Restorative Neurology and Neuroscience - Volume 15, issue 2-3

Authors: Sabel, Bernhard A.

Article Type: Other

Abstract: This is an introduction to a special issue of the journal Restorative Neurology and Neuroscience which contains a series of papers presented at a satellite symposium held in conjunction with the European Forum of Neuroscience, Berlin, July 1-2, 1998, entitled "Visual System Damage: Residual Vision and Plasticity". The symposium highlighted research findings both from animals and humans which sustained brain injury in early development and in adulthood. The findings demonstrate the degree of residual vision the …injured brain possesses and summarize the effects of drugs and training on the plasticity of the visual system. As this conference demonstrated, the visual system is able to respond in many ways in an adaptive manner to lesions inflicted early in life and in adulthood. These changes may bring about spontaneous recovery of visual functions as long as the brain contains a sufficient capacity of residual vision. Both in children and in adults, systematic visual training can help patients to regain some visual functions which have previously been considered to be irrevocably lost. By carefully assessing residual vision it is proposed that the potential for plasticity of the visual system can be utilized to achieve clinical improvement using appropriate training paradigms. Show more

Keywords: Plasticity, rehabilitation, brain injury, regeneration, training, vision, compensation, restoration

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 2-3, pp. 73-79, 1999

Authors: Payne, Bertram R.

Article Type: Research Article

Abstract: Damage of primary visual cortex in mature mammals severely disrupts vision by disconnecting much of the cognitive processing machinery of extrastriate cortex from its source of visual signals in the retina. However, equivalent lesions incurred early in postnatal life unmask a substantial latent flexibility of the brain to minimize the disruption by specific and ordered pathway expansions that bypass the lesion. The expansions shape pathways from retina through thalamus to extrastriate cortex and onto the midbrain …into new, useful forms that are retained into adult life. These useful modifications support relatively normal signal processing in a variety of structures and the sparing of certain visually guided behaviors, such as aspects of complex-pattern vision and localizing objects introduced into the visual field. Thus, both the brain and the individual are optimized, in the absence of primary visual cortex, by adaptations for useful interactions with the environment. So far, the repercussions of early visual cortex lesions have been most thoroughly documented in cats, although it is likely on the basis of known repercussions and similarity of visual system organization and developmental sequence, that broadly equivalent repercussions and adaptations occur in monkeys and humans following early lesions of primaiy visual cortex. The knowledge gained has implications for devising therapeutic strategies to attenuate defects in vision induced by cortical lesions. Show more

Keywords: Lesion-induced plasticity, behavioral sparing, visual pathways, cat, monkey, human

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 2-3, pp. 81-106, 1999

Authors: Frost, Douglas O.

Article Type: Research Article

Abstract: Lesions of eerebral targets of the retina in newborn hamsters, when combined with transection of lemniscal pathways to the primary auditory or somatosensory thalamic nuclei or the secondary thalamic visual nucleus, can induce the formation of permanent retinal projections to the deafferented non-visual structures. These projections are retinotopically organized and form functional synapses. Consequently, neurons in the auditory or somatosensory cortices, which normally are not driven by visual stimuli, become visually responsive …and have receptive field properties that ressemble, in several important ways, those of neurons in the visual cortex of normal animals. The surgically-induced retinothalamo-cortical pathways can mediate visually guided behaviors whose normal substrate, the pathway from the retina to the primary visual cortex via the thalamic dorsal lateral geniculate nucleus, is missing. Show more

Keywords: Retina, thalamus, cortex, plasticity, brain repair

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 2-3, pp. 107-113, 1999

Authors: Galuske, Ralf A.W. | Kim, Dae-Shik | Singer, Wolf

Article Type: Research Article

Abstract: Purpose - It has been proposed that experience dependent maturation and reorganization in the neocortex might be based on the activity dependent competition between different sets of axons for growth related molecules such as neurotrophins. In the present study we tested this hypothesis by examination of the effects of external administration of NGF and BDNF on the experience dependent rearrangement of thalamocortical connections after monocular deprivation (MD) in the developing cat visual cortex. …Methods - The visual cortices of kittens were infused intracortically either with BDNF, NGF or cytochrome C while the animals were subjected to MD for one week during the peak of the critical period (postnatal day 26 to postnatal day 40). Subsequently cortical neuronal responses were assessed with optical (optical imaging of intrinsic signals) and single unit recording techniques. Results - In control hemispheres treated with cytochrome C, MD had caused the expected shift of OD towards the normal eye. Also hemispheres treated with NGF exhibited a strong shift of OD towards the open eye. However, in the BDNF infused hemispheres OD had shifted towards the deprived eye in a zone extending 2.5-3.5 mm from the infusion cannula and neurons had lost their orientation selectivity. In an adjacent transition zone both eyes activated the cortex equally well and responses were again tuned for orientation and at still larger distances OD was shifted towards the normal eye. Conclusions - The present data support the concept of an involvement of neurotrophins in cortical plasticity. However, our observations suggest for both neurotrophins, NGF and BDNF, a more complex role in the developing neocortex than serving simply as the substrate of an activity dependent competition process within the visual cortex. Moreover, the outcome of our study indicaties strong differences between BDNF and NGF concerning their involvement and locus of action in developmental plasticity. Show more

