Structural brain morphometry differences and similarities between young patients with Crohn's disease in remission and healthy young and old controls.

Introduction: Crohn's disease (CD), one of the main phenotypes of inflammatory bowel disease (IBD), can affect any part of the gastrointestinal tract. It can impact the function of gastrointestinal secretions, as well as increasing the intestinal permeability leading to an aberrant immunological response and subsequent intestinal inflammation. Studies have reported anatomical and functional brain changes in Crohn's Disease patients (CDs), possibly due to increased inflammatory markers and microglial cells that play key roles in communicating between the brain, gut, and systemic immune system. To date, no studies have demonstrated similarities between morphological brain changes seen in IBD and brain morphometry observed in older healthy controls.. Methods: For the present study, twelve young CDs in remission (M = 26.08 years, SD = 4.9 years, 7 male) were recruited from an IBD Clinic. Data from 12 young age-matched healthy controls (HCs) (24.5 years, SD = 3.6 years, 8 male) and 12 older HCs (59 years, SD = 8 years, 8 male), previously collected for a different study under a similar MR protocol, were analyzed as controls. T1 weighted images and structural image processing techniques were used to extract surface-based brain measures, to test our hypothesis that young CDs have different brain surface morphometry than their age-matched young HCs and furthermore, appear more similar to older HCs. The phonemic verbal fluency (VF) task (the Controlled Oral Word Association Test, COWAT) (Benton, 1976) was administered to test verbal cognitive ability and executive control. Results/Discussion: On the whole, CDs had more brain regions with differences in brain morphometry measures when compared to the young HCs as compared to the old HCs, suggesting that CD has an effect on the brain that makes it appear more similar to old HCs. Additionally, our study demonstrates this atypical brain morphometry is associated with function on a cognitive task. These results suggest that even younger CDs may be showing some evidence of structural brain changes that demonstrate increased resemblance to older HC brains rather than their similarly aged healthy counterparts.

Tumor Volume Growth Rates and Doubling Times during Active Surveillance of IDH-mutant Low-Grade Glioma.

PURPOSE: Isocitrate dehydrogenase-mutant (IDH-mt) gliomas are incurable primary brain tumors characterized by a slow-growing phase over several years followed by a rapid-growing malignant phase. We hypothesized that tumor volume growth rate (TVGR) on MRI may act as an earlier measure of clinical benefit during the active surveillance period. EXPERIMENTAL DESIGN: We integrated three-dimensional volumetric measurements with clinical, radiologic, and molecular data in a retrospective cohort of IDH-mt gliomas that were observed after surgical resection in order to understand tumor growth kinetics and the impact of molecular genetics. RESULTS: Using log-linear mixed modeling, the entire cohort (n = 128) had a continuous %TVGR per 6 months of 10.46% [95% confidence interval (CI), 9.11%-11.83%] and a doubling time of 3.5 years (95% CI, 3.10-3.98). High molecular grade IDH-mt gliomas, defined by the presence of homozygous deletion of CDKN2A/B, had %TVGR per 6 months of 19.17% (95% CI, 15.57%-22.89%) which was significantly different from low molecular grade IDH-mt gliomas with a growth rate per 6 months of 9.54% (95% CI, 7.32%-11.80%; P < 0.0001). Using joint modeling to comodel the longitudinal course of TVGR and overall survival, we found each one natural logarithm tumor volume increase resulted in more than a 3-fold increase in risk of death (HR = 3.83; 95% CI, 2.32-6.30; P < 0.0001). CONCLUSIONS: TVGR may be used as an earlier measure of clinical benefit and correlates well with the WHO 2021 molecular classification of gliomas and survival. Incorporation of TVGR as a surrogate endpoint into future prospective studies of IDH-mt gliomas may accelerate drug development.

Unified topological inference for brain networks in temporal lobe epilepsy using the Wasserstein distance.

