Learning to stand with sensorimotor delays generalizes across directions and from hand to leg effectors.

Humans receive sensory information from the past, requiring the brain to overcome delays to perform daily motor skills such as standing upright. Because delays vary throughout the body and change over a lifetime, it would be advantageous to generalize learned control policies of balancing with delays across contexts. However, not all forms of learning generalize. Here, we use a robotic simulator to impose delays into human balance. When delays are imposed in one direction of standing, participants are initially unstable but relearn to balance by reducing the variability of their motor actions and transfer balance improvements to untrained directions. Upon returning to normal standing, aftereffects from learning are observed as small oscillations in control, yet they do not destabilize balance. Remarkably, when participants train to balance with delays using their hand, learning transfers to standing with the legs. Our findings establish that humans use experience to broadly update their neural control to balance with delays.

Population-wide cerebellar growth models of children and adolescents.

In the past, the cerebellum has been best known for its crucial role in motor function. However, increasingly more findings highlight the importance of cerebellar contributions in cognitive functions and neurodevelopment. Using a total of 7240 neuroimaging scans from 4862 individuals, we describe and provide detailed, openly available models of cerebellar development in childhood and adolescence (age range: 6-17 years), an important time period for brain development and onset of neuropsychiatric disorders. Next to a traditionally used anatomical parcellation of the cerebellum, we generated growth models based on a recently proposed functional parcellation. In both, we find an anterior-posterior growth gradient mirroring the age-related improvements of underlying behavior and function, which is analogous to cerebral maturation patterns and offers evidence for directly related cerebello-cortical developmental trajectories. Finally, we illustrate how the current approach can be used to detect cerebellar abnormalities in clinical samples.

Effect on diagnostic accuracy of cognitive reasoning tools for the workplace setting: systematic review and meta-analysis.

BACKGROUND: Preventable diagnostic errors are a large burden on healthcare. Cognitive reasoning tools, that is, tools that aim to improve clinical reasoning, are commonly suggested interventions. However, quantitative estimates of tool effectiveness have been aggregated over both workplace-oriented and educational-oriented tools, leaving the impact of workplace-oriented cognitive reasoning tools alone unclear. This systematic review and meta-analysis aims to estimate the effect of cognitive reasoning tools on improving diagnostic performance among medical professionals and students, and to identify factors associated with larger improvements. METHODS: Controlled experimental studies that assessed whether cognitive reasoning tools improved the diagnostic accuracy of individual medical students or professionals in a workplace setting were included. Embase.com, Medline ALL via Ovid, Web of Science Core Collection, Cochrane Central Register of Controlled Trials and Google Scholar were searched from inception to 15 October 2021, supplemented with handsearching. Meta-analysis was performed using a random-effects model. RESULTS: The literature search resulted in 4546 articles of which 29 studies with data from 2732 participants were included for meta-analysis. The pooled estimate showed considerable heterogeneity (I2=70%). This was reduced to I2=38% by removing three studies that offered training with the tool before the intervention effect was measured. After removing these studies, the pooled estimate indicated that cognitive reasoning tools led to a small improvement in diagnostic accuracy (Hedges' g=0.20, 95% CI 0.10 to 0.29, p<0.001). There were no significant subgroup differences. CONCLUSION: Cognitive reasoning tools resulted in small but clinically important improvements in diagnostic accuracy in medical students and professionals, although no factors could be distinguished that resulted in larger improvements. Cognitive reasoning tools could be routinely implemented to improve diagnosis in practice, but going forward, more large-scale studies and evaluations of these tools in practice are needed to determine how these tools can be effectively implemented. PROSPERO REGISTRATION NUMBER: CRD42020186994.

Addressing the inconsistent electric fields of tDCS by using patient-tailored configurations in chronic stroke: Implications for treatment.

