert et al. 1992; Chen et al. 2003) we looked for correlations between these values and age. Age was not correlated with the intensities used to stimulate either the left M1 (70-mm coil; 45.7 ± 7.1 for IHI10 and 45.8 ± 7.2 for IHI40) or the right M1 (50-mm coil; 46.2 ± 8.6 for IHI10 and 46.9 ± 8.1 for IHI40). The amplitude of the MEPs elicited by the test stimulus and by the conditioning stimulus was slightly higher for the restIHI40 but the values fell within the target range of 1–1.5 mV (see below).
During activation of the right hand the MEP elicited by the test stimulus in the resting left FDI tended to increase (from 1.23 ± 0.53 to 1.44 ± 0.67 for IHI10 and from 1.48 ± 0.58 to 1.64 ± 0.70 for IHI40), but this was not significant across the group, as reported earlier for low-strength isometric contractions (Liepert et al. 2001). As expected, the amplitude of the MEP elicited by the conditioning pulse in the right FDI increased significantly during activation of the muscle (from 1.27 ± 0.40 to 5.95 ± 1.69, P < 0.001 for IHI10 and from 1.5 ± 0.47 to 6.17 ± 2.57, P < 0.001 for IHI40).
There was an overall tendency for stronger IHI during activation of the right FDI at both ISIs, but this did not reach significance. In fact, changeIHI was quite variable ranging from more inhibition to less inhibition compared to the resting condition. Because changeIHI might be biased by the amount of IHI at rest we looked for correlations between changeIHI and restIHI; there was none for either ISI.
There was no correlation between age and changeIHI10 (Fig. 2c). However, we found a significant positive correlation between age and changeIHI40 (r = 0.444, P = 0.02) (Fig. 2d). In other words, when younger individuals activated their right hand the amount of inhibition targeting the ipsilateral (right) motor cortex increased; with increasing age this phenomenon was gradually attenuated and often reversed. Because age showed a significant correlation with the amplitude of the active MEPs we performed semi-partial correlations correcting for the change seen in the amplitude of the conditioning MEP between the resting and the active condition (changeMEP = activeMEP/restingMEP). Again no correlation was found between age and changeIHI10; the correlation between age and changeIHI40 remained and was in fact slightly stronger (r = 0.553, P = 0.006).
Gender was not significantly correlated with any of the IHI measures; in line with a previous report (De Gennaro et al. 2004) there was a tendency for a positive correlation between female gender and the amount of restIHI10 targeting the right hemisphere, but this finding did not reach significance in our group of subjects (r = 345, P = 0.07).
Finally, changeIHI was not correlated with any of the measures of corticospinal excitability elicited from the stimulation of the left M1.
Discussion
The purpose of this study was to investigate the effect of age on the interhemispheric balance between the two primary motor cortices and in particular the modulation of inhibition targeting the right M1 during activation of the right hand (changeIHI). We found that the amount of tonic inhibition (restIHI) was very variable across the group but age could not explain this variability. However, age was significantly correlated with changeIHI. As reported previously, when young individuals perform a low strength grip, the inhibition targeting the ipsilateral M1 tends to increase (Ferbert et al. 1992). Our data show that with increasing age this extra inhibition is not as strong and some degree of disinhibition may be present instead. Interestingly, the effect of age was significant for the 40 ms ISI (changeIHI40) but no correlation was found between age and changeIHI10.
Our results on changeIHI are in keeping with the findings from functional imaging studies. A number of studies have consistently shown that task-related activation is less lateralised in older individuals (for review see Ward 2006). This bilateral recruitment includes primary and non-primary motor areas; activation of the latter seems to characterise more complex tasks. Regarding the primary motor cortices, reduced deactivation of the M1 ipsilateral to the moving hand has been a common finding among studies using different scanning paradigms (Hutchinson et al. 2002; Ward and Frackowiak 2003; Naccarato et al. 2006; Ward et al. 2007). It has been hypothesized that this phenomenon could be mediated transcallosally. In support of this hypothesis, we have directly demonstrated that there is task-related reduction in interhemispheric inhibition with advancing age at least when the right hand is activated.
The differential effect of age on changeIHI10 and changeIHI40 is an interesting finding that adds to the current knowledge of the cortical circuits that these measures reflect. So far, it is thought that both short latency IHI (8–12 ms) and long latency IHI (40–50 ms) are mediated through excitatory callosal projecting neurons that are distinct from corticospinal neurones (Lee et al. 2007). In accordance with this view, corticospinal output and IHI measures in this study did not correlate. The callosal neurons are thought to activate inhibitory interneurons in the contralateral M1 (Daskalakis et al. 2002; Chen 2004), but these connections may differ for short and long latency IHI (Chen et al. 2003; Kukaswadia et al. 2005). The neurotransmitters involved are not entirely understood but there is evidence of significant involvement of GABAB-ergic activity. However, Irlbacher et al. (2007), have recently demonstrated that exogenous enhancement of GABAB activity strengthens long IHI but has little effect on short IHI at rest. Long IHI was also sensitive to GABAA agonists (Irlbacher et al. 2007). Finally, Chen et al. (2004), has shown that activation of the target muscle results in a reduction in the IHI targeting the active M1 (the opposite direction than the one studied here) measured at 8 ms but has little effect on the IHI40. We have shown that advancing age has an effect on the modulation of IHI during voluntary muscle contraction at 40 ms but not at 10 ms. We have thus provided additional evidence that IHI10 and IHI40 may respond differently to dynamic changes within the motor system and thus may represent physiologically distinct phenomena. This evidence could be strengthened in the future by testing the effect of age on IHI in both directions, i.e. the IHI targeting the motor cortices ipsilateral and contralateral to the moving hand.