Keywords: Cat visual cortex, development, ocular dominance plasticity, brain derived neurotrophic factor, nerve growth factor, optical imaging, single cell recording

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 2-3, pp. 115-124, 1999

Authors: Berardi, N. | Lodovichi, C. | Caleo, M. | Pizzorusso, T. | Maffei, L.

Article Type: Research Article

Abstract: A role for neurotrophins in regulating cortical developmental plasticity has clearly emerged in these last years. In this review we first present a summary of the early data on the action of NGF in visual cortical development and plasticity in the rat and of the actions of the other neurotrophins in the visual cortex of other mammals. In addition, in order to clarify the differerences in the results obtained with the various neurotrophins in different animal …preparations we also report new data on the action of NGF, BDNF, NT3 and NT4 in the same preparation, namely the visual cortex of the rat. We discuss old and new results in a physiological model where different neurotrophins play different roles in regulating visual cortical development and plasticity by acting on different neural targets, such as LGN afferents, intracortical circuitry and subcortical afferents and propose a tentative scheme summarizing these actions. Show more

Keywords: Neurotrophins, visual cortical plasticity, monocular deprivation, dark rearing, neurotransmitter release

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 2-3, pp. 125-136, 1999

Authors: Wörgötter, F. | Suder, K. | Fünke, K.

Article Type: Research Article

Abstract: Due to eye and object movements the visual world changes on a rather fast time scale and the neuronal network of the primary visual pathway has to immediately react to these changes. Accordingly the neuronal activity patterns in the visual thalamus and cortex show a pronounced dynamic behavior which reenters the circuitry such that the actual cell responses are also guided by the activation history of the network. Thus, spatial and temporal aspects of visual receptive …fields change not only by means of the actual visual stimulation hut also as a consequence of the state of the network. In this short review we summarize the different aspects which can influence the temporal firing patterns of cells in the visual thalamus (lateral geniculate nucleus, LGN) mainly by demonstrating how their inter-spike interval distributions will change. We then show that these firing patterns are able to change the spatial shape of receptive fields in the visual cortex (see Fig. 12 for a summary diagram). Finally, by means of a biophysical model, we will argue that the observed changes could serve to adjust the temporal and spatial resolution within the primary visual pathway to the different demands for information processing in an attentive as compared to a non-attentive state. Show more

Keywords: Time structure, attention, feedback, primary visual pathway

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 2-3, pp. 137-152, 1999

Authors: Eysel, Ulf T. | Schweigart, Georg | Mittmann, Thomas | Eyding, Dirk | Qu, Ying | Vandesande, Frans | Orban, Guy | Arckens, Lutgarde

Article Type: Research Article

Abstract: Retinal and cortical lesions are completely different events that trigger visual cortical plasticity. We therefore compared the cortical effects of homonymous lesions of the central retina with effects of cortical lesions. All in vivo experiments were performed in anaesthetized, adult cats. Retinal lesions were made with a Xenon-light photocoagulator, and cortical lesions were induced by focal application of heat or ibotenic acid injection. Both, in cortical regions representing the retinal scotoma and at the border of …small focal cortical lesions single neuron activity was initially suppressed and accompanied by a narrow area of increased activity adjacent to the region of functional loss during the first 1-2 weeks. At the same time an increased glutamatergic NMDA response and a reduction of GABAA and GABAB responses was observed around the cortical lesions in vitro. At an early stage long-term potentiation (LTP) is facilitated in those regions that were characterized by local upregulation of excitation and downregulation of inhibition after cortical lesions. Similarly, at the border of cortical scotomas in area 17 an increased glutamate level was found while inside the scotoma GAD levels were reduced. Shifts in topography of retinal representation as well as increases of receptive field size were detected as signs of lesion-induced neuronal reorganization after retinal and cortical lesions with longer survival times. A common cascade of events is triggered in the visual cortex by retinal as well as cortical lesions: reduced GABAergic inhibition and increased glutamatergic excitation, leading to increased spontaneous activity and visual excitability that is accompanied by facilitated LTP, and appears to initiate local cortical reorganization after functional disturbances in the visual system. Show more

Keywords: Lesion, plasticity, glutamate, GABA, LTP

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 2-3, pp. 153-164, 1999

Authors: Chino, Yuzo M.