Transcranial direct current stimulation (tDCS) is a promising tool to improve and speed up motor rehabilitation after stroke, but inconsistent clinical effects refrain tDCS from clinical implementation. Therefore, this study aimed to assess the need for individualized tDCS configurations in stroke, considering interindividual variability in brain anatomy and motor function representation. We simulated tDCS in individualized MRI-based finite element head models of 21 chronic stroke subjects and 10 healthy age-matched controls. An anatomy-based stimulation target, i.e. the motor hand knob, was identified with MRI, whereas a motor function-based stimulation target was identified with EEG. For each subject, we simulated conventional anodal tDCS electrode configurations and optimized electrode configurations to maximize stimulation strength within the anatomical and functional target. The normal component of the electric field was extracted and compared between subjects with stroke and healthy, age-matched controls, for both targets, during conventional and optimized tDCS. Electrical field strength was significantly lower, more variable and more frequently in opposite polarity for subjects with stroke compared to healthy age-matched subjects, both for the anatomical and functional target with conventional, i.e. non-individualized, electrode configurations. Optimized, i.e. individualized, electrode configurations increased the electrical field strength in the anatomical and functional target for subjects with stroke but did not reach the same levels as in healthy subjects. Considering individual brain structure and motor function is crucial for applying tDCS in subjects with stroke. Lack of individualized tDCS configurations in subjects with stroke results in lower electric fields in stimulation targets, which may partially explain the inconsistent clinical effects of tDCS in stroke trials.

Transcranial Direct Current Stimulation Targeting the Entire Motor Network Does Not Increase Corticospinal Excitability.

Transcranial direct current stimulation (tDCS) over the contralateral primary motor cortex of the target muscle (conventional tDCS) has been described to enhance corticospinal excitability, as measured with transcranial magnetic stimulation. Recently, tDCS targeting the brain regions functionally connected to the contralateral primary motor cortex (motor network tDCS) was reported to enhance corticospinal excitability more than conventional tDCS. We compared the effects of motor network tDCS, 2 mA conventional tDCS, and sham tDCS on corticospinal excitability in 21 healthy participants in a randomized, single-blind within-subject study design. We applied tDCS for 12 min and measured corticospinal excitability with TMS before tDCS and at 0, 15, 30, 45, and 60 min after tDCS. Statistical analysis showed that neither motor network tDCS nor conventional tDCS significantly increased corticospinal excitability relative to sham stimulation. Furthermore, the results did not provide evidence for superiority of motor network tDCS over conventional tDCS. Motor network tDCS seems equally susceptible to the sources of intersubject and intrasubject variability previously observed in response to conventional tDCS.

Purkinje Cell Activity in the Medial and Lateral Cerebellum During Suppression of Voluntary Eye Movements in Rhesus Macaques.

Volitional suppression of responses to distracting external stimuli enables us to achieve our goals. This volitional inhibition of a specific behavior is supposed to be mainly mediated by the cerebral cortex. However, recent evidence supports the involvement of the cerebellum in this process. It is currently not known whether different parts of the cerebellar cortex play differential or synergistic roles in the planning and execution of this behavior. Here, we measured Purkinje cell (PC) responses in the medial and lateral cerebellum in two rhesus macaques during pro- and anti-saccade tasks. During an antisaccade trial, non-human primates (NHPs) were instructed to make a saccadic eye movement away from a target, rather than toward it, as in prosaccade trials. Our data show that the cerebellum plays an important role not only during the execution of the saccades but also during the volitional inhibition of eye movements toward the target. Simple spike (SS) modulation during the instruction and execution periods of pro- and anti-saccades was prominent in PCs of both the medial and lateral cerebellum. However, only the SS activity in the lateral cerebellar cortex contained information about stimulus identity and showed a strong reciprocal interaction with complex spikes (CSs). Moreover, the SS activity of different PC groups modulated bidirectionally in both of regions, but the PCs that showed facilitating and suppressive activity were predominantly associated with instruction and execution, respectively. These findings show that different cerebellar regions and PC groups contribute to goal-directed behavior and volitional inhibition, but with different propensities, highlighting the rich repertoire of the cerebellar control in executive functions.

Individual differences in error-related frontal midline theta activity during visuomotor adaptation.

