The neuroconnectionist research programme.

Artificial neural networks (ANNs) inspired by biology are beginning to be widely used to model behavioural and neural data, an approach we call 'neuroconnectionism'. ANNs have been not only lauded as the current best models of information processing in the brain but also criticized for failing to account for basic cognitive functions. In this Perspective article, we propose that arguing about the successes and failures of a restricted set of current ANNs is the wrong approach to assess the promise of neuroconnectionism for brain science. Instead, we take inspiration from the philosophy of science, and in particular from Lakatos, who showed that the core of a scientific research programme is often not directly falsifiable but should be assessed by its capacity to generate novel insights. Following this view, we present neuroconnectionism as a general research programme centred around ANNs as a computational language for expressing falsifiable theories about brain computation. We describe the core of the programme, the underlying computational framework and its tools for testing specific neuroscientific hypotheses and deriving novel understanding. Taking a longitudinal view, we review past and present neuroconnectionist projects and their responses to challenges and argue that the research programme is highly progressive, generating new and otherwise unreachable insights into the workings of the brain.

Causal mapping of human brain function.

Mapping human brain function is a long-standing goal of neuroscience that promises to inform the development of new treatments for brain disorders. Early maps of human brain function were based on locations of brain damage or brain stimulation that caused a functional change. Over time, this approach was largely replaced by technologies such as functional neuroimaging, which identify brain regions in which activity is correlated with behaviours or symptoms. Despite their advantages, these technologies reveal correlations, not causation. This creates challenges for interpreting the data generated from these tools and using them to develop treatments for brain disorders. A return to causal mapping of human brain function based on brain lesions and brain stimulation is underway. New approaches can combine these causal sources of information with modern neuroimaging and electrophysiology techniques to gain new insights into the functions of specific brain areas. In this Review, we provide a definition of causality for translational research, propose a continuum along which to assess the relative strength of causal information from human brain mapping studies and discuss recent advances in causal brain mapping and their relevance for developing treatments.

A role for cortical interneurons as adversarial discriminators.

The brain learns representations of sensory information from experience, but the algorithms by which it does so remain unknown. One popular theory formalizes representations as inferred factors in a generative model of sensory stimuli, meaning that learning must improve this generative model and inference procedure. This framework underlies many classic computational theories of sensory learning, such as Boltzmann machines, the Wake/Sleep algorithm, and a more recent proposal that the brain learns with an adversarial algorithm that compares waking and dreaming activity. However, in order for such theories to provide insights into the cellular mechanisms of sensory learning, they must be first linked to the cell types in the brain that mediate them. In this study, we examine whether a subtype of cortical interneurons might mediate sensory learning by serving as discriminators, a crucial component in an adversarial algorithm for representation learning. We describe how such interneurons would be characterized by a plasticity rule that switches from Hebbian plasticity during waking states to anti-Hebbian plasticity in dreaming states. Evaluating the computational advantages and disadvantages of this algorithm, we find that it excels at learning representations in networks with recurrent connections but scales poorly with network size. This limitation can be partially addressed if the network also oscillates between evoked activity and generative samples on faster timescales. Consequently, we propose that an adversarial algorithm with interneurons as discriminators is a plausible and testable strategy for sensory learning in biological systems.

Reduction of false positives using zone-specific prostate-specific antigen density for prostate MRI-based biopsy decision strategies.

