Frontoparietal beta event characteristics are associated with early life stress and psychiatric symptoms in adults.

Recent work has found that the presence of transient, oscillatory burst-like events, particularly within the beta band (15-29 Hz), is more closely tied to disease state and behavior across species than traditional electroencephalography (EEG) power metrics. This study sought to examine whether features of beta events over frontoparietal electrodes were associated with early life stress (ELS) and the related clinical presentation. Eighteen adults with documented ELS (n = 18; ELS + ) and eighteen adults without documented ELS (n = 18; ELS-) completed eyes-closed resting state EEG as part of their participation in a larger childhood stress study. The rate, power, duration, and frequency span of transient oscillatory events were calculated within the beta band at five frontoparietal electrodes. ELS variables were positively associated with beta event rate at Fp2 and beta event duration at Pz, in that greater ELS was associated with higher resting rates and longer durations. These beta event characteristics were used to successfully distinguish between ELS + and ELS- groups. In an independent clinical dataset (n = 25), beta event power at Pz was positively correlated with ELS. Beta events deserve ongoing investigation as a potential disease marker of ELS and subsequent psychiatric treatment outcomes.

Biophysical Modeling of Frontocentral ERP Generation Links Circuit-Level Mechanisms of Action-Stopping to a Behavioral Race Model.

Human frontocentral event-related potentials (FC-ERPs) are ubiquitous neural correlates of cognition and control, but their generating multiscale mechanisms remain mostly unknown. We used the Human Neocortical Neurosolver's biophysical model of a canonical neocortical circuit under exogenous thalamic and cortical drive to simulate the cell and circuit mechanisms underpinning the P2, N2, and P3 features of the FC-ERP observed after Stop-Signals in the Stop-Signal task (SST; N = 234 humans, 137 female). We demonstrate that a sequence of simulated external thalamocortical and corticocortical drives can produce the FC-ERP, similar to what has been shown for primary sensory cortices. We used this model of the FC-ERP to examine likely circuit-mechanisms underlying FC-ERP features that distinguish between successful and failed action-stopping. We also tested their adherence to the predictions of the horse-race model of the SST, with specific hypotheses motivated by theoretical links between the P3 and Stop process. These simulations revealed that a difference in P3 onset between successful and failed Stops is most likely due to a later arrival of thalamocortical drive in failed Stops, rather than, for example, a difference in the effective strength of the input. In contrast, the same model predicted that early thalamocortical drives underpinning the P2 and N2 differed in both strength and timing across stopping accuracy conditions. Overall, this model generates novel testable predictions of the thalamocortical dynamics underlying FC-ERP generation during action-stopping. Moreover, it provides a detailed cellular and circuit-level interpretation that supports links between these macroscale signatures and predictions of the behavioral race model.

Methods and considerations for estimating parameters in biophysically detailed neural models with simulation based inference.

Biophysically detailed neural models are a powerful technique to study neural dynamics in health and disease with a growing number of established and openly available models. A major challenge in the use of such models is that parameter inference is an inherently difficult and unsolved problem. Identifying unique parameter distributions that can account for observed neural dynamics, and differences across experimental conditions, is essential to their meaningful use. Recently, simulation based inference (SBI) has been proposed as an approach to perform Bayesian inference to estimate parameters in detailed neural models. SBI overcomes the challenge of not having access to a likelihood function, which has severely limited inference methods in such models, by leveraging advances in deep learning to perform density estimation. While the substantial methodological advancements offered by SBI are promising, their use in large scale biophysically detailed models is challenging and methods for doing so have not been established, particularly when inferring parameters that can account for time series waveforms. We provide guidelines and considerations on how SBI can be applied to estimate time series waveforms in biophysically detailed neural models starting with a simplified example and extending to specific applications to common MEG/EEG waveforms using the the large scale neural modeling framework of the Human Neocortical Neurosolver. Specifically, we describe how to estimate and compare results from example oscillatory and event related potential simulations. We also describe how diagnostics can be used to assess the quality and uniqueness of the posterior estimates. The methods described provide a principled foundation to guide future applications of SBI in a wide variety of applications that use detailed models to study neural dynamics.

