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Medaglia, J. D.

Publications and source records attributed to Medaglia, J. D..

6 recordsLinked to original sources

Predicting Post-Stroke Aphasia Speech Performance from Multimodal Data with Explainable Machine Learning

Aphasia, an acquired language deficit, is the most common post-stroke focal cognitive impairment, and roughly 60% cases become chronic (duration >6 months). Aphasia therapies could be optimized if clinicians could make personalized predictions of how individual persons with aphasia (PWA) would be likely to perform on particular language tasks. However, current approaches relying on imaging, lesion volume, patient demographics, and clinical scores achieve less than 50% accuracy in predicting performance in PWA. Research algorithms using complex imaging and fMRI can make binary predictions about the presence or absence of aphasia but do not give more clinically relevant information. We aim to predict word-by-word speech accuracy in PWA to better enable personalized speech therapies. To be clinically informative, machine learning models developed for this purpose should use clinically available inputs, explain key features behind a prediction, and generalize to new PWA and previously unseen words. This study combines multimodal input features from clinical testing scores and structural MRI neuroimaging with a novel data source: word-by-word linguistic difficulty. We computed metrics of cognitive burden, such as semantic selection and recall demands, and articulatory burden, such as word length in phonemes and syllables, using naturalistic corpora containing over a billion words of English text. Retrospective training, ten-fold cross validation and 500-run bootstrapping of different machine learning models with various combinations of input features was conducted using 4620 trials. A simplified version of the best model using widely available inputs was deployed clinically through a web app, and prospective generalization was tested on 570 trials with unseen words and different naming tasks in new PWA. We found the best performances with random forest classifiers using linguistic difficulty combined with either clinical information (AUROC {+/-} SEM = 0.87 {+/-} 0.07), or all together with structural imaging connectivity (0.90 {+/-} 0.04). Classifiers using multimodal inputs significantly outperformed others employing single inputs (range 0.66-0.85, p<0.05). Extracting feature importances from the best model showed that Western Aphasia Battery scores, semantic demands, number of phonemes, and syllables were predictive of PWA speech accuracy. Structural integrity in peri-lesional brain regions predicted better language performance whereas higher connectivity of select contralateral homotopes contributed to prediction of worse speech. Without the inclusion of MRI data, lesion volume was a key predictor of PWA speech as well. A simplified, clinically ready, explainable model (publicly available as AphasiaLENS web application) predicted PWA accuracy for any user-entered word, not restricted to a standardized battery. Its prospective generalization performance was not significantly different from the best model using full inputs (AUROC ranges 0.81-0.89, p>0.05). Thus, our research can help inform individualized treatment planning for PWA, while also suggesting research targets through better understanding of brain-behavior relationships.

bioengineering↗

Individual-level Functional ConnectivityPredicts Cognitive Control Efficiency

Cognitive control (CC) is a vital component of cognition associated with problem-solving in everyday life. Many neurological and neuropsychiatric conditions have deficits associated with CC. CC is composed of multiple behaviors including switching, inhibiting, and updating. The fronto-parietal control network B (FPCN-B), the dorsal attention network (DAN), the cingulo-opercular network (CON) and the dorsal default-mode network (dorsal-DMN) have been associated with switching and inhibiting behaviors. However, our understanding of how these brain regions interact to bring about CC behaviors is still unclear. In the current study, participants performed two in-scanner tasks that required switching and inhibiting. We then used a series of support vector regression (SVR) models containing individually-estimated functional connectivity between the networks of interest derived during tasks and at rest to predict inhibition and switching behaviors in individual subjects. We observed that the combination of between-network connectivity from these individually estimated functional networks predicted accurate and timely inhibition and switching behaviors in individuals. We also observed that the relationships between canonical task-positive and task-negative networks predicted inhibiting and switching behaviors. Finally, we observed a functional dissociation between the FPCN-A and FPCNB during rest, and task performance predicted inhibiting and switching behaviors. These results suggest that individually estimated networks can predict individual CC behaviors, that between-network functional connectivity estimated within individuals is vital to understanding how CC arises, and that the fractionation of the FPCN and the DMN may be associated with different behaviors than their canonically accepted behaviors.

neuroscience↗

Glutamate-Weighted Magnetic Resonance Imaging (GluCEST) Detects Effects of Transcranial Magnetic Stimulation to the Motor Cortex

