Neurodesk: an accessible, flexible and portable data analysis environment for reproducible neuroimaging.

Neuroimaging research requires purpose-built analysis software, which is challenging to install and may produce different results across computing environments. The community-oriented, open-source Neurodesk platform ( https://www.neurodesk.org/ ) harnesses a comprehensive and growing suite of neuroimaging software containers. Neurodesk includes a browser-accessible virtual desktop, command-line interface and computational notebook compatibility, allowing for accessible, flexible, portable and fully reproducible neuroimaging analysis on personal workstations, high-performance computers and the cloud.

Non-invasive brain stimulation in the treatment of post-stroke aphasia: a scoping review.

PURPOSE: Aphasia is an acquired language impairment that commonly results from stroke. Non-invasive brain stimulation (NIBS) might accelerate aphasia recovery trajectories and has seen mounting popularity in recent aphasia rehabilitation research. The present review aimed to: (1) summarise all existing literature on NIBS as a post-stroke aphasia treatment; and (2) provide recommendations for future NIBS-aphasia research. MATERIALS AND METHODS: Databases for published and grey literature were searched using scoping review methodology. 278 journal articles, conference abstracts/posters, and books, and 38 items of grey literature, were included for analysis. RESULTS: Quantitative analysis revealed that ipsilesional anodal transcranial direct current stimulation and contralesional 1-Hz repetitive transcranial magnetic stimulation were the most widely used forms of NIBS, while qualitative analysis identified four key themes including: the roles of the hemispheres in aphasia recovery and their relationship with NIBS; heterogeneity of individuals but homogeneity of subpopulations; individualisation of stimulation parameters; and much remains under-explored in the NIBS-aphasia literature. CONCLUSIONS: Taken together, these results highlighted systemic challenges across the field such as small sample sizes, inter-individual variability, lack of protocol optimisation/standardisation, and inadequate focus on aphasiology. Four key recommendations are outlined herein to guide future research and refine NIBS methods for post-stroke aphasia treatment.

A comprehensive review of non-invasive brain stimulation (NIBS) post-stroke aphasia literature, including all study designs, was required.Review of this literature revealed that anodal transcranial direct current stimulation is the mostly commonly used type of NIBS in aphasia treatment research.Systemic challenges across the field hinder prospective translation of NIBS into aphasia practice.Aphasia rehabilitation professionals should note that further research is required before NIBS is suitable for translation into clinical practice.

Neurodesk: An accessible, flexible, and portable data analysis environment for reproducible neuroimaging.

Neuroimaging data analysis often requires purpose-built software, which can be challenging to install and may produce different results across computing environments. Beyond being a roadblock to neuroscientists, these issues of accessibility and portability can hamper the reproducibility of neuroimaging data analysis pipelines. Here, we introduce the Neurodesk platform, which harnesses software containers to support a comprehensive and growing suite of neuroimaging software (https://www.neurodesk.org/). Neurodesk includes a browser-accessible virtual desktop environment and a command line interface, mediating access to containerized neuroimaging software libraries on various computing platforms, including personal and high-performance computers, cloud computing and Jupyter Notebooks. This community-oriented, open-source platform enables a paradigm shift for neuroimaging data analysis, allowing for accessible, flexible, fully reproducible, and portable data analysis pipelines.

TMS combined with EEG: Recommendations and open issues for data collection and analysis.

Transcranial magnetic stimulation (TMS) evokes neuronal activity in the targeted cortex and connected brain regions. The evoked brain response can be measured with electroencephalography (EEG). TMS combined with simultaneous EEG (TMS-EEG) is widely used for studying cortical reactivity and connectivity at high spatiotemporal resolution. Methodologically, the combination of TMS with EEG is challenging, and there are many open questions in the field. Different TMS-EEG equipment and approaches for data collection and analysis are used. The lack of standardization may affect reproducibility and limit the comparability of results produced in different research laboratories. In addition, there is controversy about the extent to which auditory and somatosensory inputs contribute to transcranially evoked EEG. This review provides a guide for researchers who wish to use TMS-EEG to study the reactivity of the human cortex. A worldwide panel of experts working on TMS-EEG covered all aspects that should be considered in TMS-EEG experiments, providing methodological recommendations (when possible) for effective TMS-EEG recordings and analysis. The panel identified and discussed the challenges of the technique, particularly regarding recording procedures, artifact correction, analysis, and interpretation of the transcranial evoked potentials (TEPs). Therefore, this work offers an extensive overview of TMS-EEG methodology and thus may promote standardization of experimental and computational procedures across groups.

