Diffusion tensor brain imaging at 0.55T: A feasibility study.

PURPOSE: To investigate the feasibility of diffusion tensor brain imaging at 0.55T with comparisons against 3T. METHODS: Diffusion tensor imaging data with 2 mm isotropic resolution was acquired on a cohort of five healthy subjects using both 0.55T and 3T scanners. The signal-to-noise ratio (SNR) of the 0.55T data was improved using a previous SNR-enhancing joint reconstruction method that jointly reconstructs the entire set of diffusion weighted images from k-space using shared-edge constraints. Quantitative diffusion tensor parameters were estimated and compared across field strengths. We also performed a test-retest assessment of repeatability at each field strength. RESULTS: After applying SNR-enhancing joint reconstruction, the diffusion tensor parameters obtained from 0.55T data were strongly correlated ( R 2 ≥ 0 . 70 $$ {R}^2\ge 0.70 $$ ) with those obtained from 3T data. Test-retest analysis showed that SNR-enhancing reconstruction improved the repeatability of the 0.55T diffusion tensor parameters. CONCLUSION: High-resolution in vivo diffusion MRI of the human brain is feasible at 0.55T when appropriate noise-mitigation strategies are applied.

Is High-Frequency Activity at Seizure Onset Inhibitory? A Stereoelectroencephalographic Study of Motor Cortex Seizures.

OBJECTIVE: In the era of stereoelectroencephalography (SEEG), many studies have been devoted to understanding the role of interictal high-frequency oscillations. High-frequency activity (HFA) at seizure onset has been identified as a marker of epileptogenic zone. We address the physiological significance of ictal HFAs and their relation to clinical semiology. METHODS: We retrospectively identified patients with pure focal primary motor epilepsy. We selected only patients in whom SEEG electrodes were optimally placed in the motor cortex as confirmed by electrical stimulation. Based on these narrow inclusion criteria, we extensively studied 5 patients (3 males and 2 females, mean age = 22.4 years) using time-frequency analysis and time correlation with motor signs onset. RESULTS: A total of 157 analyzable seizures were recorded in 5 subjects. The first 2 subjects had tonic or clonic semiology with rare secondary generalization. Subject 3 had atonic onset followed by clonic hand/arm flexion. Subject 4 had clusters of tonic and atonic facial movements. Subject 5 had upper extremity tonic movements. The median frequency of the fast activity extracted from the Epileptogenic Zone Fingerprint pipeline in the first 4 subjects was 76 Hz (interquartile range = 21.9Hz). Positive motor signs did not occur concomitantly with high gamma activity developing in the motor cortex. Motor signs began at the end of HFAs. INTERPRETATION: This study supports the hypothesis of an inhibitory effect of ictal HFAs. The frequency range in the gamma band was associated with the direction of the clinical output effect. Changes from inhibitory to excitatory effect occurred when discharge frequency dropped to low gamma or beta. ANN NEUROL 2024.

Effective connectivity relates seizure outcome to electrode placement in responsive neurostimulation.

