Dynamic involvement of premotor and supplementary motor areas in bimanual pinch force control.

Many activities of daily living require quick shifts between symmetric and asymmetric bimanual actions. Bimanual motor control has been mostly studied during continuous repetitive tasks, while little research has been carried out in experimental settings requiring dynamic changes in motor output generated by both hands. Here, we performed functional magnetic resonance imaging (MRI) while healthy volunteers performed a visually guided, bimanual pinch force task. This enabled us to map functional activity and connectivity of premotor and motor areas during bimanual pinch force control in different task contexts, requiring mirror-symmetric or inverse-asymmetric changes in discrete pinch force exerted with the right and left hand. The bilateral dorsal premotor cortex showed increased activity and effective coupling to the ipsilateral supplementary motor area (SMA) in the inverse-asymmetric context compared to the mirror-symmetric context of bimanual pinch force control while the SMA showed increased negative coupling to visual areas. Task-related activity of a cluster in the left caudal SMA also scaled positively with the degree of synchronous initiation of bilateral pinch force adjustments, irrespectively of the task context. The results suggest that the dorsal premotor cortex mediates increasing complexity of bimanual coordination by increasing coupling to the SMA while SMA provides feedback about motor actions to the sensory system.

Multipulse transcranial magnetic stimulation of human motor cortex produces short-latency corticomotor facilitation via two distinct mechanisms.

Single-pulse transcranial magnetic stimulation (TMS) of the precentral hand representation (M1HAND) can elicit indirect waves in the corticospinal tract at a periodicity of ∼660 Hz, called I-waves. These descending volleys are produced by transsynaptic excitation of fast-conducting corticospinal axons in M1HAND. Paired-pulse TMS can induce short-interval intracortical facilitation (SICF) of motor evoked potentials (MEPs) at interpulse intervals that match I-wave periodicity. This study examined whether short-latency corticospinal facilitation engages additional mechanisms independently of I-wave periodicity. In 19 volunteers, one to four biphasic TMS pulses were applied to left M1HAND with interpulse intervals adjusted to the first peak or trough of the individual SICF curve at different intensities to probe the intensity-response relationship. Multipulse TMSHAND at individual peak latency facilitated MEP amplitudes and reduced resting motor threshold (RMT) compared with single pulses. Multipulse TMSHAND at individual trough latency also produced a consistent facilitation of MEPs and a reduction of RMT. Short-latency facilitation at trough latency was less pronounced, but the relative difference in facilitation decreased with increasing stimulus intensity. Increasing the pulse number had only a modest effect. Two mechanisms underlie short-latency facilitation caused by biphasic multipulse TMSHAND. One intracortical mechanism is related to I-wave periodicity and engages fast-conducting direct projections to spinal motoneurons. A second corticospinal mechanism does not rely on I-wave rhythmicity and may be mediated by slower-conducting indirect pyramidal tract projections from M1HAND to spinal interneurons. The latter mechanism deserves more attention in studies of the corticomotor system and its link to manual motor control using the MEP.NEW & NOTEWORTHY TMS pairs evoke SICF at interpulse intervals (IPIs) that match I-wave periodicity. Biphasic bursts with IPIs at the latency of the first peak facilitate MEPs and reduce corticomotor threshold. Bursts at the latency of the first trough facilitate MEPs and reduce corticomotor threshold to a lesser extent. TMS bursts facilitate corticomotor excitability via two mechanisms: SICF-dependently via fast-conducting direct projections from M1HAND to spinal motoneurons and SICF-independently, probably through slower-conducting indirect pyramidal tract projections.

Corticomuscular coherence is reduced in relation to dorsiflexion fatigability to the same extent in adults with cerebral palsy as in neurologically intact adults.

