Biology subjects

Beck, M. M.

Publications and source records attributed to Beck, M. M..

12 recordsLinked to original sources

bioRxiv2026

Immediate cortical responses to transcranial magnetic stimulation of the human motor leg area

Background: Immediate transcranial evoked potentials (iTEPs) are ultra-early electroencephalographic responses elicited by single-pulse transcranial magnetic stimulation (TMS) of the primary motor cortical hand area (M1-HAND). Their characteristic latency, waveform, and sensitivity to short-interval intracortical inhibition suggest a close relationship to the cortical generators of indirect corticospinal volleys (I-waves). Here, we tested the hypothesis that iTEPs constitute a fundamental physiological response of human motor cortex and therefore generalize across motor representations, including the leg representation (M1-LEG). Methods: Single-pulse TMS was delivered over the motor cortical representation of the right tibialis anterior (TA) in 16 healthy volunteers. In a subset of participants (n=10), stimulus-response curves and paired-pulse short-interval intracortical inhibition (SICI) measures were obtained. Results: TMS of M1-LEG elicited reproducible iTEPs consisting of a slow positive deflection with superimposed high-frequency peaks with topographic maxima in electrodes adjacent to the stimulation site. M1-LEG iTEPs emerged close to active motor threshold and increased in prevalence and amplitude with increasing stimulation intensity. Paired-pulse stimulation produced consistent SICI of the second and third iTEP peaks. M1-LEG stimulation also evoked conventional later TEPs with latencies and polarities closely resembling those recorded after M1-HAND stimulation. Conclusions: TMS of the human M1-LEG elicits robust iTEPs that closely resemble those recorded from M1-HAND in their timing, intensity dependence, and sensitivity to intracortical inhibition. These findings indicate that iTEPs are not specific to M1-HAND but reflect a general physiological response of human motor cortex closely linked to corticospinal I-wave generation. This broadens their utility as a non-invasive probe of excitatory and inhibitory circuit dynamics throughout the human motor system.

neuroscience↗

bioRxiv2026

Opposing modulation of cortical and corticospinal excitability across movement-related beta stages

Discrete voluntary movement depends on rapid changes in neural excitability across cortical and corticospinal circuits, yet how intrinsic movement-related neural states shape multi-level excitability remains unclear. Here, we combined individualized, state-targeted transcranial magnetic stimulation (TMS) with electroencephalography and electromyography recordings during visually cued finger movements to probe excitability across movement-related beta-band dynamics during two complementary experiments. Immediate transsynaptic cortical excitability closely tracked intrinsic beta dynamics, with attenuation of the second immediate TMS-evoked potential during beta desynchronization and recovery during the post-movement beta rebound. In contrast, corticospinal excitability showed the opposite pattern, with larger motor-evoked potentials during beta desynchronization and reduced responses during beta rebound. Together, these findings identify endogenous beta-state dynamics as a key regulator of movement-related cortical excitability and reveal a fundamental dissociation between how intrinsic brain activity tunes local cortical excitability and corticospinal output in humans.

neuroscience↗

bioRxiv2026

Direct Assessment of Short-Latency Intracortical Inhibition via Immediate TMS-Evoked Potentials

Short-interval intracortical inhibition (SICI) is the most widely used neurophysiological index of GABAergic inhibition in the human cortex. However, it is an indirect measure, inferring synaptic inhibition from suppression of peripherally recorded motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS). In the standard protocol, a subthreshold conditioning pulse suppresses the MEP evoked by a suprathreshold test pulse delivered 1-5 ms later. Interpretation is further complicated by temporal overlap with short-interval intracortical facilitation (SICF), reflecting excitatory interactions at interstimulus intervals of [~]1.5 and 2.7 ms. To overcome these limitations, we recorded immediate TMS-evoked EEG potentials (iTEPs; 1-10 ms post-stimulus) as a more direct measure of motor cortical activity in 16 healthy volunteers (20-35 years; 7 male). The conventional SICI protocol suppressed only later components of the iTEP, likely corresponding to late corticospinal volleys previously identified in epidural spinal recordings after suprathreshold TMS, while the earliest iTEP component was unaffected. Importantly, later iTEPs were suppressed to a similar extent whether conditioning-test intervals coincided with SICF peaks or troughs, and the magnitude of iTEP suppression correlated with concurrently recorded paired-pulse MEP suppression. SICI also reduced an early TEP component (N15; 10-20 ms), but paired-pulse N15 suppression showed a different dependence on stimulus intensity and did not correlate with MEP suppression. These findings demonstrate that SICI measured via MEPs does not reflect a global index of cortical GABAergic motor cortical inhibition but instead reflects inhibition within specific cortical circuits that can be investigated directly with iTEPs.