Responsive neurostimulation is a closed-loop neuromodulation therapy for drug resistant focal epilepsy. Responsive neurostimulation electrodes are placed near ictal onset zones so as to enable detection of epileptiform activity and deliver electrical stimulation. There is no standard approach for determining the optimal placement of responsive neurostimulation electrodes. Clinicians make this determination based on presurgical tests, such as MRI, EEG, magnetoencephalography, ictal single-photon emission computed tomography and intracranial EEG. Currently functional connectivity measures are not being used in determining the placement of responsive neurostimulation electrodes. Cortico-cortical evoked potentials are a measure of effective functional connectivity. Cortico-cortical evoked potentials are generated by direct single-pulse electrical stimulation and can be used to investigate cortico-cortical connections in vivo. We hypothesized that the presence of high amplitude cortico-cortical evoked potentials, recorded during intracranial EEG monitoring, near the eventual responsive neurostimulation contact sites is predictive of better outcomes from its therapy. We retrospectively reviewed 12 patients in whom cortico-cortical evoked potentials were obtained during stereoelectroencephalography evaluation and subsequently underwent responsive neurostimulation therapy. We studied the relationship between cortico-cortical evoked potentials, the eventual responsive neurostimulation electrode locations and seizure reduction. Directional connectivity indicated by cortico-cortical evoked potentials can categorize stereoelectroencephalography electrodes as either receiver nodes/in-degree (an area of greater inward connectivity) or projection nodes/out-degree (greater outward connectivity). The follow-up period for seizure reduction ranged from 1.3-4.8 years (median 2.7) after responsive neurostimulation therapy started. Stereoelectroencephalography electrodes closest to the eventual responsive neurostimulation contact site tended to show larger in-degree cortico-cortical evoked potentials, especially for the early latency cortico-cortical evoked potentials period (10-60 ms period) in six out of 12 patients. Stereoelectroencephalography electrodes closest to the responsive neurostimulation contacts (≤5 mm) also had greater significant out-degree in the early cortico-cortical evoked potentials latency period than those further away (≥10 mm) (P < 0.05). Additionally, significant correlation was noted between in-degree cortico-cortical evoked potentials and greater seizure reduction with responsive neurostimulation therapy at its most effective period (P < 0.05). These findings suggest that functional connectivity determined by cortico-cortical evoked potentials may provide additional information that could help guide the optimal placement of responsive neurostimulation electrodes.

Graph Learning for Cortical Parcellation from Tensor Decompositions of Resting-State fMRI.

Cortical parcellation has long been a cornerstone in the field of neuroscience, enabling the cerebral cortex to be partitioned into distinct, non-overlapping regions that facilitate the interpretation and comparison of complex neuroscientific data. In recent years, these parcellations have frequently been based on the use of resting-state fMRI (rsfMRI) data. In parallel, methods such as independent components analysis have long been used to identify large-scale functional networks with significant spatial overlap between networks. Despite the fact that both forms of decomposition make use of the same spontaneous brain activity measured with rsfMRI, a gap persists in establishing a clear relationship between disjoint cortical parcellations and brain-wide networks. To address this, we introduce a novel parcellation framework that integrates NASCAR, a three-dimensional tensor decomposition method that identifies a series of functional brain networks, with state-of-the-art graph representation learning to produce cortical parcellations that represent near-homogeneous functional regions that are consistent with these brain networks. Further, through the use of the tensor decomposition, we avoid the limitations of traditional approaches that assume statistical independence or orthogonality in defining the underlying networks. Our findings demonstrate that these parcellations are comparable or superior to established atlases in terms of homogeneity of the functional connectivity across parcels, task contrast alignment, and architectonic map alignment. Our methodological pipeline is highly automated, allowing for rapid adaptation to new datasets and the generation of custom parcellations in just minutes, a significant advancement over methods that require extensive manual input. We describe this integrated approach, which we refer to as Untamed, as a tool for use in the fields of cognitive and clinical neuroscientific research. Parcellations created from the Human Connectome Project dataset using Untamed, along with the code to generate atlases with custom parcel numbers, are publicly available at https://untamed-atlas.github.io.

Tuning Minimum-Norm regularization parameters for optimal MEG connectivity estimation.

The accurate characterization of cortical functional connectivity from Magnetoencephalography (MEG) data remains a challenging problem due to the subjective nature of the analysis, which requires several decisions at each step of the analysis pipeline, such as the choice of a source estimation algorithm, a connectivity metric and a cortical parcellation, to name but a few. Recent studies have emphasized the importance of selecting the regularization parameter in minimum norm estimates with caution, as variations in its value can result in significant differences in connectivity estimates. In particular, the amount of regularization that is optimal for MEG source estimation can actually be suboptimal for coherence-based MEG connectivity analysis. In this study, we expand upon previous work by examining a broader range of commonly used connectivity metrics, including the imaginary part of coherence, corrected imaginary part of Phase Locking Value, and weighted Phase Lag Index, within a larger and more realistic simulation scenario. Our results show that the best estimate of connectivity is achieved using a regularization parameter that is 1 or 2 orders of magnitude smaller than the one that yields the best source estimation. This remarkable difference may imply that previous work assessing source-space connectivity using minimum-norm may have benefited from using less regularization, as this may have helped reduce false positives. Importantly, we provide the code for MEG data simulation and analysis, offering the research community a valuable open source tool for informed selections of the regularization parameter when using minimum-norm for source space connectivity analyses.

