Phase synchrony between prefrontal noradrenergic and cholinergic signals indexes inhibitory control.

Inhibitory control is a critical executive function that allows animals to suppress their impulsive behavior in order to achieve certain goals or avoid punishment. We investigated norepinephrine (NE) and acetylcholine (ACh) dynamics and population neuronal activity in the prefrontal cortex during inhibitory control. Using fluorescent sensors to measure extracellular levels of NE and ACh, we simultaneously recorded the dynamics of prefrontal NE and ACh in mice performing an inhibitory control task. The prefrontal NE and ACh signals exhibited strong coherence at 0.4-0.8 Hz. Chemogenetic inhibition of locus coeruleus (LC) neurons that project to the basal forebrain region reduced inhibitory control performance to chance levels. However, this manipulation did not diminish the difference in NE/ACh signals between successful and failed trials; instead, it abolished the difference in NE-ACh phase synchrony between the successful and failed trials, indicating that NE-ACh phase synchrony is a task-relevant neuromodulatory feature. Chemogenetic inhibition of cholinergic neurons that project to the LC region did not impair the inhibitory control performance, nor did it abolish the difference in NE-ACh phase synchrony between successful or failed trials, further confirming the relevance of NE-ACh phase synchrony to inhibitory control. To understand the possible effect of NE-ACh synchrony on prefrontal population activity, we employed Neuropixels to record from the prefrontal cortex with and without inhibiting LC neurons that project to the basal forebrain during inhibitory control. The LC inhibition reduced the number of prefrontal neurons encoding inhibitory control. Demixed principal component analysis (dPCA) further revealed that population firing patterns representing inhibitory control were impaired by the LC inhibition. Disparities in NE-ACh phase synchrony relevant to inhibitory control occurred only in the prefrontal cortex, but not in the parietal cortex, somatosensory cortex, and the somatosensory thalamus. Taken together, these findings suggest that the LC modulates inhibitory control through its collective effect with cholinergic systems on population activity in the prefrontal cortex. Our results further revealed that NE-ACh phase synchrony is a critical neuromodulatory feature with important implications for cognitive control.

Circular Clustering With Polar Coordinate Reconstruction.

There is a growing interest in characterizing circular data found in biological systems. Such data are wide-ranging and varied, from the signal phase in neural recordings to nucleotide sequences in round genomes. Traditional clustering algorithms are often inadequate due to their limited ability to distinguish differences in the periodic component θ. Current clustering schemes for polar coordinate systems have limitations, such as being only angle-focused or lacking generality. To overcome these limitations, we propose a new analysis framework that utilizes projections onto a cylindrical coordinate system to represent objects in a polar coordinate system optimally. Using the mathematical properties of circular data, we show that our approach always finds the correct clustering result within the reconstructed dataset, given sufficient periodic repetitions of the data. This framework is generally applicable and adaptable to most state-of-the-art clustering algorithms. We demonstrate on synthetic and real data that our method generates more appropriate and consistent clustering results than standard methods. In summary, our proposed analysis framework overcomes the limitations of existing polar coordinate-based clustering methods and provides an accurate and efficient way to cluster circular data. We provide the code as open-source on GitHub.

Neurophysiological Predictors of Self-Reported Difficulty in a Virtual-Reality Driving Scenario.

Our perception of subjective difficulty in complex tasks, such as driving, is a judgment that is likely a result of dynamic interactions between distributed brain regions. In this paper, we investigate how neurophysiological markers associated with arousal state are informative of this perceived difficulty throughout a driving task. We do this by classifying subjective difficulty reports of subjects using set of features that include neural, autonomic, and eye behavioral markers. We subsequently assess the importance of these features in the classification. We find that though multiple EEG linked to cognitive control and, motor performance linked to classification of subjective difficulty, only pupil diameter, a measure of pupil-linked arousal, is strongly linked to both measured self-reported difficulty and actual task performance. We interpret our findings in the context of arousal pathways influencing performance and discuss their relevance to future brain-computer interface systems.

EEG synchronized left prefrontal transcranial magnetic stimulation (TMS) for treatment resistant depression is feasible and produces an entrainment dependent clinical response: A randomized controlled double blind clinical trial.

