John Cirillo

Corticomotor plasticity and learning of a ballistic thumb training task are diminished in older adults

This study examined changes in corticomotor excitability and plasticity after a thumb abduction training task in young and old adults. Electromyographic (EMG) recordings were obtained from right abductor pollicis brevis (APB, target muscle) and abductor digiti minimi (ADM, control muscle) in 14 young (18-24 yr) and 14 old (61-82 yr) adults. The training task consisted of 300 ballistic abductions of the right thumb to maximize peak thumb abduction acceleration (TAAcc). Transcranial magnetic stimulation (TMS) of the left primary motor cortex was used to assess changes in APB and ADM motor evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) before, immediately after, and 30 min after training. No differences in corticomotor excitability (resting and active TMS thresholds, MEP input-output curves) or SICI were observed in young and old adults before training. Motor training resulted in improvements in peak TAAcc in young (177% improvement, P < 0.001) and old (124%, P = 0.005) subjects, with greater improvements in young subjects (P = 0.002). Different thumb kinematics were observed during task performance, with increases in APB EMG related to improvements in peak TAAcc in young (r(2) = 0.46, P = 0.008) but not old (r(2) = 0.09, P = 0.3) adults. After training, APB MEPs were 50% larger (P < 0.001 compared with before) in young subjects, with no change after training in old subjects (P = 0.49), suggesting reduced use-dependent corticomotor plasticity with advancing age. These changes were specific to APB, because no training-related change in MEP amplitude was observed in ADM. No significant association was observed between change in APB MEP and improvement in TAAcc with training in individual young and old subjects. SICI remained unchanged after training in both groups, suggesting that it was not responsible for the diminished use-dependent corticomotor plasticity for this task in older adults.

Motor cortex plasticity induced by paired associative stimulation is enhanced in physically active individuals

Recent evidence indicates that regular physical activity enhances brain plasticity (i.e. the ability to reorganise neural connections) and improves neurocognitive function. However, the effect of regular physical activity on human motor cortex function is unknown. The purpose of this study was to examine motor cortex plasticity for a small hand muscle in highly active and sedentary individuals. Electromyographic recordings were obtained from the left abductor pollicis brevis (APB) muscle of 14 active and 14 sedentary subjects (aged 18–38 yrs). The extent of physical activity was assessed by questionnaire, where the physically active subjects performed >150 min per day moderate‐to‐vigorous aerobic activity on at least 5 days per week, whereas the sedentary group performed <20 min per day of physical activity on no more than 3 days per week. Transcranial magnetic stimulation (TMS) of the right hemisphere was used to assess changes in APB motor‐evoked potentials (MEPs), input–output curve (IO curve), short‐interval intracortical inhibition (SICI) and cortical silent period (CSP). Neuroplastic changes were induced using paired‐associative stimulation (PAS), which consisted of 90 paired stimuli (0.05 Hz for 30 min) of median nerve electrical stimulation at the wrist followed 25 ms later by TMS to the hand area of motor cortex. The IO curve slope was 35% steeper in individuals with increased physical activity (combined before and after PAS, P < 0.05), suggesting increased motor cortex excitability, although there was no difference in SICI or CSP between groups. PAS induced an increase in MEP amplitude in the physically active subjects (54% increase compared with before, P < 0.01), but no significant facilitation in the sedentary subjects. We conclude that participation in regular physical activity may offer global benefits to motor cortex function that enhances neuroplasticity, which could improve motor learning and neurorehabilitation in physically active individuals.

Corticomotor excitability and plasticity following complex visuomotor training in young and old adults.