BrainSuite BIDS App: Containerized Workflows for MRI Analysis.

There has been a concerted effort by the neuroimaging community to establish standards for computational methods for data analysis that promote reproducibility and portability. In particular, the Brain Imaging Data Structure (BIDS) specifies a standard for storing imaging data, and the related BIDS App methodology provides a standard for implementing containerized processing environments that include all necessary dependencies to process BIDS datasets using image processing workflows. We present the BrainSuite BIDS App, which encapsulates the core MRI processing functionality of BrainSuite within the BIDS App framework. Specifically, the BrainSuite BIDS App implements a participant-level workflow comprising three pipelines and a corresponding set of group-level analysis workflows for processing the participant-level outputs. The BrainSuite Anatomical Pipeline (BAP) extracts cortical surface models from a T1-weighted (T1w) MRI. It then performs surface-constrained volumetric registration to align the T1w MRI to a labeled anatomical atlas, which is used to delineate anatomical regions of interest in the MRI brain volume and on the cortical surface models. The BrainSuite Diffusion Pipeline (BDP) processes diffusion-weighted imaging (DWI) data, with steps that include coregistering the DWI data to the T1w scan, correcting for geometric image distortion, and fitting diffusion models to the DWI data. The BrainSuite Functional Pipeline (BFP) performs fMRI processing using a combination of FSL, AFNI, and BrainSuite tools. BFP coregisters the fMRI data to the T1w image, then transforms the data to the anatomical atlas space and to the Human Connectome Project's grayordinate space. Each of these outputs can then be processed during group-level analysis. The outputs of BAP and BDP are analyzed using the BrainSuite Statistics in R (bssr) toolbox, which provides functionality for hypothesis testing and statistical modeling. The outputs of BFP can be analyzed using atlas-based or atlas-free statistical methods during group-level processing. These analyses include the application of BrainSync, which synchronizes the time-series data temporally and enables comparison of resting-state or task-based fMRI data across scans. We also present the BrainSuite Dashboard quality control system, which provides a browser-based interface for reviewing the outputs of individual modules of the participant-level pipelines across a study in real-time as they are generated. BrainSuite Dashboard facilitates rapid review of intermediate results, enabling users to identify processing errors and make adjustments to processing parameters if necessary. The comprehensive functionality included in the BrainSuite BIDS App provides a mechanism for rapidly deploying the BrainSuite workflows into new environments to perform large-scale studies. We demonstrate the capabilities of the BrainSuite BIDS App using structural, diffusion, and functional MRI data from the Amsterdam Open MRI Collection's Population Imaging of Psychology dataset.

Multilayer brain networks can identify the epileptogenic zone and seizure dynamics.

Seizure generation, propagation, and termination occur through spatiotemporal brain networks. In this paper, we demonstrate the significance of large-scale brain interactions in high-frequency (80-200Hz) for the identification of the epileptogenic zone (EZ) and seizure evolution. To incorporate the continuity of neural dynamics, here we have modeled brain connectivity constructed from stereoelectroencephalography (SEEG) data during seizures using multilayer networks. After introducing a new measure of brain connectivity for temporal networks, named multilayer eigenvector centrality (mlEVC), we applied a consensus hierarchical clustering on the developed model to identify the EZ as a cluster of nodes with distinctive brain connectivity in the ictal period. Our algorithm could successfully predict electrodes inside the resected volume as EZ for 88% of participants, who all were seizure-free for at least 12 months after surgery. Our findings illustrated significant and unique desynchronization between EZ and the rest of the brain in the early to mid-seizure. We showed that aging and the duration of epilepsy intensify this desynchronization, which can be the outcome of abnormal neuroplasticity. Additionally, we illustrated that seizures evolve with various network topologies, confirming the existence of different epileptogenic networks in each patient. Our findings suggest not only the importance of early intervention in epilepsy but possible factors that correlate with disease severity. Moreover, by analyzing the propagation patterns of different seizures, we demonstrate the necessity of collecting sufficient data for identifying epileptogenic networks.