Persistent homology offers a powerful tool for extracting hidden topological signals from brain networks. It captures the evolution of topological structures across multiple scales, known as filtrations, thereby revealing topological features that persist over these scales. These features are summarized in persistence diagrams, and their dissimilarity is quantified using the Wasserstein distance. However, the Wasserstein distance does not follow a known distribution, posing challenges for the application of existing parametric statistical models. To tackle this issue, we introduce a unified topological inference framework centered on the Wasserstein distance. Our approach has no explicit model and distributional assumptions. The inference is performed in a completely data driven fashion. We apply this method to resting-state functional magnetic resonance images (rs-fMRI) of temporal lobe epilepsy patients collected from two different sites: the University of Wisconsin-Madison and the Medical College of Wisconsin. Importantly, our topological method is robust to variations due to sex and image acquisition, obviating the need to account for these variables as nuisance covariates. We successfully localize the brain regions that contribute the most to topological differences. A MATLAB package used for all analyses in this study is available at https://github.com/laplcebeltrami/PH-STAT.

T1-/T2-weighted ratio reveals no alterations to gray matter myelination in temporal lobe epilepsy.

Short-range functional connectivity in the limbic network is increased in patients with temporal lobe epilepsy (TLE), and recent studies have shown that cortical myelin content correlates with fMRI connectivity. We thus hypothesized that myelin may increase progressively in the epileptic network. We compared T1w/T2w gray matter myelin maps between TLE patients and age-matched controls and assessed relationships between myelin and aging. While both TLE patients and healthy controls exhibited increased T1w/T2w intensity with age, we found no evidence for significant group-level aberrations in overall myelin content or myelin changes through time in TLE.

Activation Map Reveals Language Impairment in Children with Benign Epilepsy with Centrotemporal Spikes (BECTS).

Objective: Neuropsychological evidence revealed language impairment in children with benign epilepsy with centrotemporal spikes (BECTS). This study investigates language function using task-activated fMRI. Methods: We conducted a language task fMRI study on three groups on a 3.0T MRI scanner, including a new onset drug naïve group (NODN-BECTS, n=11, age=9.6±1.6), an established epilepsy with medication-treated group (Med-BECTS, n=17, age=10.7±2.2) and a healthy control group (HC, n=18, age=10.8±1.7). We use MATLAB14 and SPM12 to pre-process and analyze the data. A one-sample t-test was used to identify task-related brain activation changes in each group, based on the general linear model (GLM). And, then two sample t-test was performed to compare different activated regions between groups. In addition, scores on the most recent Mandarin school exams were acquired to examine and contrast extra-scanner language performance. Results: Statistical results show that some language-related brain regions (such as the left superior frontal gyrus and cerebellar vermis) were additionally activated in the NODN-BECTS group compared with the HC group. Compared with NODN-BECTS and HC groups, decreased activations were found in language-related regions in the Med-BECTS group, including the left insula, superior and middle frontal gyri, and bilateral middle occipital gyri. On the Mandarin school exams, the average score for HC was 87.3±8.2, NODN was 84.8±7.8, and Med was 78.2±13.2. There was a trend toward statistical significance between the Med and the HC (p = 0.074) as well as NODN (p = 0.092) groups. No statistically significant differences were found between the HC and the NODN-BECTS groups. Significance: Language task fMRI reveals additional areas of activation in new onset BECTS compared to healthy controls which may be compensatory in nature. Antiseizure medications (ASMs) and/or longer duration of BECTS additionally appears to affect language-related regions and reduce their functional ability.

Tractography passes the test: Results from the diffusion-simulated connectivity (disco) challenge.

