Multi-scale analysis of acupuncture mechanisms for motor and sensory cortex activity based on SEEG data.

Acupuncture, a traditional Chinese therapy, is gaining attention for its impact on the brain. While existing electroencephalogram and functional magnetic resonance image research has made significant contributions, this paper utilizes stereo-electroencephalography data for a comprehensive exploration of neurophysiological effects. Employing a multi-scale approach, channel-level analysis reveals notable $\delta $-band activity changes during acupuncture. At the brain region level, acupuncture modulated connectivity between the paracentral lobule and the precentral gyrus. Whole-brain analysis indicates acupuncture's influence on network organization, and enhancing $E_{glob}$ and increased interaction between the motor and sensory cortex. Brain functional reorganization is an important basis for functional recovery or compensation after central nervous system injury. The use of acupuncture to stimulate peripheral nerve trunks, muscle motor points, acupoints, etc., in clinical practice may contribute to the reorganization of brain function. This multi-scale perspective provides diverse insights into acupuncture's effects. Remarkably, this paper pioneers the introduction of stereo-electroencephalography data, advancing our understanding of acupuncture's mechanisms and potential therapeutic benefits in clinical settings.

Multiplicative joint coding in preparatory activity for reaching sequence in macaque motor cortex.

Although the motor cortex has been found to be modulated by sensory or cognitive sequences, the linkage between multiple movement elements and sequence-related responses is not yet understood. Here, we recorded neuronal activity from the motor cortex with implanted micro-electrode arrays and single electrodes while monkeys performed a double-reach task that was instructed by simultaneously presented memorized cues. We found that there existed a substantial multiplicative component jointly tuned to impending and subsequent reaches during preparation, then the coding mechanism transferred to an additive manner during execution. This multiplicative joint coding, which also spontaneously emerged in recurrent neural networks trained for double reach, enriches neural patterns for sequential movement, and might explain the linear readout of elemental movements.

Effects of prolonged vibration to the flexor carpi radialis muscle on intracortical excitability.

Prolonged local vibration (LV) can induce neurophysiological adaptations thought to be related to long-term potentiation or depression. Yet, how changes in intracortical excitability may be involved remains to be further investigated as previous studies reported equivocal results. We therefore investigated the effects of 30 min of LV applied to the right flexor carpi radialis muscle (FCR) on both short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). SICI and ICF were measured through transcranial magnetic stimulation before and immediately after 30 min of FCR LV (vibration condition) or 30 min of rest (control condition). Measurements were performed during a low-intensity contraction (n = 17) or at rest (n = 7). No significant SICI nor ICF modulations were observed, whether measured during isometric contractions or at rest (p = 0.2). Yet, we observed an increase in inter-individual variability for post measurements after LV. In conclusion, while intracortical excitability was not significantly modulated after LV, increased inter-variability observed after LV may suggest the possibility of divergent responses to prolonged LV exposure.

Stability of transcranial magnetic stimulation electroencephalogram evoked potentials in pediatric epilepsy.

Transcranial magnetic stimulation paired with electroencephalography (TMS-EEG) can measure local excitability and functional connectivity. To address trial-to-trial variability, responses to multiple TMS pulses are recorded to obtain an average TMS evoked potential (TEP). Balancing adequate data acquisition to establish stable TEPs with feasible experimental duration is critical when applying TMS-EEG to clinical populations. Here we aim to investigate the minimum number of pulses (MNP) required to achieve stable TEPs in children with epilepsy. Eighteen children with Self-Limited Epilepsy with Centrotemporal Spikes, a common epilepsy arising from the motor cortices, underwent multiple 100-pulse blocks of TMS to both motor cortices over two days. TMS was applied at 120% of resting motor threshold (rMT) up to a maximum of 100% maximum stimulator output. The average of all 100 pulses was used as a "gold-standard" TEP to which we compared "candidate" TEPs obtained by averaging subsets of pulses. We defined TEP stability as the MNP needed to achieve a concordance correlation coefficient of 80% between the candidate and "gold-standard" TEP. We additionally assessed whether experimental or clinical factors affected TEP stability. Results show that stable TEPs can be derived from fewer than 100 pulses, a number typically used for designing TMS-EEG experiments. The early segment (15-80 ms) of the TEP was less stable than the later segment (80-350 ms). Global mean field amplitude derived from all channels was less stable than local TEP derived from channels overlying the stimulated site. TEP stability did not differ depending on stimulated hemisphere, block order, or antiseizure medication use, but was greater in older children. Stimulation administered with an intensity above the rMT yielded more stable local TEPs. Studies of TMS-EEG in pediatrics have been limited by the complexity of experimental set-up and time course. This study serves as a critical starting point, demonstrating the feasibility of designing efficient TMS-EEG studies that use a relatively small number of pulses to study pediatric epilepsy and potentially other pediatric groups.

