The functional MRI study of the visual cortical function's rebuilding in children ametropic amblyopia

Objective: To detect the pathogenetic mechanism of motion-sensitive cortical deficit in response to motion stimuli in children with anisometropic amblyopia using a blood oxygenation level-dependent functional magnetic resonance imaging technique (BOLD-fMRI). Methods: This was a case series study. Patients were collected from June to December 2017 at Tianjin Eye Hospital. Twenty-five patients who were diagnosed with anisometropic amblyopia as amblyopia group and twenty-five normal volunteers were examined as control group. A BOLD-fMRI technique on a 1.5T MRI and a horizontally moving sinusoidal grating block design were used for task conditions. All data were processed with SPM5 software, were analyzed by t test. Results: Significant fMRI activation and comparable right and left eye activation were found in the middle temporal area (MT), and Brodmann areas 19 and 37, in all control subjects; Lesser cortical activation in area MT and Brodmann areas 37, 19, and greater activation in the frontal gyrus of the lazy eye group were detected compared to the control group. Lesser cortical activation in Brodmann area 37, 18 of the contralateral eye of the amblyopic group was detected compared to the control group. Lesser cortical activation in area MT and Brodmann areas 19, 18, and greater activation in the frontal lobes of the anisometropic amblyopic eyes were detected compared to the contralateral eyes. Conclusions: The spatial extent and intensity of the visual cortex activation in the visual cortex decreases in the amblyopic eye compared to the normal control. Decreased cortical activation in the fellow eye is prevalent. A greater visual cortex area is activated when stimulating the amblyopic eye. Key words: Anisometropia; amblyopia; magnetic resonance imaging; visual motion; cortical deficit

1. Luis H. Ospina, MD* 1. *Assistant Professor, Pediatric Ophthalmology and Neuro-ophthalmology, Ste-Justine Hospital, University de Montreal, Montreal, Quebec, Canada After completing this article, readers should be able to: 1. Recognize cortical visual impairment (CVI) as an important cause of pediatric visual loss. 2. Identify the most frequent causes of pediatric CVI and, more specifically, understand the role of hypoxia as a cause of central visual damage. 3. Describe the different patterns and implications for future vision of hypoxic central visual damage occurring in preterm compared with term babies. 4. Know the clinical signs suggestive of CVI in children. 5. Discuss the involvement of visual functions other than visual acuity (ie, cognitive visual aspects) in CVI and correlate them with the likely affected neuroanatomic substrates. 6. Explain the value of using a multidisciplinary approach in rehabilitating children who have CVI early in their development. Vision loss caused by central nervous system damage often is referred to as CVI but also may be referred to as cerebral visual impairment or neurologic visual impairment. These terms refer to the fact that the primary defect may not necessarily be limited to the striate (primary visual) cortex and may affect other areas subserving vision, such as the visual associative cortex, optic radiations, and visual attention pathways. Although it is not yet certain which of these three terms best describes the visual deficit, it is clear that use of the label cortical blindness must be abandoned. That term not only evokes negative connotations for the child and the family but is inaccurate because in almost every instance, some degree of residual vision remains, and visual improvement can occur. CVI has become the greatest cause of pediatric visual impairment in developed countries (1)(2)(3)(4)(5) and is becoming increasingly prevalent in developing nations. CVI is a problem of increasing frequency for two primary reasons. First, the progress in neonatal care has resulted in improved survival of …