Finding synaptic couplings from a biophysical model of motor evoked potentials after theta-burst transcranial magnetic stimulation.

OBJECTIVE: We aimed to use measured input-output (IO) data to identify the best fitting model for motor evoked potentials. METHODS: We analyzed existing IO data before and after intermittent and continuous theta-burst stimulation (iTBS & cTBS) from a small group of subjects (18 for each). We fitted individual synaptic couplings and sensitivity parameters using variations of a biophysical model. A best performing model was selected and analyzed. RESULTS: cTBS gives a broad reduction in MEPs for amplitudes larger than resting motor threshold (RMT). Close to threshold, iTBS gives strong potentiation. The model captures individual IO curves. There is no change to the population average synaptic weights post TBS but the change in excitatory-to-excitatory synaptic coupling is strongly correlated with the experimental post-TBS response relative to baseline. CONCLUSIONS: The model describes population-averaged and individual IO curves, and their post-TBS change. Variation among individuals is accounted for with variation in synaptic couplings, and variation in sensitivity of neural response to stimulation. SIGNIFICANCE: The best fitting model could be applied more broadly and validation studies could elucidate underlying biophysical meaning of parameters.

Do age-related differences in aperiodic neural activity explain differences in resting EEG alpha?

Alpha-band oscillatory activity in human electroencephalography (EEG) becomes slower and lower in amplitude with advanced age. However, the influence of aperiodic activity on these measures has received little consideration. We investigated whether age-related differences in aperiodic activity explains differences in resting EEG peak alpha frequency and power. We assessed aperiodic activity in 85 younger and 92 older adults by fitting the 1/f-like background activity evident in EEG power spectra using the spectral parameterization ("specparam") algorithm. Across the scalp, the aperiodic exponent and offset were smaller in older compared to younger participants, reflecting a flatter 1/f-like slope and a downward broadband shift in power spectra with age. After correcting for aperiodic activity, peak alpha frequency remained slower in older adults; however, peak alpha power no longer differed statistically between age groups. The large sample size utilized in this study, as well as the depth of analysis, provides further evidence that the aperiodic component of the resting EEG signal is altered with aging and should be considered when investigating neural oscillatory activity.

Motor cortical excitability and pre-supplementary motor area neurochemistry in healthy adults with substantia nigra hyperechogenicity.

Substantia nigra (SN) hyperechogenicity, viewed with transcranial ultrasound, is a risk marker for Parkinson's disease. We hypothesized that SN hyperechogenicity in healthy adults aged 50-70 years is associated with reduced short-interval intracortical inhibition in primary motor cortex, and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-supplementary motor area (pre-SMA). Short-interval intracortical inhibition and intracortical facilitation in primary motor cortex was assessed with paired-pulse transcranial magnetic stimulation in 23 healthy adults with normal (n = 14; 61 ± 7 yrs) or abnormally enlarged (hyperechogenic; n = 9; 60 ± 6 yrs) area of SN echogenicity. Thirteen of these participants (7 SN- and 6 SN+) also underwent brain magnetic resonance spectroscopy to investigate pre-SMA neurochemistry. There was no relationship between area of SN echogenicity and short-interval intracortical inhibition in the ipsilateral primary motor cortex. There was a significant positive relationship, however, between area of echogenicity in the right SN and the magnitude of intracortical facilitation in the right (ipsilateral) primary motor cortex (p = .005; multivariate regression), evidenced by the amplitude of the conditioned motor evoked potential (MEP) at the 10-12 ms interstimulus interval. This relationship was not present on the left side. Pre-SMA glutamate did not predict primary motor cortex inhibition or facilitation. The results suggest that SN hyperechogenicity in healthy older adults may be associated with changes in excitability of motor cortical circuitry. The results advance understanding of brain changes in healthy older adults at risk of Parkinson's disease.

Personalized brain stimulation of memory networks.

