Association of Dynamic Trajectories of Time-Series Data and Life-Threatening Mass Effect in Large Middle Cerebral Artery Stroke.

Background: Life-threatening, space-occupying mass effect due to cerebral edema and/or hemorrhagic transformation is an early complication of patients with middle cerebral artery stroke. Little is known about longitudinal trajectories of laboratory and vital signs leading up to radiographic and clinical deterioration related to this mass effect.

Methods: We curated a retrospective data set of 635 patients with large middle cerebral artery stroke totaling 95,463 data points for 10 longitudinal covariates and 40 time-independent covariates.

Association of large core middle cerebral artery stroke and hemorrhagic transformation with hospitalization outcomes.

Historically, investigators have not differentiated between patients with and without hemorrhagic transformation (HT) in large core ischemic stroke at risk for life-threatening mass effect (LTME) from cerebral edema. Our objective was to determine whether LTME occurs faster in those with HT compared to those without. We conducted a two-center retrospective study of patients with ≥ 1/2 MCA territory infarct between 2006 and 2021.

Brain orchestra under spontaneous conditions: Identifying communication modules from the functional architecture of area V1.

We used two-photon imaging to record from granular and supragranular layers in mouse primary visual cortex (V1) under spontaneous conditions and applied an extension of the spike time tiling coefficient (STTC; introduced by Cutts and Eglen) to map functional connectivity architecture within and across layers. We made several observations: Approximately, 19-34% of neuronal pairs within 300 m of each other exhibit statistically significant functional connections, compared to ~10% at distances of 1mm or more. As expected, neuronal pairs with similar tuning functions exhibit a significant, though relatively small, increase in the fraction of functional inter-neuronal correlations.

Follow-up ASPECTS improves prediction of potentially lethal malignant edema in patients with large middle cerebral artery stroke.

Background: Recent studies have shown that follow-up head CT is a strong predictor of functional outcomes in patients with middle cerebral artery stroke and mechanical thrombectomy. We sought to determine whether total and/or regional follow-up Alberta Stroke Program Early CT Score (ASPECTS) are associated with important clinical outcomes during hospitalization and improve the performance of clinical prediction models of potentially lethal malignant edema (PLME).

Methods: We conducted a retrospective study of patients at three medical centers in a major North American metropolitan area with baseline and follow-up head CTs after large middle cerebral artery stroke between 2006 and 2022.

Tug-of-Peace: Visual Rivalry and Atypical Visual Motion Processing in MECP2 Duplication Syndrome of Autism.

Extracting common patterns of neural circuit computations in the autism spectrum and confirming them as a cause of specific core traits of autism is the first step toward identifying cell-level and circuit-level targets for effective clinical intervention. Studies in humans with autism have identified functional links and common anatomic substrates between core restricted behavioral repertoire, cognitive rigidity, and overstability of visual percepts during visual rivalry. To study these processes with single-cell precision and comprehensive neuronal population coverage, we developed the visual bistable perception paradigm for mice based on ambiguous moving plaid patterns consisting of two transparent gratings drifting at an angle of 120°.

Glioma genetic profiles associated with electrophysiologic hyperexcitability.

Background: Distinct genetic alterations determine glioma aggressiveness, however, the diversity of somatic mutations contributing to peritumoral hyperexcitability and seizures over the course of the disease is uncertain. This study aimed to identify tumor somatic mutation profiles associated with clinically significant hyperexcitability.

Methods: A single center cohort of adults with WHO grades 1-4 glioma and targeted exome sequencing (n = 1716) was analyzed and cross-referenced with a validated EEG database to identify the subset of individuals who underwent continuous EEG monitoring (n = 206).

Glioma genetic profiles associated with electrophysiologic hyperexcitability.

Distinct genetic alterations determine glioma aggressiveness, however the diversity of somatic mutations contributing to peritumoral hyperexcitability and seizures is uncertain. In a large cohort of patients with sequenced gliomas (n=1716), we used discriminant analysis models to identify somatic mutation variants associated with electrographic hyperexcitability in a subset with continuous EEG recording (n=206). Overall tumor mutational burdens were similar between patients with and without hyperexcitability.

