Effective Connectivity Measured Using Optogenetically Evoked Hemodynamic Signals Exhibits Topography Distinct from Resting State Functional Connectivity in the Mouse.

Brain connectomics has expanded from histological assessment of axonal projection connectivity (APC) to encompass resting state functional connectivity (RS-FC). RS-FC analyses are efficient for whole-brain mapping, but attempts to explain aspects of RS-FC (e.g., interhemispheric RS-FC) based on APC have been only partially successful. Neuroimaging with hemoglobin alone lacks specificity for determining how activity in a population of cells contributes to RS-FC. Wide-field mapping of optogenetically defined connectivity could provide insights into the brain's structure-function relationship. We combined optogenetics with optical intrinsic signal imaging to create an efficient, optogenetic effective connectivity (Opto-EC) mapping assay. We examined EC patterns of excitatory neurons in awake, Thy1-ChR2 transgenic mice. These Thy1-based EC (Thy1-EC) patterns were evaluated against RS-FC over the cortex. Compared to RS-FC, Thy1-EC exhibited increased spatial specificity, reduced interhemispheric connectivity in regions with strong RS-FC, and appreciable connection strength asymmetry. Comparing the topography of Thy1-EC and RS-FC patterns to maps of APC revealed that Thy1-EC more closely resembled APC than did RS-FC. The more general method of Opto-EC mapping with hemoglobin can be determined for 100 sites in single animals in under an hour, and is amenable to other neuroimaging modalities. Opto-EC mapping represents a powerful strategy for examining evolving connectivity-related circuit plasticity.

The Association of Dry Eye Symptom Severity and Comorbid Insomnia in US Veterans.

PURPOSE: To investigate the association between dry eye (DE) and insomnia symptom severity. METHODS: Cross-sectional study of 187 individuals seen in the Miami Veterans Affairs eye clinic. An evaluation was performed consisting of questionnaires regarding insomnia (insomnia severity index [ISI]) and DE symptoms, including ocular pain, followed by a comprehensive ocular surface examination. Using a two-step cluster analysis based on intensity ratings of ocular pain, the patient population was divided into two groups (high and low ocular pain groups: HOP and LOP). A control group was ascertained at the same time from the same clinic as defined by no symptoms of DE (Dry Eye Questionnaire 5 [DEQ5], <6). The main outcome measure was the frequency of moderate or greater insomnia in the DE groups. RESULTS: The mean age of the study sample was 63 years, and 93% were male. All insomnia complaints were rated higher in the HOP group compared with the LOP and control groups (P<0.0005). Most (61%) individuals in the HOP group experienced insomnia of at least moderate severity (ISI≥15) compared with the LOP (41%) and control groups (18%) (P<0.0005). Black race (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.2-6.0; P=0.02), depression severity (OR, 1.2; 95% CI, 1.1-1.3; P<0.0005), and DE symptom severity (DEQ5; OR, 1.1; 95% CI, 1.01-1.2; P=0.03) were significantly associated with clinical insomnia (ISI≥15) after controlling for potential confounders. CONCLUSIONS: After adjusting for demographics and medical comorbidities, we show that DE symptom severity is positively associated with insomnia severity.

Successful Coil Embolization of a Large Anterior Tibial Artery Pseudoaneurysm After Open Reduction Internal Fixation of a Bi-condylar Tibial Plateau Fracture.

Pseudoaneurysms are false aneurysms that consist of turbulent blood flow between the outside layers of the arterial wall, the tunica media and tunica adventitia. Typically, pseudoaneurysms develop after injury to an artery, most often as a result of blunt trauma. Femoral pseudoaneurysms can also develop after catheter-based vascular interventions due to laceration of the artery from access needles, insufficient time or pressure held at the access site after the procedure, amongst other causes. Rarely, arterial injury during orthopedic pinning procedures has been known to cause pseudoaneurysms. There are only two documented cases within the literature in which a patient underwent closed intermedullary nailing of a proximal tibia fracture after trauma and developed an anterior tibial artery pseudoaneurysm. There are few reports of pseudoaneurysm development as the result of external fixation device placement presumably caused by the inability to directly visualize internal anatomy.

Effect of Anti-Vascular Endothelial Growth Factor Therapy on Corneal Nerves.