Biophysical modeling of frontocentral ERP generation links circuit-level mechanisms of action-stopping to a behavioral race model.

Human frontocentral event-related potentials (FC-ERPs) are ubiquitous neural correlates of cognition and control, but their generating multiscale mechanisms remain mostly unknown. We used the Human Neocortical Neurosolver(HNN)'s biophysical model of a canonical neocortical circuit under exogenous thalamic and cortical drive to simulate the cell and circuit mechanisms underpinning the P2, N2, and P3 features of the FC-ERP observed after Stop-Signals in the Stop-Signal task (SST). We demonstrate that a sequence of simulated external thalamocortical and cortico-cortical drives can produce the FC-ERP, similar to what has been shown for primary sensory cortices. We used this model of the FC-ERP to examine likely circuit-mechanisms underlying FC-ERP features that distinguish between successful and failed action-stopping. We also tested their adherence to the predictions of the horse-race model of the SST, with specific hypotheses motivated by theoretical links between the P3 and Stop process. These simulations revealed that a difference in P3 onset between successful and failed Stops is most likely due to a later arrival of thalamocortical drive in failed Stops, rather than, for example, a difference in effective strength of the input. In contrast, the same model predicted that early thalamocortical drives underpinning the P2 and N2 differed in both strength and timing across stopping accuracy conditions. Overall, this model generates novel testable predictions of the thalamocortical dynamics underlying FC-ERP generation during action-stopping. Moreover, it provides a detailed cellular and circuit-level interpretation that supports links between these macroscale signatures and predictions of the behavioral race model.

Pre-treatment frontal beta events are associated with executive dysfunction improvement after repetitive transcranial magnetic stimulation for depression: A preliminary report.

Repetitive transcranial magnetic stimulation (rTMS) is an established clinical treatment for major depressive disorder (MDD) that has also been found to improve aspects of executive functioning. The objective of this study was to examine whether oscillatory burst-like events within the beta band (15-29 Hz) prior to treatment could predict subsequent change in self-reported executive dysfunction (EDF) across a clinical course of rTMS for MDD. Twenty-eight adults (64% female) with MDD completed the self-report Frontal Systems Behavior Scale (FrSBe) and provided eyes-closed resting-state electroencephalography (EEG) before and after a clinical course of rTMS therapy for primary MDD. The rate, power, duration, and frequency span of transient EEG measured oscillatory beta events were calculated. Events within delta/theta and alpha bands were examined to assess for beta specificity. After controlling for improvement in primary depressive symptoms, a lower rate of beta events at F3, Fz, F4, and Cz prior to rTMS treatment was associated with a larger improvement in EDF after rTMS treatment. In addition, a decrease in beta event rate at Fz pre-to-post treatment was associated with a larger improvement in EDF after treatment. Results were largely specific to the beta band. In this study, the rate of frontrocentral beta events prior to treatment significantly predicted the likelihood of subsequent improvement in EDF symptoms following a clinical course of rTMS for MDD. These preliminary findings suggest the potential utility of EEG measured beta events and rTMS for targeting EDF across an array of neuropsychiatric disorders.

A Randomized Controlled Pilot Trial Comparing Effects of Qigong and Exercise/Nutrition Training on Fatigue and Other Outcomes in Female Cancer Survivors.