OBJECTIVES: To develop and test zone-specific prostate-specific antigen density (sPSAD) combined with PI-RADS to guide prostate biopsy decision strategies (BDS). METHODS: This retrospective study included consecutive patients, who underwent prostate MRI and biopsy (01/2012-10/2018). The whole gland and transition zone (TZ) were segmented at MRI using a retrained deep learning system (DLS; nnU-Net) to calculate PSAD and sPSAD, respectively. Additionally, sPSAD and PI-RADS were combined in a BDS, and diagnostic performances to detect Grade Group ≥ 2 (GG ≥ 2) prostate cancer were compared. Patient-based cancer detection using sPSAD was assessed by bootstrapping with 1000 repetitions and reported as area under the curve (AUC). Clinical utility of the BDS was tested in the hold-out test set using decision curve analysis. Statistics included nonparametric DeLong test for AUCs and Fisher-Yates test for remaining performance metrics. RESULTS: A total of 1604 patients aged 67 (interquartile range, 61-73) with 48% GG ≥ 2 prevalence (774/1604) were evaluated. By employing DLS-based prostate and TZ volumes (DICE coefficients of 0.89 (95% confidence interval, 0.80-0.97) and 0.84 (0.70-0.99)), GG ≥ 2 detection using PSAD was inferior to sPSAD (AUC, 0.71 (0.68-0.74)/0.73 (0.70-0.76); p < 0.001). Combining PI-RADS with sPSAD, GG ≥ 2 detection specificity doubled from 18% (10-20%) to 43% (30-44%; p < 0.001) with similar sensitivity (93% (89-96%)/97% (94-99%); p = 0.052), when biopsies were taken in PI-RADS 4-5 and 3 only if sPSAD was ≥ 0.42 ng/mL/cc as compared to all PI-RADS 3-5 cases. Additionally, using the sPSAD-based BDS, false positives were reduced by 25% (123 (104-142)/165 (146-185); p < 0.001). CONCLUSION: Using sPSAD to guide biopsy decisions in PI-RADS 3 lesions can reduce false positives at MRI while maintaining high sensitivity for GG ≥ 2 cancers. CLINICAL RELEVANCE STATEMENT: Transition zone-specific prostate-specific antigen density can improve the accuracy of prostate cancer detection compared to MRI assessments alone, by lowering false-positive cases without significantly missing men with ISUP GG ≥ 2 cancers. KEY POINTS: • Prostate biopsy decision strategies using PI-RADS at MRI are limited by a substantial proportion of false positives, not yielding grade group ≥ 2 prostate cancer. • PI-RADS combined with transition zone (TZ)-specific prostate-specific antigen density (PSAD) decreased the number of unproductive biopsies by 25% compared to PI-RADS only. • TZ-specific PSAD also improved the specificity of MRI-directed biopsies by 9% compared to the whole gland PSAD, while showing identical sensitivity.

Energy expenditure does not solely explain step length-width choices during walking.

Healthy young adults have a most preferred walking speed, step length and step width that are close to energetically optimal. However, people can choose to walk with a multitude of different step lengths and widths, which can vary in both energy expenditure and preference. Here, we further investigated step length-width preferences and their relationship to energy expenditure. In line with a growing body of research, we hypothesized that people's preferred stepping patterns would not be fully explained by metabolic energy expenditure. To test this hypothesis, we used a two-alternative forced-choice paradigm. Fifteen participants walked on an oversized treadmill. Each trial, participants performed two prescribed stepping patterns and then chose the pattern they preferred. Over time, we adapted the choices such that there was 50% chance of choosing one pattern over another (equally preferred). If people's preferences are based solely on metabolic energy expenditure, then these equally preferred stepping patterns should have equal energy expenditure. In contrast, we found that energy expenditure differed across equally preferred step length-width patterns (P<0.001). On average, longer steps with higher energy expenditure were preferred over shorter and wider steps with lower energy expenditure (P<0.001). We also asked participants to rank a set of shorter, wider and longer steps from most preferred to least preferred, and from most energy expended to least energy expended. Only 7/15 participants had the same rankings for their preferences and perceived energy expenditure. Our results suggest that energy expenditure is not the only factor influencing a person's conscious gait choices.

The "Eyelet Sign" as an MRI Clue for Inflammatory Brown Syndrome.

BACKGROUND: Brown syndrome is characterized by a restrictive elevation deficit of the affected eye in adduction. Besides the well-known congenital form, different acquired etiologies including inflammation, trauma, and surgery may prevent the superior oblique (SO) tendon from gliding freely through the trochlea on attempted upgaze. We present MRI findings in pediatric and adult patients with inflammatory acquired Brown syndrome. METHODS: Retrospective review of clinical and MRI findings of 6 patients (4 children: median age 8.4 years [range 6.1-8.7]; 2 adults: age 46.4 and 51.1 years). Median follow-up was 23 months (range 1-52). RESULTS: In all 6 patients, orbital MRI demonstrated inflammatory changes of the SO tendon-trochlea complex. A striking feature was circumferential contrast enhancement of the trochlea with central sparing where the tendon passes, reminiscent of an eyelet. In all cases, the motility restriction improved either spontaneously or with systemic anti-inflammatory treatment. Although both adult patients had a history of known seronegative spondyloarthritis, there was no associated systemic condition in the children in our series. CONCLUSIONS: Both in children and in adults, MRI can provide evidence of inflammatory changes located at the trochlea-tendon complex in acquired Brown syndrome here referred to as the "eyelet sign," which may be helpful in confirming the clinical diagnosis and guide appropriate treatment.