Quantitative pupillometry and radiographic markers of intracranial midline shift: A pilot study.

Background: Asymmetric pupil reactivity or size can be early clinical indicators of midbrain compression due to supratentorial ischemic stroke or primary intraparenchymal hemorrhage (IPH). Radiographic midline shift is associated with worse functional outcomes and life-saving interventions. Better understanding of quantitative pupil characteristics would be a non-invasive, safe, and cost-effective way to improve identification of life-threatening mass effect and resource utilization of emergent radiographic imaging.

Increased Reliability of Visually-Evoked Activity in Area V1 of the MECP2-Duplication Mouse Model of Autism.

Atypical sensory processing is now thought to be a core feature of the autism spectrum. Influential theories have proposed that both increased and decreased neural response reliability within sensory systems could underlie altered sensory processing in autism. Here, we report evidence for abnormally increased reliability of visual-evoked responses in layer 2/3 neurons of adult male and female primary visual cortex in the MECP2-duplication syndrome animal model of autism.

Dexmedetomidine and Other Analgosedatives Alter Pupil Characteristics in Critically Ill Patients.

Unlabelled: In critically ill patients with neurologic disease, pupil examination abnormalities can signify evolving intracranial pathology. Analgesic and sedative medications (analgosedatives) target pupillary pathways, but it remains unknown how analgosedatives alter pupil findings in the clinical care setting. We assessed dexmedetomidine and other analgosedative associations with pupil reactivity and size in a heterogeneous cohort of critically ill patients with acute intracranial pathology.

Natural Language Processing of Radiology Reports to Detect Complications of Ischemic Stroke.

Background: Abstraction of critical data from unstructured radiologic reports using natural language processing (NLP) is a powerful tool to automate the detection of important clinical features and enhance research efforts. We present a set of NLP approaches to identify critical findings in patients with acute ischemic stroke from radiology reports of computed tomography (CT) and magnetic resonance imaging (MRI).

Methods: We trained machine learning classifiers to identify categorical outcomes of edema, midline shift (MLS), hemorrhagic transformation, and parenchymal hematoma, as well as rule-based systems (RBS) to identify intraventricular hemorrhage (IVH) and continuous MLS measurements within CT/MRI reports.

Visual Motion Coherence Responses in Human Visual Cortex.

Random dot kinematograms (RDKs) have recently been used to train subjects with cortical scotomas to perform direction of motion discrimination, partially restoring visual motion perception. To study the recovery of visual perception, it is important to understand how visual areas in normal subjects and subjects with cortical scotomas respond to RDK stimuli. Studies in normal subjects have shown that blood oxygen level-dependent (BOLD) responses in human area hV5/MT+ increase monotonically with coherence, in general agreement with electrophysiology studies in primates.

Macaque Area V2/V3 Reorganization Following Homonymous Retinal Lesions.

In the adult visual system, topographic reorganization of the primary visual cortex (V1) after retinal lesions has been extensively investigated. In contrast, the plasticity of higher order extrastriate areas following retinal lesions is less well studied. Here, we used fMRI to study reorganization of visual areas V2/V3 following the induction of permanent, binocular, homonymous retinal lesions in 4 adult macaque monkeys.

Anisocoria and Poor Pupil Reactivity by Quantitative Pupillometry in Patients With Intracranial Pathology.

Objectives: To describe the prevalence and associated risk factors of new onset anisocoria (new pupil size difference of at least 1 mm) and its subtypes: new onset anisocoria accompanied by abnormal and normal pupil reactivities in patients with acute neurologic injuries.

Design: We tested the association of patients who experienced new onset anisocoria subtypes with degree of midline shift using linear regression. We further explored differences between quantitative pupil characteristics associated with first-time new onset anisocoria and nonnew onset anisocoria at preceding observations using mixed effects logistic regression, adjusting for possible confounders.

Inhibition of Elevated Ras-MAPK Signaling Normalizes Enhanced Motor Learning and Excessive Clustered Dendritic Spine Stabilization in the MECP2-Duplication Syndrome Mouse Model of Autism.

