Medical professionals who assume multiple roles as clinicians and researchers are commonly found in hospitals worldwide. Likewise, in many Chinese hospitals, particularly among early-career medical professionals with M.D. and Ph.D. degrees, active engagement in both clinical practice and scientific research is expected. In the current ethnographic study, the cultural-historical activity theory is used to explore how three early-career neurosurgeons at a tier-one northern-Chinese hospital conduct and write research for publishing in SCI-indexed journals in addition to handling their heavy clinical workload. Drawing on multiple sources of qualitative data, including semi-structured interviews, two-week naturalistic observations, field notes, photographs, and daily activity logs with three neurosurgeons, the study findings highlight Chinese neurosurgeons conduct and write up their research using patient data and collaborating with laboratories while seeking academic language editing and peer feedback. Ethical considerations of clinician-researchers’ scholarly publishing process, implications for researching medical professionals’ boundary crossings, and future research directions are also discussed.

Background

Injury to the trigeminal nerve often results in the development of chronic pain states including tactile allodynia, or hypersensitivity to light touch, in orofacial area, but its underlying mechanisms are poorly understood. Peripheral nerve injury has been shown to cause up-regulation of thrombospondin-4 (TSP4) in dorsal spinal cord that correlates with neuropathic pain development. In this study, we examined whether injury-induced TSP4 is critical in mediating orofacial pain development in a rat model of chronic constriction injury to the infraorbital nerve.

Methods

Orofacial sensitivity to mechanical stimulation was examined in a unilateral infraorbital nerve ligation rat model. The levels of TSP4 in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 spinal cord (Vc/C2) from injured rats were examined at time points correlating with the initiation and peak orofacial hypersensitivity. TSP4 antisense and mismatch oligodeoxynucleotides were intrathecally injected into injured rats to see if antisense oligodeoxynucleotide treatment could reverse injury-induced TSP4 up-regulation and orofacial behavioural hypersensitivity.

Results

Our data indicated that trigeminal nerve injury induced TSP4 up-regulation in Vc/C2 at a time point correlated with orofacial tactile allodynia. In addition, intrathecal treatment with TSP4 antisense, but not mismatch, oligodeoxynucleotides blocked both injury-induced TSP4 up-regulation in Vc/C2 and behavioural hypersensitivity.

Conclusions

Our data support that infraorbital nerve injury leads to TSP4 up-regulation in trigeminal spinal complex that contributes to orofacial neuropathic pain states. Blocking this pathway may provide an alternative approach in management of orofacial neuropathic pain states.

Video game play induces a generalized recovery of a range of spatial visual functions in the amblyopic brain. Here we ask whether video game play also alters temporal processing in the amblyopic brain. When visual targets are presented in rapid succession, correct identification of the first target (T1) can interfere with identification of the second (T2). This is known as the "attentional blink". We measured the attentional blink in each eye of adults with amblyopia before and after 40 hours of active video game play, using a rapid serial visual presentation technique. After videogame play, we observed a ~40% reduction in the attentional blink (identifying T2 200 ms after T1) seen through the amblyopic eye and this improvement in performance transferred substantially to the untrained fellow sound eye. Our experiments show that the enhanced performance cannot be simply explained by eye patching alone, or to improved visual acuity, but is specific to videogame experience. Thus, videogame training might have important therapeutic applications for amblyopia and other visual brain disorders.

