Parent-reported problems in children with Cerebral Visual Impairment: Improving the discriminative ability from ADHD and dyslexia using screening inventories.

Daily problems of children with Cerebral Visual Impairment (CVI) are often misinterpreted as symptoms of behavioural disorders or learning disabilities instead of higher order visual function (HOVF) deficits. It is difficult to differentiate between various paediatric clinical groups based on daily manifestations. We used two CVI inventories (V-CVI-I, HVFQI) and an ADHD questionnaire (AVL) to compare parent-reported visual and behavioural problems of children with CVI, ADHD, dyslexia and neurotypical children (Age 6-15, Verbal Intelligence > 70). Our results show a higher percentage of parent-reported visual problems in children with CVI compared to all other groups, which was not affected by their visual acuity levels. On most HOVF categories, a higher percentage of parent-reported visual problems was also found in children with ADHD or dyslexia compared to neurotypical children. Children with ADHD had significantly more parent-reported behavioural problems, but more behavioural problems were reported by the parents of children with CVI compared to neurotypical children as well. Our findings complicate using the existing inventories for initial screening and referral of children with potential CVI. We propose a shortened screening list to improve the potential differentiation between CVI and ADHD or dyslexia based on parent-reported visual problems in everyday life.

Eye tracking: empirical foundations for a minimal reporting guideline.

In this paper, we present a review of how the various aspects of any study using an eye tracker (such as the instrument, methodology, environment, participant, etc.) affect the quality of the recorded eye-tracking data and the obtained eye-movement and gaze measures. We take this review to represent the empirical foundation for reporting guidelines of any study involving an eye tracker. We compare this empirical foundation to five existing reporting guidelines and to a database of 207 published eye-tracking studies. We find that reporting guidelines vary substantially and do not match with actual reporting practices. We end by deriving a minimal, flexible reporting guideline based on empirical research (Section "An empirically based minimal reporting guideline").

Pain Experience is Somatotopically Organized and Overlaps with Pain Anticipation in the Human Cerebellum.

Many fMRI studies have shown activity in the cerebellum after peripheral nociceptive stimulation. We investigated whether the areas in the cerebellum that were activated after nociceptive thumb stimulation were separate from those after nociceptive toe stimulation. In an additional experiment, we investigated the same for the anticipation of a nociceptive stimulation on the thumb or toe. For his purpose, we used fMRI after an electrical stimulation of the thumb and toe in 19 adult healthy volunteers. Following nociceptive stimulation, different areas were activated by stimulation on the thumb (lobule VI ipsilaterally and Crus II mainly contralaterally) and toe (lobules VIII-IX and IV-V bilaterally and lobule VI contralaterally), i.e., were somatotopically organized. Cerebellar areas innervated non-somatotopically by both toe and thumb stimulation were the posterior vermis and Crus I, bilaterally. In the anticipation experiment, similar results were found. However, here, the somatotopically activated areas were relatively small for thumb and negligible for toe stimulation, while the largest area was innervated non-somatotopically and consisted mainly of Crus I and lobule VI bilaterally. These findings indicate that nociceptive stimulation and anticipation of nociceptive stimulation are at least partly processed by the same areas in the cerebellum. This was confirmed by an additional conjunction analysis. Based on our findings, we hypothesize that input that is organized in a somatotopical manner reflects direct input from the spinal cord, while non-somatotopically activated parts of the cerebellum receive their information indirectly through cortical and subcortical connections, possibly involved in processing contextual emotional states, like the expectation of pain.

Kidney function, gait pattern and fall in the general population: a cohort study.