Estimating structural connectivity from diffusion-weighted magnetic resonance imaging is a challenging task, partly due to the presence of false-positive connections and the misestimation of connection weights. Building on previous efforts, the MICCAI-CDMRI Diffusion-Simulated Connectivity (DiSCo) challenge was carried out to evaluate state-of-the-art connectivity methods using novel large-scale numerical phantoms. The diffusion signal for the phantoms was obtained from Monte Carlo simulations. The results of the challenge suggest that methods selected by the 14 teams participating in the challenge can provide high correlations between estimated and ground-truth connectivity weights, in complex numerical environments. Additionally, the methods used by the participating teams were able to accurately identify the binary connectivity of the numerical dataset. However, specific false positive and false negative connections were consistently estimated across all methods. Although the challenge dataset doesn't capture the complexity of a real brain, it provided unique data with known macrostructure and microstructure ground-truth properties to facilitate the development of connectivity estimation methods.

Association of neighborhood deprivation with white matter connectome abnormalities in temporal lobe epilepsy.

OBJECTIVE: Social determinants of health, including the effects of neighborhood disadvantage, impact epilepsy prevalence, treatment, and outcomes. This study characterized the association between aberrant white matter connectivity in temporal lobe epilepsy (TLE) and disadvantage using a US census-based neighborhood disadvantage metric, the Area Deprivation Index (ADI), derived from measures of income, education, employment, and housing quality. METHODS: Participants including 74 TLE patients (47 male, mean age = 39.2 years) and 45 healthy controls (27 male, mean age = 31.9 years) from the Epilepsy Connectome Project were classified into ADI-defined low and high disadvantage groups. Graph theoretic metrics were applied to multishell connectome diffusion-weighted imaging (DWI) measurements to derive 162 × 162 structural connectivity matrices (SCMs). The SCMs were harmonized using neuroCombat to account for interscanner differences. Threshold-free network-based statistics were used for analysis, and findings were correlated with ADI quintile metrics. A decrease in cross-sectional area (CSA) indicates reduced white matter integrity. RESULTS: Sex- and age-adjusted CSA in TLE groups was significantly reduced compared to controls regardless of disadvantage status, revealing discrete aberrant white matter tract connectivity abnormalities in addition to apparent differences in graph measures of connectivity and network-based statistics. When comparing broadly defined disadvantaged TLE groups, differences were at trend level. Sensitivity analyses of ADI quintile extremes revealed significantly lower CSA in the most compared to least disadvantaged TLE group. SIGNIFICANCE: Our findings demonstrate (1) the general impact of TLE on DWI connectome status is larger than the association with neighborhood disadvantage; however, (2) neighborhood disadvantage, indexed by ADI, revealed modest relationships with white matter structure and integrity on sensitivity analysis in TLE. Further studies are needed to explore this relationship and determine whether the white matter relationship with ADI is driven by social drift or environmental influences on brain development. Understanding the etiology and course of the disadvantage-brain integrity relationship may serve to inform care, management, and policy for patients.

Application of data harmonization and tract-based spatial statistics reveals white matter structural abnormalities in pediatric patients with focal cortical dysplasia.

Our study assessed diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) in pediatric subjects with epilepsy secondary to Focal Cortical Dysplasia (FCD) to improve our understanding of structural network changes associated with FCD related epilepsy. We utilized a data harmonization (DH) approach to minimize confounding effects induced by MRI protocol differences. We also assessed correlations between DTI metrics and neurocognitive measures of the fluid reasoning index (FRI), verbal comprehension index (VCI), and visuospatial index (VSI). Data (n = 51) from 23 FCD patients and 28 typically developing controls (TD) scanned clinically on either 1.5T, 3T, or 3T-wide-bore MRI were retrospectively analyzed. Tract-based spatial statistics (TBSS) with threshold-free cluster enhancement and permutation testing with 100,000 permutations were used for statistical analysis. To account for imaging protocol differences, we employed non-parametric data harmonization prior to permutation testing. Our analysis demonstrates that DH effectively removed MRI protocol-based differences typical in clinical acquisitions while preserving group differences in DTI metrics between FCD and TD subjects. Furthermore, DH strengthened the association between DTI metrics and neurocognitive indices. Fractional anisotropy, MD, and RD metrics showed stronger correlation with FRI and VSI than VCI. Our results demonstrate that DH is an integral step to reduce the confounding effect of MRI protocol differences during the analysis of white matter tracts and highlights biological differences between FCD and healthy control subjects. Characterization of white matter changes associated with FCD-related epilepsy may better inform prognosis and treatment approaches.