Cancer-related fatigue (CRF) is a common and burdensome, often long-term side effect of cancer and its treatment. Many non-pharmacological treatments have been investigated as possible CRF therapies, including exercise, nutrition, health/psycho-education, and mind-body therapies. However, studies directly comparing the efficacy of these treatments in randomized controlled trials are lacking. To fill this gap, we conducted a parallel single blind randomized controlled pilot efficacy trial with women with CRF to directly compare the effects of Qigong (a form of mind-body intervention) (n = 11) to an intervention that combined strength and aerobic exercise, plant-based nutrition and health/psycho-education (n = 13) in a per protocol analysis. This design was chosen to determine the comparative efficacy of 2 non-pharmacologic interventions, with different physical demand intensities, in reducing the primary outcome measure of self-reported fatigue (FACIT "Additional Concerns" subscale). Both interventions showed a mean fatigue improvement of more than double the pre-established minimal clinically important difference of 3 (qigong: 7.068 ± 10.30, exercise/nutrition: 8.846 ± 12.001). Mixed effects ANOVA analysis of group × time interactions revealed a significant main effect of time, such that both groups significantly improved fatigue from pre- to post-treatment (F(1,22) = 11.898, P = .002, generalized eta squared effect size = 0.116) There was no significant difference between fatigue improvement between groups (independent samples t-test: P = .70 ), suggesting a potential equivalence or non-inferiority of interventions, which we could not definitively establish due to our small sample size. This study provides evidence from a small sample of n = 24 women with CRF that qigong improves fatigue similarly to exercise-nutrition courses. Qigong additionally significantly improved secondary measures of mood, emotion regulation, and stress, while exercise/nutrition significantly improved secondary measures of sleep/fatigue. These findings provide preliminary evidence for divergent mechanisms of fatigue improvement across interventions, with qigong providing a gentler and lower-intensity alternative to exercise/nutrition.

Fronto-central resting-state 15-29 Hz transient beta events change with therapeutic transcranial magnetic stimulation for posttraumatic stress disorder and major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD) and shows promise for posttraumatic stress disorder (PTSD), yet effectiveness varies. Electroencephalography (EEG) can identify rTMS-associated brain changes. EEG oscillations are often examined using averaging approaches that mask finer time-scale dynamics. Recent advances show some brain oscillations emerge as transient increases in power, a phenomenon termed "Spectral Events," and that event characteristics correspond with cognitive functions. We applied Spectral Event analyses to identify potential EEG biomarkers of effective rTMS treatment. Resting 8-electrode EEG was collected from 23 patients with MDD and PTSD before and after 5 Hz rTMS targeting the left dorsolateral prefrontal cortex. Using an open-source toolbox ( https://github.com/jonescompneurolab/SpectralEvents ), we quantified event features and tested for treatment associated changes. Spectral Events in delta/theta (1-6 Hz), alpha (7-14 Hz), and beta (15-29 Hz) bands occurred in all patients. rTMS-induced improvement in comorbid MDD PTSD were associated with pre- to post-treatment changes in fronto-central electrode beta event features, including frontal beta event frequency spans and durations, and central beta event maxima power. Furthermore, frontal pre-treatment beta event duration correlated negatively with MDD symptom improvement. Beta events may provide new biomarkers of clinical response and advance the understanding of rTMS.

Age-related differences in transient gamma band activity during working memory maintenance through adolescence.

Adolescence is a stage of development characterized by neurodevelopmental specialization of cognitive processes. In particular, working memory continues to improve through adolescence, with increases in response accuracy and decreases in response latency continuing well into the twenties. Human electroencephalogram (EEG) studies indicate that gamma oscillations (35-65 Hz) during the working memory delay period support the maintenance of mnemonic information guiding subsequent goal-driven behavior, which decrease in power with development. Importantly, recent electrophysiological studies have shown that gamma events, more so than sustained activity, may underlie working memory maintenance during the delay period. However, developmental differences in gamma events during working memory have not been studied. Here, we used EEG in conjunction with a novel spectral event processing approach to investigate age-related differences in transient gamma band activity during a memory guided saccade (MGS) task in 164 10- to 30-year-olds. Total gamma power was found to significantly decrease through adolescence, replicating prior findings. Results from the spectral event pipeline showed age-related decreases in the mean power of gamma events and trial-by-trial power variability across both the delay period and fixation epochs of the MGS task. In addition, we found that while event number decreased with age during the fixation period, the developmental decrease during the delay period was more dramatic, resulting in an increase in event spiking from fixation to delay in adolescence but not adulthood. While average power of the transient gamma events was found to mediate age-related differences in total gamma power in the fixation and delay periods, the number of gamma events was related to total power in only the delay period, suggesting that the power of gamma events may underlie the sustained gamma activity seen in EEG literature while the number of events may directly support age-related improvements in working memory maintenance. Our findings provide compelling new evidence for mechanistic changes in neural processing characterized by refinements in neural function as behavior becomes optimized in adulthood.

