The role of the primary motor cortex during skill acquisition on a two-degrees-of-freedom movement task

One can partially eliminate motor skills acquired through practice in the hours immediately following practice by applying repetitive transcranial stimulation (rTMS) over the primary motor cortex. The disruption of acquired levels of performance has been demonstrated on tasks that are ballistic in nature. The authors investigated whether motor recall on a discrete aiming task is degraded following a disruption of the primary motor cortex induced via rTMS. Participants (N = 16) maintained acquired performance levels and patterns of muscle activity following the application of rTMS. despite a reduction in corticospinal excitability. Disruption of the primary motor cortex during a consolidation period did not influence the retention of acquired skill in this type of discrete visuomotor task.

Primary motor cortex involvement in initial learning during visuomotor adaptation

Human motor behaviour is continually modified on the basis of errors between desired and actual movement outcomes. It is emerging that the role played by the primary motor cortex (M1) in this process is contingent upon a variety of factors, including the nature of the task being performed, and the stage of learning. Here we used repetitive TMS to test the hypothesis that M1 is intimately involved in the initial phase of sensorimotor adaptation. Inhibitory theta burst stimulation was applied to M1 prior to a task requiring modification of torques generated about the elbow/forearm complex in response to rotations of a visual feedback display. Participants were first exposed to a 30° clockwise (CW) rotation (Block A), then a 60° counterclockwise rotation (Block B), followed immediately by a second block of 30° CW rotation (A2). In the STIM condition, participants received 20s of continuous theta burst stimulation (cTBS) prior to the initial A Block. In the conventional (CON) condition, no stimulation was applied. The overt characteristics of performance in the two conditions were essentially equivalent with respect to the errors exhibited upon exposure to a new variant of the task. There were however, profound differences between the conditions in the latency of response preparation, and the excitability of corticospinal projections from M1, which accompanied phases of de-adaptation and re-adaptation (during Blocks B and A2). Upon subsequent exposure to the A rotation 24h later, the rate of re-adaptation was lower in the stimulation condition than that present in the conventional condition. These results support the assertion that primary motor cortex assumes a key role in a network that mediates adaptation to visuomotor perturbation, and emphasise that it is engaged functionally during the early phase of learning.

Contribution of primary motor cortex to compensatory balance reactions

Background: Rapid compensatory arm reactions represent important response strategies following an unexpected loss of balance. While it has been assumed that early corrective actions arise largely from sub-cortical networks, recent findings have prompted speculation about the potential role of cortical involvement. To test the idea that cortical motor regions are involved in early compensatory arm reactions, we used continuous theta burst stimulation (cTBS) to temporarily suppress the hand area of primary motor cortex (M1) in participants prior to evoking upper limb balance reactions in response to whole body perturbation. We hypothesized that following cTBS to the M1 hand area evoked EMG responses in the stimulated hand would be diminished. To isolate balance reactions to the upper limb participants were seated in an elevated tilt-chair while holding a stable handle with both hands. The chair was held vertical by a magnet and was triggered to fall backward unpredictably. To regain balance, participants used the handle to restore upright stability as quickly as possible with both hands. Muscle activity was recorded from proximal and distal muscles of both upper limbs.

Results: Our results revealed an impact of cTBS on the amplitude of the EMG responses in the stimulated hand muscles often manifest as inhibition in the stimulated hand. The change in EMG amplitude was specific to the target hand muscles and occasionally their homologous pairs on the non-stimulated hand with no consistent effects on the remaining more proximal arm muscles.

Conclusions: Present findings offer support for cortical contributions to the control of early compensatory arm reactions following whole-body perturbation.

Speed of processing in the primary motor cortex: A continuous theta burst stimulation study