Post-feedback frontal midline EEG activity has been found to correlate with error magnitude during motor adaptation. However, the role of this neuronal activity remains to be elucidated. It has been hypothesized that post-feedback frontal midline activity may represent a prediction error, which in turn may be directly related to the adaptation process or to an unspecific orienting response. To address these hypotheses, we replicated a previous visuomotor adaptation experiment with very small perturbations, likely to invoke implicit adaptation, in a new group of 60 participants and combined it with EEG recordings. We found error-related peaks in the frontal midline electrodes in the time domain. However, these were best understood as modulations of frontal midline theta activity (FMT, 4-8 Hz). Trial-level differences in FMT correlated with error magnitude. This correlation was robust even for very small errors as well as in the absence of imposed perturbations, indicating that FMT does not depend on explicit or strategic re-aiming. Within participants, trial-level differences in FMT were not related to between-trial error corrections. Between participants, individual differences in FMT-error-sensitivity did not predict differences in adaptation rate. Taken together, these results imply that FMT does not drive implicit motor adaptation. Finally, individual differences in FMT-error-sensitivity negatively correlate to motor execution noise. This suggests that FMT reflects saliency: larger execution noise means a larger standard deviation of errors so that a fixed error magnitude is less salient. In conclusion, this study suggests that frontal midline theta activity represents a saliency signal and does not directly drive motor adaptation.

Environmental Enrichment Improves Vestibular Oculomotor Learning in Mice.

We assessed the behavioral effects of environmental enrichment on contrast sensitivity, reflexive eye movements and on oculomotor learning in mice that were housed in an enriched environment for a period of 3 weeks. Research has shown that a larger cage and a more complex environment have positive effects on the welfare of laboratory mice and other animals held in captivity. It has also been shown that environmental enrichment affects various behavior and neuroanatomical and molecular characteristics. We found a clear effect on oculomotor learning. Animals that were housed in an enriched environment learned significantly faster than controls that were housed under standard conditions. In line with existing literature, the enriched group also outperformed the controls in behavioral tests for explorative behavior. Meanwhile, both visual and reflexive oculomotor performance in response to visual and vestibular stimuli was unaffected. This points toward an underlying mechanism that is specific for motor learning, rather than overall motor performance.

Theta but not beta power is positively associated with better explicit motor task learning.

Neurophysiologic correlates of motor learning that can be monitored during neurorehabilitation interventions can facilitate the development of more effective learning methods. Previous studies have focused on the role of the beta band (14-30 Hz) because of its clear response during motor activity. However, it is difficult to discriminate between beta activity related to learning a movement and performing the movement. In this study, we analysed differences in the electroencephalography (EEG) power spectra of complex and simple explicit sequential motor tasks in healthy young subjects. The complex motor task (CMT) allowed EEG measurement related to motor learning. In contrast, the simple motor task (SMT) made it possible to control for EEG activity associated with performing the movement without significant motor learning. Source reconstruction of the EEG revealed task-related activity from 5 clusters covering both primary motor cortices (M1) and 3 clusters localised to different parts of the cingulate cortex (CC). We found no association between M1 beta power and learning, but the CMT produced stronger bilateral beta suppression compared to the SMT. However, there was a positive association between contralateral M1 theta (5-8 Hz) and alpha (8-12 Hz) power and motor learning, and theta and alpha power in the posterior mid-CC and posterior CC were positively associated with greater motor learning. These findings suggest that the theta and alpha bands are more related to motor learning than the beta band, which might merely relate to the level of perceived difficulty during learning.

The use of eye-movement recording in patients with anti-Hu antibody-associated paraneoplastic neurological syndromes to objectively determine extent and course of disease.

