Self-regulation of inter-hemispheric visual cortex balance through real-time fMRI neurofeedback training.

Recent advances in neurofeedback based on real-time functional magnetic resonance imaging (fMRI) allow for learning to control spatially localized brain activity in the range of millimeters across the entire brain. Real-time fMRI neurofeedback studies have demonstrated the feasibility of self-regulating activation in specific areas that are involved in a variety of functions, such as perception, motor control, language, and emotional processing. In most of these previous studies, participants trained to control activity within one region of interest (ROI). In the present study, we extended the neurofeedback approach by now training healthy participants to control the interhemispheric balance between their left and right visual cortices. This was accomplished by providing feedback based on the difference in activity between a target visual ROI and the corresponding homologue region in the opposite hemisphere. Eight out of 14 participants learned to control the differential feedback signal over the course of 3 neurofeedback training sessions spread over 3 days, i.e., they produced consistent increases in the visual target ROI relative to the opposite visual cortex. Those who learned to control the differential feedback signal were subsequently also able to exert that control in the absence of neurofeedback. Such learning to voluntarily control the balance between cortical areas of the two hemispheres might offer promising rehabilitation approaches for neurological or psychiatric conditions associated with pathological asymmetries in brain activity patterns, such as hemispatial neglect, dyslexia, or mood disorders.

[Multifocal electroretinography in follow-up of patients treated with hydroxychloroquine]. / L'apport de l'électrorétinographie multifocale dans le suivi des patients traités par hydroxychloroquine.

INTRODUCTION: Ophthalmologic follow-up of hydroxychloroquine-treated patients is of major importance because of the risk for potentially irreversible retinal toxicity. The use of the multifocal electroretinogram for the follow-up of such patients has already been reported. We studied the capacity of the multifocal electroretinogram to detect early signs of retinal toxicity. PATIENTS AND METHODS: This study consisted of multifocal electroretinogram analysis of 28 patients treated with hydroxychloroquine for a period of 6-72 months. All patients selected had a normal clinical and paraclinical ophthalmological evaluation. A multifocal electroretinogram according to the international recommendations was obtained. We analyzed the amplitude and the implicit time for kernel 1 responses by quadrant and by ring. RESULTS: For both eyes, in both ring and quadrant analyses, the average implicit times of patients receiving hydroxychloroquine were significantly elevated (p<0.01). On the other hand, the amplitudes were not significantly attenuated. In a total of 28 patients, seven (25%) presented a significant prolongation of the implicit time and significant amplitude attenuation was found in only one patient. DISCUSSION: Implicit time prolongation in hydroxychloroquine-treated patients has already been reported. However, dissociation between amplitude and implicit time changes has, to our knowledge, never been previously described. This observation is important given that numerous studies focus exclusively on amplitude. CONCLUSION: The multifocal electroretinogram of patients receiving hydroxychloroquine can present lengthened kernel 1 implicit time, despite otherwise normal ophthalmological evaluation. Further studies are necessary to evaluate the prognostic value of mfERG responses in the early detection of patients presenting a retinotoxicity risk.

Reading with multiple preferred retinal loci: implications for training a more efficient reading strategy.

The reading strategies in individuals with central scotomas and more than one preferred retinal locus (PRL) were investigated using a scanning laser ophthalmoscope in order to understand the visual requirements that lead to the need to use more than one PRL during reading. It was found that: (1) PRL function can be deduced from variation in PRL usage for different size and length of isolated words; (2) each subject used two or more PRL to accomplish the functions of global viewing and discrimination, suggesting that these are two of the minimum requirements for reading; (3) reading strategies can change depending on the position of words in visual space; (4) line-changing strategies can revert to horizontal and vertical component movements. These findings have implications for improving reading performance through training in patients with central scotomas.

Full text reading with a central scotoma: pseudo regressions and pseudo line losses.

AIMS: To investigate the reading strategy of a patient with central scotoma, using several preferred retinal loci (PRL). METHODS: A 47 year old man with Stargardt's disease was asked to decipher texts projected onto his retina using a scanning laser ophthalmoscope. A recording of the fundus image, on which the projected texts were superimposed, was analysed frame by frame. RESULTS: The subject used a combination of three PRL, located above the scotoma and laterally to the left and right of it. He first used his left PRL to search for the beginning of a line, then switched to his right PRL, thus performing an apparent regression which was called "pseudo regression", to read the line with successive rightward saccades. To decipher a particularly difficult word, he switched to his upper PRL, showing an apparent line loss which was called ("pseudo line loss"), and then used his three PRL in combination. CONCLUSION: The patient used a complex, well structured reading strategy. These data showed that backward saccades and unexpected line losses, hitherto thought to be inappropriate and uneconomical, may in fact represent purposeful changes of PRL. It is thought that this is the first structured reading behaviour ever identified in such a condition. Such adaptive oculomotor behaviour should be taken into account when considering rehabilitation procedures.