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bioRxiv2026

No group-level changes in corticospinal excitability following low-intensity theta-burst ultrasound stimulation of the primary motor hand area.

BackgroundLow-intensity transcranial ultrasound stimulation (TUS) is a novel non-invasive brain-stimulation technique offering high spatial precision and depth penetrance. Theta burst TUS (tbTUS), featuring a temporal theta burst stimulation pattern, has been reported to facilitate corticomotor excitability, when applied to the human primary motor hand area (M1-HAND). However, replication attempts have yielded inconsistent results. MethodsFifteen healthy human participants underwent neuronavigated tbTUS targeting the left M1-HAND in the anterior wall of the precentral sulcus, as well as anterior and posterior active control sites. The three tbTUS conditions were applied in counterbalanced order on separate days. Corticospinal excitability was assessed via motor evoked potentials (MEPs) recorded before and 5, 15, 30, and 60 minutes after tbTUS, and analyzed using an rmANOVA. ResultsNone of the tbTUS conditions produced consistent group-level changes in MEP amplitude at any time point. Both intra- and inter-subject variability were high, and individual MEP changes following precentral tbTUS did not correlate with changes after control-site stimulation. ConclusionsWe did not observe reliable modulatory effects of neuronavigated tbTUS on corticospinal excitability. Methodological and hardware differences may account for discrepancies across studies. Our findings align with recent reports questioning the robustness of tbTUS-induced facilitation.

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bioRxiv2025

Not two sides of the same coin: Divergent effects of motor state on corticospinal and cortical responses to TMS of motor cortex

BackgroundTranscranial magnetic stimulation (TMS) of the motor cortex can elicit motor evoked potentials (MEPs) in target muscles, reflecting corticospinal excitability. MEP amplitudes increase with TMS intensity and can be facilitated by tonic muscle pre-activation. Since conventional transcranial evoked potentials (TEPs) also grow with increasing TMS intensity, cortical and corticospinal responses are often considered two facets of the same process. If this were true, changes in physiological motor state should modulate TEPs and MEPs in a similar manner. MethodsTo compare the state-dependency of cortical and corticospinal responses to single-pulse TMS, we simultaneously recorded TEPs and MEPs in 16 healthy young adults during relaxation and isometric contraction of the right first dorsal interosseous (FDI) muscle. For each condition, 100 biphasic TMS pulses were delivered to the left primary motor hand area at five different intensities centered around the resting motor threshold. ResultsTEP and MEP amplitudes increased with stimulation intensity. As predicted, tonic muscle contraction consistently facilitated MEP. On the contrary, muscle contraction attenuated two key peaks of the TEP (N15 and N100). The state-dependent effects of corticospinal and cortical responses were not correlated. DiscussionBoth TEPs and MEPs are reliably modulated by motor state, yet they differ in direction and their magnitudes do not scale with each other. These findings challenge the assumption that cortical and corticospinal responses are two aspects of the same process. MEP facilitation during contraction likely reflects increased spinal excitability, whereas TEP attenuation may reflect reduced responsiveness of cortico-cortical or cortico-subcortical networks.

neuroscience↗

bioRxiv2025

Rostro-caudal TMS mapping of immediate transcranial evoked potentials reveals a pericentral crescendo-decrescendo pattern

BackgroundWe recently demonstrated that single-pulse TMS of the primary sensorimotor hand area (SM1HAND) elicits an immediate transcranial evoked potential (iTEP). This iTEP response appears within 2-7 ms post-TMS, featuring high-frequency peaks superimposed on a slow positive wave. Here, we used a linear TMS-EEG mapping approach to characterize the rostro-caudal iTEP expression and compared it to that of motor-evoked potentials (MEPs). MethodsIn 15 healthy young volunteers (9 females), we identified the iTEP hotspot in left SM1HAND. We applied single biphasic TMS pulses at an intensity of 110% of resting motor threshold over six cortical sites along a rostro-caudal axis (2 cm rostral to 3 cm caudal to the SM1HAND hotspot). We analyzed site-specific iTEP and MEP responses. ResultsiTEP magnitude decreased rostrally and caudally from the SM1HAND hotspot. MEPs exhibited a similar rostro-caudal crescendo-decrescendo pattern. While iTEP and MEP response profiles were similar, normalized iTEP amplitudes decayed less rapidly at the first postcentral site. DiscussionThese findings support the idea that pericentral iTEPs reflect a direct response signature of the pericentral cortex, possibly involving a synchronized TMS-induced excitation of cortical pyramidal tract neurons. Similar but non-identical rostro-caudal patterns suggest that iTEPs and MEPs may arise from overlapping but distinct neuronal populations.

