Objective
For most patients, resolution of upper limb impairment during the first 6 months poststroke is 70% of the maximum possible. We sought to identify candidate mechanisms of this proportional ...recovery. We hypothesized that proportional resolution of upper limb impairment depends on ipsilesional corticomotor pathway function, is mirrored by proportional recovery of excitability in this pathway, and is unaffected by upper limb therapy dose.
Methods
Upper limb impairment was measured in 93 patients at 2, 6, 12, and 26 weeks after first‐ever ischemic stroke. Motor evoked potentials (MEPs) and motor threshold were recorded from extensor carpi radialis using transcranial magnetic stimulation, and fractional anisotropy (FA) in the posterior limbs of the internal capsules was determined with diffusion‐weighted magnetic resonance imaging.
Results
Initial impairment score, presence of MEPs and FA asymmetry were the only predictors of impairment resolution, indicating a key role for corticomotor tract function. By 12 weeks, upper limb impairment resolved by 70% in patients with MEPs regardless of their initial impairment, and ipsilesional rest motor threshold also resolved by 70%. Resolution of impairment was insensitive to upper limb therapy dose.
Interpretation
These findings indicate that upper limb impairment resolves by 70% of the maximum possible, regardless of initial impairment, but only for patients with intact corticomotor function. Impairment resolution seems to reflect spontaneous neurobiological processes that involve the ipsilesional corticomotor pathway. A better understanding of these mechanisms could lead to interventions that increase resolution of impairment above 70%. Ann Neurol 2015;78:848–859
Abstract Background Non-invasive brain stimulation techniques may be useful adjuvants to promote recovery after stroke. They are typically used to facilitate ipsilesional cortical excitability ...directly, or indirectly by suppressing contralesional cortical excitability and reducing interhemispheric inhibition from the contralesional to ipsilesional hemisphere. However, most of the evidence for this approach comes from studies of patients at the chronic stage of recovery. Hypothesis We hypothesized that corticomotor excitability and interhemispheric inhibition would initially be asymmetric, with greater interhemispheric inhibition from contralesional to ipsilesional M1. We also hypothesized that balancing of corticomotor excitability and interhemispheric inhibition would be associated with greater improvements in paretic upper-limb impairment and function. Methods We conducted a retrospective analysis of longitudinal data collected from 46 patients during the first six months after stroke. Transcranial magnetic stimulation was used to measure rest motor threshold, stimulus-response curves, and ipsilateral silent periods from the extensor carpi radialis muscles of both upper limbs. Analyses of variance and linear regression modeling were used to evaluate the effect of time on corticomotor excitability and interhemispheric inhibition in both hemispheres, and associations between these effects and improvements in paretic upper-limb impairment and function. Results All participants had subcortical damage and only two had motor cortex involvement. As expected, ipsilesional corticomotor excitability was initially suppressed and increased over time, and this increase was associated with improved upper-limb impairment and function. However, interhemispheric inhibition was symmetrical and stable over time, and there was no evidence for a decrease in contralesional corticomotor excitability. Conclusions Neuromodulation interventions applied during spontaneous recovery may be more beneficial if they facilitate ipsilesional corticomotor excitability directly.
•Retinal prostheses have now been implanted in over 500 people with profound vision loss.•They are suitable for people with vision loss from outer retinal degenerative diseases, like retinitis ...pigmentosa.•Current devices can allow users to localize high-contrast objects and assist orientation skills.
Retinal prostheses are designed to restore a basic sense of sight to people with profound vision loss. They require a relatively intact posterior visual pathway (optic nerve, lateral geniculate nucleus and visual cortex). Retinal implants are options for people with severe stages of retinal degenerative disease such as retinitis pigmentosa and age-related macular degeneration.
There have now been three regulatory-approved retinal prostheses. Over five hundred patients have been implanted globally over the past 15 years. Devices generally provide an improved ability to localize high-contrast objects, navigate, and perform basic orientation tasks. Adverse events have included conjunctival erosion, retinal detachment, loss of light perception, and the need for revision surgery, but are rare. There are also specific device risks, including overstimulation (which could cause damage to the retina) or delamination of implanted components, but these are very unlikely.
Current challenges include how to improve visual acuity, enlarge the field-of-view, and reduce a complex visual scene to its most salient components through image processing. This review encompasses the work of over 40 individual research groups who have built devices, developed stimulation strategies, or investigated the basic physiology underpinning retinal prostheses. Current technologies are summarized, along with future challenges that face the field.
Post-saccadic oscillations (PSOs) reflect movements of gaze that result from motion of the pupil and lens relative to the eyeball rather than eyeball rotations. Here, we analyzed the characteristics ...of PSOs in subjects with age-related macular degeneration (AMD), retinitis pigmentosa (RP), and normal vision (NV). Our aim was to assess the differences in PSOs between people with vision loss and healthy controls because PSOs affect retinal image stability after each saccade.
