Teaching and Training with Open Science: From Classroom Teaching Tool to Professional Development.

In order for open science to reach its full potential to reduce barriers in science and increase access to the field, data and tools need to be accompanied by training and other supporting resources to make them truly accessible to prospective and new users. Further, these educational resources must be tailored to meet the needs of many different user profiles, such as neuroscientists of many specialties, computational scientists, and educators. In this article, we will describe some of the approaches the Allen Institute has taken to support working scientists, students, and educators at multiple career stages and paths to use our open science resources.

Mapping Human Neuronal Diversity in the Search for New Therapeutics: Using Real Human Neuron Data Sets to Build Student Quantitative Skills.

Case studies are a high impact educational practice that engage students in collaborative problem solving through storytelling. HITS, an NSF funded research coordination network dedicated to exposing students to high-throughput discovery science, drove creation of this case. In this case, students imagine themselves as researchers developing new therapeutic drugs for epilepsy. Specifically, students work with the Allen Cell Types Database, which is the result of collaborative, interdisciplinary open science. Neurosurgeons partnered with the Allen institute to provide living human brain tissue for electrophysiological, morphological, and transcriptomic study. Students collaborate to collect and organize data, investigate a research question they identified, and perform fundamental statistical analyses to address their question. By leveraging the unique Cell Types dataset the case enhances student knowledge of epilepsy, illuminates high-throughput scientific approaches, and builds quantitative and research related skills. The case is also versatile and was implemented in two distinct courses. The case can also be taught in different modalities, in person or remote, with a combination of synchronous and asynchronous work. Indirect and direct measures along with quantitative and qualitative approaches were used for case assessment and improvement. Students performed well on case related exam questions, reported high confidence in their achievement of the learning outcomes, and enjoyed the case's link to neurological disease, real research data and advanced technological approaches. Our assessment findings and instructor implementation experiences are also included to facilitate the adoption or adaptation of the case for a variety of courses and/or modalities in neuroscience and STEM related curricula.

Does Organelle Shape Matter?: Exploring Patterns in Cell Shape and Structure with High-Throughput (HT) Imaging.

Organelle structure has been studied and visualized for decades; however, publicly available databases that use improved high-throughput microscopy of gene-edited cell lines have recently revolutionized the amount and quality of information now available for use in undergraduate classes. This lesson demonstrates how the use of high-throughput (HT) microscopy has generated data describing organelle structure and variability. Students access, analyze, and evaluate cell structure images using the Allen Institute for Cell Science's Allen Cell Explorer. Students synthesize the information to make recommendations and propose a future experiment. Using web-based tools and a realistic scenario that merges antimicrobial drug screens with eukaryotic cell perturbations and structure, this case study provides a guided tour of the powerful applications of high-throughput microscopy.

Electrocorticography to Investigate Age-Related Brain Lateralization on Pediatric Motor Inhibition.

Response inhibition refers to the ability to suppress inappropriate actions that interfere with goal-driven behavior. The inferior frontal gyrus (IFG) is known to be associated with inhibition of a motor response by assuming executive control over motor cortex outputs. This study aimed to evaluate the pediatric development of response inhibition through subdural electrocorticography (ECoG) recording. Subdural ECoG recorded neural activities simultaneously during a Go/No-Go task, which was optimized for children. Different frequency power [theta: 4-8 Hz; beta: 12-40 Hz; high-gamma (HG): 70-200 Hz] was estimated within the IFG and motor cortex. Age-related analysis was computed by each bandpass power ratio between Go and No-Go conditions, and phase-amplitude coupling (PAC) over IFG by using the modulating index metric in two conditions. For all the eight pediatric patients, HG power was more activated in No-Go trials than in Go trials, in either right- or left-side IFG when available. In the IFG region, the power over theta and HG in No-Go conditions was higher than those in Go conditions, with significance over the right side (p < 0.05). The age-related lateralization from both sides to the right side was observed from the ratio of HG power and PAC value between the No-Go and Go trials. In the pediatric population, the role of motor inhibition was observed in both IFG, with age-related lateralization to the right side, which was proved in the previous functional magnetic resonance imaging studies. In this study, the evidence correlation of age and response inhibition was observed directly by the evidence of cortical recordings.