BACKGROUND: Synchronizing a TMS pulse with a person's underlying EEG rhythm can modify the brain's response. It is unclear if synchronizing rTMS trains might boost the antidepressant effect of TMS. In this first-in-human trial, we demonstrated that a single TMS pulse over the prefrontal cortex produces larger effects in the anterior cingulate depending on when it is fired relative to the individual's EEG alpha phase. OBJECTIVE/HYPOTHESES: We had three hypotheses. 1) It is feasible to synchronize repetitive TMS (rTMS) delivery to a person's preferred prefrontal alpha phase in each train of every session during a 30-visit TMS depression treatment course. 2) EEG-synchronized rTMS would produce progressive entrainment greater than unsynchronized (UNSYNC) rTMS. And 3) SYNC TMS would have better antidepressant effects than UNSYNC (remission, final Hamilton Depression Rating <10). METHODS: We enrolled (n = 34) and treated (n = 28) adults with treatment resistant depression (TRD) and randomized them to receive six weeks (30 treatments) of left prefrontal rTMS at their individual alpha frequency (IAF) (range 6-13 Hz). Prior to starting the clinical trial, all patients had an interleaved fMRI-EEG-TMS (fET) scan to determine which phase of their alpha rhythm would produce the largest BOLD response in their dorsal anterior cingulate. Our clinical EEG-rTMS system then delivered the first TMS pulse in each train time-locked to this patient-specific 'preferred phase' of each patient's left prefrontal alpha oscillation. We randomized patients (1:1) to SYNC or UNSYNC, and all were treated at their IAF. Only the SYNC patients had the first pulse of each train for all sessions synchronized to their individualized preferred alpha phase (75 trains/session ×30 sessions, 2250 synchronizations per patient over six weeks). The UNSYNC group used a random firing with respect to the alpha wave. All other TMS parameters were balanced between the two groups. The system interfaced with a MagStim Horizon air-cooled Fig. 8 TMS coil. All patients were treated at their IAF, coil in the F3 position, 120 % MT, frequency 6-13 Hz, 40 pulses per train, average 15-s inter-train interval, 3000 pulses per session. All patients, raters, and treaters were blinded. RESULTS: In the intent to treat (ITT) sample, both groups had significant clinical improvement from baseline with no significant between-group differences, with the USYNC group having mathematically more remitters but fewer responders. (ITT -15 SYNC; 13 UNSYNC, response 5 (33 %), 1 (7 %), remission 2 (13 %), 6 (46 %). The same was true with the completer sample - 12 SYNC; 12 UNSYNC, response 4, 4 (both 30 %), remission 2 (17 %), 3 (25 %)). The clinical EEG phase synchronization system performed well with no failures. The average treatment session was approximately 90 min, with 30 min for placing the EEG cap and the actual TMS treatment for 45 min (which included gathering 10 min of resting EEG). Four subjects (1 SYNC) withdrew before six weeks of treatment. All 24 completer patients were treated for six weeks despite the trial occurring during the COVID pandemic. SYNC patients exhibited increased post-stimulation EEG entrainment over the six weeks. A detailed secondary analysis of entrainment data in the SYNC group showed that responders and non-responders in this group could be cleanly separated based on the total number of sessions with entrainment and the session-to-session precision of the entrained phase. For the SYNC group only, depression improvement was greater when more sessions were entrained at similar phases. CONCLUSIONS: Synchronizing prefrontal TMS with a patient's prefrontal alpha frequency in a blinded clinical trial is possible and produces progressive EEG entrainment in synchronized patients only. There was no difference in overall clinical response in this small clinical trial. A secondary analysis showed that the consistency of the entrained phase across sessions was significantly associated with response outcome only in the SYNC group. These effects may not simply be due to how the stimulation is delivered but also whether the patient's brain can reliably entrain to a precise phase. EEG-synchronized clinical delivery of TMS is feasible and requires further study to determine the best method for determining the phase for synchronization.

Biomarkers predict the efficacy of closed-loop rTMS treatment for refractory depression.