‘Temporally urgent’ reactions are extremely rapid, spatially precise movements that are evoked following discrete stimuli. The involvement of primary motor cortex (M1) and its relationship to stimulus intensity in such reactions is not well understood. Continuous theta burst stimulation (cTBS) suppresses focal regions of the cortex and can assess the involvement of motor cortex in speed of processing. The primary objective of this study was to explore the involvement of M1 in speed of processing with respect to stimulus intensity. Thirteen healthy young adults participated in this experiment. Behavioral testing consisted of a simple button press using the index finger following median nerve stimulation of the opposite limb, at either high or low stimulus intensity. Reaction time was measured by the onset of electromyographic activity from the first dorsal interosseous (FDI) muscle of each limb. Participants completed a 30 min bout of behavioral testing prior to, and 15 min following, the delivery of cTBS to the motor cortical representation of the right FDI. The effect of cTBS on motor cortex was measured by recording the average of 30 motor evoked potentials (MEPs) just prior to, and 5 min following, cTBS. Paired t-tests revealed that, of thirteen participants, five demonstrated a significant attenuation, three demonstrated a significant facilitation and five demonstrated no significant change in MEP amplitude following cTBS. Of the group that demonstrated attenuated MEPs, there was a biologically significant interaction between stimulus intensity and effect of cTBS on reaction time and amplitude of muscle activation. This study demonstrates the variability of potential outcomes associated with the use of cTBS and further study on the mechanisms that underscore the methodology is required. Importantly, changes in motor cortical excitability may be an important determinant of speed of processing following high intensity stimulation.

Human parietal and primary motor cortical interactions are selectively modulated during the transport and grip formation of goal-directed hand actions

Posterior parietal cortex (PPC) constitutes a critical cortical node in the sensorimotor system in which goal-directed actions are computed. This information then must be transferred into commands suitable for hand movements to the primary motor cortex (M1). Complexity arises because reach-to-grasp actions not only require directing the hand towards the object (transport component), but also preshaping the hand according to the features of the object (grip component). Yet, the functional influence that specific PPC regions exert over ipsilateral M1 during the planning of different hand movements remains unclear in humans. Here we manipulated transport and grip components of goal-directed hand movements and exploited paired-pulse transcranial magnetic stimulation (ppTMS) to probe the functional interactions between M1 and two different PPC regions, namely superior parieto-occipital cortex (SPOC) and the anterior region of the intraparietal sulcus (aIPS), in the left hemisphere. We show that when the extension of the arm is required to contact a target object, SPOC selectively facilitates motor evoked potentials, suggesting that SPOC-M1 interactions are functionally specific to arm transport. In contrast, a different pathway, linking the aIPS and ipsilateral M1, shows enhanced functional connections during the sensorimotor planning of grip. These results support recent human neuroimaging findings arguing for specialized human parietal regions for the planning of arm transport and hand grip during goal-directed actions. Importantly, they provide new insight into the causal influences these different parietal regions exert over ipsilateral motor cortex for specific types of planned hand movements

Duration-dependent effects of the BDNF Val66Met polymorphism on anodal tDCS induced motor cortex plasticity in older adults: a group and individual perspective

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.

Timing of response differentiation in human motor cortex during a speeded Go/No-go task

We explored the brain's ability to quickly prevent a pre-potent but unwanted motor response. To address this, transcranial magnetic stimulation was delivered over the motor cortex (hand representation) to probe excitability changes immediately after somatosensory cues prompted subjects to either move as fast as possible or withhold movement. Our results showed a difference in motor cortical excitability 90 ms post-stimulus contingent on cues to either promote or prevent movement. We suggest that our study design emphasizing response speed coupled with well-defined early probes allowed us to extend upon similar past investigations into the timing of response inhibition.

Transcallosal connectivity of the human cortical motor network

The organizational and architectural configuration of white matter pathways connecting brain regions has ramifications for all facets of the human condition, including manifestations of incipient neurodegeneration. Although diffusion tensor imaging (DTI) has been used extensively to visualize white matter connectivity, due to the widespread presence of crossing fibres, the lateral projections of the corpus callosum are not normally detected using this methodology. Detailed knowledge of the transcallosal connectivity of the human cortical motor network has therefore remained elusive. We employed constrained spherical deconvolution (CSD) tractography - an approach that is much less susceptible to the influence of crossing fibres, in order to derive complete in-vivo characterizations of white matter pathways connecting specific motor cortical regions to their counterparts and other loci in the opposite hemisphere. The revealed patterns of connectivity closely resemble those derived from anatomical tracing in primates. It was established that dorsal premotor cortex (PMd) and supplementary motor area (SMA) have extensive interhemispheric connectivity - exhibiting both dense homologous projections, and widespread structural relations with every other region in the contralateral motor network. Through this in-vivo portrayal, the importance of non-primary motor regions for interhemispheric communication is emphasized. Additionally, distinct connectivity profiles were detected for the anterior and posterior subdivisions of primary motor cortex. The present findings provide a comprehensive representation of transcallosal white matter projections in humans, and have the potential to inform the development of models and hypotheses relating structural and functional brain connectivity.