Teaching Neuroscience: Reviving Neuroanatomy, Notes on the 2022 Society for Neuroscience Professional Development Workshop on Teaching.

Students often find neuroanatomy a daunting exercise of rote memorization in a dead language. This workshop was designed to enliven the teaching of neuroanatomy. We recast the topic by extending it to the cellular and sub-cellular levels, animating it by learning to build a brain, and infusing the topic with the lively arts. Due to COVID's interference with the usual schedule of Society for Neuroscience (SfN) events, the 2021 Professional Development Workshop on Teaching was held as a webinar on April 12, 2022 with a follow-up question and answer session on June 7. In this workshop, not only were innovative teaching methods presented, but also the very definition of neuroanatomy was pushed to the limits-even reaching into the molecular and subcellular level. The presenters provided means of engaging students that were no cost, low cost, or well within the reach of most academic institutions. Judging by the attendance, this webinar was quite successful in its goals. Our speakers presented exciting and varied approaches to teaching neuroanatomy. Kaitlyn Casimo presented how the vast resources of the Allen Institute could be employed. Marc Nahmani described how open data resources could be utilized in creating a Course-Based Undergraduate Research Experience (CURE) on neural microanatomy. Erika Fanselow presented novel ways to overcome one of students' big hurdles in grasping neuroanatomy: understanding 3-D relationships. Len White described a creative approach in teaching neuroanatomy by incorporating the humanities, particularly art and literature. This article presents synopses of the presentations, which are written by the four presenters. Additionally, prompted by questions from the viewers, we have constructed a table of our favorite resources. A video of the original presentations as well as links to the subsequent Q & A sessions is available at https://neuronline.sfn.org/training/teaching-neuroscience-reviving-neuroanatomy/.

Enhancing Student Research Experiences with Open Data from the Allen Brain Map.

The Allen Brain Map is the main data repository for the Allen Institute for Brain Science, containing big, open datasets commonly used in neuroscience research (Allen Institute for Brain Science, 2022). Open data from the Allen Brain Map can be used to teach core concepts in neuroscience, data analysis methods, and other critical skills and knowledge to neuroscience students. These datasets can be used as the main data source for completely online lab experiences, or analyzed in combination with data students collect themselves. Applications may range in scope and format from a short worksheet used in a single class session to a coding tutorial to a guided independent research project. While open online data cannot fully replace lab experiences for learning techniques, they can be used to expose students to analysis of big data, introduce resources widely used in the field, and teach skills like statistics and coding. This article reviews potential assignment formats where big and open data can be applied, introduces selected popular resources and sample use cases for each, and discusses benefits and limitations of open online data for lab experiences. Some specific applications in the context of distance learning are also detailed.

A Course-Based Research Experience Using the Allen Brain Map: From Research Question to Poster Session.

San Francisco, CA A major challenge in implementing course-based undergraduate research experiences (CUREs) is for students to collect enough data for a robust analysis given the time and equipment available. One approach to mitigating this constraint in a CURE is to use massive open datasets such as those from the Allen Brain Map, produced by the Allen Institute for Brain Science. We describe a multi-week CURE module in which students generate a research question that can be addressed using at least two datasets of the Allen Brain Map, perform their analysis, and produce a conference-style poster detailing their findings. This article includes an adaptable CURE assignment, tutorials introducing students to selected datasets from the Allen Brain Map, and a summary of student outcomes.

Spontaneous Variation in Electrocorticographic Resting-State Connectivity.

Prior studies using functional magnetic resonance imaging, electroencephalography, and magnetoencephalography have observed both structured patterns in resting-state functional connectivity and spontaneous longitudinal variation in connectivity patterns independent of a task. In this first study using electrocorticography (ECoG), we characterized spontaneous, intersession variation in resting-state functional connectivity not linked to a task. We evaluated pairwise connectivity between electrodes using three measures (phase locking value [PLV], amplitude correlation, and coherence) for six canonical frequency bands, capturing different characteristics of time-evolving signals. We grouped electrodes into 10 functional regions and used intraclass correlation (ICC) to estimate pairwise longitudinal stability. We found that stronger PLV (PLV ≥0.4) in theta through gamma bands and strong correlation in all bands (R2's ≥0.6) are linked to substantial stability (ICC ≥0.6), but that stability does not imply strong phase locking or amplitude correlation. There was no notable link between strong coherence and high ICC. All within-region PLVs are markedly stable across frequencies. In addition, we highlight interaction patterns across several regions: parahippocampal/entorhinal cortex is characterized by stable, weak functional connectivity except self-connections. Dorsolateral prefrontal cortex connectivity is weak and unstable, except self-connections. Inferior parietal lobule has little stability despite narrow connectivity bounds. We confirm prior studies linking functional connectivity strength and intersession variability, extending into higher frequencies than other modalities, with greater spatial specificity than scalp electrophysiology. We suggest further studies quantitatively compare ECoG to other modalities and/or use these findings as a baseline to capture functional connectivity and dynamics linked to perturbations with a task or disease state.

