Slow-oscillatory tACS does not modulate human motor cortical response to repeated plasticity paradigms.

Previous history of activity and learning modulates synaptic plasticity and can lead to saturation of synaptic connections. According to the synaptic homeostasis hypothesis, neural oscillations during slow-wave sleep play an important role in restoring plasticity within a functional range. However, it is not known whether slow-wave oscillations-without the concomitant requirement of sleep-play a causal role in human synaptic homeostasis. Here, we aimed to answer this question using transcranial alternating current stimulation (tACS) to induce slow-oscillatory activity in awake human participants. tACS was interleaved between two plasticity-inducing interventions: motor learning, and paired associative stimulation (PAS). The hypothesis tested was that slow-oscillatory tACS would prevent homeostatic interference between motor learning and PAS, and facilitate plasticity from these successive interventions. Thirty-six participants received sham and active fronto-motor tACS in two separate sessions, along with electroencephalography (EEG) recordings, while a further 38 participants received tACS through a control montage. Motor evoked potentials (MEPs) were recorded throughout the session to quantify plasticity changes after the different interventions, and the data were analysed with Bayesian statistics. As expected, there was converging evidence that motor training led to excitatory plasticity. Importantly, we found moderate evidence against an effect of active tACS in restoring PAS plasticity, and no evidence of lasting entrainment of slow oscillations in the EEG. This suggests that, under the conditions tested here, slow-oscillatory tACS does not modulate synaptic homeostasis in the motor system of awake humans.

Motor training is improved by concurrent application of slow oscillating transcranial alternating current stimulation to motor cortex.

Physical exercise and neurorehabilitation involve repetitive training that can induce changes in motor performance arising from neuroplasticity. Retention of these motor changes occurs via an encoding process, during which rapid neuroplastic changes occur in response to training. Previous studies show that transcranial alternating current stimulation (tACS), a form of non-invasive brain stimulation, can enhance encoding of a cognitive learning task during wakefulness. However, the effect of tACS on motor processes in the awake brain is unknown. In this study, forty-two healthy 18-35 year old participants received either 0.75 Hz (active) tACS (or sham stimulation) for 30 min during a ballistic thumb abduction motor training task. Training-related behavioural effects were quantified by assessing changes in thumb abduction acceleration, and neuroplastic changes were quantified by measuring motor evoked potential (MEP) amplitude of the abductor pollicis brevis muscle. These measures were reassessed immediately after the motor training task to quantify short-term changes, and then 24 h later to assess longer-term changes. Thumb abduction acceleration in both active and sham stimulation conditions increased immediately after the motor learning, consistent with effective training. Critically, participants in the active group maintained significantly higher thumb acceleration 24 h later (t40 = 2.810, P = 0.044). There were no significant changes or inter-group differences in MEPs for both conditions. The results suggest that 0.75 Hz tACS applied during motor training enhances the effectiveness of motor training, which manifests as enhancement in longer-term task benefits.

Unconscious Influences on "Free Will" Movement Initiation: Slow-wave Brain Stimulation and the Readiness Potential.

A central objective in the study of volition has been to identify how changes in neural activity relate to voluntary-"free will"-movement. The readiness potential (RP) is observed in the EEG as a slow-building signal that precedes action onset. Many consider the RP as a marker of an underlying preparatory process for initiating voluntary movement. However, the RP may emerge from ongoing slow-wave brain oscillations that influence the timing of movement initiation in a phase-dependent manner. Transcranial alternating current stimulation (tACS) enables brain oscillations to be entrained at the frequency of stimulation. We delivered tACS at a slow-wave frequency over frontocentral motor areas while participants (n = 30) performed a simple, self-paced button press task. During the active tACS condition, participants showed a tendency to initiate actions in the phase of the tACS cycle that corresponded to increased negative potentials across the frontocentral motor region. Comparisons of premovement EEG activity observed over frontocentral and central scalp electrodes showed earlier onset and increased amplitude of RPs from active stimulation compared with sham stimulation. This suggests that movement-related activity in the brain can be modulated by the delivery of weak, nonconsciously perceptible alternating currents over frontocentral motor regions. We present novel findings that support existing theories, which suggest the timing of voluntary movement is influenced by the phase of slow-changing oscillating brain states.