PURPOSE: Vascular endothelial growth factor (VEGF) is a trophic factor for corneal nerves (CNs). Despite its widespread use to treat a variety of retinal diseases, the effect of repetitive intravitreal (IV) anti-VEGF injections on CN is not known. METHODS: Retrospective case-control study. CN parameters were compared between eyes in 39 individuals who received anti-VEGF injections in one eye only. Next, we compared CN parameters between 50 eyes of 50 individuals with a history of IV anti-VEGF injections and 80 eyes of 80 individuals without a history of injection. In vivo confocal microscopic examination was conducted using the ConfoScan 4. Images were analyzed by the Corneal Nerve Analysis tool. Paired and independent t test methodologies were used to compare nerve parameters, and multivariable linear regression analysis was performed to control for potential confounders. RESULTS: In 39 patients (own controls), eyes with a history of IV injection had lower CN length density, total length, nerve fibers, bifurcations, and branches (P < 0.005) compared to the fellow eyes without injection. Similar findings were seen in the eyes of 50 individuals with a history of injection compared to 80 individuals without injection. A history of IV injections and ethnicity remained significantly associated with the CN length density and explained 32% of the variability (R = 0.56). CONCLUSIONS: We found decreased CN parameters in eyes with a history of anti-VEGF injections compared to eyes without such a history.

Designing a large field-of-view two-photon microscope using optical invariant analysis.

Conventional two-photon microscopy (TPM) is capable of imaging neural dynamics with subcellular resolution, but it is limited to a field-of-view (FOV) diameter [Formula: see text]. Although there has been recent progress in extending the FOV in TPM, a principled design approach for developing large FOV TPM (LF-TPM) with off-the-shelf components has yet to be established. Therefore, we present a design strategy that depends on analyzing the optical invariant of commercially available objectives, relay lenses, mirror scanners, and emission collection systems in isolation. Components are then selected to maximize the space-bandwidth product of the integrated microscope. In comparison with other LF-TPM systems, our strategy simplifies the sequence of design decisions and is applicable to extending the FOV in any microscope with an optical relay. The microscope we constructed with this design approach can image [Formula: see text] lateral and [Formula: see text] axial resolution over a 7-mm diameter FOV, which is a 100-fold increase in FOV compared with conventional TPM. As a demonstration of the potential that LF-TPM has on understanding the microarchitecture of the mouse brain across interhemispheric regions, we performed in vivo imaging of both the cerebral vasculature and microglia cell bodies over the mouse cortex.

Assessment of Somatosensory Function in Patients With Idiopathic Dry Eye Symptoms.

IMPORTANCE: Somatosensory dysfunction likely underlies dry eye (DE) symptoms in many individuals yet remains an understudied component of the disease. Its presence has important diagnostic and therapeutic implications. OBJECTIVE: To assess the integrity of nociceptive system processes in persons with DE and ocular pain using quantitative sensory testing (QST) techniques applied at a site remote from the eye. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study conducted at Miami Veterans Affairs Hospital included 118 individuals with a wide variety of DE symptoms and signs. The study was conducted from October 31, 2013, to January 28, 2016. INTERVENTIONS: Individuals completed questionnaires regarding ocular symptoms (5-Item Dry Eye Questionnaire [DEQ5], Ocular Surface Disease Index [OSDI], and Neuropathic Pain Symptom Inventory modified for the eye [NPSI-E]), psychological status, and medication use and underwent an ocular surface examination. The QST metrics included measures of vibratory and thermal thresholds and cold and hot pain temporal summation (surrogate measures of central sensitization) on the forearm. MAIN OUTCOMES AND MEASURES: Correlations among DE and ocular pain symptom severity with QST metrics measured on the forearm. The OSDI score ranges from 0 to 100, with 100 indicating the most severe DE symptoms. The DEQ5 score ranges from 0 to 22, with the highest score indicating the most severe symptoms, and the NPSI-E score ranges from 0 to 100, with the highest score indicating the most severe symptoms. Psychological state was measured with the 9-item Patient Health Questionnaire, the PTSD Checklist-Military Version for PTSD, and the Symptom Checklist-90 for anxiety. RESULTS: Of the 118 patients who participated in the study, 105 (88.9%) were men (mean [SD] age, 60 [10] years), and a mean of 41% had PTSD, 10% depression, and 0.93% anxiety. Using stepwise linear regression analyses, significant associations were identified between overall DE symptom severity and posttraumatic stress disorder scores and tear breakup time (DEQ5 model: R = 0.54; OSDI model: R = 0.61, P < .001). All other variables (ie, demographics, comorbidities, medications, tear film factors, and QST metrics) dropped out of these models. When specifically considering neuropathic-like qualities of DE pain, however, anxiety and hot pain temporal summation at the forearm explained 17% of the variability in ocular burning (R = 0.41; P < .001), and PTSD score, tear breakup time, and hot pain temporal summation at the forearm explained 25% of the variability in sensitivity to wind (R = 0.50; P < .001) and 30% of the variability in total NPSI-E scores (R = 0.55; P < .001). CONCLUSIONS AND RELEVANCE: Our findings demonstrate that neuropathic-like DE pain symptom severity correlates with quantitative measures of pain sensitivity at a site remote from the eye. This result provides additional evidence that DE symptoms are not only manifestations of a local disorder but also involve somatosensory dysfunction beyond the trigeminal system.