Context-dependent relationship in high-resolution micro-ECoG studies during finger movements.

OBJECTIVE: The activation of the sensorimotor cortex as measured by electrocorticographic (ECoG) signals has been correlated with contralateral hand movements in humans, as precisely as the level of individual digits. However, the relationship between individual and multiple synergistic finger movements and the neural signal as detected by ECoG has not been fully explored. The authors used intraoperative high-resolution micro-ECoG (µECoG) on the sensorimotor cortex to link neural signals to finger movements across several context-specific motor tasks. METHODS: Three neurosurgical patients with cortical lesions over eloquent regions participated. During awake craniotomy, a sensorimotor cortex area of hand movement was localized by high-frequency responses measured by an 8 × 8 µECoG grid of 3-mm interelectrode spacing. Patients performed a flexion movement of the thumb or index finger, or a pinch movement of both, based on a visual cue. High-gamma (HG; 70-230 Hz) filtered µECoG was used to identify dominant electrodes associated with thumb and index movement. Hand movements were recorded by a dataglove simultaneously with µECoG recording. RESULTS: In all 3 patients, the electrodes controlling thumb and index finger movements were identifiable approximately 3-6-mm apart by the HG-filtered µECoG signal. For HG power of cortical activation measured with µECoG, the thumb and index signals in the pinch movement were similar to those observed during thumb-only and index-only movement, respectively (all p > 0.05). Index finger movements, measured by the dataglove joint angles, were similar in both the index-only and pinch movements (p > 0.05). However, despite similar activation across the conditions, markedly decreased thumb movement was observed in pinch relative to independent thumb-only movement (all p < 0.05). CONCLUSIONS: HG-filtered µECoG signals effectively identify dominant regions associated with thumb and index finger movement. For pinch, the µECoG signal comprises a combination of the signals from individual thumb and index movements. However, while the relationship between the index finger joint angle and HG-filtered signal remains consistent between conditions, there is not a fixed relationship for thumb movement. Although the HG-filtered µECoG signal is similar in both thumb-only and pinch conditions, the actual thumb movement is markedly smaller in the pinch condition than in the thumb-only condition. This implies a nonlinear relationship between the cortical signal and the motor output for some, but importantly not all, movement types. This analysis provides insight into the tuning of the motor cortex toward specific types of motor behaviors.

Changes in resting-state connectivity in pediatric temporal lobe epilepsy.

OBJECTIVE Functional connectivity magnetic resonance imaging (fcMRI) is a form of fMRI that allows for analysis of blood oxygen level-dependent signal changes within a task-free, resting paradigm. This technique has been shown to have efficacy in evaluating network connectivity changes with epilepsy. Presurgical data from patients with unilateral temporal lobe epilepsy were evaluated using the fcMRI technique to define connectivity changes within and between the diseased and healthy temporal lobes using a within-subjects design. METHODS Using presurgical fcMRI data from pediatric patients with unilateral temporal lobe epilepsy, the authors performed seed-based analyses within the diseased and healthy temporal lobes. Connectivity within and between temporal lobe seeds was measured and compared. RESULTS In the cohort studied, local ipsilateral temporal lobe connectivity was significantly increased on the diseased side compared to the healthy temporal lobe. Connectivity of the diseased side to the healthy side, on the other hand, was significantly reduced when compared to connectivity of the healthy side to the diseased temporal lobe. A statistically significant regression was observed when comparing the changes in local ipsilateral temporal lobe connectivity to the changes in inter-temporal lobe connectivity. A statistically significant difference was also noted in ipsilateral connectivity changes between patients with and those without mesial temporal sclerosis. CONCLUSIONS Using fcMRI, significant changes in ipsilateral temporal lobe and inter-temporal lobe connectivity can be appreciated in unilateral temporal lobe epilepsy. Furthermore, fcMRI may have a role in the presurgical evaluation of patients with intractable temporal lobe epilepsy.

