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Background Anodal transcranial direct current stimulation (a-tDCS) can facilitate primary motor cortex (M1), but the modulation of motor evoked potentials (MEPs) by a-tDCS varies between participants, and may depend on the balance between early versus late I-wave recruitment, as assessed by the difference in MEP latency between latero-medial and anterior-posterior cortical currents induced by transcranial magnetic stimulation (TMS). Objective To date, the dependence of tDCS after-effects on I-wave recruitment has only been investigated in intrinsic hand muscles. In order to better understand the effects of tDCS across the upper limb, the present study examined I-wave recruitment and MEP modulation by a-tDCS or dual-hemisphere tDCS in muscles of the forearm (Extensor Carpi Radialis; ECR) and proximal upper limb (Biceps Brachii; BB). Methods We conducted a randomized double-blind study with 18 healthy adults. Each received anodal, dual-hemisphere, or sham tDCS over M1 in separate sessions (tDCS, 1 mA for 15 min). Results Linear regression analyzes showed a-tDCS modulated MEP size dependent on the latency difference in the ECR ( P = 0.01) but not BB ( P = 0.28). Individuals with small MEP latency differences showed the expected facilitation of ECR MEPs after a-tDCS, whereas those with large MEP latency differences had suppressed ECR MEPs after a-tDCS. This relationship was not present after dual-hemisphere or sham tDCS in either muscle (all P > 0.32). Conclusions I-wave recruitment can predict the after-effects of a-tDCS in the distal but not proximal upper limb. These findings provide further insight into the variability of tDCS after-effects, and the relationship between I-wave recruitment and putative mechanisms of tDCS. [ABSTRACT FROM AUTHOR]

Background Non-invasive brain stimulation techniques may be useful adjuvants to promote recovery after stroke. They are typically used to facilitate ipsilesional cortical excitability directly, or indirectly by suppressing contralesional cortical excitability and reducing interhemispheric inhibition from the contralesional to ipsilesional hemisphere. However, most of the evidence for this approach comes from studies of patients at the chronic stage of recovery. Hypothesis We hypothesized that corticomotor excitability and interhemispheric inhibition would initially be asymmetric, with greater interhemispheric inhibition from contralesional to ipsilesional M1. We also hypothesized that balancing of corticomotor excitability and interhemispheric inhibition would be associated with greater improvements in paretic upper-limb impairment and function. Methods We conducted a retrospective analysis of longitudinal data collected from 46 patients during the first six months after stroke. Transcranial magnetic stimulation was used to measure rest motor threshold, stimulus-response curves, and ipsilateral silent periods from the extensor carpi radialis muscles of both upper limbs. Analyses of variance and linear regression modeling were used to evaluate the effect of time on corticomotor excitability and interhemispheric inhibition in both hemispheres, and associations between these effects and improvements in paretic upper-limb impairment and function. Results All participants had subcortical damage and only two had motor cortex involvement. As expected, ipsilesional corticomotor excitability was initially suppressed and increased over time, and this increase was associated with improved upper-limb impairment and function. However, interhemispheric inhibition was symmetrical and stable over time, and there was no evidence for a decrease in contralesional corticomotor excitability. Conclusions Neuromodulation interventions applied during spontaneous recovery may be more beneficial if they facilitate ipsilesional corticomotor excitability directly. [ABSTRACT FROM AUTHOR]

Impairment or interruption of oxygen supply compromises brain function and plays a role in neurological and neurodegenerative conditions. Creatine is a naturally occurring compound involved in the buffering, transport, and regulation of cellular energy, with the potential to replenish cellular adenosine triphosphate without oxygen. Creatine is also neuroprotective in vitro against anoxic/hypoxic damage. Dietary creatine supplementation has been associated with improved symptoms in neurological disorders defined by impaired neural energy provision. Here we investigate, for the first time in humans, the utility of creatine as a dietary supplement to protect against energetic insult. The aim of this study was to assess the influence of oral creatine supplementation on the neurophysiological and neuropsychological function of healthy young adults during acute oxygen deprivation. Fifteen healthy adults were supplemented with creatine and placebo treatments for 7 d, which increased brain creatine on average by 9.2%. A hypoxic gas mixture (10% oxygen) was administered for 90 min, causing global oxygen deficit and impairing a range of neuropsychological processes. Hypoxia-induced decrements in cognitive performance, specifically attentional capacity, were restored when participants were creatine supplemented, and corticomotor excitability increased. A neuromodulatory effect of creatine via increased energy availability is presumed to be a contributing factor of the restoration, perhaps by supporting the maintenance of appropriate neuronal membrane potentials. Dietary creatine monohydrate supplementation augments neural creatine, increases corticomotor excitability, and prevents the decline in attention that occurs during severe oxygen deficit. This is the first demonstration of creatine's utility as a neuroprotective supplement when cellular energy provision is compromised. [ABSTRACT FROM AUTHOR]

