Perceptual Function and Category-Selective Neural Organization in Children with Resections of Visual Cortex.

The consequences of cortical resection, a treatment for humans with pharmaco-resistant epilepsy, provide a unique opportunity to advance our understanding of the nature and extent of cortical (re)organization. Despite the importance of visual processing in daily life, the neural and perceptual sequellae of occipitotemporal resections remain largely unexplored. Using psychophysical and fMRI investigations, we compared the neural and visuoperceptual profiles of 10 children or adolescents following unilateral cortical resections and their age- and gender-matched controls. Dramatically, with the exception of two individuals, both of whom had relatively greater cortical alterations, all patients showed normal perceptual performance on tasks of intermediate- and high-level vision, including face and object recognition. Consistently, again with the exception of the same two individuals, both univariate and multivariate fMRI analyses revealed normal selectivity and representational structure of category-selective regions. Furthermore, the spatial organization of category-selective regions obeyed the typical medial-to-lateral topographic organization albeit unilaterally in the structurally preserved hemisphere rather than bilaterally. These findings offer novel insights into the malleability of cortex in the pediatric population and suggest that, although experience may be necessary for the emergence of neural category-selectivity, this emergence is not necessarily contingent on the integrity of particular cortical structures.SIGNIFICANCE STATEMENT One approach to reduce seizure activity in patients with pharmaco-resistant epilepsy involves the resection of the epileptogenic focus. The impact of these resections on the perceptual behaviors and organization of visual cortex remain largely unexplored. Here, we characterized the visuoperceptual and neural profiles of ventral visual cortex in a relatively large sample of post-resection pediatric patients. Two major findings emerged. First, most patients exhibited preserved visuoperceptual performance across a wide-range of visual behaviors. Second, normal topography, magnitude, and representational structure of category-selective organization were uncovered in the spared hemisphere. These comprehensive imaging and behavioral investigations uncovered novel evidence concerning the neural representations and visual functions in children who have undergone cortical resection, and have implications for cortical plasticity more generally.

Microsurgical resection of a high-grade occipital arteriovenous malformation after staged embolization.

The authors demonstrate the case of a 16-year-old girl with a large symptomatic occipital arteriovenous malformation (AVM). The staged embolization was performed to downgrade the AVM from Spetzler-Martin (S-M) Grade IV (Supplementary S-M Grade 7) to Grade III (Supplementary S-M Grade 5). The patient developed a subacute progressive visual field defect after the final time of embolization. MRI revealed an enlarged draining venous ectasia of the AVM compressing the visual cortex. Postoperatively, good radiological results were achieved, and the patient reported an improvement in her symptoms. The detailed operative technique and surgical nuances (including the surgical features of the AVM postembolization) of the marginal dissection and removal are illustrated in this video atlas. The video can be found here: https://youtu.be/2MZq5patcJI .

Electrical stimulation of the human homolog of the medial superior temporal area induces visual motion blindness.

Despite tremendous advances in neuroscience research, it is still unclear how neuronal representations of sensory information give rise to the contents of our perception. One of the first and also the most compelling pieces of evidence for direct involvement of cortical signals in perception comes from electrical stimulation experiments addressing the middle temporal (MT) area and the medial superior temporal (MST) area: two neighboring extrastriate cortical areas of the monkey brain housing direction-sensitive neurons. Here we have combined fMRI with electrical stimulation in a patient undergoing awake brain surgery, to separately probe the functional significance of the human homologs, i.e., area hMT and hMST, on motion perception. Both the stimulation of hMT and hMST made it impossible for the patient to perceive the global visual motion of moving random dot patterns. Although visual motion blindness was predominantly observed in the contralateral visual field, stimulation of hMST also affected the ipsilateral hemifield. These results suggest that early visual cortex up to the stage of MT is not sufficient for the perception of global visual motion. Rather, visual motion information must be mediated to higher-tier cortical areas, including hMST, to gain access to conscious perception.

New methods devised specify the size and color of the spots monkeys see when striate cortex (area V1) is electrically stimulated.