BACKGROUND: The finding that transcranial magnetic stimulation (TMS) can enhance memory performance via stimulation of parietal sites within the Cortical-Hippocampal Network counts as one of the most exciting findings in this field in the past decade. However, the first independent effort aiming to fully replicate this finding found no discernible influence of TMS on memory performance. OBJECTIVE: We examined whether this might relate to interindividual spatial variation in brain connectivity architecture, and the capacity of personalisation methodologies to overcome the noise inherent across independent scanners and cohorts. METHODS: We implemented recently detailed personalisation methodology to retrospectively compute individual-specific parietal targets and then examined relation to TMS outcomes. RESULTS: Closer proximity between actual and novel fMRI-personalized targets associated with greater improvement in memory performance. CONCLUSION: These findings demonstrate the potential importance of aligning brain stimulation targets according to individual-specific differences in brain connectivity, and extend upon recent findings in prefrontal cortex.

The influence of sensory potentials on transcranial magnetic stimulation - Electroencephalography recordings.

OBJECTIVE: It remains unclear to what extent Transcranial Magnetic Stimulation-evoked potentials (TEPs) reflect sensory (auditory and somatosensory) potentials as opposed to cortical excitability. The present study aimed to determine; a) the extent to which sensory potentials contaminate TEPs using a spatially-matched sham condition, and b) whether sensory potentials reflect auditory or somatosensory potentials alone, or a combination of the two. METHODS: Twenty healthy participants received active or sham stimulation, with the latter consisting a sham coil click combined with scalp electrical stimulation. Two additional conditions i) electrical stimulation and ii) auditory stimulation alone, were included in a subset of 13 participants. RESULTS: Signals from active and sham stimulation were correlated in spatial and temporal domains > 55 ms post-stimulation. Relative to auditory or electrical stimulation alone, sham stimulation resulted in a) larger potentials, b) stronger correlations with active stimulation and c) a signal that was not a linear sum of electrical and auditory stimulation alone. CONCLUSIONS: Sensory potentials can confound interpretations of TEPs at timepoints > 55 ms post-stimulation. Furthermore, TEP contamination cannot be explained by auditory or somatosensory potentials alone, but instead reflects a non-linear interaction between both. SIGNIFICANCE: Future studies may benefit from controlling for sensory contamination using spatially-matched sham conditions, and which consist of combined auditory and somatosensory stimulation.

Does predictive cueing of presentation time modulate alpha power and facilitate visual working memory performance in younger and older adults?

Selective attention and working memory (WM) are vulnerable to age-related decline. Older adults perform worse on, and are less able to modulate alpha power (8-12 Hz) than younger adults in tasks involving cues about 'where' or 'when' a memory set will appear. However, no study has investigated whether alpha power is modulated by cues predicting the presentation time of a memory set. Here, we recorded electroencephalography while 24 younger (18-33 years) and 23 older (60-77 years) adults completed a modified delay match-to-sample task where participants were cued to the duration of a memory set (0.1 s or 0.5 s). We found: (1) predictive cues increased WM storage; (2) no differences in preparatory alpha power between predictive and neutral cue types, but preparatory alpha suppression was weaker in older adults; (3) retention period oscillatory power differed between presentation times, but these differences were no longer present when comparing trial types from the onset of the memory set; and (4) oscillatory power in the preparatory and retention periods were unrelated to performance. Our results suggest that preparatory alpha power is not modulated by predictive cues towards presentation time, however, reductions in alpha/beta power during visual WM retention may be linked to encoding, rather than retention.

Designing and comparing cleaning pipelines for TMS-EEG data: A theoretical overview and practical example.

Combining transcranial magnetic stimulation (TMS) with electroencephalography (EEG) is growing in popularity as a method for probing the reactivity and connectivity of neural circuits in basic and clinical research. However, using EEG to measure the neural responses to TMS is challenging due to the unique artifacts introduced by combining the two techniques. In this paper, we overview the artifacts present in TMS-EEG data and the offline cleaning methods used to suppress these unwanted signals. We then describe how open science practices, including the development of open-source toolboxes designed for TMS-EEG analysis (e.g., TESA - the TMS-EEG signal analyser), have improved the availability and reproducibility of TMS-EEG cleaning methods. We provide theoretical and practical considerations for designing TMS-EEG cleaning pipelines and then give an example of how to compare different pipelines using TESA. We show that changing even a single step in a pipeline designed to suppress decay artifacts results in TMS-evoked potentials (TEPs) with small differences in amplitude and spatial topography. The variability in TEPs resulting from the choice of cleaning pipeline has important implications for comparing TMS-EEG findings between research groups which use different online and offline approaches. Finally, we discuss the challenges of validating cleaning pipelines and recommend that researchers compare outcomes from TMS-EEG experiments using multiple pipelines to ensure findings are not related to the choice of cleaning methods. We conclude that the continued improvement, availability, and validation of cleaning pipelines is essential to ensure TMS-EEG reaches its full potential as a method for studying human neurophysiology.