The effect of simultaneous contractions of ipsilateral muscles on changes in corticospinal excitability induced by paired associative stimulation (PAS)

Consideration was given to means of increasing the reliability and muscle specificity of paired associative stimulation (PAS) by utilising the phenomenon of crossed-facilitation. Eight participants completed three separate sessions: isometric flexor contractions of the left wrist at 20% of maximum voluntary contraction (MVC) simultaneously with PAS (20s intervals; 14 min duration) delivered at the right median nerve and left primary motor cortex (MI); isometric contractions at 20% of MVC: and PAS only ( 14 min). Eight further participants completed two sessions of longer duration PAS (28 min): either alone or in conjunction with flexion contractions of the left wrist. Thirty motor potentials (MEPs) were evoked in the right flexor (rFCR) and extensor (rECR) carpi radialis muscles by magnetic stimulation of left M1 Prior to the interventions, immediately post-intervention, and 10 min post-intervention. Both 14 and 28 min of combined PAS and (left wrist flexion) contractions resulted in reliable increases in rFCR MEP amplitude, which were not present in rECR. In the PAS only conditions, 14 min of stimulation gave rise to unreliable increases in MEP amplitudes in rFCR and rECR, whereas 28 min of PAS induced small (unreliable) changes only for rFCR. These results support the conclusion that changes in the excitability of the corticospinal pathway induced by PAS interact with those associated with contraction of the muscles ipsilateral to the site of cortical stimulation. Furthermore, focal contractions applied by the opposite limb increase the extent and muscle specificity of the induced changes in excitability associated with PAS. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Movement-related potentials in high-functioning autism and Asperger's disorder

Autism and Asperger's disorder (AD) are neurodevelopmental conditions that affect cognitive and social-communicative function. Using a movement-related potential (MRP) paradigm, we investigated the clinical and neurobiological issue of 'disorder separateness' versus 'disorder variance' in autism and AD. This paradigm has been used to assess basal ganglia/supplementary motor functioning in Parkinson's disease. Three groups (high functioning autism [HFA]: 16 males, 1 female; mean age 12y 5mo [SD 4y 4mo]; AD: 11 males, 2 females; mean age 13y 5mo [SD 3y 8mo]; comparison group: 13 males, 8 females; mean age 13y 10mo, [SD 3y 11 mo]) completed a cued motor task during electroencephalogram recording of MRPs. The HFA group showed reduced peak amplitude at Cz, indicating less activity over the supplementary motor area during movement preparation. Although an overall significant between-group effect was found for early slope and peak amplitude, subanalysis revealed that the group with AD did not differ significantly from either group. However, it is suggested that autism and AD may be dissociated on the basis of brain-behaviour correlations of IQ with specific neurobiological measures. The overlap between MRP traces for autism and Parkinson's disease suggests that the neurobiological wiring of motor functioning in autism may bypass the supplementary motor area/primary motor cortex pathway.

Dual-task interference: Attentional and neurophysiological influences

Performing two tasks simultaneously often degrades performance of one or both tasks. While this dual-task interference is classically interpreted in terms of shared attentional resources, where two motor tasks are performed simultaneously interactions within primary motor cortex (i.e., activity-dependent coupling) may also be a contributing factor. In the present study TMS (transcranial magnetic stimulation) was used to examine the contribution of activity-dependent coupling to dual-task interference during concurrent performance of a bimanual coordination task and a discrete probe reaction time (RT) task involving the foot. Experiments 1 and 2 revealed that activity-dependent coupling within the leg corticomotor pathway was greater during dual-task performance than single-task performance, and this was associated with interference on the probe RT task (i.e., increased RT). Experiment 3 revealed that dual-task interference occurred regardless of whether the dual-task involved two motor tasks or a motor and cognitive task, however activity-dependent coupling was present only when a dual motor task was performed. This suggests that activity-dependent coupling is less detrimental to performance than attentional processes operating upstream of the corticomotor system. Finally, while prioritising the RT task reduced, but did not eliminate, dual-task interference the contribution of activity-dependent coupling to dual-task interference was not affected by task prioritisation. This suggests that although activity-dependent coupling may contribute to dual motor-task interference, attentional processes appear to be more important. It also suggests that activity-dependent coupling may not be subject to modulation by attentional processes. (C) 2009 Elsevier B.V. All rights reserved.

