Biomedical subjects

Monica A Gorassini

Publications and source records attributed to Monica A Gorassini.

5 recordsLinked to original sources

PubMed2006

Changes in cortically related intermuscular coherence accompanying improvements in locomotor skills in incomplete spinal cord injury.

In human spinal cord injury, the neuronal mechanisms mediating the improvement of locomotor function in response to intensive treadmill training are not well understood. In this study, we examined if such recovery is mediated, in part, by increases in residual corticospinal drive to muscles of the leg during walking. To do this, we measured the coherence of electromyogram (EMG) activity between two antagonist muscles (intermuscular coherence), specifically at frequencies between 24 and 40 Hz, which is thought to indicate common drive to two muscles from corticospinal inputs. In 12 subjects with incomplete spinal cord injury, intermuscular coherence was measured between hamstrings and vastus lateralis EMG that was activated during walking on a motorized treadmill. Before training, appreciable coherence in the 24-40 Hz frequency band was only present in subjects with moderate volitional motor strength in their leg muscles (n = 8 subjects) compared with subjects with little or no leg muscle strength (n = 4 subjects), reconfirming that 24-40 Hz frequency coherence is likely mediated by common supraspinal inputs. After training, increases in 24-40 Hz coherence only occurred in the eight subjects with moderate leg muscle strength who also exhibited improvements in locomotor recovery as assessed by the 21 point WISCI II scale (termed responders). In contrast, development of intermuscular coherence in the 24-40 Hz frequency band did not occur in the four subjects with absent or weak muscle strength. These subjects also did not improve in their locomotor ability as reflected in unchanging WISCI II scores (termed nonresponders). Lower-frequency coherence (5-18 Hz), which is thought to contain common drive from spinal inputs, did not change in either group. In a subset of subjects that were previously assessed with transcranial magnetic stimulation (TMS) before and after training (n = 5 responders and 3 nonresponders), there was a significant and positive relationship between increases in 24-40 Hz coherence and increases in evoked muscle responses to TMS of the primary motor cortex. Taken together, increases in higher-frequency EMG coherence in subjects with residual voluntary muscle strength and its parallel relation to changes in TMS-evoked responses provides further evidence that improvements in locomotor function from treadmill training are mediated, in part, by increases in corticospinal drive to muscles of the leg during walking.

Adult↗

PubMed2005

Increases in corticospinal tract function by treadmill training after incomplete spinal cord injury.

In this study, we examined if several months of intensive locomotor training increases the function of spared corticospinal tract pathways after chronic spinal cord injury (SCI) in association with the recovery of locomotor function. Transcranial magnetic stimulation (TMS) at incrementing levels of intensity was applied over the motor cortex supplying either the tibialis anterior or vastus lateralis muscles, and the resulting peak-to-peak amplitude of the motor-evoked potentials (MEPs) were measured to obtain a recruitment curve both before and after training. In the majority of subjects (7/8), 3-5 mo of daily intensive training increased the responses to TMS in at least one of the leg muscles tested (9/13). On average, across all muscles tested MEP(max), which was evoked at high stimulation intensities, increased by 46% and MEP(h), which was evoked at intermediate stimulation intensities, increased by 45% (both significantly different from 0), indicating an increase in corticospinal tract connectivity from training. The slope of the sigmoid function fit to the recruitment curve increased by 24% after training (significantly different), indicating an expansion and/or increased excitability of corticospinal circuits supplying muscles to the lower leg. We also observed that the average duration of the silent period measured at MEP(max) increased after training from 130 to 178 ms, suggesting that training had effects on cortical circuits thought to mediate this long-lasting inhibition. The percentage increase in MEP(max) was positively and significantly correlated to the degree of locomotor recovery as assessed by the WISCI II score, the distance a subject could walk in 6 min, and the amplitude of the locomotor EMG activity, suggesting that the corticospinal tract, in part, mediated the functional locomotor recovery produced from training.

Adult↗

PubMed2005

Persistent inward currents in motoneuron dendrites: implications for motor output.

The dendrites of motoneurons are not, as once thought, passive conduits for synaptic inputs. Instead they have voltage-dependent channels that provide the capacity to generate a very strong persistent inward current (PIC). The amplitude of the PIC is proportional to the level of neuromodulatory input from the brainstem, which is mediated primarily by the monoamines serotonin and norepinephrine. During normal motor behavior, monoaminergic drive is likely to be moderately strong and the dendritic PIC generates many of the characteristic features of motor unit firing patterns. Most of the PIC activates at or below recruitment threshold and thus motor unit firing patterns exhibit a linear increase just above recruitment. The dendritic PIC allows motor unit derecruitment to occur at a lower input level than recruitment, thus providing sustained tonic firing with little or no synaptic input, especially in low-threshold units. However the dendritic PIC can be readily deactivated by synaptic inhibition. The overall amplification due to the dendritic PIC and other effects of monoamines on motoneurons greatly increases the input-output gain of the motor pool. Thus the brainstem neuromodulatory input provides a mechanism by which the excitability of motoneurons can be varied for different motor behaviors. This control system is lost in spinal cord injury but PICs nonetheless recover near-normal amplitudes in the months following the initial injury. The relationship of these findings to the cause of the spasticity syndrome developing after spinal cord injury is discussed.

