The functional role of the precuneus.

Recent advancements in computational approaches and neuroimaging techniques have refined our understanding of the precuneus. While previously believed to be largely a visual processing region, the importance of the precuneus in complex cognitive functions has been previously less familiar due to a lack of focal lesions in this deeply seated region, but also a poor understanding of its true underlying anatomy. Fortunately, recent studies have revealed significant information on the structural and functional connectivity of this region, and this data has provided a more detailed mechanistic understanding of the importance of the precuneus in healthy and pathologic states. Through improved resting-state functional MRI analyses, it has become clear that the function of the precuneus can be better understood based on its functional association with large scale brain networks. Dual default mode network systems have been well explained in recent years in supporting episodic memory and theory of mind; however, a novel 'para-cingulate' network, which is a subnetwork of the larger central executive network, with likely significant roles in self-referential processes and related psychiatric symptoms is introduced here and requires further clarification. Importantly, detailed anatomic studies on the precuneus structural connectivity inside and beyond the cingulate cortex has demonstrated the presence of large structural white matter connections, which provide an additional layer of meaning to the structural-functional significance of this region and its association with large scale brain networks. Together, the structural-functional connectivity of the precuneus has provided central elements which can model various neurodegenerative diseases and psychiatric disorders, such as Alzheimer's disease and depression.

Personalized, parcel-guided non-invasive transcranial magnetic stimulation for the treatment of post-concussive syndrome: safety and proof of concept.

OBJECTIVE: To determine the safety and proof of concept of a parcel-guided, repetitive Transcranial Magnetic Stimulation (rTMS) in patients who develop a heterogeneous array of symptoms, known collectively as post-concussive syndrome (PCS), following traumatic brain injury (TBI). METHODS: We performed a retrospective review of off-label, individualized, parcel-guided rTMS in 19 patients from December 2020 to May 2023. Patients had at least one instance of mild, moderate, or severe TBI and developed symptoms not present prior to injury. rTMS targets were identified based on machine learning connectomic software using functional connectivity anomaly matrices compared to healthy controls. EuroQol (EQ-5D), as a measurement of quality of life, and additional questionnaires dependent on individual's symptoms were submitted prior to, after, and during follow-up from rTMS. RESULTS: Nineteen patients showed improvement in EQ-5D and Rivermead Post Concussion Symptoms Questionnaires - 3 after treatment and follow-up. For nine patients who developed depression, five (55%) attained response and remission based on the Beck Depression Inventory after treatment. Eight of ten patients with anxiety had a clinically significant reduction in Generalized Anxiety Disorder-7 scores during follow-up. CONCLUSION: Parcel-guided rTMS is safe and may be effective in reducing PCS symptoms following TBI and should incite further controlled studies.

Functional connectivity reveals different brain networks underlying the idiopathic foreign accent syndrome.

Foreign accent syndrome (FAS) is characterized by new onset speech that is perceived as foreign. Available data from acquired cases suggests focal brain damage in language and sensorimotor brain networks, but little remains known about abnormal functional connectivity in idiopathic cases of FAS without structural damage. Here, connectomic analyses were completed on three patients with idiopathic FAS to investigate unique functional connectivity abnormalities underlying accent change for the first time. Machine learning (ML)-based algorithms generated personalized brain connectomes based on a validated parcellation scheme from the Human Connectome Project (HCP). Diffusion tractography was performed on each patient to rule out structural fiber damage to the language system. Resting-state-fMRI was assessed with ML-based software to examine functional connectivity between individual parcellations within language and sensorimotor networks and subcortical structures. Functional connectivity matrices were created and compared against a dataset of 200 healthy subjects to identify abnormally connected parcellations. Three female patients (28-42 years) who presented with accent changes from Australian English to Irish (n = 2) or American English to British English (n = 1) demonstrated fully intact language system structural connectivity. All patients demonstrated functional connectivity anomalies within language and sensorimotor networks in numerous left frontal regions and between subcortical structures in one patient. Few commonalities in functional connectivity anomalies were identified between all three patients, specifically 3 internal-network parcellation pairs. No common inter-network functional connectivity anomalies were identified between all patients. The current study demonstrates specific language, and sensorimotor functional connectivity abnormalities can exist and be quantitatively shown in the absence of structural damage 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.

Endoscopic-assisted surgical approach for butterfly glioma surgery.