Transcranial magnetic stimulation (TMS) is used in several FDA-approved treatments and, increasingly, to treat neurological disorders in off-label uses. However, the mechanism by which TMS causes physiological change is unclear, as are the origins of response variability in the general population. Ideally, objective in vivo biomarkers could shed light on these unknowns and eventually inform personalized interventions. Continuous theta burst stimulation (cTBS) is a form of TMS which has been observed to reduce motor evoked potentials (MEPs) for 60 minutes or longer post-stimulation, although the consistency of this effect and its mechanism continue to be under debate. Here, we use glutamate-weighted chemical exchange saturation transfer (gluCEST) magnetic resonance imaging (MRI) at ultra-high magnetic field (7T) to measure changes in glutamate concentration at the site of cTBS. We find that gluCEST signal in the ipsilateral hemisphere of the brain generally decreases in response to cTBS, whereas consistent changes were not detected in the contralateral or in subjects receiving a sham stimulation. One Sentence SummaryWe used glutamate-weighted Chemical Exchange Saturation Transfer (GluCEST) imaging to detect changes in glutamate contrast in the brains of young, healthy adults undergoing transcranial magnetic stimulation (TMS) to the motor cortex.

neuroscience↗

Simulated attack reveals how lesions affect network properties in post-stroke aphasia

Aphasia is one of the most prevalent cognitive syndromes caused by stroke. The rarity of premorbid imaging and heterogeneity of lesion size and extent obfuscates the links between the local effects of the lesion, global anatomical network organization, and aphasia symptoms. We applied a simulated attack approach to examine the effects of 39 stroke lesions on network topology by simulating their effects in a control sample of 36 healthy brain networks. We focused on measures of global network organization thought to support overall brain function and resilience in the whole brain and within the left hemisphere. After removing lesion volume from the network topology measures and behavioral scores (the Western Aphasia Battery Aphasia Quotient; WAB-AQ), four behavioral factor scores obtained from a neuropsychological battery, and a factor sum), we compared the behavioral variance accounted for by simulated post-stroke connectomes to that observed in the randomly permuted data. Overall, global measures of network topology in the whole brain and left hemisphere accounted for 10% variance or more of the WAB-AQ and the lexical factor score beyond lesion volume and null permutations. Streamline networks provided more reliable point estimates than FA networks. Edge weights and network efficiency were weighted most highly in predicting the WAB-AQ for FA networks. Overall, our results suggest that global network measures can provide modest statistical value predicting overall aphasia severity, but less value in predicting specific behaviors. Variability in estimates could be induced by premorbid ability, deafferentation and diaschisis, and neuroplasticity following stroke.

neuroscience↗

MXtrodes: MXene-infused bioelectronic interfaces for multiscale electrophysiology and stimulation

Soft bioelectronic interfaces for mapping and modulating excitable networks at high resolution and at large scale can enable paradigm-shifting diagnostics, monitoring, and treatment strategies. Yet, current technologies largely rely on materials and fabrication schemes that are expensive, do not scale, and critically limit the maximum attainable resolution and coverage. Solution processing is a cost-effective manufacturing alternative, but biocompatible conductive inks matching the performance of conventional metals are lacking. Here, we introduce MXtrodes, a novel class of soft, high-resolution, large-scale bioelectronic interfaces enabled by Ti3C2 MXene and scalable solution processing. We show that the electrochemical properties of MXtrodes exceed those of conventional materials, and do not require conductive gels when used in epidermal electronics. Furthermore, we validate MXtrodes in a number of applications ranging from mapping large scale neuromuscular networks in humans to delivering cortical microstimulation in small animal models. Finally, we demonstrate that MXtrodes are compatible with standard clinical neuroimaging modalities.

bioengineering↗

Subgraphs of functional brain networks identify dynamical constraints of cognitive control

Brain anatomy and physiology support the human ability to navigate a complex space of perceptions and actions. To maneuver across an ever-changing landscape of mental states, the brain invokes cognitive control - a set of dynamic processes that engage and disengage different sets of brain regions to modulate attention, switch between tasks, and inhibit prepotent responses. Current theory suggests that cooperative and competitive interactions between brain areas may mediate processes of network reorganization that support transitions between dynamical states. In this study, we used a quantitative approach to identify distinct topological states of functional interactions and examine how their expression relates to cognitive control processes and behavior. In particular, we acquired fMRI BOLD signal in twenty-eight healthy subjects as they performed two cognitive control tasks - a local-global perception switching task using Navon figures and a Stroop interference task - each with low cognitive control demand and high cognitive control demand conditions. Based on these data, we constructed dynamic functional brain networks and used a parts-based network decomposition technique called non-negative matrix factorization to identify putative cognitive control subgraphs whose temporal expression captured key dynamical states involved in control processes. Our results demonstrate that the temporal expression of these functional subgraphs reflect cognitive demands and are associated with individual differences in task-based performance. These findings offer insight into how coordinated changes in the cooperative and competitive roles of distributed brain networks map trajectories between cognitively demanding brain states.

neuroscience↗