Article Type: Research Article

Abstract: The mature visual cortex is capable of reorganizing its functional connections in response to retinal injuries. Although this phenomenon is well established, there are a number of unresolved issues. This paper will review some of the more critical aspects of adult plasticity including those based on our most recent findings. Our preliminary data indicate that a large-scale reorganization of cortical maps following retinal injuries may require an increase in synaptic strengths at key cortical sites promoted …by long-term, repeated use. Show more

Keywords: Adult plasticity, visual experience, topographic map reorganization, retinal lesions, visual cortex

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 2-3, pp. 165-176, 1999

Authors: Sabel, Bernhard A.

Article Type: Research Article

Abstract: Lesions in the central nervous system often lead to loss of vision due to visual system involvement. In the course of weeks or months, some vision can recover in rats, cats, monkeys, and humans, though it is mostly incomplete. This paper reviews the current knowledge of the under-lying neurobiological mechanism of recovery of vision, particularly those observed in adult rats with partial optic nerve crush (ONC). Immediately after ONC, rats are almost completely blind, evident by …their inability to perform visual tasks such as brightness and pattern discrimination and they fail to orient towards small, moving targets. Within about two weeks, however, rats significantly recover some of their lost visual functions despite the fact that only about 10 % of the retinal ganglion cells (RGCs) maintain a viable connection with their brain tar-gets. Molecular, anatomical and physiological studies have identified some of the neurobiological determinants of this visual restitution. Immediately following ONC there is a massive soma swelling of about 80 % of the RGCs with subsequent cell death due to apoptosis and necrosis. The remaining 20 % survive with or without axonal connection to their target and undergo marked changes: (i) about half of these RGCs experience a moderate, reversible soma swelling, (ii) there is a loss of anterograde axonal transport in the optic nerve which partially recovers after several weeks, and (iii) many of the surviving RGCs undergo alterations in gene expression, particularly that of the NR1 recep-tor and the immediate early gene, c-jun. While these changes may be part of an adaptive program of the cells to cope with the trauma, cell sur-vival in the retina does not correlate well with subsequent recovery of vision. We have therefore also studied plasticity in the down stream denervated brain structures which are innervated by retinofugal pathways, particularly the superior colliculus. Here we found (i) recovery of metabolic activity and (ii) changes in gene expression, such as an up-regulation of the enhancer of split (R esp-1) gene. When viewed together with studies on recovery of vision and neuronal reorganization done in other laboratories it is clear that recovery of vision involves simultaneous plasticity in the damaged structure itself and, transsynaptically, in down-stream structures such as the tectum, the lateral geniculate nucleus and visual cortex. Considering both pre-clinical and clinical evidence, I propose the biological substrate underlying restoration of vision as follows: surviving neurons within areas of partial damage which corresponds clinically to transition zones located between intact and deficient visual field sectors act in concert with down-stream areas, which themselves undergo dramatic reorganization to cope with a condition of reduced, but residual input. Restitution of vision is therefore a multifactorial event of within-systems plasticity, involving neurobiological alterations along the entire retinofugal axis. It is likely that these mechanisms are also responsible for visual improvements that are seen both in animals and patients after prolonged visual restitution training. Show more

Keywords: Recovery, rehabilitation, vision, plasticity, blindness, restitution

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 2-3, pp. 177-200, 1999

Authors: Schiefer, U. | Skalej, M. | Dietrich, T.J. | Braun, C.

Article Type: Research Article

Abstract: Clinical detection and follow-up of homonymous visual field defects require appropriate perimetric procedures: since postgeniculate lesions are usually characterised by absolute scotomata, time consuming threshold methods can be replaced by supraliminal strategies with comparatively high stimulus densities. Compared with equidistant rectangular grids, a centripetal stimulus condensation represents the physi-ological conditions more adequately and thus is more effective. It allows one to differentiate central changes of the visual field, like macular sparing or …splitting, which also interfere with reading performance. This procedure requires test points to be located to either side of the verti-cal meridian, rather than directly on it. Multimodal assessment of visual subfunctions (using static, kinetic or colour test points, random dot patterns or optokinetic stimulation) specifies the effect of the lesion in different channels or regions of the visual pathways. Automation of perimetric procedures and continuous monitoring of fixation are important tools, enhancing the quality of examination and follow-up. The above mentioned psychophysical techniques for detection of functional defects and documentation of eventual recovery, as well as matching neuroimaging findings, are demonstrated by illustrative cases. Show more

Keywords: Perimetry, homonymous hemianopia, macular sparing, macular splitting, recovery, follow-up, automation, neuroimaging, MRI, fMRI

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 2-3, pp. 201-217, 1999

Authors: Innocenti, Giorgio M. | Kiper, Daniel C. | Knyazeva, Maria G. | Deonna, Thierry W.

