Jayne M. Kalmar

Does elimination of afferent input modify the changes in rat motoneurone properties that occur following chronic spinal cord transection

The purpose of this study was to determine the effects of 6–8 weeks of chronic spinal cord isolation (SI, removal of descending, ascending and afferent inputs), compared with the same duration of spinal cord transection (ST, removal of descending input only) on hindlimb motoneurone biophysical properties. Adult female Sprague–Dawley rats were placed into three groups: (1) control (no removal of inputs), (2) ST and (3) SI. The electrophysiological properties from sciatic nerve motoneurones were recorded from deeply anaesthetized rats. Motoneurones in SI rats had significantly (P < 0.01) lower rheobase currents and higher spike afterhyperpolarization amplitudes and input resistances compared with motoneurones in control rats. A higher percentage (χ2, P= 0.01) of motoneurones in SI than control rats demonstrated frequency‐current (f–I) relationships consistent with activation of persistent inward currents. Motoneurone steady state f–I slopes determined by increasing steps of 500 ms current pulses were significantly lower (P < 0.02) in SI than control rats. Motoneurone spike frequency adaptation measured using 30 s square‐wave current injections (1.5–3.0 nA above the estimated rhythmic firing threshold), was similar for control and SI motoneurones. Changes in motoneurone properties following SI did not differ from ST. These findings indicate that the removal of afferent and ascending inputs along with descending inputs has little additional affect on motoneurone properties than removal of descending inputs alone. This study is the first to demonstrate that intact ascending and afferent input does not modify the effects of spinal transection on basic and rhythmic firing properties of rat hindlimb motoneurones.

Recovery of static stability following a concussion

The purpose of this study was to use centre of pressure (COP) measurements to determine if static balance deficits had recovered when concussed athletes were cleared to return to play. Nine concussed varsity football players were matched with nine teammates who served as controls. Static balance in the anterior-posterior (A/P) and medial-lateral (M/L) directions was assessed during quiet stance with eyes open and eyes closed. Results showed that concussed football players displayed greater A/P COP displacements in the acute phase, which recovered by RTP; however, COP velocity remained elevated compared to controls even at RTP, particularly in the A/P direction. This balance control deficit in the A/P direction may suggest vestibular impairment, likely due to poor sensorimotor integration of the lateral vestibulospinal tract. The observed persistence of balance control deficits in concussed football players at RTP are usually undetected by traditional assessments because the current study used higher-order COP analysis. Future RTP balance measures may want to incorporate higher-order measures of balance.

Cortical hypoexcitability persists beyond the symptomatic phase of a concussion

Abstract Primary objective: The purpose of this research was to assess cortical excitability, voluntary activation of muscle and force sensation beyond the initial highly symptomatic period post-concussion (1–4 weeks post-injury). It was hypothesized that reduced excitability of the motor cortex may impair muscle activation and alter perceptions of force and effort. Research design: Eight concussed varsity football players were age- and position-matched with eight healthy teammates to control for training and body size. Healthy controls had not suffered a concussion in the previous 12 months. Methods and procedures: Paired-pulse transcranial magnetic stimulation was used to assess cortical excitability, voluntary activation was calculated using cortical twitch interpolation technique and sense of force was determined using constant-force sensation contractions. Main outcomes and results: The concussed group had lower intra-cortical facilitation (p = 0.036), lower maximal voluntary muscle activation (p = 0.038) and greater perceptions of force (p < 0.05), likely due to compensatory increases in upstream drive, than their healthy matched teammates. Conclusions: Taken together, these findings suggest a state of hypoexcitability that persists beyond the immediate acute phase of a concussion and may result in neuromuscular impairments that would call to question the athlete’s readiness to return to sport.

Whole‐body hypothermia has central and peripheral influences on elbow flexor performance

The superimposed twitch technique was used to study the effect of whole‐body hypothermia on maximal voluntary activation of elbow flexors. Seven subjects [26.4 ± 4 years old (mean ± SD)] were exposed to 60 min of either immersion in 8°C water (hypothermia) or sitting in 22°C air (control). Voluntary activation was assessed during brief (3 s) maximal voluntary contractions (MVCs) and then during a 2 min fatiguing sustained MVC. Hypothermia (core temperature 34.8 ± 0.9°C) decreased maximal voluntary torque from 98.2 ± 1.0 to 82.8 ± 5.8% MVC (P < 0.001) and increased central conduction time from 7.9 ± 0.4 to 9.1 ± 0.7 ms (P < 0.05). Hypothermia also decreased maximal resting twitch amplitude from 17.6 ± 4.0 to 10.0 ± 1.7% MVC (P < 0.005) and increased the time‐to‐peak twitch tension from 55.4 ± 4.0 to 79.0 ± 11.7 ms (P < 0.001). During the 2 min contraction, hypothermia decreased initial torque (P < 0.01) but attenuated the subsequent rate of torque decline (control from 95.5 ± 4 to 29.4 ± 8% MVC; and hypothermia from 85.3 ± 8 to 37.3 ± 5% MVC; P < 0.01). Cortical superimposed twitches increased as fatigue developed but were always lower in the hypothermic conditions. Cortical superimposed twitches increased from a value of 0.4 ± 0.3% MVC prefatigue to 3.9 ± 1.4% MVC postfatigue (P < 0.001) in the hypothermic conditions and from 1.7 ± 0.9 to 5.5 ± 2.3% MVC in control conditions. Our results suggest that hypothermia decreases MVCs primarily via peripheral mechanisms and attenuates the rate of fatigue development by reducing central fatigue.