Corrective Saccades in Unilateral and Bilateral Vestibular Hypofunction During Slow Rotation Expressed by Visually Enhanced VOR and VOR Suppression: Role of the Cerebellum.

In clinical practice, the head impulse test paradigm (HIMP) and the suppression head impulse paradigm (SHIMP) stimulate high-frequency head movements so that the visual system is temporarily suppressed. The two tests could also be useful tools for vestibular assessment at low frequencies: VVOR (visually enhanced vestibulo-ocular reflex) and VORS (vestibulo-ocular reflex suppression). The aim of this study is to analyze the eye movements typically found during VVOR and VORS testing in patients with unilateral and bilateral vestibular hypofunction. Twenty patients with unilateral vestibular hypofunction, three patients with bilateral vestibular hypofunction, and ten patients with normal vestibular function (control group) were analyzed through VVOR and VORS testing with an Otometrics ICS Impulse system. During the VVOR test, patients with unilateral vestibular hypofunction exhibited corrective saccades to the same direction of the nystagmus fast phase toward the healthy side when the head rotates toward the affected side, while patients with bilateral vestibular hypofunction exhibited corrective saccades to the opposite side of head movements to each side. During the VORS test, patients with unilateral vestibular hypofunction seem to exhibit larger corrective saccades to the healthy side when the head was moved to this side, while patients with bilateral vestibular hypofunction did not exhibit corrective saccades during head movements to either side. Our data suggest that the VVOR and VORS tests yield the same diagnostic information as the HIMP and SHIMP tests in unilateral and bilateral vestibular hypofunction, and can contribute to the diagnosis of a peripheral vestibular loss as well as the affected side.

From Prior Information to Saccade Selection: Evolution of Frontal Eye Field Activity during Natural Scene Search.

Prior knowledge about our environment influences our actions. How does this knowledge evolve into a final action plan and how does the brain represent this? Here, we investigated this question in the monkey oculomotor system during self-guided search of natural scenes. In the frontal eye field (FEF), we found a subset of neurons, "Early neurons," that contain information about the upcoming saccade long before it is executed, often before the previous saccade had even ended. Crucially, much of this early information did not relate to the actual saccade that would eventually be selected. Rather, it related to prior information about the probabilities of possible upcoming saccades based on the presaccade fixation location. Nearer to the time of saccade onset, a greater proportion of these neurons' activities related to the saccade selection, although prior information continued to influence activity throughout. A separate subset of FEF neurons, "Late neurons," only represented the final action plan near saccade onset and not prior information. Our results demonstrate how, across the population of FEF neurons, prior information evolves into definitive saccade plans.

Evaluation of Changes in Depression, Anxiety, and Social Anxiety Using Smartphone Sensor Features: Longitudinal Cohort Study.

