Different current intensities of anodal transcranial direct current stimulation do not differentially modulate motor cortex plasticity

Transcranial direct current stimulation (tDCS) is a noninvasive technique that modulates the excitability of neurons within the motor cortex (M1). Although the aftereffects of anodal tDCS on modulating cortical excitability have been described, there is limited data describing the outcomes of different tDCS intensities on intracortical circuits. To further elucidate the mechanisms underlying the aftereffects of M1 excitability following anodal tDCS, we used transcranial magnetic stimulation (TMS) to examine the effect of different intensities on cortical excitability and short-interval intracortical inhibition (SICI). Using a randomized, counterbalanced, crossover design, with a one-week wash-out period, 14 participants (6 females and 8 males, 22–45 years) were exposed to 10 minutes of anodal tDCS at 0.8, 1.0, and 1.2 mA. TMS was used to measure M1 excitability and SICI of the contralateral wrist extensor muscle at baseline, immediately after and 15 and 30 minutes following cessation of anodal tDCS. Cortical excitability increased, whilst SICI was reduced at all time points following anodal tDCS. Interestingly, there were no differences between the three intensities of anodal tDCS on modulating cortical excitability or SICI. These results suggest that the aftereffect of anodal tDCS on facilitating cortical excitability is due to the modulation of synaptic mechanisms associated with long-term potentiation and is not influenced by different tDCS intensities.

Short-interval intracortical inhibition is not affected by varying visual feedback in an isometric task in biceps brachiii muscle

Purpose : To establish if visual feedback and force requirements influence SICI.

Methods : SICI was assessed from 10 healthy adults (5 males and 5 females aged between 21 and 35 years) in three submaximal isometric elbow flexion torque levels [5, 20, and 40% of maximal voluntary contraction (MVC)] and with two tasks differing in terms of visual feedback. Single-pulse and paired-pulse motor-evoked potentials (MEPs), supramaximal M-wave, and background surface electromyogram (sEMG) were recorded from the biceps brachii muscle.

Results : Repeated measures MANOVA was used for statistical analyses. Background sEMG did not differ between tasks (F = 0.4, P = 0.68) nor was task × torque level interaction observed (F = 1.2, P = 0.32), whereas background sEMG increased with increasing torque levels (P = 0.001). SICI did not differ between tasks (F = 0.9, P = 0.43) and no task × torque level interaction was observed (F = 2.3, P = 0.08). However, less SICI was observed at 40% MVC compared to the 5 and 20% MVC torque levels (P = 0.01–0.001).

Conclusion : SICI was not altered by performing the same task with differing visual feedback. However, SICI decreased with increasing submaximal torque providing further evidence that SICI is one mechanism of modulating cortical excitability and plays a role in force gradation.

Formation of cortical plasticity in older adults following tDCS and motor training

Neurodegeneration accompanies the process of natural aging, reducing the ability to perform functional daily activities. Transcranial direct current stimulation (tDCS) alters neuronal excitability and motor performance; however its beneficial effect on the induction of primary motor cortex (M1) plasticity in older adults is unclear. Moreover, little is known as to whether the tDCS electrode arrangement differentially affects M1 plasticity and motor performance in this population. In a double-blinded, cross-over trial, we compared unilateral, bilateral and sham tDCS combined with visuomotor tracking, on M1 plasticity and motor performance of the non-dominant upper limb, immediately post and 30 min following stimulation. We found (a) unilateral and bilateral tDCS decreased tracking error by 12–22% at both time points; with sham decreasing tracking error by 10% at 30 min only, (b) at both time points, motor evoked potentials (MEPs) were facilitated (38–54%) and short-interval intracortical inhibition was released (21–36%) for unilateral and bilateral conditions relative to sham, (c) there were no differences between unilateral and bilateral conditions for any measure. These findings suggest that tDCS modulated elements of M1 plasticity, which improved motor performance irrespective of the electrode arrangement. The results provide preliminary evidence indicating that tDCS is a safe non-invasive tool to preserve or improve neurological function and motor control in older adults.