Preservation of electrophysiological functional connectivity after partial corpus callosotomy: case report.

Prior studies of functional connectivity following callosotomy have disagreed in the observed effects on interhemispheric functional connectivity. These connectivity studies, in multiple electrophysiological methods and functional MRI, have found conflicting reductions in connectivity or patterns resembling typical individuals. The authors examined a case of partial anterior corpus callosum connection, where pairs of bilateral electrocorticographic electrodes had been placed over homologous regions in the left and right hemispheres. They sorted electrode pairs by whether their direct corpus callosum connection had been disconnected or preserved using diffusion tensor imaging and native anatomical MRI, and they estimated functional connectivity between pairs of electrodes over homologous regions using phase-locking value. They found no significant differences in any frequency band between pairs of electrodes that had their corpus callosum connection disconnected and those that had an intact connection. The authors' results may imply that the corpus callosum is not an obligatory mediator of connectivity between homologous sites in opposite hemispheres. This interhemispheric synchronization may also be linked to disruption of seizure activity.

BCI Use and Its Relation to Adaptation in Cortical Networks.

Brain-computer interfaces (BCIs) carry great potential in the treatment of motor impairments. As a new motor output, BCIs interface with the native motor system, but acquisition of BCI proficiency requires a degree of learning to integrate this new function. In this review, we discuss how BCI designs often take advantage of the brain's motor system infrastructure as sources of command signals. We highlight a growing body of literature examining how this approach leads to changes in activity across cortex, including beyond motor regions, as a result of learning the new skill of BCI control. We discuss the previous research identifying patterns of neural activity associated with BCI skill acquisition and use that closely resembles those associated with learning traditional native motor tasks. We then discuss recent work in animals probing changes in connectivity of the BCI control site, which were linked to BCI skill acquisition, and use this as a foundation for our original work in humans. We present our novel work showing changes in resting state connectivity across cortex following the BCI learning process. We find substantial, heterogeneous changes in connectivity across regions and frequencies, including interactions that do not involve the BCI control site. We conclude from our review and original work that BCI skill acquisition may potentially lead to significant changes in evoked and resting state connectivity across multiple cortical regions. We recommend that future studies of BCIs look beyond motor regions to fully describe the cortical networks involved and long-term adaptations resulting from BCI skill acquisition.

An interspecies comparative study of invasive electrophysiological functional connectivity.

Introduction: Resting-state connectivity patterns have been observed in humans and other mammal species, and can be recorded using a variety of different technologies. Functional connectivity has been previously compared between species using resting-state fMRI, but not in electrophysiological studies. Methods: We compared connectivity with implanted electrodes in humans (electrocorticography) to macaques and sheep (microelectrocorticography), which are capable of recording neural data at high frequencies with spatial precision. We specifically examined synchrony, implicated in functional integration between regions. Results: We found that connectivity strength was overwhelmingly similar in humans and monkeys for pairs of two different brain regions (prefrontal, motor, premotor, parietal), but differed more often within single brain regions. The two connectivity measures, correlation and phase locking value, were similar in most comparisons. Connectivity strength agreed more often between the species at higher frequencies. Where the species differed, monkey synchrony was stronger than human in all but one case. In contrast, human and sheep connectivity within somatosensory cortex diverged in almost all frequencies, with human connectivity stronger than sheep. Discussion: Our findings imply greater heterogeneity within regions in humans than in monkeys, but comparable functional interactions between regions in the two species. This suggests that monkeys may be effectively used to probe resting-state connectivity in humans, and that such findings can then be validated in humans. Although the discrepancy between humans and sheep is larger, we suggest that findings from sheep in highly invasive studies may be used to provide guidance for studies in other species.

Regional Patterns of Cortical Phase Synchrony in the Resting State.