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bioRxiv2024

Methodological choices matter: A systematic comparison of TMS-EEG studies targeting the primary motor cortex

BackgroundTranscranial magnetic stimulation (TMS) triggers time-locked cortical activity that can be recorded with electroencephalography (EEG). Transcranial evoked potentials (TEPs) are widely used to probe brain responses to TMS. MethodsHere, we systematically reviewed 137 published experiments that studied TEPs elicited from TMS to the human primary motor cortex (M1) in healthy individuals to investigate the impact of methodological choices. We scrutinized prevalent methodological choices and assessed how consistently they were reported in published papers. We extracted amplitudes and latencies from reported TEPs and compared total cortical activation and specific TEP peaks and components. ResultsReporting of methodological details was overall sufficient, but some relevant information regarding the TMS settings and the recording and pre-processing of EEG data were missing in more than 25% of the included experiments. The published TEP latencies and amplitudes confirm the prototypical TEP waveform of M1, comprising distinct N15, P30, N45, P60, N100, and P180 peaks. However, variations in amplitude and latencies were evident across studies. Higher stimulation intensities were associated with overall larger TEP amplitudes. Active noise masking during TMS generally resulted in lower TEP amplitudes compared to no or passive masking but did not specifically impact those TEP peaks linked to long-latency sensory processing. Studies implementing independent component analysis (ICA) for artifact removal generally reported lower TEP amplitudes. ConclusionSome aspects of reporting practices could be improved in TEP studies to enable replication. Methodological choices, including TMS intensity and the use of noise masking or ICA, introduce systematic differences in reported TEP amplitudes. Further investigation into the significance of these and other methodological factors and their interactions is warranted.

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bioRxiv2023

Transcranial magnetic stimulation of primary motor cortex elicits a site-specific immediate transcranial evoked potential

BackgroundTranscranial evoked potentials (TEPs) measured via electroencephalography (EEG) are widely used to study the cortical responses to transcranial magnetic stimulation (TMS). Immediate transcranial evoked potentials (i-TEPs) have been obscured by pulse and muscular artifacts. Thus, the TEP peaks that are commonly reported have latencies that are too long to be caused by direct excitation of cortical neurons. MethodsIn 14 healthy individuals, we recorded i-TEPs evoked by a single biphasic TMS pulse targeting the primary motor hand area (M1HAND) or parietal or midline control sites. Sampling EEG at 50 kHz enabled us to reduce the duration of the TMS pulse artifact to a few milliseconds, while minor adjustments of the TMS coil tilt or position enabled us to avoid cranial muscular twitches during the experiment. ResultsWe observed an early positive EEG deflection starting after approx. 2 ms combined with a series of peaks with an inter-peak interval of [~]1.1-1.4 ms in electrodes overlying the stimulated sensorimotor region. This multi-peak i-TEP response was only evoked by TMS of the M1HAND region and was modified by changes in stimulation intensity and current direction. DiscussionSingle-pulse TMS of the M1HAND evokes an immediate local multi-peak response at the cortical site of stimulation. Our results suggest that the observed i-TEP patterns are genuine cortical responses evoked by TMS caused by synchronized excitation of pyramidal neurons in the targeted precentral cortex. This notion needs to be corroborated in future studies, including further investigations into the potential contribution of instrumental or physiological artifacts.