Monitoring Changes in TMS-Evoked EEG and EMG Activity During 1†Hz rTMS of the Healthy Motor Cortex.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique capable of inducing neuroplasticity as measured by changes in peripheral muscle electromyography (EMG) or electroencephalography (EEG) from pre-to-post stimulation. However, temporal courses of neuromodulation during ongoing rTMS are unclear. Monitoring cortical dynamics via TMS-evoked responses using EMG (motor-evoked potentials; MEPs) and EEG (transcranial-evoked potentials; TEPs) during rTMS might provide further essential insights into its mode of action - temporal course of potential modulations. The objective of this study was to first evaluate the validity of online rTMS-EEG and rTMS-EMG analyses, and second to scrutinize the temporal changes of TEPs and MEPs during rTMS. As rTMS is subject to high inter-individual effect variability, we aimed for single-subject analyses of EEG changes during rTMS. Ten healthy human participants were stimulated with 1,000 pulses of 1 Hz rTMS over the motor cortex, while EEG and EMG were recorded continuously. Validity of MEPs and TEPs measured during rTMS was assessed in sensor and source space. Electrophysiological changes during rTMS were evaluated with model fitting approaches on a group- and single-subject level. TEPs and MEPs appearance during rTMS was consistent with past findings of single pulse experiments. Heterogeneous temporal progressions, fluctuations or saturation effects of brain activity were observed during rTMS depending on the TEP component. Overall, global brain activity increased over the course of stimulation. Single-subject analysis revealed inter-individual temporal courses of global brain activity. The present findings are in favor of dose-response considerations and attempts in personalization of rTMS protocols.

Transcranial static magnetic field stimulation of the supplementary motor area decreases corticospinal excitability in the motor cortex: a pilot study.

Transcranial static magnetic field stimulation (tSMS) is a non-invasive brain stimulation technique that is portable and easy to use. Long-term, home-based treatments with tSMS of the supplementary motor area (SMA) are promising for movement disorders and other brain diseases. The aim of the present work was to investigate the potential of SMA-tSMS for reducing corticospinal excitability. We completed an open pilot study in which twenty right-handed healthy subjects (8 females; age: 31.3 ± 5.4 years) completed two 30-min sessions (at least one week apart) of SMA-tSMS. We assessed corticospinal excitability by applying transcranial magnetic stimulation (TMS) over the primary motor cortex, recording 30 motor evoked potentials (MEPs) from either the left or right first dorsal interosseous (FDI, 'hotspot' muscle) and extensor carpi radialis (ECR, 'offspot' muscle) in each session before and after (up to 30 min) tSMS. We observed moderate-to-extreme level of Bayesian evidence for a reduction of MEP amplitude after 30 min of tSMS over SMA compared to baseline. Thus, tSMS applied over SMA may reduce corticospinal excitability. These findings, if confirmed with double-blind, placebo-controlled experiments, support the potential of targeting the SMA for neuromodulating a large motor network in future therapeutic applications of tSMS.

[Identifying the neurostimulation target for treatment of cognitive impairment in aging and early cerebral small vessel disease]. / Vybor misheni neiromodulyatsii dlya korrektsii kognitivnykh rasstroistv pri starenii i rannei tserebral'noi mikroangiopatii.

OBJECTIVE: To develop individualized approaches to the use of neuromodulation as a non-pharmacological treatment of cognitive impairment (CI) based on the assessment of compensatory brain reserves in functional MRI (fMRI). MATERIAL AND METHODS: Twenty-one adults over 45 years of age, representing a continuum from healthy norm to mild cognitive impairment due to aging and early cerebral small vessel disease, were studied. All participants underwent fMRI while performing two executive tasks - a modified Stroop task and selective counting. To assess the ability to compensate for CI in real life, functional activation and connectivity were analyzed using the BRIEF-MoCA score as a covariate, which is the difference in ratings between the Behavior Rating Inventory of Executive Function (BRIEF) and the Montreal Cognitive Assessment Scale (MoCA). RESULTS: Both fMRI tasks were associated with activation of areas of the frontoparietal control network, as well as supplementary motor area (SMA) and the pre-SMA, the lateral premotor cortex, and the cerebellum. An increase in pre- SMA connectivity was observed during the tasks. The BRIEF-MoCA score correlated firstly with connectivity of the left dorsolateral prefrontal cortex (DLPFC) and secondly with involvement of the occipital cortex during the counting task. CONCLUSIONS: The developed technique allows identification of the functionally relevant target within the left DLPFC in patients with CI in aging and early cerebral microangiopathy.