Background: Gait disturbance is proposed as a mechanism for higher risk of fall in kidney disease patients. We investigated the association of kidney function with gait pattern in the general population and tested whether the association between impaired kidney function and fall is more pronounced in subjects with lower gait function. Methods: We included 1430 participants (mean age: 60 years) from the Rotterdam Study. Kidney function was assessed using estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). We assessed global gait, gait velocity and seven independent gait domains: Rhythm, Phases, Variability, Pace, Tandem, Turning and Base of Support. Regression models adjusted for cardiometabolic and neurological factors were used. We evaluated whether participants with impaired kidney function and impaired gait fell more in the previous year. Results: The study population had a median (interquartile range) ACR of 3.6 (2.5-6.2) mg/g and mean ± SD eGFR of 87.6 ± 15 mL/min/1.73 m2. Higher ACR and lower eGFR were associated with lower global gait score [per doubling of ACR: -0.10, 95% confidence interval (CI): -0.14 to -0.06, and per SD eGFR:-0.09, 95% CI: -0.14 to -0.03] and slower gait speed (ACR: -1.44 cm/s, CI: -2.12 to -0.76; eGFR: -1.55 cm/s, CI: -2.43 to -0.67). Worse kidney function was associated with lower scores in Variability domain. The association between impaired kidney function and history of fall was present only in participants with lower gait scores [odds ratio (95% CI): ACR: 1.34 (1.09-1.65); eGFR: 1.58 (1.07-2.33)]. Conclusions: We observed a graded association between lower kidney function and impaired gait suggesting that individuals with decreased kidney function, even at an early stage, need to be evaluated for gait abnormalities and might benefit from fall prevention programmes.

The influence of cervical movement on eye stabilization reflexes: a randomized trial.

To investigate the influence of the amount of cervical movement on the cervico-ocular reflex (COR) and vestibulo-ocular reflex (VOR) in healthy individuals. Eye stabilization reflexes, especially the COR, are changed in neck pain patients. In healthy humans, the strength of the VOR and the COR are inversely related. In a cross-over trial the amplitude of the COR and VOR (measured with a rotational chair with eye tracking device) and the active cervical range of motion (CROM) was measured in 20 healthy participants (mean age 24.7). The parameters were tested before and after two different interventions (hyperkinesia: 20 min of extensive active neck movement; and hypokinesia: 60 min of wearing a stiff neck collar). In an additional replication experiment the effect of prolonged (120 min) hypokinesia on the eye reflexes were tested in 11 individuals. The COR did not change after 60 min of hypokinesia, but did increase after prolonged hypokinesia (median change 0.220; IQR 0.168, p = 0.017). The VOR increased after 60 min of hypokinesia (median change 0.155, IQR 0.26, p = 0.003), but this increase was gone after 120 min of hypokinesia. Both reflexes were unaffected by cervical hyperkinesia. Diminished neck movements influences both the COR and VOR, although on a different time scale. However, increased neck movements do not affect the reflexes. These findings suggest that diminished neck movements could cause the increased COR in patients with neck complaints.

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 patients do not benefit from cerebellar or M1 transcranial direct current stimulation during force-field reaching adaptation.

Several studies have identified transcranial direct current stimulation (tDCS) as a potential tool in the rehabilitation of cerebellar disease. Here, we tested whether tDCS could alleviate motor impairments of subjects with cerebellar degeneration. Three groups took part in this study: 20 individuals with cerebellar degeneration, 20 age-matched controls, and 30 young controls. A standard reaching task with force-field perturbations was used to compare motor adaptation among groups and to measure the effect of stimulation of the cerebellum or primary motor cortex (M1). Cerebellar subjects and age-matched controls were tested during each stimulation type (cerebellum, M1, and sham) with a break of 1 wk among each of the three sessions. Young controls were tested during one session under one of three stimulation types (anodal cerebellum, cathodal cerebellum, or sham). As expected, individuals with cerebellar degeneration had a reduced ability to adapt to motor perturbations. Importantly, cerebellar patients did not benefit from anodal stimulation of the cerebellum or M1. Furthermore, no stimulation effects could be detected in aging and young controls. The present null results cannot exclude more subtle tDCS effects in larger subject populations and between-subject designs. Moreover, it is still possible that tDCS affects motor adaptation in cerebellar subjects and control subjects under a different task or with alternative stimulation parameters. However, for tDCS to become a valuable tool in the neurorehabilitation of cerebellar disease, stimulation effects should be present in group sizes commonly used in this rare patient population and be more consistent and predictable across subjects and tasks.NEW & NOTEWORTHY Transcranial direct current stimulation (tDCS) has been identified as a potential tool in the rehabilitation of cerebellar disease. We investigated whether tDCS of the cerebellum and primary motor cortex could alleviate motor impairments of subjects with cerebellar degeneration. The present study did not find stimulation effects of tDCS in young controls, aging controls, and individuals with cerebellar degeneration during reach adaptation. Our results require a re-evaluation of the clinical potential of tDCS in cerebellar patients.