The long term effects of sports concussion on retired Australian football players: a study using Transranial Magnetic Stimulation

This study investigated corticomotor excitability and inhibition, cognitive functioning, and fine motor dexterity in retired elite and amateur Australian football (AF) players who had sustained concussions during their playing careers. Forty male AF players who played at the elite level (n=20; mean age 49.7±5.7 years) or amateur level (n=20; mean age 48.4±6.9 years), and had sustained on average 3.2 concussions 21.9 years previously, were compared with 20 healthy age-matched male controls (mean age 47.56±6.85 years). All participants completed assessments of fine dexterity, visuomotor reaction time, spatial working memory (SWM), and associative learning (AL). Transcranial magnetic stimulation (TMS) was used to measure corticospinal excitability: stimulus-response (SR) curves and motor evoked potential (MEP) 125% of active motor threshold (aMT); and intracortical inhibition: cortical silent period (cSP), short-interval intracortical inhibition (SICI), and long-interval intracortical inhibition (LICI). Healthy participants performed better in dexterity (p=0.003), reaction (p=0.003), and movement time (p=0.037) than did both AF groups. Differences between AF groups were found in AL (p=0.027) and SWM (p=0.024). TMS measures revealed that both AF groups showed reduced cSP duration at 125% aMT (p>0.001) and differences in SR curves (p>0.001) than did healthy controls. Similarly, SICI (p=0.012) and LICI (p=0.009) were reduced in both AF groups compared with controls. Regression analyses revealed a significant contribution to differences in motor outcomes with the three measures of intracortical inhibition. The measures of inhibition differed, however, in terms of which performance measure they had a significant and unique predictive relationship with, reflecting the variety of participant concussion injuries. This study is the first to demonstrate differences in motor control and intracortical inhibition in AF players who had sustained concussions during their playing career two decades previously.

Effects of vitamin D supplementation on neuroplasticity in older adults: a double-blinded, placebo-controlled randomised trial

Summary - Vitamin D can improve muscle function and reduce falls, but whether it can strengthen neural connections within the brain and nervous system is not known. This 10-week randomised controlled trial indicates that treatment with 2,000 IU/day vitamin D3 does not significantly alter neuroplasticity relative to placebo in older adults.
Introduction - The purpose of this study was to examine the effects of vitamin D supplementation on neuroplasticity, serum brain-derived neurotrophic factor (BDNF) and muscle strength and function in older adults.
Methods - This was a 10-week double-blinded, placebo-controlled randomised trial in which 26 older adults with 25-hydroxyvitamin D [25OHD] concentrations 25–60 nmol/L were randomised to 2,000 IU/day vitamin D3 or matched placebo. Single- and paired-pulse transcranial magnetic stimulation applied over the motor cortex was used to assess changes in motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI), as measures of corticospinal excitability and inhibition respectively, by recording electromyography (EMG) responses to stimulation from the wrist extensors. Changes in muscle strength, stair climbing power, gait (timed-up-and-go), dynamic balance (four square step test), serum 25(OH)D and BDNF concentrations were also measured.
Results - After 10 weeks, mean 25(OH)D levels increased from 46 to 81 nmol/L in the vitamin D group with no change in the placebo group. The vitamin D group experienced a significant 8–11 % increase in muscle strength and a reduction in cortical excitability (MEP amplitude) and SICI relative to baseline (all P < 0.05), but these changes were not significantly different from placebo. There was no effect of vitamin D on muscle power, function or BDNF.
Conclusions - Daily supplementation with 2,000 IU vitamin D3 for 10 weeks had no significant effect on neuroplasticity compared to placebo, but the finding that vitamin D treatment alone was associated with a decrease in corticospinal excitability and intracortical inhibition warrants further investigation as this suggests that it may improve the efficacy of neural transmission within the corticospinal pathway.

