Discernible interindividual patterns of global efficiency decline during theoretical brain surgery.

The concept of functional localization within the brain and the associated risk of resecting these areas during removal of infiltrating tumors, such as diffuse gliomas, are well established in neurosurgery. Global efficiency (GE) is a graph theory concept that can be used to simulate connectome disruption following tumor resection. Structural connectivity graphs were created from diffusion tractography obtained from the brains of 80 healthy adults. These graphs were then used to simulate parcellation resection in every gross anatomical region of the cerebrum by identifying every possible combination of adjacent nodes in a graph and then measuring the drop in GE following nodal deletion. Progressive removal of brain parcellations led to patterns of GE decline that were reasonably predictable but had inter-subject differences. Additionally, as expected, there were deletion of some nodes that were worse than others. However, in each lobe examined in every subject, some deletion combinations were worse for GE than removing a greater number of nodes in a different region of the brain. Among certain patients, patterns of common nodes which exhibited worst GE upon removal were identified as "connectotypes". Given some evidence in the literature linking GE to certain aspects of neuro-cognitive abilities, investigating these connectotypes could potentially mitigate the impact of brain surgery on cognition.

Preclinical in vivo animal models of intervertebral disc degeneration. Part 1: A systematic review.

Intervertebral disc degeneration (IVDD), a widely recognized cause of lower back pain, is the leading cause of disability worldwide. A myriad of preclinical in vivo animal models of IVDD have been described in the literature. There is a need for critical evaluation of these models to better inform researchers and clinicians to optimize study design and ultimately, enhance experimental outcomes. The purpose of this study was to conduct an extensive systematic literature review to report the variability of animal species, IVDD induction method, and experimental timepoints and endpoints used in in vivo IVDD preclinical research. A systematic literature review of peer-reviewed manuscripts featured on PubMed and EMBASE databases was conducted in accordance with PRISMA guidelines. Studies were included if they reported an in vivo animal model of IVDD and included details of the species used, how disc degeneration was induced, and the experimental endpoints used for analysis. Two-hundred and fifty-nine (259) studies were reviewed. The most common species, IVDD induction method and experimental endpoint used was rodents(140/259, 54.05%), surgery (168/259, 64.86%) and histology (217/259, 83.78%), respectively. Experimental timepoint varied greatly between studies, ranging from 1 week (dog and rodent models), to >104 weeks in dog, horse, monkey, rabbit, and sheep models. The two most common timepoints used across all species were 4 weeks (49 manuscripts) and 12 weeks (44 manuscripts). A comprehensive discussion of the species, methods of IVDD induction and experimental endpoints is presented. There was great variability across all categories: animal species, method of IVDD induction, timepoints and experimental endpoints. While no animal model can replicate the human scenario, the most appropriate model should be selected in line with the study objectives to optimize experimental design, outcomes and improve comparisons between studies.

Graph Theory Measures and Their Application to Neurosurgical Eloquence.

Improving patient safety and preserving eloquent brain are crucial in neurosurgery. Since there is significant clinical variability in post-operative lesions suffered by patients who undergo surgery in the same areas deemed compensable, there is an unknown degree of inter-individual variability in brain 'eloquence'. Advances in connectomic mapping efforts through diffusion tractography allow for utilization of non-invasive imaging and statistical modeling to graphically represent the brain. Extending the definition of brain eloquence to graph theory measures of hubness and centrality may help to improve our understanding of individual variability in brain eloquence and lesion responses. While functional deficits cannot be immediately determined intra-operatively, there has been potential shown by emerging technologies in mapping of hub nodes as an add-on to existing surgical navigation modalities to improve individual surgical outcomes. This review aims to outline and review current research surrounding novel graph theoretical concepts of hubness, centrality, and eloquence and specifically its relevance to brain mapping for pre-operative planning and intra-operative navigation in neurosurgery.

A connectivity model of the anatomic substrates underlying Gerstmann syndrome.