Fronto-central resting-state 15-29Hz transient beta events change with therapeutic transcranial magnetic stimulation for posttraumatic stress disorder and major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD) and shows promise for posttraumatic stress disorder (PTSD), yet effectiveness varies. Electroencephalography (EEG) can identify rTMS-associated brain changes. EEG oscillations are often examined using averaging approaches that mask finer time-scale dynamics. Recent advances show some brain oscillations emerge as transient increases in power, a phenomenon termed "Spectral Events," and that event characteristics correspond with cognitive functions. We applied Spectral Event analyses to identify potential EEG biomarkers of effective rTMS treatment. Resting 8-electrode EEG was collected from 23 patients with MDD and PTSD before and after 5Hz rTMS targeting the left dorsolateral prefrontal cortex. Using an open-source toolbox ( https://github.com/jonescompneurolab/SpectralEvents ), we quantified event features and tested for treatment associated changes. Spectral Events in delta/theta (1-6 Hz), alpha (7-14 Hz), and beta (15-29 Hz) bands occurred in all patients. rTMS-induced improvement in comorbid MDD PTSD were associated with pre-to post-treatment changes in fronto-central electrode beta event features, including frontal beta event frequency spans and durations, and central beta event maxima power. Furthermore, frontal pre-treatment beta event duration correlated negatively with MDD symptom improvement. Beta events may provide new biomarkers of clinical response and advance the understanding of rTMS.

Detecting Spontaneous Neural Oscillation Events in Primate Auditory Cortex.

Electrophysiological oscillations in the brain have been shown to occur as multicycle events, with onset and offset dependent on behavioral and cognitive state. To provide a baseline for state-related and task-related events, we quantified oscillation features in resting-state recordings. We developed an open-source wavelet-based tool to detect and characterize such oscillation events (OEvents) and exemplify the use of this tool in both simulations and two invasively-recorded electrophysiology datasets: one from human, and one from nonhuman primate (NHP) auditory system. After removing incidentally occurring event-related potentials (ERPs), we used OEvents to quantify oscillation features. We identified ∼2 million oscillation events, classified within traditional frequency bands: δ, θ, α, ß, low γ, γ, and high γ. Oscillation events of 1-44 cycles could be identified in at least one frequency band 90% of the time in human and NHP recordings. Individual oscillation events were characterized by nonconstant frequency and amplitude. This result necessarily contrasts with prior studies which assumed frequency constancy, but is consistent with evidence from event-associated oscillations. We measured oscillation event duration, frequency span, and waveform shape. Oscillations tended to exhibit multiple cycles per event, verifiable by comparing filtered to unfiltered waveforms. In addition to the clear intraevent rhythmicity, there was also evidence of interevent rhythmicity within bands, demonstrated by finding that coefficient of variation of interval distributions and Fano factor (FF) measures differed significantly from a Poisson distribution assumption. Overall, our study provides an easy-to-use tool to study oscillation events at the single-trial level or in ongoing recordings, and demonstrates that rhythmic, multicycle oscillation events dominate auditory cortical dynamics.

Biophysical and Architectural Mechanisms of Subthalamic Theta under Response Conflict.