Previous studies with transcranial magnetic stimulation (TMS) have shown that advancing age may influence plasticity induction in human motor cortex (M1), but these changes have been assessed with TMS‐induced paradigms or simple motor tasks. The aim of this study was to examine changes in corticospinal excitability and intracortical inhibition as markers of corticomotor plasticity following complex motor training in young and old adults. Electromyographic recordings were obtained from the right first dorsal interosseous (FDI) muscle of 16 young (20–35 years) and 16 older (aged 60–75 years) adults before and after motor skill training. Motor training consisted of three 6‐minute blocks of a complex visuomotor task that required matching the metacarpophalangeal (MCP) joint angle of the index finger using abduction–adduction movements. Single‐ and paired‐pulse TMS over the left M1 was used to assess changes in right FDI motor‐evoked potentials (MEPs) and short‐interval intracortical inhibition (SICI) before and after each training block. Visuomotor tracking performance was diminished in old compared with young adults throughout training. However, improvement in tracking error was similar for young and old adults (7–24% increase in each training block). For young and old adults, motor training increased FDI MEP amplitude (≥ 20%) and reduced the magnitude of SICI (≥ 19%) after each visuomotor training block, reflecting use‐dependent plasticity. However, no difference in corticomotor plasticity (change in MEP or SICI) was observed between young and old adults. Further studies are needed to identify the experimental or behavioral factors that might contribute to the maintenance of corticomotor plasticity in older adults.

Differential modulation of motor cortex excitability in BDNF Met allele carriers following experimentally induced and use-dependent plasticity.

The purpose of this study was to investigate how healthy young subjects with one of three variants of the brain‐derived neurotrophic factor (BDNF) gene modulate motor cortex excitability following experimentally induced and use‐dependent plasticity interventions. Electromyographic recordings were obtained from the right first dorsal interosseous (FDI) muscle of 12 Val/Val, ten Val/Met and seven Met/Met genotypes (aged 18–39 years). Transcranial magnetic stimulation of the left hemisphere was used to assess changes in FDI motor‐evoked potentials (MEPs) following three separate interventions involving paired associative stimulation, a simple ballistic task and complex visuomotor tracking task using the index finger. Val/Val subjects increased FDI MEPs following all interventions (≥ 25%, P < 0.01), whereas the Met allele carriers only showed increased MEPs after the simple motor task (≥ 26%, P < 0.01). In contrast to the simple motor task, there was no significant change in MEPs for the Val/Met subjects (7%, P = 0.50) and a reduction in MEPs for the Met/Met group (−38%, P < 0.01) following the complex motor task. Despite these differences in use‐dependent plasticity, the performance of both motor tasks was not different between BDNF genotypes. We conclude that modulation of motor cortex excitability is strongly influenced by the BDNF polymorphism, with the greatest differences observed for the complex motor task. We also found unique motor cortex plasticity in the rarest form of the BDNF polymorphism (Met/Met subjects), which may have implications for functional recovery after disease or injury to the nervous system in these individuals.

Low-frequency fatigue and neuromuscular performance after exercise-induced damage to elbow flexor muscles

The purpose of this study was to quantify the association between low-frequency fatigue (LFF) and the increase in EMG and force fluctuations after eccentric exercise of elbow flexor muscles. Ten subjects performed two tasks involving voluntary isometric contractions of elbow flexors: a maximum voluntary contraction (MVC) and a constant-force task at five submaximal target forces (5, 10, 20, 40, 60% MVC) while EMG was recorded from biceps and triceps brachii. A third task involved electrical stimulation of biceps brachii at 12 frequencies (1-100 Hz). These tasks were performed before, after, and 2 h and 24 h after concentric or eccentric exercise. MVC force declined after eccentric exercise (34% decline) and remained depressed 24 h later (22% decline), whereas the reduced force following concentric exercise (32%) was recovered 2 h later. Biceps brachii EMG and force fluctuations during the submaximal voluntary contractions increased after eccentric exercise (both approximately 2x greater) with the greatest effect at low forces. LFF was equivalent immediately after both types of exercise (50-60% reduction in 20:100 Hz force) with a slower recovery following eccentric exercise. A significant association was found between the change in LFF and EMG (r(2) values up to 0.52), with the strongest correlations observed at low forces (20% MVC) and at 2 h after exercise. In contrast, there were no significant associations between LFF and force fluctuations during voluntary or electrically evoked contractions, suggesting that other physiological factors located within the muscle are likely to be playing a major role in the impaired motor performance after eccentric exercise.