Creating a prosthetic device for the blind is a central future task. Our research examines the feasibility of producing a prosthetic device based on electrical stimulation of primary visual cortex (area V1), an area that remains intact for many years after loss of vision attributable to damage to the eyes. As an initial step in this effort, we believe that the research should be carried out in animals, as it has been in the creation of the highly successful cochlear implant. We chose the rhesus monkey, whose visual system is similar to that of man. We trained monkeys on two tasks to assess the size, contrast, and color of the percepts created when single sites in area V1 are stimulated through microelectrodes. Here, we report that electrical stimulation within the central 5° of the visual field representation creates a small spot that is between 9 and 26 min of arc in diameter and has a contrast ranging between 2.6% and 10%. The dot generated by the stimulation in the majority of cases was darker than the background viewed by the animal and was composed of a variety of low-contrast colors. These findings can be used as inputs to models of electrical stimulation in area V1. On the basis of these findings, we derive what kinds of images would be expected when implanted arrays of electrodes are stimulated through a camera attached to the head whose images are converted into electrical stimulation using appropriate algorithms.

Robot-assisted implantation of a microelectrode array in the occipital lobe as a visual prosthesis: technical note.

The prospect of direct interaction between the brain and computers has been investigated in recent decades, revealing several potential applications. One of these is sight restoration in profoundly blind people, which is based on the ability to elicit visual perceptions while directly stimulating the occipital cortex. Technological innovation has led to the development of microelectrodes implantable on the brain surface. The feasibility of implanting a microelectrode on the visual cortex has already been shown in animals, with promising results. Current research has focused on the implantation of microelectrodes into the occipital brain of blind volunteers. The technique raises several technical challenges. In this technical note, the authors suggest a safe and effective approach for robot-assisted implantation of microelectrodes in the occipital lobe for sight restoration.

An examination of linking hypotheses drawn from the perceptual consequences of experimentally induced changes in neural circuitry.

Because targeted early experiential manipulations alter both perception and the response properties of particular cells in the striate cortex, they have been used as evidence for linking hypotheses between the two. However, such hypotheses assume that the effects of the early biased visual input are restricted to just the specific cell population and/or visual areas of interest and that the neural populations that contribute to the visual perception itself do not change. To examine this assumption, we measured the consequences for vision of an extended period of early monocular deprivation (MD) on a kitten (from 19 to 219 days of age) that began well before, and extended beyond, bilateral ablation of visual cortical areas 17 and 18 at 132 days of age. In agreement with previous work, the lesion reduced visual acuity by only a factor of two indicating that the neural sites, other than cortical areas 17 and 18, that support vision in their absence have good spatial resolution. However, these sites appear to be affected profoundly by MD as the effects on vision were just as severe as those observed following MD imposed on normal animals. The pervasive effects of selected early visual deprivation across many cortical areas reported here and elsewhere, together with the potential for perception to be mediated at a different neural site following deprivation than after typical rearing, points to a need for caution in the use of data from early experiential manipulations for formulation of linking hypotheses.

Protocol for human brain organoid transplantation into a rat visual cortex to model neural repair.

Human stem-cell-derived organoids represent a promising substrate for transplantation-based neural repair. Here, we describe a protocol for transplanting forebrain organoids into an injured adult rat visual cortex. This protocol includes surgical details for craniectomy, aspiration injury, organoid transplantation, and cranioplasty. This platform represents a valuable tool for investigating the efficacy of organoids as structured grafts for neural repair. For complete details on the use and execution of this protocol, please refer to Jgamadze et al.1.

Visual percepts evoked with an intracortical 96-channel microelectrode array inserted in human occipital cortex.

BACKGROUNDA long-held goal of vision therapy is to transfer information directly to the visual cortex of blind individuals, thereby restoring a rudimentary form of sight. However, no clinically available cortical visual prosthesis yet exists.METHODSWe implanted an intracortical microelectrode array consisting of 96 electrodes in the visual cortex of a 57-year-old person with complete blindness for a 6-month period. We measured thresholds and the characteristics of the visual percepts elicited by intracortical microstimulation.RESULTSImplantation and subsequent explantation of intracortical microelectrodes were carried out without complications. The mean stimulation threshold for single electrodes was 66.8 ± 36.5 µA. We consistently obtained high-quality recordings from visually deprived neurons and the stimulation parameters remained stable over time. Simultaneous stimulation via multiple electrodes was associated with a significant reduction in thresholds (P < 0.001, ANOVA) and evoked discriminable phosphene percepts, allowing the blind participant to identify some letters and recognize object boundaries.CONCLUSIONSOur results demonstrate the safety and efficacy of chronic intracortical microstimulation via a large number of electrodes in human visual cortex, showing its high potential for restoring functional vision in the blind.TRIAL REGISTRATIONClinicalTrials.gov identifier NCT02983370.FUNDINGThe Spanish Ministerio de Ciencia Innovación y Universidades, the Generalitat Valenciana (Spain), the Europan Union's Horizon 2020 programme, the Bidons Egara Research Chair of the University Miguel Hernández (Spain), and the John Moran Eye Center of the University of Utah.