Caloric restriction does not offset age-associated changes in the biophysical properties of motoneurons.

Age-associated changes in neuromuscular function may be due to a loss of motor neurons as well as changes in their biophysical properties. Neuronal damage imposed by reactive oxygen species may contribute to age-related deficits in CNS function. Thus we hypothesized that aging would alter the functional properties of motoneurons and that caloric-restriction would offset these changes. Intracellular recordings were made from lumbar motoneurons of old Fisher Brown Norway (FBN) fed ad libitum (oldAL, 30.8+/-1.3 mo) or on a fortified calorie-restricted diet from 14 wk of age (oldCR, 31.0+/-1.8 mo). Basic and rhythmic firing properties recorded from these aged motoneurons (MNs) were compared with properties recorded from young FBN controls (young, 8.4+/-4.6 mo). Compared with young MNs, old MNs had a 104% greater (P<0.001) afterhyperpolarization potential (AHP), a 21.1% longer AHP half-decay time (P<0.05), 28.7% lower rheobase (P<0.001), 49.7% greater (P<0.001) input resistance, 21.1% (P<0.0001) less spike frequency adaptation, lower minimal (30.2%, P<0.0001) and maximal (16.7%, P<0.0001) steady-state firing frequencies, a lower (35.5%, P<0.0001) frequency-current slope, and an increased incidence of persistent inward current. Because basic properties became more diverse in old MNs and the slope of the frequency-current relationship, which is normally similar for high- and low-threshold MNs, was lower in the old group, we conclude that aging alters the biophysical properties of MNs in a fashion that cannot be simply attributed to a loss of high-threshold MNs. Surprisingly, caloric restriction, which is known to attenuate aging-associated changes in hindlimb muscles, had no effect on the progress of aging in the innervating MNs.

An evaluation of paired motor unit estimates of persistent inward current in human motoneurons

Persistent inward current (PIC) plays an important role in setting the input-output gain of motoneurons. In humans, these currents are estimated by calculating the difference between synaptic input at motor unit recruitment and derecruitment (ΔF) derived from paired motor unit recordings. The primary objective of this study was to use the relationship between reciprocal inhibition (RI) and PIC to estimate the contribution of PIC relative to other motoneuron properties that result in nonlinear motor unit firing behavior. This study also assessed the contribution of other intrinsic properties (spike threshold accommodation and spike frequency adaptation) to ΔF estimates of PIC in human motor units by using ramps with varying rates of rise and duration. It was hypothesized that slower rates of ramp rise and longer ramp durations would inflate ΔF estimates of PIC, and RI and PIC values would only be correlated during the ramp with the fastest rate of rise and shortest duration when spike threshold accommodation and spike frequency adaptation is minimized. Fourteen university-aged participants took part in this study. Paired motor unit recordings were made from the right soleus muscle during ramp contractions of plantar flexors with three different rates of rise and durations. ΔF estimates of PIC increased with decreased rates of ramp rise (P < 0.01) and increased ramp durations (P < 0.01), most likely due to spike frequency adaptation. A correlation (r = 0.41; P < 0.03) between ΔF and RI provides evidence that PIC is the primary contributor to ΔF in shorter ramps with faster rates of rise.

Dynamic stability and steering control following a sport-induced concussion

Loss of balance control is one of the cardinal symptoms following a concussion; however, the ability to detect the duration of these balance impairments seems to largely depend on task type and complexity. Typical balance assessment tools are simplistic and do not challenge dynamic balance control. Changing direction represents an internal perturbation that challenges the balance control system. The purpose of this study was to examine the effects of a concussion on dynamic stability and steering control. Nine male intercollegiate North American football players who experienced a concussion (CONC) were tested during the symptomatic phase (acute) and again once they had been cleared to return to play (RTP) while the controls (age- and position-matched teammates) were tested at a single time point coinciding with the acute phase testing of their matched injured player. All participants performed a steering task, requiring them to walk straight or turn in the direction of a visual cue located either 60° or 45° to the left or right of the centre line. CONC demonstrated increased swing time variability, segmental re-orientation variability, and the amount of time it took the centre of mass to reach the minimum lateral dynamic stability margin. These results suggest that CONC were more unstable and adopted a conservative gait strategy. Differences in the variability measures persisted even after the athlete was cleared to RTP. Overall, the findings reveal that intercollegiate football players with concussions have difficulty controlling temporal characteristics of gait, which cause dynamic instability to persist even at RTP.