Why is IHI40 not enhanced during voluntary contraction in older individuals? One possible explanation is age-related failure of the involved pathways. MRI studies have reported age-related reduced fractional anisotropy within the corpus callosum suggesting callosal fibre degeneration (for review see Minati et al. 2007). However, for callosal degeneration to be the cause of our finding, one would expect some effect on IHI10 as well. Another possibility is that the inhibitory circuits with which the callosal fibres synapse are less excitable. Previous studies have provided some evidence of age-related reductions in cortical inhibition. For example, GABAA-ergic short-interval intracortical inhibition (SICI) assessed with a biphasic stimulator (Peinemann et al. 2001) and cortical reciprocal inhibition (Hortobagyi et al. 2006) are reduced in older individuals. However, Wasserman et al. (2002) failed to show a correlation between SICI and advancing age in a large series of normal subjects. Others have found increased SICI in middle-aged adults (Kossev et al. 2002). Further experiments, which include active conditions are needed to study these associations in the aging brain. Finally, it should be noted that although TMS-measured IHI is thought to reflect mainly transcallosal connections, Gerloff et al. (1998) has demonstrated a role for other pathways involving subcortical and/or spinal structures, the exact nature of which is unclear. Age related changes in these pathways may therefore also contribute to the correlations that we have observed.
Another question is whether the age-related reduced activity reported in multiple inhibitory systems, including IHI is an inevitable consequence of neurodegeneration or in fact represents a compensation strategy of the aging brain. Similar changes have been described in response to brain injury and have been interpreted as markers of cortical reorganization (Ward and Cohen 2004; Talelli et al. 2006). The relative preservation of changeIHI10 could suggest that the release from inhibition is not uncontrolled or at least it occurs in a hierarchical manner. For example, IHI10 may be important for direct suppression of mirror activity in the contralateral M1 (Duque et al. 2005). Longer latency IHI40, on the other hand, may reflect polysynaptic pathways extending even beyond the primary motor cortices. In that case relatively less inhibition in an active state could allow bilateral recruitment if that was necessary. In this study, there was no correlation between changeIHI40 (or any other IHI measure) and any of the measures of corticospinal excitability despite the fact that the latter appeared to be compromised in older individuals. This finding could mean that changeIHI40 does not reflect an adaptation to the failing corticospinal pathways. However, it should be kept in mind that if compensatory mechanisms are indeed operating with increasing age (or decreasing corticospinal output) TMS may not measure the real deficit but the compensated deficit. The next reasonable step could be to study a series of elderly individuals known to have different levels of manual dexterity and look for correlations between electrophysiological and behavioural measures, including mirror movements during performance of complex motor tasks.
We found variable effects of age on parameters relating to corticospinal excitability. Motor thresholds were not affected in keeping with previous reports (Wassermann 2002; Oliviero et al. 2006; Hortobagyi et al. 2006). We have found negative correlations between age and the amplitude of the active MEP at most stimulation intensities, between age and the amplitude of maximum MEP and finally between age and the total area under the recruitment curve (AUC). These results are in agreement with previous findings of reduced amplitude of the MEPs elicited during an isometric contraction (Oliviero et al. 2006; Sale and Semmler 2005). The values derived from the Boltzmann model did not add extra information, since there was no correlation between age and the maximal slope of the curve or the stimulation intensity required to obtain 50% MEPmax (I50). Pitcher et al. (2003) have previously reported that I50 significantly increased with increasing age. In other words, the recruitment of the MEPs was slower at low stimulation intensities. The authors discussed that this finding may reflect reduced excitability or asynchronous activation of spinal motorneurons. In this study we did not perform measures of spinal excitability mainly due to time limitations. We have, however, constructed our RCs during background activation of the target muscle; that means that some a-motorneurons are already activated and the resulting measures are thus less subject to changes in spinal cord excitability (Day et al. 1989). We propose that increasing age does have a detrimental effect on the total output of primary motor cortex and that the mechanisms underlying (or compensating for) this effect are variable; thus a summary variable such as the AUC might be more suitable as a surrogate marker of overall corticospinal output.
In conclusion, this study has shown for the first time that there is an age-related reduction in the extra inhibition targeting the right hemisphere during an isometric handgrip with the right hand. These changes may underlie the bihemispheric pattern of activation seen in functional imaging studies of older individuals performing a unimanual hand task. Should our findings be confirmed, studies of interhemispheric balance may prove to be a useful marker of reorganization in the aging brain.

aging
transcranial magnetic stimulation
interhemispheric inhibition
motor system