PURPOSE: Fatigue is frequent in adults with cerebral palsy (CP) and it is unclear whether this is due to altered corticospinal drive. We aimed to compare changes in corticospinal drive following sustained muscle contractions in adults with CP and neurologically intact (NI) adults. METHODS: Fourteen adults with CP [age 37.6 (10.1), seven females, GMFCS levels I-II] and ten NI adults [age 35.4 (10.3), 6 females] performed 1-min static dorsiflexion at 30% of maximal voluntary contraction (MVC) before and after a submaximal contraction at 60% MVC. Electroencephalography (EEG) and electromyography (EMG) from the anterior tibial muscle were analyzed to quantify the coupling, expressed by corticomuscular coherence (CMC). RESULTS: Adults with CP had lower MVCs but similar time to exhaustion during the relative load of the fatigability trial. Both groups exhibited fatigability-related changes in EMG median frequency and EMG amplitude. The CP group showed lower beta band (16-35 Hz) CMC before fatigability, but both groups decreased beta band CMC following fatigability. There was a linear correlation between decrease of beta band CMC and fatigability-related increase in EMG. CONCLUSION: Fatigability following static contraction until failure was related to decreased beta band CMC in both NI adults and adults with CP. Our findings indicate that compensatory mechanisms to fatigability are present in both groups, and that fatigability affects the corticospinal drive in the same way. We suggest that the perceived physical fatigue in CP is related to the high relative load of activities of daily living rather than any particular physiological mechanism.

Directed connectivity between primary and premotor areas underlying ankle force control in young and older adults.

The control of ankle muscle force is an integral component of walking and postural control. Aging impairs the ability to produce force steadily and accurately, which can compromise functional capacity and quality of life. Here, we hypothesized that reduced force control in older adults would be associated with altered cortico-cortical communication within a network comprising the primary motor area (M1), the premotor cortex (PMC), parietal, and prefrontal regions. We examined electroencephalographic (EEG) responses from fifteen younger (20-26 â€‹yr) and fifteen older (65-73 â€‹yr) participants during a unilateral dorsiflexion force-tracing task. Dynamic Causal Modelling (DCM) and Parametric Empirical Bayes (PEB) were used to investigate how directed connectivity between contralateral M1, PMC, parietal, and prefrontal regions was related to age group and precision in force production. DCM and PEB analyses revealed that the strength of connections between PMC and M1 were related to ankle force precision and differed by age group. For young adults, bidirectional PMC-M1 coupling was negatively related to task performance: stronger backward M1-PMC and forward PMC-M1 coupling was associated with worse force precision. The older group exhibited deviations from this pattern. For the PMC to M1 coupling, there were no age-group differences in coupling strength; however, within the older group, stronger coupling was associated with better performance. For the M1 to PMC coupling, older adults followed the same pattern as young adults - with stronger coupling accompanied by worse performance - but coupling strength was lower than in the young group. Our results suggest that bidirectional M1-PMC communication is related to precision in ankle force production and that this relationship changes with aging. We argue that the observed differences reflect compensatory reorganization that counteracts age-related sensorimotor declines and contributes to maintaining performance.

Getting to grips with endoscopy - Learning endoscopic surgical skills induces bi-hemispheric plasticity of the grasping network.

Endoscopic surgery requires skilled bimanual use of complex instruments that extend the peri-personal workspace. To delineate brain structures involved in learning such surgical skills, 48 medical students without surgical experience were randomly assigned to five training sessions on a virtual-reality endoscopy simulator or to a non-training group. Brain activity was probed with functional MRI while participants performed endoscopic tasks. Repeated task performance in the scanner was sufficient to enhance task-related activity in left ventral premotor cortex (PMv) and the anterior Intraparietal Sulcus (aIPS). Simulator training induced additional increases in task-related activation in right PMv and aIPS and reduced effective connectivity from left to right PMv. Skill improvement after training scaled with stronger task-related activation of the lateral left primary motor hand area (M1-HAND). The results suggest that a bilateral fronto-parietal grasping network and left M1-HAND are engaged in bimanual learning of tool-based manipulations in an extended peri-personal space.

Modulation of fronto-parietal connections during the rubber hand illusion.