Focal laser-lesions activate an endogenous population of neural stem/progenitor cells in the adult visual cortex.

CNS lesions stimulate adult neurogenic niches. Endogenous neural stem/progenitor cells represent a potential resource for CNS regeneration. Here, we investigate the response to unilateral focal laser-lesions applied to the visual cortex of juvenile rats. Within 3 days post-lesion, an ipsilateral increase of actively cycling cells was observed in cortical layer one and in the callosal white matter within the lesion penumbra. The cells expressed the neural stem/progenitor cell marker Nestin and the 473HD-epitope. Tissue prepared from the lesion area by micro-dissection generated self-renewing, multipotent neurospheres, while cells from the contralateral visual cortex did not. The newly formed neural stem/progenitor cells in the lesion zone might support neurogenesis, as suggested by the expression of Pax6 and Doublecortin, a marker of newborn neurons. We propose that focal laser-lesions may induce the emergence of stem/progenitor cells with neurogenic potential. This could underlie the beneficial effects of laser application in neurosurgery.

Relationships between brain tumor and optic tract or calcarine fissure are involved in visual field deficits after surgery for brain tumor.

PURPOSE: Diffusion tensor tractography provides useful information regarding the surgical strategy for brain tumors. The goal of the present study was to analyze relationships between visual field deficits and the locations of brain tumors compared with optic tracts as visualized by tractography, and compared with the calcarine fissure. METHODS: Subjects comprised 11 patients with brain tumor in the occipital lobe or atrium of the lateral ventricle who underwent surgery between October 2006 and February 2009. Tumors were categorized as Type A, with almost all the optic tract in the occipital lobe or atrium of the lateral ventricle running close to and stretched by the brain tumor; and Type B, with the optic tract running at least partially distant to the brain tumor and remaining unstretched. RESULTS: Those type A optic tracts that were laterally compressed by brain tumors (Cases 1-3) displayed hemianopsia after surgery. When the brain tumor was located rostro-medial to the calcarine fissure and optic tracts were compressed caudally by the tumor, lower quadrant hemianopsia remained after surgery (Cases 4, 5). In other cases, the visual field remained or improved to normal after surgery. CONCLUSION: The relationship between optic tracts or the calcarine fissure, and brain tumors in the occipital lobe or atrium of the lateral ventricle is related to visual field deficits after surgery. In particular, those Type A optic tracts that are compressed laterally show hemianopsia of the visual field after surgery.

Brain Morphometric and Functional Magnetic Resonance Imaging Study on Patients with Visual Field Defects Resulting from Suprasellar Tumors: Preoperative and Postoperative Assessment.

OBJECTIVE: The aim of this study was to investigate the structural and functional changes in the visual cortex in patients with suprasellar tumor with recovery of visual field defects at different times before and after surgical decompression of the optic nerves. METHODS: Twenty-one patients with suprasellar tumor with visual field defects were scanned with structural images and resting-state functional magnetic resonance imaging at 1 week preoperation, 1 week postoperation, and 1 month postoperation. Paired-sample t test was performed on the gray matter volume (GMV) within the occipital cortex, and the significance level was set at false discovery rate (FDR)-adjusted P < 0.05 voxel level to define the region of interest (ROI). One-way analysis of variance was performed on GMV and amplitude of low frequency fluctuation (ALFF) within the ROI. Pearson coefficients were calculated between changes of GMV and ALFF within the ROI and clinical factors. RESULTS: The GMV in the bilateral pericalcarine cortex increased significantly at 1 month postoperation compared with the preoperative period (FDR-adjusted P < 0.05), with correlation to visual field defects. ALFF values in the bilateral pericalcarine cortex at 1 month postoperation were significantly higher than preoperative values. CONCLUSIONS: The postoperative visual improvement can be reflected in the increased GMV and ALFF of the bilateral pericalcarine cortex at 1 month postoperation, which suggests that an experience-dependent plasticity of the visual cortex was induced by an increase in sensory input.

Prolonged learning and split-brain cats.

A definite relation is shown between interhemispheric transfer and speed of learning. Split-brain cats were trained in a variety of discriminations, and the success or failure of interhemispheric transfer was evaluated with regard to rate of learning. When interhemispheric transfer succeeds, learning time is normal; when interhemispheric transfer fails, learning time is prolonged, becoming at least twice that of normal. Retention is also poor in those animals that exhibit prolonged learning. A normal learning curve appears to be the product of interaction between both cerebral hemispheres during learning.