The Gerstmann syndrome is a constellation of neurological deficits that include agraphia, acalculia, left-right discrimination and finger agnosia. Despite a growing interest in this clinical phenomenon, there remains controversy regarding the specific neuroanatomic substrates involved. Advancements in data-driven, computational modelling provides an opportunity to create a unified cortical model with greater anatomic precision based on underlying structural and functional connectivity across complex cognitive domains. A literature search was conducted for healthy task-based functional MRI and PET studies for the four cognitive domains underlying Gerstmann's tetrad using the electronic databases PubMed, Medline, and BrainMap Sleuth (2.4). Coordinate-based, meta-analytic software was utilized to gather relevant regions of interest from included studies to create an activation likelihood estimation (ALE) map for each cognitive domain. Machine-learning was used to match activated regions of the ALE to the corresponding parcel from the cortical parcellation scheme previously published under the Human Connectome Project (HCP). Diffusion spectrum imaging-based tractography was performed to determine the structural connectivity between relevant parcels in each domain on 51 healthy subjects from the HCP database. Ultimately 102 functional MRI studies met our inclusion criteria. A frontoparietal network was found to be involved in the four cognitive domains: calculation, writing, finger gnosis, and left-right orientation. There were three parcels in the left hemisphere, where the ALE of at least three cognitive domains were found to be overlapping, specifically the anterior intraparietal area, area 7 postcentral (7PC) and the medial intraparietal sulcus. These parcels surround the anteromedial portion of the intraparietal sulcus. Area 7PC was found to be involved in all four domains. These regions were extensively connected in the intraparietal sulcus, as well as with a number of surrounding large-scale brain networks involved in higher-order functions. We present a tractographic model of the four neural networks involved in the functions which are impaired in Gerstmann syndrome. We identified a 'Gerstmann Core' of extensively connected functional regions where at least three of the four networks overlap. These results provide clinically actionable and precise anatomic information which may help guide clinical translation in this region, such as during resective brain surgery in or near the intraparietal sulcus, and provides an empiric basis for future study.

Eigenvector PageRank difference as a measure to reveal topological characteristics of the brain connectome for neurosurgery.

PURPOSE: Applying graph theory to the human brain has the potential to help prognosticate the impacts of intracerebral surgery. Eigenvector (EC) and PageRank (PR) centrality are two related, but uniquely different measures of nodal centrality which may be utilized together to reveal varying neuroanatomical characteristics of the brain connectome. METHODS: We obtained diffusion neuroimaging data from a healthy cohort (UCLA consortium for neuropsychiatric phenomics) and applied a personalized parcellation scheme to them. We ranked parcels based on weighted EC and PR, and then calculated the difference (EP difference) and correlation between the two metrics. We also compared the difference between the two metrics to the clustering coefficient. RESULTS: While EC and PR were consistent for top and bottom ranking parcels, they differed for mid-ranking parcels. Parcels with a high EC centrality but low PR tended to be in the medial temporal and temporooccipital regions, whereas PR conferred greater importance to multi-modal association areas in the frontal, parietal and insular cortices. The EP difference showed a weak correlation with clustering coefficient, though there was significant individual variation. CONCLUSIONS: The relationship between PageRank and eigenvector centrality can identify distinct topological characteristics of the brain connectome such as the presence of unimodal or multimodal association cortices. These results highlight how different graph theory metrics can be used alone or in combination to reveal unique neuroanatomical features for further clinical study.

Delayed, Progressive Multivessel Occlusion After Resection of a Recurrent Glioma.

Glioblastoma multiforme (GBM) is one of the most common primary brain tumors with an aggressive natural history consistent with a median survival of less than two years. Most clinical research has primarily focused on improving overall survival through aggressive cytoreductive surgery and adjuvant radiochemotherapy. However, far less clinical guidance has been given for unexpected instances of neurologic decline following safe glioma resection in the setting of vascular etiology. Here, we report a 50-year-old man who presented to our clinic with a seizure. His preoperative magnetic resonance imaging (MRI) demonstrated a left hippocampal glioblastoma. Ten months following total resection, the patient presented again with rapid loss of vision and hemorrhagic papilledema. An MRI demonstrated a recurrence of his glioma, which was partially resected with no complications. Eight days after surgery, the patient suddenly became unresponsive and imaging revealed moderate blood in the resection cavity, which was evacuated in the operating room. Follow-up scans showed a posterior cerebral artery infarction, and two days later, a middle cerebral artery infarction, upon which care was withdrawn. We do not propose a mechanism by which this delayed ischemia occurred, especially as the middle cerebral artery was not damaged during surgery, however, we note that delayed ischemia may be one mechanism of damage following glioma resection, which should be studied further to improve patient outcomes.

Anatomy and white-matter connections of the precuneus.

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.

Anatomy and White Matter Connections of the Superior Parietal Lobule.

BACKGROUND: The superior parietal lobule (SPL) is involved in somatosensory and visuospatial integration with additional roles in attention, written language, and working memory. A detailed understanding of the exact location and nature of associated white matter tracts could improve surgical decisions and subsequent postoperative morbidity related to surgery in and around this gyrus. OBJECTIVE: To characterize the fiber tracts of the SPL based on relationships to other well-known neuroanatomic structures through diffusion spectrum imaging (DSI)-based fiber tracking validated by gross anatomical dissection as ground truth. METHODS: Neuroimaging data of 10 healthy, adult control subjects was obtained from a publicly accessible database published in Human Connectome Project for subsequent tractographic analyses. White matter tracts were mapped between both cerebral hemispheres, and a lateralization index was calculated based on resultant tract volumes. Post-mortem dissections of 10 cadavers identified the location of major tracts and validated our tractography results based on qualitative visual agreement. RESULTS: We identified 9 major connections of the SPL: U-fiber, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, middle longitudinal fasciculus, extreme capsule, vertical occipital fasciculus, cingulum, and corpus callosum. There was no significant fiber lateralization detected. CONCLUSION: The SPL is an important region implicated in a variety of tasks involving visuomotor and visuospatial integration. Improved understanding of the fiber bundle anatomy elucidated in this study can provide invaluable information for surgical treatment decisions related to this region.