Does visual sensitivity improve between 5 and 8 years? A study of automated visual field examination.

In 74 normal subjects (62 children aged 5-8 years and 12 adults), we tested the widely-held belief that visual sensitivity improves substantially during childhood. Maturation of the retino-striate pathways is generally invoked to account for age-related changes in visual sensitivity. We evaluated the extent to which attentional factors unduly emphasized the effect of age on the purely physiological mechanisms. After a specially-designed familiarization procedure, sensitivity was fully evaluated at two locations in the superior temporal field using a bracketing technique (Octopus 2000R). False-positive (FP) and false-negative (FN) catch-trials were interspersed with the sequence of stimuli. Analyses demonstrated that: (1) age affected sensitivity; and (2) the general level of attentiveness varied not only with age, but also among subjects in the same age group. We then estimated the extent to which improved visual sensitivity may reflect a concomitant evolution of vigilance. Firstly, controlled variance analyses indicated that factors for evaluating attentiveness (rate of FN responses, slope of the psychometric function at the median, and goodness of fit) were indeed much better predictors than age of the sensitivity measured. Secondly and more significantly, the grouping of subjects into homogeneous subgroups, on the basis of their attentional performance, showed that children as young as 5 years may have a visual sensitivity that is only marginally lower than that of adults.

Automated visual field examination in children aged 5-8 years. Part I: Experimental validation of a testing procedure.

In 106 children aged 5-8 years, we determined how much training was needed to stabilize the response strategy prior to actual visual field assessment and we evaluated the reliability and acceptable duration of automated static perimetry (Octopus 2000R). A specially designed familiarization procedure was used to train the children to: (1) gaze at the center of the visual field while paying attention to light stimuli projected onto the periphery and (2) press the buzzer only when light stimuli were perceived. The subsequent examination phase consisted of 15 successive identical blocks of 27 trials (12 stimulus trials, 12 false-positive catch-trials, and three false-negative catch-trials), and was stopped before the end if signs of fatigue appeared. Age had a marked influence both on endurance (the number of blocks performed increased significantly) and on response reliability (false-positive responses decreased between 5- and 6-year-olds). The increase in false-negative responses toward the end indicates that examination is no longer reliable, and should be stopped. We concluded that most children as young as five can undergo examination by automated static perimetry. Changes regarding learning, stimulus intensity and testing procedure are suggested in order to adapt the examination to age, level of vigilance and health condition of the children.

Automated visual field examination in children aged 5-8 years. Part II: Normative values.

We determined normative values for the visual sensitivity threshold in 118 children aged 5-8 years, using automated static perimetry (Octopus 2000R, program 32). In addition, 17 normal adults were tested. The children first underwent a familiarization procedure. One week later, quantitative examination was performed according to a specially designed schedule divided into three phases. For each of the 76 points tested, mean thresholds and standard deviations were calculated as a function of age. In contrast to previous studies, sensitivity difference between adults and children over the central 30 degrees of the visual field emerged only for the youngest age groups (5- and 6-year olds). Both the response rate in false-negative trials, and values of a within-subject threshold variability index, suggested that 5- and 6-year-olds' higher thresholds were inflated by non physiological factors, such as vigilance and cognitive processes. For these ages, the data reported here should therefore be considered as an approximation of the upper level of the thresholds. In contrast, our results for 7- and 8 year-old children provided reliable normative values for light sensitivity across the visual field.

Feasibility of automated visual field examination in children between 5 and 8 years of age.