Characterizing changes in the excitability of corticospinal projections to proximal muscles of the upper limb

Background: There has been an explosion of interest in methods of exogenous brain stimulation that induce changes in the excitability of human cerebral cortex. The expectation is that these methods may promote recovery of function following brain injury. To assess their effects on motor output, it is typical to assess the state of corticospinal projections from primary motor cortex to muscles of the hand, via electromyographic responses to transcranial magnetic stimulation. If a range of stimulation intensities is employed, the recruitment curves (RCs) obtained can, at least for intrinsic hand muscles, be fitted by a sigmoid function.

Objective/hypothesis: To establish whether sigmoid fits provide a reliable basis upon which to characterize the input–output properties of the corticospinal pathway for muscles proximal to the hand, and to assess as an alternative the area under the (recruitment) curve (AURC).

Methods: A comparison of the reliability of these measures, using RCs obtained for muscles that are frequently the targets of rehabilitation.

Results: The AURC is an extremely reliable measure of the state of corticospinal projections to hand and forearm muscles, which has both face and concurrent validity. Construct validity is demonstrated by detection of widely distributed (across muscles) changes in corticospinal excitability induced by paired associative stimulation (PAS).

Conclusion(s): The parameters derived from sigmoid fits are unlikely to provide an adequate means to assess the effectiveness of therapeutic regimes. The AURC can be employed to characterize corticospinal projections to a range of muscles, and gauge the efficacy of longitudinal interventions in clinical rehabilitation.

Paired associative transcranial alternating current stimulation increases the excitability of corticospinal projections in humans

Many types of non-invasive brain stimulation alter corticospinal excitability (CSE). Paired associative stimulation (PAS) has attracted particular attention as its effects ostensibly adhere to Hebbian principles of neural plasticity. In prototypical form, a single electrical stimulus is directed to a peripheral nerve in close temporal contiguity with transcranial magnetic stimulation delivered to the contralateral primary motor cortex (M1). Repeated pairing of the two discrete stimulus events (i.e. association) over an extended period either increases or decreases the excitability of corticospinal projections from M1, contingent on the interstimulus interval. We studied a novel form of associative stimulation, consisting of brief trains of peripheral afferent stimulation paired with short bursts of high frequency (≥80 Hz) transcranial alternating current stimulation (tACS) over contralateral M1. Elevations in the excitability of corticospinal projections to the forearm were observed for a range of tACS frequency (80, 140 and 250 Hz), current (1, 2 and 3 mA) and duration (500 and 1000 ms) parameters. The effects were at least as reliable as those brought about by PAS or transcranial direct current stimulation. When paired with tACS, muscle tendon vibration also induced elevations of CSE. No such changes were brought about by the tACS or peripheral afferent stimulation alone. In demonstrating that associative effects are expressed when the timing of the peripheral and cortical events is not precisely circumscribed, these findings suggest that multiple cellular pathways may contribute to a long term potentiation-type response. Their relative contributions will differ depending on the nature of the induction protocol that is used.

Modulation of human corticospinal excitability by paired associative stimulation

Paired Associative Stimulation (PAS) has come to prominence as a potential therapeutic intervention for the treatment of brain injury/disease, and as an experimental method with which to investigate Hebbian principles of neural plasticity in humans. Prototypically, a single electrical stimulus is directed to a peripheral nerve in advance of transcranial magnetic stimulation (TMS) delivered to the contralateral primary motor cortex (M1). Repeated pairing of the stimuli (i.e., association) over an extended period may increase or decrease the excitability of corticospinal projections from M1, in manner that depends on the interstimulus interval (ISI). It has been suggested that these effects represent a form of associative long-term potentiation (LTP) and depression (LTD) that bears resemblance to spike-timing dependent plasticity (STDP) as it has been elaborated in animal models. With a large body of empirical evidence having emerged since the cardinal features of PAS were first described, and in light of the variations from the original protocols that have been implemented, it is opportune to consider whether the phenomenology of PAS remains consistent with the characteristic features that were initially disclosed. This assessment necessarily has bearing upon interpretation of the effects of PAS in relation to the specific cellular pathways that are putatively engaged, including those that adhere to the rules of STDP. The balance of evidence suggests that the mechanisms that contribute to the LTP- and LTD-type responses to PAS differ depending on the precise nature of the induction protocol that is used. In addition to emphasizing the requirement for additional explanatory models, in the present analysis we highlight the key features of the PAS phenomenology that require interpretation.