Identification of overlapping and interacting networks reveals intrinsic spatiotemporal organization of the human brain.

The human brain is a complex network that exhibits dynamic fluctuations in activity across space and time. Depending on the analysis method, canonical brain networks identified from resting-state fMRI (rs-fMRI) are typically constrained to be either orthogonal or statistically independent in their spatial and/or temporal domains. We avoid imposing these potentially unnatural constraints through the combination of a temporal synchronization process ("BrainSync") and a three-way tensor decomposition method ("NASCAR") to jointly analyze rs-fMRI data from multiple subjects. The resulting set of interacting networks comprises minimally constrained spatiotemporal distributions, each representing one component of functionally coherent activity across the brain. We show that these networks can be clustered into six distinct functional categories and naturally form a representative functional network atlas for a healthy population. This functional network atlas could help explore group and individual differences in neurocognitive function, as we demonstrate in the context of ADHD and IQ prediction.

Brainstorm-DUNEuro: An integrated and user-friendly Finite Element Method for modeling electromagnetic brain activity.

Human brain activity generates scalp potentials (electroencephalography - EEG), intracranial potentials (iEEG), and external magnetic fields (magnetoencephalography - MEG). These electrophysiology (e-phys) signals can often be measured simultaneously for research and clinical applications. The forward problem involves modeling these signals at their sensors for a given equivalent current dipole configuration within the brain. While earlier researchers modeled the head as a simple set of isotropic spheres, today's magnetic resonance imaging (MRI) data allow for a detailed anatomic description of brain structures and anisotropic characterization of tissue conductivities. We present a complete pipeline, integrated into the Brainstorm software, that allows users to automatically generate an individual and accurate head model based on the subject's MRI and calculate the electromagnetic forward solution using the finite element method (FEM). The head model generation is performed by integrating the latest tools for MRI segmentation and FEM mesh generation. The final head model comprises the five main compartments: white-matter, gray-matter, CSF, skull, and scalp. The anisotropic brain conductivity model is based on the effective medium approach (EMA), which estimates anisotropic conductivity tensors from diffusion-weighted imaging (DWI) data. The FEM electromagnetic forward solution is obtained through the DUNEuro library, integrated into Brainstorm, and accessible with either a user-friendly graphical interface or scripting. With tutorials and example data sets available in an open-source format on the Brainstorm website, this integrated pipeline provides access to advanced FEM tools for electromagnetic modeling to a broader neuroscience community.

Meta Transfer of Self-Supervised Knowledge: Foundation Model in Action for Post-Traumatic Epilepsy Prediction.

Despite the impressive advancements achieved using deep-learning for functional brain activity analysis, the heterogeneity of functional patterns and scarcity of imaging data still pose challenges in tasks such as prediction of future onset of Post-Traumatic Epilepsy (PTE) from data acquired shortly after traumatic brain injury (TBI). Foundation models pre-trained on separate large-scale datasets can improve the performance from scarce and heterogeneous datasets. For functional Magnetic Resonance Imaging (fMRI), while data may be abundantly available from healthy controls, clinical data is often scarce, limiting the ability of foundation models to identify clinically-relevant features. We overcome this limitation by introducing a novel training strategy for our foundation model by integrating meta-learning with self-supervised learning to improve the generalization from normal to clinical features. In this way we enable generalization to other downstream clinical tasks, in our case prediction of PTE. To achieve this, we perform self-supervised training on the control dataset to focus on inherent features that are not limited to a particular supervised task while applying meta-learning, which strongly improves the model's generalizability using bi-level optimization. Through experiments on neurological disorder classification tasks, we demonstrate that the proposed strategy significantly improves task performance on small-scale clinical datasets. To explore the generalizability of the foundation model in downstream applications, we then apply the model to an unseen TBI dataset for prediction of PTE using zero-shot learning. Results further demonstrated the enhanced generalizability of our foundation model.