Modulation of cortical excitability and interhemispheric inhibition prior to rhythmic unimanual contractions

The objective of this study was to investigate premotor modulation of motor cortical excitability between rhythmic unimanual finger contractions. Applying TMS at rest prior to an anticipated contraction provides a measure of cortical excitability that reflects premotor modulatory drive and is uncontaminated by the alterations in spinal and cortical excitability that occur during muscle activation. We hypothesized that premotor structures contribute to unimanual movement through the modulation of intracortical and interhemispheric inhibitory circuits within the primary motor cortex and that this premotor modulation would be evident at rest between contractions. Thus, we used transcranial magnetic stimulation (TMS) to assess short interval intracortical inhibition (SICI) and interhemispheric inhibition (IHI) in a 500-ms epoch prior to a planned contraction of the right FDI in 10 participants (21.4±1.9 years). These measures of inhibition were made in three different states: (1) at complete rest (with no plan to contract), (2) at rest between rhythmic contractions, and (3) during low level contractions. Cortical excitability was enhanced prior to a contraction and during a contraction compared to at rest (F₂,₁₈=758.3, p<0.001). IHI was also increased prior to a contraction compared to at rest and during a contraction while SICI was only reduced during a contraction (F₂,₃₈=30.3, p<0.001).We used this pre-contraction protocol to investigate the cortical mechanisms of unimanual control. However, this protocol would be a useful tool to investigate any neuromuscular adaptation that may occur as a result of altered premotor modulation of cortical excitability, such as neuromuscular fatigue, training and movement disorders.

Cortical Mechanisms of Central Fatigue and Sense of Effort

The purpose of this study was to investigate cortical mechanisms upstream to the corticospinal motor neuron that may be associated with central fatigue and sense of effort during and after a fatigue task. We used two different isometric finger abduction protocols to examine the effects of muscle activation and fatigue the right first dorsal interosseous (FDI) of 12 participants. One protocol was intended to assess the effects of muscle activation with minimal fatigue (control) and the other was intended to elicit central fatigue (fatigue). We hypothesized that high frequency repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area (SMA) would hasten recovery from central fatigue and offset a fatigue-induced increase in sense of effort by facilitating the primary motor cortex (M1). Constant force-sensation contractions were used to assess sense of effort associated with muscle contraction. Paired-pulse TMS was used to assess intracortical inhibition (ICI) and facilitation (ICF) in the active M1 and interhemispheric inhibitory (IHI) was assessed to determine if compensation occurs via the resting M1. These measures were made during and after the muscle contraction protocols. Corticospinal excitability progressively declined with fatigue in the active hemisphere. ICF increased at task failure and ICI was also reduced at task failure with no changes in IHI found. Although fatigue is associated with progressive reductions in corticospinal excitability, compensatory changes in inhibition and facilitation may act within, but not between hemispheres of the M1. rTMS of the SMA following fatigue enhanced recovery of maximal voluntary force and higher levels of ICF were associated with lower sense of effort following stimulation. rTMS of the SMA may have reduced the amount of upstream drive required to maintain motor output, thus contributing to a lower sense of effort and increased rate of recovery of maximal force.

Cortical mechanisms of mirror activation during maximal and submaximal finger contractions in Parkinson's disease.

BACKGROUND Mirror movements are often reported in the early stages of Parkinsons disease (PD) and have been attributed to bilateral activation of the primary motor cortex; however, the precise cortical mechanisms are still unclear. Subclinical mirror activation (MA) that accompanies mirror movement has also been reported in healthy aging adults. OBJECTIVE To characterize mirror activation and determine the cortical mechanisms of MA in individuals with PD who demonstrate mirror movements. HYPOTHESIS 5 Hz rTMS to the supplementary motor area (SMA) will reduce MA by increasing interhemispheric inhibition (IHI) of the ipsilateral motor cortex. METHODS MA was assessed using surface electromyography during maximal and submaximal unimanual contractions of the first dorsal interosseous in 7 individuals with PD with mirror movements (PD-MM: 70.9 ± 13.9 years; UPDRS III: 28.0 ± 8.2), 7 individuals with PD without mirror movements (PD-NM: 71 ± 10.1 years; UPDRS III: 27.8 ± 6.7) and 7 healthy controls (74.4 ± 6.0 years). IHI of the ipsilateral motor cortex was assessed using paired-pulse transcranial magnetic stimulation. RESULTS MA was enhanced in both PD groups during submaximal contractions, with the latest onset of activation in PD-NM. Ipsilateral motor cortex excitability was the highest in PDMM; however, IHI did not differ between PD and controls. 5 Hz rTMS to the SMA reduced IHI in PD-NM; however, did not affect MA. CONCLUSIONS IHI may not be the sole contributor to the expression of overt mirror movements in PD. Expression of overt mirror movement may be due to the combination of enhanced ipsilateral motor cortex excitability and an earlier onset of electromyographic activation in the mirror hand (mirror activation) in PDMM.