Action Potentials↗

PubMed2004

Role of motoneurons in the generation of muscle spasms after spinal cord injury.

Motoneurons in the spinal cord have intrinsic voltage-dependent persistent inward currents (PICs; e.g. persistent calcium currents) that amplify synaptic inputs by three- to five-fold in addition to providing a sustained excitatory drive that allows motoneurons to fire repetitively following a brief synaptic excitation. In this study, we examined whether prolonged involuntary muscle spasms in subjects with long-term injury to the spinal cord are mediated by the activation of PICs in the motoneuron. To examine this in the human, we used a paired motor unit analysis technique where the firing frequency of one motor unit of the pair (control unit) was used to estimate the synaptic drive to the motoneuron pool, including the drive to a second higher-threshold motor unit of the pair (test unit). The degree to which a motoneuron PIC helped to sustain the discharge of a test motor unit (self-sustained firing) was determined from the reduction in control unit firing at de-recruitment (DeltaF) compared with recruitment of the test unit. This DeltaF value corresponds to the reduction in synaptic drive needed to counteract the intrinsic PIC and, thus, was used an indirect measure of this current. In the nine motor unit pairs studied, the average estimated synaptic drive, or control unit firing rate, required to recruit a test motor unit at the onset of a muscle spasm was significantly higher (by 43%) than the estimated synaptic drive during de-recruitment at the end of a muscle spasm. This indicated that a motoneuron PIC, and associated self-sustained firing, facilitated the firing of the test units during the prolonged muscle spasms. In addition, in all subjects tested (seven out of seven), we observed that following a muscle spasm or voluntary contraction, spontaneous and self-sustained firing of motor units could continue for many seconds, even minutes, at very low discharge rates (average 5.2 +/- 1.6 Hz) with extremely low spike-to-spike variability (coefficient of variation = 5.4 +/- 1.6%). Moreover, increases in synaptic drive (noise) to the spontaneously firing units with voluntary muscle contractions or muscle spasms increased both the mean firing rate of the motor units in addition to their firing variability. This suggests that the slow spontaneous firing commonly observed in chronic spinal injury likely occurs without appreciable synaptic noise and is likely driven to a substantial degree by PICs intrinsic to the motoneuron because it is self-sustained and very regular.

Chronic Disease↗

PubMed2004

Role of persistent sodium and calcium currents in motoneuron firing and spasticity in chronic spinal rats.

After chronic spinal injury, motoneurons spontaneously develop two persistent inward currents (PICs): a TTX-sensitive persistent sodium current (sodium PIC) and a nimodipine-sensitive persistent calcium current (calcium PIC). In the present paper, we examined how these PICs contributed to motoneuron firing. Adult rats were spinalized at the S(2) sacral level, and after 2 months intracellular recordings were made from sacrocaudal motoneurons in vitro. The PICs and repetitive firing were measured with slow triangular voltage and current ramps, respectively. The sodium PIC was examined after blocking the calcium PIC with nimodipine (20 microM; n = 12). It was always activated subthreshold, and during current ramps in nimodipine, it produced a sodium plateau that assisted in initiating and maintaining firing (self-sustained firing). The sodium PIC oscillated off and on during firing and helped initiate each spike, and near threshold this caused abnormally slow firing (2.82 +/- 1.21 Hz). A low dose of TTX (0.5 microM) blocked the sodium PIC, sodium plateau, and very slow firing prior to affecting the spike itself. The calcium PIC was estimated as the current blocked by nimodipine or current remaining in TTX (2 microM; n = 13). In 59% of motoneurons, the calcium PIC was activated subthreshold to firing and produced a plateau that assisted in initiating and sustaining firing because nimodipine significantly increased the firing threshold current and decreased the self-sustained firing. In the remaining motoneurons (41%), the calcium PIC was activated suprathreshold to firing and during current ramps did not initially affect firing but eventually was activated and caused an acceleration in firing followed by self-sustained firing, which were blocked by nimodipine. The frequency-current (F-I) slope was 3.0 +/- 1.0 Hz/nA before the calcium PIC activation (primary range), 6.3 +/- 3.6 Hz/nA during the calcium PIC onset (secondary range; acceleration), and 2.1 +/- 1.3 Hz/nA with the calcium PIC steadily activated (tertiary range). Nimodipine eliminated the secondary and tertiary ranges, leaving a linear F-I slope of 3.7 +/- 1.0 Hz/nA. A single low-threshold shock to the dorsal root evoked a many-second-long discharge, the counterpart of a muscle spasm in the awake chronic spinal rat. This long-lasting reflex was caused by the motoneuron PICs because when the activation of the voltage-dependent PICs was prevented by hyperpolarization, the same dorsal root stimulation only produced a brief excitatory postsynaptic potential (<1 s). Both the calcium and sodium PIC were involved because nimodipine only partly reduced the reflex and there remained very slow firing mediated by the sodium PIC.

Action Potentials↗