The Reproducibility of Bio-Acoustic Features is Associated With Sample Duration, Speech Task, and Gender.

Bio-acoustic properties of speech show evolving value in analyzing psychiatric illnesses. Obtaining a sufficient speech sample length to quantify these properties is essential, but the impact of sample duration on the stability of bio-acoustic features has not been systematically explored. We aimed to evaluate bio-acoustic features' reproducibility against changes in speech durations and tasks. We extracted source, spectral, formant, and prosodic features in 185 English-speaking adults (98 w, 87 m) for reading-a-story and counting tasks. We compared features at 25% of the total sample duration of the reading task to those obtained from non-overlapping randomly selected sub-samples shortened to 75%, 50%, and 25% of total duration using intraclass correlation coefficients. We also compared the features extracted from entire recordings to those measured at 25% of the duration and features obtained from 50% of the duration. Further, we compared features extracted from reading-a-story to counting tasks. Our results show that the number of reproducible features (out of 125) decreased stepwise with duration reduction. Spectral shape, pitch, and formants reached excellent reproducibility. Mel-frequency cepstral coefficients (MFCCs), loudness, and zero-crossing rate achieved excellent reproducibility only at a longer duration. Reproducibility of source, MFCC derivatives, and voicing probability (VP) was poor. Significant gender differences existed in jitter, MFCC first-derivative, spectral skewness, pitch, VP, and formants. Around 97% of features in both genders were not reproducible across speech tasks, in part due to the short counting task duration. In conclusion, bio-acoustic features are less reproducible in shorter samples and are affected by gender.

Regular aerobic exercise is positively associated with hippocampal structure and function in young and middle-aged adults.

Regular exercise has numerous benefits for brain health, including the structure and function of the hippocampus. The hippocampus plays a critical role in memory function, and is altered in a number of psychiatric disorders associated with memory impairments (e.g., depression and schizophrenia), as well as healthy aging. While many studies have focused on how regular exercise may improve hippocampal integrity in older individuals, less is known about these effects in young to middle-aged adults. Therefore, we assessed the associations of regular exercise and cardiorespiratory fitness with hippocampal structure and function in these age groups. We recruited 40 healthy young to middle-aged adults, comprised of two groups (n = 20) who self-reported either high or low levels of exercise, according to World Health Organization guidelines. We assessed cardiorespiratory fitness using a graded exercise test (VO2 max) and hippocampal structure via manual tracing of T1-weighted magnetic resonance images. We also assessed hippocampal function using magnetic resonance spectroscopy to derive estimates of N-acetyl-aspartate concentration and hippocampal-dependent associative memory and pattern separation tasks. We observed evidence of increased N-acetyl-aspartate concentration and associative memory performance in individuals engaging in high levels of exercise. However, no differences in hippocampal volume or pattern separation capacity were observed between groups. Cardiorespiratory fitness was positively associated with left and right hippocampal volume and N-acetyl-aspartate concentration. However, no associations were observed between cardiorespiratory fitness and associative memory or pattern separation. Therefore, we provide evidence that higher levels of exercise and cardiorespiratory fitness are associated with improved hippocampal structure and function. Exercise may provide a low-risk, effective method of improving hippocampal integrity in an early-to-mid-life stage.

Repetitive transcranial magnetic stimulation (rTMS) in autism spectrum disorder: protocol for a multicentre randomised controlled clinical trial.

INTRODUCTION: There are no well-established biomedical treatments for the core symptoms of autism spectrum disorder (ASD). A small number of studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, may improve clinical and cognitive outcomes in ASD. We describe here the protocol for a funded multicentre randomised controlled clinical trial to investigate whether a course of rTMS to the right temporoparietal junction (rTPJ), which has demonstrated abnormal brain activation in ASD, can improve social communication in adolescents and young adults with ASD. METHODS AND ANALYSIS: This study will evaluate the safety and efficacy of a 4-week course of intermittent theta burst stimulation (iTBS, a variant of rTMS) in ASD. Participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (n=150, aged 14-40 years) will receive 20 sessions of either active iTBS (600 pulses) or sham iTBS (in which a sham coil mimics the sensation of iTBS, but no active stimulation is delivered) to the rTPJ. Participants will undergo a range of clinical, cognitive, epi/genetic, and neurophysiological assessments before and at multiple time points up to 6 months after iTBS. Safety will be assessed via a structured questionnaire and adverse event reporting. The study will be conducted from November 2020 to October 2024. ETHICS AND DISSEMINATION: The study was approved by the Human Research Ethics Committee of Monash Health (Melbourne, Australia) under Australia's National Mutual Acceptance scheme. The trial will be conducted according to Good Clinical Practice, and findings will be written up for scholarly publication. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12620000890932).

