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Humans routinely shift their sleepiness and wakefulness levels in response to emotional factors. The diversity of emotional factors that modulates sleep-wake levels suggests that the ascending arousal network may be intimately linked with networks that mediate mood. Indeed, while animal studies have identified select limbic structures that play a role in sleep-wake regulation, the breadth of corticolimbic structures that directly modulates arousal in humans remains unknown. We investigated whether select regional activation of the corticolimbic network through direct electrical stimulation can modulate sleep-wake levels in humans, as measured by subjective experience and behavior. We performed intensive inpatient stimulation mapping in two human participants with treatment resistant depression, who underwent intracranial implantation with multi-site, bilateral depth electrodes. Stimulation responses of sleep-wake levels were measured by subjective surveys (i.e. Stanford Sleepiness Scale and visual-analog scale of energy) and a behavioral arousal score. Biomarker analyses of sleep-wake levels were performed by assessing spectral power features of resting-state electrophysiology. Our findings demonstrated three regions whereby direct stimulation modulated arousal, including the orbitofrontal cortex (OFC), subgenual cingulate (SGC), and, most robustly, ventral capsule (VC). Modulation of sleep-wake levels was frequency-specific: 100Hz OFC, SGC, and VC stimulation promoted wakefulness, whereas 1Hz OFC stimulation increased sleepiness. Sleep-wake levels were correlated with gamma activity across broad brain regions. Our findings provide evidence for the overlapping circuitry between arousal and mood regulation in humans. Furthermore, our findings open the door to new treatment targets and the consideration of therapeutic neurostimulation for sleep-wake disorders. • Direct electrical stimulation of corticolimbic sites modulates sleep-wake levels in humans. • Stimulation response of sleep-wake levels is frequency specific. • Gamma activity across multiple subregions is associated with increased wakefulness. • Neurostimulation strategies for refractory sleep-wake disorders may be feasible. [ABSTRACT FROM AUTHOR]

Recent decades have seen a steady increase in noncontrast head CT utilization in the emergency department with a concurrent rise in the practice of physician assistants (PAs) and nurse practitioners (NPs). The goal of this study was to identify ordering and patient characteristics predictive of positive noncontrast head CTs in the ED. We hypothesized NP/PAs would have lower positivity rates compared to physicians, suggestive of relative overutilization. We retrospectively identified ED patients who underwent noncontrast head CTs at a single institution: a nonlevel 1 trauma center, during a 7-year period, recording examination positivity, ordering provider training/experience, and multiple additional ordering/patient attributes. Exam positivity was defined as any intracranial abnormality necessitating a change in acute management, such as acute hemorrhage, hydrocephalus, herniation, or worsening prior findings. 6624 patients met inclusion criteria. 4.6% (280/6107) of physician exams were positive while 3.7% (19/517) of NP/PA exams were positive; however, differences were not significant. Increasing provider experience was not associated with positivity. Attributes with increased positivity were patient age (p < 0.001), daytime exam (p < 0.05), and indications regarding malignancy (p < 0.001) or focal neurologic deficit (p = 0.001). Attributes with decreased positivity were indications of trauma (p < 0.001) or vertigo/dizziness (p < 0.05). We found no significant difference in rates of exam positivity between physicians and NP/PAs, even accounting for years of experience. This suggests increasing utilization of head CTs in the ED is not due to the increasing presence of NP/PAs, and may be reflective of general practice trends and clear diagnostic algorithms leading to head CT. [ABSTRACT FROM AUTHOR]

Coarse measures of socioeconomic status, such as parental income or parental education, have been linked to differences in white matter development. However, these measures do not provide insight into specific aspects of an individual's environment and how they relate to brain development. On the other hand, educational intervention studies have shown that changes in an individual's educational context can drive measurable changes in their white matter. These studies, however, rarely consider socioeconomic factors in their results. In the present study, we examined the unique relationship between educational opportunity and white matter development, when controlling other known socioeconomic factors. To explore this question, we leveraged the rich demographic and neuroimaging data available in the ABCD study, as well the unique data-crosswalk between ABCD and the Stanford Education Data Archive (SEDA). We find that educational opportunity is related to accelerated white matter development, even when accounting for other socioeconomic factors, and that this relationship is most pronounced in white matter tracts associated with academic skills. These results suggest that the school a child attends has a measurable relationship with brain development for years to come. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: An increasing number of neurological complications and corresponding radiological findings have been reported in patients with COVID-19 infection. The purpose of this study is to systematically review the current literature on COVID-19-associated neuroradiological findings and examine the prevalence of different findings in patients with both severe and mild COVID-19 infection.Materials and Methods: A comprehensive literature search of the PubMed and Embase databases was performed. Any studies reporting CT or MRI neuroimaging findings in patients with confirmed COVID-19 infection were included. Patient demographics, main radiological findings, neurological symptoms, and severity of COVID-19 infection were tabulated and quantified according to infection severity.Results: Sixty-one studies published between 2019 and 2020 comprising 711 patients were analyzed according to severity of respiratory symptoms. The main neuroradiological findings for patients with mild classification were cranial nerve abnormalities, ischemic infarction, and white matter abnormalities, while the main findings in patients with severe classification were white matter abnormalities, ischemic infarction, and hemorrhagic events.Conclusion: Neuroradiological manifestations in COVID-19 infection are highly heterogeneous and differ based on the severity of COVID-19 infection. Cranial nerve abnormalities appear exclusive to mild infection, with a high degree of olfactory tract involvement, while hemorrhagic events are more common in severe infection. Notably, ischemic infarction was equally prevalent in both mild and severe COVID-19 infection. Healthcare providers treating COVID-19 patients should be aware of these potential complications and consider neurological assessment and neuroimaging studies when indicated. [ABSTRACT FROM AUTHOR]