TMS stimulus-response asymmetry in left- and right handed individuals

There have been inconsistencies in the literature regarding asymmetrical neural control and results of experiments using TMS techniques. Therefore, the aim of this study was to further our understanding of the neural relationships that may underlie performance asymmetry with respect to the distal muscles of the hand using a TMS stimulus–response curve technique. Twenty-four male subjects (12 right handed, 12 left handed) participated in a TMS stimulus–response (S–R) curve trial. Focal TMS was applied over the motor cortex to find the optimal position for the first dorsal interossei muscle and to determine rest threshold (RTh). Seven TMS intensities ranging from 90 to 150 % of RTh were delivered in 10 % increments. One single TMS block consisted of 16 stimuli at each intensity. Peak-to-peak amplitudes were measured and the S–R curve generated. In right-handed subjects, the mean difference in slopes between the right and left hand was −0.011 ± 0.03, while the mean difference between hands in left-handed subjects was −0.049 ± 0.08. Left-handed normalized data in right handers displayed a mean of 1.616 ± 1.019 (two-tailed t test p < 0.05). The left-handed group showed a significant change in the normalized slope as indicated by a mean of 1.693 ± 0.149 (two-tailed t test p < 0.00006). The results found in this study reinforce previous work which suggests that there is an asymmetry in neural drive that exists in both left- and right-handed individuals. However, the results show that the non-dominant motor hemisphere displays a greater amount of excitability than the dominant, which goes against the conventional dogma. This asymmetry indicates that the non-dominant hemisphere may have a higher level of excitation or a lower level of inhibition for both groups of participants.

An examination of the influence of visuomotor associations on interpersonal motor resonance

The adaptation account of mirror neurons in humans proposes that mirror systems have been selected for in evolution to facilitate social cognition. By contrast, a recent "association" account of mirror neurons in humans argues that mirror systems are not the result of a specific adaptation, but of sensorimotor learning arising from concurrent visual and motor activity. Here, we used transcranial magnetic stimulation (TMS) and electromyography (EMG) to evaluate whether visuomotor associations affect interpersonal motor resonance, a putative measure of mirror system activity. 18 participants underwent two TMS sessions exploring whether visuomotor associations established throughout one׳s lifespan, namely common movements and movements generated from one׳s own perspective, are associated with increased putative mirror system activity. Our results showed no overall difference in interpersonal motor resonance to common versus uncommon actions, or actions presented from an egocentric (self) versus an allocentric (other) perspective. We did, however, observe increased interpersonal motor resonance within the abductor digiti minimi (ADM) muscle in response to allocentric compared to egocentric movements. As the association model predicts stronger mirror system response to actions with stronger visuomotor associations, such as common movements and those presented from an egocentric perspective, our findings provide little evidence to support the association model.

Breakdown in central motor control can be attenuated by motor practice and neuro-modulation of the primary motor cortex

The performance of a repetitive index finger flexion–extension task at maximal voluntary rate (MVR) begins to decline just a few seconds into the task and we have previously postulated that this breakdown has a central origin. To test this hypothesis, we have combined two objectives; to determine whether motor practice can lessen the performance deterioration in an MVR task, and whether further gains can be achieved with a transcranial magnetic stimulation (TMS) protocol that increases corticomotor excitability (CME). Eleven right-handed subjects participated in a randomized crossover study design that consisted of a 15-min interventional TMS at I-wave periodicity (ITMS) and single-pulsed Sham intervention prior to six 10-s practice sets of a repetitive finger flexion–extension task at MVR. Motor-evoked potentials (MEPs) were recorded from the first dorsal interosseous muscle. The starting movement rate, and the percentage decline in rate by the end of the MVR were quantitated. Training of the MVR task improved the sustainability of the task by reducing the decline in movement rate. CME increased steadily after each training bout, and this increase was maintained up to 20 min after the last bout. ITMS further increased CME, and was associated with an increase in both the starting rate of the MVR task and its sustainability, when compared to Sham. The results implicate central motor processes in the performance and sustainability of the MVR task, and indicate that MVR kinematics can improve with short-term training and with non-invasive neuro-modulation.

