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Evidence of self-sustained motoneuron firing in young and older adults
Journal of Electromyography and Kinesiology 16 (2006) 25–31 www.elsevier.com/locate/jelekin
Evidence of self-sustained motoneuron firing in young and older adults Gary Kamen *, Ryan Sullivan, Scott Rubinstein, Anita Christie Department of Exercise Science, Totman 160A, University of Massachusetts – Amherst, Amherst, MA 01003, United States Received 15 December 2004; received in revised form 31 May 2005; accepted 9 June 2005
Abstract Motoneurons demonstrate a type of self-sustained firing behavior that seems to be produced by a prolonged period of depolarization caused by intrinsic long-term changes in the motoneuron. Such self-sustained firing behavior has previously been reported in human motor units. The purpose of the present study was to investigate the occurrence of self-sustained firing behavior in older adults. Eight young (mean age 24 yrs) and eight older (mean age 73 yrs) individuals participated in the investigation. While subjects produced light dorsiflexion contractions, a brief vibration stimulus was applied to the tibialis anterior muscle. Motor unit recordings were also obtained from the tibialis anterior muscle. Self-sustained firing behavior was evidenced by the appearance of new motor unit recruitment following vibration, even as the motor units that fired before the vibratory stimulus maintained a steady firing rate. The proportion of motor units exhibiting self-sustained firing activity was similar in both young and older adults (approx. 23% of trials). We conclude that self-sustained firing behavior is a ubiquitous phenomenon that does not seem to be affected by the aging process. Ó 2005 Elsevier Ltd. All rights reserved. Keywords: Motor unit; Vibration; Plateau potentials; Aging; Tibialis anterior
1. Introduction It has now been well demonstrated that motoneurons exhibit a type of bistable firing behavior. Short bursts of excitation initiate long periods of self-sustained firing. These periods of motoneuron activity that occur in the absence of synaptic input can be extinguished by a short burst of inhibitory potentials. Self-sustained firing behavior has been demonstrated in several animal species [4,16,21], as well as in humans [18,35]. Self-sustained firing behavior is generally believed to be produced by ‘‘plateau potentials’’ (cf. [8,26]) manifested as a sustained period of depolarization in a *
Corresponding author. Tel.: +1 413 545 0784; fax: +1 413 545 2906. E-mail address: [email protected] (G. Kamen). 1050-6411/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.jelekin.2005.06.008
neuron. Inward Ca++-mediated currents produced by L-type Ca++ channels are responsible for these prolonged depolarizations. Thus, plateau potentials represent a change in the intrinsic properties of motoneurons and are thought to serve the function of amplifying synaptic input [22]. There are several changes that have been noted in aged motoneurons that could impact the proportion of motor units that exhibit self-sustained firing in older humans. Changes have been noted in the passive properties of motoneurons in aged animals. Motoneuron input resistance increases in old cats, although there seems to be no change in resting membrane potential or spike amplitude [7]. Ca++ influx into the motor nerve terminal increases with advancing age [1]. On the other hand, the duration of striatal Ca++-mediated plateau potentials is decreased in aged animals [13]. Changes in Ca++
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kinetics, then, could be the source of either an increase or a decrease in self-sustained motor unit firing in older humans [40]. An increase in the prevalence of self-sustained firing in older individuals, for example, might serve as a compensatory mechanism for the age-related loss of motor neurons [39,44], the diminution in function of the Ia-motoneuron monosynaptic EPSP [5], and/or the loss of corticomotoneuron connections [14]. Self-sustained firing has been observed in human motoneurons [18]. In a typical protocol, subjects are asked to produce a light voluntary contraction. Additional input is then supplied to the motoneuron pool, such as from an external vibratory stimulus which provides additional motoneuron drive via the Ia-amotoneuron synapse. The recruitment of new motor units which remain active when the vibration stimulus is removed is evidence of self-sustained firing. Previous studies have demonstrated that self-sustained firing can be modified by monoamine concentration in human motoneurons [41]. The purpose of this study was to determine whether self-sustained firing is present in older adults.