PURPOSE: Gliomas that spread along the white matter tracts of the corpus callosum to both hemispheres have traditionally been considered surgically challenging largely due to the relative complexity of safely achieving complete resections. We present a series of endoscopic-assisted resections of butterfly gliomas with post-operative radiological assessment of EOR and clinical outcome data. METHODS: Retrospective review of patients who underwent surgical resection of a butterfly glioma from 2007 to 2020. Butterfly gliomas were defined as gliomas, which appeared to arise from the corpus callosum with significant bilateral extension. All records were retrospectively reviewed with operative/clinical outcomes and complications recorded. RESULTS: 70 patients who underwent an endoscopic-assisted transcortical or interhemispheric approach for butterfly glioma resection met inclusion criteria. A unilateral transcortical approach was used in 86% of cases and an interhemispheric approach in 14%. The endoscope enhanced the visualization of the contralateral hemisphere and allowed for resection of tumor, not reached by standard microscopic visualization, in 100% of cases. 90% of resections resulted in greater than a 95% resection rate. Neurological deficits mostly consisted of motor (10%) and memory (6%) deficits and were most common with posterior tumors of the splenium. CONCLUSION: The endoscopic-assisted transcortical or interhemispheric approach for butterfly glioma resection is effective in achieving a greater than 95% resection with minimal complications. An angled approach allows careful maneuvering around complex anatomic structures and difficult corners, and should be examined further for its clinical benefits in a prospective manner.

Transcranial magnetic stimulation for post-operative neurorehabilitation in neuro-oncology: a review of the literature and future directions.

INTRODUCTION: Transcranial magnetic stimulation (TMS) is a neuromodulation technology capable of targeted stimulation and inhibition of cortical areas. Repetitive TMS (rTMS) has demonstrated efficacy in the treatment of several neuropsychiatric disorders, and novel uses of rTMS for neurorehabilitation in patients with acute and chronic neurologic deficits are being investigated. However, studies to date have primarily focused on neurorehabilitation in stroke patients, with little data supporting its use for neurorehabilitation in brain tumor patients. METHODS: We performed a review of the current available literature regarding uses of rTMS for neurorehabilitation in post-operative neuro-oncologic patients. RESULTS: Data have demonstrated that rTMS is safe in the post-operative neuro-oncologic patient population, with minimal adverse effects and no documented seizures. The current evidence also demonstrates potential effectiveness in terms of neurorehabilitation of motor and language deficits. CONCLUSIONS: Although data are overall limited, both safety and effectiveness have been demonstrated for the use of rTMS for neurorehabilitation in the neuro-oncologic population. More randomized controlled trials and specific comparisons of contralateral versus ipsilateral rTMS protocols should be explored. Further work may also focus on individualized, patient-specific TMS treatment protocols for optimal functional recovery.

The Impact of a Mobile Phone Application for Retention of Bleeding Control Skills.

BACKGROUND: The American College of Surgeons Bleeding Control Course (B-Con) empowers bystanders with hemorrhage control skills to manage prehospital emergencies, but demonstrates poor skill retention. The point of care use of a free Stop the Bleed mobile phone application on the retention of hemorrhage control skills from the B-Con Course was explored. METHODS: Convenience sample of college students previously trained in B-Con were randomized into mobile application (MA) or control groups. The use of a mobile application during a simulated emergency scenario with tourniquet and situational awareness skills was assessed. Wound packing skill retention without intervention was also assessed. Survey data allowed for comparison of participant perceptions of skills with actual performances. RESULTS: MA (n = 30) was superior to control (n = 32) in correct tourniquet application (62.5% versus 30.0%; P = 0.01) with longer placement times (163 sec versus 95 sec; P < 0.001) and in calling 911 (31.3% versus 3.3%, P = 0.004). Participants maintain inflated perceptions of their skills, but generally feel underprepared for a future bleeding emergency. CONCLUSIONS: Mobile apps improve tourniquet and situational awareness skills and may serve as potential aids to improve bystander hemorrhage control skills in real-time, but require further prospective investigation into its use.

Simpson's Grading Scale for WHO Grade I Meningioma Resection in the Modern Neurosurgical Era: Are We Really Asking the Right Question?