Multi-shell connectome DWI-based graph theory measures for the prediction of temporal lobe epilepsy and cognition.

Temporal lobe epilepsy (TLE) is the most common epilepsy syndrome that empirically represents a network disorder, which makes graph theory (GT) a practical approach to understand it. Multi-shell diffusion-weighted imaging (DWI) was obtained from 89 TLE and 50 controls. GT measures extracted from harmonized DWI matrices were used as factors in a support vector machine (SVM) analysis to discriminate between groups, and in a k-means algorithm to find intrinsic structural phenotypes within TLE. SVM was able to predict group membership (mean accuracy = 0.70, area under the curve (AUC) = 0.747, Brier score (BS) = 0.264) using 10-fold cross-validation. In addition, k-means clustering identified 2 TLE clusters: 1 similar to controls, and 1 dissimilar. Clusters were significantly different in their distribution of cognitive phenotypes, with the Dissimilar cluster containing the majority of TLE with cognitive impairment (χ2 = 6.641, P = 0.036). In addition, cluster membership showed significant correlations between GT measures and clinical variables. Given that SVM classification seemed driven by the Dissimilar cluster, SVM analysis was repeated to classify Dissimilar versus Similar + Controls with a mean accuracy of 0.91 (AUC = 0.957, BS = 0.189). Altogether, the pattern of results shows that GT measures based on connectome DWI could be significant factors in the search for clinical and neurobehavioral biomarkers in TLE.

The presence, nature and network characteristics of behavioural phenotypes in temporal lobe epilepsy.

The relationship between temporal lobe epilepsy and psychopathology has had a long and contentious history with diverse views regarding the presence, nature and severity of emotional-behavioural problems in this patient population. To address these controversies, we take a new person-centred approach through the application of unsupervised machine learning techniques to identify underlying latent groups or behavioural phenotypes. Addressed are the distinct psychopathological profiles, their linked frequency, patterns and severity and the disruptions in morphological and network properties that underlie the identified latent groups. A total of 114 patients and 83 controls from the Epilepsy Connectome Project were administered the Achenbach System of Empirically Based Assessment inventory from which six Diagnostic and Statistical Manual of Mental Disorders-oriented scales were analysed by unsupervised machine learning analytics to identify latent patient groups. Identified clusters were contrasted to controls as well as to each other in order to characterize their association with sociodemographic, clinical epilepsy and morphological and functional imaging network features. The concurrent validity of the behavioural phenotypes was examined through other measures of behaviour and quality of life. Patients overall exhibited significantly higher (abnormal) scores compared with controls. However, cluster analysis identified three latent groups: (i) unaffected, with no scale elevations compared with controls (Cluster 1, 37%); (ii) mild symptomatology characterized by significant elevations across several Diagnostic and Statistical Manual of Mental Disorders-oriented scales compared with controls (Cluster 2, 42%); and (iii) severe symptomatology with significant elevations across all scales compared with controls and the other temporal lobe epilepsy behaviour phenotype groups (Cluster 3, 21%). Concurrent validity of the behavioural phenotype grouping was demonstrated through identical stepwise links to abnormalities on independent measures including the National Institutes of Health Toolbox Emotion Battery and quality of life metrics. There were significant associations between cluster membership and sociodemographic (handedness and education), cognition (processing speed), clinical epilepsy (presence and lifetime number of tonic-clonic seizures) and neuroimaging characteristics (cortical volume and thickness and global graph theory metrics of morphology and resting-state functional MRI). Increasingly dispersed volumetric abnormalities and widespread disruptions in underlying network properties were associated with the most abnormal behavioural phenotype. Psychopathology in these patients is characterized by a series of discrete latent groups that harbour accompanying sociodemographic, clinical and neuroimaging correlates. The underlying neurobiological patterns suggest that the degree of psychopathology is linked to increasingly dispersed abnormal brain networks. Similar to cognition, machine learning approaches support a novel developing taxonomy of the comorbidities of epilepsy.