2. Methods 2.1. Subjects Eight older (mean age = 73.0 yrs) and eight young (mean age = 23.8 yrs) females, free of neurological and cardiovascular disorders participated in this investigation. All subjects were moderately active, as assessed with a Physical Activity Response Questionnaire. The procedures used in this investigation were reviewed and approved by the Human Ethics Review Board at the University of Massachusetts – Amherst. All participants signed an informed consent document prior to testing. 2.2. Procedures Each participant visited the Exercise Neuroscience Laboratory on one occasion for testing. Subjects were seated in a custom-made chair designed for measuring force during isolated isometric dorsiflexion contraction. The hip and knee of the dominant leg were maintained at 90° with adjustable straps placed across the waist and thigh, and with a metal brace placed over the anterior distal femur, superior to the patella. A flat metal bar wrapped in foam padding was tightened over the distal metatarsal, providing an immovable resistance for isometric dorsiflexion. The ankle and foot were also secured with a foam brace to restrict any antero-posterior or medio-lateral displacement. The non-dominant foot was placed on a box covered in foam padding to prevent using resistance in this leg to enhance force. Subjects
were instructed to sit erect with arms folded across the abdomen during all dorsiflexion trials. At the beginning of the session, each subjectÕs maximal voluntary force during dorsiflexion was determined. Subjects were asked to perform three maximal voluntary contractions (MVCs) of the tibialis anterior (TA), with 2 min rest between each trial. The maximum force value achieved across the three trials was deemed the MVC force value, and subsequent tasks were scaled to this value. A trace was then presented to subjects on a computer screen. The trace consisted of a 5-s preparatory period with the subject relaxed, a 3-s ramp up to 10% MVC, a period of 11 s at a constant force of 10% MVC, and a 3-s ramp down to 0% MVC. On the same screen the real-time force output of the subjects was displayed as a moving red line. Subjects were instructed to match the requisite force trajectory by gradually producing an isometric dorsiflexion contraction to increase force to 10% MVC, holding a constant 10% MVC contraction for 11 s, then slowly decreasing force to zero. During the constant force phase, a 100 Hz vibration was applied to the distal TA using a therapeutic vibrator (Zeniter TVR TMT-18, Heiwa Electronic Industrial Co. Ltd., Japan). Vibration was applied for 1 s, approximately 4–6 cm below the needle insertion site. The site for vibration was marked with a pen to ensure accurate placement of the vibrator with each trial. The vibration was applied between the 14th and the 15th second of the contraction when subjects were holding a 10% MVC effort. Subjects were given 5–10 practice trials, until they felt comfortable with the task and with the vibration. Each subject then completed 10–15 trials for recording, until 10 trials with accurate force traces and clear MUAPs were achieved. 2.3. Force recordings Isometric force was applied by subjects in an axis parallel to dorsiflexion, against the flat metal bar over the distal metatarsals. The force exerted during dorsiflexion was measured by a strain gauge force transducer (Interface Model MB-10, Scotsdale, AZ) secured to each side of the immovable metal bar. The force signal was amplified using a custom-built bridge amplifier. The signal was sent to an A/D converter (Data Translation Model DT 2801) and was sampled at 50 Hz on a personal computer. This signal was used to provide real-time feedback of force output to subjects using DasyLab software (Data Acquisition System Laboratory, DasyTec USA, Inc., Amherst, NH). The force signal was also sent to a second A/D converter (WIN-30 data acquisition board, United Electronics, Watertown, MA) and sampled at 50 Hz on a second personal computer, using DasyLab software to store the data for analysis.
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2.4. Motor unit recordings Intramuscular EMG activity was recorded from the TA using a 25-gauge stainless steel needle electrode. This electrode contained a cannula housing four platinum– iridium wires in a square array, terminating at a side port 7.5 mm from the tip. Each wire had a diameter of 50 lm, with 200 lm between wires. This configuration provided three separate channels of motor unit action potential (MUAP) data, based on the geometric orientation of the muscle fibers to the electrode recording site [33]. The needle was inserted approximately one half of the distance between the lateral malleolus and the tibial tuberosity. A stainless steel plate electrode was taped to the lateral surface of the patella of the dominant knee, which served as a ground electrode. The intramuscular EMG signals were amplified through a Dantec Counterpoint Electromyograph (Dantec Electronik Medicinsk, Skovlunde, Denmark) and viewed on a digital oscilloscope (Gould 2608 Thermo Electron Corporation, Valley View, OH). The proper position of the needle within the muscle was determined by high frequency MUAP activity during a 20% MVC contraction. This activity was assessed visually by the appearance of distinct action potentials on the oscilloscope, and audibly by cues from the Dantec EMG amplifier and speaker. The three channels of EMG activity were also sent from the amplifier through an A/D converter (WIN-30 data acquisition board, United Electronics, Watertown, MA) to a personal computer. The signals were sampled at 25.6 kHz using DasyLab software and were stored for further analysis. A customized program was used to identify distinct motor units using a template-matching algorithm [33]. This technique also allowed for the identification of multiple action potentials that were temporally superimposed upon one another. Trained operators manually corrected for any computational errors or misidentifications to ensure 100% accurate identification. Those motor units active both before and after the application of vibration were identified and referred to as control units [18]. The vibration evokes the tonic vibratory reflex, (TVR) which results in the recruitment of additional motor units during vibration. Those newly recruited motor units that demonstrated selfsustained firing by continuing to fire after the vibration had been removed, were identified and referred to as test units.
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ended until the start of the ramp down in force (post). For the test units this included a period of stable force in the post-vibration interval only, from the time vibration ended until the start of the ramp down in force. Doublets (inter-firing intervals of less than 10 ms) were included in these calculations, though such doublets were rare in this experiment. Long intervals (inter-firing intervals greater than 200 ms) were excluded for both control and test units. 2.6. Statistical analysis t-Tests were used to examine possible differences in several measures, both between the older and young groups and pre and post-vibration. Differences between groups were investigated using independent t-tests for the measures of MVC force, percent occurrence of self-sustained firing, firing rates of control and test motor units, and the force level at which the test units dropped out. Differences in force and firing rate of the control motor unit pre and post-vibration were also investigated in the young and older subjects using paired-sample t-tests. Effect size (ES) was evaluated using procedures described by Thomas and Nelson [38].
3. Results 3.1. Force The mean (±SD) MVC values for the young and older groups were 165.7 ± 36.19 N and 143.8 ± 24.93 N, respectively. There were no significant differences in MVC between these two groups (p > 0.05; ES = 0.68). The mean force of the young and older groups pre and post-vibration is displayed in Fig. 1. No significant differences were found in the force pre and post-vibration in either the older (p > 0.05; ES = 0.06) or young group (p > 0.05; ES = 0.27).