Effects of Slow Oscillatory Transcranial Alternating Current Stimulation on Motor Cortical Excitability Assessed by Transcranial Magnetic Stimulation.

Converging evidence suggests that transcranial alternating current stimulation (tACS) may entrain endogenous neural oscillations to match the frequency and phase of the exogenously applied current and this entrainment may outlast the stimulation (although only for a few oscillatory cycles following the cessation of stimulation). However, observing entrainment in the electroencephalograph (EEG) during stimulation is extremely difficult due to the presence of complex tACS artifacts. The present study assessed entrainment to slow oscillatory (SO) tACS by measuring motor cortical excitability across different oscillatory phases during (i.e., online) and outlasting (i.e., offline) stimulation. 30 healthy participants received 60 trials of intermittent SO tACS (0.75 Hz; 16 s on/off interleaved) at an intensity of 2 mA peak-to-peak. Motor cortical excitability was assessed using transcranial magnetic stimulation (TMS) of the hand region of the primary motor cortex (M1HAND) to induce motor evoked potentials (MEPs) in the contralateral thumb. MEPs were acquired at four time-points within each trial - early online, late online, early offline, and late offline - as well as at the start and end of the overall stimulation period (to probe longer-lasting aftereffects of tACS). A significant increase in MEP amplitude was observed from pre- to post-tACS (paired-sample t-test; t29 = 2.64, P = 0.013, d = 0.48) and from the first to the last tACS block (t29 = -2.93, P = 0.02, d = 0.54). However, no phase-dependent modulation of excitability was observed. Therefore, although SO tACS had a facilitatory effect on motor cortical excitability that outlasted stimulation, there was no evidence supporting entrainment of endogenous oscillations as the underlying mechanism.

Gamma coherence mediates interhemispheric integration during multiple object tracking.

Our ability to track the paths of multiple visual objects moving between the hemifields requires effective integration of information between the two cerebral hemispheres. Coherent neural oscillations in the gamma band (35-70 Hz) are hypothesized to drive this information transfer. Here we manipulated the need for interhemispheric integration using a novel multiple object tracking (MOT) task in which stimuli either moved between the two visual hemifields, requiring interhemispheric integration, or moved within separate visual hemifields. We used electroencephalography (EEG) to measure interhemispheric coherence during the task. Human observers (21 women; 20 men) were poorer at tracking objects between versus within hemifields, reflecting a cost of interhemispheric integration. Critically, gamma coherence was greater in trials requiring interhemispheric integration, particularly between sensors over parieto-occipital areas. In approximately half of the participants, the observed cost of integration was associated with a failure of the cerebral hemispheres to become coherent in the gamma band. Moreover, individual differences in this integration cost correlated with endogenous gamma coherence at these same sensors, although with generally opposing relationships for the real and imaginary part of coherence. The real part (capturing synchronization with a near-zero phase lag) benefited between-hemifield tracking; imaginary coherence was detrimental. Finally, instantaneous phase coherence over the tracking period uniquely predicted between-hemifield tracking performance, suggesting that effective integration benefits from sustained interhemispheric synchronization. Our results show that gamma coherence mediates interhemispheric integration during MOT and add to a growing body of work demonstrating that coherence drives communication across cortically distributed neural networks.NEW & NOTEWORTHY Using a multiple object tracking paradigm, we were able to manipulate the need for interhemispheric integration on a per-trial basis, while also having an objective measure of integration efficacy (i.e., tracking performance). We show that tracking performance reflects a cost of integration, which correlates with individual differences in interhemispheric EEG coherence. Gamma coherence appears to uniquely benefit between-hemifield tracking, predicting performance both across participants and across trials.

Current challenges: the ups and downs of tACS.