Amblyopia is a developmental disorder that results in a wide range of visual deficits. One proven approach to recovering vision in adults with amblyopia is perceptual learning (PL). Recent evidence suggests that neuromodulators can enhance adult plasticity. In this pilot study, we asked whether donepezil, a cholinesterase inhibitor, enhances visual PL in adults with amblyopia. Nine adults with amblyopia were first trained on a low-contrast single-letter identification task while taking a daily dose (5 mg) of donepezil throughout training. Following 10,000 trials of training, participants showed improved contrast sensitivity for identifying single letters. However, the magnitude of improvement was no greater than, and the rate of improvement was slower than, that obtained in a previous study in which six adults with amblyopia were trained using an identical task and protocol but without donepezil (Chung et al., 2012). In addition, we measured transfer of learning effects to other tasks and found that for donepezil, the post-pre performance ratios in both a size-limited (acuity) and a spacing-limited (crowding) task were not significantly different from those found in the previous study without donepezil administration. After an interval of several weeks, six participants returned for a second course of training on identifying flanked (crowded) letters, again with concurrent donepezil administration. Although this task has previously been shown to be highly amenable to PL in adults with amblyopia (Chung et al., 2012; Hussain et al., 2012), only one observer in our study showed significant learning over 10,000 trials of training. Auxiliary experiments showed that the lack of a learning effect on this task during donepezil administration was not due to either the order of training of the two tasks or the use of a sequential training paradigm. Our results reveal that cholinergic enhancement with donepezil during training does not improve or speed up PL of single-letter identification in adults with amblyopia, and importantly, it may even halt learning and transfer related to a crowding task. Clinical Trial Registration: This study was registered with ClinicalTrials.gov (NCT03109314).

Human adults with normal vision are capable of improving performance on visual tasks through repeated practice. Previous work has shown that enhancing synaptic levels of acetylcholine (ACh) in healthy human adults with donepezil (trade name: Aricept) can increase the magnitude and specificity of perceptual learning (PL) for motion direction discrimination in the perifovea. In the current study, we ask whether increasing the synaptic levels of ACh in healthy human adults with donepezil boosts learning of low-contrast isolated letter identification and high-contrast flanked letter identification in normal peripheral vision. Two groups of observers performed sequential training over multiple days while ingesting donepezil. One group trained on isolated low-contrast letters in Phase 1 and crowded high-contrast letters in Phase 2, and the other group performed the reverse sequence, thereby enabling us to differentiate possible effects of drug and training order on PL of letter identification. All testing and training were performed monocularly in peripheral vision, at an eccentricity of 10 degrees along the lower vertical meridian. Our experimental design allowed us to evaluate the effects of sequential training and to ask whether increasing cholinergic signaling boosted learning and/or transfer of low-contrast isolated letter identification and high-contrast flanked letter identification in normal peripheral vision. We found that both groups improved on each of the two tasks. However, our results revealed an effect of training task order on flanked letter identification: Observers who trained on isolated targets first showed rapid early improvement in flanked letter identification but little to no additional improvement after 30 training blocks, while observers who first trained with flanked letters improved gradually on flanked letter identification over the entire 100-block course of training. In addition, we found no effect of donepezil on PL of either isolated or flanked letter identification. In other words, donepezil neither boosted nor blocked learning to identify isolated low-contrast letters or learning to uncrowd in normal peripheral vision.

Amblyopia is a developmental abnormality that results in deficits for a wide range of visual tasks, most notably, the reduced ability to see fine details, the loss in contrast sensitivity especially for small objects and the difficulty in seeing objects in clutter (crowding). The primary goal of this study was to evaluate whether crowding can be ameliorated in adults with amblyopia through perceptual learning using a flanked letter identification task that was designed to reduce crowding, and if so, whether the improvements transfer to untrained visual functions: visual acuity, contrast sensitivity and the size of visual span (the amount of information obtained in one fixation). To evaluate whether the improvements following this training task were specific to training with flankers, we also trained another group of adult observers with amblyopia using a single letter identification task that was designed to improve letter contrast sensitivity, not crowding. Following 10,000 trials of training, both groups of observers showed improvements in the respective training task. The improvements generalized to improved visual acuity, letter contrast sensitivity, size of the visual span, and reduced crowding. The magnitude of the improvement for each of these measurements was similar in the two training groups. Perceptual learning regimens aimed at reducing crowding or improving letter contrast sensitivity are both effective in improving visual acuity, contrast sensitivity for near-acuity objects and reducing the crowding effect, and could be useful as a clinical treatment for amblyopia.