2.5. Motor unit firing rates Mean firing rates of motor units were calculated during periods of steady force for both control and test units. For the control units this included intervals of stable force from the time 10% MVC was reached up until the start of vibration (pre) and from the time vibration
Fig. 1. Mean and standard deviation of the force exerted by the young (Y) and older (O) groups during the 10% MVC contractions. Data are presented pre (white bars) and post-vibration (solid bars). No change in force was observed in either group as a result of the vibration stimulus.
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3.2. Self-sustained firing and MU firing rates Sample behavior of a control motor unit which began firing before the vibration and a test motor unit which began firing after the vibration are presented in Fig. 2. Note the continuous, self-sustained firing of a newly recruited motor unit after removal of the vibration. This self-sustained firing behavior was observed in 22.8% (29/127) of the trials in the young subjects and in 23.1% (25/108) of the trials in the older subjects. There was no significant difference in the frequency of occurrence of self-sustained firing between the two groups (p > 0.05; ES = 0.02). In the trials in which self-sustained firing was observed, there were no significant differences in the mean firing rates of the control units pre and post vibration, in either the older (p > 0.05; ES = 0.06) or young group (p > 0.05; ES = 0.04). Mean firing rates of the control units pre and post-vibration are presented for each group in Fig. 3. The overall mean firing rate of the control unit in the young subjects was 12.32 ± 2.80 Hz, which was not significantly different from that of the older subjects at 10.61 ± 2.22 Hz (p > 0.05; ES = 0.98). The mean firing rate of the test motor units in the young group was 13.03 ± 11.58 Hz. Although the mean firing rate of the test unit in the older group was slightly lower at 10.25 ± 2.01 Hz, this difference was not statistically significant (p > 0.05; ES = 0.51). The percent MVC at which the test unit dropped out was also not significantly different between the two groups (p > 0.05;
Fig. 3. Mean and standard deviation of the firing rates of control motor units for the young (Y) and older (O) groups. Data are presented pre- (white bars) and post-vibration (solid bars). That control unit firing rate remained constant before and after the vibration stimulus is evidence that central drive to the motoneuron pool did not change.
ES = 0.31). The mean dropout force level was 2.43 ± 2.29% MVC for the young group, and 3.26 ± 3.24% MVC for the older group.
4. Discussion Until recently, motoneuron activity was thought to be regulated by a passive process involving purely synaptic activation. The algebraic sum of the EPSPs and IPSPs impinging on the motoneuron soma and dendrites was thought to determine the probability of action potential occurrence. Now, it has been well demonstrated that an active process is operative as well. This active
Fig. 2. Sample recording showing of evidence of self-sustained firing. Vertical bars represent individual firings of the control (lower) and test (upper) motor units. Sample MUAPs of the control and test units are shown in the insets. Note that the test unit does not fire prior to vibration, and continues to fire after the removal of the vibration stimulus. Superimposed on the control unit firing is the force trace from this trial.
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process involves the appearance of a prolonged state of depolarization resulting in plateau potentials. It appears that plateau potentials serve to amplify and lengthen motoneuron activity following synaptic input. The self-sustained firing behavior produced by plateau potentials seems to be a ubiquitous phenomenon, having been observed now in a number of species, as well as a number of cellular systems. Plateau potentials have been observed in both invertebrates [12,37] and vertebrate species, in a wide variety of central nervous system neurons, such as the subthalamus [36], the lateral geniculate nucleus [34], the striatum [13], the hippocampus [29], pancreatic islet cells [11], the cerebellum [6], and in neocortical pyramidal cells [9]. That plateau potentials may be an active mechanism during voluntary movement is suggested by the data of Eken and Kiehn [15]. Motor units in unrestrained rats displayed a type of bistable behavior in which units shifted their firing frequency between 9–12 pps and 20–25 pps. Self-sustained firing behavior has also been observed in motoneurons repeatedly activated over a short time interval [17]. The paired-unit recording technique has now been used in several studies to demonstrate self-sustained firing in human motor units [18,25]. The control unit is used as an indicator of the common drive to the motoneuron pool. Since motor units tend to increase and decrease their firing rates in a temporally locked fashion, it is reasonable to expect that the synaptic influences on one motoneuron (the control unit) should be similar to those of another concurrently active motoneuron (the test unit), unless there are other competitive influences on the second motoneuron. That the test unit continued firing many seconds after the vibration ceased is evidence of self-sustained firing in the test motor unit. The fact that the test unit discharge activity continued even after the force (and thus the central drive) was reduced, is further evidence of self-sustained firing in the test motor unit. The frequency of self-sustained firing behavior observed in the present study (23%) is consistent with the 35% frequency of occurrence observed in a sample of feline motoneurons [32]. The frequency of SSF is somewhat noteworthy considering that the Lee and Heckman study [32] involved a decerebrate preparation in which SSF might be easier to elicit. Bistable discharge behavior characteristic of motoneurons displaying plateau potentials is easier to elicit in low-threshold motoneurons [3]. Older adults typically exhibit a loss of large motoneurons [30], so one might have expected selfsustained discharge behavior to be exhibited more often in older adults than in young adults. Other evidence exists to support the idea that selfsustained firing may differ in young and older adults. There are a number of known changes in Ca++ that impact the aging process [40] and these factors could