BACKGROUND: The assessment of behaviors related to mental health typically relies on self-report data. Networked sensors embedded in smartphones can measure some behaviors objectively and continuously, with no ongoing effort. OBJECTIVE: This study aims to evaluate whether changes in phone sensor-derived behavioral features were associated with subsequent changes in mental health symptoms. METHODS: This longitudinal cohort study examined continuously collected phone sensor data and symptom severity data, collected every 3 weeks, over 16 weeks. The participants were recruited through national research registries. Primary outcomes included depression (8-item Patient Health Questionnaire), generalized anxiety (Generalized Anxiety Disorder 7-item scale), and social anxiety (Social Phobia Inventory) severity. Participants were adults who owned Android smartphones. Participants clustered into 4 groups: multiple comorbidities, depression and generalized anxiety, depression and social anxiety, and minimal symptoms. RESULTS: A total of 282 participants were aged 19-69 years (mean 38.9, SD 11.9 years), and the majority were female (223/282, 79.1%) and White participants (226/282, 80.1%). Among the multiple comorbidities group, depression changes were preceded by changes in GPS features (Time: r=-0.23, P=.02; Locations: r=-0.36, P<.001), exercise duration (r=0.39; P=.03) and use of active apps (r=-0.31; P<.001). Among the depression and anxiety groups, changes in depression were preceded by changes in GPS features for Locations (r=-0.20; P=.03) and Transitions (r=-0.21; P=.03). Depression changes were not related to subsequent sensor-derived features. The minimal symptoms group showed no significant relationships. There were no associations between sensor-based features and anxiety and minimal associations between sensor-based features and social anxiety. CONCLUSIONS: Changes in sensor-derived behavioral features are associated with subsequent depression changes, but not vice versa, suggesting a directional relationship in which changes in sensed behaviors are associated with subsequent changes in symptoms.

A smartphone-based online system for fall detection with alert notifications and contextual information of real-life falls.

BACKGROUND: Falls are a leading cause of accidental deaths and injuries worldwide. The risk of falling is especially high for individuals suffering from balance impairments. Retrospective surveys and studies of simulated falling in lab conditions are frequently used and are informative, but prospective information about real-life falls remains sparse. Such data are essential to address fall risks and develop fall detection and alert systems. Here we present the results of a prospective study investigating a proof-of-concept, smartphone-based, online system for fall detection and notification. METHODS: The system uses the smartphone's accelerometer and gyroscope to monitor the participants' motion, and falls are detected using a regularized logistic regression. Data on falls and near-fall events (i.e., stumbles) is stored in a cloud server and fall-related variables are logged onto a web portal developed for data exploration, including the event time and weather, fall probability, and the faller's location and activity before the fall. RESULTS: In total, 23 individuals with an elevated risk of falling carried the phones for 2070 days in which the model classified 14,904,000 events. The system detected 27 of the 37 falls that occurred (sensitivity = 73.0 %) and resulted in one false alarm every 46 days (specificity > 99.9 %, precision = 37.5 %). 42.2 % of the events falsely classified as falls were validated as stumbles. CONCLUSIONS: The system's performance shows the potential of using smartphones for fall detection and notification in real-life. Apart from functioning as a practical fall monitoring instrument, this system may serve as a valuable research tool, enable future studies to scale their ability to capture fall-related data, and help researchers and clinicians to investigate real-falls.

High-resolution mapping of DNA polymerase fidelity using nucleotide imbalances and next-generation sequencing.

DNA polymerase fidelity is affected by both intrinsic properties and environmental conditions. Current strategies for measuring DNA polymerase error rate in vitro are constrained by low error subtype sensitivity, poor scalability, and lack of flexibility in types of sequence contexts that can be tested. We have developed the Magnification via Nucleotide Imbalance Fidelity (MagNIFi) assay, a scalable next-generation sequencing assay that uses a biased deoxynucleotide pool to quantitatively shift error rates into a range where errors are frequent and hence measurement is robust, while still allowing for accurate mapping to error rates under typical conditions. This assay is compatible with a wide range of fidelity-modulating conditions, and enables high-throughput analysis of sequence context effects on base substitution and single nucleotide deletion fidelity using a built-in template library. We validate this assay by comparing to previously established fidelity metrics, and use it to investigate neighboring sequence-mediated effects on fidelity for several DNA polymerases. Through these demonstrations, we establish the MagNIFi assay for robust, high-throughput analysis of DNA polymerase fidelity.

Sensorimotor priors are effector dependent.