Transcranial magnetic stimulation (TMS) is a non-invasive FDA-approved therapy for major depressive disorder (MDD), specifically for treatment-resistant depression (TRD). Though offering promise for those with TRD, its effectiveness is less than one in two patients (i.e., less than 50%). Limits on efficacy may be due to individual patient variability, but to date, there are no established biomarkers or measures of target engagement that can predict efficacy. Additionally, TMS efficacy is typically not assessed until a six-week treatment ends, precluding interim re-evaluations of the treatment. Here, we report results using a closed-loop phase-locked repetitive TMS (rTMS) treatment that synchronizes the delivery of rTMS based on the timing of the pulses relative to a patient's individual electroencephalographic (EEG) prefrontal alpha oscillation indexed by functional magnetic resonance imaging (fMRI). Among responders, synchronized rTMS produces two systematic changes in brain dynamics: a reduction in global cortical excitability and enhanced phase entrainment of cortical dynamics. These effects predict clinical outcomes in the synchronized treatment group but not in an active-treatment unsynchronized control group. The systematic decrease in excitability and increase in entrainment correlated with treatment efficacy at the endpoint and intermediate weeks during the synchronized treatment. Specifically, we show that weekly biomarker tracking enables efficacy prediction and dynamic adjustments through a treatment course, improving the overall response rates. This innovative approach advances the prospects of individualized medicine in MDD and holds potential for application in other neuropsychiatric disorders.

Pupil-linked arousal correlates with neural activity prior to sensorimotor decisions.

Objective.Sensorimotor decisions require the brain to process external information and combine it with relevant knowledge prior to actions. In this study, we explore the neural predictors of motor actions in a novel, realistic driving task designed to study decisions while driving.Approach.Through a spatiospectral assessment of functional connectivity during the premotor period, we identified the organization of visual cortex regions of interest into a distinct scene processing network. Additionally, we identified a motor action selection network characterized by coherence between the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC).Main results.We show that steering behavior can be predicted from oscillatory power in the visual cortex, DLPFC, and ACC. Power during the premotor periods (specific to the theta and beta bands) correlates with pupil-linked arousal and saccade duration.Significance.We interpret our findings in the context of network-level correlations with saccade-related behavior and show that the DLPFC is a key node in arousal circuitry and in sensorimotor decisions.

Increased entrainment and decreased excitability predict efficacious treatment of closed-loop phase-locked rTMS for treatment-resistant depression.

Transcranial magnetic stimulation (TMS) is an FDA-approved therapy for major depressive disorder (MDD), specifically for patients who have treatment-resistant depression (TRD). However, TMS produces response or remission in about 50% of patients but is ineffective for the other 50%. Limits on efficacy may be due to individual patient variability, but to date, there are no good biomarkers or measures of target engagement. In addition, TMS efficacy is typically not assessed until a six-week treatment ends, precluding the evaluation of intermediate improvements during the treatment duration. Here, we report on results using a closed-loop phase-locked repetitive TMS (rTMS) treatment that synchronizes the delivery of rTMS based on the timing of the pulses relative to a patient's individual electroencephalographic (EEG) prefrontal alpha oscillation informed by functional magnetic resonance imaging (fMRI). We find that, in responders, synchronized delivery of rTMS produces two systematic changes in brain dynamics. The first change is a decrease in global cortical excitability, and the second is an increase in the phase entrainment of cortical dynamics. These two effects predict clinical outcomes in the synchronized treatment group but not in an active-treatment unsynchronized control group. The systematic decrease in excitability and increase in entrainment correlated with treatment efficacy at the endpoint and intermediate weeks during the synchronized treatment. Specifically, we show that weekly tracking of these biomarkers allows for efficacy prediction and potential of dynamic adjustments through a treatment course, improving the overall response rates.

Pupil-linked arousal modulates network-level EEG signatures of attention reorienting during immersive multitasking.

Objective. When multitasking, we must dynamically reorient our attention between different tasks. Attention reorienting is thought to arise through interactions of physiological arousal and brain-wide network dynamics. In this study, we investigated the relationship between pupil-linked arousal and electroencephalography (EEG) brain dynamics in a multitask driving paradigm conducted in virtual reality. We hypothesized that there would be an interaction between arousal and EEG dynamics and that this interaction would correlate with multitasking performance.Approach. We collected EEG and eye tracking data while subjects drove a motorcycle through a simulated city environment, with the instructions to count the number of target images they observed while avoiding crashing into a lead vehicle. The paradigm required the subjects to continuously reorient their attention between the two tasks. Subjects performed the paradigm under two conditions, one more difficult than the other.Main results. We found that task difficulty did not strongly correlate with pupil-linked arousal, and overall task performance increased as arousal level increased. A single-trial analysis revealed several interesting relationships between pupil-linked arousal and task-relevant EEG dynamics. Employing exact low-resolution electromagnetic tomography, we found that higher pupil-linked arousal led to greater EEG oscillatory activity, especially in regions associated with the dorsal attention network and ventral attention network (VAN). Consistent with our hypothesis, we found a relationship between EEG functional connectivity and pupil-linked arousal as a function of multitasking performance. Specifically, we found decreased functional connectivity between regions in the salience network (SN) and the VAN as pupil-linked arousal increased, suggesting that improved multitasking performance at high arousal levels may be due to a down-regulation in coupling between the VAN and the SN. Our results suggest that when multitasking, our brain rebalances arousal-based reorienting so that individual task demands can be met without prematurely reorienting to competing tasks.