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potentially affect the probability of self-sustained firing. The generation of plateau potentials is controlled by neuromodulators, particularly norepinephrine and serotonin [10,20] released from cells originating in the brainstem. These neuromodulators exist in reduced concentration in the aged spinal cord [27] and cerebral cortex [31]. Thus, on the basis of neuromodulator concentration, one might expect the probability of selfsustained firing to be lower in older adults than in young adults. The serotonergic descending system is likely tonically active in the human, as it is in the decerebrate cat [20]. These pathways would be most useful in situations requiring tonic activity, such as standing and other postural control tasks. These are activities that are frequently required in both older and young adults. Thus, it is logical to expect that these pathways would frequently be used in both groups of subjects. Since norepinephrine and serotonin are in reduced supply, at least in aged rat motoneurons, the presence of selfsustained firing in equal frequency in both young and older adults is an interesting finding. One possibility is that the levels in human serotonergic and noradrenergic systems is different from what it is in the rat, and that the concentrations are quite adequate in the aging human. A second possibility is that only small concentrations of these neuromodulators are required to modify human motoneurons and produce plateau potentials. The density of axosomatic synapses is reduced in aged rats [28], leading to the speculation that descending influences on motoneuron dendrites may be reduced as well. A related possibility is that human motoneurons are adaptive, and that the L-type Ca++ channels are more sensitive to these neuromodulators in aging humans. This might represent a type of compensatory behavior in the aging motoneuron, to maintain self-sustained firing behavior in the reduced monoamine environment. A previous observation involving motor unit discharge behavior in older adults further suggests the possibility that self-sustained firing may be an active phenomenon in older humans. During an active voluntary contraction, individual motor units sometimes exhibited prolonged firing, and were derecruited at muscular forces considerable lower than the recruitment force [23]. These and other observations (cited above) led to the possibility that plateau potentials might be responsible for some motor behavior in older adults. In the present study, evidence of self-sustained firing was seen in an appreciable proportion of trials. In order to record single motor unit action potentials, the electrode configuration we used was intentionally selective. Indeed, self-sustained firing behavior might have been observed even more often, had we recorded from many more motor units in the muscle, perhaps from multiple
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sites. One factor which may have determined whether SSF behavior was observed may have been whether the electrode was placed in an area favorable for new recruitment of motor units with recruitment thresholds close to that of the control unit. Nearby high-threshold motor units are less likely to be recruited by the additional Ia input from the vibration stimulus. In the present study, no differences in maximal dorsiflexion strength were observed between young and older adults. Many studies have reported an age-related loss in muscular strength, including dorsiflexion strength [2,43]. However, there are exceptions. Kent-Braun et al. [24] found no differences in dorsiflexion force between young and older sedentary adults. Similar results were reported by Horstmann et al. [19]. Over a 12-yrperiod, Winegard et al. [42] noted that the rate of strength loss is considerably less in the dorsiflexors than in the plantarflexors. It would seem that differences in maximal dorsiflexion force between the two subject groups probably bear little on the present results. The task of producing a maximal contraction involves large contraction forces and large numbers of motor units. The present study was conducted at relatively low contraction forces, and utilized relatively small numbers of motor units. We conclude that self-sustained firing is a pattern of motor unit discharge behavior that seems to be present in both older and young adults. Indeed, such selfsustained firing behavior is a ubiquitous phenomenon present in both invertebrate and vertebrate species and in a variety of CNS systems. Older adults may benefit from the role that such self-sustained firing may play, in allowing motoneuron activity in the presence of minimal synaptic input, particularly in postural control activities.
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Gary Kamen received his Ph.D. in Exercise Science from the University of Massachusetts. Following academic appointments at Indiana University and Boston University, he joined the Department of Exercise Science at UMass-Amherst in 1995. Dr. KamenÕs area of expertise is Human Motor Control. His research activities have been designed to understand how processes such as long-term exercise and aging produce adaptations in the neuromuscular system. These projects, supported by NIH and other sponsors, have culminated in the publication of over 100 books, book chapters, articles and research abstracts at national and international meetings. He has served as a reviewer for over 20 journals and numerous granting agencies. He is currently a Fellow of the Research Consortium, AAHPERD, the American College of Sports Medicine, and the American Academy of Kinesiology and Physical Education. Ryan Sullivan is an exercise physiologist at Fitcorp in Boston, Ma. He received his BS in Exercise Science from the University of Massachusetts-Amherst in 2003. His senior thesis in the Exercise Neuroscience laboratory involved the study of intrinsic motor unit properties in young and older adults.
Scott Rubinstein is a research specialist in the Spinal Cord Injury Center at the Department of Veterans Affairs Health Care System in Palo Alto, CA. He received his BS in Kinesiology from the University of Texas at Austin in 2000, and his MS in Exercise Science in 2004 from the University of Massachusetts at Amherst. As a student in the Exercise Neuroscience laboratory, his focus was in motor unit behavior in older adults during neuromuscular fatigue. He presented these results at the biennial conference of the International Society of Electrophysiology and Kinesiology in Boston, MA in 2004. Additional research consisted of intrinsic motor unit properties as well a firing rate behavior during ramping muscle contractions. Anita Christie received a B.Sc. in Neuroscience and an M.Sc. in Applied Health Sciences from Brock University. She is currently a doctoral student in the Exercise Science Department at the University of Massachusetts, Amherst, under the supervision of Dr. Gary Kamen. Her research is primarily focused on aging and the neuromuscular control of movement.