Tracking the Immediate and Short-Term Effects of Continuous Theta Burst Stimulation on Dynamic Brain States.

Continuous Theta Burst Stimulation (cTBS) has been shown to modulate cortical oscillations and induce cortical inhibitory effects. Electroencephalography (EEG) studies have shown some immediate effects of cTBS on brain activity. To investigate both immediate effects and short-term effects of cTBS on dynamic brain changes, cTBS was applied to 22 healthy participants over their left motor cortex. We recorded eyes-open, resting-state EEG and performance in the Nine-Hole Peg Test (NHPT) before cTBS, immediately after cTBS, and 80 minutes after cTBS. We identified nine states using a Hidden Markov Model (HMM)-based approach to describe the process of dynamic brain changes. The spatial activation, temporal profiles of HMM states and behavioral performance of NHPT were assessed and compared. cTBS altered the temporal profiles of S1-S5 immediately after cTBS and the temporal profiles of S5, S6 and S7 80 min after cTBS. Moreover, cTBS improved motor function of the left hand. State 1 was characterized as the activation of right occipito-temporal area, and NHPT behavioral performance of the left hand positively correlated with the occurrence of state 1, and negatively correlated with the interval time of state 1 after cTBS. The transitions between S1 or S7 and other states showed dynamic reconfiguration during after-effect sustained time after cTBS. These results suggest that the dynamic characteristics of state 1 are potential biomarkers for characterizing the aftereffect changes of cTBS.

Recruitment of the premotor cortex during arithmetic operations by the monkey.

Arithmetic operations are complex mental processes rooted in the abstract concept of numerosity. Despite the significance, the neural architecture responsible for these operations has remained largely uncharted. In this study, we explored the presence of specific neuronal activity in the dorsal premotor cortex of the monkey dedicated to numerical addition and subtraction. Our findings reveal that many of these neural activities undergo a transformation, shifting their coding from arithmetic to motor representations. These motor representations include information about which hand to use and the number of steps involved in the action. We consistently observed that cells related to the right-hand encoded addition, while those linked to the left-hand encoded subtraction, suggesting that arithmetic operations and motor commands are intertwining with each other. Furthermore, we used a multivariate decoding technique to predict the monkey's behaviour based on the activity of these arithmetic-related cells. The classifier trained to discern arithmetic operations, including addition and subtraction, not only predicted the arithmetic decisions but also the subsequent motor actions of the right and left-hand. These findings imply a cognitive extension of the motor cortex's function, where inherent neural systems are repurposed to facilitate arithmetic operations.

M2M-InvNet: Human Motor Cortex Mapping From Multi-Muscle Response Using TMS and Generative 3D Convolutional Network.

Transcranial magnetic stimulation (TMS) is often applied to the motor cortex to stimulate a collection of motor evoked potentials (MEPs) in groups of peripheral muscles. The causal interface between TMS and MEP is the selective activation of neurons in the motor cortex; moving around the TMS 'spot' over the motor cortex causes different MEP responses. A question of interest is whether a collection of MEP responses can be used to identify the stimulated locations on the cortex, which could potentially be used to then place the TMS coil to produce chosen sets of MEPs. In this work we leverage our previous report on a 3D convolutional neural network (CNN) architecture that predicted MEPs from the induced electric field, to tackle an inverse imaging task in which we start with the MEPs and estimate the stimulated regions on the motor cortex. We present and evaluate five different inverse imaging CNN architectures, both conventional and generative, in terms of several measures of reconstruction accuracy. We found that one architecture, which we propose as M2M-InvNet, consistently achieved the best performance.

Accelerometry as a tool for measuring the effects of transcranial magnetic stimulation.