BACKGROUND AND PURPOSE: Paraneoplastic neurological syndromes with Hu-antibodies (Hu-PNS) are immune-mediated disorders in patients with malignancies, most frequently small cell lung cancer, affecting both the peripheral and central nervous system (CNS). In Hu-PNS, brainstem and cerebellar involvement are common. Here, we assessed whether eye-movement disturbances can be used for diagnosis and monitoring of CNS involvement in Hu-PNS. METHODS: Twenty-nine patients with Hu-PNS (17 females; mean age, 63.2 years,) and 14 healthy age-matched controls (seven females; mean age, 60.2 years) were included. Saccadic and smooth pursuit eye movements in response to visual stimuli were recorded with video-oculography. Eye movements were scored quantitatively (number of correction saccades, saccadic intrusions, and saccades during fixation period) and qualitatively by two eye-movement experts. In 20 patients, up to three follow-up measurements were made during subsequent hospital visits with fixed 4-week intervals. Disease course was assessed using the modified Rankin Scale. RESULTS: Eye movements were disturbed in 26 of 29 Hu-PNS patients, with horizontal eye movements being in general more impaired. Moreover, in 12 of the 14 Hu-PNS patients without clinical CNS involvement, eye movements were disturbed. Changes in eye-movement control over a period of up to 12 weeks were significantly correlated with the clinical response to treatment (ρ = 0.52, p = 0.02). CONCLUSIONS: Hu-PNS often affects eye-movement control, also in the absence of CNS signs or symptoms. Eye-movement recordings in Hu-PNS patients might be a useful tool to objectively monitor progression and treatment efficacy in Hu-PNS patients.

Developmental changes in visual search are determined by changing visuospatial abilities and task repetition: A longitudinal study in adolescents.

Using a longitudinal study design, a group of 94 adolescents participated in a visual search task and a visuospatial ability task yearly for four consecutive years. We analyzed the association between changes in visuospatial ability and changes in visual search performance and behavior and estimated additional effects of age and task repetition. Visuospatial ability was measured with the Design Organization Test (DOT). Search performance was analyzed in terms of reaction time and response accuracy. Search behavior was analyzed in terms of the number of fixations per trial, the saccade amplitude, and the distribution of fixations over different types of elements. We found that both the increase in age and the yearly repetition of the DOT had a positive effect on visuospatial ability. We show that the acceleration of visual search during childhood can be explained by the increase in visuospatial abilities with age during adolescence. With the yearly task repetition, visual search became faster and more accurate, while fewer fixations were made with larger saccade amplitudes. The combination of increasing visuospatial ability and task repetition makes visual search more effective and might increase the performance of many daily tasks during adolescence.

No effect of anodal tDCS on motor cortical excitability and no evidence for responders in a large double-blind placebo-controlled trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) has emerged as a non-invasive brain stimulation technique. Most studies show that anodal tDCS increases cortical excitability. However, this effect has been found to be highly variable. OBJECTIVE: To test the effect of anodal tDCS on cortical excitability and the interaction effect of two participant-specific factors that may explain individual differences in sensitivity to anodal tDCS: the Brain Derived Neurotrophic Factor Val66Met polymorphism (BDNF genotype) and the latency difference between anterior-posterior and lateromedial TMS pulses (APLM latency). METHODS: In 62 healthy participants, cortical excitability over the left motor cortex was measured before and after anodal tDCS at 2 mA for 20 min in a pre-registered, double-blind, randomized, placebo-controlled trial with repeated measures. RESULTS: We did not find a main effect of anodal tDCS, nor an interaction effect of the participant-specific predictors. Moreover, further analyses did not provide evidence for the existence of responders and non-responders. CONCLUSION: This study indicates that anodal tDCS at 2 mA for 20 min may not reliably affect cortical excitability.

Continuing medical education during pandemic waves of COVID-19: Consensus from medical faculties in Asia, Australia and Europe.

This article was migrated. The article was marked as recommended. Medical faculties have the responsibility to train tomorrow's doctors and in a crisis face the challenge of delivering students into the workforce promptly and safely. Worldwide, medical faculties have faced unprecedented disruptions from viral outbreaks and pandemics including SARS, Ebola, H1N1 and COVID-19 which bring unique challenges. Currently there is worldwide disruption to medical faculties and medical education due to COVID-19. Despite close links with clinical medicine and the known risks of pandemics, many medical faculties have been caught off guard without pandemic planning in place, to deal with an exponential rise in infections and deaths, overwhelmed health services and widespread community risk of transmission. Assessing transmission risk of COVID-19 in teaching, clinical and community attachments and continuing medical education is paramount as medical faculties face subsequent pandemics waves. Consensus statements based on best available evidence and international expertise from medical faculties in Asia, Australia and Europe were developed to help guide the protection of staff and students, priorities on teaching activities and further educational development. Infection prevention, infection control, contact tracing and medical surveillance are detailed to minimise transmission and to enhance safety. Recommendations on teaching activities planning can enhance responsiveness of medical faculties to tackle subsequent waves of COVID-19 infection. A global approach and dialogue are encouraged.