Evidence of self-sustained motoneuron firing in young and older adults Gary Kamen *, Ryan Sullivan, Scott Rubinstein, Anita Christie Department of Exercise Science, Totman 160A, University of Massachusetts – Amherst, Amherst, MA 01003, United States Received 15 December 2004; received in revised form 31 May 2005; accepted 9 June 2005
Abstract Motoneurons demonstrate a type of self-sustained firing behavior that seems to be produced by a prolonged period of depolarization caused by intrinsic long-term changes in the motoneuron. Such self-sustained firing behavior has previously been reported in human motor units. The purpose of the present study was to investigate the occurrence of self-sustained firing behavior in older adults. Eight young (mean age 24 yrs) and eight older (mean age 73 yrs) individuals participated in the investigation. While subjects produced light dorsiflexion contractions, a brief vibration stimulus was applied to the tibialis anterior muscle. Motor unit recordings were also obtained from the tibialis anterior muscle. Self-sustained firing behavior was evidenced by the appearance of new motor unit recruitment following vibration, even as the motor units that fired before the vibratory stimulus maintained a steady firing rate. The proportion of motor units exhibiting self-sustained firing activity was similar in both young and older adults (approx. 23% of trials). We conclude that self-sustained firing behavior is a ubiquitous phenomenon that does not seem to be affected by the aging process. Ó 2005 Elsevier Ltd. All rights reserved. Keywords: Motor unit; Vibration; Plateau potentials; Aging; Tibialis anterior
1. Introduction It has now been well demonstrated that motoneurons exhibit a type of bistable firing behavior. Short bursts of excitation initiate long periods of self-sustained firing. These periods of motoneuron activity that occur in the absence of synaptic input can be extinguished by a short burst of inhibitory potentials. Self-sustained firing behavior has been demonstrated in several animal species [4,16,21], as well as in humans [18,35]. Self-sustained firing behavior is generally believed to be produced by ‘‘plateau potentials’’ (cf. [8,26]) manifested as a sustained period of depolarization in a *
Corresponding author. Tel.: +1 413 545 0784; fax: +1 413 545 2906. E-mail address: [email protected] (G. Kamen). 1050-6411/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.jelekin.2005.06.008
neuron. Inward Ca++-mediated currents produced by L-type Ca++ channels are responsible for these prolonged depolarizations. Thus, plateau potentials represent a change in the intrinsic properties of motoneurons and are thought to serve the function of amplifying synaptic input [22]. There are several changes that have been noted in aged motoneurons that could impact the proportion of motor units that exhibit self-sustained firing in older humans. Changes have been noted in the passive properties of motoneurons in aged animals. Motoneuron input resistance increases in old cats, although there seems to be no change in resting membrane potential or spike amplitude [7]. Ca++ influx into the motor nerve terminal increases with advancing age [1]. On the other hand, the duration of striatal Ca++-mediated plateau potentials is decreased in aged animals [13]. Changes in Ca++
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kinetics, then, could be the source of either an increase or a decrease in self-sustained motor unit firing in older humans [40]. An increase in the prevalence of self-sustained firing in older individuals, for example, might serve as a compensatory mechanism for the age-related loss of motor neurons [39,44], the diminution in function of the Ia-motoneuron monosynaptic EPSP [5], and/or the loss of corticomotoneuron connections [14]. Self-sustained firing has been observed in human motoneurons [18]. In a typical protocol, subjects are asked to produce a light voluntary contraction. Additional input is then supplied to the motoneuron pool, such as from an external vibratory stimulus which provides additional motoneuron drive via the Ia-amotoneuron synapse. The recruitment of new motor units which remain active when the vibration stimulus is removed is evidence of self-sustained firing. Previous studies have demonstrated that self-sustained firing can be modified by monoamine concentration in human motoneurons [41]. The purpose of this study was to determine whether self-sustained firing is present in older adults.
