Thomas M. Hamm

Force-Independent Distribution of Correlated Neural Inputs to Hand Muscles During Three-Digit Grasping

The ability to modulate digit forces during grasping relies on the coordination of multiple hand muscles. Because many muscles innervate each digit, the CNS can potentially choose from a large number of muscle coordination patterns to generate a given digit force. Studies of single-digit force production tasks have revealed that the electromyographic (EMG) activity scales uniformly across all muscles as a function of digit force. However, the extent to which this finding applies to the coordination of forces across multiple digits is unknown. We addressed this question by asking subjects (n = 8) to exert isometric forces using a three-digit grip (thumb, index, and middle fingers) that allowed for the quantification of hand muscle coordination within and across digits as a function of grasp force (5, 20, 40, 60, and 80% maximal voluntary force). We recorded EMG from 12 muscles (6 extrinsic and 6 intrinsic) of the three digits. Hand muscle coordination patterns were quantified in the amplitude and frequency domains (EMG-EMG coherence). EMG amplitude scaled uniformly across all hand muscles as a function of grasp force (muscle x force interaction: P = 0.997; cosines of angle between muscle activation pattern vector pairs: 0.897-0.997). Similarly, EMG-EMG coherence was not significantly affected by force (P = 0.324). However, coherence was stronger across extrinsic than that across intrinsic muscle pairs (P = 0.0039). These findings indicate that the distribution of neural drive to multiple hand muscles is force independent and may reflect the anatomical properties or functional roles of hand muscle groups.

Influence of Fatigue on Hand Muscle Coordination and EMG-EMG Coherence During Three-Digit Grasping

Fingertip force control requires fine coordination of multiple hand muscles within and across the digits. While the modulation of neural drive to hand muscles as a function of force has been extensively studied, much less is known about the effects of fatigue on the coordination of simultaneously active hand muscles. We asked eight subjects to perform a fatiguing contraction by gripping a manipulandum with thumb, index, and middle fingers while matching an isometric target force (40% maximal voluntary force) for as long as possible. The coordination of 12 hand muscles was quantified as electromyographic (EMG) muscle activation pattern (MAP) vector and EMG-EMG coherence. We hypothesized that muscle fatigue would cause uniform changes in EMG amplitude across all muscles and an increase in EMG-EMG coherence in the higher frequency bands but with an invariant heterogeneous distribution across muscles. Muscle fatigue caused a 12.5% drop in the maximum voluntary contraction force (P < 0.05) at task failure and an increase in the SD of force (P < 0.01). Although EMG amplitude of all muscles increased during the fatiguing contraction (P < 0.001), the MAP vector orientation did not change, indicating that a similar muscle coordination pattern was used throughout the fatiguing contraction. Last, EMG-EMG coherence (0-35 Hz) was significantly greater at the end than at the beginning of the fatiguing contraction (P < 0.01) but was heterogeneously distributed across hand muscles. These findings suggest that similar mechanisms are involved for modulating and sustaining digit forces in nonfatiguing and fatiguing contractions, respectively.

Characteristics and Organization of Discharge Properties in Rat Hindlimb Motoneurons

The discharge properties of hindlimb motoneurons in ketamine-xylazine anesthetized rats were measured to assess contributions of persistent intrinsic currents to these characteristics and to determine their distribution in motoneuron pools. Most motoneurons (30/37) responded to ramp current injections with adapting patterns of discharge and the frequency-current (f-I) relations of nearly all motoneurons included a steep subprimary range of discharge. Despite the prevalence of adapting f-I relations, responses included indications that persistent inward currents (PICs) were activated, including increased membrane noise and prepotentials before discharge, as well as counterclockwise hysteresis and secondary ranges in f-I relations. Examination of spike thresholds and afterhyperpolarization (AHP) trajectories during repetitive discharge revealed systematic changes in threshold and trajectory within the subprimary, primary, and secondary f-I ranges. These changes in the primary and secondary ranges were qualitatively similar to those described previously for cat motoneurons. Within the subprimary range, AHP trajectories often included shallow approaches to threshold following recruitment and slope of the AHP ramp consistently increased until the subprimary range was reached. We suggest that PICs activated near recruitment contributed to these slope changes and formation of the subprimary range. Discharge characteristics were strongly correlated with motoneuron size, using input conductance as an indicator of size. Discharge adaptation, recruitment current, and frequency increased with input conductance, whereas both subprimary and primary f-I gains decreased. These results are discussed with respect to potential mechanisms and their functional implications.