Participants completed a horizontal saccade task and their gaze was measured using a pupil-based eye tracker. Oscillations occurring in the 80 to 200 ms post-saccadic period were described with a damped oscillation model. We compared the amplitude, decay time constant, and frequency of the PSOs for the three different groups. We also examined the correlation between these PSO parameters and the amplitude, peak velocity, and final deceleration of the preceding saccades.
Subjects with vision loss (AMD, n = 6, and RP, n = 5) had larger oscillation amplitudes, longer decay constants, and lower frequencies than subjects with NV (n = 7). The oscillation amplitudes increased with increases in saccade deceleration in all three groups. The other PSO parameters, however, did not show consistent correlations with either saccade amplitude or peak velocity.
Post-saccadic fixation stability in AMD and RP is reduced due to abnormal PSOs. The differences with respect to NV are not due to differences in saccade kinematics, suggesting that anatomic and neuronal variations affect the suspension of the iris and the lens in the patients' eyes.
The ability to live independently after stroke depends on the recovery of upper limb function. We hypothesized that bilateral priming with active-passive movements before upper limb physiotherapy ...would promote rebalancing of corticomotor excitability and would accelerate upper limb recovery at the subacute stage.
A single-center randomized controlled trial of bilateral priming was conducted with 57 patients randomized at the subacute stage after first-ever ischemic stroke. The PRIMED group made device-assisted mirror symmetrical bimanual movements before upper limb physiotherapy, every weekday for 4 weeks. The CONTROL group was given intermittent cutaneous electric stimulation of the paretic forearm before physiotherapy. Assessments were made at baseline, 6, 12, and 26 weeks. The primary end point was the proportion of patients who reached their plateau for upper limb function at 12 weeks, measured with the Action Research Arm Test.
Odds ratios indicated that PRIMED participants were 3× more likely than controls to reach their recovery plateau by 12 weeks. Intention-to-treat and per-protocol analyses showed a greater proportion of PRIMED participants achieved their plateau by 12 weeks (intention to treat, χ2=4.25; P=0.039 and per protocol, χ2=3.99; P=0.046). ANOVA of per-protocol data showed PRIMED participants had greater rebalancing of corticomotor excitability than controls at 12 and 26 weeks and interhemispheric inhibition at 26 weeks (all P<0.05).
Bilateral priming accelerated recovery of upper limb function in the initial weeks after stroke.
URL: http://www.anzctr.org.au. Unique identifier: ANZCTR1260900046822.
Most eye-movement studies in patients with visual field defects have examined the strategies that patients use while exploring a visual scene, but they have not investigated saccade kinematics. In ...healthy vision, saccade trajectories follow the remarkably stereotyped "main sequence": saccade duration increases linearly with saccade amplitude; peak velocity also increases linearly for small amplitudes, but approaches a saturation limit for large amplitudes. Recent theories propose that these relationships reflect the brain's attempt to optimize vision when planning eye movements. Therefore, in patients with bilateral retinal damage, saccadic behavior might differ to optimize vision under the constraints imposed by the visual field defects.
We compared saccadic behavior of patients with central vision loss, due to age-related macular degeneration (AMD), and patients with peripheral vision loss, due to retinitis pigmentosa (RP), to that of controls with normal vision (NV) using a horizontal saccade task.
Both patient groups demonstrated deficits in saccade reaction times and target localization behavior, as well as altered saccade kinematics. Saccades were generally slower and the shape of the velocity profiles were often atypical, especially in the patients with RP. In the patients with AMD, the changes were far less dramatic. For both groups, saccade kinematics were affected most when the target was in the subjects' blind field.
We conclude that defects of the central and peripheral retina have distinct effects on the saccade main sequence, and that visual inputs play an important role in planning the kinematics of a saccade.
Cortical auditory evoked potential (CAEP) thresholds have been shown to correlate well with behaviourally determined hearing thresholds. Growth functions of CAEPs show promise as an alternative to ...single level detection for objective hearing threshold estimation; however, the accuracy and clinical relevance of this method is not well examined.
In this study, we used temporal and spectral CAEP features to generate feature growth functions. Spectral features may be more robust than traditional peak-picking methods where CAEP morphology is variable, such as in children or hearing device users. Behavioural hearing thresholds were obtained and CAEPs were recorded in response to a 1 kHz puretone from twenty adults with no hearing loss. Four features, peak-to-peak amplitude, root-mean-square, peak spectral power and peak phase-locking value (PLV) were extracted from the CAEPs. Functions relating each feature with stimulus level were used to calculate objective hearing threshold estimates. We assessed the performance of each feature by calculating the difference between the objective estimate and the behaviourally-determined threshold.