The non-invasive delivery of electric currents through the scalp (transcranial electrical stimulation) is a popular tool for neuromodulation, mostly due to its highly adaptable nature (waveform, montage) and tolerability at low intensities (< 2 mA). Applied rhythmically, transcranial alternating current stimulation (tACS) may entrain neural oscillations in a frequency- and phase-specific manner, providing a causal perspective on brain-behaviour relationships. While the past decade has seen many behavioural and electrophysiological effects of tACS that suggest entrainment-mediated effects in the brain, it has been difficult to reconcile such reports with the weak intracranial field strengths (< 1 V/m) achievable at conventional intensities. In this review, we first describe the ongoing challenges faced by users of tACS. We outline the biophysics of electrical brain stimulation and the factors that contribute to the weak field intensities achievable in the brain. Since the applied current predominantly shunts through the scalp-stimulating the nerves that innervate it-the plausibility of transcutaneous (rather than transcranial) effects of tACS is also discussed. In examining the effects of tACS on brain activity, the complex problem of salvaging electrophysiological recordings from artefacts of tACS is described. Nevertheless, these challenges by no means mark the rise and fall of tACS: the second part of this review outlines the recent advancements in the field. We describe some ways in which artefacts of tACS may be better managed using high-frequency protocols, and describe innovative methods for current interactions within the brain that offer either dynamic or more focal current distributions while also minimising transcutaneous effects.

Differentiating Beyond Name Agreement for Picture Naming: Insight From Age-Related Selection Deficits.

Purpose Pictures consistently referred to by the same name (high agreement) are named faster than pictures that elicit inconsistent responses across individuals (low agreement). Although this effect is more pronounced in older adults apparently due to slower lexical selection, it is unclear whether this is consistent for different types of low agreement pictures. We investigated whether pictures with different sources of disagreement have differing selection requirements, as indexed by naming latencies. Method Picture naming latencies were compared for 20 young (ages 18-35 years) and 20 older adults (ages 60-80 years) across 3 object naming conditions: high name agreement, low name agreement due to multiple correct names, and low agreement due to abbreviations and elaborations. Results Compared to high agreement items, responses were slower specifically for low agreement items with multiple names, and to a lesser extent, items with abbreviations and elaborations ( p < .001). Older adults were slower than younger adults, especially for low agreement items with abbreviations and elaborations ( p = .031). Conclusions Our findings indicate differential lexical selection requirements for low agreement pictures, depending on the reason for agreement being low. This demonstrates the importance of differentiating the source of disagreement in any experimental or clinical assessment of picture naming.

Improved language production with transcranial direct current stimulation in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is an atypical parkinsonian disorder that can present with language production deficits in addition to the characteristic progressive parkinsonian motor symptoms. Although typical parkinsonism treatments such as pharmacotherapy are not effective in PSP, non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) have shown promise for treating cognitive deficits relating to this disorder. We report the case of KN, who presented with reduced verbal fluency and connected speech production in the context of PSP. KN completed a set of language tasks, followed by an alternate version of the tasks in conjunction with either sham or active tDCS over the left dorsolateral prefrontal cortex (DLPFC) across four sessions. Results showed improved performance with active stimulation compared to sham stimulation for phonemic fluency and action naming, as well as mixed results suggesting possible benefits for connected speech production. There were no benefits of active stimulation for control tasks, indicating that tDCS can produce specific benefits for phonemic fluency, action naming, and connected speech production in PSP. These promising, preliminary findings warrant further investigation into whether these benefits of tDCS can be a useful therapeutic tool for PSP patients to maintain language.

Age-related differences in idea generation and selection for propositional language.

Conceptual preparation mechanisms such as novel idea generation and selection from amongst competing alternatives are critical for language production and may contribute to age-related language deficits. This study investigated whether older adults show diminished idea generation and selection abilities, compared to younger adults. Twenty younger (18-35 years) and 20 older (60-80 years) adults completed two novel experimental tasks, an idea generation task and a selection task. Older participants were slower than younger participants overall on both tasks. Importantly, this difference was more pronounced for task conditions with greater demands on generation and selection. Older adults were also significantly reduced on a semantic, but not phonemic, word fluency task. Overall, the older group showed evidence of age-related decline specific to idea generation and selection ability. This has implications for the message formulation stage of propositional language decline in normal aging.