Accumulating evidence suggests that parieto-frontal connections play a role in adjusting body ownership during the Rubber Hand Illusion (RHI). Using a motor version of the rubber hand illusion paradigm, we applied single-site and dual-site transcranial magnetic stimulation (TMS) to investigate cortico-spinal and parietal-frontal connectivity during perceived rubber hand ownership. Healthy volunteers received a conditioning TMS pulse over left anterior intraparietal sulcus (aIPS) and a test TMS pulse over left primary motor cortex (M1). Motor Evoked Potentials (MEPs) were recorded at rest and during three RHI conditions: (i) agency and ownership, (ii) agency but no ownership and (iii) neither agency nor ownership. Parietal-motor communication differed among experimental conditions. The induction of action ownership was associated with an inhibitory parietal-to-motor connectivity, which was comparable to the aIPS-to-M1 inhibition present at rest. This aIPS-to-M1 inhibition disappeared during movement conditions not inducing ownership. Cortico-spinal excitability was not significantly modulated during the motor RHI as indicated by the task-constant MEP amplitude elicited by the M1 test pulse alone. Our results indicate that the perceived ownership over the rubber hand is associated with normal parietal-motor communication. This communication is disturbed if the sensorimotor conflict between one's own hand and the rubber hand is not resolved.

Induction of motor associative plasticity in the posterior parietal cortex-primary motor network.

There is anatomical and functional connectivity between the primary motor cortex (M1) and posterior parietal cortex (PPC) that plays a role in sensorimotor integration. In this study, we applied corticocortical paired-associative stimuli to ipsilateral PPC and M1 (parietal ccPAS) in healthy right-handed subjects to test if this procedure could modulate M1 excitability and PPC-M1 connectivity. One hundred and eighty paired transcranial magnetic stimuli to the PPC and M1 at an interstimulus interval (ISI) of 8 ms were delivered at 0.2 Hz. We found that parietal ccPAS in the left hemisphere increased the excitability of conditioned left M1 assessed by motor evoked potentials (MEPs) and the input-output curve. Motor behavior assessed by the Purdue pegboard task was unchanged compared with controls. At baseline, conditioning stimuli over the left PPC potentiated MEPs from left M1 when ISI was 8 ms. This interaction significantly attenuated at 60 min after left parietal ccPAS. Additional experiments showed that parietal ccPAS induced plasticity was timing-dependent, was absent if ISI was 100 ms, and could also be seen in the right hemisphere. Our results suggest that parietal ccPAS can modulate M1 excitability and PPC-M1 connectivity and is a new approach to modify motor excitability and sensorimotor interaction.

Older and younger adults differ in time course of skill acquisition but not in overall improvement in a bimanual visuomotor tracking task.

Manual motor performance declines with age, but the extent to which age influences the acquisition of new skills remains a topic of debate. Here, we examined whether older healthy adults show less training-dependent performance improvements during a single session of a bimanual pinch task than younger adults. We also explored whether physical and cognitive factors, such as grip strength or motor-cognitive ability, are associated with performance improvements. Healthy younger (n = 16) and older (n = 20) adults performed three training blocks separated by short breaks. Participants were tasked with producing visually instructed changes in pinch force using their right and left thumb and index fingers. Task complexity was varied by shifting between bimanual mirror-symmetric and inverse-asymmetric changes in pinch force. Older adults generally displayed higher visuomotor force tracking errors during the more complex inverse-asymmetric task compared to younger adults. Both groups showed a comparable net decrease in visuomotor force tracking error over the entire session, but their improvement trajectories differed. Young adults showed enhanced visuomotor tracking error only in the first block, while older adults exhibited a more gradual improvement over the three training blocks. Furthermore, grip strength and performance on a motor-cognitive test battery scaled positively with individual performance improvements during the first block in both age groups. Together, the results show subtle age-dependent differences in the rate of bimanual visuomotor skill acquisition, while overall short-term learning ability is maintained.

Short periods of bipolar anodal TDCS induce no instantaneous dose-dependent increase in cerebral blood flow in the targeted human motor cortex.