GABA and primary motor cortex inhibition in young and older adults: a multimodal reliability study

The effects of healthy aging on γ-aminobutyric acid (GABA) within primary motor cortex (M1) remain poorly understood. Studies have reported contrasting results, potentially due to limitations with the common assessment technique. The aim of the present study was to investigate the effect of healthy aging on M1 GABA concentration and neurotransmission using a multimodal approach. Fifteen young and sixteen older adults participated in this study. Magnetic resonance spectroscopy (MRS) was used to measure M1 GABA concentration. Single-pulse and threshold-tracking paired-pulse transcranial magnetic stimulation (TMS) protocols were used to examine cortical silent period duration, short- and long-interval intracortical inhibition (SICI and LICI), and late cortical disinhibition (LCD). The reliability of TMS measures was examined with intraclass correlation coefficient analyses. SICI at 1 ms was reduced in older adults (15.13 ± 2.59%) compared with young (25.66 ± 1.44%; P = 0.002). However, there was no age-related effect for cortical silent period duration, SICI at 3 ms, LICI, or LCD (all P > 0.66). The intersession reliability of threshold-tracking measures was good to excellent for both young (range 0.75-0.96) and older adults (range 0.88-0.93). Our findings indicate that extrasynaptic inhibition may be reduced with advancing age, whereas GABA concentration and synaptic inhibition are maintained. Furthermore, MRS and threshold-tracking TMS provide valid and reliable assessment of M1 GABA concentration and neurotransmission, respectively, in young and older adults.NEW & NOTEWORTHY γ-Aminobutyric acid (GABA) in primary motor cortex was assessed in young and older adults using magnetic resonance spectroscopy and threshold-tracking paired-pulse transcranial magnetic stimulation. Older adults exhibited reduced extrasynaptic inhibition (short-interval intracortical inhibition at 1 ms) compared with young, whereas GABA concentration and synaptic inhibition were similar between age groups. We demonstrate that magnetic resonance spectroscopy and threshold-tracking provide valid and reliable assessments of primary motor cortex GABA concentration and neurotransmission, respectively.

Impaired Organization of Paired-Pulse TMS-Induced I-Waves After Human Spinal Cord Injury

Paired-pulse transcranial magnetic stimulation (TMS) of the human motor cortex results in consecutive facilitatory motor-evoked potential (MEP) peaks in surface electromyography in intact humans. Here, we tested the effect of an incomplete cervical spinal cord injury (SCI) on early (first) and late (second and third) MEP peaks in a resting intrinsic finger muscle. We found that all peaks had decreased amplitude in SCI subjects compared with controls. The second and third peaks were delayed with the third peak also showing an increased duration. The delay of the third peak was smaller than that seen in controls at lower stimulation intensity, suggesting lesser influence of decreased corticospinal inputs. A mathematical model showed that after SCI the third peak aberrantly contributed to spinal motoneurone recruitment, regardless on the motor unit threshold tested. Temporal and spatial aspects of the late peaks correlated with MEP size and hand motor output. Thus, early and late TMS-induced MEP peaks undergo distinct modulation after SCI, with the third peak likely reflecting a decreased ability to summate descending volleys at the spinal level. We argue that the later corticospinal inputs on the spinal cord might be crucial for recruitment of motoneurones after human SCI.