Genetic and environmental influence on resting state networks in young male and female adults: a cartographer mapping study.

We propose a unique, minimal assumption, approach based on variance analyses (compared with standard approaches) to investigate genetic influence on individual differences on the functional connectivity of the brain using 65 monozygotic and 65 dizygotic healthy young adult twin pairs' low-frequency oscillation resting state functional Magnetic Resonance Imaging (fMRI) data from the Human Connectome Project. Overall, we found high number of genetically-influenced functional (GIF) connections involving posterior to posterior brain regions (occipital/temporal/parietal) implicated in low-level processes such as vision, perception, motion, categorization, dorsal/ventral stream visuospatial, and long-term memory processes, as well as high number across midline brain regions (cingulate) implicated in attentional processes, and emotional responses to pain. We found low number of GIF connections involving anterior to anterior/posterior brain regions (frontofrontal > frontoparietal, frontotemporal, frontooccipital) implicated in high-level processes such as working memory, reasoning, emotional judgment, language, and action planning. We found very low number of GIF connections involving subcortical/noncortical networks such as basal ganglia, thalamus, brainstem, and cerebellum. In terms of sex-specific individual differences, individual differences in males were more genetically influenced while individual differences in females were more environmentally influenced in terms of the interplay of interactions of Task positive networks (brain regions involved in various task-oriented processes and attending to and interacting with environment), extended Default Mode Network (a central brain hub for various processes such as internal monitoring, rumination, and evaluation of self and others), primary sensorimotor systems (vision, audition, somatosensory, and motor systems), and subcortical/noncortical networks. There were >8.5-19.1 times more GIF connections in males than females. These preliminary (young adult cohort-specific) findings suggest that individual differences in the resting state brain may be more genetically influenced in males and more environmentally influenced in females; furthermore, standard approaches may suggest that it is more substantially nonadditive genetics, rather than additive genetics, which contribute to the differences in sex-specific individual differences based on this young adult (male and female) specific cohort. Finally, considering the preliminary cohort-specific results, based on standard approaches, environmental influences on individual differences may be substantially greater than that of genetics, for either sex, frontally and brain-wide. [Correction added on 10 May 2023, after first online publication: added: functional Magnetic Resonance Imaging. Added: individual differences in, twice. Added statement between furthermore … based on standard approaches.].

Perioperative ischaemic brain injury and plasma neurofilament light: a secondary analysis of two prospective cohort studies.

BACKGROUND: Ischaemic brain infarction can occur without acute neurological symptoms (covert strokes) or with symptoms (overt strokes), both associated with poor health outcomes. We conducted a pilot study of the incidence of preoperative and postoperative (intraoperative or postoperative) covert strokes, and explored the relationship of postoperative ischaemic brain injury to blood levels of neurofilament light, a biomarker of neuronal damage. METHODS: We analysed 101 preoperative (within 2 weeks of surgery) and 58 postoperative research MRIs on postoperative days 2-9 from two prospective cohorts collected at the University of Wisconsin (NCT01980511 and NCT03124303). Participants were aged >65 yr and undergoing non-intracranial, non-carotid surgery. RESULTS: Preoperative covert stroke was identified in 2/101 participants (2%; Bayesian 95% confidence interval [CI], 0.2-5.4). This rate was statistically different from the postoperative ischaemic brain injury rate of 7/58 (12%, 4.9-21.3%; P=0.01) based on postoperative imaging. However, in a smaller group of participants with paired imaging (n=30), we did not identify the same effect (P=0.67). Patients with postoperative brain injury had elevated peak neurofilament light levels (median [inter-quartile range], 2.34 [2.24-2.64] log10 pg ml-1) compared with those without (1.86 [1.48-2.21] log10 pg ml-1; P=0.025). Delirium severity scores were higher in those with postoperative brain injury (19 [17-21]) compared with those without (7 [4-12]; P=0.01). CONCLUSION: Although limited by a small sample size, these data suggest that preoperative covert stroke occurs more commonly than previously anticipated. Plasma neurofilament light is a potential screening biomarker for postoperative ischaemic brain injury.