Poor tolerance of motor cortex rTMS in chronic migraine

Background:
Two small studies had evaluated the efficacy of rTMS in migraine. One tested high frequency rTMS over the dorsolateral prefrontal cortex while the other evaluated 1 Hz rTMS over the vertex.
Aim:
To test the feasibility of 10 Hz rTMS of motor cortex as an adjunctive therapy in patients with chronic migraine.
Materials and Methods:
We randomized (2:1 ratio) chronic migraine patients on medical preventive treatment to receive either rTMS or sham therapy for 10 sessions. rTMS (80% resting motor threshold, 10Hz, 20 trains, 5 secs/train, inter-train interval 1 min, total 1000 stimuli/session) was applied over the right motor cortex.
Result:
Nine patients were randomized. Six received rTMS
and three had sham therapy. Three patients in the rTMS arm withdrew from the study due to increased headache frequency and discomfort from the treatment. The remaining six cases (3 rTMS, 3 sham) completed the study. The study was prematurely stopped due to the significant worsening of headache from rTMS. No significant differences in outcome measures were found between real and sham rTMS.
Conclusion:
Although the study was terminated prematurely, the high dropout rate (50%) due to worsening headaches suggested that rTMS over the motor cortex is poorly tolerated in chronic migraine.

Using transcranial magnetic stimulation to quantify electrophysiological changes following concussive brain injury: a systematic review

Mild traumatic brain injury (mTBI) and sports concussion are a growing public health concern, with increasing demands for more rigorous methods to quantify changes in the brain post-injury. Electrophysiology, and in particular, transcranial magnetic stimulation (TMS), have been demonstrated to provide prognostic value in a range of neurological conditions; however, no review has quantified the efficacy of TMS in mTBI/concussion. In the present study, we present a systematic review and critical evaluation of the scientific literature from 1990 to 2014 that has used TMS to investigate corticomotor excitability responses at short-term (< 12 months), medium-term (1-5 years), and long-term (> 5 years) post-mTBI/concussion. Thirteen studies met the selection criteria, with six studies presenting short-term changes, five studies presenting medium-term changes, and two studies presenting long-term changes. Irrespective of time post-concussion, change in intracortical inhibition was the most reported observation. Other findings included increased stimulation threshold, and slowed neurological conduction time. Although currently limited, the data suggest that TMS has prognostic value in detecting neurophysiological changes post-mTBI/concussion.

Increased cross-education of muscle strength and reduced corticospinal inhibition following eccentric strength training

AIM: Strength training of one limb results in a substantial increase in the strength of the untrained limb, however, it remains unknown what the corticospinal responses are following either eccentric or concentric strength training and how this relates to the cross-education of strength. The aim of this study was to determine if eccentric or concentric unilateral strength training differentially modulates corticospinal excitability, inhibition and the cross-transfer of strength. METHODS: Changes in contralateral (left limb) concentric strength, eccentric strength, motor-evoked potentials, short-interval intracortical inhibition and silent period durations were analyzed in groups of young adults who exercised the right wrist flexors with either eccentric (N=9) or concentric (N=9) contractions for 12 sessions over 4weeks. Control subjects (N=9) did not train. RESULTS: Following training, both groups exhibited a significant strength gain in the trained limb (concentric group increased concentric strength by 64% and eccentric group increased eccentric strength by 62%) and the extent of the cross-transfer of strength was 28% and 47% for the concentric and eccentric group, respectively, which was different between groups (P=0.031). Transcranial magnetic stimulation revealed that eccentric training reduced intracortical inhibition (37%), silent period duration (15-27%) and increased corticospinal excitability (51%) compared to concentric training for the untrained limb (P=0.033). There was no change in the control group. CONCLUSION: The results show that eccentric training uniquely modulates corticospinal excitability and inhibition of the untrained limb to a greater extent than concentric training. These findings suggest that unilateral eccentric contractions provide a greater stimulus in cross-education paradigms and should be an integral part of the rehabilitative process following unilateral injury to maximize the response.