A Neuroanatomically Grounded Optimal Control Model of the Compensatory Eye Movement System in Mice.

We present a working model of the compensatory eye movement system in mice. We challenge the model with a data set of eye movements in mice (n =34) recorded in 4 different sinusoidal stimulus conditions with 36 different combinations of frequency (0.1-3.2 Hz) and amplitude (0.5-8°) in each condition. The conditions included vestibular stimulation in the dark (vestibular-ocular reflex, VOR), optokinetic stimulation (optokinetic reflex, OKR), and two combined visual/vestibular conditions (the visual-vestibular ocular reflex, vVOR, and visual suppression of the VOR, sVOR). The model successfully reproduced the eye movements in all conditions, except for minor failures to predict phase when gain was very low. Most importantly, it could explain the interaction of VOR and OKR when the two reflexes are activated simultaneously during vVOR stimulation. In addition to our own data, we also reproduced the behavior of the compensatory eye movement system found in the existing literature. These include its response to sum-of-sines stimuli, its response after lesions of the nucleus prepositus hypoglossi or the flocculus, characteristics of VOR adaptation, and characteristics of drift in the dark. Our model is based on ideas of state prediction and forward modeling that have been widely used in the study of motor control. However, it represents one of the first quantitative efforts to simulate the full range of behaviors of a specific system. The model has two separate processing loops, one for vestibular stimulation and one for visual stimulation. Importantly, state prediction in the visual processing loop depends on a forward model of residual retinal slip after vestibular processing. In addition, we hypothesize that adaptation in the system is primarily adaptation of this model. In other words, VOR adaptation happens primarily in the OKR loop.

Predicting Upper Limb Motor Impairment Recovery after Stroke: A Mixture Model.

OBJECTIVE: Spontaneous recovery is an important determinant of upper extremity recovery after stroke and has been described by the 70% proportional recovery rule for the Fugl-Meyer motor upper extremity (FM-UE) scale. However, this rule is criticized for overestimating the predictability of FM-UE recovery. Our objectives were to develop a longitudinal mixture model of FM-UE recovery, identify FM-UE recovery subgroups, and internally validate the model predictions. METHODS: We developed an exponential recovery function with the following parameters: subgroup assignment probability, proportional recovery coefficient r k , time constant in weeks τ k , and distribution of the initial FM-UE scores. We fitted the model to FM-UE measurements of 412 first-ever ischemic stroke patients and cross-validated endpoint predictions and FM-UE recovery cluster assignment. RESULTS: The model distinguished 5 subgroups with different recovery parameters ( r1 = 0.09, τ1 = 5.3, r2 = 0.46, τ2 = 10.1, r3 = 0.86, τ3 = 9.8, r4 = 0.89, τ4 = 2.7, r5 = 0.93, τ5 = 1.2). Endpoint FM-UE was predicted with a median absolute error of 4.8 (interquartile range [IQR] = 1.3-12.8) at 1 week poststroke and 4.2 (IQR = 1.3-9.8) at 2 weeks. Overall accuracy of assignment to the poor (subgroup 1), moderate (subgroups 2 and 3), and good (subgroups 4 and 5) FM-UE recovery clusters was 0.79 (95% equal-tailed interval [ETI] = 0.78-0.80) at 1 week poststroke and 0.81 (95% ETI = 0.80-0.82) at 2 weeks. INTERPRETATION: FM-UE recovery reflects different subgroups, each with its own recovery profile. Cross-validation indicates that FM-UE endpoints and FM-UE recovery clusters can be well predicted. Results will contribute to the understanding of upper limb recovery patterns in the first 6 months after stroke. ANN NEUROL 2020;87:383-393 Ann Neurol 2020;87:383-393.

The Vestibular Drive for Balance Control Is Dependent on Multiple Sensory Cues of Gravity.

