Age-related behavioral resilience in smartphone touchscreen interaction dynamics.

We experience a life that is full of ups and downs. The ability to bounce back after adverse life events such as the loss of a loved one or serious illness declines with age, and such isolated events can even trigger accelerated aging. How humans respond to common day-to-day perturbations is less clear. Here, we infer the aging status from smartphone behavior by using a decision tree regression model trained to accurately estimate the chronological age based on the dynamics of touchscreen interactions. Individuals (N = 280, 21 to 87 y of age) expressed smartphone behavior that appeared younger on certain days and older on other days through the observation period that lasted up to ~4 y. We captured the essence of these fluctuations by leveraging the mathematical concept of critical transitions and tipping points in complex systems. In most individuals, we find one or more alternative stable aging states separated by tipping points. The older the individual, the lower the resilience to forces that push the behavior across the tipping point into an older state. Traditional accounts of aging based on sparse longitudinal data spanning decades suggest a gradual behavioral decline with age. Taken together with our current results, we propose that the gradual age-related changes are interleaved with more complex dynamics at shorter timescales where the same individual may navigate distinct behavioral aging states from one day to the next. Real-world behavioral data modeled as a complex system can transform how we view and study aging.

Surgical Management of Diabetic Macular Edema.

PURPOSE OF REVIEW: Diabetic macular edema (DME) is the accumulation of fluid in the extracellular space within the macula and is a major cause of visual impairment among patients with diabetes. First-line treatment for DME includes pharmacotherapy with intravitreal anti-vascular endothelial growth factor medications and intravitreal corticosteroids. Alternative therapeutic strategies include laser photocoagulation for non-center involving DME, and surgical options such as pars plana vitrectomy (PPV) with or without internal limiting membrane (ILM) peel in cases with vitreoretinal interface anomalies or DME refractory to pharmacotherapy, and the Port Delivery System (PDS) for sustained release of anti-vascular endothelial growth factor (VEGF) medication. Our aim is to review the existing literature on surgical management of DME including imaging changes in chronic DME and the clinical relevance of surgical intervention. RECENT FINDINGS: Imaging changes associated with DME and a worse prognosis include disorganization of the retinal layer, disruption of both the external limiting membrane (ELM) and ellipsoid zone, and vitreomacular interface abnormalities. Studies involving pars plana vitrectomy with and without ILM peel show anatomic improvement but may not always be associated with significant change in visual outcomes. Early studies lacked detailed imaging of the retinal layers and PPV was likely performed as a last resort. In addition, the novel PDS is surgically implanted into the pars plana and works as a drug reservoir with controlled release of drug. However, it has been recalled in patients with wet age-related macular degeneration due to issues with dislodgement. Surgical interventions for DME include pars plana vitrectomy with and without ILM peel and new surgical therapies for DME such as the PDS and subretinal gene therapy have the potential to reduce the risk of DME progression.

Ophthalmic manifestations of coronavirus disease 2019 and ocular side effects of investigational pharmacologic agents.

PURPOSE OF REVIEW: To compile and report the ocular manifestations of coronavirus disease 2019 (COVID-19) infection and summarize the ocular side effects of investigational treatments of this disease. RECENT FINDINGS: Conjunctivitis is by far the most common ocular manifestation of COVID-19 with viral particles being isolated from tears/secretions of infected individuals. Multiple therapeutic options are being explored across a variety of medication classes with diverse ocular side effects. SUMMARY: Eye care professionals must exercise caution, as conjunctivitis may be the presenting or sole finding of an active COVID-19 infection. While no currently studied therapeutic agents have been found to reliably treat COVID-19, early vaccination trials are progressing and show promise. A video abstract is available for a more detailed summary. VIDEO ABSTRACT: http://links.lww.com/COOP/A36.

The spinal reflex cannot be perceptually separated from voluntary movements.

