Although it has long been known that practicing a motor task with one limb can improve performance with the limb opposite, the mechanisms remain poorly understood. Here we tested the hypothesis that improved performance with the untrained limb on a fastest possible (i.e. ballistic) movement task depends partly on cortical circuits located ipsilateral to the trained limb. The idea that crossed effects, which are important for the learning process, might occur in the 'untrained' hemisphere following ballistic training is based on the observation that tasks requiring strong descending drive generate extensive bilateral cortical activity. Twenty-one volunteers practiced a ballistic index finger abduction task with their right hand, and corticospinal excitability was assessed in two hand muscles (first dorsal interosseus, FDI; adductor digiti minimi, ADM). Eight control subjects did not train. After training, repetitive transcranial magnetic stimulation (rTMS; 15 min at 1 Hz) was applied to the left (trained) or right (untrained) motor cortex to induce a 'virtual lesion'. A third training group received sham rTMS, and control subjects received rTMS to the right motor cortex. Performance and corticospinal excitability (for FDI) increased in both hands for training but not control subjects. rTMS of the left, trained motor cortex specifically reduced training-induced gains in motor performance for the right, trained hand, and rTMS of the right, untrained motor cortex specifically reduced performance gains for the left, untrained hand. Thus, cortical processes within the untrained hemisphere, ipsilateral to the trained hand, contribute to early retention of ballistic performance gains for the untrained limb.

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Rodent models of transcranial magnetic stimulation (TMS) play a crucial role in aiding the understanding of the cellular and molecular mechanisms underlying TMS induced plasticity. Rodent-specific TMS have previously been used to deliver focal stimulation at the cost of stimulus intensity (12 mT). Here we describe two novel TMS coils designed to deliver repetitive TMS (rTMS) at greater stimulation intensities whilst maintaining spatial resolution. Two circular coils (8 mm outer diameter) were constructed with either an air or pure iron-core. Peak magnetic field strength for the air and iron-cores were 90 and 120 mT, respectively, with the iron-core coil exhibiting less focality. Coil temperature and magnetic field stability for the two coils undergoing rTMS, were similar at 1 Hz but varied at 10 Hz. Finite element modeling of 10 Hz rTMS with the iron-core in a simplified rat brain model suggests a peak electric field of 85 and 12.7 V/m, within the skull and the brain, respectively. Delivering 10 Hz rTMS to the motor cortex of anaesthetized rats with the iron-core coil significantly increased motor evoked potential amplitudes immediately after stimulation (n = 4). Our results suggest these novel coils generate modest magnetic and electric fields, capable of altering cortical excitability and provide an alternative method to investigate the mechanisms underlying rTMS-induced plasticity in an experimental setting.

The phenomenon of cross-limb transfer, in which unilateral strength training can result in bilateral strength gains, has recently been tested for ballistic movements. Performance gains associated with repetitive motor practice, and the associated transfer, occur within a few minutes. In this study, young and older adults were trained to perform ballistic abductions of their dominant (right) index finger as quickly as possible. Performance was assessed bilaterally before, during, and after this training. Both groups exhibited large performance gains in the right hand as a result of training (P < 0.001; young 84% improvement, older 70% improvement), which were not significantly different between groups (P = 0.40). Transcranial magnetic stimulation revealed that the performance improvements were accompanied by increases in excitability, together with decreases in intracortical inhibition, of the projections to both the trained muscle and the homologous muscle in the contralateral limb (P < 0.05). The young group also exhibited performance improvements as a result of cross-limb transfer in the left (untrained) hand (P < 0.005), equivalent to 75% of the performance increase in the trained hand. In contrast, there were no significant performance gains in the left hand for the older group (P = 0.23). This was surprising given that the older group exhibited a significantly greater degree of mirror activity than the young group (P < 0.01) in the left first dorsal interosseus muscle (FDI) during right hand movements. Our findings suggest that older adults exhibit a reduced capacity for cross-limb transfer, which may have implications for motor rehabilitation programs after stroke.

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We investigated how volitional contractions affect interhemispheric inhibition (IHI) from the active to the passive hemisphere. Younger and older adults isometrically contracted their dominant thumb (abductor pollicis brevis, APB) to various force targets. In ballistic contraction trials, transcranial magnetic stimulation (TMS) was administered very shortly after the onset of APB activity. In tonic contraction trials, TMS was delivered while the target force was maintained. In control trials both thumbs remained quiescent. In all trials, a test stimulus (TS) was directed to the APB hotspot in the non-dominant hemisphere (130% left APB resting motor threshold, RMT). In half the trials, a conditioning stimulus (130% right APB RMT) was applied to the APB hotspot in the dominant hemisphere 10 ms prior to the TS. Targeted ballistic contractions of the right APB were found to modulate (increase) IHI measured in the left APB, as previously reported for tonic contractions. Furthermore, the extent of the IHI increase was found to scale with the strength of the contralateral ballistic or tonic contraction. Less pronounced, but statistically significant, IHI increases were also observed in the left abductor digiti minimi and extensor carpi radialis during right APB contraction. For these muscles, however, the extent of the IHI modulation was independent of APB contraction strength. The capacity to modulate inhibition during contractions was unaffected by advancing age. During volitional actions, the ability to modulate IHI most adaptively in the homologous muscle of the resting limb may contribute to the prevention of mirror movements.

The brain derived neurotrophic factor (BDNF) Val66Met polymorphism and stimulation duration are thought to play an important role in modulating motor cortex plasticity induced by non-invasive brain stimulation (NBS). In the present study we sought to determine whether these factors interact or exert independent effects in older adults. Fifty-four healthy older adults (mean age = 66.85 years) underwent two counterbalanced sessions of 1.5 mA anodal transcranial direct current stimulation (atDCS), applied over left M1 for either 10 or 20 min. Single pulse transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability (CSE) before and every 5 min for 30 min following atDCS. On a group level, there was an interaction between stimulation duration and BDNF genotype, with Met carriers (n = 13) showing greater post-intervention potentiation of CSE compared to Val66Val homozygotes homozygotes (n = 37) following 20 min (p = 0.002) but not 10 min (p = 0.219) of stimulation. Moreover, Met carriers, but not Val/Val homozygotes, exhibited larger responses to TMS (p = 0.046) after 20 min atDCS, than following 10 min atDCS. On an individual level, two-step cluster analysis revealed a considerable degree of inter-individual variability, with under half of the total sample (42%) showing the expected potentiation of CSE in response to atDCS across both sessions. Intra-individual variability in response to different durations of atDCS was also apparent, with one-third of the total sample (34%) exhibiting LTP-like effects in one session but LTD-like effects in the other session. Both the inter-individual (p = 0.027) and intra-individual (p = 0.04) variability was associated with BDNF genotype. In older adults, the BDNF Val66Met polymorphism along with stimulation duration appears to play a role in modulating tDCS-induced motor cortex plasticity. The results may have implications for the design of NBS protocols for healthy and diseased aged populations.

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