Synchronized phase estimates between oscillating neuronal signals at the macroscale level reflect coordinated activities between neuronal assemblies. Recent electrophysiological evidence suggests the presence of significant spontaneous phase synchrony within the resting state. The purpose of this study was to investigate phase synchrony, including directional interactions, in resting state subdural electrocorticographic recordings to better characterize patterns of regional phase interactions across the lateral cortical surface during the resting state. We estimated spontaneous phase locking value (PLV) as a measure of functional connectivity, and phase slope index (PSI) as a measure of pseudo-causal phase interactions, across a broad range of canonical frequency bands and the modulation of the amplitude envelope of high gamma (amHG), a band that is believed to best reflect the physiological processes giving rise to the functional magnetic resonance imaging BOLD signal. Long-distance interactions had higher PLVs in slower frequencies (≤theta) than in higher ones (≥beta) with amHG behaving more like slow frequencies, and a general trend of increasing frequency band of significant PLVs when moving across the lateral surface along an anterior-posterior axis. Moreover, there was a strong trend of frontal-to-parietal directional phase synchronization, measured by PSI across multiple frequencies. These findings, which are likely indicative of coordinated and structured spontaneous cortical interactions, are important in the study of time scales and directional nature of resting state functional connectivity, and may ultimately contribute to a better understanding of how spontaneous synchrony is linked to variation in regional architecture across the lateral cortical surface.

Directional patterns of cross frequency phase and amplitude coupling within the resting state mimic patterns of fMRI functional connectivity.

Functional imaging investigations into the brain's resting state interactions have yielded a wealth of insight into the intrinsic and dynamic neural architecture supporting cognition and behavior. Electrophysiological studies however have highlighted the fact that synchrony across large-scale cortical systems is composed of spontaneous interactions occurring at timescales beyond the traditional resolution of fMRI, a feature that limits the capacity of fMRI to draw inference on the true directional relationship between network nodes. To approach the question of directionality in resting state signals, we recorded resting state functional MRI (rsfMRI) and electrocorticography (ECoG) from four human subjects undergoing invasive epilepsy monitoring. Using a seed-point based approach, we employed phase-amplitude coupling (PAC) and biPhase Locking Values (bPLV), two measures of cross-frequency coupling (CFC) to explore both outgoing and incoming connections between the seed and all non-seed, site electrodes. We observed robust PAC between a wide range of low-frequency phase and high frequency amplitude estimates. However, significant bPLV, a CFC measure of phase-phase synchrony, was only observed at specific narrow low and high frequency bandwidths. Furthermore, the spatial patterns of outgoing PAC connectivity were most closely associated with the rsfMRI connectivity maps. Our results support the hypothesis that PAC is relatively ubiquitous phenomenon serving as a mechanism for coordinating high-frequency amplitudes across distant neuronal assemblies even in absence of overt task structure. Additionally, we demonstrate that the spatial distribution of a seed-point rsfMRI sensorimotor network is strikingly similar to specific patterns of directional PAC. Specifically, the high frequency activities of distal patches of cortex owning membership in a rsfMRI sensorimotor network were most likely to be entrained to the phase of a low frequency rhythm engendered from the neural populations at the seed-point, suggestive of greater directional coupling from the seed out to the site electrodes.

Resting state functional connectivity of the nucleus accumbens in youth with a family history of alcoholism.

Adolescents with a family history of alcoholism (FHP) are at heightened risk for developing alcohol use disorders (AUDs). The nucleus accumbens (NAcc), a key brain region for reward processing, is implicated in the development of AUDs. Thus, functional connectivity of the NAcc may be an important marker of risk in FHP youth. Resting state functional magnetic resonance imaging (rs-fcMRI) was used to examine the intrinsic connectivity of the NAcc in 47 FHP and 50 family history negative (FHN) youth, ages 10-16 years old. FHP and FHN adolescents showed significant group differences in resting state synchrony between the left NAcc and bilateral inferior frontal gyri and the left postcentral gyrus (PG). Additionally, FHP youth differed from FHN youth in right NAcc functional connectivity with the left orbitofrontal cortex (OFC), left superior temporal gyrus, right cerebellum, left PG, and right occipital cortex. These results indicate that FHP youth have less segregation between the NAcc and executive functioning brain regions, and less integration with reward-related brain areas, such as the OFC. The findings of the current study highlight that premorbid atypical connectivity of appetitive systems, in the absence of heavy alcohol use, may be a risk marker in FHP adolescents.