Improved conceptual generation and selection with transcranial direct current stimulation in older adults.

INTRODUCTION: Normal aging is associated with deficits in various aspects of spoken language production, including idea generation and selection, and involves activity in frontal brain areas including left inferior frontal cortex (LIFG). These conceptual preparation processes, largely involving executive control, precede formulation and articulation stages and are critical for language production. Noninvasive brain stimulation (e.g., transcranial direct current stimulation, tDCS) has proven beneficial for age-related fluency and naming deficits, but this has not been extended to conceptual preparation mechanisms. METHOD: We investigated whether tDCS could facilitate idea generation and selection in 24 older adults aged 60-80 years. In the first phase, participants completed an idea generation test and a selection test with no stimulation. In the second phase they completed an alternate version of the tests in conjunction with either active or sham stimulation. Active stimulation applied 1-mA anodal tDCS over LIFG for the test duration (10 min). RESULTS: Responses were faster following active stimulation than following sham. Furthermore, improvements were specific to test conditions involving novel generation (p = .030) and selection (p = .001) and were not observed in control conditions for which these mechanisms were minimally involved. CONCLUSIONS: We concluded that tDCS benefits conceptual preparation mechanisms. This preliminary evidence is an important step for addressing age-related decline in propositional language generation, which is integral to conversational speech. This approach could also be extended toward rehabilitation in neurological patients with deficits in these processes.

No Evidence for Phase-Specific Effects of 40 Hz HD-tACS on Multiple Object Tracking.

Phase synchronization drives connectivity between neural oscillators, providing a flexible mechanism through which information can be effectively and selectively routed between task-relevant cortical areas. The ability to keep track of objects moving between the left and right visual hemifields, for example, requires the integration of information between the two cerebral hemispheres. Both animal and human studies have suggested that coherent (or phase-locked) gamma oscillations (30-80 Hz) might underlie this ability. While most human evidence has been strictly correlational, high-density transcranial alternating current stimulation (HD-tACS) has been used to manipulate ongoing interhemispheric gamma phase relationships. Previous research showed that 40 Hz tACS delivered bilaterally over human motion complex could bias the perception of a bistable ambiguous motion stimulus (Helfrich et al., 2014). Specifically, this work showed that in-phase (0° offset) stimulation boosted endogenous interhemispheric gamma coherence and biased perception toward the horizontal (whereby visual tokens moved between visual hemifields-requiring interhemispheric integration). By contrast, anti-phase (180° offset) stimulation decreased interhemispheric gamma coherence and biased perception toward the vertical (whereby tokens moved within separate visual hemifields). Here we devised a multiple object tracking arena comprised of four quadrants whereby discrete objects moved either entirely within the left and right visual hemifields, or could cross freely between visual hemifields, thus requiring interhemispheric integration. Using the same HD-tACS montages as Helfrich et al. (2014), we found no phase-specific effect of 40 Hz stimulation on overall tracking performance. While tracking performance was generally lower during between-hemifield trials (presumably reflecting a cost of integration), this difference was unchanged by in- vs. anti-phase stimulation. Our null results could be due to a failure to reliably modulate coherence in our study, or that our task does not rely as heavily on this network of coherent gamma oscillations as other visual integration paradigms.

Neural Oscillations and the Initiation of Voluntary Movement.

The brain processes involved in the planning and initiation of voluntary action are of great interest for understanding the relationship between conscious awareness of decisions and the neural control of movement. Voluntary motor behavior has generally been considered to occur when conscious decisions trigger movements. However, several studies now provide compelling evidence that brain states indicative of forthcoming movements take place before a person becomes aware of a conscious decision to act. While such studies have created much debate over the nature of 'free will,' at the very least they suggest that unconscious brain processes are predictive of forthcoming movements. Recent studies suggest that slow changes in neuroelectric potentials may play a role in the timing of movement onset by pushing brain activity above a threshold to trigger the initiation of action. Indeed, recent studies have shown relationships between the phase of low frequency oscillatory activity of the brain and the onset of voluntary action. Such studies, however, cannot determine whether this underlying neural activity plays a causal role in the initiation of movement or is only associated with the intentional behavior. Non-invasive transcranial alternating current brain stimulation can entrain neural activity at particular frequencies in order to assess whether underlying brain processes are causally related to associated behaviors. In this review, we examine the evidence for neural coding of action as well as the brain states prior to action initiation and discuss whether low frequency alternating current brain stimulation could influence the timing of a persons' decision to act.