Reduced subgenual cingulate-dorsolateral prefrontal connectivity as an electrophysiological marker for depression.

Major Depressive Disorder (MDD) is a widespread mental illness that causes considerable suffering, and neuroimaging studies are trying to reduce this burden by developing biomarkers that can facilitate detection. Prior fMRI- and neurostimulation studies suggest that aberrant subgenual Anterior Cingulate (sgACC)-dorsolateral Prefrontal Cortex (DLPFC) functional connectivity is consistently present within MDD. Combining the need for reliable depression markers with the electroencephalogram's (EEG) high clinical utility, we investigated whether aberrant EEG sgACC-DLPFC functional connectivity could serve as a marker for depression. Source-space Amplitude Envelope Correlations (AEC) of 20 MDD patients and 20 matched controls were contrasted using non-parametric permutation tests. In addition, extracted AEC values were used to (a) correlate with characteristics of depression and (b) train a Support Vector Machine (SVM) to determine sgACC-DLPFC connectivity's discriminative power. FDR-thresholded statistical maps showed reduced sgACC-DLPFC AEC connectivity in MDD patients relative to controls. This diminished AEC connectivity is located in the beta-1 (13-17 Hz) band and is associated with patients' lifetime number of depressive episodes. Using extracted sgACC-DLPFC AEC values, the SVM achieved a classification accuracy of 84.6% (80% sensitivity and 89.5% specificity) indicating that EEG sgACC-DLPFC connectivity has promise as a biomarker for MDD.

Chronic anemia: The effects on the connectivity of white matter.

Chronic anemia is commonly observed in patients with hemoglobinopathies, mainly represented by disorders of altered hemoglobin (Hb) structure (sickle cell disease, SCD) and impaired Hb synthesis (e.g. thalassemia syndromes, non-SCD anemia). Both hemoglobinopathies have been associated with white matter (WM) alterations. Novel structural MRI research in our laboratory demonstrated that WM volume was diffusely lower in deep, watershed areas proportional to anemia severity. Furthermore, diffusion tensor imaging analysis has provided evidence that WM microstructure is disrupted proportionally to Hb level and oxygen saturation. SCD patients have been widely studied and demonstrate lower fractional anisotropy (FA) in the corticospinal tract and cerebellum across the internal capsule and corpus callosum. In the present study, we compared 19 SCD and 15 non-SCD anemia patients with a wide range of Hb values allowing the characterization of the effects of chronic anemia in isolation of sickle Hb. We performed a tensor analysis to quantify FA changes in WM connectivity in chronic anemic patients. We calculated the volumetric mean of FA along the pathway of tracks connecting two regions of interest defined by BrainSuite's BCI-DNI atlas. In general, we found lower FA values in anemic patients; indicating the loss of coherence in the main diffusion direction that potentially indicates WM injury. We saw a positive correlation between FA and hemoglobin in these same regions, suggesting that decreased WM microstructural integrity FA is highly driven by chronic hypoxia. The only connection that did not follow this pattern was the connectivity within the left middle-inferior temporal gyrus. Interestingly, more reductions in FA were observed in non-SCD patients (mainly along with intrahemispheric WM bundles and watershed areas) than the SCD patients (mainly interhemispheric).

A hybrid high-resolution anatomical MRI atlas with sub-parcellation of cortical gyri using resting fMRI.