Cross-sectional studies have linked differences in white matter tissue properties to reading skills. However, past studies have reported a range of, sometimes conflicting, results. Some studies suggest that white matter properties act as individual-level traits predictive of reading skill, whereas others suggest that reading skill and white matter develop as a function of an individual's educational experience. In the present study, we tested two hypotheses: a) that diffusion properties of the white matter reflect stable brain characteristics that relate to stable individual differences in reading ability or b) that white matter is a dynamic system, linked with learning over time. To answer these questions, we examined the relationship between white matter and reading in a five-year longitudinal dataset and a series of large-scale, single-observation, cross-sectional datasets (N = 14,249 total participants). We find that gains in reading skill correspond to longitudinal changes in the white matter. However, in the cross-sectional datasets, we find no evidence for the hypothesis that individual differences in white matter predict reading skill. These findings highlight the link between dynamic processes in the white matter and learning. [ABSTRACT FROM AUTHOR]

During late childhood behavioral changes, such as increased risk-taking and emotional reactivity, have been associated with the maturation of cortico-cortico and cortico-subcortical circuits. Understanding microstructural changes in both white matter and subcortical regions may aid our understanding of how individual differences in these behaviors emerge. Restriction spectrum imaging (RSI) is a framework for modelling diffusion-weighted imaging that decomposes the diffusion signal from a voxel into hindered, restricted, and free compartments. This yields greater specificity than conventional methods of characterizing diffusion. Using RSI, we quantified voxelwise restricted diffusion across the brain and measured age associations in a large sample (n = 8086) from the Adolescent Brain and Cognitive Development (ABCD) study aged 9–14 years. Older participants showed a higher restricted signal fraction across the brain, with the largest associations in subcortical regions, particularly the basal ganglia and ventral diencephalon. Importantly, age associations varied with respect to the cytoarchitecture within white matter fiber tracts and subcortical structures, for example age associations differed across thalamic nuclei. This suggests that age-related changes may map onto specific cell populations or circuits and highlights the utility of voxelwise compared to ROI-wise analyses. Future analyses will aim to understand the relevance of this microstructural developmental for behavioral outcomes. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) and schizophrenia (SCZ) are heritable brain disorders that involve dysregulation of the dopaminergic system. Epidemiological studies have reported potential comorbidity between the disorders, and movement disturbances are common in patients with SCZ before treatment with antipsychotic drugs. Despite this, little is known about shared genetic etiology between the disorders. We analyzed recent large genome-wide association studies on patients with SCZ (N = 77,096) and PD (N = 417,508) using a conditional/conjunctional false discovery rate (FDR) approach to evaluate overlap in common genetic variants and improve statistical power for genetic discovery. Using a variety of biological resources, we functionally characterized the identified genomic loci. We observed genetic enrichment in PD conditional on associations with SCZ and vice versa, indicating polygenic overlap. We then leveraged this cross-trait enrichment using conditional FDR analysis and identified 9 novel PD risk loci and 1 novel SCZ locus at conditional FDR <.01. Furthermore, we identified 9 genomic loci jointly associated with PD and SCZ at conjunctional FDR <.05. There was an even distribution of antagonistic and agonistic effect directions among the shared loci, in line with the insignificant genetic correlation between the disorders. Of 67 genes mapped to the shared loci, 65 are expressed in the human brain and show cell type–specific expression profiles. Altogether, the study increases understanding of the genetic architectures underlying SCZ and PD, indicating that common molecular genetic mechanisms may contribute to overlapping pathophysiological and clinical features between the disorders. [ABSTRACT FROM AUTHOR]