Both voluntary and involuntary movements activate sensors in the muscles, skin, tendon and joints. As limb movement can result from a mixture of spinal reflexes and voluntary motor commands, the cortical centres underlying conscious proprioception might either aggregate or separate the sensory inputs generated by voluntary movements from those generated by involuntary movements such as spinal reflexes. We addressed whether healthy volunteers could perceive the contribution of a spinal reflex during movements that combined both reflexive and voluntary contributions. Volunteers reported the reflexive contribution in leg movements that were partly driven by the knee-jerk reflex induced by a patellar tendon tap and partly by voluntary motor control. In one condition, participants were instructed to kick back in response to a tendon tap. The results were compared to reflexes in a resting baseline condition without voluntary movement. In a further condition, participants were instructed to kick forwards after a tap. Volunteers reported the perceived reflex contribution by repositioning the leg to the perceived maximum displacement to which the reflex moved the leg after each tendon tap. In the resting baseline condition, the reflex was accurately perceived. We found a near-unity slope of linear regressions of perceived on actual reflexive displacement. Both the slope value and the quality of regression fit in individual volunteers were significantly reduced when volunteers were instructed to generate voluntary backward kicks as soon as they detected the tap. In the kick forward condition, kinematic analysis showed continuity of reflex and voluntary movements, but the reflex contribution could be estimated from electromyography (EMG) recording on each trial. Again, participants' judgements of reflexes showed a poor relation to reflex EMG, in contrast to the baseline condition. In sum, we show that reflexes can be accurately perceived from afferent information. However, the presence of voluntary movement significantly impairs reflex perception. We suggest that perceptual separation between voluntary and reflex movement is poor at best. Our results imply that the brain has no clear marker for perceptually separating voluntary and involuntary movement. Attribution of body movement to voluntary or involuntary motor commands is surprisingly poor when both are present.

Rapid functional reorganization of the forelimb cortical representation after thoracic spinal cord injury in adult rats.

Thoracic spinal cord injured rats rely largely on forelimbs to walk, as their hindlimbs are dysfunctional. This increased limb use is accompanied by expansion of the cortical forelimb sensory representation. It is unclear how quickly the representational changes occur and whether they are at all related to the behavioral adaptation. Using blood oxygenation level dependent functional mangetic resonance imaging (BOLD-fMRI) we show that major plastic changes of the somato-sensory map can occur as early as one day after injury. The extent of map increase was variable between animals, and some animals showed a reduction in map size. However, at three or seven days after injury a significant enhancement of the forelimb representation was evident in all the animals. In a behavioral test for precise limb control, crossing of a horizontal ladder, the injured rats relied almost entirely on their forelimbs; they initially made more mistakes than at 7 days post injury. Remarkably, in the individual animals the behavioral performance seen at seven days was proportional to the physiological change present at one day after injury. The rapid increase in cortical representation of the injury-spared body part may provide the additional neural substrate necessary for high level behavioral adaptation.

Using voluntary motor commands to inhibit involuntary arm movements.

A hallmark of voluntary motor control is the ability to stop an ongoing movement. Is voluntary motor inhibition a general neural mechanism that can be focused on any movement, including involuntary movements, or is it mere termination of a positive voluntary motor command? The involuntary arm lift, or 'floating arm trick', is a distinctive long-lasting reflex of the deltoid muscle. We investigated how a voluntary motor network inhibits this form of involuntary motor control. Transcranial magnetic stimulation of the motor cortex during the floating arm trick produced a silent period in the reflexively contracting deltoid muscle, followed by a rebound of muscle activity. This pattern suggests a persistent generator of involuntary motor commands. Instructions to bring the arm down voluntarily reduced activity of deltoid muscle. When this voluntary effort was withdrawn, the involuntary arm lift resumed. Further, voluntary motor inhibition produced a strange illusion of physical resistance to bringing the arm down, as if ongoing involuntarily generated commands were located in a 'sensory blind-spot', inaccessible to conscious perception. Our results suggest that voluntary motor inhibition may be a specific neural function, distinct from absence of positive voluntary motor commands.

Somatotopic astrocytic activity in the somatosensory cortex.