Late dominance of the right hemisphere during narrative comprehension.

PET and fMRI studies suggest that auditory narrative comprehension is supported by a bilateral multilobar cortical network. The superior temporal resolution of magnetoencephalography (MEG) makes it an attractive tool to investigate the dynamics of how different neuroanatomic substrates engage during narrative comprehension. Using beta-band power changes as a marker of cortical engagement, we studied MEG responses during an auditory story comprehension task in 31 healthy adults. The protocol consisted of two runs, each interleaving 7 blocks of the story comprehension task with 15 blocks of an auditorily presented math task as a control for phonological processing, working memory, and attention processes. Sources at the cortical surface were estimated with a frequency-resolved beamformer. Beta-band power was estimated in the frequency range of 16-24 Hz over 1-sec epochs starting from 400 msec after stimulus onset until the end of a story or math problem presentation. These power estimates were compared to 1-second epochs of data before the stimulus block onset. The task-related cortical engagement was inferred from beta-band power decrements. Group-level source activations were statistically compared using non-parametric permutation testing. A story-math contrast of beta-band power changes showed greater bilateral cortical engagement within the fusiform gyrus, inferior and middle temporal gyri, parahippocampal gyrus, and left inferior frontal gyrus (IFG) during story comprehension. A math-story contrast of beta power decrements showed greater bilateral but left-lateralized engagement of the middle frontal gyrus and superior parietal lobule. The evolution of cortical engagement during five temporal windows across the presentation of stories showed significant involvement during the first interval of the narrative of bilateral opercular and insular regions as well as the ventral and lateral temporal cortex, extending more posteriorly on the left and medially on the right. Over time, there continued to be sustained right anterior ventral temporal engagement, with increasing involvement of the right anterior parahippocampal gyrus, STG, MTG, posterior superior temporal sulcus, inferior parietal lobule, frontal operculum, and insula, while left hemisphere engagement decreased. Our findings are consistent with prior imaging studies of narrative comprehension, but in addition, they demonstrate increasing right-lateralized engagement over the course of narratives, suggesting an important role for these right-hemispheric regions in semantic integration as well as social and pragmatic inference processing.

Network phenotypes and their clinical significance in temporal lobe epilepsy using machine learning applications to morphological and functional graph theory metrics.

Machine learning analyses were performed on graph theory (GT) metrics extracted from brain functional and morphological data from temporal lobe epilepsy (TLE) patients in order to identify intrinsic network phenotypes and characterize their clinical significance. Participants were 97 TLE and 36 healthy controls from the Epilepsy Connectome Project. Each imaging modality (i.e., Resting-state functional Magnetic Resonance Imaging (RS-fMRI), and structural MRI) rendered 2 clusters: one comparable to controls and one deviating from controls. Participants were minimally overlapping across the identified clusters, suggesting that an abnormal functional GT phenotype did not necessarily mean an abnormal morphological GT phenotype for the same subject. Morphological clusters were associated with a significant difference in the estimated lifetime number of generalized tonic-clonic seizures and functional cluster membership was associated with age. Furthermore, controls exhibited significant correlations between functional GT metrics and cognition, while for TLE participants morphological GT metrics were linked to cognition, suggesting a dissociation between higher cognitive abilities and GT-derived network measures. Overall, these findings demonstrate the existence of clinically meaningful minimally overlapping phenotypes of morphological and functional GT networks. Functional network properties may underlie variance in cognition in healthy brains, but in the pathological state of epilepsy the cognitive limits might be primarily related to structural cerebral network properties.