2. Methods 2.1. Subjects Eight older (mean age = 73.0 yrs) and eight young (mean age = 23.8 yrs) females, free of neurological and cardiovascular disorders participated in this investigation. All subjects were moderately active, as assessed with a Physical Activity Response Questionnaire. The procedures used in this investigation were reviewed and approved by the Human Ethics Review Board at the University of Massachusetts – Amherst. All participants signed an informed consent document prior to testing. 2.2. Procedures Each participant visited the Exercise Neuroscience Laboratory on one occasion for testing. Subjects were seated in a custom-made chair designed for measuring force during isolated isometric dorsiflexion contraction. The hip and knee of the dominant leg were maintained at 90° with adjustable straps placed across the waist and thigh, and with a metal brace placed over the anterior distal femur, superior to the patella. A flat metal bar wrapped in foam padding was tightened over the distal metatarsal, providing an immovable resistance for isometric dorsiflexion. The ankle and foot were also secured with a foam brace to restrict any antero-posterior or medio-lateral displacement. The non-dominant foot was placed on a box covered in foam padding to prevent using resistance in this leg to enhance force. Subjects
were instructed to sit erect with arms folded across the abdomen during all dorsiflexion trials. At the beginning of the session, each subjectÕs maximal voluntary force during dorsiflexion was determined. Subjects were asked to perform three maximal voluntary contractions (MVCs) of the tibialis anterior (TA), with 2 min rest between each trial. The maximum force value achieved across the three trials was deemed the MVC force value, and subsequent tasks were scaled to this value. A trace was then presented to subjects on a computer screen. The trace consisted of a 5-s preparatory period with the subject relaxed, a 3-s ramp up to 10% MVC, a period of 11 s at a constant force of 10% MVC, and a 3-s ramp down to 0% MVC. On the same screen the real-time force output of the subjects was displayed as a moving red line. Subjects were instructed to match the requisite force trajectory by gradually producing an isometric dorsiflexion contraction to increase force to 10% MVC, holding a constant 10% MVC contraction for 11 s, then slowly decreasing force to zero. During the constant force phase, a 100 Hz vibration was applied to the distal TA using a therapeutic vibrator (Zeniter TVR TMT-18, Heiwa Electronic Industrial Co. Ltd., Japan). Vibration was applied for 1 s, approximately 4–6 cm below the needle insertion site. The site for vibration was marked with a pen to ensure accurate placement of the vibrator with each trial. The vibration was applied between the 14th and the 15th second of the contraction when subjects were holding a 10% MVC effort. Subjects were given 5–10 practice trials, until they felt comfortable with the task and with the vibration. Each subject then completed 10–15 trials for recording, until 10 trials with accurate force traces and clear MUAPs were achieved. 2.3. Force recordings Isometric force was applied by subjects in an axis parallel to dorsiflexion, against the flat metal bar over the distal metatarsals. The force exerted during dorsiflexion was measured by a strain gauge force transducer (Interface Model MB-10, Scotsdale, AZ) secured to each side of the immovable metal bar. The force signal was amplified using a custom-built bridge amplifier. The signal was sent to an A/D converter (Data Translation Model DT 2801) and was sampled at 50 Hz on a personal computer. This signal was used to provide real-time feedback of force output to subjects using DasyLab software (Data Acquisition System Laboratory, DasyTec USA, Inc., Amherst, NH). The force signal was also sent to a second A/D converter (WIN-30 data acquisition board, United Electronics, Watertown, MA) and sampled at 50 Hz on a second personal computer, using DasyLab software to store the data for analysis.
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2.4. Motor unit recordings Intramuscular EMG activity was recorded from the TA using a 25-gauge stainless steel needle electrode. This electrode contained a cannula housing four platinum– iridium wires in a square array, terminating at a side port 7.5 mm from the tip. Each wire had a diameter of 50 lm, with 200 lm between wires. This configuration provided three separate channels of motor unit action potential (MUAP) data, based on the geometric orientation of the muscle fibers to the electrode recording site [33]. The needle was inserted approximately one half of the distance between the lateral malleolus and the tibial tuberosity. A stainless steel plate electrode was taped to the lateral surface of the patella of the dominant knee, which served as a ground electrode. The intramuscular EMG signals were amplified through a Dantec Counterpoint Electromyograph (Dantec Electronik Medicinsk, Skovlunde, Denmark) and viewed on a digital oscilloscope (Gould 2608 Thermo Electron Corporation, Valley View, OH). The proper position of the needle within the muscle was determined by high frequency MUAP activity during a 20% MVC contraction. This activity was assessed visually by the appearance of distinct action potentials on the oscilloscope, and audibly by cues from the Dantec EMG amplifier and speaker. The three channels of EMG activity were also sent from the amplifier through an A/D converter (WIN-30 data acquisition board, United Electronics, Watertown, MA) to a personal computer. The signals were sampled at 25.6 kHz using DasyLab software and were stored for further analysis. A customized program was used to identify distinct motor units using a template-matching algorithm [33]. This technique also allowed for the identification of multiple action potentials that were temporally superimposed upon one another. Trained operators manually corrected for any computational errors or misidentifications to ensure 100% accurate identification. Those motor units active both before and after the application of vibration were identified and referred to as control units [18]. The vibration evokes the tonic vibratory reflex, (TVR) which results in the recruitment of additional motor units during vibration. Those newly recruited motor units that demonstrated selfsustained firing by continuing to fire after the vibration had been removed, were identified and referred to as test units.
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ended until the start of the ramp down in force (post). For the test units this included a period of stable force in the post-vibration interval only, from the time vibration ended until the start of the ramp down in force. Doublets (inter-firing intervals of less than 10 ms) were included in these calculations, though such doublets were rare in this experiment. Long intervals (inter-firing intervals greater than 200 ms) were excluded for both control and test units. 2.6. Statistical analysis t-Tests were used to examine possible differences in several measures, both between the older and young groups and pre and post-vibration. Differences between groups were investigated using independent t-tests for the measures of MVC force, percent occurrence of self-sustained firing, firing rates of control and test motor units, and the force level at which the test units dropped out. Differences in force and firing rate of the control motor unit pre and post-vibration were also investigated in the young and older subjects using paired-sample t-tests. Effect size (ES) was evaluated using procedures described by Thomas and Nelson [38].
3. Results 3.1. Force The mean (±SD) MVC values for the young and older groups were 165.7 ± 36.19 N and 143.8 ± 24.93 N, respectively. There were no significant differences in MVC between these two groups (p > 0.05; ES = 0.68). The mean force of the young and older groups pre and post-vibration is displayed in Fig. 1. No significant differences were found in the force pre and post-vibration in either the older (p > 0.05; ES = 0.06) or young group (p > 0.05; ES = 0.27).