The development of self-regulated learning during the pre-clinical stage of medical school: a comparison between a lecture-based and a problem-based curriculum.

Society expects physicians to always improve their competencies and to be up to date with developments in their field. Therefore, an important aim of medical schools is to educate future medical doctors to become self-regulated, lifelong learners. However, it is unclear if medical students become better self-regulated learners during the pre-clinical stage of medical school, and whether students develop self-regulated learning skills differently, dependent on the educational approach of their medical school. In a cross-sectional design, we investigated the development of 384 medical students' self-regulated learning skills with the use of the Self-Regulation of Learning Self-Report Scale. Next, we compared this development in students who enrolled in two distinct medical curricula: a problem-based curriculum and a lectured-based curriculum. Analysis showed that more skills decreased than increased during the pre-clinical stage of medical school, and that the difference between the curricula was mainly caused by a decrease in the skill evaluation in the lecture-based curriculum. These findings seem to suggest that, irrespective of the curriculum, self-regulated learning skills do not develop during medical school.

Eye movements in patients with Whiplash Associated Disorders: a systematic review.

BACKGROUND: Many people with Whiplash Associated Disorders (WAD) report problems with vision, some of which may be due to impaired eye movements. Better understanding of such impaired eye movements could improve diagnostics and treatment strategies. This systematic review surveys the current evidence on changes in eye movements of patients with WAD and explains how the oculomotor system is tested. METHODS: Nine electronic data bases were searched for relevant articles from inception until September 2015. All studies which investigated eye movements in patients with WAD and included a healthy control group were screened for inclusion. Qualifying studies were retrieved and independently assessed for methodological quality using the Methodology Checklists provided by the Scottish Intercollegiate Guidelines Network. RESULTS: Fourteen studies out of 833 unique hits were included. Ten studies reported impaired eye movements in patients with WAD and in four studies no differences compared to healthy controls were found. Different methods of eye movement examination were used in the ten studies: in five studies, the smooth pursuit neck torsion test was positive, in two more the velocity and stability of head movements during eye-coordination tasks were decreased, and in another three studies the cervico-ocular reflex was elevated. CONCLUSIONS: Overall the reviewed studies show deficits in eye movement in patients with WAD, but studies and results are varied. When comparing the results of the 14 relevant publications, one should realise that there are significant differences in test set-up and patient population. In the majority of studies patients show altered compensatory eye movements and smooth pursuit movements which may impair the coordination of head and eyes.

Trajectories of decline in cognition and daily functioning in preclinical dementia.

INTRODUCTION: Although preclinical dementia is characterized by decline in cognition and daily functioning, little is known on their temporal sequence. We investigated trajectories of cognition and daily functioning in preclinical dementia, during 18 years of follow-up. METHODS: In 856 dementia cases and 1712 controls, we repetitively assessed cognition and daily functioning with memory complaints, mini-mental state examination (MMSE), instrumental activities of daily living (IADL), and basic activities of daily living (BADL). RESULTS: Dementia cases first reported memory complaints 16 years before diagnosis, followed by decline in MMSE, IADL, and finally BADL. Vascular dementia related to earlier decline in daily functioning but later in cognition, compared with Alzheimer's disease. Higher education related to larger preclinical cognitive decline, whereas apolipoprotein E (APOE) ε4 carriers declined less in daily functioning. DISCUSSION: These results emphasize the long hierarchical preclinical trajectory of functional decline in dementia. Furthermore, they show that various pathologic, environmental, and genetic factors may influence these trajectories of decline.