The presence of carbohydrate in the human mouth has been associated with the facilitation of motor output and improvements in physical performance. Oral receptors have been identified as a potential mode of afferent transduction for this novel form of nutrient signalling that is distinct from taste. In the current study oral exposure to carbohydrate was combined with a motor task in a neuroimaging environment to identify areas of the brain involved in this phenomenon. A mouth-rinsing protocol was conducted whilst carbohydrate (CHO) and taste-matched placebo (PLA) solutions were delivered and recovered from the mouths of 10 healthy volunteers within a double-blind, counterbalanced design. This protocol eliminates post-oral factors and controls for the perceptual qualities of solutions. Functional magnetic resonance imaging of the brain was used to identify cortical areas responsive to oral carbohydrate during rest and activity phases of a hand-grip motor task. Mean blood-oxygen-level dependent signal change experienced in the contralateral primary sensorimotor cortex was larger for CHO compared with PLA during the motor task when contrasted with a control condition. Areas of activation associated with CHO exclusively were observed over the primary taste cortex and regions involved in visual perception. Regions in the limbic system associated with reward were also significantly more active with CHO. This is the first demonstration that oral carbohydrate signalling can increase activation within the primary sensorimotor cortex during physical activity and enhance activation of neural networks involved in sensory perception. [ABSTRACT FROM AUTHOR]

Background. The relationship between structural and functional integrity of descending motor pathways can predict the potential for motor recovery after stroke. The authors examine the relationship between brain imaging biomarkers within contralesional and ipsilesional hemispheres and hand function in well-recovered patients after subcortical stroke at the level of the internal capsule. Objective. Measures of functional activation and integrity of the ipsilesional corticospinal tract might predict paretic hand function. Methods. A total of 14 patients in the chronic stable phase of motor recovery after subcortical stroke and 24 healthy age-matched individuals participated in the study. Functional MRI was used to examine BOLD contrast during passive wrist flexion–extension and paced or maximum-velocity active fist clenching. Functional integrity of the corticospinal pathway was assessed by transcranial magnetic stimulation to obtain motor-evoked potentials (MEPs) in the first dorsal interosseus muscle of the paretic and nonparetic hands. Fractional anisotropy and the proportion of traces between hemispheres in the posterior limb of both internal capsules were quantified using diffusion-weighted MRI. Results. Patients with smaller MEPs had a weaker paretic hand and more primary motor cortex activation in their affected hemisphere. Asymmetry between white matter tracts of either hemisphere was associated with reduced precision grip strength and increased BOLD activation within the contralesional dorsal premotor cortex for demanding hand tasks. Conclusion. There may be beneficial reorganization in contralesional secondary motor areas with increasing damage to the corticospinal tract after subcortical stroke. Associations between clinical, functional, and structural integrity measures in chronic stroke may lead to a better understanding of motor recovery processes. [ABSTRACT FROM PUBLISHER]

Proximal upper limb muscles are represented bilaterally in primary motor cortex. Goal-directed upper limb movement requires precise control of proximal and distal agonist and antagonist muscles. Failure to suppress antagonist muscles can lead to abnormal movement patterns, such as those commonly experienced in the proximal upper limb after stroke. We examined whether noninvasive brain stimulation of primary motor cortex could be used to improve selective control of the ipsilateral proximal upper limb. Thirteen healthy participants performed isometric left elbow flexion by contracting biceps brachii (BB; agonist) and left forearm pronation (BB antagonist) before and after 20 min of cathodal transcranial direct current stimulation (c-tDCS) or sham tDCS of left M1. During the tasks, motor evoked potentials (MEPs) in left BB were acquired using single-pulse transcranial magnetic stimulation of right M1 150-270 ms before muscle contraction. As expected, left BB MEPs were facilitated before flexion and suppressed before pronation. After c-tDCS, left BB MEP amplitudes were reduced compared with sham stimulation, before pronation but not flexion, indicating that c-tDCS enhanced selective muscle activation of the ipsilateral BB in a taskspecific manner. The potential for c-tDCS to improve BB antagonist control correlated with BB MEP amplitude for pronation relative to flexion, expressed as a selectivity ratio. This is the first demonstration that selective muscle activation in the proximal upper limb can be improved after c-tDCS of ipsilateral M1 and that the benefits of c-tDCS for selective muscle activation may be most effective in cases where activation strategies are already suboptimal. These findings may have relevance for the use of tDCS in rehabilitation after stroke. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the involvement of the parietal cortex during motor imagery (MI). In experiment one, participants imagined a sequence of upper limb movements during FMRI scanning. Statistical parametric mapping revealed a network of activation consistent with previous MI research, including activation in right and left inferior and superior parietal cortex. In experiment two, participants imagined a sequence of upper limb movements while real or sham single-pulse TMS was delivered over the scalp area corresponding to each individual’s left or right superior parietal cortex. At the end of each trial, participants moved their upper limbs to the position that would result from executing the sequence of movements. TMS degraded accuracy of MI compared to sham stimulation, and both accuracy and confidence decreased with real and sham stimulation later in the MI sequence. The effects of TMS were similar when delivered to either hemisphere. The results of this study provide evidence of the crucial role of SPL in MI, and may have implications for rehabilitation from brain injury. [ABSTRACT FROM AUTHOR]