The timing of transcranial magnetic stimulation relative to the phase of prefrontal alpha EEG modulates downstream target engagement.

BACKGROUND: The communication through coherence model posits that brain rhythms are synchronized across different frequency bands and that effective connectivity strength between interacting regions depends on their phase relation. Evidence to support the model comes mostly from electrophysiological recordings in animals while evidence from human data is limited. METHODS: Here, an fMRI-EEG-TMS (fET) instrument capable of acquiring simultaneous fMRI and EEG during noninvasive single pulse TMS applied to dorsolateral prefrontal cortex (DLPFC) was used to test whether prefrontal EEG alpha phase moderates TMS-evoked top-down influences on subgenual, rostral and dorsal anterior cingulate cortex (ACC). Six runs (276 total trials) were acquired in each participant. Phase at each TMS pulse was determined post-hoc using single-trial sorting. Results were examined in two independent datasets: healthy volunteers (HV) (n = 11) and patients with major depressive disorder (MDD) (n = 17) collected as part of an ongoing clinical trial. RESULTS: In both groups, TMS-evoked functional connectivity between DLPFC and subgenual ACC (sgACC) depended on the EEG alpha phase. TMS-evoked DLPFC to sgACC fMRI-derived effective connectivity (EC) was modulated by EEG alpha phase in healthy volunteers, but not in the MDD patients. Top-down EC was inhibitory for TMS pulses during the upward slope of the alpha wave relative to TMS timed to the downward slope of the alpha wave. Prefrontal EEG alpha phase dependent effects on TMS-evoked fMRI BOLD activation of the rostral anterior cingulate cortex were detected in the MDD patient group, but not in the healthy volunteer group. DISCUSSION: Results demonstrate that TMS-evoked top-down influences vary as a function of the prefrontal alpha rhythm, and suggest potential clinical applications whereby TMS is synchronized to the brain's internal rhythms in order to more efficiently engage deep therapeutic targets.

Pupillary response is associated with the reset and switching of functional brain networks during salience processing.

The interface between processing internal goals and salient events in the environment involves various top-down processes. Previous studies have identified multiple brain areas for salience processing, including the salience network (SN), dorsal attention network, and the locus coeruleus-norepinephrine (LC-NE) system. However, interactions among these systems in salience processing remain unclear. Here, we simultaneously recorded pupillometry, EEG, and fMRI during an auditory oddball paradigm. The analyses of EEG and fMRI data uncovered spatiotemporally organized target-associated neural correlates. By modeling the target-modulated effective connectivity, we found that the target-evoked pupillary response is associated with the network directional couplings from late to early subsystems in the trial, as well as the network switching initiated by the SN. These findings indicate that the SN might cooperate with the pupil-indexed LC-NE system in the reset and switching of cortical networks, and shed light on their implications in various cognitive processes and neurological diseases.

Neurophysiological markers of emotion regulation predict efficacy of entrepreneurship education.

Recent evidence shows that programs targeting the socio-emotional dimensions of entrepreneurship-e.g., resilience, personal initiative, and empathy-are more highly correlated with success along with key business metrics, such as sales and survival, than programs with a narrow, technical bent-e.g., accounting and finance. We argue that programs designed to foster socio-emotional skills are effective in improving entrepreneurship outcomes because they improve the students' ability to regulate their emotions. They enhance the individuals' disposition to make more measured, rational decisions. We test this hypothesis studying a randomized controlled trial (RCT, RCT ID: AEARCTR-0000916) of an entrepreneurship program in Chile. We combine administrative data, surveys, and neuro-psychological data from lab-in-the-field measurements. A key methodological contribution of this study is the use of the electroencephalogram (EEG) to quantify the impact of emotional responses. We find that the program has a positive and significant impact on educational outcomes and, in line with the findings of other studies in the literature, we find no impact on self-reported measures of socio-emotional skills (e.g., grit and locus of control) and creativity. Our novel insight comes from the finding that the program has a significant impact on neurophysiological markers, decreasing arousal (a proxy of alertness), valence (a proxy for withdrawal from or approachability to an event or stimuli), and neuro-psychological changes to negative stimuli.