Article Type: Research Article

Abstract: MS is a little girl who suffered severe, bilateral destruction of her primary visual areas at six weeks, after premature birth at 30 weeks. Between the ages of 4.5 and 5.5 years she partially recovered different aspects of visual function, and, in particular, the ability to segregate fig-ures from background, based on texture cues. The recovery might have been due to the compensatory role of the remaining visual areas that could have acquired response properties similar …to those of the primary visual areas. This is not supported by the available FMRI (functional magnetic resonance imaging) responses to visual stimuli. Instead, abnormalities in the pattern of stimulus-induced changes of interhemi-spheric EEG-coherence in this patient suggest that her visual callosal connections, and possibly other cortico-cortical connections have re-organized abnormally. Since cortico-cortical connections, including the callosal ones appear to be involved in perceptual binding and figure-background segregation, their reorganization could be an important element in the functional recovery after early lesion, and/or in the residual perceptual impairment. Show more

Keywords: Visual cortex, human, cat, ferret, corpus callosum, connections

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 2-3, pp. 219-227, 1999

Authors: Werth, R. | Moehrenschlager, M.

Article Type: Research Article

Abstract: Sixteen children aged 1 to 15 years who were blind due to an ischemic postgeniculate cerebral lesion after perinatal asphyxia and 6 children aged 1 to 13 years who were blinded after a postgeniculate traumatic cerebral lesion participated in a systematic visual field training. Thirty-one children who were blind due to a postgeniculate lesion following perinatal asphyxia and 12 children who suffered from blindness after a traumatic postgeniculate lesion served as controls. These children received no …visual field training or an ineffective visual field training. The extension of the functional visual field and the functional luminance difference threshold were assessed with a specially designed arc perime-ter. In all children blindness had already persisted for at least one year. Visual functions developed within a training period of three months in 15 of 22 children who received visual field training whereas there was no spontaneous recovery in the control group. The functional luminance difference threshold was still elevated above normal in the case of 5 children who recovered from blindness. In 2 children the latency of sac-cades elicited by light targets in the formerly blind visual area was significantly longer than the latency of saccades elicited by targets in the normal area of the visual field. Light scatter was controlled in order to exclude that the widening of the visual field during training which we interpreted as a sign of the development of visual functions was an effect of scattering light. The findings support the assumption that system-atic stimulation of cerebrally blind areas may facilitate the development of visual functions in brain damaged children. The cerebral lesions associated with the impaired visual functions which improved during the treatment are in agreement with the assumption that spared tissue in the striate and extrastriate visual cortex and underlying white matter is the anatomical basis of the shrinkage of the blind areas. Show more

Keywords: Visual plasticity, brain damage, infancy, visual field training, perimetry, homonymous visual field defect

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 2-3, pp. 229-241, 1999

Authors: Wessinger, C. Mark | Fendrich, Robert | Gazzaniga, Michael S.

Article Type: Research Article

Abstract: Using stabilized visual field mapping techniques, seven hemianopic subjects were extensively investigated for residual visual abilities. Iso-lated islands of detection abilities were demonstrated by four of these subjects. Additional abilities demonstrated within these islands included saccadic and verbal localization, wavelength discrimination, form discrimination, and motion detection. These abilities were also accompanied by low-confidence ratings, and thus have the character of blindsight. It is noteworthy that different subjects demonstrated different abilities at different …visual field locations, underscoring the between and within subject variability often observed with blindsight. Furthermore, magnetic resonance images obtained for each subject demonstrated variable sparing of occipital cortex. Such cortical sparing, in conjunction with the behavioral variability, supports the notion that some instances of blindsight are mediated by remnants of the primary visual pathway. Show more

Keywords: Blindsight, hemianopia, stabilized visual field mapping, residual vision, islands of vision