Anodal transcranial direct current stimulation (aTDCS) of primary motor hand area (M1-HAND) can enhance corticomotor excitability, but it is still unknown which current intensity produces the strongest effect on intrinsic neural firing rates and synaptic activity. Magnetic resonance imaging (MRI) combined with pseudo-continuous Arterial Spin Labeling (pcASL MRI) can map regional cortical blood flow (rCBF). The measured rCBF signal is sensitive to regional changes in neuronal activity due to neurovascular coupling. Therefore, concurrent TDCS and pcASL MRI may reveal the relationship between current intensity and TDCS-induced changes in overall firing rates and synaptic activity in the cortical target. Here we employed pcASL MRI to map acute rCBF changes during short-duration aTDCS of left M1-HAND. Using the rCBF response as a proxy for regional neuronal activity, we investigated if short-duration aTDCS produces an instantaneous dose-dependent rCBF increase in the targeted M1-HAND that may be useful for individual dosing. Nine healthy right-handed participants received 30 s of aTDCS at 0.5, 1.0, 1.5, and 2.0 mA with the anode placed over left M1-HAND and cathode over the right supraorbital region. Concurrent pcASL MRI at 3 T probed TDCS-related rCBF changes in the targeted M1-HAND. Movement-induced rCBF changes were also assessed. Apart from a subtle increase in rCBF at 0.5 mA, short-duration aTDCS did not modulate rCBF in the M1-HAND relative to no-stimulation periods. None of the participants showed a dose-dependent increase in rCBF during aTDCS, even after accounting for individual differences in TDCS-induced electrical field strength. In contrast, finger movements led to robust activation of left M1-HAND before and after aTDCS. Short-duration bipolar aTDCS does not produce consistant instantaneous dose-dependent rCBF increases in the targeted M1-HAND at conventional intensity ranges. Therefore, the regional hemodynamic response profile to short-duration aTDCS may not be suited to inform individual dosing of TDCS intensity.

Multimodal Assessment of Precentral Anodal TDCS: Individual Rise in Supplementary Motor Activity Scales With Increase in Corticospinal Excitability.

BACKGROUND: Transcranial direct current stimulation (TDCS) targeting the primary motor hand area (M1-HAND) may induce lasting shifts in corticospinal excitability, but after-effects show substantial inter-individual variability. Functional magnetic resonance imaging (fMRI) can probe after-effects of TDCS on regional neural activity on a whole-brain level. OBJECTIVE: Using a double-blinded cross-over design, we investigated whether the individual change in corticospinal excitability after TDCS of M1-HAND is associated with changes in task-related regional activity in cortical motor areas. METHODS: Seventeen healthy volunteers (10 women) received 20 min of real (0.75 mA) or sham TDCS on separate days in randomized order. Real and sham TDCS used the classic bipolar set-up with the anode placed over right M1-HAND. Before and after each TDCS session, we recorded motor evoked potentials (MEP) from the relaxed left first dorsal interosseus muscle after single-pulse transcranial magnetic stimulation(TMS) of left M1-HAND and performed whole-brain fMRI at 3 Tesla while participants completed a visuomotor tracking task with their left hand. We also assessed the difference in MEP latency when applying anterior-posterior and latero-medial TMS pulses to the precentral hand knob (AP-LM MEP latency). RESULTS: Real TDCS had no consistent aftereffects on mean MEP amplitude, task-related activity or motor performance. Individual changes in MEP amplitude, measured directly after real TDCS showed a positive linear relationship with individual changes in task-related activity in the supplementary motor area and AP-LM MEP latency. CONCLUSION: Functional aftereffects of classical bipolar anodal TDCS of M1-HAND on the motor system vary substantially across individuals. Physiological features upstream from the primary motor cortex may determine how anodal TDCS changes corticospinal excitability.

Does pericentral mu-rhythm "power" corticomotor excitability? - A matter of EEG perspective.

BACKGROUND: Electroencephalography (EEG) and single-pulse transcranial magnetic stimulation (spTMS) of the primary motor hand area (M1-HAND) have been combined to explore whether the instantaneous expression of pericentral mu-rhythm drives fluctuations in corticomotor excitability, but this line of research has yielded diverging results. OBJECTIVES: To re-assess the relationship between the mu-rhythm power expressed in left pericentral cortex and the amplitude of motor potentials (MEP) evoked with spTMS in left M1-HAND. METHODS: 15 non-preselected healthy young participants received spTMS to the motor hot spot of left M1-HAND. Regional expression of mu-rhythm was estimated online based on a radial source at motor hotspot and informed the timing of spTMS which was applied either during epochs belonging to the highest or lowest quartile of regionally expressed mu-power. Using MEP amplitude as dependent variable, we computed a linear mixed-effects model, which included mu-power and mu-phase at the time of stimulation and the inter-stimulus interval (ISI) as fixed effects and subject as a random effect. Mu-phase was estimated by post-hoc sorting of trials into four discrete phase bins. We performed a follow-up analysis on the same EEG-triggered MEP data set in which we isolated mu-power at the sensor level using a Laplacian montage centered on the electrode above the M1-HAND. RESULTS: Pericentral mu-power traced as radial source at motor hot spot did not significantly modulate the MEP, but mu-power determined by the surface Laplacian did, showing a positive relation between mu-power and MEP amplitude. In neither case, there was an effect of mu-phase on MEP amplitude. CONCLUSION: The relationship between cortical oscillatory activity and cortical excitability is complex and minor differences in the methodological choices may critically affect sensitivity.