The Simpson grading scale for the classification of the extent of meningioma resection provided a tremendous movement forward in 1957 suggesting increasing the extent of resection improves recurrence rates. However, equal, if not greater, movements forward have been made in the neurosurgical community over the last half a century owing to improvements in neuroimaging capabilities, microsurgical techniques, and radiotherapeutic strategies. Sughrue et al proposed the idea that these advancements have altered what a "recurrence" and "subtotal resection" truly means in modern neurosurgery compared with Simpson's era, and that a mandated use of the Simpson Scale is likely less clinically relevant today. A subsequent period of debate ensued in the literature which sought to re-examine the clinical value of using the Simpson Scale in modern neurosurgery. While a large body of evidence has recently been provided, these data generally continue to support the clinical importance of gross tumor resection as well as the value of adjuvant radiation therapy and the importance of recently updated World Health Organization classifications. However, there remains a negligible interval benefit in performing overly aggressive surgery and heroic maneuvers to remove the last bit of tumor, dura, and/or bone just for the simple act of achieving a lower Simpson score. Ultimately, meningioma surgery may be better contextualized as a continuous set of weighted risk-benefit decisions throughout the entire operation.

Eloquent noneloquence: redefinition of cortical eloquence based on outcomes of superficial cerebral cavernous malformation resection.

OBJECTIVE: Cerebral cavernous malformations (CMs) are pathological lesions that cause discrete cortical disruption with hemorrhage, and their transcortical resections can cause additional iatrogenic disruption. The analysis of microsurgically treated CMs might identify areas of "eloquent noneloquence," or cortex that is associated with unexpected deficits when injured or transgressed. METHODS: Patients from a consecutive microsurgical series of superficial cerebral CMs who presented to the authors' center over a 13-year period were retrospectively analyzed. Neurological outcomes were measured using the modified Rankin Scale (mRS), and new, permanent neurological or cognitive symptoms not detected by changes in mRS scores were measured as additional functional decline. Patients with multiple lesions and surgical encounters for different lesions within the study interval were represented within the cohort as multiple patient entries. Virtual object models for CMs and approach trajectories to subcortical lesions were merged into a template brain model for subtyping and Quicktome connectomic analyses. Parcellation outputs from the models were analyzed for regional cerebral clustering. RESULTS: Overall, 362 CMs were resected in 346 patients, and convexity subtypes were the most common (132/362, 36.5%). Relative to the preoperative mRS score, 327 of 362 cases (90.3%) were in patients who improved or remained stable, 35 (9.7%) were in patients whose conditions worsened, and 47 (13.0%) were in patients who had additional functional decline. Machine learning analyses of lesion objects and trajectory cylinder mapping identified 7 hotspots of novel eloquence: supplementary motor area (bilateral), anterior cingulate cortex (bilateral), posterior cingulate cortex (bilateral), anterior insula (left), frontal pole (right), mesial temporal lobe (left), and occipital cortex (right). CONCLUSIONS: Transgyral and transsulcal resections that circumvent areas of traditional eloquence and navigate areas of presumed noneloquence may nonetheless result in unfavorable outcomes, demonstrating that brain long considered by neurosurgeons to be noneloquent may be eloquent. Eloquent hotspots within multiple large-scale networks redefine the neurosurgical concept of eloquence and call for more refined dissection techniques that maximize transsulcal dissection, intracapsular resection, and tissue preservation. Human connectomics, awareness of brain networks, and prioritization of cognitive outcomes require that we update our concept of cortical eloquence and incorporate this information into our surgical strategies.

Functional outcomes in MRI-guided laser interstitial therapy for temporal lobe epilepsy: a systematic review and meta-analysis.

OBJECTIVE: The use of MRI-guided laser interstitial thermal therapy (MRgLITT) has emerged as a promising treatment option for patients with drug-resistant temporal lobe epilepsy (TLE). Although the minimally invasive approach holds promise as an effective treatment for achieving seizure freedom, a comprehensive review of its impact on functional outcomes is still warranted. To address this need, this review aims to summarize data pertaining to the functional and neurocognitive outcomes following MRgLITT for TLE. METHODS: Four primary electronic databases were screened following PRISMA guidelines by two independent reviewers. All functional data related to cognitive, behavioral, and emotional outcomes were gathered and analyzed as well as the neuropsychological tests issued to assess pre- and postoperative outcomes. The functional outcomes assessed were grouped into the 5 most common categories: verbal cognition, visual cognition, cognitive emotion, visual deficits, and other higher-order cognitive functioning. RESULTS: A total of 4184 studies were screened and ultimately 408 patients from 14 studies were included for analysis. Changes in functional areas were assessed by comparing pre- and postoperative scores across a comprehensive set of 31 different functional and cognitive assessments, and were tabulated as the percentage of patients whose status improved, declined, or was maintained, where possible. In verbal (n = 112) and visual (n = 42) cognition, the rates of patients experiencing a decline were 20.4% and 13.5%, respectively, and the rates of improvement were 24.9% and 16.7%, respectively. Other functional outcomes assessed, including cognitive emotion (n = 150), visual deficits (n = 325), and higher-order cognitive processes like attention/processing (n = 19), motor cognition (n = 18), and general executive function (n = 4), exhibited varying rates of decline, ranging from 10.5% to 25%. CONCLUSIONS: MRgLITT is an effective and minimally invasive surgical alternative treatment for TLE, but there is an observable impact on patient functioning and cognitive status. This review demonstrates the need for standardized methods that can accurately capture and quantify the associated risk of MRgLITT to optimize its effect on patient quality of life moving forward.