Corticospinal Plasticity in Bilateral Primary Motor Cortices Induced by Paired Associative Stimulation to the Dominant Hemisphere Does Not Differ between Young and Older Adults.

Older adults have been shown to exhibit a reduction in the lateralization of neural activity. Although neuroplasticity induced by noninvasive brain stimulation has been reported to be attenuated in the targeted motor cortex of older adults, it remains possible that the plasticity effects may instead manifest in a more distributed (bilateral) network. Furthermore, attention, which modulates neuroplasticity in young adults, may influence these effects. To address these questions, plasticity was induced in young (19-32 years) and older (65-78 years) adults using transcranial magnetic stimulation (TMS) paired with peripheral nerve stimulation. The plasticity effects induced by this paired associative stimulation (PAS) protocol in the targeted and nontargeted hemispheres were probed using TMS-induced motor-evoked potentials (MEPs) recorded from the abductor pollicis brevis (APB) muscle of each hand. PAS-induced effects were highly variable across individuals, with only half of the participants in each group demonstrating the expected increase in MEP amplitude. Contrary to predictions, however, PAS-induced corticospinal plasticity manifests predominately in the targeted hemisphere for both young and older adults. Attention to the target hand did not enhance corticospinal plasticity. The results suggest that plasticity does not manifest differently across bilateral corticospinal pathways between young and older adults.

Brain changes following four weeks of unimanual motor training: Evidence from fMRI-guided diffusion MRI tractography.

We have reported reliable changes in behavior, brain structure, and function in 24 healthy right-handed adults who practiced a finger-thumb opposition sequence task with their left hand for 10 min daily, over 4 weeks. Here, we extend these findings by using diffusion MRI to investigate white-matter changes in the corticospinal tract, basal-ganglia, and connections of the dorsolateral prefrontal cortex. Twenty-three participant datasets were available with pre-training and post-training scans. Task performance improved in all participants (mean: 52.8%, SD: 20.0%; group P < 0.01 FWE) and widespread microstructural changes were detected across the motor system of the "trained" hemisphere. Specifically, region-of-interest-based analyses of diffusion MRI (n = 22) revealed significantly increased fractional anisotropy (FA) in the right caudate nucleus (4.9%; P < 0.05 FWE), and decreased mean diffusivity in the left nucleus accumbens (-1.3%; P < 0.05 FWE). Diffusion MRI tractography (n = 22), seeded by sensorimotor cortex fMRI activation, also revealed increased FA in the right corticospinal tract (mean 3.28%; P < 0.05 FWE) predominantly reflecting decreased radial diffusivity. These changes were consistent throughout the entire length of the tract. The left corticospinal tract did not show any changes. FA also increased in white matter connections between the right middle frontal gyrus and both right caudate nucleus (17/22 participants; P < 0.05 FWE) and right supplementary motor area (18/22 participants; P < 0.05 FWE). Equivalent changes in FA were not seen in the left (non-trained) hemisphere. In combination with our functional and structural findings, this study provides detailed, multifocal evidence for widespread neuroplastic changes in the human brain resulting from motor training. Hum Brain Mapp 38:4302-4312, 2017. © 2017 Wiley Periodicals, Inc.

Brain changes following four weeks of unimanual motor training: Evidence from behavior, neural stimulation, cortical thickness, and functional MRI.