Cortical signatures of precision grip force control in children, adolescents, and adults.

Human dexterous motor control improves from childhood to adulthood, but little is known about the changes in cortico-cortical communication that support such ontogenetic refinement of motor skills. To investigate age-related differences in connectivity between cortical regions involved in dexterous control, we analyzed electroencephalographic data from 88 individuals (range 8-30 years) performing a visually guided precision grip task using dynamic causal modelling and parametric empirical Bayes. Our results demonstrate that bidirectional coupling in a canonical 'grasping network' is associated with precision grip performance across age groups. We further demonstrate greater backward coupling from higher-order to lower-order sensorimotor regions from late adolescence in addition to differential associations between connectivity strength in a premotor-prefrontal network and motor performance for different age groups. We interpret these findings as reflecting greater use of top-down and executive control processes with development. These results expand our understanding of the cortical mechanisms that support dexterous abilities through development.

Probing Context-Dependent Modulations of Ipsilateral Premotor-Motor Connectivity in Relapsing-Remitting Multiple Sclerosis.

Objective: We employed dual-site TMS to test whether ipsilateral functional premotor-motor connectivity is altered in relapsing-remitting Multiple Sclerosis (RR-MS) and is related to central fatigue. Methods: Twelve patients with RR-MS and 12 healthy controls performed a visually cued Pinch-NoPinch task with their right hand. During the reaction time (RT) period of Pinch and No-Pinch trials, single-site TMS was applied to the left primary motor cortex (M1) or dual-site TMS was applied to the ipsilateral dorsal premotor cortex (PMd) and to M1. We traced context-dependent changes of corticospinal excitability and premotor-motor connectivity by measuring Motor-Evoked Potentials (MEPs) in the right first dorsal interosseus muscle. Central fatigue was evaluated with the Fatigue Scale for Motor and Cognitive Functions (FSMS). Results: In both groups, single-pulse TMS revealed a consistent increase in mean MEP amplitude during the Reaction Time (RT) period relative to a resting condition. Task-related corticospinal facilitation increased toward the end of the RT period in Pinch trials, while it decreased in No-Pinch trials. Again, this modulation of MEP facilitation by trial type was comparable in patients and controls. Dual-site TMS showed no significant effect of a conditioning PMd pulse on ipsilateral corticospinal excitability during the RT period in either group. However, patients showed a trend toward a relative attenuation in functional PMd-M1 connectivity at the end of the RT period in No-Pinch trials, which correlated positively with the severity of motor fatigue (r = 0.69; p = 0.007). Conclusions: Dynamic regulation of corticospinal excitability and ipsilateral PMd-M1 connectivity is preserved in patients with RR-MS. MS-related fatigue scales positively with an attenuation of premotor-to-motor functional connectivity during cued motor inhibition. Significance: The temporal, context-dependent modulation of ipsilateral premotor-motor connectivity, as revealed by dual-site TMS of ipsilateral PMd and M1, constitutes a promising neurophysiological marker of fatigue in MS.

Functional and Structural Plasticity Co-express in a Left Premotor Region During Early Bimanual Skill Learning.