Translingual neural stimulation affects resting-state functional connectivity in mild-moderate traumatic brain injury.

BACKGROUND AND PURPOSE: Traumatic brain injury (TBI) can lead to movement and balance deficits. In addition to physical therapy, brain-based neurorehabilitation efforts have begun to show promise in improving these deficits. The present study investigated the effectiveness of translingual neural stimulation (TLNS) on patients with mild-to-moderate TBI (mmTBI) and related brain connectivity using a resting-state functional connectivity (RSFC) approach. METHODS: Resting-state images with 5-min on GE750 3T scanner were acquired from nine participants with mmTBI. Paired t-test was used for calculating changes in RSFC and behavioral scores before and after the TLNS intervention. The balance and movement performances related to mmTBI were evaluated by Sensory Organization Test (SOT) and Dynamic Gait Index (DGI). RESULTS: Compared to pre-TLNS intervention, significant behavioral changes in SOT and DGI were observed. The analysis revealed increased RSFC between the left postcentral gyrus and left inferior parietal lobule and left Brodmann Area 40, as well as the increased RSFC between the right culmen and right declive, indicating changes due to TLNS treatment. However, there were no correlations between the sensory/somatomotor (or visual or cerebellar) network and SOT/DGI behavioral performance. CONCLUSIONS: Although the limited sample size may have led to lack of significant correlations with functional assessments, these results provide preliminary evidence that TLNS in conjunction with physical therapy can induce brain plasticity in TBI patients with balance and movement deficits.

BCI-FES With Multimodal Feedback for Motor Recovery Poststroke.

An increasing number of research teams are investigating the efficacy of brain-computer interface (BCI)-mediated interventions for promoting motor recovery following stroke. A growing body of evidence suggests that of the various BCI designs, most effective are those that deliver functional electrical stimulation (FES) of upper extremity (UE) muscles contingent on movement intent. More specifically, BCI-FES interventions utilize algorithms that isolate motor signals-user-generated intent-to-move neural activity recorded from cerebral cortical motor areas-to drive electrical stimulation of individual muscles or muscle synergies. BCI-FES interventions aim to recover sensorimotor function of an impaired extremity by facilitating and/or inducing long-term motor learning-related neuroplastic changes in appropriate control circuitry. We developed a non-invasive, electroencephalogram (EEG)-based BCI-FES system that delivers closed-loop neural activity-triggered electrical stimulation of targeted distal muscles while providing the user with multimodal sensory feedback. This BCI-FES system consists of three components: (1) EEG acquisition and signal processing to extract real-time volitional and task-dependent neural command signals from cerebral cortical motor areas, (2) FES of muscles of the impaired hand contingent on the motor cortical neural command signals, and (3) multimodal sensory feedback associated with performance of the behavioral task, including visual information, linked activation of somatosensory afferents through intact sensorimotor circuits, and electro-tactile stimulation of the tongue. In this report, we describe device parameters and intervention protocols of our BCI-FES system which, combined with standard physical rehabilitation approaches, has proven efficacious in treating UE motor impairment in stroke survivors, regardless of level of impairment and chronicity.

Alterations in white matter microstructural properties after lingual strength exercise in patients with dysphagia.