Objective To explore the patterns of motor and linguistic activation in cortical and its correlations with abnormal gray matter in patients with malformations of cortical development(MCD)and epilepsy.Methods Seven MCD patients with epilepsy(2 patients with focal cortical dysplasia,2 heterotopia,2 schizencephaly,and 1 polymicrogyria)underwent blood-oxygen-level-dependent(BOLD)functional MRI(fMRI)in a 3 T MR scanner when practicing bilateral fingers tapping,toes twisting,verb generation,and picture naming.Functional images were post-processed by using SPM 5 software based on a general linear model(GLM)to generate activations above a uniform threshold with the cluster size (≥30 voxels,P ＜0.001 corrected).The activations were recognized and classified by two experienced neuroradiologists,and then compared with that in abnormal gray matter.Results The clusters and intensities of motor activations were mainly located in the sensormotor cortex(SMC)and premotor area (PMA).In linguistic tasks,activations produced by verb generation were found in language-associated cortical regions and PMA with higher activation in Wemicke area,picture naming significantly in the visual cortex,and language in Broca area.Combination of the two linguistic tasks produced significant clusters and intensities in language cortex.For MCD patients with abnormal cortical abnormalities,motor and language task could produce neuronal activities within normal as well as abnormal cortex regions.In 6 patients who underwent resective surgery,epileptic seizures decreased significantly,and the follow-up images demonstrated no new neurological dysfunctions and cognitive impairments.Conclusions fMRI can visualize neuronal activities in patients with MCD and epilepsy and demonstrate the motor and linguistic activations occurring in normal and abnormal gray matter.It should be cautious for surgery in patient with MCD and epilepsy. Key words: Cerebral cortex; Nervous system abnormalities; Grey matter heterotopia; Epileptic foci; Magnetic resonance imaging

The optic radiations are major white matter pathways funneling visual information from the lateral geniculate nuclei to the visual cortex in the occipital lobe. Given their relevance in visual processing and in several brain disorders, the optic radiations have been extensively investigated by using magnetic resonance imaging and diffusion tensor imaging tractography [1]. Herein, we use a powerful diffusion signal modeling, namely Constrained Spherical Deconvolution, in order to provide an exhaustive connectivity profile of the connections between the lateral geniculate nucleus and the visual cortex in the healthy brain, as well as pulvinar connectivity with visual-related structures. In addition, taking into account that visual deficits may precede motor symptoms’ onset in Parkinson’s Disease [2], we assessed whether the intracranial visual system can be involved at the early stage of the disease. Our connectivity analysis revealed that the optic radiations are mainly distributed in V1 and V2. Furthermore, we found significant alterations of optic radiations connectivity distribution in Parkinson’s Disease patients, with decreased lateral geniculate nucleus-V2 density as well as significant increase of optic radiations’ mean diffusivity. Voxel Based Morphometry analysis also showed significant reduction of visual cortical volumes and of the optic radiation in the patients group. In conclusion, our findings provide a reliable connectivity profile of the optic radiations, suggesting extrastriate-lateral geniculate nucleus connections in human brain. Finally, we showed that visual system alterations can be detected at early stages of Parkinson’s Disease.

The aim of this study was to examine the secondary visual cortex functional disorder in patients with glaucoma and large pituitary adenoma by functional magnetic resonance imaging, and to determine the correlation between visual field defect and primary visual cortex activation. Results showed that single eye stimulation resulted in bilateral visual cortex activation in patients with glaucoma or large pituitary adenoma. Compared with the normal control group, the extent and intensity of visual cortex activation was decreased after left and right eye stimulation, and functional magnetic resonance imaging revealed a correlation between visual field defects and visual cortex activation in patients with glaucoma and large pituitary adenoma. These functional magnetic resonance imaging data suggest that anterior optic pathway lesions can cause secondary functional disorder of the visual cortex, and that visual defects are correlated with visual cortex activation.