2.5. Motor unit firing rates Mean firing rates of motor units were calculated during periods of steady force for both control and test units. For the control units this included intervals of stable force from the time 10% MVC was reached up until the start of vibration (pre) and from the time vibration
Fig. 1. Mean and standard deviation of the force exerted by the young (Y) and older (O) groups during the 10% MVC contractions. Data are presented pre (white bars) and post-vibration (solid bars). No change in force was observed in either group as a result of the vibration stimulus.
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3.2. Self-sustained firing and MU firing rates Sample behavior of a control motor unit which began firing before the vibration and a test motor unit which began firing after the vibration are presented in Fig. 2. Note the continuous, self-sustained firing of a newly recruited motor unit after removal of the vibration. This self-sustained firing behavior was observed in 22.8% (29/127) of the trials in the young subjects and in 23.1% (25/108) of the trials in the older subjects. There was no significant difference in the frequency of occurrence of self-sustained firing between the two groups (p > 0.05; ES = 0.02). In the trials in which self-sustained firing was observed, there were no significant differences in the mean firing rates of the control units pre and post vibration, in either the older (p > 0.05; ES = 0.06) or young group (p > 0.05; ES = 0.04). Mean firing rates of the control units pre and post-vibration are presented for each group in Fig. 3. The overall mean firing rate of the control unit in the young subjects was 12.32 ± 2.80 Hz, which was not significantly different from that of the older subjects at 10.61 ± 2.22 Hz (p > 0.05; ES = 0.98). The mean firing rate of the test motor units in the young group was 13.03 ± 11.58 Hz. Although the mean firing rate of the test unit in the older group was slightly lower at 10.25 ± 2.01 Hz, this difference was not statistically significant (p > 0.05; ES = 0.51). The percent MVC at which the test unit dropped out was also not significantly different between the two groups (p > 0.05;
Fig. 3. Mean and standard deviation of the firing rates of control motor units for the young (Y) and older (O) groups. Data are presented pre- (white bars) and post-vibration (solid bars). That control unit firing rate remained constant before and after the vibration stimulus is evidence that central drive to the motoneuron pool did not change.
ES = 0.31). The mean dropout force level was 2.43 ± 2.29% MVC for the young group, and 3.26 ± 3.24% MVC for the older group.
4. Discussion Until recently, motoneuron activity was thought to be regulated by a passive process involving purely synaptic activation. The algebraic sum of the EPSPs and IPSPs impinging on the motoneuron soma and dendrites was thought to determine the probability of action potential occurrence. Now, it has been well demonstrated that an active process is operative as well. This active
Fig. 2. Sample recording showing of evidence of self-sustained firing. Vertical bars represent individual firings of the control (lower) and test (upper) motor units. Sample MUAPs of the control and test units are shown in the insets. Note that the test unit does not fire prior to vibration, and continues to fire after the removal of the vibration stimulus. Superimposed on the control unit firing is the force trace from this trial.
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process involves the appearance of a prolonged state of depolarization resulting in plateau potentials. It appears that plateau potentials serve to amplify and lengthen motoneuron activity following synaptic input. The self-sustained firing behavior produced by plateau potentials seems to be a ubiquitous phenomenon, having been observed now in a number of species, as well as a number of cellular systems. Plateau potentials have been observed in both invertebrates [12,37] and vertebrate species, in a wide variety of central nervous system neurons, such as the subthalamus [36], the lateral geniculate nucleus [34], the striatum [13], the hippocampus [29], pancreatic islet cells [11], the cerebellum [6], and in neocortical pyramidal cells [9]. That plateau potentials may be an active mechanism during voluntary movement is suggested by the data of Eken and Kiehn [15]. Motor units in unrestrained rats displayed a type of bistable behavior in which units shifted their firing frequency between 9–12 pps and 20–25 pps. Self-sustained firing behavior has also been observed in motoneurons repeatedly activated over a short time interval [17]. The paired-unit recording technique has now been used in several studies to demonstrate self-sustained firing in human motor units [18,25]. The control unit is used as an indicator of the common drive to the motoneuron pool. Since motor units tend to increase and decrease their firing rates in a temporally locked fashion, it is reasonable to expect that the synaptic influences on one motoneuron (the control unit) should be similar to those of another concurrently active motoneuron (the test unit), unless there are other competitive influences on the second motoneuron. That the test unit continued firing many seconds after the vibration ceased is evidence of self-sustained firing in the test motor unit. The fact that the test unit discharge activity continued even after the force (and thus the central drive) was reduced, is further evidence of self-sustained firing in the test motor unit. The frequency of self-sustained firing behavior observed in the present study (23%) is consistent with the 35% frequency of occurrence observed in a sample of feline motoneurons [32]. The frequency of SSF is somewhat noteworthy considering that the Lee and Heckman study [32] involved a decerebrate preparation in which SSF might be easier to elicit. Bistable discharge behavior characteristic of motoneurons displaying plateau potentials is easier to elicit in low-threshold motoneurons [3]. Older adults typically exhibit a loss of large motoneurons [30], so one might have expected selfsustained discharge behavior to be exhibited more often in older adults than in young adults. Other evidence exists to support the idea that selfsustained firing may differ in young and older adults. There are a number of known changes in Ca++ that impact the aging process [40] and these factors could