Introduction: Motor skill learning already triggers the functional reorganization of regional brain activity after short periods of training. Recent studies suggest that microstructural change may emerge at similar timescales, but the spatiotemporal profiles of functional and structural plasticity have rarely been traced in parallel. Recently, we demonstrated that 5 days of endoscopic skill training induces changes in task-related brain activity in the ventral premotor cortex (PMv) and other areas of the frontoparietal grasping network. Here, we analyzed microstructural data, collected during the same experiment to investigate if microstructural plasticity overlaps temporally and spatially with the training-induced changes in task-related brain activity. Materials and Methods: Thirty-nine students were divided into a full-routine group (n = 20), that underwent three endoscopy training sessions in the MR-scanner as well as a 5-day virtual reality (VR)-endoscopy training and a brief-routine group (n = 19), that only performed the in-scanner endoscopy training sessions. Diffusion Tensor Imaging (DTI)-derived fractional anisotropy (FA) and resting-state functional magnetic resonance imaging (rs-fMRI) were collected at baseline, after the first and after the last VR-training session. Results: The full-routine group showed significant FA changes in a left-hemispheric subcortical cluster underlying the PMv region, for which we previously demonstrated functional plasticity during endoscopy training in the same sample. Functional (task-related fMRI) and structural (FA) changes showed the largest change from the first to the second scan, suggesting similar temporal dynamics. In the full-routine group, the FA change in the subcortical cluster underlying the left PMv scaled positively with the individual improvement in endoscopic surgery. Conclusion: Microstructural white-matter plasticity mirrors the spatiotemporal profile of task-dependent plasticity during a 5-day course of endoscopy skill training. The observed similarities motivate future research on the interplay between functional and structural plasticity during early skill acquisition.

Can Transcranial Electrical Stimulation Localize Brain Function?

Transcranial electrical stimulation (TES) uses constant (TDCS) or alternating currents (TACS) to modulate brain activity. Most TES studies apply low-intensity currents through scalp electrodes (≤2 mA) using bipolar electrode arrangements, producing weak electrical fields in the brain (<1 V/m). Low-intensity TES has been employed in humans to induce changes in task performance during or after stimulation. In analogy to focal transcranial magnetic stimulation, TES-induced behavioral effects have often been taken as evidence for a causal involvement of the brain region underlying one of the two stimulation electrodes, often referred to as the active electrode. Here, we critically review the utility of bipolar low-intensity TES to localize human brain function. We summarize physiological substrates that constitute peripheral targets for TES and may mediate subliminal or overtly perceived peripheral stimulation during TES. We argue that peripheral co-stimulation may contribute to the behavioral effects of TES and should be controlled for by "sham" TES. We discuss biophysical properties of TES, which need to be considered, if one wishes to make realistic assumptions about which brain regions were preferentially targeted by TES. Using results from electric field calculations, we evaluate the validity of different strategies that have been used for selective spatial targeting. Finally, we comment on the challenge of adjusting the dose of TES considering dose-response relationships between the weak tissue currents and the physiological effects in targeted cortical areas. These considerations call for caution when attributing behavioral effects during or after low-intensity TES studies to a specific brain region and may facilitate the selection of best practices for future TES studies.

No trace of phase: Corticomotor excitability is not tuned by phase of pericentral mu-rhythm.

BACKGROUND: The motor potentials evoked by transcranial magnetic stimulation (TMS) over the motor hand area (M1-HAND) show substantial inter-trial variability. Pericentral mu-rhythm oscillations, might contribute to inter-trial variability. Recent studies targeting mu-activity based on real-time electroencephalography (EEG) reported an influence of mu-power and mu-phase on the amplitude of motor evoked potentials (MEPs) in a preselected group with strong pericentral mu-activity. Other studies that determined mu-power or mu-phase based on post-hoc trial sorting according in non-preselected individuals were largely negative. OBJECTIVES: To reassess if cortico-spinal activity is modulated by the mu-rhythm, we applied single-pulse TMS to the M1-HAND conditional on the phase of the intrinsically expressed pericentral mu-rhythm in 14 non-preselected healthy young participants. METHODS: TMS was given at 0, 90, 180, and 270° of the mu-phase. Based on the absence of effects of mu-phase or mu-power when analyzing the mean MEP amplitudes, we also computed a linear mixed effects model, which included mu-phase, mu-power, inter-stimulus interval (ISIs) as fixed effects, treating the subject factor as a random effect. RESULTS: Mixed model analysis revealed a significant effect of mu-power and ISI, but no effect of mu-phase and no interactions. MEP amplitude scaled linearly with lower mu-power or longer ISIs, but these modulatory effects were very small relative to inter-trial MEP variability. CONCLUSION: Our largely negative results are in agreement with previous offline TMS-EEG studies and point to a possible influence of ISI. Future research needs to clarify under which circumstances the responsiveness of human the M1-HAND to TMS depends on the synchronicity with mu-power and mu-phase.