During sensorimotor tasks, subjects use sensory feedback but also prior information. It is often assumed that the sensorimotor prior is just given by the experiment and that the details for acquiring this prior (e.g., the effector) are irrelevant. However, recent research has suggested that the construction of priors is nontrivial. To test if the sensorimotor details matter for the construction of a prior, we designed two tasks that differ only in the effectors that subjects use to indicate their estimate. For both a typical reaching setting and an atypical wrist rotation setting, prior and feedback uncertainty matter as quantitatively predicted by Bayesian statistics. However, in violation of simple Bayesian models, the importance of the prior differs across effectors. Subjects overly rely on their prior in the typical reaching case compared with the wrist case. The brain is not naively Bayesian with a single and veridical prior. NEW & NOTEWORTHY Traditional Bayesian models often assume that we learn statistics of movements and use the information as a prior to guide subsequent movements. The effector is merely a reporting modality for information processing. We asked subjects to perform a visuomotor learning task with different effectors (finger or wrist). Surprisingly, we found that prior information is used differently between the effectors, suggesting that learning of the prior is related to the movement context such as the effector involved or that naive models of Bayesian behavior need to be extended.

A muscle-activity-dependent gain between motor cortex and EMG.

Whether one is delicately placing a contact lens on the surface of the eye or lifting a heavy weight from the floor, the motor system must produce a wide range of forces under different dynamical loads. How does the motor cortex, with neurons that have a limited activity range, function effectively under these widely varying conditions? In this study, we explored the interaction of activity in primary motor cortex (M1) and muscles (electromyograms, EMGs) of two male rhesus monkeys for wrist movements made during three tasks requiring different dynamical loads and forces. Despite traditionally providing adequate predictions in single tasks, in our experiments, a single linear model failed to account for the relation between M1 activity and EMG across conditions. However, a model with a gain parameter that increased with the target force remained accurate across forces and dynamical loads. Surprisingly, this model showed that a greater proportion of EMG changes were explained by the nonlinear gain than the linear mapping from M1. In addition to its theoretical implications, the strength of this nonlinearity has important implications for brain-computer interfaces (BCIs). If BCI decoders are to be used to control movement dynamics (including interaction forces) directly, they will need to be nonlinear and include training data from broad data sets to function effectively across tasks. Our study reinforces the need to investigate neural control of movement across a wide range of conditions to understand its basic characteristics as well as translational implications. NEW & NOTEWORTHY We explored the motor cortex-to-electromyogram (EMG) mapping across a wide range of forces and loading conditions, which we found to be highly nonlinear. A greater proportion of EMG was explained by a nonlinear gain than a linear mapping. This nonlinearity allows motor cortex to control the wide range of forces encountered in the real world. These results unify earlier observations and inform the next-generation brain-computer interfaces that will control movement dynamics and interaction forces.

Unfavorable Structural and Functional Outcomes in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis.

BACKGROUND: Recurrent optic neuritis (rON) associated with myelin oligodendrocyte glycoprotein (MOG)-specific antibodies has been initially reported to show a better clinical outcome than aquaporin-4 (AQP4)-seropositive ON in neuromyelitis optica spectrum disorder (NMOSD). Here, we characterize clinical and neuroimaging findings in severe cases of MOG antibody-positive and AQP4 antibody-negative bilateral rON. METHODS: Three male adults with rON (ages 18, 44, and 63 years) were evaluated with optical coherence tomography (OCT), MRI, cerebrospinal fluid (CSF), and serological studies. RESULTS: All patients experienced >7 relapses of ON with severe reduction of visual acuity and partial response to steroid treatment. Optic nerves were affected bilaterally, although unilateral relapses were more frequent than simultaneous bilateral recurrences. Patients were MOG-seropositive but repeatedly tested negative for AQP4 antibodies. OCT showed severe thinning of the peripapillary retinal nerve fiber layer. On MRI, contrast-enhancing lesions extended over more than half the length of the optic nerve. CSF analyses during ON episodes were normal. Severe visual deficits accumulated over time in 2 of 3 patients, despite immunosuppressive therapy. CONCLUSIONS: MOG-seropositive and AQP4-seronegative rON may be associated with an aggressive disease course and poor functional and structural outcomes. In contrast to previous reports, the severity and pattern of retinal and optic nerve damage closely resembled phenotypes commonly observed in AQP4-seropositive rON without fulfilling current diagnostic criteria for NMOSD.

Linear-nonlinear-time-warp-poisson models of neural activity.