OBJECTIVES: Central nervous system effects of lingual strengthening exercise to treat dysphagia remain largely unknown. This pilot study measured changes in microstructural white matter to capture alterations in neural signal processing following lingual strengthening exercise. METHODS: Diffusion-weighted images were acquired from seven participants with dysphagia of varying etiologies, before and after lingual strengthening exercise (20 reps, 3×/day, 3 days/week, 8 weeks), using a 10-min diffusion sequence (9 b0, 56 directions with b1000) on GE750 3T scanner. Tract-Based Spatial Statistics evaluated voxel-based group differences for fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity and local diffusion homogeneity (LDH). Paired t-tests evaluated treatment differences on each metric (P < 0.05). RESULTS: After lingual strengthening exercise, lingual pressure generation increased (avg increase = 46.1 hPa; nonsignificant P = 0.52) with these changes in imaging metrics: (1) decrease in fractional anisotropy, forceps minor; (2) increase in mean diffusivity, right inferior fronto-occipital fasciculus (IFOF); (3) decrease in mean diffusivity, left uncinate fasciculus; (4) decrease in axial diffusivity, both left IFOF and left uncinate fasciculus; (5) increase in LDH, right anterior thalamic radiation and (6) decrease in LDH, temporal portion of right superior longitudinal fasciculus. There was a positive correlation between diffusion tensor imaging metrics and change in lingual pressure generation in left IFOF and the temporal portion of right superior longitudinal fasciculus. CONCLUSIONS: These findings suggest that lingual strengthening exercise can induce changes in white matter structural and functional properties in a small group of patients with dysphagia of heterogeneous etiologies. These procedures should be repeated with a larger group of patients to improve interpretation of overall lingual strengthening exercise effects on cortical structure and function.

Insights from the IronTract challenge: Optimal methods for mapping brain pathways from multi-shell diffusion MRI.

Limitations in the accuracy of brain pathways reconstructed by diffusion MRI (dMRI) tractography have received considerable attention. While the technical advances spearheaded by the Human Connectome Project (HCP) led to significant improvements in dMRI data quality, it remains unclear how these data should be analyzed to maximize tractography accuracy. Over a period of two years, we have engaged the dMRI community in the IronTract Challenge, which aims to answer this question by leveraging a unique dataset. Macaque brains that have received both tracer injections and ex vivo dMRI at high spatial and angular resolution allow a comprehensive, quantitative assessment of tractography accuracy on state-of-the-art dMRI acquisition schemes. We find that, when analysis methods are carefully optimized, the HCP scheme can achieve similar accuracy as a more time-consuming, Cartesian-grid scheme. Importantly, we show that simple pre- and post-processing strategies can improve the accuracy and robustness of many tractography methods. Finally, we find that fiber configurations that go beyond crossing (e.g., fanning, branching) are the most challenging for tractography. The IronTract Challenge remains open and we hope that it can serve as a valuable validation tool for both users and developers of dMRI analysis methods.

Characterizing the relationship between lesion-activation distance using fMRI and verbal measures in brain tumor patients.

Functional resonance magnetic imaging (fMRI) allows for identification of eloquent cortex in pre-treatment planning. Previous studies have shown a correlation among lesion to activation distance (LAD) measures and morbidity and mortality. This study investigates the relationship between LAD, well-established language centers (Wernicke's and Broca's), and language performance measures. We included a sample population of brain tumor patients that received language fMRI (verbal fluency and sentence verification) for pre-treatment assessment (n = 51). LAD to the nearest language area was measured and divided into groups ≤ 10 mm and > 10 mm. Verbal fluency scores were compared between these groups. Additionally, patients were divided into similar groups based on LAD to either Broca's or Wernicke's areas, and the verbal fluency scores and sentence verification accuracy (n = 29) were subsequently compared between groups. Brain tumor patients with LAD ≤ 10 mm to either language area had significantly lower verbal fluency scores (p = 0.028). The difference in verbal fluency scores between groups with LAD ≤ 10 mm and > 10 mm to Wernicke's area trends toward significance (p = 0.067). The sentence verification accuracy was significantly lower in patients with LAD ≤ 10 mm to either language area (p = 0.039). These findings suggest that there exists a significant relationship between LAD to language centers and measures; greater language deficits are seen when LAD ≤ 10 mm.