The cortico-basal ganglia circuit is needed to suppress prepotent actions and to facilitate controlled behavior. Under conditions of response conflict, the frontal cortex and subthalamic nucleus (STN) exhibit increased spiking and theta band power, which are linked to adaptive regulation of behavioral output. The electrophysiological mechanisms underlying these neural signatures of impulse control remain poorly understood. To address this lacuna, we constructed a novel large-scale, biophysically principled model of the subthalamopallidal (STN-globus pallidus externus) network and examined the mechanisms that modulate theta power and spiking in response to cortical input. Simulations confirmed that theta power does not emerge from intrinsic network dynamics but is robustly elicited in response to cortical input as burst events representing action selection dynamics. Rhythmic burst events of multiple cortical populations, representing a state of conflict where cortical motor plans vacillate in the theta range, led to prolonged STN theta and increased spiking, consistent with empirical literature. Notably, theta band signaling required NMDA, but not AMPA, currents, which were in turn related to a triphasic STN response characterized by spiking, silence, and bursting periods. Finally, theta band resonance was also strongly modulated by architectural connectivity, with maximal theta arising when multiple cortical populations project to individual STN "conflict detector" units because of an NMDA-dependent supralinear response. Our results provide insights into the biophysical principles and architectural constraints that give rise to STN dynamics during response conflict, and how their disruption can lead to impulsivity and compulsivity.SIGNIFICANCE STATEMENT The subthalamic nucleus exhibits theta band power modulation related to cognitive control over motor actions during conditions of response conflict. However, the mechanisms of such dynamics are not understood. Here we developed a novel biophysically detailed and data-constrained large-scale model of the subthalamopallidal network, and examined the impacts of cellular and network architectural properties that give rise to theta dynamics. Our investigations implicate an important role for NMDA receptors and cortico-subthalamic nucleus topographical connectivities in theta power modulation.

Neural Mechanisms Underlying Human Auditory Evoked Responses Revealed By Human Neocortical Neurosolver.

Auditory evoked fields (AEFs) are commonly studied, yet their underlying neural mechanisms remain poorly understood. Here, we used the biophysical modelling software Human Neocortical Neurosolver (HNN) whose foundation is a canonical neocortical circuit model to interpret the cell and network mechanisms contributing to macroscale AEFs elicited by a simple tone, measured with magnetoencephalography. We found that AEFs can be reproduced by activating the neocortical circuit through a layer specific sequence of feedforward and feedback excitatory synaptic drives, similar to prior simulation of somatosensory evoked responses, supporting the notion that basic structures and activation patterns are preserved across sensory regions. We also applied the modeling framework to develop and test predictions on neural mechanisms underlying AEF differences in the left and right hemispheres, as well as in hemispheres contralateral and ipsilateral to the presentation of the auditory stimulus. We found that increasing the strength of the excitatory synaptic cortical feedback inputs to supragranular layers simulates the commonly observed right hemisphere dominance, while decreasing the input latencies and simultaneously increasing the number of cells contributing to the signal accounted for the contralateral dominance. These results provide a direct link between human data and prior animal studies and lay the foundation for future translational research examining the mechanisms underlying alteration in this fundamental biomarker of auditory processing in healthy cognition and neuropathology.

Thalamocortical Mechanisms Regulating the Relationship between Transient Beta Events and Human Tactile Perception.

Transient neocortical events with high spectral power in the 15-29 Hz beta band are among the most reliable predictors of sensory perception. Prestimulus beta event rates in primary somatosensory cortex correlate with sensory suppression, most effectively 100-300 ms before stimulus onset. However, the neural mechanisms underlying this perceptual association are unknown. We combined human magnetoencephalography (MEG) measurements with biophysical neural modeling to test potential cellular and circuit mechanisms that underlie observed correlations between prestimulus beta events and tactile detection. Extending prior studies, we found that simulated bursts from higher-order, nonlemniscal thalamus were sufficient to drive beta event generation and to recruit slow supragranular inhibition acting on a 300 ms timescale to suppress sensory information. Further analysis showed that the same beta-generating mechanism can lead to facilitated perception for a brief period when beta events occur simultaneously with tactile stimulation before inhibition is recruited. These findings were supported by close agreement between model-derived predictions and empirical MEG data. The postevent suppressive mechanism explains an array of studies that associate beta with decreased processing, whereas the during-event facilitatory mechanism may demand a reinterpretation of the role of beta events in the context of coincident timing.