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 2-3, pp. 243-253, 1999

Authors: Kerkhoff, Georg

Article Type: Research Article

Abstract: In the first part of this review, different types of homonymous Visual Field Disorders (VFDs) and their resulting visual disabilities are ana-lyzed in 313 patients with VFDs and 141 patients without VFDs from a neurorehabilitation centre for adults. Homonymous hemianopia was the most frequent visual field loss (54.7 %), followed by hemiamblyopia (23.3 %), quadrantanopia (15.3 %) and paracentral scotomata (6.7 %). About 70 % of all VFD patients had a visual field sparing of 5° …or less (macula or foveal sparing). Patients with VFDs frequently showed two types of disabilities: hemianopic alexia was subjectively reported and objectively found in 5090 % of all patients, and visual exploration deficits in the scotoma were complained and found in 1770 % of the VFD patients. While hemianopic alexia was related to parafoveal visual field sparing, and additionally to visual acuity in patients with bilateral VFDs, visual exploration deficits were correlated to the size of the area in the scotoma in which the patient searched for a stimulus with saccadic eye movements (search field). The size of the search field in the intact hemifield was not related to visual exploration deficits in unilateral VFDs. As a third disability, visual-spatial deficits in VFD patients are summarized. In the second part, restorative and compensatory treatment approaches for postchiasmatic VFDs are reviewed. Partial restitution of blind regions in the visual field is achieved in the majority of patients treated with purely restorative methods including saccadic localization or light detection in the scotoma. However, the amount of the visual field recovered is limited to 512° (mean) in 90 % of these patients. Compensatory treatments seek to improve the substitution of the lost field region by large-scale saccadic eye move-ments to the scotoma, spatially organized search strategies in both visual hemifields, and by training small-scale eye movements required for reading. Significant improvements in these areas are achieved in 95 % of all VFD patients with these treatment techniques, with documented transfer to visually related activities of daily living. Furthermore, a significant though limited visual field increase of 57° is achieved in 30 50 % of patients treated in this way. In the final section, promising approaches that might lead to new treatment techniques for VFDs are reviewed. Among these are the gaze-dependant modulation of scotomata, training-dependant enlargement of the useful field of view, a nd t he uncovering of residual visuomotor capacities to visual stimuli in a scotoma. Show more

Keywords: Hemianopia, recovery, reading, visual search, space perception, gaze

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 2-3, pp. 255-271, 1999

Authors: Kasten, Erich | Poggel, Dorothe A. | Müller-Oehring, Eva | Gothe, Janna | Schulte, Tilman | Sabel, Bernard A.

Article Type: Research Article

Abstract: Purpose: Brain damage is often accompanied by visual field defects which have been considered to be non-treatable. In recent years, however, new diagnostice methods have revealed hitherto unknown residual vision, which was found, for instance, in transition zones near the blind visual field sectors and in spared islands of vision within the blind regions ("blindsight"). Furthermore, animal studies revealed a high degree of plasticity in the visual system suggesting the possibility that recovery of vision may …be induced by systematic visual training. Methods: Here we summarize a series of studies with patients suffering from visual field defects after brain lesion using some most recently developed computer-based programs for the diagnosis and treatment of visual field defects. Specifically, high-resolution perimetry (HRP) was applied to first diagnose residual function in or near the "blind" sector of the visual field. Thereafter, visual restitution training (VRT, see Kasten et al., Nature med. 4, 1998, p. 1083) was used daily for 6 months to provide systematic stimulation of these areas of residual vision. Results: In a number of studies, we have observed not only residual visual functions within or near the field defect, but we were also able to follow the course of spontaneous recovery of visual functions within weeks or months after visual system damage. Furthermore, even long after spontancous recovery is complete, computer-based visual restitution training (VRT) in or near the areas of residual vision results in a significant enlargement of intact areas, both after optic nerve damage and postchiasmatic lesions. Using VRT, we found a border shift of about 5 degrees of visual angle which cannot be explained by eye movements or eccentric fixation. We observed a transfer of this training effects to other tasks such as form and color detection, as well as to tests of visual exploration which were not specifically trained. Moreover, 72 % of the patients reported subjective improvements of vision. Training-induced visual field enlargement persisted for at least one year, even in the absence of training beyond 6 months of treatment. Conclusions: The visual system possesses a remarkable plasticity which becomes apparent in visual field enlargement during spontaneous recovery and specifie visual training. Animal studies indicate that a minimum number of residual neurons surviving the lesion, in the order of 10%, provides a sufficient substrate for recovery of vision. Though the precise mechanisms of training-induced visual field enlargement need to be further explored, VRT can be introduced for routine clinical treatment of patients with visual field defects. Show more

Keywords: Plasticity, functional restitution, visual field defects, residual neuronal structures, training, rehabilitation

Citation: Restorative Neurology and Neuroscience, vol. 15, no. 2-3, pp. 273-287, 1999