Brain abscesses following carotid blowout syndrome: a case report.

We report a case of intracranial abscesses development in a patient with head and neck cancer after emergent treatment of carotid blowout syndrome with coil embolization. Our patient is a 60-year-old male who presented with hemoptysis and hematemesis, which raised concerns for impending carotid blowout syndrome. Endovascular occlusion was successfully achieved, and the patient was discharged in stable condition. Ten days later, the patient reported headaches and right facial pain, and magnetic resonance imaging revealed multiple intracranial abscesses. Broad-spectrum intravenous antibiotics were administered, leading to a variable response with some abscesses decreasing in size and others increasing. Seven weeks from discharge, the patient had no neurological deficits, and all abscesses had decreased in size.

A parcellation-based connectomic model of hemispatial neglect.

BACKGROUND AND PURPOSE: Hemispatial neglect is characterized by a reduced awareness to stimuli on the contralateral side. Current literature suggesting that damage to the right parietal lobe and attention networks may cause hemispatial neglect is conflicting and can be improved by investigating a connectomic model of the "neglect system" and the anatomical specificity of regions involved in it. METHODS: A meta-analysis of voxel-based morphometry magnetic resonance imaging (MRI) studies of hemispatial neglect was used to identify regions associated with neglect. We applied parcellation schemes to these regions and performed diffusion spectrum imaging (DSI) tractography to determine their connectivity. By overlaying neglect areas and maps of the attention networks, we studied the relationship between them. RESULTS: The meta-analysis generated a list of 13 right hemisphere parcellations. These 13 neglect-related parcellations were predominantly linked by the superior longitudinal fasciculus (SLF) throughout a fronto-parietal-temporal network. We found that the dorsal and ventral attention networks showed partial overlap with the neglect system and included various other higher-order networks. CONCLUSIONS: We provide an anatomically specific connectomic model of the neurobehavioral substrates underlying hemispatial neglect. Our model suggests a fronto-parietal-temporal network linked via the SLF supports the functions impaired in neglect and implicates various higher-order networks which are not limited to the attention networks.

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.

Deconvoluting human Brodmann area 8 based on its unique structural and functional connectivity.

Brodmann area 8 (BA8) is traditionally defined as the prefrontal region of the human cerebrum just anterior to the premotor cortices and enveloping most of the superior frontal gyrus. Early studies have suggested the frontal eye fields are situated at its most caudal aspect, causing many to consider BA8 as primarily an ocular center which controls contralateral gaze and attention. However, years of refinement in cytoarchitectural studies have challenged this traditional anatomical definition, providing a refined definition of its boundaries with neighboring cortical areas and the presence of meaningful subdivisions. Furthermore, functional imaging studies have suggested its involvement in a diverse number of higher-order functions, such as motor, cognition, and language. Thus, our traditional working definition of BA8 has likely been insufficient to truly understand the complex structural and functional significance of this area. Recently, large-scale multi-modal neuroimaging approaches have allowed for improved mapping of the neural connectivity of the human brain. Insight into the structural and functional connectivity of the brain connectome, comprised of large-scale brain networks, has allowed for greater understanding of complex neurological functioning and pathophysiological diseases states. Simultaneously, the structural and functional connectivity of BA8 has recently been highlighted in various neuroimaging studies and detailed anatomic dissections. However, while Brodmann's nomenclature is still widely used today, such as for clinical discussions and the communication of research findings, the importance of the underlying connectivity of BA8 requires further review.

Ischemic Stroke in a Seven-Year-Old Female With Down Syndrome and Newly Discovered Moyamoya Syndrome.

Moyamoya represents a rare, progressive cerebrovascular disease, characterized by a gradual stenosis of the intracranial internal carotid arteries, thereby increasing the risk of stroke. Down syndrome is known to be a predisposing factor for Moyamoya syndrome. This review discusses a distinctive case of a seven-year-old female with Down syndrome who manifested with Moyamoya syndrome, evident from acute stroke-like symptoms.