Objective: To investigate the effect of caloric restriction on the plasticity of the visual cortex in monocular-deprived adult amblyopic mice, and to explore possible molecular mechanisms. Methods: This was an experimental study. A total of 54 neonatal healthy Kunming mice were randomly divided into 3 groups: a control group (n=18), a monocular deprivation+ad libitum (MD+AL) group (n=18), and a monocular deprivation+caloric restriction (MD+CR) group (n=18). MD model of mice was established at postpartum 21 days, and deprivation factors were removed at postpartum 35 days. At their postpartum 63 days, visual acuity and electrophysiological tests were used to detect visual function changes, and the expression levels of the proteins involved in plasticity in the visual cortex (postsynaptic density 95, PSD95; synaptophysin, SYP; growth-associated protein 43, GAP-43) were measured by immunohistochemistry and Western Blot. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression level of the insulin-like growth factor-1 (IGF-1). Two-way repeated measurement analysis was used to compare data from each group. Results: The final numbers for the control group, MD+AL group and MD+CR group were 14, 18 and 18 mice, respectively. The percentage of weight increase in the MD+CR mice was significantly lower than the percent increase in the MD+AL group (P<0.05) from the beginning of the first week. The visual acuity of the MD+AL group was significantly lower than the acuity in both the control and MD+CR groups (P<0.05). The expression levels of the three synaptic-associated proteins (PSD95, SYP, GAP-43) in the MD+AL group were all lower than levels in the control and MD+CR groups. RT-PCR showed the level of IGF-1 mRNA in the MD+AL group was significantly lower than the level in the control and MD+CR groups (P<0.05), but increased significantly in the MD+CR group (P<0.05). Conclusions: CR can improve the visual function of adult MD mice, increase the expression of synapse-related proteins in the visual cortex, and reactivate the plasticity of the adult visual cortex. Further research shows IGF-1 may be involved in regulating these effects. Key words: caloric restriction; form deprivation; amblyopia; visual function; mice

Background The formation of amblyopia is closely associated with glutamate receptors of visual cortex, and researches determined that the expression of metabolic glutamate receptor 1 (mGluR1) in the visual cortex of amblyopic rats is down-regulated.However, the effect of mGluR1 on synaptic transmission of neurons in the visual cortex is unclear. Objective This study was to investigate the role of mGluR1 in the synaptic transmission efficiency of neurons in the primary visual cortex of monocular form-deprivated rats. Methods Sixteen 14-day-old SD rats were randomly divided into normal control group and form-deprivation group, with 8 rats in each group.The eyelids of the left eyes were sutured to establish the monocular form-deprivation models in the rats of the form-deprivation group, and the visual cortex slices were prepared until 31 days after modeling and incubated in artificial cerebrospinal fluid with 3, 5-dihydroxyphenylglycine (DHPG), LY367385+ DHPG, 2-methyl-6-(phenyl acetylene) pyridine hydrochloride(MPEP)+ DHPG and LY367385+ MPEP+ DHPG, respectively.The field excitatory postsynaptic potential (fEPSP) of neurons in the visual cortex of V1 area was detected by extracellular microelectrode recording.The use and care of the animals followed the statement for the Use of Animals in Ophthalmic and Vision Research. Results The slope value before drug treatment was set as 100%, the fEPSP-slopes of the normal control group and the form-deprivation group were increased to (136.4±17.3)% and (120.7±12.8)% after DHPG induction with significant difference between the two groups (t=2.280; P<0.05). The fEPSP-slopes of the normal control group were (114.9±9.3)% and (112.6±15.3)% after LY367385 and MPEP treatment, and those of the form-deprivation group were (107.3±6.0)% and (110.1±4.1)%, which were significantly lower than those after DHPG induction (normal control group: t=2.641, 2.915; both at P<0.05; form-deprivation group: t=2.410, 2.372; both at P<0.05). The fEPSP-slopes of the normal control group and the form-deprivation group were (104.5±2.2)% and (102.8±14.9)% after LY367385+ MPEP treatment, which were lower than that after DHPG induction (t=3.080, 2.306; both at P<0.05). Conclusions The effect of mGluR1 on the synaptic transmission of neurons in the visual cortex weakens after monocular form-deprivation in rats.Both mGluR1 and mGluR5 participate in the neuronic synaptic transmission on visual cortex area and appear to be equivalent contribution. Key words: Electrophysiology; Excitatory amino acid agonists/pharmacology; Excitatory amino acid antagonists/pharmacology; Phenylacetates/pharmacology; Receptors, metabotropic glutamate/physiology; Visual cortex/growth & development; Neuronic synaptic transmission/drug effect; Form deprivation; Rats, SD