Vestibular signals, which encode head movement in space as well as orientation relative to gravity, contribute to the ongoing muscle activity required to stand. The strength of this vestibular contribution changes with the presence and quality of sensory cues of balance. Here we investigate whether the vestibular drive for standing balance also depends on different sensory cues of gravity by examining vestibular-evoked muscle responses when independently varying load and gravity conditions. Standing subjects were braced by a backboard structure that limited whole-body sway to the sagittal plane while load and vestibular cues of gravity were manipulated by: (a) loading the body downward at 1.5 and 2 times body weight (i.e., load cues), and/or (b) exposing subjects to brief periods (20 s) of micro- (<0.05 g) and hyper-gravity (∼1.8 g) during parabolic flights (i.e., vestibular cues). A stochastic electrical vestibular stimulus (0-25 Hz) delivered during these tasks evoked a vestibular-error signal and corrective muscles responses that were used to assess the vestibular drive to standing balance. With additional load, the magnitude of the vestibular-evoked muscle responses progressively increased, however, when these responses were normalized by the ongoing muscle activity, they decreased and plateaued at 1.5 times body weight. This demonstrates that the increased muscle activity necessary to stand with additional load is accompanied a proportionally smaller increase in vestibular input. This reduction in the relative vestibular contribution to balance was also observed when we varied the vestibular cues of gravity, but only during an absence (<0.05 g) and not an excess (∼1.8 g) of gravity when compared to conditions with normal 1 g gravity signals and equivalent load signals. Despite these changes, vestibular-evoked responses were observed in all conditions, indicating that vestibular cues of balance contribute to upright standing even in the near absence of a vestibular signal of gravity (i.e., micro-gravity). Overall, these experiments provide evidence that both load and vestibular cues of gravity influence the vestibular signal processing for the control of standing balance.

TMS motor mapping: Comparing the absolute reliability of digital reconstruction methods to the golden standard.

BACKGROUND: Changes in transcranial magnetic stimulation motor map parameters can be used to quantify plasticity in the human motor cortex. The golden standard uses a counting analysis of motor evoked potentials (MEPs) acquired with a predefined grid. Recently, digital reconstruction methods have been proposed, allowing MEPs to be acquired with a faster pseudorandom procedure. However, the reliability of these reconstruction methods has never been compared to the golden standard. OBJECTIVE: To compare the absolute reliability of the reconstruction methods with the golden standard. METHODS: In 21 healthy subjects, both grid and pseudorandom acquisition were performed twice on the first day and once on the second day. The standard error of measurement was calculated for the counting analysis and the digital reconstructions. RESULTS: The standard error of measurement was at least equal using digital reconstructions. CONCLUSION: Pseudorandom acquisition and digital reconstruction can be used in intervention studies without sacrificing reliability.

Individual Differences in Motor Noise and Adaptation Rate Are Optimally Related.

Individual variations in motor adaptation rate were recently shown to correlate with movement variability or "motor noise" in a forcefield adaptation task. However, this finding could not be replicated in a meta-analysis of adaptation experiments. Possibly, this inconsistency stems from noise being composed of distinct components that relate to adaptation rate in different ways. Indeed, previous modeling and electrophysiological studies have suggested that motor noise can be factored into planning noise, originating from the brain, and execution noise, stemming from the periphery. Were the motor system optimally tuned to these noise sources, planning noise would correlate positively with adaptation rate, and execution noise would correlate negatively with adaptation rate, a phenomenon familiar in Kalman filters. To test this prediction, we performed a visuomotor adaptation experiment in 69 subjects. Using a novel Bayesian fitting procedure, we succeeded in applying the well-established state-space model of adaptation to individual data. We found that adaptation rate correlates positively with planning noise (ß = 0.44; 95% HDI = [0.27 0.59]) and negatively with execution noise (ß = -0.39; 95% HDI = [-0.50 -0.30]). In addition, the steady-state Kalman gain calculated from planning and execution noise correlated positively with adaptation rate (r = 0.54; 95% HDI = [0.38 0.66]). These results suggest that motor adaptation is tuned to approximate optimal learning, consistent with the "optimal control" framework that has been used to explain motor control. Since motor adaptation is thought to be a largely cerebellar process, the results further suggest the sensitivity of the cerebellum to both planning noise and execution noise.