Dynamical consequences of regional heterogeneity in the brain's transcriptional landscape.

Brain regions vary in their molecular and cellular composition, but how this heterogeneity shapes neuronal dynamics is unclear. Here, we investigate the dynamical consequences of regional heterogeneity using a biophysical model of whole-brain functional magnetic resonance imaging (MRI) dynamics in humans. We show that models in which transcriptional variations in excitatory and inhibitory receptor (E:I) gene expression constrain regional heterogeneity more accurately reproduce the spatiotemporal structure of empirical functional connectivity estimates than do models constrained by global gene expression profiles or MRI-derived estimates of myeloarchitecture. We further show that regional transcriptional heterogeneity is essential for yielding both ignition-like dynamics, which are thought to support conscious processing, and a wide variance of regional-activity time scales, which supports a broad dynamical range. We thus identify a key role for E:I heterogeneity in generating complex neuronal dynamics and demonstrate the viability of using transcriptomic data to constrain models of large-scale brain function.

Neurophysiological effects of repetitive transcranial magnetic stimulation (rTMS) in treatment resistant depression.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is effective for treatment resistant depression (TRD), but little is known about rTMS' effects on neurophysiological markers. We previously identified neurophysiological markers in depression (N45 and N100) of GABA receptor mediated inhibition. Here, we indexed TMS-electroencephalographic (TMS-EEG) effects of rTMS. METHODS: TMS-EEG data was analyzed from a double blind 2:1 randomized active (10 Hz left/bilateral):sham rTMS TRD trial. Participants underwent TMS-EEG over left dorsolateral prefrontal cortex (DLPFC) before and after 6 weeks of rTMS. 30 had useable datasets. TMS-evoked potentials (TEP) and components (N45, N100, P60) were examined with global mean field analysis (GMFA) and locally in DLPFC regions of interest. RESULTS: The N45 amplitude differed between active and sham groups over time, N100 amplitude did not. N45 (t = 2.975, p = 0.007) and N100 amplitudes (t = 2.177, p = 0.042) decreased after active rTMS, demonstrating alterations in cortical inhibition. TEP amplitudes decreased after active rTMS in left (t = 4.887, p < 0.001) and right DLPFC (t = 4.403, p < 0.001) not sham rTMS, demonstrating alterations in cortical excitability. CONCLUSIONS: Our results provide important new knowledge regarding rTMS effects on TMS-EEG measures in TRD, suggesting rTMS reduces neurophysiological markers of inhibition and excitability. SIGNIFICANCE: These findings uncover potentially important neurophysiological mechanisms of rTMS action.

Assessing cerebellar-cortical connectivity using concurrent TMS-EEG: a feasibility study.

Combined single-pulse transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been used to probe the features of local networks in the cerebral cortex. Here, we investigated whether we can use this approach to explore long-range connections between the cerebellum and cerebral cortex. Ten healthy adults received single-pulse suprathreshold TMS to the cerebellum and an occipital/parietal control site with double-cone and figure-of-eight coils while cerebral activity was recorded. A multisensory electrical control condition was used to simulate the sensation of the double-cone coil at the cerebellar site. Two cleaning pipelines were compared, and the spatiotemporal relationships of the EEG output between conditions were examined at sensor and source levels. Cerebellar stimulation with the double-cone coil resulted in large artifact in the EEG trace. The addition of SOUND filtering to the cleaning pipeline improved the signal such that further analyses could be undertaken. The cortical potentials evoked by the active TMS conditions showed strong relationships with the responses to the multisensory control condition after ∼50 ms. A distinct parietal component at ∼42 ms was found following cerebellar double-cone stimulation. Although evoked potentials differed across all conditions at early latencies, it is unclear as to whether these represented TMS-related network activation of the cerebellarthalamocortical tract, or whether components were dominated by sensory contamination and/or coil-driven artifact. This study highlights the need for caution when interpreting outcomes from cerebellar TMS-EEG studies.NEW & NOTEWORTHY This is the first study to systematically assess the feasibility of obtaining TMS-evoked potentials from cerebellar stimulation with concurrent EEG. An innovative control condition using electrical stimulation was modified to mimic the sensory aspects of cerebellar stimulation with a double-cone coil, and a state-of-the art cleaning pipeline was trialled. The extent of artifact contamination in signals from stimulation of a cerebellar and an occipital/parietal control site using two TMS coil types was highlighted.