Amblyopia can be classified as stimulus-deprivation amblyopia, strabismic amblyopia, anisometropic amblyopia, ametropic amblyopia, mridional amblyopia, and idiopathic amblyopia. Two factors are involved in the production of amblyopia, namely deprivation of form vision and abnormal binocular interaction. Amblyopia develops only in the critical period, when neural plasticity makes the visual system vulnerable to any abnormal experience such as strabismus, a blurred image or occlusion. The principle underlying the restoration of VA is to promote the use of the amblyopic eye or eyes. This can be achieved by refractive adaptation, occlusion of the better eye, cycloplegic drugs alone or in combination with optical penalization, refractive surgery, and systemic drugs. Ideally, treatment is discontinued when equal VA is obtained. It is recognised that compliance plays a key role in the successful outcome of occlusion therapy. Noncompliance is a common problem encountered in amblyopia treatment.

Binocular summation in strabismic amblyopia is typically reported as being absent or greatly reduced in behavioral studies and is thought to be because of a preferential loss of excitatory interactions between the eyes. Here, we studied how excitatory and suppressive interactions contribute to binocular contrast interactions along the visual cortical hierarchy of humans with strabismic and anisometropic amblyopia in both sexes, using source-imaged steady-state visual evoked potentials (SSVEP) over a wide range of relative contrast between the two eyes. Dichoptic parallel grating stimuli modulated at unique temporal frequencies in each eye allowed us to quantify spectral response components associated with monocular inputs (self-terms) and the response components because of interaction of the inputs of the two eyes [intermodulation (IM) terms]. Although anisometropic amblyopes revealed a similar pattern of responses to normal-vision observers, strabismic amblyopes exhibited substantially reduced IM responses across cortical regions of interest (V1, V3a, hV4, hMT+ and lateral occipital cortex), indicating reduced interocular interactions in visual cortex. A contrast gain control model that simultaneously fits self- and IM-term responses within each cortical area revealed different patterns of binocular interactions between individuals with normal and disrupted binocularity. Our model fits show that in strabismic amblyopia, the excitatory contribution to binocular interactions is significantly reduced in both V1 and extra-striate cortex, whereas suppressive contributions remain intact. Our results provide robust electrophysiological evidence supporting the view that disruption of binocular interactions in strabismus or amblyopia is because of preferential loss of excitatory interactions between the eyes.SIGNIFICANCE STATEMENT We studied how excitatory and suppressive interactions contribute to binocular contrast interactions along the visual cortical hierarchy of humans with normal and amblyopic vision, using source-imaged SSVEP and frequency-domain analysis of dichoptic stimuli over a wide range of relative contrast between the two eyes. A dichoptic contrast gain control model was used to characterize these interactions in amblyopia and provided a quantitative comparison to normal vision. Our model fits revealed different patterns of binocular interactions between normal and amblyopic vision. Strabismic amblyopia significantly reduced excitatory contributions to binocular interactions, whereas suppressive contributions remained intact. Our results provide robust evidence supporting the view that the preferential loss of excitatory interactions disrupts binocular interactions in strabismic amblyopia.

Visual areas I and II of cerebral cortex of rabbit.

Objective To investigate the visual function after part-time occlusion therapy in amblyopia children whose corrected visual acuity recovered to normal. Methods Investigate the binocular vision of 70 cases amblyopia children whose corrected visual acuity had recovered to normal.According to whether patching dominant eye during treatment the children were divided into 2 groups (A and B).The statistically difference of simultaneous perception,fusion function and stereopsis in two groups was analyzed.Results Forty-two (91.3％) and 26 (95.8％) children got the simultaneous perception in group A and group B respectively,and the differences between two groups were not significant (P ＞0.05).Groups A had two children (4.3％) and groups B had only one child (4.2％)own the normal aggregative fusion range,two groups did not show any difference (P ＞0.05),respectively,36 children (78.3％) and 17 children (70.8％) had the normal divided fusion range in group A and group B,the recovery rate did not show any significant difference (P ＞0.05).Fifteen (32.6％)and 10 (41.7％) patients acquired the far stereoscopic vision in group A and group B respectively,the recovery rate also did not show any significant difference.Six (13.0％) and 3 (12.5％) children got the normal near stereoscopic vision in group A and group B respectively,the recovery rate did not show any significant difference (P ＞0.05).After treatment,among the 70 cases of amblyopia children 25 (35.7％) got the normal far stereoscopic vision and only 7 (10.0％) got the near stereoscopic vision,there were statistically significant difference between far and near stereoscopic vision (P ＜0.05). Conclusions After amblyopia treatment,although the children obtain the normal visual acuity,in the short term the binocular vision still can not completely become normal.Part-time occlusion therapy dose not produce significant effect to binocular vision development. Key words: Amblyopia; Part-time occlusion; Binocular vision