Although different aspects of neuroplasticity can be quantified with behavioral probes, brain stimulation, and brain imaging assessments, no study to date has combined all these approaches into one comprehensive assessment of brain plasticity. Here, 24 healthy right-handed participants practiced a sequence of finger-thumb opposition movements for 10 min each day with their left hand. After 4 weeks, performance for the practiced sequence improved significantly (P < 0.05 FWE) relative to a matched control sequence, with both the left (mean increase: 53.0% practiced, 6.5% control) and right (21.0%; 15.8%) hands. Training also induced significant (cluster p-FWE < 0.001) reductions in functional MRI activation for execution of the trained sequence, relative to the control sequence. These changes were observed as clusters in the premotor and supplementary motor cortices (right hemisphere, 301 voxel cluster; left hemisphere 700 voxel cluster), and sensorimotor cortices and superior parietal lobules (right hemisphere 864 voxel cluster; left hemisphere, 1947 voxel cluster). Transcranial magnetic stimulation over the right ("trained") primary motor cortex yielded a 58.6% mean increase in a measure of motor evoked potential amplitude, as recorded at the left abductor pollicis brevis muscle. Cortical thickness analyses based on structural MRI suggested changes in the right precentral gyrus, right post central gyrus, right dorsolateral prefrontal cortex, and potentially the right supplementary motor area. Such findings are consistent with LTP-like neuroplastic changes in areas that were already responsible for finger sequence execution, rather than improved recruitment of previously nonutilized tissue. Hum Brain Mapp 38:4773-4787, 2017. © 2017 Wiley Periodicals, Inc.

Stimulus uncertainty enhances long-term potentiation-like plasticity in human motor cortex.

Plasticity can be induced in human cortex using paired associative stimulation (PAS), which repeatedly and predictably pairs a peripheral electrical stimulus with transcranial magnetic stimulation (TMS) to the contralateral motor region. Many studies have reported small or inconsistent effects of PAS. Given that uncertain stimuli can promote learning, the predictable nature of the stimulation in conventional PAS paradigms might serve to attenuate plasticity induction. Here, we introduced stimulus uncertainty into the PAS paradigm to investigate if it can boost plasticity induction. Across two experimental sessions, participants (n = 28) received a modified PAS paradigm consisting of a random combination of 90 paired stimuli and 90 unpaired (TMS-only) stimuli. Prior to each of these stimuli, participants also received an auditory cue which either reliably predicted whether the upcoming stimulus was paired or unpaired (no uncertainty condition) or did not predict the upcoming stimulus (maximum uncertainty condition). Motor evoked potentials (MEPs) evoked from abductor pollicis brevis (APB) muscle quantified cortical excitability before and after PAS. MEP amplitude increased significantly 15 min following PAS in the maximum uncertainty condition. There was no reliable change in MEP amplitude in the no uncertainty condition, nor between post-PAS MEP amplitudes across the two conditions. These results suggest that stimulus uncertainty may provide a novel means to enhance plasticity induction with the PAS paradigm in human motor cortex. To provide further support to the notion that stimulus uncertainty and prediction error promote plasticity, future studies should further explore the time course of these changes, and investigate what aspects of stimulus uncertainty are critical in boosting plasticity.

A hierarchy of timescales explains distinct effects of local inhibition of primary visual cortex and frontal eye fields.

Within the primate visual system, areas at lower levels of the cortical hierarchy process basic visual features, whereas those at higher levels, such as the frontal eye fields (FEF), are thought to modulate sensory processes via feedback connections. Despite these functional exchanges during perception, there is little shared activity between early and late visual regions at rest. How interactions emerge between regions encompassing distinct levels of the visual hierarchy remains unknown. Here we combined neuroimaging, non-invasive cortical stimulation and computational modelling to characterize changes in functional interactions across widespread neural networks before and after local inhibition of primary visual cortex or FEF. We found that stimulation of early visual cortex selectively increased feedforward interactions with FEF and extrastriate visual areas, whereas identical stimulation of the FEF decreased feedback interactions with early visual areas. Computational modelling suggests that these opposing effects reflect a fast-slow timescale hierarchy from sensory to association areas.

Different Stimulation Frequencies Alter Synchronous Fluctuations in Motor Evoked Potential Amplitude of Intrinsic Hand Muscles-a TMS Study.