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bioRxiv2023

Hebbian priming of human spinal motor learning

Learning or relearning of motor skills requires plasticity in relevant neural circuits. Motor recovery following lesions to the corticospinal system can be augmented through neuromodulation techniques targeting the affected or compensatory neural circuits. By repeatedly pairing transcranial magnetic stimulation of the primary motor cortex (M1) and motoneuronal electrical stimulation (i.e., paired corticomotoneuronal stimulation, PCMS) timed to arrive at the corticomotoneuronal (CM) synapses in close temporal proximity, spike-timing-dependent bidirectional changes in CM transmission can be induced in humans (Taylor & Martin, 2009). PCMS-induced increases in CM transmission have been demonstrated to transiently improve motor control in patients with spinal cord injury (Bunday & Perez 2012), whereas effects on the malleability of neural circuits are entirely unexplored. We hypothesized that PCMS can prime mechanisms of subsequent motor learning exclusively when directed to the neural circuitry underpinning the motor behavior. In three experiments, we provide the first evidence ( Experiment I) and a double-blinded, sham-controlled replication ( Experiment II) that PCMS targeting the spinal CM synapses can prime subsequent learning of rapid finger movements relying on spinal neuroplasticity. Finally, we demonstrate that the effects of PCMS are circuit-specific and bidirectional. When PCMS was timed to arrive at a facilitatory interval in M1 but an inhibitory interval at the CM synapses subsequent learning was transiently impeded ( Experiment III). Taken together, our results provide proof-of-principle that non-invasively induced plasticity governed by Hebbian learning rules interacts with experience-dependent plasticity in the spinal cord with positive implications for motor learning. Our results offer a mechanistic rationale for priming sensorimotor training with individualized PCMS to enhance the effects of motor practice in neurorehabilitation. HighlightsO_LIPaired corticomotoneuronal stimulations (PCMS) promote ballistic motor learning and facilitate corticospinal excitability compared to rest and sham protocols. C_LIO_LIA double-blinded sham experiment replicates priming effects of PCMS on ballistic motor learning and demonstrates long-term benefits of combined PCMS and motor practice. C_LIO_LIThe facilitating effect of PCMS on ballistic motor learning is circuit-specific with superior effects on ballistic motor learning after facilitating PCMS compared to control protocols. C_LI

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bioRxiv2021

Behavioural variability and cortical electrophysiological signals depend on recent outcomes during human reinforcement motor learning

The history of our actions and the outcomes of these represent important information, which can inform choices, and efficiently guide future behaviour. While unsuccessful (S-) outcomes are expected to lead to more explorative motor states and increased behavioural variability, successful (S+) outcomes lead to reinforcement of the previous action and thus exploitation. Here, we show that during reinforcement motor learning, humans attribute different values to previous actions when they experience S- vs. S+ outcomes. Behavioural variability after S- outcomes is influenced more by the previous outcomes compared to what is observed after S+ outcomes. Using electroencephalography, we show that neural oscillations of the prefrontal cortex encode the level of reinforcement (high beta frequencies) and reflect the detection of reward prediction errors (theta frequencies). The results suggest that S+ experiences overwrite previous motor states to a greater extent than S- experiences and that modulations in neural oscillations in the prefrontal cortex play a potential role in encoding the (changes in) movement variability state during reinforcement motor learning.

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bioRxiv2020

Development of functional corticomuscular connectivity from childhood to adulthood during precision grip with the dominant and non-dominant hand

How does the neural control of manual movements mature from childhood to adulthood? Here, we investigated developmental differences in functional corticomuscular connectivity using coherence techniques in 91 individuals recruited from four different age groups covering the age range 8-30y. EEG and EMG were recorded while participants performed a unimanual visual force-tracing task requiring fine control of the force produced in a precision grip with both the dominant and non-dominant hand. Using beamforming methods, we reconstructed source activity from EEG data displaying peak coherence with the active FDI muscle during the task in order to assess functional corticomuscular connectivity. Our results revealed that coherence was greater in adolescents and adults than in children and that the difference in coherence between children and adults was driven by a greater magnitude of descending (cortex-to-muscle) coherence. This was paralleled by the observation of a posterior-to-anterior shift in the cortical sources displaying corticomuscular coherence within the contralateral hemisphere from late adolescence. Finally, we observed that corticomuscular coherence was higher on the non-dominant compared to the dominant hand across age groups. These findings provide a detailed characterization of differences in task-related corticomuscular connectivity for individuals at different stages of typical ontogenetic development that may be related to the maturational refinement of dexterous motor control. Key points- Fine motor control is gradually refined during human motor development, but little is known about the underlying neurophysiological mechanisms. - Here, we used EEG and EMG to investigate functional corticomuscular connectivity during a precision grip with the dominant and non-dominant hand in 91 typically developed children, adolescents and adults (age range 8-30y). - We show that older adolescents and adults are characterized by greater levels of corticomuscular coherence compared to children and that this is mainly driven by greater magnitudes of descending coherence (cortex-to-muscle). This is paralleled by a more anterior cortical site of coherence in older adolescents and adults compared to younger individuals. - These results help us better understand the ontogenetic development of task-related functional connectivity in sensorimotor networks.

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bioRxiv2019

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 yr) and fifteen older (65-73 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 age-related differences reflect compensatory mechanisms whereby older adults maintain performance in the face of declines in the sensorimotor system.

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