OBJECTIVE: We predicted that accelerometry would be a viable alternative to electromyography (EMG) for assessing fundamental Transcranial Magnetic Stimulation (TMS) measurements (e.g. Resting Motor Threshold (RMT), recruitment curves, latencies). NEW METHOD: 21 participants were tested. TMS evoked responses were recorded with EMG on the First Dorsal Interosseus muscle and an accelerometer on the index fingertip. TMS was used to determine the (EMG-defined) RMT, then delivered at a range of intensities allowing determination of both the accelerometry-defined RMT and measurement of recruitment curves. RESULTS: RMT assessed by EMG was significantly lower than for accelerometry (t(19)=-3.84, p<.001, mean±SD EMG = 41.1±5.28% MSO (maximum stimulator output), Jerk = 44.55±5.82% MSO), though RMTs calculated for each technique were highly correlated (r(18)=.72, p<.001). EMG/Accelerometery recruitment curves were strongly correlated (r(14)=.98, p<.001), and Bayesian model comparison indicated they were equivalent (BF01>9). Latencies measured with EMG were lower and more consistent than those identified using accelerometry (χ2(1)=80.38, p<.001, mean±SD EMG=27.01±4.58 ms, Jerk=48.4±15.33 ms). COMPARISON WITH EXISTING METHODS: EMG is used as standard by research groups that study motor control and neurophysiology, but accelerometry has not yet been considered as a potential tool to assess measurements such as the overall magnitude and latency of the evoked response. CONCLUSIONS: While EMG provides more sensitive and reliable measurements of RMT and latency, accelerometry provides a reliable alternative to measure of the overall magnitude of TMS evoked responses.

Bilateral Whisker Representations in the Primary Somatosensory Cortex in Robo3cKO Mice Are Reflected in the Primary Motor Cortex.

In Robo3cKO mice, midline crossing defects of the trigeminothalamic projections from the trigeminal principal sensory nucleus result in bilateral whisker maps in the somatosensory thalamus and consequently in the face representation area of the primary somatosensory (S1) cortex (Renier et al., 2017; Tsytsarev et al., 2017). We investigated whether this bilateral sensory representation in the whisker-barrel cortex is also reflected in the downstream projections from the S1 to the primary motor (M1) cortex. To label these projections, we injected anterograde viral axonal tracer in S1 cortex. Corticocortical projections from the S1 distribute to similar areas across the ipsilateral hemisphere in control and Robo3cKO mice. Namely, in both genotypes they extend to the M1, premotor/prefrontal cortex (PMPF), secondary somatosensory (S2) cortex. Next, we performed voltage-sensitive dye imaging (VSDi) in the left hemisphere following ipsilateral and contralateral single whisker stimulation. While controls showed only activation in the contralateral whisker barrel cortex and M1 cortex, the Robo3cKO mouse left hemisphere was activated bilaterally in both the barrel cortex and the M1 cortex. We conclude that the midline crossing defect of the trigeminothalamic projections leads to bilateral whisker representations not only in the thalamus and the S1 cortex but also downstream from the S1, in the M1 cortex.

Preparatory activity and the expansive null-space.

The study of the cortical control of movement experienced a conceptual shift over recent decades, as the basic currency of understanding shifted from single-neuron tuning towards population-level factors and their dynamics. This transition was informed by a maturing understanding of recurrent networks, where mechanism is often characterized in terms of population-level factors. By estimating factors from data, experimenters could test network-inspired hypotheses. Central to such hypotheses are 'output-null' factors that do not directly drive motor outputs yet are essential to the overall computation. In this Review, we highlight how the hypothesis of output-null factors was motivated by the venerable observation that motor-cortex neurons are active during movement preparation, well before movement begins. We discuss how output-null factors then became similarly central to understanding neural activity during movement. We discuss how this conceptual framework provided key analysis tools, making it possible for experimenters to address long-standing questions regarding motor control. We highlight an intriguing trend: as experimental and theoretical discoveries accumulate, the range of computational roles hypothesized to be subserved by output-null factors continues to expand.

Effects of sensory afferent input on motor cortex excitability of agonist and antagonist muscles.

In this study, we aimed to analyze control mechanisms of short-latency afferent inhibition (SAI) during motor output exertion from an agonist or antagonist muscle. The motor task involved index finger abduction (agonist) and adduction (antagonist). In Experiment 1, motor-evoked potentials (MEPs) were recorded from the first dorsal interosseous (FDI) muscle with and without SAI at three output force levels. In Experiment 2, MEPs were recorded with and without SAI at various time points immediately before the muscle output. Experiment 1 showed that inhibition decreased with an increase in muscle output in the agonist muscle but increased in the antagonist muscle. Experiment 2 showed a decreasing trend of inhibition in the agonist muscle immediately before contraction but showed no significant change in the antagonist muscle. MEPs without electrical stimulation during the reaction time increased in both directions of movement as compared to those in the resting state. These results suggest that SAI modulation strongly influences smooth motor output. Analyzing the inhibitory or enhanced mechanisms during the performance of motor output by SAI in patients with motor impairment and comparing them with the mechanisms seen in healthy participants will improve our understanding of the neurophysiological mechanisms relevant to various situations (e.g., rehabilitation and sports).