Deep Metric Representation Learning for Clinical Resting State fMRI.

With growing size of resting state fMRI datasets and advances in deep learning methods, there are ever increasing opportunities to leverage progress in deep learning to solve challenging tasks in neuroimaging. In this work, we build upon recent advances in deep metric learning, to learn embeddings of rs-fMRI data, which can then be potentially used for several downstream tasks. We propose an efficient training method for our model and compare our method with other widely used models. Our experimental results indicate that deep metric learning can be used as an additional refinement step to learn representations of fMRI data, that significantly improves performance on downstream modeling tasks.

Multimodal Neurophysiological Transformer for Emotion Recognition.

Understanding neural function often requires multiple modalities of data, including electrophysiogical data, imaging techniques, and demographic surveys. In this paper, we introduce a novel neurophysiological model to tackle major challenges in modeling multimodal data. First, we avoid non-alignment issues between raw signals and extracted, frequency-domain features by addressing the issue of variable sampling rates. Second, we encode modalities through "cross-attention" with other modalities. Lastly, we utilize properties of our parent transformer architecture to model long-range dependencies between segments across modalities and assess intermediary weights to better understand how source signals affect prediction. We apply our Multimodal Neurophysiological Transformer (MNT) to predict valence and arousal in an existing open-source dataset. Experiments on non-aligned multimodal time-series show that our model performs similarly and, in some cases, outperforms existing methods in classification tasks. In addition, qualitative analysis suggests that MNT is able to model neural influences on autonomic activity in predicting arousal. Our architecture has the potential to be fine-tuned to a variety of downstream tasks, including for BCI systems.

Daily prefrontal closed-loop repetitive transcranial magnetic stimulation (rTMS) produces progressive EEG quasi-alpha phase entrainment in depressed adults.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation modality that can treat depression, obsessive-compulsive disorder, or help smoking cessation. Research suggests that timing the delivery of TMS relative to an endogenous brain state may affect efficacy and short-term brain dynamics. OBJECTIVE: To investigate whether, for a multi-week daily treatment of repetitive TMS (rTMS), there is an effect on brain dynamics that depends on the timing of the TMS relative to individuals' prefrontal EEG quasi-alpha rhythm (between 6 and 13 Hz). METHOD: We developed a novel closed-loop system that delivers personalized EEG-triggered rTMS to patients undergoing treatment for major depressive disorder. In a double blind study, patients received daily treatments of rTMS over a period of six weeks and were randomly assigned to either a synchronized or unsynchronized treatment group, where synchronization of rTMS was to their prefrontal EEG quasi-alpha rhythm. RESULTS: When rTMS is applied over the dorsal lateral prefrontal cortex (DLPFC) and synchronized to the patient's prefrontal quasi-alpha rhythm, patients develop strong phase entrainment over a period of weeks, both over the stimulation site as well as in a subset of areas distal to the stimulation site. In addition, at the end of the course of treatment, this group's entrainment phase shifts to be closer to the phase that optimally engages the distal target, namely the anterior cingulate cortex (ACC). These entrainment effects are not observed in the group that is given rTMS without initial EEG synchronization of each TMS train. CONCLUSIONS: The entrainment effects build over the course of days/weeks, suggesting that these effects engage neuroplastic changes which may have clinical consequences in depression or other diseases.

A multimodal deep learning system to distinguish late stages of AMD and to compare expert vs. AI ocular biomarkers.