Laminar dynamics of high amplitude beta bursts in human motor cortex.

Motor cortical activity in the beta frequency range is one of the strongest and most studied movement-related neural signals. At the single trial level, beta band activity is often characterized by transient, high amplitude, bursting events rather than slowly modulating oscillations. The timing of these bursting events is tightly linked to behavior, suggesting a more dynamic functional role for beta activity than previously believed. However, the neural mechanisms underlying beta bursts in sensorimotor circuits are poorly understood. To address this, we here leverage and extend recent developments in high precision MEG for temporally resolved laminar analysis of burst activity, combined with a neocortical circuit model that simulates the biophysical generators of the electrical currents which drive beta bursts. This approach pinpoints the generation of beta bursts in human motor cortex to distinct excitatory synaptic inputs to deep and superficial cortical layers, which drive current flow in opposite directions. These laminar dynamics of beta bursts in motor cortex align with prior invasive animal recordings within the somatosensory cortex, and suggest a conserved mechanism for somatosensory and motor cortical beta bursts. More generally, we demonstrate the ability for uncovering the laminar dynamics of event-related neural signals in human non-invasive recordings. This provides important constraints to theories about the functional role of burst activity for movement control in health and disease, and crucial links between macro-scale phenomena measured in humans and micro-circuit activity recorded from animal models.

Whole-head OPM-MEG enables noninvasive assessment of functional connectivity.

A recent paper by Boto et al. established reliability of noninvasive functional connectivity measurements with a new whole-head optically pumped magnetometer magnetoencephalography (OPM-MEG) system. This rapidly developing technology enables a conformal sensor array to accommodate different head sizes and opens up new avenues for experiments in more naturalistic settings.

Pain phenotypes classified by machine learning using electroencephalography features.

Pain is a multidimensional experience mediated by distributed neural networks in the brain. To study this phenomenon, EEGs were collected from 20 subjects with chronic lumbar radiculopathy, 20 age and gender matched healthy subjects, and 17 subjects with chronic lumbar pain scheduled to receive an implanted spinal cord stimulator. Analysis of power spectral density, coherence, and phase-amplitude coupling using conventional statistics showed that there were no significant differences between the radiculopathy and control groups after correcting for multiple comparisons. However, analysis of transient spectral events showed that there were differences between these two groups in terms of the number, power, and frequency-span of events in a low gamma band. Finally, we trained a binary support vector machine to classify radiculopathy versus healthy subjects, as well as a 3-way classifier for subjects in the 3 groups. Both classifiers performed significantly better than chance, indicating that EEG features contain relevant information pertaining to sensory states, and may be used to help distinguish between pain states when other clinical signs are inconclusive.

A Brief Report on an 8-Week Course of Mindfulness-based Care for Chronic Pain in the Treatment of Veterans With Back Pain: Barriers Encountered to Treatment Engagement and Lessons Learned.