The amplitude of motor-evoked potentials (MEPs) elicited with transcranial magnetic stimulation (TMS) varies from trial-to-trial. Synchronous oscillations in cortical neuronal excitability contribute to this variability, however it is not known how different frequencies of stimulation influence MEP variability, and whether these oscillations are rhythmic or aperiodic. We stimulated the motor cortex with TMS at different regular (i.e., rhythmic) rates, and compared this with pseudo-random (aperiodic) timing. In 18 subjects, TMS was applied at three regular frequencies (0.05 Hz, 0.2 Hz, 1 Hz) and one aperiodic frequency (mean 0.2 Hz). MEPs (n = 50) were recorded from three intrinsic hand muscles of the left hand with different functional and anatomical relations. MEP amplitude correlation was highest for the functionally related muscle pair, less for the anatomically related muscle pair and least for the functionally- and anatomically-unrelated muscle pair. MEP correlations were greatest with 1 Hz, and least for stimulation at 0.05 Hz. Corticospinal neuron synchrony is higher with shorter TMS intervals. Further, corticospinal neuron synchrony is similar irrespective of whether the stimulation is periodic or aperiodic. These findings suggest TMS frequency is a crucial consideration for studies using TMS to probe correlated activity between muscle pairs.

Associative plasticity in the human motor cortex is enhanced by concurrently targeting separate muscle representations with excitatory and inhibitory protocols.

Paired associative stimulation (PAS) induces changes in the excitability of human sensorimotor cortex that outlast the procedure. PAS typically involves repeatedly pairing stimulation of a peripheral nerve that innervates an intrinsic hand muscle with transcranial magnetic stimulation over the representation of that muscle in the primary motor cortex. Depending on the timing of the stimuli (interstimulus interval of 25 or 10 ms), PAS leads to either an increase (PAS25) or a decrease (PAS10) in excitability. Both protocols, however, have been associated with an increase in excitability of nearby muscle representations not specifically targeted by PAS. Based on these spillover effects, we hypothesized that an additive, excitability-enhancing effect of PAS25 applied to one muscle representation may be produced by simultaneously applying PAS25 or PAS10 to a nearby representation. In different experiments prototypical PAS25 targeting the left thumb representation [abductor pollicis brevis (APB)] was combined with either PAS25 or PAS10 applied to the left little finger representation [abductor digiti minimi (ADM)] or, in a control experiment, with PAS10 also targeting the APB. In an additional control experiment PAS10 targeted both representations. The plasticity effects were quantified by measuring the amplitude of motor evoked potentials (MEPs) recorded before and after PAS. As expected, prototypical PAS25 was associated with an increase in MEP amplitude in the APB muscle. This effect was enhanced when PAS also targeted the ADM representation but only when a different interstimulus timing (PAS10) was used. These results suggest that PAS-induced plasticity is modified by concurrently targeting separate motor cortical representations with excitatory and inhibitory protocols.

Increased intracortical inhibition in elderly adults with anterior-posterior current flow: A TMS study.

OBJECTIVE: All previous studies using TMS to assess short-interval intracortical inhibition (SICI) in older adults have used a conventional coil orientation, which produces posterior-to-anterior (PA) current flow in the motor cortex. However, no studies have examined SICI in older adults by reversing the coil to induce anterior-to-posterior (AP) current flow, which is considered more sensitive at detecting SICI. Therefore, we investigated age-related changes in SICI using both PA and AP TMS across different conditioning stimulus intensities and muscle activation states. METHODS: In 22 young and 20 older adults, SICI was assessed using PA and AP coil orientations, across a range of conditioning stimulus intensities (70-90% active motor threshold), and whilst participants kept their first dorsal interosseous (FDI) muscle either relaxed or active (2N force). RESULTS: There were no age-related differences in SICI using conventional PA TMS in resting or active FDI muscle. However, SICI was increased in elderly participants when assessed with reverse coil AP TMS in resting FDI. CONCLUSIONS: Coil orientation is a key factor to consider when assessing age-related differences in SICI. SIGNIFICANCE: Reverse coil AP TMS can reveal age-related changes in SICI, which were previously not evident with conventional PA TMS. This may have implications for the assessment of SICI in some clinical populations that may show subtle differences in SICI circuitry.