Visual search accelerates during adolescence.

We studied changes in visual-search performance and behavior during adolescence. Search performance was analyzed in terms of reaction time and response accuracy. Search behavior was analyzed in terms of the objects fixated and the duration of these fixations. A large group of adolescents (N = 140; age: 12-19 years; 47% female, 53% male) participated in a visual-search experiment in which their eye movements were recorded with an eye tracker. The experiment consisted of 144 trials (50% with a target present), and participants had to decide whether a target was present. Each trial showed a search display with 36 Gabor patches placed on a hexagonal grid. The target was a vertically oriented element with a high spatial frequency. Nontargets differed from the target in spatial frequency, orientation, or both. Search performance and behavior changed during adolescence; with increasing age, fixation duration and reaction time decreased. Response accuracy, number of fixations, and selection of elements to fixate upon did not change with age. Thus, the speed of foveal discrimination increases with age, while the efficiency of peripheral selection does not change. We conclude that the way visual information is gathered does not change during adolescence, but the processing of visual information becomes faster.

Cerebellar transcranial direct current stimulation interacts with BDNF Val66Met in motor learning.

BACKGROUND: Cerebellar transcranial direct current stimulation has been reported to enhance motor associative learning and motor adaptation, holding promise for clinical application in patients with movement disorders. However, behavioral benefits from cerebellar tDCS have been inconsistent. OBJECTIVE: Identifying determinants of treatment success is necessary. BDNF Val66Met is a candidate determinant, because the polymorphism is associated with motor skill learning and BDNF is thought to mediate tDCS effects. METHODS: We undertook two cerebellar tDCS studies in subjects genotyped for BDNF Val66Met. Subjects performed an eyeblink conditioning task and received sham, anodal or cathodal tDCS (N = 117, between-subjects design) or a vestibulo-ocular reflex adaptation task and received sham and anodal tDCS (N = 51 subjects, within-subjects design). Performance was quantified as a learning parameter from 0 to 100%. We investigated (1) the distribution of the learning parameter with mixture modeling presented as the mean (M), standard deviation (S) and proportion (P) of the groups, and (2) the role of BDNF Val66Met and cerebellar tDCS using linear regression presented as the regression coefficients (B) and odds ratios (OR) with equally-tailed intervals (ETIs). RESULTS: For the eyeblink conditioning task, we found distinct groups of learners (MLearner = 67.2%; SLearner = 14.7%; PLearner = 61.6%) and non-learners (MNon-learner = 14.2%; SNon-learner = 8.0%; PNon-learner = 38.4%). Carriers of the BDNF Val66Met polymorphism were more likely to be learners (OR = 2.7 [1.2 6.2]). Within the group of learners, anodal tDCS supported eyeblink conditioning in BDNF Val66Met non-carriers (B = 11.9% 95%ETI = [0.8 23.0]%), but not in carriers (B = 1.0% 95%ETI = [-10.2 12.1]%). For the vestibulo-ocular reflex adaptation task, we found no effect of BDNF Val66Met (B = -2.0% 95%ETI = [-8.7 4.7]%) or anodal tDCS in either carriers (B = 3.4% 95%ETI = [-3.2 9.5]%) or non-carriers (B = 0.6% 95%ETI = [-3.4 4.8]%). Finally, we performed additional saccade and visuomotor adaptation experiments (N = 72) to investigate the general role of BDNF Val66Met in cerebellum-dependent learning and found no difference between carriers and non-carriers for both saccade (B = 1.0% 95%ETI = [-8.6 10.6]%) and visuomotor adaptation (B = 2.7% 95%ETI = [-2.5 7.9]%). CONCLUSIONS: The specific role for BDNF Val66Met in eyeblink conditioning, but not vestibulo-ocular reflex adaptation, saccade adaptation or visuomotor adaptation could be related to dominance of the role of simple spike suppression of cerebellar Purkinje cells with a high baseline firing frequency in eyeblink conditioning. Susceptibility of non-carriers to anodal tDCS in eyeblink conditioning might be explained by a relatively larger effect of tDCS-induced subthreshold depolarization in this group, which might increase the spontaneous firing frequency up to the level of that of the carriers.