Isabella M. Young

Bio: Isabella M. Young is an academic researcher. The author has contributed to research in topics: Medicine & Tractography. The author has an hindex of 4, co-authored 31 publications receiving 55 citations.

The Frontal Aslant Tract and Supplementary Motor Area Syndrome: Moving towards a Connectomic Initiation Axis

Abstract: Connectomics is the use of big data to map the brain's neural infrastructure; employing such technology to improve surgical planning may improve neuro-oncological outcomes. Supplementary motor area (SMA) syndrome is a well-known complication of medial frontal lobe surgery. The 'localizationist' view posits that damage to the posteromedial bank of the superior frontal gyrus (SFG) is the basis of SMA syndrome. However, surgical experience within the frontal lobe suggests that this is not entirely true. In a study on n = 45 patients undergoing frontal lobe glioma surgery, we sought to determine if a 'connectomic' or network-based approach can decrease the likelihood of SMA syndrome. The control group (n = 23) underwent surgery avoiding the posterior bank of the SFG while the treatment group (n = 22) underwent mapping of the SMA network and Frontal Aslant Tract (FAT) using network analysis and DTI tractography. Patient outcomes were assessed post operatively and in subsequent follow-ups. Fewer patients (8.3%) in the treatment group experienced transient SMA syndrome compared to the control group (47%) (p = 0.003). There was no statistically significant difference found between the occurrence of permanent SMA syndrome between control and treatment groups. We demonstrate how utilizing tractography and a network-based approach decreases the likelihood of transient SMA syndrome during medial frontal glioma surgery. We found that not transecting the FAT and the SMA system improved outcomes which may be important for functional outcomes and patient quality of life.

Anatomy and white-matter connections of the precuneus

Abstract: Purpose Advances in neuroimaging have provided an understanding of the precuneus’(PCu) involvement in functions such as visuospatial processing and cognition. While the PCu has been previously determined to be apart of a higher-order default mode network (DMN), recent studies suggest the presence of possible dissociations from this model in order to explain the diverse functions the PCu facilitates, such as in episodic memory. An improved structural model of the white-matter anatomy of the PCu can demonstrate its unique cerebral connections with adjacent regions which can provide additional clarity on its role in integrating information across higher-order cerebral networks like the DMN. Furthermore, this information can provide clinically actionable anatomic information that can support clinical decision making to improve neurologic outcomes such as during cerebral surgery. Here, we sought to derive the relationship between the precuneus and underlying major white-mater bundles by characterizing its macroscopic connectivity. Methods Structural tractography was performed on twenty healthy adult controls from the Human Connectome Project (HCP) utilizing previously demonstrated methodology. All precuneus connections were mapped in both cerebral hemispheres and inter-hemispheric differences in resultant tract volumes were compared with an unpaired, corrected Mann–Whitney U test and a laterality index (LI) was completed. Ten postmortem dissections were then performed to serve as ground truth by using a modified Klingler technique with careful preservation of relevant white matter bundles. Results The precuneus is a heterogenous cortical region with five major types of connections that were present bilaterally. (1) Short association fibers connect the gyri of the precuneus and connect the precuneus to the superior parietal lobule and the occipital cortex. (2) Four distinct parts of the cingulum bundle connect the precuneus to the frontal lobe and the temporal lobe. (3) The middle longitudinal fasciculus from the precuneus connects to the superior temporal gyrus and the dorsolateral temporal pole. (4) Parietopontine fibers travel as part of the corticopontine fibers to connect the precuneus to pontine regions. (5) An extensive commissural bundle connects the precuneus bilaterally. Conclusion We present a summary of the anatomic connections of the precuneus as part of an effort to understand the function of the precuneus and highlight key white-matter pathways to inform surgical decision-making. Our findings support recent models suggesting unique fiber connections integrating at the precuneus which may suggest finer subsystems of the DMN or unique networks, but further study is necessary to refine our model in greater quantitative detail.

Advances in microfluidic in vitro systems for neurological disease modeling

Abstract: Neurological disorders are the leading cause of disability and the second largest cause of death worldwide. Despite significant research efforts, neurology remains one of the most failure-prone areas of drug development. The complexity of the human brain, boundaries to examining the brain directly in vivo, and the significant evolutionary gap between animal models and humans, all serve to hamper translational success. Recent advances in microfluidic in vitro models have provided new opportunities to study human cells with enhanced physiological relevance. The ability to precisely micro-engineer cell-scale architecture, tailoring form and function, has allowed for detailed dissection of cell biology using microphysiological systems (MPS) of varying complexities from single cell systems to "Organ-on-chip" models. Simplified neuronal networks have allowed for unique insights into neuronal transport and neurogenesis, while more complex 3D heterotypic cellular models such as neurovascular unit mimetics and "Organ-on-chip" systems have enabled new understanding of metabolic coupling and blood-brain barrier transport. These systems are now being developed beyond MPS toward disease specific micro-pathophysiological systems, moving from "Organ-on-chip" to "Disease-on-chip." This review gives an outline of current state of the art in microfluidic technologies for neurological disease research, discussing the challenges and limitations while highlighting the benefits and potential of integrating technologies. We provide examples of where such toolsets have enabled novel insights and how these technologies may empower future investigation into neurological diseases.

Reducing the Cognitive Footprint of Brain Tumor Surgery.

Abstract: The surgical management of brain tumors is based on the principle that the extent of resection improves patient outcomes. Traditionally, neurosurgeons have considered that lesions in "non-eloquent" cerebrum can be more aggressively surgically managed compared to lesions in "eloquent" regions with more known functional relevance. Furthermore, advancements in multimodal imaging technologies have improved our ability to extend the rate of resection while minimizing the risk of inducing new neurologic deficits, together referred to as the "onco-functional balance." However, despite the common utilization of invasive techniques such as cortical mapping to identify eloquent tissue responsible for language and motor functions, glioma patients continue to present post-operatively with poor cognitive morbidity in higher-order functions. Such observations are likely related to the difficulty in interpreting the highly-dimensional information these technologies present to us regarding cognition in addition to our classically poor understanding of the functional and structural neuroanatomy underlying complex higher-order cognitive functions. Furthermore, reduction of the brain into isolated cortical regions without consideration of the complex, interacting brain networks which these regions function within to subserve higher-order cognition inherently prevents our successful navigation of true eloquent and non-eloquent cerebrum. Fortunately, recent large-scale movements in the neuroscience community, such as the Human Connectome Project (HCP), have provided updated neural data detailing the many intricate macroscopic connections between cortical regions which integrate and process the information underlying complex human behavior within a brain "connectome." Connectomic data can provide us better maps on how to understand convoluted cortical and subcortical relationships between tumor and human cerebrum such that neurosurgeons can begin to make more informed decisions during surgery to maximize the onco-functional balance. However, connectome-based neurosurgery and related applications for neurorehabilitation are relatively nascent and require further work moving forward to optimize our ability to add highly valuable connectomic data to our surgical armamentarium. In this manuscript, we review four concepts with detailed examples which will help us better understand post-operative cognitive outcomes and provide a guide for how to utilize connectomics to reduce cognitive morbidity following cerebral surgery.