The Impact of the Addition of a Virtual Reality Trainer on Skill Retention of Tourniquet Application for Hemorrhage Control Among Emergency Medical Technician Students: A Pilot Study.

INTRODUCTION: Trauma is a leading cause of preventable death in the United States. Emergency Medical Technicians (EMTs) often arrive first at the scene of traumatic injuries to perform life-saving skills such as tourniquet placement. While current EMT courses teach and test tourniquet application, studies have shown efficacy and retention of EMT skills such as tourniquet placement decay over time, with educational interventions needed to improve retention of skills. METHODS: A prospective randomized pilot study was conducted to determine differences in retention of tourniquet placement among 40 EMT students after initial training. Participants were randomly assigned to either a virtual reality (VR) intervention or a control group. The VR group received instruction from a refresher VR program 35 days after initial training as a supplement to their EMT course. Both the VR and control participants' tourniquet skills were assessed 70 days after initial training by blinded instructors.  Results: There was no significant difference in correct tourniquet placement between both groups (Control, 63% vs Intervention, 57%, p = 0.57). It was found that 9/21 participants (43%) in the VR intervention group failed to correctly apply the tourniquet while 7/19 of the control participants (37%) failed in tourniquet application. Additionally, the VR group was more likely to fail the tourniquet application due to improper tightening than the control group during the final assessment (p = 0.04).  Conclusion: In this pilot study, using a VR headset in conjunction with in-person training did not improve the efficacy and retention of tourniquet placement skills. Participants who received the VR intervention were more likely to have errors relating to haptics, rather than procedure-related errors.

Connectomic insight into unique stroke patient recovery after rTMS treatment.

An improved understanding of the neuroplastic potential of the brain has allowed advancements in neuromodulatory treatments for acute stroke patients. However, there remains a poor understanding of individual differences in treatment-induced recovery. Individualized information on connectivity disturbances may help predict differences in treatment response and recovery phenotypes. We studied the medical data of 22 ischemic stroke patients who received MRI scans and started repetitive transcranial magnetic stimulation (rTMS) treatment on the same day. The functional and motor outcomes were assessed at admission day, 1 day after treatment, 30 days after treatment, and 90 days after treatment using four validated standardized stroke outcome scales. Each patient underwent detailed baseline connectivity analyses to identify structural and functional connectivity disturbances. An unsupervised machine learning (ML) agglomerative hierarchical clustering method was utilized to group patients according to outcomes at four-time points to identify individual phenotypes in recovery trajectory. Differences in connectivity features were examined between individual clusters. Patients were a median age of 64, 50% female, and had a median hospital length of stay of 9.5 days. A significant improvement between all time points was demonstrated post treatment in three of four validated stroke scales utilized. ML-based analyses identified distinct clusters representing unique patient trajectories for each scale. Quantitative differences were found to exist in structural and functional connectivity analyses of the motor network and subcortical structures between individual clusters which could explain these unique trajectories on the Barthel Index (BI) scale but not on other stroke scales. This study demonstrates for the first time the feasibility of using individualized connectivity analyses in differentiating unique phenotypes in rTMS treatment responses and recovery. This personalized connectomic approach may be utilized in the future to better understand patient recovery trajectories with neuromodulatory treatment.

Use of Cognitive Aids to Augment Point of Care Hemorrhage Control Skills in Laypersons.

OBJECTIVE: The Stop the Bleed course aims to improve bystander hemorrhage control skills and may be improved with point-of-care aids. We sought to create and examine a variety of cognitive aids to identify an optimal method to augment bystander hemorrhage control skills in an emergency scenario. METHODS: Randomized trial of 346 college students. Effects of a visual or visual-audio aid on hemorrhage control skills were assessed through randomization into groups with and without prior training or familiarization with aids compared with controls. Tourniquet placement, wound packing skills, and participant comfortability were assessed during a simulated active shooter scenario. RESULTS: A total of 325 (94%) participants were included in the final analyses. Participants who had attended training (odds ratio [OR], 12.67; P = 9.3 × 10-11), were provided a visual-audio aid (OR, 1.96; P = 0.04), and were primed on their aid (OR, 2.23; P = 0.01) were superior in tourniquet placement with less errors (P < 0.05). Using an aid did not improve wound packing scores compared with bleeding control training alone (P > 0.05). Aid use improved comfortability and likelihood to intervene emergency hemorrhage scenarios (P < 0.05). CONCLUSIONS: Using cognitive aids can improve bystander hemorrhage control skills with the strongest effects if they were previously trained and used an aid which combined visual and audio feedback that they were previously introduced to during the course training.