Modulation of intracortical circuits in primary motor cortex during automatic action tendencies.

Humans display automatic action tendencies toward emotional stimuli, showing faster automatic behavior (i.e., approaching a positive stimulus and avoiding a negative stimulus) than regulated behavior (i.e., avoiding a positive stimulus and approaching a negative stimulus). Previous studies have shown that the primary motor cortex is involved in the processing of automatic actions, with higher motor evoked potential amplitudes during automatic behavior elicited by single-pulse transcranial magnetic stimulation. However, it is unknown how intracortical circuits are involved with automatic action tendencies. Here, we measured short-interval intracortical inhibition and intracortical facilitation within the primary motor cortex by using paired-pulse transcranial magnetic stimulation protocols during a manikin task, which has been widely used to explore approaching and avoiding behavior. Results showed that intracortical facilitation was stronger during automatic behavior than during regulated behavior. Moreover, there was a significant negative correlation between reaction times and intracortical facilitation effect during automatic behavior: individuals with short reaction times had stronger faciliatory activity, as shown by higher intracortical facilitation. By contrast, no significant difference was found for short-interval intracortical inhibition between automatic behavior and regulated behavior. The results indicated that the intracortical facilitation circuit, mediated by excitatory glutamatergic neurons, in the primary motor cortex, plays an important role in mediating automatic action tendencies. This finding further supports the link between emotional perception and the action system.

The phase of tACS-entrained pre-SMA beta oscillations modulates motor inhibition.

Inhibitory control has been linked to beta oscillations in the fronto-basal ganglia network. Here we aim to investigate the functional role of the phase of this oscillatory beta rhythm for successful motor inhibition. We applied 20 Hz transcranial alternating current stimulation (tACS) to the pre-supplementary motor area (pre-SMA) while presenting stop signals at 4 (Experiment 1) and 8 (Experiment 2) equidistant phases of the tACS entrained beta oscillations. Participants showed better inhibitory performance when stop signals were presented at the trough of the beta oscillation whereas their inhibitory control performance decreased with stop signals being presented at the oscillatory beta peak. These results are consistent with the communication through coherence theory, in which postsynaptic effects are thought to be greater when an input arrives at an optimal phase within the oscillatory cycle of the target neuronal population. The current study provides mechanistic insights into the neural communication principles underlying successful motor inhibition and may have implications for phase-specific interventions aimed at treating inhibitory control disorders such as PD or OCD.

Motor oscillations reveal new correlates of error processing in the human brain.

It has been demonstrated that during motor responses, the activation of the motor cortical regions emerges in close association with the activation of the medial frontal cortex implicated with performance monitoring and cognitive control. The present study explored the oscillatory neurodynamics of response-related potentials during correct and error responses to test the hypothesis that such continuous communication would modify the characteristics of motor potentials during performance errors. Electroencephalogram (EEG) was recorded at 64 electrodes in a four-choice reaction task and response-related potentials (RRPs) of correct and error responses were analysed. Oscillatory RRP components at extended motor areas were analysed in the theta (3.5-7 Hz) and delta (1-3 Hz) frequency bands with respect to power, temporal synchronization (phase-locking factor, PLF), and spatial synchronization (phase-locking value, PLV). Major results demonstrated that motor oscillations differed between correct and error responses. Error-related changes (1) were frequency-specific, engaging delta and theta frequency bands, (2) emerged already before response production, and (3) had specific regional topographies at posterior sensorimotor and anterior (premotor and medial frontal) areas. Specifically, the connectedness of motor and sensorimotor areas contra-lateral to the response supported by delta networks was substantially reduced during errors. Also, there was an error-related suppression of the phase stability of delta and theta oscillations at these areas. This synchronization reduction was accompanied by increased temporal synchronization of motor theta oscillations at bi-lateral premotor regions and by two distinctive error-related effects at medial frontal regions: (1) a focused fronto-central enhancement of theta power and (2) a separable enhancement of the temporal synchronization of delta oscillations with a localized medial frontal focus. Together, these observations indicate that the electrophysiological signatures of performance errors are not limited to the medial frontal signals, but they also involve the dynamics of oscillatory motor networks at extended cortical regions generating the movement. Also, they provide a more detailed picture of the medial frontal processes activated in relation to error processing.