Ageing shows a pattern of cerebellar degeneration analogous, but not equal, to that in patients suffering from cerebellar degenerative disease.

Ageing generally leads to impairments in cognitive function and the ability to execute and learn new movements. While the causes of these impairments are often multi-factorial, integrity of the cerebellum in an elderly population is an important predictive factor of both motor function and cognitive function. A similar association between cerebellar integrity and function is true for cerebellar patients. We set out to investigate the analogies between the pattern of cerebellar degeneration of a healthy ageing population and cerebellar patients. We quantified cerebellar regional volumes by applying voxel-based morphometry (VBM) to a publicly available dataset of MR images obtained in 313 healthy subjects aged between 18 and 96 years and a dataset of MR images of 21 cerebellar patients. We observed considerable overlap in regions with the strongest loss of cerebellar volume in the two datasets. In both datasets, the anterior lobe of the cerebellum (lobules I-V) and parts of the superior cerebellum (primarily lobule VI) showed the strongest degeneration of cerebellar volume. However, the most significant voxels in cerebellar patients were shifted posteriorly (lobule VII) compared to the voxels that degenerate most with age in the healthy population. The results showed a pattern of significant degeneration of the posterior motor region (lobule VIIIb) in both groups, and significant degeneration of lobule IX and X in the healthy population, but not in cerebellar patients. Furthermore, we saw strong volumetric degeneration of functionally defined cerebellar regions associated with cerebral somatomotor function in both groups. Predominance of degeneration in the anterior lobe and lobule VI suggests impairment of motor function in both groups, while we suggest that the posterior shift of degeneration in cerebellar patients would be associated with relatively stronger impairment of higher motor function and cognitive function. Thus, these results may explain the specific symptomology associated with cerebellar degeneration in ageing and in cerebellar patients.

Gait patterns in COPD: the Rotterdam Study.

Gait disturbances in patients with chronic obstructive pulmonary disease (COPD) may lead to disability and falls. As studies assessing gait kinematics in COPD are sparse, we investigated associations of COPD with various gait domains and explored a potential link with falling. Gait was measured within the prospective, population-based Rotterdam Study (age ≥55 years) using an electronic walkway and summarised into seven gait domains: Rhythm, Variability, Phases, Pace, Tandem, Turning and Base of Support. Rhythm is a temporal gait aspect that includes cadence and reflects how quickly steps are taken. Persons with COPD (n=196) exhibited worse Rhythm (-0.21 SD, 95% CI -0.36- -0.06 SD) compared with persons with normal lung function (n=898), independent of age, sex, height, education, smoking or analgesic use, especially when dyspnoea and severe airflow limitation or frequent exacerbations (Global Initiative for Chronic Obstructive Lung Disease group D: -0.83 SD, 95% CI -1.25- -0.41 SD) were present. A lower forced expiratory volume in 1 s was associated with worse Rhythm and Pace, including lower cadence and gait velocity, respectively. Importantly, fallers with COPD had significantly worse Rhythm than nonfallers with COPD. This study demonstrates that persons with COPD exhibit worse Rhythm, especially fallers with COPD. The degree of Rhythm deterioration was associated with the degree of airflow limitation, symptoms and frequency of exacerbations.

Late effects of adjuvant chemotherapy for breast cancer on fine motor function.