We compared the accuracy of the estimates using each feature and found that the peak PLV feature performed best, with a mean threshold error of 2.7 dB and standard deviation of 5.9 dB from behavioural threshold across subjects. We also examined the relation between recording time, data quality and threshold estimate errors, and found that on average for a single threshold, 12.7 minutes of recording was needed for a 95% confidence that the threshold estimate was within 20 dB of the behavioural threshold using the peak-to-peak amplitude feature, while 14 minutes is needed for the peak PLV feature. These results show that the PLV of CAEPs can be used to find a clinically relevant hearing threshold estimate. Its potential stability in differing morphology may be an advantage in testing infants or cochlear implant users.
•Growth functions provide clinically viable objective estimates of hearing threshold.•Cortical response peak-to-peak amplitudes and phase locking values are suitable.•Best threshold estimates are consistently within 6 dB of behavioural threshold.•13 min testing time for ±20 dB accuracy with single electrode recording.
Cochlear implant users require fitting of electrical threshold and comfort levels for optimal access to sound. In this study, we used single-channel cortical auditory evoked responses (CAEPs) ...obtained from 20 participants using a Nucleus device. A fully objective method to estimate threshold levels was developed, using growth function fitting and the peak phase-locking value feature. Results demonstrated that growth function fitting is a viable method for estimating threshold levels in cochlear implant users, with a strong correlation (r = 0.979, p < 0.001) with behavioral thresholds. Additionally, we compared the threshold estimates using CAEPs acquired from a standard montage (Cz to mastoid) against using a montage of recording channels near the cochlear implant, simulating recording from the device itself. The correlation between estimated and behavioural thresholds remained strong (r = 0.966, p < 0.001), however the recording time needed to be increased to produce a similar estimate accuracy. Finally, a method for estimating comfort levels was investigated, and showed that the comfort level estimates were mildly correlated with behavioral comfort levels (r = 0.50, p = 0.024).
•Cortical phase-locking value growth functions predicted hearing thresholds.•Objective cochlear implant threshold estimates vs behavioral threshold: r = 0.979•Method is robust with recording location next to cochlear implant: r = 0.966•Five minutes of testing gives threshold estimation error of 12.9 ± 19.9% DR.
One strategy to improve the effectiveness of prosthetic vision devices is to process incoming images to ensure that key information can be perceived by the user. This paper presents the first ...comprehensive results of vision function testing for a suprachoroidal retinal prosthetic device utilizing of 20 stimulating electrodes. Further, we investigate whether using image filtering can improve results on a light localization task for implanted participants compared to minimal vision processing. No controlled implanted participant studies have yet investigated whether vision processing methods that are not task-specific can lead to improved results.
Three participants with profound vision loss from retinitis pigmentosa were implanted with a suprachoroidal retinal prosthesis. All three completed multiple trials of a light localization test, and one participant completed multiple trials of acuity tests. The visual representations used were: Lanczos2 (a high quality Nyquist bandlimited downsampling filter); minimal vision processing (MVP); wide view regional averaging filtering (WV); scrambled; and, system off.
Using Lanczos2, all three participants successfully completed a light localization task and obtained a significantly higher percentage of correct responses than using MVP (Formula: see text) or with system off (Formula: see text). Further, in a preliminary result using Lanczos2, one participant successfully completed grating acuity and Landolt C tasks, and showed significantly better performance (Formula: see text) compared to WV, scrambled and system off on the grating acuity task.
Participants successfully completed vision tasks using a 20 electrode suprachoroidal retinal prosthesis. Vision processing with a Nyquist bandlimited image filter has shown an advantage for a light localization task. This result suggests that this and targeted, more advanced vision processing schemes may become important components of retinal prostheses to enhance performance. ClinicalTrials.gov Identifier: NCT01503576.
Retinal prostheses provide vision to blind patients by eliciting phosphenes through electrical stimulation. This study explored whether character identification and image localization could be ...achieved through direct multiple-electrode stimulation with a suprachoroidal retinal prosthesis.
Two of three retinitis pigmentosa patients implanted with a suprachoroidal electrode array were tested on three psychophysical tasks. Electrode patterns were stimulated to elicit perception of simple characters, following which percept localization was tested using either static or dynamic images. Eye tracking was used to assess the association between accuracy and eye movements.
In the character identification task, accuracy ranged from 2.7% to 93.3%, depending on the patient and character. In the static image localization task, accuracy decreased from near perfect to <20% with decreasing contrast (patient 1). Patient 2 scored up to 70% at 100% contrast. In the dynamic image localization task, patient 1 recognized the trajectory of the image up to speeds of 64 deg/s, whereas patient 2 scored just above chance. The degree of eye movement in both patients was related to accuracy and, to some extent, stimulus direction.
The ability to identify characters and localize percepts demonstrates the capacity of the suprachoroidal device to provide meaningful information to blind patients. The variation in scores across all tasks highlights the importance of using spatial cues from phosphenes, which becomes more difficult at low contrast. The use of spatial information from multiple electrodes and eye-movement compensation is expected to improve performance outcomes during real-world prosthesis use in a camera-based system. (ClinicalTrials.gov number, NCT01603576.).
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