The effects of a protein enriched diet with lean red meat combined with a multi-modal exercise program on muscle and cognitive health and function in older adults: study protocol for a randomised controlled trial

BACKGROUND: Age-related muscle wasting has been strongly implicated with falls and fractures in the elderly, but it has also been associated with cognitive decline and dementia. Progressive resistance training (PRT) and adequate dietary protein are recognised as important contributors to the maintenance of muscle health and function in older adults. However, both factors also have the potential to improve brain function and prevent cognitive decline via several pathways, including the regulation of various growth and neurotrophic factors [insulin-like growth factor-1 (IGF-1)]; brain-derived growth factor (BDNF)] and/or the modulation of systemic inflammation. The primary aim of this study is to investigate whether a modest increase in dietary protein achieved through the consumption of lean red meat three days per week, when combined with PRT, can enhance muscle mass, size and strength and cognitive function in community-dwelling older people. METHODS/DESIGN: The study design is a 48-week randomised controlled trial consisting of a 24-week intervention with a 24-week follow-up. Men and women (n=152) aged 65 years and over residing in the community will be randomly allocated to: 1) PRT and provided with 220 g (raw weight) of lean red meat to be cooked and divided into two 80 g servings on each of the three days that they complete their exercise session, or 2) control PRT in which participants will be provided with and advised to consume ≥1 serving (~1/2 cup) of rice and/or pasta or 1 medium potato on each of the three training days. The primary outcome measures will be muscle mass, size and strength and cognitive function. Secondary outcomes will include changes in: muscle function, neural health (corticospinal excitability and inhibition and voluntary activation), serum IGF-1 and BDNF, adipokines and inflammatory markers, fat mass and inter-/intra-muscular fat, blood pressure, lipids and health-related quality of life. All outcome measures will be assessed at baseline and 24 weeks, with the exception of cognitive function and the various neurobiological and inflammatory markers which will also be assessed at week 12. DISCUSSION: The findings from this study will provide important new information on whether a modest increase in dietary protein achieved through the ingestion of lean red meat can enhance the effects of PRT on muscle mass, size and strength as well as cognitive function in community-dwelling older adults. If successful, the findings will form the basis for more precise exercise and nutrition guidelines for the management and prevention of age-related changes in muscle and neural health and cognitive function in the elderly. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12613001153707 . Date registered 16(th) October, 2013.

Isometric exercise induces analgesia and reduces inhibition in patellar tendinopathy

BACKGROUND: Few interventions reduce patellar tendinopathy (PT) pain in the short term. Eccentric exercises are painful and have limited effectiveness during the competitive season. Isometric and isotonic muscle contractions may have an immediate effect on PT pain. METHODS: This single-blinded, randomised cross-over study compared immediate and 45 min effects following a bout of isometric and isotonic muscle contractions. Outcome measures were PT pain during the single-leg decline squat (SLDS, 0-10), quadriceps strength on maximal voluntary isometric contraction (MVIC), and measures of corticospinal excitability and inhibition. Data were analysed using a split-plot in time-repeated measures analysis of variance (ANOVA). RESULTS: 6 volleyball players with PT participated. Condition effects were detected with greater pain relief immediately from isometric contractions: isometric contractions reduced SLDS (mean±SD) from 7.0±2.04 to 0.17±0.41, and isotonic contractions reduced SLDS (mean±SD) from 6.33±2.80 to 3.75±3.28 (p<0.001). Isometric contractions released cortical inhibition (ratio mean±SD) from 27.53%±8.30 to 54.95%±5.47, but isotonic contractions had no significant effect on inhibition (pre 30.26±3.89, post 31.92±4.67; p=0.004). Condition by time analysis showed pain reduction was sustained at 45 min postisometric but not isotonic condition (p<0.001). The mean reduction in pain scores postisometric was 6.8/10 compared with 2.6/10 postisotonic. MVIC increased significantly following the isometric condition by 18.7±7.8%, and was significantly higher than baseline (p<0.001) and isotonic condition (p<0.001), and at 45 min (p<0.001). CONCLUSIONS: A single resistance training bout of isometric contractions reduced tendon pain immediately for at least 45 min postintervention and increased MVIC. The reduction in pain was paralleled by a reduction in cortical inhibition, providing insight into potential mechanisms. Isometric contractions can be completed without pain for people with PT. The clinical implications are that isometric muscle contractions may be used to reduce pain in people with PT without a reduction in muscle strength.