AIM: To observe the therapy effect of standard prescription on ametrop amblyopia in hyperopic children. METHODS: This study included 270 cases(54 eyes)with complete data, and followed up 24mo. All the amblyopic children were given standard prescription and were divided into progressive addition glass group, under corrected group and full corrected group. And all were observed for their therapy effect and the average healing time in low hyperopic, moderate hyperopic and high hyperopic children with ametropic amblyopia respectively. RESULTS: In low hyperopic children, the difference of the therapy effect of the three corrected methods were insignificant in two years. The meam cure time of the three corrected methods were(7.33±2.11)mo in progressive addition glass group;(9.0±3.71)mo in under corrected grope;(12.5±5.17)mo in full corrected group. Three groups of independent samples by paired <i>t</i>-test showed: the difference between progressive addition glass group and under corrected grope(<i>t</i>=1.66, <i>P</i>>0.05)was statistically insignificant; the difference between progressive addition glass group and full corrected grope(<i>t</i>=3.92, <i>P</i><0.01)was statistically significant; the difference between under corrected grope and full corrected grope(<i>t</i>=2.33, <i>P</i><0.05)was statistically significant. In moderate hyperopic chileren, the differences of the therapy effect of the three corrected methods were significant in two years(<i>χ</i>²=6.75; <i>P</i><0.05). The difference between progressive addition glass group and under corrected grope(<i>χ</i>²=6.3; <i>P</i><0.01)was statistically significant; the difference between progressive addition glass group and full corrected grope(<i>χ</i>²=8.1; <i>P</i><0.005)was statistically significant. The mean cure time of the three corrected methods were(14.0±4.87)mo in progressive addition glass group;(16.93±4.58)mo in under corrected grope;(17.93±4.42)mo in full corrected group. Three groups of independent samples by paired <i>t</i>-test showed: the difference between progressive addition glass group and under corrected grope(<i>t</i>=2.88, <i>P</i><0.01)was statistically significant; the difference between progressive addition glass group and full corrected grope(<i>t</i>=3.9, <i>P</i><0.01)was statistically significant; the difference between under corrected grope and full corrected grope(<i>t</i>=1.01, <i>P</i>>0.05)was statistically insignificant. In high hyperopic amblyopic children, the difference of the therapy effect and the healing time of the three corrected methods were insignificant in two years.(<i>χ</i>²=2.43, <i>P</i>>0.05. <i>t</i>=1.49, <i>P</i>>0.05; <i>t</i>=1.46,<i>P</i>>0.05; <i>t</i>=1.11, <i>P</i>>0.05). CONCLUSION: Under standard prescription, application of progressive multifocal glasses provides a new effective treatment for ametropic amblyopia in hyperopic children, and makes up the deficiency of the whole straightening and under correction in clinical treatment.