Prominent models of spike trains assume only one source of variability - stochastic (Poisson) spiking - when stimuli and behavior are fixed. However, spike trains may also reflect variability due to internal processes such as planning. For example, we can plan a movement at one point in time and execute it at some arbitrary later time. Neurons involved in planning may thus share an underlying time course that is not precisely locked to the actual movement. Here we combine the standard Linear-Nonlinear-Poisson (LNP) model with Dynamic Time Warping (DTW) to account for shared temporal variability. When applied to recordings from macaque premotor cortex, we find that time warping considerably improves predictions of neural activity. We suggest that such temporal variability is a widespread phenomenon in the brain which should be modeled.

Pain: A Statistical Account.

Perception is seen as a process that utilises partial and noisy information to construct a coherent understanding of the world. Here we argue that the experience of pain is no different; it is based on incomplete, multimodal information, which is used to estimate potential bodily threat. We outline a Bayesian inference model, incorporating the key components of cue combination, causal inference, and temporal integration, which highlights the statistical problems in everyday perception. It is from this platform that we are able to review the pain literature, providing evidence from experimental, acute, and persistent phenomena to demonstrate the advantages of adopting a statistical account in pain. Our probabilistic conceptualisation suggests a principles-based view of pain, explaining a broad range of experimental and clinical findings and making testable predictions.

Nucleotide-time alignment for molecular recorders.

Using a DNA polymerase to record intracellular calcium levels has been proposed as a novel neural recording technique, promising massive-scale, single-cell resolution monitoring of large portions of the brain. This technique relies on local storage of neural activity in strands of DNA, followed by offline analysis of that DNA. In simple implementations of this scheme, the time when each nucleotide was written cannot be determined directly by post-hoc DNA sequencing; the timing data must be estimated instead. Here, we use a Dynamic Time Warping-based algorithm to perform this estimation, exploiting correlations between neural activity and observed experimental variables to translate DNA-based signals to an estimate of neural activity over time. This algorithm improves the parallelizability of traditional Dynamic Time Warping, allowing several-fold increases in computation speed. The algorithm also provides a solution to several critical problems with the molecular recording paradigm: determining recording start times and coping with DNA polymerase pausing. The algorithm can generally locate DNA-based records to within <10% of a recording window, allowing for the estimation of unobserved incorporation times and latent neural tunings. We apply our technique to an in silico motor control neuroscience experiment, using the algorithm to estimate both timings of DNA-based data and the directional tuning of motor cortical cells during a center-out reaching task. We also use this algorithm to explore the impact of polymerase characteristics on system performance, determining the precision of a molecular recorder as a function of its kinetic and error-generating properties. We find useful ranges of properties for DNA polymerase-based recorders, providing guidance for future protein engineering attempts. This work demonstrates a useful general extension to dynamic alignment algorithms, as well as direct applications of that extension toward the development of molecular recorders, providing a necessary stepping stone for future biological work.

Using noise to shape motor learning.

Each of our movements is selected from any number of alternative movements. Some studies have shown evidence that the central nervous system (CNS) chooses to make the specific movements that are least affected by motor noise. Previous results showing that the CNS has a natural tendency to minimize the effects of noise make the direct prediction that if the relationship between movements and noise were to change, the specific movements people learn to make would also change in a predictable manner. Indeed, this has been shown for well-practiced movements such as reaching. Here, we artificially manipulated the relationship between movements and visuomotor noise by adding noise to a motor task in a novel redundant geometry such that there arose a single control policy that minimized the noise. This allowed us to see whether, for a novel motor task, people could learn the specific control policy that minimized noise or would need to employ other compensation strategies to overcome the added noise. As predicted, subjects were able to learn movements that were biased toward the specific ones that minimized the noise, suggesting not only that the CNS can learn to minimize the effects of noise in a novel motor task but also that artificial visuomotor noise can be a useful tool for teaching people to make specific movements. Using noise as a teaching signal promises to be useful for rehabilitative therapies and movement training with human-machine interfaces. NEW & NOTEWORTHY: Many theories argue that we choose to make the specific movements that minimize motor noise. Here, by changing the relationship between movements and noise, we show that people actively learn to make movements that minimize noise. This not only provides direct evidence for the theories of noise minimization but presents a way to use noise to teach specific movements to improve rehabilitative therapies and human-machine interface control.