Persistent Currents and Discharge Patterns in Rat Hindlimb Motoneurons

We report here the first direct measurements of persistent inward currents (PICs) in rat hindlimb motoneurons, obtained from ketamine-xylazine anesthetized rats during slow voltage ramps performed by single-electrode somatic voltage clamp. Most motoneurons expressed PICs and current-voltage (I-V) relations often contained a negative-slope region (NSR; 13/19 cells). PICs activated at -52.7 ± 3.89 mV, 9 mV negative to spike threshold. NSR onset was -44.2 ± 4.1 mV. PIC amplitudes were assessed by maximum inward currents measured relative to extrapolated leak current and to NSR-onset current. PIC conductance at potentials just positive to activation was assessed by the relative change in slope conductance (g(in)/g(leak)). PIC amplitudes varied widely; some exceeded 5 and 10 nA relative to current at NSR onset or leak current, respectively. PIC amplitudes did not vary significantly with input conductance, but PIC amplitudes normalized by recruitment current decreased with increasing input conductance. Similarly, g(in)/g(leak) decreased with increasing input conductance. Currents near resting potential on descending limbs of I-V relations were often outward, relative to ascending-limb currents. This residual outward current was correlated with increases in leak conductance on the descending limb and with input conductance. Excluding responses with accommodation, residual outward currents matched differences between recruitment and derecruitment currents, suggesting a role for residual outward current in frequency adaptation. Comparison of potentials for PIC activation and NSR onset with interspike trajectories during discharge demonstrated correspondence between PIC activation and frequency-current (f-I) range boundaries. Contributions of persistent inward and outward currents to motoneuron discharge characteristics are discussed.

The use of Coherence Spectra to Determine Common Synaptic Inputs to Motoneurone Pools of the Cat During Fictive Locomotion

Our understanding of the organisation of the central commands directed to motoneurone pools during motor activity in mammals has been limited by the difficulty of determining the identity of segmental neurones that carry those commands to motoneurones. In rhythmic activities like locomotion, those commands are transmitted by interneuronal elements of spinal central pattern generators (CPG: Grillner, 1981; Gelfand, Orlovsky & Shik., 1988), whose identity and organisation remain to be determined. The present work was undertaken to investigate the organisation of the CPG for locomotion by determining which motoneurone pools receive a common synaptic input during locomotion, as indicated by patterns of synchronisation. Previous work suggests that synaptic inputs that are common to motoneurones are capable of producing a synchronised discharge of those motoneurones (Sears & Stagg, 1976; Kirkwood & Sears, 1978). The use of correlation methods in the time domain has demonstrated synchronisation between motoneurones in various forms of motor activity (Kirkwood, Sears, Tuck & Westgaard, 1982; Datta & Stephens, 1990).

Modulation of inhibitory strength and kinetics facilitates regulation of persistent inward currents and motoneuron excitability following spinal cord injury

Spasticity is commonly observed after chronic spinal cord injury (SCI) and many other central nervous system disorders (e.g., multiple sclerosis, stroke). SCI-induced spasticity has been associated with motoneuron hyperexcitability partly due to enhanced activation of intrinsic persistent inward currents (PICs). Disrupted spinal inhibitory mechanisms also have been implicated. Altered inhibition can result from complex changes in the strength, kinetics, and reversal potential (E(Cl(-))) of γ-aminobutyric acid A (GABA(A)) and glycine receptor currents. Development of optimal therapeutic strategies requires an understanding of the impact of these interacting factors on motoneuron excitability. We employed computational methods to study the effects of conductance, kinetics, and E(Cl(-)) of a dendritic inhibition on PIC activation and motoneuron discharge. A two-compartment motoneuron with enhanced PICs characteristic of SCI and receiving recurrent inhibition from Renshaw cells was utilized in these simulations. This dendritic inhibition regulated PIC onset and offset and exerted its strongest effects at motoneuron recruitment and in the secondary range of the current-frequency relationship during PIC activation. Increasing inhibitory conductance compensated for moderate depolarizing shifts in E(Cl(-)) by limiting PIC activation and self-sustained firing. Furthermore, GABA(A) currents exerted greater control on PIC activation than glycinergic currents, an effect attributable to their slower kinetics. These results suggest that modulation of the strength and kinetics of GABA(A) currents could provide treatment strategies for uncontrollable spasms.

Organization of recurrent inhibition and facilitation in motoneuron pools innervating dorsiflexors of the cat hindlimb