Astrocytes play a crucial role in maintaining neuronal function and monitoring their activity. According to neuronal activity maps, the body is represented topographically in the somatosensory cortex. In rats, neighboring cortical areas receive forelimb (FL) and hindlimb (HL) sensory inputs. Whether astrocytic activity is also restricted to the cortical area receiving the respective peripheral sensory inputs is not known. Using wide field optical imaging we measured changes in the concentration of astrocytic calcium within the FL and HL sensorimotor cortex in response to peripheral sensory inputs. Mapping the calcium signals upon electrical stimulation of the forepaw and hindpaw we found activity largely restricted to the FL and HL area, respectively. In comparison to neuronal activity the time course of the astrocytic calcium activity was considerably slower. The signal took 6 s to peak after the onset of a 2 Hz and 2 s long electrical stimulation of the hindpaw and 8 s for a 4 s stimulation. The astrocytic signals were delayed relative to cerebral blood flow measured using laser speckle imaging. The intensity of both the astrocytic and neuronal signals in the HL sensorimotor cortex declined with increase in stimulation frequency. Moreover, blocking neuronal input by tetrodotoxin abolished astrocytic calcium signals. We suggest that the topographical representation of the body is not only true for cortical neurons but also for astrocytes. The maps and the frequency-dependent activations reflect strong reciprocal neuroglial communication and provide a new experimental approach to explore the role of astrocytes in health and disease.

Heterogeneous spine loss in layer 5 cortical neurons after spinal cord injury.

A large thoracic spinal cord injury disconnects the hindlimb (HL) sensory-motor cortex from its target, the lumbar spinal cord. The fate of the synaptic structures of the axotomized cortical neurons is not well studied. We evaluated the density of spines on axotomized corticospinal neurons at 3, 7, and 21 days after the injury in adult mice expressing yellow fluorescence protein in a subset of layer 5 neurons. Spine density of the dendritic segment proximal to the soma (in layer 5) declined as early as 3 days after injury, far preceding the onset of somatic atrophy. In the distal segment (in layer 2/3), spine loss was slower and less severe than in the proximal segment. Axotomy of corticospinal axons in the brainstem (pyramidotomy) induced a comparable reduction of spine density, demonstrating that the loss is not restricted to the neurons axotomized in the thoracic spinal cord. Surprisingly, in both forms of injury, the spine density of putative non-axotomized layer 5 neurons was reduced as well. The spine loss may reflect fast rearrangements of cortical circuits after axotomy, for example, by a disconnection of HL cortical neurons from synaptic inputs that no longer provide useful information.

Common multi-day rhythms in smartphone behavior.

The idea that abnormal human activities follow multi-day rhythms is found in ancient beliefs on the moon to modern clinical observations in epilepsy and mood disorders. To explore multi-day rhythms in healthy human behavior our analysis includes over 300 million smartphone touchscreen interactions logging up to 2 years of day-to-day activities (N401 subjects). At the level of each individual, we find a complex expression of multi-day rhythms where the rhythms occur scattered across diverse smartphone behaviors. With non-negative matrix factorization, we extract the scattered rhythms to reveal periods ranging from 7 to 52 days - cutting across age and gender. The rhythms are likely free-running - instead of being ubiquitously driven by the moon - as they did not show broad population-level synchronization even though the sampled population lived in northern Europe. We propose that multi-day rhythms are a common trait, but their consequences are uniquely experienced in day-to-day behavior.

A Retrospective Cohort Study on the Difficulties of Diagnosing and Managing Glaucoma in Patients with Coexistent Neurodegenerative Disease.