Cortical stimulation depth of nTMS investigated in a cohort of convexity meningiomas above the primary motor cortex.

BACKGROUND: In clinical routine, navigated transcranial magnetic stimulation (nTMS) is usually applied down to 25 mm. Yet, besides clinical experience and mathematical models, the penetration depth remains unclear. This study aims to investigate the maximum cortical stimulation depth of nTMS in patients with meningioma above the primary motor cortex, causing a displacement of the primary motor cortex away from the skull. NEW METHOD: nTMS stimulation data was reviewed regarding the maximum depth of stimulations eliciting motor-evoked potentials (MEPs). Additionally, electric field values and stimulation intensity were analyzed. RESULTS: Out of a consecutive cohort of 17 meningioma cases, 3 cases of meningioma located in motor-eloquent regions of the upper extremity and 3 cases of the lower extremity were analyzed after fulfilling all inclusion criteria. Regarding the upper extremity motor representations, the MEP could be elicited at a stimulation depth of up to 44 mm, with an electric field of 69 V/m. These results were found in 1 case with the maximum potential distance to the cortex being higher than the maximum stimulation depth eliciting MEPs. For the lower extremities, a maximum depth of 40 mm was recorded (electric field 64 V/m). COMPARISON WITH EXISTING METHODS: None available CONCLUSIONS: The effect of nTMS is not limited to superficial cortical stimulation alone. Depending on electric-field intensity and focality, nTMS stimulation can be applied at a depth of 44 mm. In all cases, electric field strength was comparable and no superficial cortex with comparable electric field strength was observed to elicit MEPs.

The role of dorsal premotor cortex in joint action inhibition.

Behavioral interpersonal coordination requires smooth negotiation of actions in time and space (joint action-JA). Inhibitory control may play a role in fine-tuning appropriate coordinative responses. To date, little research has been conducted on motor inhibition during JA and on the modulatory influence that premotor areas might exert on inhibitory control. Here, we used an interactive task in which subjects were required to reach and open a bottle using one hand. The bottle was held and stabilized by a co-actor (JA) or by a mechanical holder (vice clamp, no-JA). We recorded two TMS-based indices of inhibition (short-interval intracortical inhibition-sICI; cortical silent period-cSP) during the reaching phase of the task. These reflect fast intracortical (GABAa-mediated) and slow corticospinal (GABAb-mediated) inhibition. Offline continuous theta burst stimulation (cTBS) was used to interfere with dorsal premotor cortex (PMd), ventral premotor cortex (PMv), and control site (vertex) before the execution of the task. Our results confirm a dissociation between fast and slow inhibition during JA coordination and provide evidence that premotor areas drive only slow inhibitory mechanisms, which in turn may reflect behavioral co-adaptation between trials. Exploratory analyses further suggest that PMd, more than PMv, is the key source of modulatory drive sculpting movements, according to the socio-interactive context.

Understanding functional brain reorganization for naturalistic piano playing in novice pianists.

Learning to play the piano is a unique complex task, integrating multiple sensory modalities and higher order cognitive functions. Longitudinal neuroimaging studies on adult novice musicians show training-related functional changes in music perception tasks. The reorganization of brain activity while actually playing an instrument was studied only on a very short time frame of a single fMRI session, and longer interventions have not yet been performed. Thus, our aim was to investigate the dynamic complexity of functional brain reorganization while playing the piano within the first half year of musical training. We scanned 24 novice keyboard learners (female, 18-23 years old) using fMRI while they played increasingly complex musical pieces after 1, 6, 13, and 26 weeks of training. Playing music evoked responses bilaterally in the auditory, inferior frontal, and supplementary motor areas, and the left sensorimotor cortex. The effect of training over time, however, invoked widespread changes encompassing the right sensorimotor cortex, cerebellum, superior parietal cortex, anterior insula and hippocampus, among others. As the training progressed, the activation of these regions decreased while playing music. Post hoc analysis revealed region-specific time-courses for independent auditory and motor regions of interest. These results suggest that while the primary sensory, motor, and frontal regions are associated with playing music, the training decreases the involvement of higher order cognitive control and integrative regions, and basal ganglia. Moreover, training might affect distinct brain regions in different ways, providing evidence in favor of the dynamic nature of brain plasticity.