We present a new high-quality, single-subject atlas with sub-millimeter voxel resolution, high SNR, and excellent gray-white tissue contrast to resolve fine anatomical details. The atlas is labeled into two parcellation schemes: 1) the anatomical BCI-DNI atlas, which is manually labeled based on known morphological and anatomical features, and 2) the hybrid USCBrain atlas, which incorporates functional information to guide the sub-parcellation of cerebral cortex. In both cases, we provide consistent volumetric and cortical surface-based parcellation and labeling. The intended use of the atlas is as a reference template for structural coregistration and labeling of individual brains. A single-subject T1-weighted image was acquired five times at a resolution of 0.547 mm × 0.547 mm × 0.800 mm and averaged. Images were processed by an expert neuroanatomist using semi-automated methods in BrainSuite to extract the brain, classify tissue-types, and render anatomical surfaces. Sixty-six cortical and 29 noncortical regions were manually labeled to generate the BCI-DNI atlas. The cortical regions were further sub-parcellated into 130 cortical regions based on multi-subject connectivity analysis using resting fMRI (rfMRI) data from the Human Connectome Project (HCP) database to produce the USCBrain atlas. In addition, we provide a delineation between sulcal valleys and gyral crowns, which offer an additional set of 26 sulcal subregions per hemisphere. Lastly, a probabilistic map is provided to give users a quantitative measure of reliability for each gyral subdivision. Utility of the atlas was assessed by computing Adjusted Rand Indices (ARIs) between individual sub-parcellations obtained through structural-only coregistration to the USCBrain atlas and sub-parcellations obtained directly from each subject's resting fMRI data. Both atlas parcellations can be used with the BrainSuite, FreeSurfer, and FSL software packages.

Age differences in the functional architecture of the human brain.

The intrinsic functional organization of the brain changes into older adulthood. Age differences are observed at multiple spatial scales, from global reductions in modularity and segregation of distributed brain systems, to network-specific patterns of dedifferentiation. Whether dedifferentiation reflects an inevitable, global shift in brain function with age, circumscribed, experience-dependent changes, or both, is uncertain. We employed a multimethod strategy to interrogate dedifferentiation at multiple spatial scales. Multi-echo (ME) resting-state fMRI was collected in younger (n = 181) and older (n = 120) healthy adults. Cortical parcellation sensitive to individual variation was implemented for precision functional mapping of each participant while preserving group-level parcel and network labels. ME-fMRI processing and gradient mapping identified global and macroscale network differences. Multivariate functional connectivity methods tested for microscale, edge-level differences. Older adults had lower BOLD signal dimensionality, consistent with global network dedifferentiation. Gradients were largely age-invariant. Edge-level analyses revealed discrete, network-specific dedifferentiation patterns in older adults. Visual and somatosensory regions were more integrated within the functional connectome; default and frontoparietal control network regions showed greater connectivity; and the dorsal attention network was more integrated with heteromodal regions. These findings highlight the importance of multiscale, multimethod approaches to characterize the architecture of functional brain aging.

Deep Quantile Regression for Uncertainty Estimation in Unsupervised and Supervised Lesion Detection.

Despite impressive state-of-the-art performance on a wide variety of machine learning tasks in multiple applications, deep learning methods can produce over-confident predictions, particularly with limited training data. Therefore, quantifying uncertainty is particularly important in critical applications such as lesion detection and clinical diagnosis, where a realistic assessment of uncertainty is essential in determining surgical margins, disease status and appropriate treatment. In this work, we propose a novel approach that uses quantile regression for quantifying aleatoric uncertainty in both supervised and unsupervised lesion detection problems. The resulting confidence intervals can be used for lesion detection and segmentation. In the unsupervised setting, we combine quantile regression with the Variational AutoEncoder (VAE). The VAE is trained on lesion-free data, so when presented with an image with a lesion, it tends to reconstruct a lesion-free version of the image. To detect the lesion, we then compare the input (lesion) and output (lesion-free) images. Here we address the problem of quantifying uncertainty in the images that are reconstructed by the VAE as the basis for principled outlier or lesion detection. The VAE models the output as a conditionally independent Gaussian characterized by its mean and variance. Unfortunately, joint optimization of both mean and variance in the VAE leads to the well-known problem of shrinkage or underestimation of variance. Here we describe an alternative Quantile-Regression VAE (QR-VAE) that avoids this variance shrinkage problem by directly estimating conditional quantiles for the input image. Using the estimated quantiles, we compute the conditional mean and variance for the input image from which we then detect outliers by thresholding at a false-discovery-rate corrected p-value. In the supervised setting, we develop binary quantile regression (BQR) for the supervised lesion segmentation task. We show how BQR can be used to capture uncertainty in lesion boundaries in a manner that characterizes expert disagreement.