Diffusion tensor imaging of brain plasticity after occipital lobectomy.

Reorganization involving residual visual pathways with unilateral damage to the primary visual cortex was previously described. Using diffusion tensor imaging, we measured water diffusion-related changes in the optic radiation contralateral to occipital lobe ablation in children with intractable epilepsy. We studied 10 children who had undergone a resection of the unilateral occipital cortex and 13 control subjects. Diffusion tensor imaging was acquired using a 1.5 Tesla magnetic resonance scanner. Fiber bundles representing optic radiation were tracked. Diffusion parameters included mean fractional anisotropy, apparent diffusion coefficient, and diffusion parallel and perpendicular to the fiber tract. In the surgical group, fractional anisotropy values of optic radiation contralateral to the side of resection exhibited a significant positive partial correlation (r = 0.752, P = 0.019) with duration of time between surgery and diffusion tensor imaging acquisition, after controlling for age. The apparent diffusion coefficient and parallel diffusivity were higher in the surgical versus the control group, but did not differ among patients. After unilateral resection of the occipital lobe, the contralateral optic radiation undergoes significant changes in anisotropy. Such structural white-matter changes may represent an adaptive response because of unilateral occipital ablation, and may account for plasticity changes observed in functional magnetic resonance imaging.

Prime-sight in a blindsight subject.

A subject (D.B.) who had no experience of visual stimuli in a field defect caused by visual cortex damage but could discriminate them ('blindsight') nevertheless reported visible after-images of the stimuli when they were turned off ('prime-sight'). This was investigated using projected visual stimuli of varying colors, contrasts, shapes and spatial frequencies, and by measuring the properties of the after-images, including their duration, size scaling, color and interocular transfer, comparing the capacity of the blindsight and prime-sight modes. These phenomena offer a unique opportunity to compare conscious and unconscious neural events in response to the same visual events.

Multi-scale, multi-modal analysis uncovers complex relationship at the brain tissue-implant neural interface: new emphasis on the biological interface.

OBJECTIVE: Implantable neural electrode devices are important tools for neuroscience research and have an increasing range of clinical applications. However, the intricacies of the biological response after implantation, and their ultimate impact on recording performance, remain challenging to elucidate. Establishing a relationship between the neurobiology and chronic recording performance is confounded by technical challenges related to traditional electrophysiological, material, and histological limitations. This can greatly impact the interpretations of results pertaining to device performance and tissue health surrounding the implant. APPROACH: In this work, electrophysiological activity and immunohistological analysis are compared after controlling for motion artifacts, quiescent neuronal activity, and material failure of devices in order to better understand the relationship between histology and electrophysiological outcomes. MAIN RESULTS: Even after carefully accounting for these factors, the presence of viable neurons and lack of glial scarring does not convey single unit recording performance. SIGNIFICANCE: To better understand the biological factors influencing neural activity, detailed cellular and molecular tissue responses were examined. Decreases in neural activity and blood oxygenation in the tissue surrounding the implant, shift in expression levels of vesicular transporter proteins and ion channels, axon and myelin injury, and interrupted blood flow in nearby capillaries can impact neural activity around implanted neural interfaces. Combined, these tissue changes highlight the need for more comprehensive, basic science research to elucidate the relationship between biology and chronic electrophysiology performance in order to advance neural technologies.

Relationship between cortical resection and visual function after occipital lobe epilepsy surgery.

OBJECTIVE In this study, the authors investigated long-term clinical and visual outcomes of patients after occipital lobe epilepsy (OLE) surgery and analyzed the relationship between visual cortical resection and visual function after OLE surgery. METHODS A total of 42 consecutive patients who were diagnosed with OLE and underwent occipital lobe resection between June 1995 and November 2013 were included. Clinical, radiological, and histopathological data were reviewed retrospectively. Seizure outcomes were categorized according to the Engel classification. Visual function after surgery was assessed using the National Eye Institute Visual Functioning Questionnaire 25. The relationship between the resected area of the visual cortex and visual function was demonstrated by multivariate linear regression models. RESULTS After a mean follow-up period of 102.2 months, 27 (64.3%) patients were seizure free, and 6 (14.3%) patients had an Engel Class II outcome. Nineteen (57.6%) of 33 patients had a normal visual field or quadrantanopia after surgery (normal and quadrantanopia groups). Patients in the normal and quadrantanopia groups had better vision-related quality of life than those in the hemianopsia group. The resection of lateral occipital areas 1 and 2 of the occipital lobe was significantly associated with difficulties in general vision, peripheral vision, and vision-specific roles. In addition, the resection of intraparietal sulcus 3 or 4 was significantly associated with decreased social functioning. CONCLUSIONS The authors found a favorable seizure control rate (Engel Class I or II) of 78.6%, and 57.6% of the subjects had good visual function (normal vision or quadrantanopia) after OLE surgery. Lateral occipital cortical resection had a significant effect on visual function despite preservation of the visual field.