BACKGROUND: Adjuvant chemotherapy for breast cancer has been associated with deterioration of fine motor skill. Which aspects of motor performance are underlying this problem is unclear but important because manual motor deterioration could affect quality of life. The current study aims to investigate late effects of adjuvant chemotherapy for breast cancer on fine motor function, using both speed and accuracy measures. METHOD: We compared fine motor function of 174 women who had received adjuvant Cyclophosphamide Methotrexate 5-Fluorouracil chemotherapy for breast cancer on average 20 years ago with that of a population sample of 195 women without a history of cancer. Fine motor function was measured with the Purdue Pegboard Test and the Archimedes spiral test. RESULTS: The group of chemotherapy-exposed breast cancer survivors was slower in drawing an Archimedes spiral than the reference group. Furthermore, in the chemotherapy-exposed subjects, we found that older age is related to more crossings of the spiral template, more return movements, and more deviations from the template. Such relationships were not observed within the reference group. No significant between-group differences were found for any of the Purdue Pegboard measures. CONCLUSIONS: Compared with a population-based reference group, Cyclophosphamide Methotrexate 5-Fluorouracil chemotherapy-exposed breast cancer survivors demonstrated motor slowing while drawing an Archimedes spiral, on average 20 years after completion of primary treatment. Furthermore, the Archimedes spiral test is a more sensitive measure than the Purdue Pegboard Test to assess fine manual motor performance in long-term breast cancer survivors following chemotherapy.

Cerebellar transcranial direct current stimulation effects on saccade adaptation.

Saccade adaptation is a cerebellar-mediated type of motor learning in which the oculomotor system is exposed to repetitive errors. Different types of saccade adaptations are thought to involve distinct underlying cerebellar mechanisms. Transcranial direct current stimulation (tDCS) induces changes in neuronal excitability in a polarity-specific manner and offers a modulatory, noninvasive, functional insight into the learning aspects of different brain regions. We aimed to modulate the cerebellar influence on saccade gains during adaptation using tDCS. Subjects performed an inward (n = 10) or outward (n = 10) saccade adaptation experiment (25% intrasaccadic target step) while receiving 1.5 mA of anodal cerebellar tDCS delivered by a small contact electrode. Compared to sham stimulation, tDCS increased learning of saccadic inward adaptation but did not affect learning of outward adaptation. This may imply that plasticity mechanisms in the cerebellum are different between inward and outward adaptation. TDCS could have influenced specific cerebellar areas that contribute to inward but not outward adaptation. We conclude that tDCS can be used as a neuromodulatory technique to alter cerebellar oculomotor output, arguably by engaging wider cerebellar areas and increasing the available resources for learning.

The role of cerebellar volume in cognition in the general elderly population.

BACKGROUND: It is unknown whether the cerebellum affects cognitive function in an aging community-dwelling population. In a population-based study on 3745 nondemented individuals aged 45 years and above, we investigated the relationship between cerebellar volume and cognitive function. METHODS: Brain volumes were obtained using automatic tissue segmentation of magnetic resonance imaging scans. Cognitive functioning was assessed using MMSE and cognitive compound scores of global cognition, executive function, information processing speed, memory, and motor speed. Linear regression modeling was used to study the associations between cerebellar volumes and cognitive measures, independent of cerebral volumes. RESULTS: We found a relationship between larger cerebellar volume and better global cognition, executive function, information processing speed, and motor speed. After adjustment for cerebral volume, only cerebellar gray matter volume remained borderline significantly associated with global cognition and information processing speed. After Bonferroni correction, the few associations found between cerebellar volume and cognition disappeared. CONCLUSIONS: We only found a minor relationship between larger cerebellar volume and better cognition in healthy older adults, which further attenuated after correcting for cerebral volume. Our findings support the notion that cerebellar volume has an influence on cognition in aging, but that it is not the major leading structure.

Patterns of cognitive function in aging: the Rotterdam Study.