Abstract The incidence of recurrent inhibition and facilitation in motor nuclei innervating the dorsiflexors of the ankle and digits was examined in spinalized, decerebrate cats. Motoneurons innervating the anterior and posterior portions of the tibialis anterior (TAa and TAp, respectively) received strong recurrent inhibition following stimulation of either of the homonymous muscle nerves. Both motoneuron species received substantial recurrent inhibition from the semitendinosus (St), but stimulation of the nerve to the extensor digitorum longus (EDL), an ankle flexor synergist, evoked smaller recurrent IPSPs. TA motoneurons received mainly facilitation from hindlimb extensors of the hip and ankle. Motoneurons of the EDL and extensor digitorum brevis (EDB), synergists which share mechanical action at the metatarsophalangeal joint and the digits, received little recurrent inhibition in response to stimulation of the nerve to either muscle. Overall, stimulation of heteronymous flexor nerves (including TAa, TAp, and St) failed to evoke responses in most of the EDB and EDL neurons tested (50–83%), and the amplitude of recurrent inhibitory responses was small. Recurrent facilitation from the extensors was more common in these motor nuclei. Most responses recorded in EDB motoneurons following either flexor or extensor nerve stimulation were recurrent facilitations. The sensitivity of this facilitation in EDB motoneurons to injection of polarizing current and its central latency indicate that it is mediated by a disinhibitory, trisynaptic pathway. Stimulation of the nerve to EDB produced recurrent IPSPs in some flexor motoneurons, but these potentials were infrequent and their amplitude was usually small. Based on a comparison of the distribution of recurrent inhibition to published reports of the activities of TAa, TAp, EDL, and EDB during different forms of locomotion, we conclude that recurrent inhibition is large for motor nuclei that exhibit stereotypical activity, while motor nuclei that are activated independently receive and produce little recurrent inhibition. Despite the absence of recurrent inhibition in some motor nuclei, recurrent circuits may still participate in their control through disinhibitory, facilitatory mechanisms.

Assessment of across-muscle coherence using multi-unit vs. single-unit recordings

Coherence between electromyographic (EMG) signals has been used to identify correlated neural inputs to motor units (MUs) innervating different muscles. Simulations using a motor-unit model (Fuglevand et al. 1992) were performed to determine the ability of coherence between two multi-unit EMGs (mEMG) to detect correlated MU activity and the range of correlation strengths in which mEMG coherence can be usefully employed. Coherence between motor-unit and mEMG activities in two muscles was determined as we varied the strength of a 30-Hz periodic common input, the number of correlated MU pairs and variability of MU discharge relative to the common input. Pooled and mEMG coherence amplitudes positively and negatively accelerated, respectively, toward the strongest and most widespread correlating inputs. Furthermore, the relation between pooled and mEMG coherence was also nonlinear and was essentially the same whether correlation strength varied by changing common input strength or its distribution. However, the most important finding is that while the mEMG coherence saturates at the strongest common input strengths, this occurs at common input strengths greater than found in most physiological studies. Thus, we conclude that mEMG coherence would be a useful measure in many experimental conditions and our simulation results suggest further guidelines for using and interpreting coherence between mEMG signals.

Across-muscle coherence is modulated as a function of wrist posture during two-digit grasping.

The purpose of this study was to investigate the extent to which correlated neural inputs, quantified as EMG-EMG coherence across intrinsic and extrinsic hand muscles, varied as a function of wrist angle during a constant force precision grip task. Eight adults (5 males; mean age 29 years) participated in the experiment. Subjects held an object using a two-digit precision grip at a constant force at a flexed, neutral, and extended wrist posture, while the EMG activity from intrinsic and extrinsic hand muscles was recorded through intramuscular fine-wire electrodes. The integral of z-transformed coherence computed across muscles pairs was greatest in the flexed wrist posture and significantly greater than EMG-EMG coherence measured in the neutral and extended wrist posture (P < 0.01 and 0.05, respectively). Furthermore, EMG-EMG coherence did not differ statistically between the extrinsic and intrinsic muscle pairs, even though it tended to be greater for the extrinsic muscle pair (P ≥ 0.063). These findings lend support to the notion of a functional role of correlated neural inputs to hand muscles for the task-dependent coordination of hand muscle activity that is likely mediated by somatosensory feedback.

Differential contributions of somatic and dendritic calcium-dependent potassium currents to the control of motoneuron excitability following spinal cord injury

The hyperexcitability of alpha-motoneurons and accompanying spasticity following spinal cord injury (SCI) have been attributed to enhanced persistent inward currents (PICs), including L-type calcium and persistent sodium currents. Factors controlling PICs may offer new therapies for managing spasticity. Such factors include calcium-activated potassium (KCa) currents, comprising in motoneurons an after-hyperpolarization-producing current (IKCaN) activated by N/P-type calcium currents, and a second current (IKCaL) activated by L-type calcium currents (Li and Bennett in J neurophysiol 97:767–783, 2007). We hypothesize that these two currents offer differential control of PICs and motoneuron excitability based on their probable somatic and dendritic locations, respectively. We reproduced SCI-induced PIC enhancement in a two-compartment motoneuron model that resulted in persistent dendritic plateau potentials. Removing dendritic IKCaL eliminated primary frequency range discharge and produced an abrupt transition into tertiary range firing without significant changes in the overall frequency gain. However, IKCaN removal mainly increased the gain. Steady-state analyses of dendritic membrane potential showed that IKCaL limits plateau potential magnitude and strongly modulates the somatic injected current thresholds for plateau onset and offset. In contrast, IKCaN had no effect on the plateau magnitude and thresholds. These results suggest that impaired function of IKCaL may be an important intrinsic mechanism underlying PIC-induced motoneuron hyperexcitability following SCI.