Enhanced Depth Imaging Optical Coherence Tomography of Optic Nerve Head Drusen: A Comparison of Cases with and without Visual Field Loss.

PURPOSE: Enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD OCT) has been recognized as the most sensitive tool to diagnose optic nerve head drusen (ONHD). The relationship between OCT characteristics and visual loss has not been well documented. This study compares EDI SD OCT-determined morphologic characteristics of drusen in eyes with or without visual field (VF) defects. DESIGN: Descriptive study of patients attending the neuro-ophthalmology service of Moorfields Eye Hospital between January 2013 and October 2014. SUBJECTS: Patients with diagnosed ONHD and EDI SD OCT imaging of the optic nerve head. METHODS: Eyes with and without VF defects were compared with regard to retinal nerve fiber layer (RNFL) thickness, drusen morphology, size, extent, visibility on funduscopy, ultrasound, and fundus autofluorescence. MAIN OUTCOME MEASURES: Difference in OCT characteristics of ONHD between patients with or without VF defects. RESULTS: Of 38 patients, 69 eyes with ONHD were included. Thirty-three eyes had a normal VF with average mean deviation (MD) -0.96 (±1.2) dB and pattern standard deviation (PSD) 1.6 (±0.3) dB (group I), and 36 eyes had VF defects with MD -13.7 (±10.4) dB and PSD 7.2 (±3.6) dB (group II). Mean global RNFL thickness was 62 (±20.9) µm in the latter group and 99.0 (±12.9) µm in group I. In group I, the predominant drusen type was peripapillary drusen, of variable size. In group II, most eyes had confluent (P < 0.02) and large (>500 µm; P < 0.003) drusen, and drusen were more commonly visible on funduscopy (P = 0.001), ultrasound (P = 0.013), and autofluorescence (P = 0.002). Differences between the 2 groups reached statistical significance in a clustered analysis. RNFL thinning and autofluorescence showed relative sparing of the temporal sector. Sixty-four percent of patients with a VF defect in 1 eye also had a VF defect in their fellow eye. CONCLUSIONS: Drusen size and drusen type as classified by OCT morphologic characteristics are significantly different in patients with or without VF defects. Confluent, large, and autofluorescent drusen were more commonly found in patients with VF defects. These findings may assist in clarifying how drusen give rise to visual loss, which is currently not known.

Strabismus Measurements with Novel Video Goggles.

PURPOSE: To assess the validity of a novel, simplified, noninvasive test for strabismus using video goggles. DESIGN: Cross-sectional method comparison study in which the new test, the strabismus video goggles, is compared with the existing reference standard, the Hess screen test. PARTICIPANTS: We studied 41 adult and child patients aged ≥6 years with ocular misalignment owing to congenital or acquired paralytic or comitant strabismus and 17 healthy volunteers. METHODS: All participants were tested with binocular infrared video goggles with built-in laser target projection and liquid crystal display shutters for alternate occlusion of the eyes and the conventional Hess screen test. In both tests, ocular deviations were measured on a 9-point target grid located at 0±15° horizontal and vertical eccentricity. MAIN OUTCOME MEASURES: Horizontal and vertical ocular deviations at 9 different gaze positions of each eye were measured by the strabismus video goggles and the Hess screen test. Agreement was quantified as the intraclass correlation coefficient. Secondary outcomes were the utility of the goggles in patients with visual suppression and in children. RESULTS: There was good agreement between the strabismus video goggles and the Hess screen test in the measurements of horizontal and vertical deviation (intraclass correlation coefficient horizontal 0.83, 95% confidence interval [0.77, 0.88], vertical 0.76, 95% confidence interval [0.68, 0.82]). Both methods reproduced the characteristic strabismus patterns in the 9-point grid. In contrast to Hess screen testing, strabismus video goggle measurements were even possible in patients with comitant strabismus and visual suppression. CONCLUSIONS: The new device is simple and is fast and accurate in measuring ocular deviations, and the results are closely correlated with those obtained using the conventional Hess screen test. It can even be used in patients with visual suppression who are not suitable for the Hess screen test. The device can be applied in children as young as 6 years of age.