Persons with amblyopia, especially those with strabismus, are known to exhibit abnormal fixational eye movements. In this paper, we compared six characteristics of fixational eye movements among normal control eyes (n=16), the non-amblyopic fellow eyes and the amblyopic eyes of anisometropic (n=14) and strabismic amblyopes (n=14). These characteristics include the frequency, magnitude of landing errors, amplitude and speed of microsaccades, and the amplitude and speed of slow drifts. Fixational eye movements were recorded using retinal imaging while observers monocularly fixated a 1° cross. Eye position data were recovered using a cross-correlation procedure. We found that in general, the characteristics of fixational eye movements are not significantly different between the fellow eyes of amblyopes and controls, and that the strabismic amblyopic eyes are always different from the other groups. Next, we determined the primary factors that limit fixation stability and visual acuity in amblyopic eyes by examining the relative importance of the different oculomotor characteristics, adding acuity (for fixation stability) or fixation stability (for acuity), and the type of amblyopia, as predictive factors in a multiple linear regression model. We show for the first time that the error magnitude of microsaccades, acuity, amplitude and frequency of microsaccades are primary factors limiting fixation stability; while the error magnitude, fixation stability, amplitude of drifts and amplitude of microsaccades are the primary factors limiting acuity. A mediation analysis showed that the effects of error magnitude and amplitude of microsaccades on acuity could be explained, at least in part, by their effects on fixation stability.

Unlabelled

Abnormal visual experience during a sensitive period of development disrupts neuronal circuitry in the visual cortex and results in abnormal spatial vision or amblyopia. Here we examined whether playing video games can induce plasticity in the visual system of adults with amblyopia. Specifically 20 adults with amblyopia (age 15-61 y; visual acuity: 20/25-20/480, with no manifest ocular disease or nystagmus) were recruited and allocated into three intervention groups: action videogame group (n = 10), non-action videogame group (n = 3), and crossover control group (n = 7). Our experiments show that playing video games (both action and non-action games) for a short period of time (40-80 h, 2 h/d) using the amblyopic eye results in a substantial improvement in a wide range of fundamental visual functions, from low-level to high-level, including visual acuity (33%), positional acuity (16%), spatial attention (37%), and stereopsis (54%). Using a cross-over experimental design (first 20 h: occlusion therapy, and the next 40 h: videogame therapy), we can conclude that the improvement cannot be explained simply by eye patching alone. We quantified the limits and the time course of visual plasticity induced by video-game experience. The recovery in visual acuity that we observed is at least 5-fold faster than would be expected from occlusion therapy in childhood amblyopia. We used positional noise and modelling to reveal the neural mechanisms underlying the visual improvements in terms of decreased spatial distortion (7%) and increased processing efficiency (33%). Our study had several limitations: small sample size, lack of randomization, and differences in numbers between groups. A large-scale randomized clinical study is needed to confirm the therapeutic value of video-game treatment in clinical situations. Nonetheless, taken as a pilot study, this work suggests that video-game play may provide important principles for treating amblyopia, and perhaps other cortical dysfunctions.

Trial registration

ClinicalTrials.gov NCT01223716.

What determines how much an organism can learn? One possibility is that the neural factors that limit sensory performance prior to learning, place an upper limit on the amount of learning that can take place. We tested this idea by comparing learning on a sensory task where performance is limited by cortical mechanisms, at two retinal eccentricities. Prior to learning, visual performance at the two eccentricities was either unmatched or equated in two different ways (through spatial scaling or visual crowding). The magnitude of learning was equivalent when initial levels of performance were matched regardless of how performance was equated. The magnitude of learning was a constant proportion of initial performance. This Weber-like law for perceptual learning demonstrates that it should be possible to predict the degree of perceptual improvement and the final level of performance that can be achieved via sensory training, regardless of what cortical constraint limits performance.