Within the next 1.5 decades, 1 in 7 U.S. adults is anticipated to suffer from age-related macular degeneration (AMD), a degenerative retinal disease which leads to blindness if untreated. Optical coherence tomography angiography (OCTA) has become a prime technique for AMD diagnosis, specifically for late-stage neovascular (NV) AMD. Such technologies generate massive amounts of data, challenging to parse by experts alone, transforming artificial intelligence into a valuable partner. We describe a deep learning (DL) approach which achieves multi-class detection of non-AMD vs. non-neovascular (NNV) AMD vs. NV AMD from a combination of OCTA, OCT structure, 2D b-scan flow images, and high definition (HD) 5-line b-scan cubes; DL also detects ocular biomarkers indicative of AMD risk. Multimodal data were used as input to 2D-3D Convolutional Neural Networks (CNNs). Both for CNNs and experts, choroidal neovascularization and geographic atrophy were found to be important biomarkers for AMD. CNNs predict biomarkers with accuracy up to 90.2% (positive-predictive-value up to 75.8%). Just as experts rely on multimodal data to diagnose AMD, CNNs also performed best when trained on multiple inputs combined. Detection of AMD and its biomarkers from OCTA data via CNNs has tremendous potential to expedite screening of early and late-stage AMD patients.

Neural Encoding of Active Multi-Sensing Enhances Perceptual Decision-Making via a Synergistic Cross-Modal Interaction.

Most perceptual decisions rely on the active acquisition of evidence from the environment involving stimulation from multiple senses. However, our understanding of the neural mechanisms underlying this process is limited. Crucially, it remains elusive how different sensory representations interact in the formation of perceptual decisions. To answer these questions, we used an active sensing paradigm coupled with neuroimaging, multivariate analysis, and computational modeling to probe how the human brain processes multisensory information to make perceptual judgments. Participants of both sexes actively sensed to discriminate two texture stimuli using visual (V) or haptic (H) information or the two sensory cues together (VH). Crucially, information acquisition was under the participants' control, who could choose where to sample information from and for how long on each trial. To understand the neural underpinnings of this process, we first characterized where and when active sensory experience (movement patterns) is encoded in human brain activity (EEG) in the three sensory conditions. Then, to offer a neurocomputational account of active multisensory decision formation, we used these neural representations of active sensing to inform a drift diffusion model of decision-making behavior. This revealed a multisensory enhancement of the neural representation of active sensing, which led to faster and more accurate multisensory decisions. We then dissected the interactions between the V, H, and VH representations using a novel information-theoretic methodology. Ultimately, we identified a synergistic neural interaction between the two unisensory (V, H) representations over contralateral somatosensory and motor locations that predicted multisensory (VH) decision-making performance.SIGNIFICANCE STATEMENT In real-world settings, perceptual decisions are made during active behaviors, such as crossing the road on a rainy night, and include information from different senses (e.g., car lights, slippery ground). Critically, it remains largely unknown how sensory evidence is combined and translated into perceptual decisions in such active scenarios. Here we address this knowledge gap. First, we show that the simultaneous exploration of information across senses (multi-sensing) enhances the neural encoding of active sensing movements. Second, the neural representation of active sensing modulates the evidence available for decision; and importantly, multi-sensing yields faster evidence accumulation. Finally, we identify a cross-modal interaction in the human brain that correlates with multisensory performance, constituting a putative neural mechanism for forging active multisensory perception.

Integrating neural and ocular attention reorienting signals in virtual reality.

Objective.Reorienting is central to how humans direct attention to different stimuli in their environment. Previous studies typically employ well-controlled paradigms with limited eye and head movements to study the neural and physiological processes underlying attention reorienting. Here, we aim to better understand the relationship between gaze and attention reorienting using a naturalistic virtual reality (VR)-based target detection paradigm.Approach.Subjects were navigated through a city and instructed to count the number of targets that appeared on the street. Subjects performed the task in a fixed condition with no head movement and in a free condition where head movements were allowed. Electroencephalography (EEG), gaze and pupil data were collected. To investigate how neural and physiological reorienting signals are distributed across different gaze events, we used hierarchical discriminant component analysis (HDCA) to identify EEG and pupil-based discriminating components. Mixed-effects general linear models (GLM) were used to determine the correlation between these discriminating components and the different gaze events time. HDCA was also used to combine EEG, pupil and dwell time signals to classify reorienting events.Main results.In both EEG and pupil, dwell time contributes most significantly to the reorienting signals. However, when dwell times were orthogonalized against other gaze events, the distributions of the reorienting signals were different across the two modalities, with EEG reorienting signals leading that of the pupil reorienting signals. We also found that the hybrid classifier that integrates EEG, pupil and dwell time features detects the reorienting signals in both the fixed (AUC = 0.79) and the free (AUC = 0.77) condition.Significance.We show that the neural and ocular reorienting signals are distributed differently across gaze events when a subject is immersed in VR, but nevertheless can be captured and integrated to classify target vs. distractor objects to which the human subject orients.