Fourteen neurologically healthy, right-handed subjects performed a choice-hand reaction time (RT) task, which involved wrist flexion or extension of either the left or right hand to one of three fixed target locations corresponding to 45° flexion, 20° flexion, or 20° extension from the starting position. In each trial, a pre-cue provided information regarding the forthcoming target location. The hand was specified by the imperative signal. Focal transcranial magnetic stimulation (TMS) was delivered over the hand motor area of either the right or left hemisphere at set times during the foreperiod, and at random intervals during the RT interval defined by electromyography onset. As expected, an increase in corticomotor excitability was observed in the agonist of the responding hand over the RT interval. When the cue appeared at a location that required flexion with either hand, an increase in excitability was observed following stimulation over the hemisphere ipsilateral to the responding hand, indicating activation of the homologous muscle. However, when the cue appeared at a location at which the response would require flexion with one hand and extension with the other, the modulation of excitability was also based on the direction of the response. This direction-specific effect was only observed for TMS delivered to the left hemisphere during the left-hand movement, and suggested goal-based preparation in the left hemisphere independent of whether the actual movement is made with the right or left hand. These results indicate that both the homologous-muscle and the directional-specific constraints affect the corticomotor excitability of the non-responding hand. [ABSTRACT FROM AUTHOR]

The hypothesis that motor imagery and actual movement involve overlapping neural structures in the central nervous system is supported by multiple lines of evidence. The aim of this study was to examine the modulation of corticomotor excitability during two types of strategies for motor imagery: Kinesthetic Motor Imagery (KMI) and Visual Motor Imagery (VMI) in a phasic thumb movement task. Transcranial magnetic stimulation (TMS) was applied over the contralateral motor cortex (M1) to elicit motor evoked potentials (MEPs) in the dominant abductor pollicis brevis (APB) and abductor digiti minimi (ADM). In a separate experiment, transcutaneous electrical stimuli were delivered to the median nerve at the dominant wrist, to elicit F-waves from APB. Imagined task performance was paced with a 1 Hz auditory metronome, and stimuli were delivered either 50 ms before (ON phase), or 450 ms after (OFF phase), the metronome beeps. Recordings were also made during two control conditions: Rest, and a Visual Static Imagery (VSI) condition. Significant MEP amplitude facilitation occurred only in APB, and only during the ON phase of KMI. F-wave persistence and amplitude were unaffected by imagery. These results demonstrate that kinesthetic, but not visual, motor imagery modulates corticomotor excitability, primarily at the supraspinal level. These findings have implications for the definition of motor imagery, and for its therapeutic applications. [ABSTRACT FROM AUTHOR]

Rhythmic movements are inherently more stable and easier to perform when they are synchronised with a periodic stimulus, as opposed to syncopated between the beats of a pacing stimulus. Although this behavioural phenomenon is well documented, its neurophysiological basis is poorly understood. In a first experiment, we demonstrated that all healthy subjects ( N=8) performing index finger abduction in time with an auditory metronome exhibited transitions from syncopation to synchronisation when the metronome tempo was scaled from 0.8 to 2.0 Hz. Subjects’ mean transition frequency was 1.7±0.2 Hz. In a second experiment, we used paired-pulse transcranial magnetic stimulation to examine short-latency intracortical inhibition (sICI) directed towards the first dorsal interosseous (FDI) muscle in healthy subjects ( N=9) who made synchronised and syncopated phasic finger movements in time with metronome pacing of 1.0 Hz. Despite the equivalence between the patterns in terms of task performance and corticospinal excitability of FDI at this movement frequency, there was significantly greater sICI during syncopation than during synchronisation. From this result, we infer that the stability of movement patterns may be contingent upon excitability of inhibitory networks within primary motor cortex. [ABSTRACT FROM AUTHOR]