The correspondence between EMG and EEG measures of changes in cortical excitability following transcranial magnetic stimulation.

KEY POINTS: TMS is commonly used to study excitatory/inhibitory neurotransmission in cortical circuits. Changes in cortical excitability following TMS are typically measured from hand (using EMG; limited to motor cortex) or scalp (using EEG); however, it is unclear whether these two measures represent the same activity when assessing motor cortex. We found that TMS-EMG and TMS-EEG measures of motor cortex excitability are differentially affected by sensory confounds at different time points, masking any actual relationship between them in the time domain. In the frequency domain, local high-frequency oscillations in EEG recordings were minimally confounded by sensory artefacts and demonstrated strong correlations with EMG measures of cortical excitability across time, regardless of TMS intensity or waveform. Therefore, despite the effects of sensory artefacts, the two measures of motor cortex excitability share a response component, suggesting that they index a similar cortical activity and perhaps the same neuronal population. ABSTRACT: Transcranial magnetic stimulation (TMS) is a powerful tool for investigating cortical circuits. Changes in cortical excitability following TMS are typically assessed by measuring changes in either conditioned motor-evoked potentials (MEPs) following paired-pulse TMS over motor cortex or evoked potentials measured with electroencephalography following single-pulse TMS (TEPs). However, it is unclear whether these two measures of cortical excitability index the same cortical response. Twenty-four healthy participants received local and interhemispheric paired-pulse TMS over motor cortex with eight inter-pulse intervals, sub- and suprathreshold conditioning intensities, and two different pulse waveforms, while MEPs were recorded from a hand muscle. TEPs were also recorded in response to single-pulse TMS using the conditioning pulse alone. The relationships between TEPs and conditioned-MEPs were evaluated using metrics sensitive to both their magnitude at each time point and their overall shape across time. The impacts of undesired sensory potentials resulting from TMS pulse and muscle contractions were also assessed on both measures. Both conditioned-MEPs and TEPs were sensitive to re-afferent somatosensory activity following motor-evoked responses, but over different post-stimulus time points. Moreover, the amplitude of low-frequency oscillations in TEPs was strongly correlated with the sensory potentials, whereas early and local high-frequency responses showed minimal relationships. Accordingly, conditioned-MEPs did not correlate with TEPs in the time domain but showed high shape similarity with the amplitude of high-frequency oscillations in TEPs. Therefore, despite the effects of sensory confounds, the TEP and MEP measures share a response component, suggesting that they index a similar cortical response and perhaps the same neuronal populations.

Modeling motor-evoked potentials from neural field simulations of transcranial magnetic stimulation.

OBJECTIVE: To develop a population-based biophysical model of motor-evoked potentials (MEPs) following transcranial magnetic stimulation (TMS). METHODS: We combined an existing MEP model with population-based cortical modeling. Layer 2/3 excitatory and inhibitory neural populations, modeled with neural-field theory, are stimulated with TMS and feed layer 5 corticospinal neurons, which also couple directly but weakly to the TMS pulse. The layer 5 output controls mean motoneuron responses, which generate a series of single motor-unit action potentials that are summed to estimate a MEP. RESULTS: A MEP waveform was generated comparable to those observed experimentally. The model captured TMS phenomena including a sigmoidal input-output curve, common paired pulse effects (short interval intracortical inhibition, intracortical facilitation, long interval intracortical inhibition) including responses to pharmacological interventions, and a cortical silent period. Changes in MEP amplitude following theta burst paradigms were observed including variability in outcome direction. CONCLUSIONS: The model reproduces effects seen in common TMS paradigms. SIGNIFICANCE: The model allows population-based modeling of changes in cortical dynamics due to TMS protocols to be assessed in terms of changes in MEPs, thus allowing a clear comparison between population-based modeling predictions and typical experimental outcome measures.