Functional magnetic resonance (MR) imaging is a complex, specialized examination that is able to noninvasively measure information critical to patient care such as hemispheric language lateralization ( 1 ). Diagnostic functional MR imaging requires extensive patient interaction as well as the coordinated efforts of the entire health care team. We observed in our practice at an academic center that the times to perform functional MR imaging examinations were excessively lengthy, making scheduling of the examination difficult. The purpose of our project was to reduce functional MR imaging acquisition times by increasing the efficiency of our workflow, using specific quality tools to drive improvement of functional MR imaging. We assembled a multidisciplinary team and retrospectively reviewed all functional MR imaging examinations performed at our institution from January 2013 to August 2015. We identified five key drivers: (a) streamlined protocols, (b) consistent patient monitoring, (c) clear visual slides and audio, (d) improved patient understanding, and (e) minimized patient motion. We then implemented four specific interventions over a period of 10 months: (a) eliminating intravenous contrast medium, (b) reducing repeated language paradigms, (c) updating technologist and physician checklists, and (d) updating visual slides and audio. Our mean functional MR imaging acquisition time was reduced from 76.3 to 53.2 minutes, while our functional MR imaging examinations remained of diagnostic quality. As a result, we reduced our routine scheduling time for functional MR imaging from 2 hours to 1 hour, improving patient comfort and satisfaction as well as saving time for additional potential MR imaging acquisitions. Our efforts to optimize functional MR imaging workflow constitute a practice quality improvement project that is beneficial for patient care and can be applied broadly to other functional MR imaging practices. ©RSNA, 2017.

To map developing areas of activation with functional magnetic resonance (MR) imaging in sedated children by using passive auditory and visual tasks. Forty children between 2 months and 9 years old were examined and grouped according to age. Children were selected from patients referred to undergo brain MR imaging. Patients received pentobarbital (3.0-7.0 mg per kilogram of body weight) or chloral hydrate (50-75 mg/kg). The functional MR imaging study was performed at the end of the examination. Paradigms consisted of flashing lights at 8 Hz displayed on special goggles and a prerecorded mother's voice presented through headphones. Activation maps were obtained from a paired t test with a P value of.0005 (uncorrected). The visual stimulus produced statistically significant negative values in the rostral aspect of the primary visual area (28 [90%] of 31 patients). The auditory paradigm activated either temporal or frontal areas in 26 (68%) of 31 patients. There was more frontal activation in the older children. Visual and auditory cortices can be activated in children who have been sedated. Visual responses show negative values in the rostral visual cortex, independent of age. Auditory activation is seen in temporal and frontal lobes.

Objective To investigate the significance of blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) and ambulatory urodynamics monitoring (AUM) to find the cause of primary monosymptomatic nocturnal enuresis (PMNE) in children. Methods Thirty-seven children with PMNE (20 males and 17 females) were selected, with a mean age of (11.3±4.1) years old.A clinical management tool, 3-day urination record, daytime BOLD-fMRI scan, conventional urodynamics (CUD) and AUM were performed respectively.Thirty-seven gender-age matched children(19 males, 18 females) who would receive surgery treatment because of upper urinary tract disease and were confirmed to have no lower urinary tract dysfunction by CUD were enrolled as controls, with a mean age of (11.1±2.9) years old, and 13 cases underwent BOLD-fMRI scanning. Results It was found that the ALFF value of the left middle frontal gyrus of PMNE was decreased and the ReHo value of the left superior occipital gyrus was increased compared with the control group by the resting BOLD-fMRI.The maximum voiding volume of PNME children was (303.11±87.48) mL, the total urine volume at night was (568.65±208.48) mL, and the nighttime bladder volume was (217.43±81.53) mL.The incidence of maximum voiding volume reduction, nocturnal polyuria and decreased nocturnal bladder volume were 24.32% and 56.76%, and 64.86%, respectively.However, AUM results showed that maximum detrusor pressure in the PMNE group was (39.22±7.78) cmH2O(1 cmH2O=0.098 kPa), which was statistically significantly higher than that in CUD (32.22±9.00) cmH2O, and the difference was statistically significant (P 0.05). Conclusions The abnormal functions of the left middle frontal gyrus and left superior occipital gyrus, nighttime DO and the decrease of bladder capacity at night are considered to be key causes of enuresis in children with PMNE.AUM and resting state BOLD-fMRI evaluations are helpful in differentiating the pathogenesis of PMNE. Key words: Enuresis; Ambulatory urodynamics monitoring; Functional magnetic resonance imaging; Resting state