Optimal timing of post-operative enoxaparin after neurosurgery: A single institution experience.

PURPOSE: Venous thromboembolism (VTE) is a well-known problem in patients with intracranial tumors, especially high-grade gliomas. Optimal management of VTE complications is critical given that the development of deep vein thrombosis (DVT) and/or pulmonary embolism can exacerbate medical comorbidities and increase mortality. However, little is known about the optimum time to initiate post-operative anticoagulant prophylaxis. Therefore, there is a keen interest amongst neurosurgeons to develop evidence-based protocols to prevent VTE in post-operative brain tumor patients. METHODS: We retrospectively identified adult patients who underwent elective craniotomy for intracranial tumor resection between 2012 and 2017. Patients were categorized according to the time at which they began receiving prophylactic enoxaparin in the immediate post-operative period, within one day (POD 1), two days (POD 2), three days (POD 3), five days (POD 5), or seven days (POD 7). RESULTS: A total of 1087 patients had a craniotomy for intracranial tumor resection between 2012 and 2017. Multivariate binomial logistic regression analysis demonstrated that initiation of prophylactic enoxaparin within 72 h of surgery was protective against the likelihood of developing a lower extremity DVT (OR: 0.32; CI: 0.10-0.95; p = 0.049) while controlling for possible risk factors for DVTs identified on univariate analysis. Furthermore, complication rates between the anticoagulation and non-anticoagulation groups were not statistically significant. CONCLUSION: Initiating anticoagulant prophylaxis with subcutaneous enoxaparin sodium 40 mg once per day within 72 h of surgery can be done safely while reducing the risk of developing lower extremity DVT.

Anatomy and White Matter Connections of the Middle Frontal Gyrus.

BACKGROUND: The middle frontal gyrus (MFG) is involved in attention, working memory, and language-related processing. A detailed understanding of the subcortical white matter tracts connected within the MFG can facilitate improved navigation of white matter lesions in and around this gyrus and explain the postoperative morbidity after surgery. We aimed to characterize the fiber tracts within the MFG according to their connection to neuroanatomic structures through the use of diffusion spectrum imaging-based fiber tractography and validate the findings by gross anatomic dissection for qualitative visual agreement. METHODS: Tractography analysis was completed using diffusion imaging data from 10 healthy, adult subjects enrolled in the Human Connectome Project. We assessed the MFG as a whole component according to its fiber connectivity with other neural regions. Mapping was completed on all tracts within both hemispheres, with the resultant tract volumes used to calculate a lateralization index. A modified Klingler technique was used on 10 postmortem dissections to demonstrate the location and orientation of the major tracts. RESULTS: Two major connections of the MFG were identified: the superior longitudinal fasciculus, which connects the MFG to parts of the inferior parietal lobule, posterior temporal lobe, and lateral occipital cortex; and the inferior fronto-occipital fasciculus, which connected the MFG to the lingual gyrus and cuneus. Intra- and intergyral short association, U-shaped fibers were also identified. CONCLUSIONS: Subcortical white matter pathways integrated within the MFG include the superior longitudinal fasciculus and inferior fronto-occipital fasciculus. The MFG is implicated in a variety of tasks involving attention and memory, making it an important cortical region. The postoperative neurologic outcomes related to surgery in and around the MFG could be clarified in the context of the anatomy of the fiber bundles highlighted in the present study.

Anatomy and White Matter Connections of the Parahippocampal Gyrus.

BACKGROUND: The parahippocampal gyrus is understood to have a role in high cognitive functions including memory encoding and retrieval and visuospatial processing. A detailed understanding of the exact location and nature of associated white tracts could significantly improve postoperative morbidity related to declining capacity. Through diffusion tensor imaging-based fiber tracking validated by gross anatomic dissection as ground truth, we have characterized these connections based on relationships to other well-known structures. METHODS: Diffusion imaging from the Human Connectome Project for 10 healthy adult controls was used for tractography analysis. We evaluated the parahippocampal gyrus as a whole based on connectivity with other regions. All parahippocampal gyrus tracts were mapped in both hemispheres, and a lateralization index was calculated with resultant tract volumes. RESULTS: We identified 2 connections of the parahippocampal gyrus: inferior longitudinal fasciculus and cingulum. Lateralization of the cingulum was detected (P < 0.05). CONCLUSIONS: The parahippocampal gyrus is an important center for memory processing. Subtle differences in executive functioning following surgery for limbic tumors may be better understood in the context of the fiber-bundle anatomy highlighted by this study.