The inflexible repetitive behaviors and "insistence on sameness" seen in autism imply a defect in neural processes controlling the balance between stability and plasticity of synaptic connections in the brain. It has been proposed that abnormalities in the Ras-ERK/MAPK pathway, a key plasticity-related cell signaling pathway known to drive consolidation of clustered synaptic connections, underlie altered learning phenotypes in autism. However, a link between altered Ras-ERK signaling and clustered dendritic spine plasticity has yet to be explored in an autism animal model The formation and stabilization of dendritic spine clusters is abnormally increased in the MECP2-duplication syndrome mouse model of syndromic autism, suggesting that ERK signaling may be increased.

Excessive Formation and Stabilization of Dendritic Spine Clusters in the -Duplication Syndrome Mouse Model of Autism.

Autism-associated genetic mutations may perturb the balance between stability and plasticity of synaptic connections in the brain. Here, we report an increase in the formation and stabilization of dendritic spines in the cerebral cortex of the mouse model of -duplication syndrome, a high-penetrance form of syndromic autism. Increased stabilization is mediated entirely by spines that form cooperatively in 10-μm clusters and is observable across multiple cortical areas both spontaneously and following motor training.

Characteristics and Outcomes of Latinx Patients With COVID-19 in Comparison With Other Ethnic and Racial Groups.

Background: There is a limited understanding of the impact of coronavirus disease 2019 (COVID-19) on the Latinx population. We hypothesized that Latinx patients would be more likely to be hospitalized and admitted to the intensive care unit (ICU) than White patients.

Methods: We analyzed all patients with COVID-19 in 12 Massachusetts hospitals between February 1 and April 14, 2020.

Contribution of apical and basal dendrites to orientation encoding in mouse V1 L2/3 pyramidal neurons.

Pyramidal neurons integrate synaptic inputs from basal and apical dendrites to generate stimulus-specific responses. It has been proposed that feed-forward inputs to basal dendrites drive a neuron's stimulus preference, while feedback inputs to apical dendrites sharpen selectivity. However, how a neuron's dendritic domains relate to its functional selectivity has not been demonstrated experimentally.

The Visual Cortex in Context.

In this article, we review the anatomical inputs and outputs to the mouse primary visual cortex, area V1. Our survey of data from the Allen Institute Mouse Connectivity project indicates that mouse V1 is highly interconnected with both cortical and subcortical brain areas. This pattern of innervation allows for computations that depend on the state of the animal and on behavioral goals, which contrasts with simple feedforward, hierarchical models of visual processing.

Inhibitory Units: An Organizing Nidus for Feature-Selective SubNetworks in Area V1.

Neuronal circuits often display small-world network architecture characterized by neuronal cliques of dense local connectivity communicating with each other through a limited number of cells that participate in multiple cliques. The principles by which such cliques organize to encode information remain poorly understood. Similarly tuned pyramidal cells that preferentially target each other may form multicellular encoding units performing distinct computational tasks.

Estimating average single-neuron visual receptive field sizes by fMRI.

The noninvasive estimation of neuronal receptive field (RF) properties in vivo allows a detailed understanding of brain organization as well as its plasticity by longitudinal following of potential changes. Visual RFs measured invasively by electrophysiology in animal models have traditionally provided a great extent of our current knowledge about the visual brain and its disorders. Voxel-based estimates of population RF (pRF) by functional magnetic resonance imaging (fMRI) in humans revolutionized the field and have been used extensively in numerous studies.

Internal Gain Modulations, But Not Changes in Stimulus Contrast, Preserve the Neural Code.

Neurons in primary visual cortex are strongly modulated both by stimulus contrast and by fluctuations of internal inputs. An important question is whether the population code is preserved under these conditions. Changes in stimulus contrast are thought to leave the population code invariant, whereas the effect of internal gain modulations remains unknown.

Increased Axonal Bouton Stability during Learning in the Mouse Model of MECP2 Duplication Syndrome.

duplication syndrome is an X-linked form of syndromic autism caused by genomic duplication of the region encoding methyl-CpG-binding protein 2 (MECP2). Mice overexpressing demonstrate social impairment, behavioral inflexibility, and altered patterns of learning and memory. Previous work showed abnormally increased stability of dendritic spines formed during motor training in the apical tuft of primary motor cortex (area M1) corticospinal neurons in the MECP2 duplication mouse model.