BACKGROUND: Chronic pain and associated symptoms are debilitating for veterans. Medical costs of treatments are high and current treatment options, most notably with opioid medications, have been associated with significant risk. Mindfulness-based interventions appear promising for chronic pain, but require additional testing in veteran care settings. OBJECTIVE: This project was designed to test the feasibility of engaging and retaining veterans with chronic lower back pain in a new mindfulness protocol tailored for veterans, mindfulness-based care for chronic pain (MBCP). Clinical outcomes were also assessed. DESIGN: An open pilot trial of an 8-week MBCP course that included meditation, gentle yoga, and psychoeducation. SUBJECTS: Twenty-two veterans (mean age=49.77; 18% women) were recruited from a VA Medical Center in the Northeastern US. After screening for inclusion/exclusion criteria, 20 were eligible at baseline. MEASURES: Veterans were assessed at baseline and postintervention for functional impairment, pain intensity and bothersomeness, depression, and mindfulness. RESULTS: The average number of sessions completed was 5; only 4 (20%) attended all sessions. Eleven of the 20 participants (55%) attended 5 or more sessions and had complete preintervention and postintervention visits. Five of the 11 had a clinically meaningful decrease in pain intensity and in depressive symptoms, while 6 of 11 had a meaningful decrease in pain bothersomeness and functional impairment. CONCLUSIONS: It was challenging to enroll and retain participants in this study, even with our intervention designed for veterans. We discuss possible adaptations and refinements in MBCP for veterans with chronic pain to enhance feasibility and improve upon these interventions.

Is Alpha Asymmetry a Byproduct or Cause of Spatial Attention? New Evidence Alpha Neurofeedback Controls Measures of Spatial Attention.

Cued spatial attention differentially modulates alpha power in attended relative to non-attended brain representations, termed the alpha asymmetry. Yet a causal role for alpha in attention is debated. In this issue of Neuron, Bagherzadeh et al., (2019) utilize neurofeedback to train alpha asymmetry and causally impact measures of spatial attention.

Human Neocortical Neurosolver (HNN), a new software tool for interpreting the cellular and network origin of human MEG/EEG data.

Magneto- and electro-encephalography (MEG/EEG) non-invasively record human brain activity with millisecond resolution providing reliable markers of healthy and disease states. Relating these macroscopic signals to underlying cellular- and circuit-level generators is a limitation that constrains using MEG/EEG to reveal novel principles of information processing or to translate findings into new therapies for neuropathology. To address this problem, we built Human Neocortical Neurosolver (HNN, https://hnn.brown.edu) software. HNN has a graphical user interface designed to help researchers and clinicians interpret the neural origins of MEG/EEG. HNN's core is a neocortical circuit model that accounts for biophysical origins of electrical currents generating MEG/EEG. Data can be directly compared to simulated signals and parameters easily manipulated to develop/test hypotheses on a signal's origin. Tutorials teach users to simulate commonly measured signals, including event related potentials and brain rhythms. HNN's ability to associate signals across scales makes it a unique tool for translational neuroscience research.

Neurons carry information in the form of electrical signals. Each of these signals is too weak to detect on its own. But the combined signals from large groups of neurons can be detected using techniques called EEG and MEG. Sensors on or near the scalp detect changes in the electrical activity of groups of neurons from one millisecond to the next. These recordings can also reveal changes in brain activity due to disease. But how do EEG/MEG signals relate to the activity of neural circuits? While neuroscientists can rarely record electrical activity from inside the human brain, it is much easier to do so in other animals. Computer models can then compare these recordings from animals to the signals in human EEG/MEG to infer how the activity of neural circuits is changing. But building and interpreting these models requires advanced skills in mathematics and programming, which not all researchers possess. Neymotin et al. have therefore developed a user-friendly software platform that can help translate human EEG/MEG recordings into circuit-level activity. Known as the Human Neocortical Neurosolver, or HNN for short, the open-source tool enables users to develop and test hypotheses on the neural origin of EEG/MEG signals. The model simulates the electrical activity of cells in the outer layers of the human brain, the neocortex. By feeding human EEG/MEG data into the model, researchers can predict patterns of circuit-level activity that might have given rise to the EEG/MEG data. The HNN software includes tutorials and example datasets for commonly measured signals, including brain rhythms. It is free to use and can be installed on all major computer platforms or run online. HNN will help researchers and clinicians who wish to identify the neural origins of EEG/MEG signals in the healthy or diseased brain. Likewise, it will be useful to researchers studying brain activity in animals, who want to know how their findings might relate to human EEG/MEG signals. As HNN is suitable for users without training in computational neuroscience, it offers an accessible tool for discoveries in translational neuroscience.