A robust variational autoencoder using beta divergence.

The presence of outliers can severely degrade learned representations and performance of deep learning methods and hence disproportionately affect the training process, leading to incorrect conclusions about the data. For example, anomaly detection using deep generative models is typically only possible when similar anomalies (or outliers) are not present in the training data. Here we focus on variational autoencoders (VAEs). While the VAE is a popular framework for anomaly detection tasks, we observe that the VAE is unable to detect outliers when the training data contains anomalies that have the same distribution as those in test data. In this paper we focus on robustness to outliers in training data in VAE settings using concepts from robust statistics. We propose a variational lower bound that leads to a robust VAE model that has the same computational complexity as the standard VAE and contains a single automatically-adjusted tuning parameter to control the degree of robustness. We present mathematical formulations for robust variational autoencoders (RVAEs) for Bernoulli, Gaussian and categorical variables. The RVAE model is based on beta-divergence rather than the standard Kullback-Leibler (KL) divergence. We demonstrate the performance of our proposed ß-divergence-based autoencoder for a variety of image and categorical datasets showing improved robustness to outliers both qualitatively and quantitatively. We also illustrate the use of our robust VAE for detection of lesions in brain images, formulated as an anomaly detection task. Finally, we suggest a method to tune the hyperparameter of RVAE which makes our model completely unsupervised.

Effective connectivity differs between focal cortical dysplasia types I and II.

OBJECTIVE: To determine whether brain connectivity differs between focal cortical dysplasia (FCD) types I and II. METHODS: We compared cortico-cortical evoked potentials (CCEPs) as measures of effective brain connectivity in 25 FCD patients with drug-resistant focal epilepsy who underwent intracranial evaluation with stereo-electroencephalography (SEEG). We analyzed the amplitude and latency of CCEP responses following ictal-onset single-pulse electrical stimulation (iSPES). RESULTS: In comparison to FCD type II, patients with type I demonstrated significantly larger responses in the electrodes near the ictal-onset zone (<50 mm). These findings persisted when controlling for the location of the epileptogenic zone, as noted in patients with temporal lobe epilepsies, as well as controlling for seizure type, as noted in patients with focal to bilateral tonic-clonic seizures (FBTCS). In type II, the root mean square (RMS) of CCEP responses dropped substantially from the early segment (10-60 ms) to the middle and late segments (60-600 ms). The middle and late CCEP latency segments showed the largest differences between FCD types I and II. SIGNIFICANCE: Focal cortical dysplasia type I may have a greater degree of cortical hyperexcitability as compared with FCD type II. In addition, FCD type II displays a more restrictive area of hyperexcitability in both temporal and spatial domains. In patients with FBTCS and type I FCD, the increased amplitudes of RMS in the middle and late CCEP periods appear consistent with the cortico-thalamo-cortical network involvement of FBTCS. The notable differences in degree and extent of hyperexcitability may contribute to the different postsurgical seizure outcomes noted between these two pathological substrates.

Quantile Regression for Uncertainty Estimation in VAEs with Applications to Brain Lesion Detection.

The Variational AutoEncoder (VAE) has become one of the most popular models for anomaly detection in applications such as lesion detection in medical images. The VAE is a generative graphical model that is used to learn the data distribution from samples and then generate new samples from this distribution. By training on normal samples, the VAE can be used to detect inputs that deviate from this learned distribution. The VAE models the output as a conditionally independent Gaussian characterized by means and variances for each output dimension. VAEs can therefore use reconstruction probability instead of reconstruction error for anomaly detection. Unfortunately, joint optimization of both mean and variance in the VAE leads to the well-known problem of shrinkage or underestimation of variance. We describe an alternative VAE model, Quantile-Regression VAE (QR-VAE), that avoids this variance shrinkage problem by estimating conditional quantiles for the given input image. Using the estimated quantiles, we compute the conditional mean and variance for input images under the Gaussian model. We then compute reconstruction probability using this model as a principled approach to outlier or anomaly detection. We also show how our approach can be used for heterogeneous thresholding of images for detecting lesions in brain images.