Aim: To investigate the limitations of diagnosing glaucoma in patients with coexistent neurodegenerative disease (NDD) by collecting information on demographics, examination findings, optical coherence tomography (OCT), and visual field (VF) tests. Materials and methods: Retrospective cohort study of patients with primary open-angle glaucoma and coexistent dementia, multiple sclerosis (MS), Parkinson's disease (PD), or cerebrovascular accident (CVA) from 2014 to 2020. We included patients with a minimum of 3 years of follow-up. Demographics, ophthalmic exam, OCT, and VF findings were reported and compared across NDD groups using the Chi-squared and analysis of variance tests. Results: We included 199 patients with glaucoma and coexistent NDD, including dementia (51.3%), CVA (11.2%), PD (18.1%), and MS (19.6%). Cupping, neuroretinal rim thinning, pallor, and peripapillary atrophy of the optic nerve were most frequently observed. There was a high number of missing values from OCT to VF tests, and zero patients had a complete OCT or VF test. Additionally, 67.8 and 77.4% of patients received <1 OCT and VF/year, respectively. Retinal nerve fiber layer (RNFL) thinning was observed most frequently in the superior (33.2% OD and 30.7% OS) and inferior (25.6% OD and 30.2% OS) quadrants, with the most significant thinning seen in CVA patients compared to other NDDs (p < 0.05). Glaucoma hemifield tests (GHTs) were abnormal in 23.1% OD and 22.6% OS, and the average mean deviation was -7.43 [standard deviation (SD) 8.23] OD and -8.79 (SD 7.99) OS. Conclusion: The OCT and VF tests are frequently unavailable and may be confounded in patients with coexistent glaucoma and NDDs, complicating glaucoma diagnosis and management. Clinical significance: Diagnosing and managing glaucoma in patients with coexistent NDD is difficult, given the lack of available and reliable OCT and VF testing data. Providers may be forced to rely on intraocular pressure (IOP) and other imperfect measures. How to cite this article: Ciociola EC, Patel K, Blahnik T, et al. A Retrospective Cohort Study on the Difficulties of Diagnosing and Managing Glaucoma in Patients with Coexistent Neurodegenerative Disease. J Curr Glaucoma Pract 2023;17(3):126-133.

The effect of a brief, unplanned treatment delay on neovascular age-related macular degeneration patients: a retrospective cohort study.

Non-compliance to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy can result in increased disease activity in neovascular age-related macular degeneration (nAMD). Our study aims to determine effects of unplanned delay in anti-VEGF injection treatment for nAMD. This retrospective observational study included patients with delays in receiving intravitreal injections for nAMD treatment from March to May 2020 by at least 21 days. Baseline demographic and clinical characteristics, visual acuity (VA), central macular thickness (CMT) measured on optical coherence tomography (OCT), and duration of delayed treatment were analyzed for 3 time points, the pre-delay visit (v1) and post-delay visits (v2 and v3). Data were compared to age-matched controls treated for nAMD in 2019 without delay. Demographic characteristics were compared using two-sample t-tests for continuous variables and Pearson's chi-square tests for categorical variables. For the two primary outcomes of interest, VA and CMT, means and standard deviations were reported for each combination of group and time. Each outcome was modeled using a linear mixed model with the group, time and group-time interaction as fixed effects. A total of 69 patients (99 eyes) in the treatment delay group and 44 patients (69 eyes) in the control group were identified. Statistically significant differences between control and delayed groups were detected for VA (difference in mean logMAR = 0.16; 95% CI 0.06, 0.27; p = 0.002) and CMT (difference in mean CMT = 29; 95% CI 12, 47; p = 0.001) at v2. No differences were detected for v1 and v3 time points for both outcomes. An unplanned delay in intravitreal injection treatment for nAMD resulted in an increase in CMT and worsening of VA compared to controls observed at v2. At v3, CMT and VA recovered to near v1 levels. This study demonstrates that a one-time, brief interruption in treatment for nAMD results in reversible, temporary worsening.

Temporal clusters of age-related behavioral alterations captured in smartphone touchscreen interactions.

Smartphones touchscreen interactions may help resolve if and how real-world behavioral dynamics are shaped by aging. Here, in a sample spanning the adult life span (16 to 86 years, N = 598, accumulating 355 million interactions), we clustered the smartphone interactions according to their next inter-touch interval dynamics. There were age-related behavioral losses at the clusters occupying short intervals (∼100 ms, R2 ∼ 0.8) but gains at the long intervals (∼4 s, R2 ∼ 0.4). Our approach revealed a sophisticated form of behavioral aging where individuals simultaneously demonstrated accelerated aging in one behavioral cluster versus a deceleration in another. Contrary to the common notion of a simple behavioral decline with age based on conventional cognitive tests, we show that the nature of aging systematically varies according to the underlying dynamics. Of all the imaginable factors determining smartphone interactions, age-sensitive cognitive and behavioral processes may dominatingly shape smartphone dynamics.

A model of healthy aging based on smartphone interactions reveals advanced behavioral age in neurological disease.