Cognitive impairment is an important hallmark of dementia, but deterioration of cognition also occurs frequently in non-demented elderly individuals. In more than 3,000 non-demented persons, aged 45-99 years, from the population-based Rotterdam Study we studied cross-sectional age effects on cognitive function across various domains. All participants underwent an extensive cognitive test battery that tapped into processing speed, executive function, verbal fluency, verbal recall and recognition, visuospatial ability and fine motor skills. General cognitive function was assessed by the g-factor, which was derived from principal component analysis and captured 49.2 % of all variance in cognition. We found strongest associations for age with g-factor [difference in z-score -0.59 per 10 years; 95 % confidence interval (CI) -0.62 to -0.56], fine motor skill (-0.53 per 10 years; 95 % CI -0.56 to -0.50), processing speed (-0.49 per 10 years; 95 % CI -0.51 to -0.46), and visuospatial ability (-0.48 per 10 years; 95 % CI -0.51 to -0.45). In contrast, the effect size for the association between age and immediate recall was only -0.25 per 10 years (95 % CI -0.28 to -0.22), which was significantly smaller than the relation between age and fine motor skill (P < 0.001). In conclusion, in non-demented persons of 45 years and older, general cognition deteriorates with aging. More specifically, fine motor skill, processing speed and visuospatial ability, but not memory, are affected most by age.

Cognition and gait show a distinct pattern of association in the general population.

BACKGROUND: With brain aging, cognition and gait deteriorate in several domains. However, the interrelationship between cognitive and gait domains remains unclear. We investigated the independent associations between cognitive and gait domains in a community-dwelling population. METHODS: In the Rotterdam Study, 1232 participants underwent cognitive and gait assessment. Cognitive assessment included memory, information processing speed, fine motor speed, and executive function. Gait was summarized into seven independent domains: Rhythm, Variability, Phases, Pace, Tandem, Turning, and Base of Support. With multivariate linear regression, independent associations between cognitive and gait domains were investigated. RESULTS: Information processing speed associated with Rhythm, fine motor speed with Tandem, and executive function with Pace. The effect sizes corresponded to a 5- to 10-year deterioration in gait. CONCLUSIONS: Cognition and gait show a distinct pattern of association. These data accentuate the close, but complicated, relation between cognition and gait, and they may aid in unraveling the broader spectrum of the effects of brain aging.

Cerebellar activation related to saccadic inaccuracies.

Using functional MRI, we assessed activity in the human cerebellum related to the properties of post-saccadic visual errors that drive the plasticity of saccadic eye movements. In the scanner subjects executed blocks of saccadic eye movements toward a target that could be randomly displaced during the saccade. Such an intra-saccadic shift was randomly forward or backward, and could be either small or large. Post-saccadic visual errors induced activation in several cerebellar areas. These areas included, but were not limited to, the oculomotor vermis which is known for its role in saccadic control. Large errors yielded more activation in the cerebellar hemispheres, whereas small errors induced more activation in the vermis. Forward shifts induced more activation than backward shifts. Our results suggest that the differences in cerebellar activation patterns for different sizes and directions of post-saccadic errors could underlie the behavioral differences observed between various saccadic adaptation paradigms. In addition, the outcome argues for an extended range of cerebellar target areas in electrophysiological studies on saccadic eye movement control.

Visuomotor cerebellum in human and nonhuman primates.

In this paper, we will review the anatomical components of the visuomotor cerebellum in human and, where possible, in non-human primates and discuss their function in relation to those of extracerebellar visuomotor regions with which they are connected. The floccular lobe, the dorsal paraflocculus, the oculomotor vermis, the uvula-nodulus, and the ansiform lobule are more or less independent components of the visuomotor cerebellum that are involved in different corticocerebellar and/or brain stem olivocerebellar loops. The floccular lobe and the oculomotor vermis share different mossy fiber inputs from the brain stem; the dorsal paraflocculus and the ansiform lobule receive corticopontine mossy fibers from postrolandic visual areas and the frontal eye fields, respectively. Of the visuomotor functions of the cerebellum, the vestibulo-ocular reflex is controlled by the floccular lobe; saccadic eye movements are controlled by the oculomotor vermis and ansiform lobule, while control of smooth pursuit involves all these cerebellar visuomotor regions. Functional imaging studies in humans further emphasize cerebellar involvement in visual reflexive eye movements and are discussed.