Corticospinal Tract Microstructure Predicts Distal Arm Motor Improvements in Chronic Stroke.

BACKGROUND AND PURPOSE: The corticospinal tract (CST) is a crucial brain pathway for distal arm and hand motor control. We aimed to determine whether a diffusion tensor imaging (DTI)-derived CST metric predicts distal upper extremity (UE) motor improvements in chronic stroke survivors. METHODS: We analyzed clinical and neuroimaging data from a randomized controlled rehabilitation trial. Participants completed clinical assessments and neuroimaging at baseline and clinical assessments 4 months later, postintervention. Using univariate linear regression analysis, we determined the linear relationship between the DTI-derived CST fractional anisotropy asymmetry (FAasym) and the percentage of baseline change in log-transformed average Wolf Motor Function Test time for distal items (ΔlnWMFT-distal_%). The least absolute shrinkage and selection operator (LASSO) linear regressions with cross-validation and bootstrapping were used to determine the relative weighting of CST FAasym, other brain metrics, clinical outcomes, and demographics on distal motor improvement. Logistic regression analyses were performed to test whether the CST FAasym can predict clinically significant UE motor improvement. RESULTS: lnWMFT-distal significantly improved at the group level. Baseline CST FAasym explained 26% of the variance in ΔlnWMFT-distal_%. A multivariate LASSO model including baseline CST FAasym, age, and UE Fugl-Meyer explained 39% of the variance in ΔlnWMFT-distal_%. Further, CST FAasym explained more variance in ΔlnWMFT-distal_% than the other significant predictors in the LASSO model. DISCUSSION AND CONCLUSIONS: CST microstructure is a significant predictor of improvement in distal UE motor function in the context of an UE rehabilitation trial in chronic stroke survivors with mild-to-moderate motor impairment.Video Abstract available for more insight from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A350).

Validation of semi-automated anatomically labeled SEEG contacts in a brain atlas for mapping connectivity in focal epilepsy.

OBJECTIVE: Stereotactic electroencephalography (SEEG) has been widely used to explore the epileptic network and localize the epileptic zone in patients with medically intractable epilepsy. Accurate anatomical labeling of SEEG electrode contacts is critically important for correctly interpreting epileptic activity. We present a method for automatically assigning anatomical labels to SEEG electrode contacts using a 3D-segmented cortex and coregistered postoperative CT images. METHOD: Stereotactic electroencephalography electrode contacts were spatially localized relative to the brain volume using a standard clinical procedure. Each contact was then assigned an anatomical label by clinical epilepsy fellows. Separately, each contact was automatically labeled by coregistering the subject's MRI to the USCBrain atlas using the BrainSuite software and assigning labels from the atlas based on contact locations. The results of both labeling methods were then compared, and a subsequent vetting of the anatomical labels was performed by expert review. RESULTS: Anatomical labeling agreement between the two methods for over 17 000 SEEG contacts was 82%. This agreement was consistent in patients with and without previous surgery (P = .852). Expert review of contacts in disagreement between the two methods resulted in agreement with the atlas based over manual labels in 48% of cases, agreement with manual over atlas-based labels in 36% of cases, and disagreement with both methods in 16% of cases. Labels deemed incorrect by the expert review were then categorized as either in a region directly adjacent to the correct label or as a gross error, revealing a lower likelihood of gross error from the automated method. SIGNIFICANCE: The method for semi-automated atlas-based anatomical labeling we describe here demonstrates potential to assist clinical workflow by reducing both analysis time and the likelihood of gross anatomical error. Additionally, it provides a convenient means of intersubject analysis by standardizing the anatomical labels applied to SEEG contact locations across subjects.