AIMS: To investigate how young children develop the ability to undergo a visual field evaluation using regular automated perimetry. METHODS: The study included 42 normal girls aged 5, 6, 7, and 8 years. Twelve locations in the 15 degrees eccentricity were tested in one eye, using an Octopus 2000R perimeter with a two level strategy. False positive and false negative catch trials were presented. The examination was performed three times in succession. Before the examination procedure, a specially designed programme was conducted for progressive familiarisation. RESULTS: During the familiarisation procedure, it was found that all of the 5-year-old children, seven of the 6-year-old children, and three of the 7-year-old children were unable to perform immediately, and correctly, the instructions given during the familiarisation phase; these children took from 30 seconds to 3 minutes to comply with the examiner's requests. With the exception of one 5-year-old child, all tested subjects completed the planned procedure. The mean proportion of false negative answers in catch trials was 1.6%. The mean proportion of false positive answers was 12.2%. The quadratic dependency on age suggested by the averages was not significant (F(3,116) = 0.88; p = 0.45). Detection stimulus improved with age, as shown by the fact that probability of perceiving dim stimulus increases significantly (F(3,116) = 12.68; p < 0.0001). CONCLUSION: Children did remarkably well regarding both the duration of the examination and the reliability of the answers. A preliminary familiarisation phase with a specially designed adaptation programme was found to be mandatory with children aged 7 or under. To our knowledge, this is the first time that such an investigation has been performed.

[Automated static perimetry in the child: methodologic and practical problems]. / Périmétrie statique automatisée chez l'enfant: problèmes méthodologiques et pratiques.

PURPOSE: In a pediatric population, the use of computerized static perimetry is known as particularly difficult. The specific difficulties which may occur when testing young subjects are stability of fixation, ability to maintain concentration, resistance throughout the procedure, and reliability of the answers. It seems important to investigate and to develop appropriate strategies for the examination of children aged 8 years and younger according to their ability to undergo visual field evaluation using automated static perimetry. PATIENTS AND METHODS: Eighty normal children aged 5 to 8 years old were evaluated using an Octopus 2000R perimeter, with a one-level strategy. Adaptation of the procedure were included. RESULTS: The analysis of answers and false-positive catch-trials showed that children as young as five years old did remarkably well regarding both the duration of the examination and the reliability of answers. CONCLUSIONS: Automated static perimetry examination can provide reliable results in children as young as five years old once a familiarization procedure has been conducted and if the duration of examination does not exceed the child's capacity to remain task focused.

Angioscotomata and morphological features of related vessels in automated perimetry.

AIMS: To determine principles which regulate the occurrence of angioscotomata in automated static perimetry, variations in light sensitivity were correlated with the location and diameter of neighbouring retinal vessels. METHODS: Ten normal eyes were tested with the Octopus 2000R, using a 0.431 degree light stimulus. Sensitivity was quantified in points located around the blind spot, according to a regular, 0.5 degree constant, grid pattern. From 336 to 443 locations were tested in each eye. The resulting printouts were superimposed on corresponding fundus photographs. At each tested point, the following five additional variables were evaluated: the diameters of the closest and the second closest vessel (in 0.1 degree units); the distances of the apparent location of the tested point to the closest and the second closest vessel (in 0.25 degree units); and the distance between the two closest vessels (in 0.25 degree units). Altogether, 3869 locations were tested and 23,214 values were quantified. RESULTS: The following two conditions were found to be related to a reduction in sensitivity: (1) proximity (< 0.25 degree) to a large vessel (> or = 0.5 degree in diameter); (2) proximity (< 0.25 degree) to one of two adjacent (< 0.5 degree distant), moderately large vessels (0.3 degree to 0.4 degree in diameter). In condition 1, sensitivity was 51.3% and specificity was 92.2%; in condition 2, sensitivity was 16.2% and specificity was 98.3%; and with a combination of conditions 1 and 2, sensitivity was 67.6% and specificity was 90.5%. Increase by 0.1 degree of an adjacent vessel which was 0.4 degree in diameter markedly affected light sensitivity. CONCLUSION: Modifications in vessel diameter are observed in a number of circumstances, including adaptive vascular response to changes in ambient conditions and obstructive disorders of retinal vessels. These findings indicate that changes in vessel diameter over time can result in fluctuation of sensitivity. It is concluded that, in contrast with what is commonly stated, when ocular media are unaltered and the subject's collaboration is adequate, temporal variations in measured thresholds do not necessarily reflect functional changes in nervous tissues in the visual pathways.

[The Gray Scale of the Octopus N1 perimetry analysis program in neuro-ophthalmology]. / L'échelle des gris ("Greyscale") du programme d'analyse périmetrique Octopus N1 pour la neuro-ophtalmologie.

The gray scale of the Octopus neuro-ophthalmologic program N1 shows the difference between actual values and age-related normality. This permits optimal visualization of slight relative scotomas. The interpolation algorithm is computed for the four individual quadrants of the visual field, enabling either lateral hemianopic or fascicular defects to be sharply delineated. In addition, the N1 program automatically provides a global, nonsectorial gray scale which is useful for demonstrating visual defects which are not delineated by either the horizontal or the vertical meridian.