Spatiospectral brain networks reflective of improvisational experience.

Musical improvisers are trained to categorize certain musical structures into functional classes, which is thought to facilitate improvisation. Using a novel auditory oddball paradigm (Goldman et al., 2020) which enables us to disassociate a deviant (i.e. musical chord inversion) from a consistent functional class, we recorded scalp EEG from a group of musicians who spanned a range of improvisational and classically trained experience. Using a spatiospectral based inter and intra network connectivity analysis, we found that improvisers showed a variety of differences in connectivity within and between large-scale cortical networks compared to classically trained musicians, as a function of deviant type. Inter-network connectivity in the alpha band, for a time window leading up to the behavioural response, was strongly linked to improvisation experience, with the default mode network acting as a hub. Spatiospectral networks post response were substantially different between improvisers and classically trained musicians, with greater inter-network connectivity (specific to the alpha and beta bands) seen in improvisers whereas those with more classical training had largely reduced inter-network activity (mostly in the gamma band). More generally, we interpret our findings in the context of network-level correlates of expectation violation as a function of subject expertise, and we discuss how these may generalize to other and more ecologically valid scenarios.

Scale-specific dynamics of high-amplitude bursts in EEG capture behaviorally meaningful variability.

Cascading high-amplitude bursts in neural activity, termed avalanches, are thought to provide insight into the complex spatially distributed interactions in neural systems. In human neuroimaging, for example, avalanches occurring during resting-state show scale-invariant dynamics, supporting the hypothesis that the brain operates near a critical point that enables long range spatial communication. In fact, it has been suggested that such scale-invariant dynamics, characterized by a power-law distribution in these avalanches, are universal in neural systems and emerge through a common mechanism. While the analysis of avalanches and subsequent criticality is increasingly seen as a framework for using complex systems theory to understand brain function, it is unclear how the framework would account for the omnipresent cognitive variability, whether across individuals or tasks. To address this, we analyzed avalanches in the EEG activity of healthy humans during rest as well as two distinct task conditions that varied in cognitive demands and produced behavioral measures unique to each individual. In both rest and task conditions we observed that avalanche dynamics demonstrate scale-invariant characteristics, but differ in their specific features, demonstrating individual variability. Using a new metric we call normalized engagement, which estimates the likelihood for a brain region to produce high-amplitude bursts, we also investigated regional features of avalanche dynamics. Normalized engagement showed not only the expected individual and task dependent variability, but also scale-specificity that correlated with individual behavior. Our results suggest that the study of avalanches in human brain activity provides a tool to assess cognitive variability. Our findings expand our understanding of avalanche features and are supportive of the emerging theoretical idea that the dynamics of an active human brain operate close to a critical-like region and not a singular critical-state.

Strategies to Improve Convolutional Neural Network Generalizability and Reference Standards for Glaucoma Detection From OCT Scans.

Purpose: To develop and evaluate methods to improve the generalizability of convolutional neural networks (CNNs) trained to detect glaucoma from optical coherence tomography retinal nerve fiber layer probability maps, as well as optical coherence tomography circumpapillary disc (circle) b-scans, and to explore impact of reference standard (RS) on CNN accuracy. Methods: CNNs previously optimized for glaucoma detection from retinal nerve fiber layer probability maps, and newly developed CNNs adapted for glaucoma detection from optical coherence tomography b-scans, were evaluated on an unseen dataset (i.e., data collected at a different site). Multiple techniques were used to enhance CNN generalizability, including augmenting the training dataset, using multimodal input, and training with confidently rated images. Model performance was evaluated with different RS. Results: Training with data augmentation and training on confident images enhanced the accuracy of the CNNs for glaucoma detection on a new dataset by 5% to 9%. CNN performance was optimal when a similar RS was used to establish labels both for the training and the testing sets. However, interestingly, the CNNs described here were robust to variation in the RS. Conclusions: CNN generalizability can be improved with data augmentation, multiple input image modalities, and training on images with confident ratings. CNNs trained and tested with the same RS achieved best accuracy, suggesting that choosing a thorough and consistent RS for training and testing improves generalization to new datasets. Translational Relevance: Strategies for enhancing CNN generalizability and for choosing optimal RS should be standard practice for CNNs before their deployment for glaucoma detection.