Successful Reorganization of Category-Selective Visual Cortex following Occipito-temporal Lobectomy in Childhood.

Investigations of functional (re)organization in children who have undergone large cortical resections offer a unique opportunity to elucidate the nature and extent of cortical plasticity. We report findings from a 3-year investigation of a child, U.D., who underwent surgical removal of the right occipital and posterior temporal lobes at age 6 years 9 months. Relative to controls, post-surgically, U.D. showed age-appropriate intellectual performance and visuoperceptual face and object recognition skills. Using fMRI at five different time points, we observed a persistent hemianopia and no visual field remapping. In category-selective visual cortices, however, object- and scene-selective regions in the intact left hemisphere were stable early on, but regions subserving face and word recognition emerged later and evinced competition for cortical representation. These findings reveal alterations in the selectivity and topography of category-selective regions when confined to a single hemisphere and provide insights into dynamic functional changes in extrastriate cortical architecture.

Optic radiation tractography integrated into simulated treatment planning for Gamma Knife surgery.

OBJECT: No definitive method of preventing visual field deficits after stereotactic radiosurgery for lesions near the optic radiation (OR) has been available so far. The authors report the results of integrating OR tractography based on diffusion tensor (DT) magnetic resonance imaging into simulated treatment planning for Gamma Knife surgery (GKS). METHODS: Data from imaging studies performed in 10 patients who underwent GKS for treatment of arteriovenous malformations (AVMs) located adjacent to the OR were used for the simulated treatment planning. Diffusion tensor images performed without the patient's head being secured by a stereotactic frame were used for DT tractography, and the OR was visualized by means of software developed by the authors. Data from stereotactic 3D imaging studies performed after frame fixation were coregistered with the data from DT tractography. The combined images were transferred to a GKS treatment-planning workstation. Delivered doses and distances between the treated lesions and the OR were analyzed and correlated with posttreatment neurological changes. RESULTS: In patients presenting with migraine with visual aura or occipital lobe epilepsy, the OR was located within 11 mm from AVMs. In a patient who developed new quadrantanopia after GKS, the OR had received 32 Gy. A maximum dose to the OR of less than 12 Gy did not cause new visual field deficits. A maximum dose to the OR of 8 Gy or more was significantly related to neurological change (p < 0.05), including visual field deficits and development or improvement of migraine. CONCLUSIONS: Integration of OR tractography into GKS represents a promising tool for preventing GKS-induced visual disturbances and headaches. Single-session irradiation at a dose of 8 Gy or more was associated with neurological change.

Monocular denervation of visual nuclei modulates APP processing and sAPPα production: A possible role on neural plasticity.

Amyloid precursor protein (APP) is essential to physiological processes such as synapse formation and neural plasticity. Sequential proteolysis of APP by beta- and gamma-secretases generates amyloid-beta peptide (Aß), the main component of senile plaques in Alzheimer Disease. Alternative APP cleavage by alpha-secretase occurs within Aß domain, releasing soluble α-APP (sAPPα), a neurotrophic fragment. Among other functions, sAPPα is important to synaptogenesis, neural survival and axonal growth. APP and sAPPα levels are increased in models of neuroplasticity, which suggests an important role for APP and its metabolites, especially sAPPα, in the rearranging brain. In this work we analyzed the effects of monocular enucleation (ME), a classical model of lesion-induced plasticity, upon APP content, processing and also in secretases levels. Besides, we addressed whether α-secretase activity is crucial for retinotectal remodeling after ME. Our results showed that ME induced a transient reduction in total APP content. We also detected an increase in α-secretase expression and in sAPP production concomitant with a reduction in Aß and ß-secretase contents. These data suggest that ME facilitates APP processing by the non-amyloidogenic pathway, increasing sAPPα levels. Indeed, the pharmacological inhibition of α-secretase activity reduced the axonal sprouting of ipsilateral retinocollicular projections from the intact eye after ME, suggesting that sAPPα is necessary for synaptic structural rearrangement. Understanding how APP processing is regulated under lesion conditions may provide new insights into APP physiological role on neural plasticity.