The Resting Motor Threshold--Restless or Resting? A Repeated Threshold Hunting Technique to Track Dynamic Changes in Resting Motor Threshold.

BACKGROUND: The resting motor threshold (RMT) is used to individually adjust the intensity of transcranial magnetic stimulation (TMS) intensity and is assumed to be stable. Here we challenge this notion by showing that RMT expresses acute context-dependent fluctuations. METHOD: In twelve participants, the RMT of the right first dorsal interosseus muscle was repeatedly determined using a threshold-hunting procedure while participants performed motor imagery and visual attention tasks with the right or left hand. Data were analyzed using repeated-measure ANOVA. RESULTS: RMT differed depending on which hand performed the task (P = 0.003). RMT of right FDI was lower during motor imagery than during visual attention of the right hand (P = 0.002), but did not differ between left-hand tasks (P = 0.988). CONCLUSIONS: State-dependent changes of RMT occur in absence of overt motor activity and can be captured online by threshold hunting. These fluctuations need to be considered when RMT is used to individually adjust TMS intensity for plasticity-inducing protocols.

Participation of the classical speech areas in auditory long-term memory.

Accumulating evidence suggests that storing speech sounds requires transposing rapidly fluctuating sound waves into more easily encoded oromotor sequences. If so, then the classical speech areas in the caudalmost portion of the temporal gyrus (pSTG) and in the inferior frontal gyrus (IFG) may be critical for performing this acoustic-oromotor transposition. We tested this proposal by applying repetitive transcranial magnetic stimulation (rTMS) to each of these left-hemisphere loci, as well as to a nonspeech locus, while participants listened to pseudowords. After 5 minutes these stimuli were re-presented together with new ones in a recognition test. Compared to control-site stimulation, pSTG stimulation produced a highly significant increase in recognition error rate, without affecting reaction time. By contrast, IFG stimulation led only to a weak, non-significant, trend toward recognition memory impairment. Importantly, the impairment after pSTG stimulation was not due to interference with perception, since the same stimulation failed to affect pseudoword discrimination examined with short interstimulus intervals. Our findings suggest that pSTG is essential for transforming speech sounds into stored motor plans for reproducing the sound. Whether or not the IFG also plays a role in speech-sound recognition could not be determined from the present results.

Mapping different intra-hemispheric parietal-motor networks using twin Coil TMS.

BACKGROUND: Accumulating evidence suggests anatomical and functional differences in connectivity between the anterior and posterior parts of the inferior-parietal lobule (IPL) and the frontal motor areas. OBJECTIVE/HYPOTHESIS: This study investigates whether different intra-hemispheric parietal-motor interactions can be observed along the anterior-posterior axis of the IPL in the resting human brain. METHODS: We use a twin coil transcranial magnetic stimulation technique to test intra-hemispheric interactions between three points adjacent to the intra-parietal sulcus (anterior, central, posterior) and the ipsilateral primary motor cortex (M1) at rest in both hemispheres. RESULTS: We found that stimulation of the anterior IPL resulted in an inhibition of the ipsilateral M1 in both hemispheres. Stimulation of the central and posterior IPL resulted in a facilitatory effect on ipsilateral M1 in the left but not for the right hemisphere. Additionally we show that there is considerable inter-subject variability concerning the optimal parietal facilitatory and inhibitory position. CONCLUSIONS: The IPL has distinct inhibitory and facilitatory connections to the ipsilateral M1. Whereas inhibitory connections are observed in both hemispheres, facilitatory connections are asymmetric. These parietal-motor networks may represent the basis for the functional differences between these regions in reaching and grasping tasks and mirror the functional asymmetry observed in the motor system. From a practical point of view, we note that the inter-subject variability means that future TMS studies of the parietal area might consider a hot-spot localization similar to the procedures commonly used for M1.