Smartphones offer unique opportunities to trace the convoluted behavioral patterns accompanying healthy aging. Here we captured smartphone touchscreen interactions from a healthy population (N = 684, ∼309 million interactions) spanning 16 to 86 years of age and trained a decision tree regression model to estimate chronological age based on the interactions. The interactions were clustered according to their next interval dynamics to quantify diverse smartphone behaviors. The regression model well-estimated the chronological age in health (mean absolute error = 6 years, R2 = 0.8). We next deployed this model on a population of stroke survivors (N = 41) to find larger prediction errors such that the estimated age was advanced by 6 years. A similar pattern was observed in people with epilepsy (N = 51), with prediction errors advanced by 10 years. The smartphone behavioral model trained in health can be used to study altered aging in neurological diseases.

Large cognitive fluctuations surrounding sleep in daily living.

Cognitive output and physical activity levels fluctuate surrounding sleep. The ubiquitous digitization of behavior via smartphones is a promising avenue for addressing how these fluctuations occur in daily living. Here, we logged smartphone touchscreen interactions to proxy cognitive fluctuations and contrasted these to physical activity patterns logged on wrist-worn actigraphy. We found that both cognitive and physical activities were dominated by diurnal (∼24 h) and infra-radian (∼7 days) rhythms. The proxy measures of cognitive performance-tapping speed, unlocking speed, and app locating speed-contained lower-powered diurnal rhythm than physical activity. The difference between cognitive and physical activity was vivid during bedtime as people continued to interact with their smartphones at physical rest. The cognitive performance measures in this period were worse than those in the hour before or after bedtime. We suggest that the rhythms underlying cognitive activity in the real world are distinct from those underlying physical activity, and this discord may be a hallmark of modern human behavior.

Striatal dopamine synthesis capacity reflects smartphone social activity.

Striatal dopamine and smartphone behavior have both been linked with behavioral variability. Here, we leverage day-to-day logs of natural, unconstrained smartphone behavior and establish a correlation between a measure of smartphone social activity previously linked with behavioral variability and a measure of striatal dopamine synthesis capacity using [18F]-DOPA PET in (N = 22) healthy adult humans. Specifically, we find that a higher proportion of social app interactions correlates with lower dopamine synthesis capacity in the bilateral putamen. Permutation tests and penalized regressions provide evidence that this link between dopamine synthesis capacity and social versus non-social smartphone interactions is specific. These observations provide a key empirical grounding for current speculations about dopamine's role in digital social behavior.

Artificial neural network trained on smartphone behavior can trace epileptiform activity in epilepsy.

A range of abnormal electrical activity patterns termed epileptiform discharges can occur in the brains of persons with epilepsy. These epileptiform discharges can be monitored and recorded with implanted devices that deliver therapeutic neurostimulation. These continuous recordings provide an opportunity to study the behavioral correlates of epileptiform discharges as the patients go about their daily lives. Here, we captured the smartphone touchscreen interactions in eight patients in conjunction with electrographic recordings (accumulating 35,714 h) and by using an artificial neural network model addressed if the behavior reflected the epileptiform discharges. The personalized model outputs based on smartphone behavioral inputs corresponded well with the observed electrographic data (R: 0.2-0.6, median 0.4). The realistic reconstructions of epileptiform activity based on smartphone use demonstrate how day-to-day digital behavior may be converted to personalized markers of disease activity in epilepsy.

Trait-like nocturnal sleep behavior identified by combining wearable, phone-use, and self-report data.

Using polysomnography over multiple weeks to characterize an individual's habitual sleep behavior while accurate, is difficult to upscale. As an alternative, we integrated sleep measurements from a consumer sleep-tracker, smartphone-based ecological momentary assessment, and user-phone interactions in 198 participants for 2 months. User retention averaged >80% for all three modalities. Agreement in bed and wake time estimates across modalities was high (rho = 0.81-0.92) and were adrift of one another for an average of 4 min, providing redundant sleep measurement. On the ~23% of nights where discrepancies between modalities exceeded 1 h, k-means clustering revealed three patterns, each consistently expressed within a given individual. The three corresponding groups that emerged differed systematically in age, sleep timing, time in bed, and peri-sleep phone usage. Hence, contrary to being problematic, discrepant data across measurement modalities facilitated the identification of stable interindividual differences in sleep behavior, underscoring its utility to characterizing population sleep and peri-sleep behavior.