Subcortical contribution to late TMS-induced I-waves in intact humans

Paired-pulse transcranial magnetic stimulation (TMS) of the human motor cortex results in consecutive facilitatory motor evoked potential (MEP) peaks in surface electromyography. It has been proposed that early and late MEP peaks involve different mechanisms of action; however, little is known about the characteristics of the later peaks. Using paired-pulse TMS over the hand motor cortex at different test (S1) and conditioning (S2) interstimulus intervals and intensities we examined early (first) and late (second and third) MEP peaks in a resting finger muscle. We demonstrate that the third peak had reduced amplitude and duration compared with the second, regardless of the S1 intensity. Higher S2 intensity increased the amplitude of the third but not the second peak, suggesting that the third peak had a higher threshold. The interval between the second and third peak was longer than between the first and second peak in all conditions even though all peaks had a similar latency dispersion. No differences were found in the amplitude, duration, and threshold of the first and second peaks. A threshold electrical S2 over the cervicomedullary junction facilitated the second and third but not the first peak similarly to TMS. Our results indicate that the third MEP peak is smaller and has higher threshold than the second peak and the similarities between the first and second peak suggest that this is less likely explained by a reduced effectiveness in recruitment. We argue that subcortical pathways might contribute to differences found between late TMS-induced peaks in intact humans.

Threshold tracking primary motor cortex inhibition: The influence of current direction

Paired‐pulse transcranial magnetic stimulation (TMS) can be used to probe inhibitory activity in primary motor cortex (M1). Recruitment of descending volleys with TMS depends on the induced current direction in M1. Anterior‐posterior (AP) stimulation preferentially activates late indirect‐ (I‐) waves that are most susceptible to paired‐pulse TMS. Threshold tracking TMS can assess intracortical inhibition; however, previous studies have only used a current direction that preferentially recruits early I‐waves [posterior‐anterior (PA)]. Our objective was to examine intracortical inhibition with threshold tracking TMS designed to preferentially recruit early vs. late I‐waves with PA and AP stimulation respectively. Electromyographic recordings were obtained from the right first dorsal interosseous muscle of 15 participants (21–50 years). Motor evoked potentials elicited by TMS over left M1 were recorded for PA, AP and lateromedial (LM) induced currents, with I‐wave recruitment calculated as the onset latency difference between PA‐LM and AP‐LM. Short‐ and long‐interval intracortical inhibition (SICI and LICI) were examined across a range of conditioning stimulus intensities and interstimulus intervals (3 and 100–260 ms) with threshold tracking TMS for PA and AP stimulation. SICI and LICI were greater for AP compared with PA current direction using threshold tracking. In addition, the efficacy of late I‐wave recruitment was associated with the extent of SICI for AP but not PA stimulation, and was not associated with LICI. These findings indicate that threshold tracking with an AP‐induced current provides a more robust and sensitive measure of M1 intracortical inhibition than PA.

Sequencing human ribs into anatomical order by quantitative multivariate methods

Little research has focussed on methods to anatomically sequence ribs. Correct anatomical sequencing of ribs assists in determining the location and distribution of regional trauma, age estimation, number of puncture wounds, number of individuals, and personal identification. The aim of the current study is to develop a method for placing fragmented and incomplete rib sets into correct anatomical position. Ribs 2-10 were used from eleven cadavers of an Australian population. Seven variables were measured from anatomical locations on the rib. General descriptive statistics were calculated for each variable along with an analysis of variance (ANOVA) and ANOVA with Bonferroni statistics. Considerable overlap was observed between ribs for univariate methods. Bivariate and multivariate methods were then applied. Results of the ANOVA with post hoc Bonferroni statistics show that ratios of various dimensions of a single rib could be used to sequence it within adjacent ribs. Using multiple regression formulae, the most accurate estimation of the anatomical rib number occurs when the entire rib is found in isolation. This however, is not always possible. Even when only the head and neck of the rib are preserved, a modified multivariate regression formula assigned 91.95% of ribs into correct anatomical position or as an adjacent rib. Using multivariate methods it is possible to sequence a single human rib with a high level of accuracy and they are superior to univariate methods. Left and right ribs were found to be highly symmetrical. Some rib dimensions were greater in males than in females, but overall the level of sexual dimorphism was low.