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potentially affect the probability of self-sustained firing. The generation of plateau potentials is controlled by neuromodulators, particularly norepinephrine and serotonin [10,20] released from cells originating in the brainstem. These neuromodulators exist in reduced concentration in the aged spinal cord [27] and cerebral cortex [31]. Thus, on the basis of neuromodulator concentration, one might expect the probability of selfsustained firing to be lower in older adults than in young adults. The serotonergic descending system is likely tonically active in the human, as it is in the decerebrate cat [20]. These pathways would be most useful in situations requiring tonic activity, such as standing and other postural control tasks. These are activities that are frequently required in both older and young adults. Thus, it is logical to expect that these pathways would frequently be used in both groups of subjects. Since norepinephrine and serotonin are in reduced supply, at least in aged rat motoneurons, the presence of selfsustained firing in equal frequency in both young and older adults is an interesting finding. One possibility is that the levels in human serotonergic and noradrenergic systems is different from what it is in the rat, and that the concentrations are quite adequate in the aging human. A second possibility is that only small concentrations of these neuromodulators are required to modify human motoneurons and produce plateau potentials. The density of axosomatic synapses is reduced in aged rats [28], leading to the speculation that descending influences on motoneuron dendrites may be reduced as well. A related possibility is that human motoneurons are adaptive, and that the L-type Ca++ channels are more sensitive to these neuromodulators in aging humans. This might represent a type of compensatory behavior in the aging motoneuron, to maintain self-sustained firing behavior in the reduced monoamine environment. A previous observation involving motor unit discharge behavior in older adults further suggests the possibility that self-sustained firing may be an active phenomenon in older humans. During an active voluntary contraction, individual motor units sometimes exhibited prolonged firing, and were derecruited at muscular forces considerable lower than the recruitment force [23]. These and other observations (cited above) led to the possibility that plateau potentials might be responsible for some motor behavior in older adults. In the present study, evidence of self-sustained firing was seen in an appreciable proportion of trials. In order to record single motor unit action potentials, the electrode configuration we used was intentionally selective. Indeed, self-sustained firing behavior might have been observed even more often, had we recorded from many more motor units in the muscle, perhaps from multiple
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sites. One factor which may have determined whether SSF behavior was observed may have been whether the electrode was placed in an area favorable for new recruitment of motor units with recruitment thresholds close to that of the control unit. Nearby high-threshold motor units are less likely to be recruited by the additional Ia input from the vibration stimulus. In the present study, no differences in maximal dorsiflexion strength were observed between young and older adults. Many studies have reported an age-related loss in muscular strength, including dorsiflexion strength [2,43]. However, there are exceptions. Kent-Braun et al. [24] found no differences in dorsiflexion force between young and older sedentary adults. Similar results were reported by Horstmann et al. [19]. Over a 12-yrperiod, Winegard et al. [42] noted that the rate of strength loss is considerably less in the dorsiflexors than in the plantarflexors. It would seem that differences in maximal dorsiflexion force between the two subject groups probably bear little on the present results. The task of producing a maximal contraction involves large contraction forces and large numbers of motor units. The present study was conducted at relatively low contraction forces, and utilized relatively small numbers of motor units. We conclude that self-sustained firing is a pattern of motor unit discharge behavior that seems to be present in both older and young adults. Indeed, such selfsustained firing behavior is a ubiquitous phenomenon present in both invertebrate and vertebrate species and in a variety of CNS systems. Older adults may benefit from the role that such self-sustained firing may play, in allowing motoneuron activity in the presence of minimal synaptic input, particularly in postural control activities.
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Gary Kamen received his Ph.D. in Exercise Science from the University of Massachusetts. Following academic appointments at Indiana University and Boston University, he joined the Department of Exercise Science at UMass-Amherst in 1995. Dr. KamenÕs area of expertise is Human Motor Control. His research activities have been designed to understand how processes such as long-term exercise and aging produce adaptations in the neuromuscular system. These projects, supported by NIH and other sponsors, have culminated in the publication of over 100 books, book chapters, articles and research abstracts at national and international meetings. He has served as a reviewer for over 20 journals and numerous granting agencies. He is currently a Fellow of the Research Consortium, AAHPERD, the American College of Sports Medicine, and the American Academy of Kinesiology and Physical Education. Ryan Sullivan is an exercise physiologist at Fitcorp in Boston, Ma. He received his BS in Exercise Science from the University of Massachusetts-Amherst in 2003. His senior thesis in the Exercise Neuroscience laboratory involved the study of intrinsic motor unit properties in young and older adults.
Scott Rubinstein is a research specialist in the Spinal Cord Injury Center at the Department of Veterans Affairs Health Care System in Palo Alto, CA. He received his BS in Kinesiology from the University of Texas at Austin in 2000, and his MS in Exercise Science in 2004 from the University of Massachusetts at Amherst. As a student in the Exercise Neuroscience laboratory, his focus was in motor unit behavior in older adults during neuromuscular fatigue. He presented these results at the biennial conference of the International Society of Electrophysiology and Kinesiology in Boston, MA in 2004. Additional research consisted of intrinsic motor unit properties as well a firing rate behavior during ramping muscle contractions. Anita Christie received a B.Sc. in Neuroscience and an M.Sc. in Applied Health Sciences from Brock University. She is currently a doctoral student in the Exercise Science Department at the University of Massachusetts, Amherst, under the supervision of Dr. Gary Kamen. Her research is primarily focused on aging and the neuromuscular control of movement.